Hepatitis C Virus Ebook

Alternative Hepatitis C Treatments

The therapeutic goals of Natural treatment for Hepatitis C are as follows: Decrease iral load Normalize liver enzyme levels. Enhance/regulate immune system function. Strengthen and promote healthy liver function. Protect the liver, prevent further damage. Virological response; i.e. viral clearance, viral reduction or elimination of the virus. Starve the virus by limiting levels of iron. Optimizing cellular levels of glutathione in the body, making detoxification of the liver possible and enhancing the immune system. Stimulate regeneration of the damaged liver cells. Use of antioxidants to combat the effects of free-radicals generated by the virus. Reduce inflammation. Slow viral replication. Replace all of the inflammation-damaged liver cells. Regulate immune function/prevent auto-immune problems. Cancer preventative measures. Reverse fibrosis to prevent and improve cirrhosis

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Hepatitis B arthritisdermatitis syndrome

Hepatitis B vasculitis Treating hepatitis B vas-culitis is difficult. The standard treatment for serious vasculitis, corticosteroids combined with an immunosuppressant such as cyclophosphamide, is often needed to control the vasculitis but has the negative effect of promoting viral replication. The approach usually used is to control the vasculitis and then to start treatment with antiviral drugs. The largest experience with this type of sequential immunosuppressant antiviral therapy for hepatitis B vasculitis is from a group in France headed by Dr. Luc Guillevin. They report good results, with approximately 80 percent of patients surviving five years. hepatitis C The cause of an illness previously called non-A, non-B hepatitis was identified in 1989 and the illness renamed hepatitis C. Approximately 170 million people worldwide and 3 million in the United States are chronic carriers of hepatitis C. In the United States, it is the commonest cause of chronic hepatitis and...

Hepatitis and acute liver disease

Hepatitis A, B, E viruses other viruses e.g. Epstein-Barr virus Vascular damage Severe hypotension, Budd-Chiari syndrome Autoimmune hepatitis Tumour infiltration Hepatitis Hepatitis (inflammation of the liver) can occur as a result of infection, toxins, drugs and autoimmune, vascular or biliary disease. Rapidly progressive damage causes acute liver disease, while more insidious damage leads to chronic liver disease. Life-threatening liver failure can occur in both cases.

Case example Hepatitis B

HBV is one of the most common infectious diseases of the world, with over 350 million long-term carriers of the virus. The current medication (interferon) for chronic carriers only helps a proportion of those treated and is not a cure. It is a potentially fatal liver disease and the world's ninth biggest killer. However, only fewer than 20 of the population at risk are vaccinated. Among those vaccinated, about 10 fail to develop protective levels of antibody and may be at risk for infection. Viral vaccines have not been used because of safety considerations. Newer hepatitis B vaccines that are likely to reduce the incidence of nonresponsiveness and have immunotherapeutic value are under investigation.87 DNA vaccines are under investigation but are beyond the scope of this discussion. Recombinant protein vaccines are available and highly effective. The HBV small envelope protein (HBsAg-S) has the ability to self-assemble into VLPs discussed in Section 10.1.2. About 100 HBsAg-S...

Adolescent Female with Tremor Depression and Hepatitis

The slightly low ceruloplasmin level in the setting of elevated transaminases and neurologic symptoms raised the suspicion of hepatolenticular degeneration (Wilson's disease). A serum copper was obtained but at 171 mg dL (26.9 mmol L) was within the normal range of 60-190 (9.4-29.9). A more careful eye examination showed a golden brown band of pigment encircling the posterior cornea near the limbus of both eyes. An ophthalmologist performed a slit-lamp examination confirming the presence of Kayser-Fleischer rings. An MRI of the brain with T2 weighting demonstrated possible hyperintensity of the basal ganglia, a finding often seen in Wilson's disease. A baseline 24-hour urine collection was assayed for copper to further support the presumptive diagnosis of Wilson's disease, and a complete urine collection was documented by volume (840 mL day) and urine creatinine (0.9 g day). Baseline urinary copper excretion was elevated at 154 mg day (2.43 mmol day) (reference range,

Hepatitis D Virus HDV

An uncommon version of the hepatitis virus in the United states, it infects about 15 million people around the world. In the United states, hepatitis D infection occurs more often among adults than children. However, children from underdeveloped countries where hepatitis D is endemic are more likely to contract the virus through breaks in the skin. Cause The virus requires the presence of hepatitis B virus to produce infection, so the frequency of hepatitis D closely parallels hepatitis B. Transmission from mother to child has not been documented in the United States. Hepatitis D is spread primarily through contaminated needles and exposure to blood products. sexual transmission of hepatitis D is less efficient than for hepatitis B. Symptoms Hepatitis D cannot be distinguished from other causes of hepatitis. The development of a new episode of acute hepatitis in a patient with known chronic hepatitis B infection should prompt a search for evidence of a new hepatitis D infection....

Did It Just OnceA 37Year Old Man with Hepatitis C

This 37-year-old white male, a native of Appalachia, worked as a banker and was married with two children. He had no significant past medical history. The bank closed the local branch and laid him off while transferring others. He could not find a job despite multiple efforts and interviews. He started frequenting bars and became acquainted with a group of people who used drugs. After much insistence from his peers, he decided to try a dose of intravenous cocaine. A partner injected him with a needle that had been previously used by others in the group. Three weeks later, and because of concerns about infections, he visited his primary care physician (PCP), who ordered acute hepatitis and HIV viral serologies and liver tests. The hepatitis C antibody (anti-HCV) and anti-HIV were negative, and liver enzymes were mildly elevated to less than 2 times the upper limit of normal (ULN). His PCP discussed these findings and the clinical history with a specialist in a close tertiary center....

Hepatitis

HBV can be prevented by practicing safe sex, avoiding contact with the blood of someone who is infected, not sharing drug injection equipment, and receiving a vaccination. All who are infected with HIV should be treated for HBV. If they have not been exposed to the virus, they should receive an HBV vaccine. Currently there are three FDA approved treatments for Hepatitis B. interferon alpha, lamivudine, and, most recently adefovir. Interferon alpha is successful in eliminating the virus in up to 40 percent of people that take the drug. It is less successful in HIV positive patients. It is an intramuscular injection that is given daily for 16 weeks. Side effects are similar to a person suffering the flu. Muscle aches and pains are reported as constant in almost all patients. Exhaustion, headache, and upset stomach have also been widely reported. Depression is also common, and the drug is not recommended in patients that have suffered from severe depressive episodes in the past....

Hepatitis A

HCV disease may progress more rapidly in people with HIV. Studies conducted before the use of haart showed that HIV could speed HCV disease progression. But HAART's boost to the immune system may help to slow HCV-related liver damage. Coinfected people usually have higher HCV viral loads than people with HCV alone, but much controversy remains about HCV disease progression in coinfection. Further research is needed to confirm whether HCV does make HIV disease worse. In 1999, HCV was categorized as an opportunistic infection because of the potentially serious health consequences of living with two chronic viral infections. Because of the overlap in modes of transmission between the two viruses, it is recommended that people with HIV undergo HCV antibody testing. In most people who have been infected with HCV antibodies develop within three months. For those with a positive antibody test result, a viral load test can diagnose current HCV infection. Hepatitis D Virus Hepatitis E...

Hepatitis B

Formerly known as serum hepatitis, this is the most common preventable infectious disease in the United States. The virus can destroy the liver and is 100 times more transmissible than the AIDS virus. It is believed that there are 300,000 cases a year, of which only about 15,000 are reported about 1.25 million Americans are carriers, which means they are infectious for the rest of their lives. Almost 6,000 Americans each year die from acute hepatitis B or complications of the infection around the world, the fatality rate is two million. It can be prevented by vaccine, but of the group who accounts for the most infections those aged 15 to 39 only about 5 percent ever get vaccinated. Cause The hepatitis B virus (HBV) is carried in the blood and is also found in saliva, semen, and other bodily fluids. It is transmitted much the same as the AIDS virus, but hepatitis B is even easier to catch. One drop of infected blood contains hundreds of thousands of virus one drop of blood with HIV...

Hepatitis C

The virus that causes hepatitis C was identified in 1988 and was first known as non-A, non-B hepatitis. in the United States, hepatitis C virus is linked to 20 percent of all clinical hepatitis cases and is the leading cause of chronic hepatitis. it causes liver cancer, kills up to 10,000 Americans a year, and causes almost half of all deaths from liver failure. More than half of all patients exposed to the virus become carriers, and up to 20 percent of these carriers develop cirrhosis, a severe liver disease. About five out of every 100 infants born to HCV-infected women become infected at the time of birth. There is no way to prevent this from happening. Most infants infected with hepatitis C at birth have no symptoms and do well during childhood scientists do not know if these children will have problems from the infection as they grow older. Cause Most children are infected at birth from infected mothers. There is no evidence that breastfeeding spreads hepatitis C, but infected...

HCV infection

Hepatitis C virus (HCV) is a single-stranded hepatotrophic RNA virus which causes a chronic infection of the liver that may lead to the development of cirrhosis and hepatocellular carcinoma. Hepatitis C virus has developed several strategies to evade the immune system resulting in failure to eradicate the virus in most infected individuals 48 . A recent report provides evidence that HCV may evade the attack from the innate immune system by inducing the degradation of TRIF, one of the TLR adaptor proteins 49 . NS3 impedes both IRF-3 and NF-kB activation by reducing functional TRIF abundance and by generating cleavage products with dominant-negative activity 49 . Thus, HCV has not only developed strategies to avoid attack from the adaptive immune system, but also from the innate immune system. HCV core and NS3 proteins may also activate TLR2 in monocytes and macrophages to induce TNF-a, IL-6 and IL-8 production through NF-kB, JNK p38 AP-1 and ERK pathways 46 . These changes may...

Hepatitis A virus

Hepatitis A is an RNA virus belonging to the family Picornaviridae and is present throughout the world. Hepatitis A is usually spread by direct contact from one person to another via the fecal-oral route. There have been many examples of outbreaks of hepatitis A due to contaminated food or water. Some of the incriminated foods include raw shellfish, milk, potato salad, and orange juice. The incubation period following exposure is around 30 days, with a range of 15-50 days. This long incubation period can make tracing the source of infection very difficult. Clinically, hepatitis A may be mild or even asymptomatic, especially in children. In adults, it usually begins with flulike symptoms of headache, myalgia, anorexia, nausea, vomiting, and headache. This is then followed by the development of jaundice. In hepatitis A, the rule is that the disease is self-limiting and long-term consequences are unusual, but occasionally the hepatitis can become fulminant. While during the acute...

Hepatitis E virus

Hepatitis E virus was first described in 1977 and is a small RNA virus from the Caliciviridae family. It is usually transmitted in contaminated drinking water, and probably in food as well, but this has not been documented. Person-to-person spread also occurs. Hepatitis E has an incubation period of 2-9 weeks, although most people develop symptoms around 40 days postexposure. Clinically, the disease is very much like hepatitis A, with constitutional symptoms followed by jaundice. Patients usually recover but the mortality rate has been reported to be as high as 3 in some instances, especially in pregnant women. The diagnosis is made serologically.

Viral hepatitis

Many viruses infect the liver as well as other organs, but the hepatitis viruses A, B, C, D, E and G primarily target the liver. Hepatitis A virus is the commonest cause of viral hepatitis and, like the hepatitis E virus, is transmitted via the faecal-oral route through contaminated food or water. Infection is short-lived (about 6 weeks) and never becomes chronic, although it can be severe and even fatal. Infection induces immunity and a vaccine is available. Hepatitis B and C viruses are transmitted by blood and sexual contact, or from mother to child. They can cause acute hepatitis, as well as chronic hepatitis that may progress to cirrhosis. In the acute phase of hepatitis B infection, patients may develop liver failure. However most develop immunity and recover, with about 10 remaining chronically infected. Acute hepatitis C infection is rarely severe, but results in chronic infection in the majority of infected individuals. Hepatitis D virus only infects individuals with...

Types of Hepatitis

The liver responds to any injury in three different ways (1) inflammation, generically called hepatitis, which can be of different nature (leukocytic, lymphocytic, plasmo a cytic, etc.) (2) cholestasis, which represents an impairment of the bile flow at any point from the sinusoidal membrane to the extrahepatic bile ducts and (3) a combination of both. Cholestasis can be caused by drugs, toxins, virus, and blockage of the biliary tree at any level and from multiple causes (stones, strictures, tumors, etc.). A cholestatic injury is characterized by elevation of alkaline phosphatase and bilirubin, which is normally secreted into bile. Cholestatic injury may occur in a pure form with no evident parenchymal damage or may be accompanied by hepatocellular damage.1 A hepatitic injury is characterized by an elevation of transamin-ases and represents hepatocellular damage and necrosis. It can be related to multiple causes such as bacteria, drugs, toxins, virus, autoimmunity, metabolic...

Recombinant DNA technology

Hepatitis B surface antigen was expressed in potatoes.12 The glycosylation status of a protein must be clearly established.13 Although most physiological proteins are glycoproteins, glycosylation is not necessarily required for bio-activity. Recombinant human interleukin (IL) 2 produced in E. coli is not glycosylated but retains full biological potency.14 However, immunogenicity issues should also be considered.

AIDS Drug Assistance Program

Peter Duesberg has written many books and articles on his theories that state that illegal drug use leads to AIDS. He has reportedly had himself injected with HIV to prove it does not cause AIDS. San Francisco ACT-uP (not part of the nationwide ACT-uP network) holds that HIV does not cause AIDS and that HIV medications are the culprit in killing people. President Thabo Mbeki of South Africa publicly doubts whether AIDS is caused by HIV and suggests it is the result of whites wanting to kill black Africans. Boyd Graves, a lawyer from California believes he has uncovered proof that HIV is derived from research done in the united States with the Visna virus from sheep. He believes it is part of a continuing eugenics program the united States government funded through the Special Virus Cancer Program, which created the virus and injected it in humans through hepatitis B vaccines tested in gay and African populations. Results of an official government investigation can be found on the...

Mechanisms of Viral Tumorigenesis

In the case of the HPVs (and other small DNA tumor viruses), the viral oncogene products inactivate both the Rb and the p53 tumor suppressor pathways (Nevins, 2001). Strikingly, these pathways are often crippled during the development of nonviral tumors as well. Inactivation of these tumor suppressor pathways not only provides a proliferative stimulus, but also elicits genetic instability, in part by decreasing the likelihood of growth arrest and or apoptosis in response to DNA damage (zur Hausen, 2002). The ensuing mutations in cellular growth control genes undoubtedly play a role in further carcinogenic progression. However, despite these accumulated mutations, the proliferation of HPV-induced cervical cancer cells requires continued expression of the viral E6 and E7 oncogenes (von Knebel Doeberitz et al., 1988 Hwang et al., 1993). The mechanisms of herpesvirus transformation are more complex and appear to involve modulation of cellular signaling and cell cycle control pathways by...

Prospects for Prevention and Treatment

The identification of a human tumor virus immediately suggests strategies for tumor prevention and control. Public heath measures can be instituted to protect the population from exposure or to identify carriers or people at elevated risk of cancer. Successful examples of this approach are the elimination of HBV and HCV from the blood supply and the use of Pap screening to identify women with HPV-induced cervical dysplasia. In a more recent example, maternal-to-infant transmission of HTLV-1 is reduced if carrier mothers refrain from breast-feeding (Hino et al., 1997). Another well-established modality to control viral infection is vaccination. An effective hepatitis B vaccine is already reducing the incidence of chronic hepatitis B virus infection and hepatocellular carcinoma (Huang and Lin, 2000), and on the basis of clinical trials demonstrating protection against persistent high-risk HPV infection and the development of precancerous lesions, HPV vaccines were recently approved for...

The Structure Function Relationship in a Protein

Another example of the importance of the three-dimensional structure for function is illustrated in Figure 11 (see color insert after page 40). The reader should now see that the depicted protein is mostly formed by P-strands. It has two domains and a quaternary structure. It is an enzyme encoded by the virus responsible for hepatitis C. This virus enters the host cell and synthesizes a single, long amino acid chain that is later broken into smaller fragments, each of which encodes one of its functions. The enzyme shown in the figure breaks up the long polyprotein. It is a protease that is, an enzyme that catalyzes the cleavage of peptide bonds.

Blood poisoning See septicemia

The blood used at most hospitals is from volunteer donors who are not paid for giving blood or blood products. Each blood donor must answer medical history questions and be given a limited physical examination before being accepted as a donor. All donated blood is tested for hepatitis, syphilis, and antibodies to immunodeficiency viruses including the aids virus. These tests decrease the chances of transfusion-related infections. Most transfusions do not cause any problems, but mild side effects may include symptoms of an allergic reaction such as headache, fever, itching, increased breathing effort, or rash. This type of reaction can usually be treated with medication if the child needs more transfusions in the future. Serious reactions are rare. The most common serious side effect is serum hepatitis, an infection of the liver.

Crystalinduced arthritis

The diagnosis of the autoimmune conditions listed under Cause is discussed in the relevant sections of this book. Hepatitis B infection is associated with a small number of cases of cryoglobu-linemia. The blood tests reliably show infection and differentiate between past exposure with immunity and current active infection. Blood tests for HCV have proven more difficult. Currently, a second generation ELISA (enzyme-linked immunosorbent assay) is usually done as a screening test and confirmed by a RIBA (recombinant-based immunoblot assay) test. Most doctors would then go on to request an HCV RNA test before starting treatment. This confirms the actual presence of the virus in the blood being tested rather than just the body's reaction to the virus, which the first two tests look at. Because the HCV is present in the blood in very low numbers, it was difficult to find before modern molecular biology techniques became available. When the hepatitis B or C viruses are the underlying cause,...

The Chemical Basics of Polymerization

Reactions at ribose-phosphate bonds require protonation and deprotonation events, and can thus benefit from acid-base catalysis. Ribose hydroxyls are poor nucleophiles unless they are deprotonated to the oxyanion. The relevant leaving groups (generally another ribose hy-droxyl) are unstable until they acquire a proton. The cleavage rates for several ribozymes vary in a log-linear fashion with pH, implying a single deprotonation event at the rate-limiting step. For many years, the substituents responsible for proton transfers were thought to be metal hydrates, and the evidence is strong that this is the case for at lease some ribozymes. A metal-bound water is more acidic than free water (e.g., pKa 11.42 for Mg(H20)g vs. 15.7 for H2O), allowing proton exchange to occur more readily near neutral pH. For the hammerhead ribozyme, this relationship is retained for a variety of metal ions, with the net reaction rate shifted according to the pKa of the hydrated metal. In recent years...

Influence Of Environmental Factors

And positive tuberculin-test reactions (Shirakawa, 1997). Similar effects were also reported by Matricardi et al. (2000). The percentage of children suffering from allergy of the upper respiratory tracts and having raised IgE concentration was lower if children had recovered from hepatitis A, Toxoplasma gondii, Helicobacter pylorii or orofecal infections. Gereda et al. (2000) highlighted the value of Th1 lymphocyte stimulation with endotoxins. Saito et al. (2003) presented a very interesting hypothesis according to which toll-like receptors (TLR) are molecules responsible for an hereditary and acquired immunogeni-city because they recognize molecules present on the surface of microorganisms - the Cpg motif (Akira et al., 2001).

Aetiology Pathogenesis

Many other viruses have been evaluated in the etipathogenesis of pSS and, among them, HCV virus has yielded a considerable interest due to the histological similarities between pSS sialoadenitis and sialoadenitis observed in HCV-infected patients (Delaleu et al., 2005). However, HCV patients present certain features that may allow to clinically differentiating them from pSS, including hepatic involvement and a different immunologic pattern, characterized by a higher prevalence of cryoglobulins and hypocomplementemia, and a lower prevalence of anti-Ro SSA and anti-La SSB (Ramos-Casals et al., 2002). These facts received attention in the newly proposed American-European consensus criteria, where HCV is listed as an illegibility criterion in clinical studies investigating pSS (Vitali et al., 2002).

Differential diagnosis

Differential diagnosis of pSS basically includes all those diseases, which may potentially cause dry-ness of the eyes and of the mouth. Most of them have been included in the recent Exclusion Criteria including past history of head and neck radiation therapy, hepatitis C infection, acquired immunodeficiency disease (AIDS), pre-existing lymphoma, sarcoidosis, graft-vs-host disease and use of antic-holinergic drugs (within four half-lives of the drug) (Vitali et al., 2002).

Bountiful Ligase Ribozymes As Evolutionary Fodder

Even the small, classic, endonucleolytic ribozymes such as the hammerhead, hairpin, VS and hepatitis delta ribozymes, catalyze both the forward cleavage reaction and the reverse ligation reaction, using a 2',3' cyclic phosphate to activate the reaction. Freezing out large-scale RNA motions either through compact tertiary structure or through the formation of engineered crosslinks is thought to determine where the ligation cleavage equilibrium lies. The ligation reaction for the hairpin ribozyme is favored 6-30 fold over the cleavage reaction,34 36 and ligation by the HDV and VS ribozymes is also notable.37 40 Introduction of a disulfide crosslink into the hammerhead ribozyme was recendy shown to accelerate the rate of ligation without altering the cleavage rate, thereby shifting the equilibrium to favor ligation over cleavage 41. It might be possible to re-engineer the abundant new small RNA-cleaving ribozymes into ligases by similarly freezing out their large-scale motions.

Results And Discussion

We further tested the reactivity of these MAbs by IFA on Vero cells expressing recombinant EGFP-N protein. The SARS-CoV (Ubani strain) N gene was cloned into pEGFP-C2 vector (Clontech), and Vero cells were transfected with plasmid pEGFP-C2-N. MAb SA 46-4 showed the highest sensitivity and specificity in recognizing the EGFP-N protein in Vero cells, but the other two MAbs showed weak fluorescence and high background (data not show). To further confirm the specificity of MAb SA 46-4, it was tested for cross-reactivity with other coronaviruses and arteriviruses. It did not cross-react with porcine transmissible gastroenteritis virus (TGEV), mouse hepatitis virus (MHV), or porcine reproductive and respiratory syndrome virus (PRRSV).

Drug eruption See eruption

Drug fever The elevation of body temperature that occurs as an unwanted manifestation of drug action. Drugs can induce fever by several mechanisms these include allergic reactions, drug-induced tissue damage, acceleration of tissue metabolism, constriction of blood vessels in the skin with resulting decrease in loss of body heat, and direct action on the temperature-regulating center in the brain. The most common form of drug fever is associated with allergic reactions. It may be the only allergic manifestation apparent, or it may be part of a complex of allergic symptoms that can include skin rash, hives, joint swelling and pain, enlarged lymph glands, hemolytic anemia, or hepatitis. The fever usually appears about seven to 10 days after starting the drug and may vary from low-grade to alarmingly high levels. It may be sustained or intermittent, but it usually persists for as long as

Coronavirus S Proteins And Their Receptors

Several coronavirus cell-surface receptors have been identified. Aminopeptidase N (APN, CD 13) was shown to be the receptor for canine coronavirus, feline infectious peritonitis virus, HCoV-229E, porcine epidemic diarrhea virus, and transmissible gastroenteritis virus, all of which are group 1 coronaviruses.39, 40 Members of the pleiotropic family of carcinoembryonic antigen-cell adhesion molecules (CEACAMs) were identified as receptors for the group 2 pathogen murine hepatitis virus,41-43 whereas bovine group 2 coronaviruses bind to 9-O-acetylated sialic acids.44 In 2003, ACE2 was identified as a functional cellular for SARS-CoV.45 The role of ACE2 in HCoV-NL63 Discrete, independently folded, receptor-binding domains (RBDs) of the S proteins of several coronaviruses have been described.72-77 The first 330 amino acids of the 769-residue S1 subunit of the murine hepatitis virus S protein is sufficient to bind its receptor,

Occupational Hazards In The Ed

For the next 20 to 30 years, your workplace will be a chaotic, messy, and tense environment. For some, the confines of the emergency room seem like a more dangerous work environment than the clinic, operating room, or ward. You will often be performing invasive procedures under time pressure, with blood splattering everywhere. Patients may not necessarily divulge any possible pathogens they may be carrying. And, all sorts of nasty bugs and critters make the ED their very special home. Here, brave emergency physicians are at an increased risk for exposure to everything from multidrug-resistant tuberculosis to hepatitis B and C, from HIV to potential biological warfare agents. The ED is, after all, one of the top locations where medical students have been exposed to accidental needle-sticks.2 Although there is the potential of being exposed to an infectious agent, most modern emergency departments take all sorts of steps to minimize the risk. As a result of universal precautions, the...

Treatment and Outcome

Most types of drug-induced hepatitis are treated by stopping the offending drug. The outcome depends on how severe the liver injury is. it ranges from rapid reversal of mildly abnormal liver function tests to death from liver failure. hepatitis B A common viral infection transmitted from person to person by blood or body fluids that results in acute and chronic liver inflammation, cirrhosis, and liver cancer. in the united states, approximately 200,000 cases occur annually. The liver complications of hepatitis B infection are the most frequent and serious ones, but musculoskele-tal symptoms can also occur.

Trypsin Mediated Proteolysis Of S Protein

The precise requirement and role of glycoprotein processing for coronavirus entry and membrane fusion is not well defined. Many coronaviruses, such as mouse hepatitis virus (MHV), contain a furin cleavage site within S that yields S1 and S2 subunits 10,11 This site, however, is not absolutely required for infection, although lack of cleavage lowers S-mediated cell-cell fusion.11 In contrast, SARS-CoV S, both when overexpressed in cells, and on mature virions, is predominantly in a full-length, unprocessed form (Fig. 1A, left-hand lane). However, cell-to-cell fusion mediated by SARS-CoV S was enhanced by pretreatment of effector cells with trypsin.9 Thus, the role of proteolysis of SARS-CoV S by trypsin-like proteases in cell-free virus infection was examined.

Mechanisms Involved in RVInduced Neuronal Damage

The induction of apoptosis in RV-infected neurons has recently been proposed as a potential pathogenic mechanism 18 , although the use of an attenuated strain in studies on which this proposal was based raise questions about the relevance to street RV infection. Moreover, since apoptosis is likely a host defense mechanism that leads to a self-limiting virus infection, it is not clear why a rabies strain that is well-adapted to its natural host would trigger a mechanism detrimental to its own survival. In fact, adenoviruses 33 and human hepatitis C virus 36 contain genes that act to interfere with apoptosis, thus allowing cell survival and virus replication. Those findings and our own demonstration that the pathogenicity of a particular RV strain correlates inversely with its ability to induce programmed cell death 30 argue against any strict correlation between viral pathogenesis and virus-induced cell death. Together, the most significant factor underlying the lethal outcome of an RV...

GALT gutassociated lymphoid tissue

Gamma globulin A type of protein found in the blood. It is made up of antibodies. When gamma globulins are extracted from the blood of many people and combined, they can be used to prevent or treat infections. They are used in what are sometimes called vaccines for hepatitis A and chicken pox. Gamma globulins are synthesized by lymphocytes and plasma cells in response to an antigenic challenge. The ability to resist infection is related to concentration of such proteins.

Genital secretions 197

Biopharming represents another point on the continuum. In general, biopharming appears to be a creature of giant corporations, not family farms. Boosters of biopharming insist that their products will be cheaper than current drugs. Examples include edible vaccines against disorders such as hepatitis B and diarrhea, in the form of genetically modified (GM) bananas, corn, tomato juice, lettuce, and potatoes. These foods must be eaten raw (cooking would destroy the vaccines). The use of edible vaccines to treat autoimmune diseases is currently being studied. Enthusiasts insist that edible vaccines could be valuable in developing countries that lack facilities to refrigerate and deliver standard vaccines. Critics point out that it will be hard to provide consistent doses. In discussions of drugbearing plants, concerns over safety and environmental damage have been and continue to be expressed.

Hepatic steatosis See steatosis

Hepatitis Hepatitis is an irritation or inflammation of the liver with a variety of causes, including viral infections, bacterial infections, autoimmune diseases, and chemical and medication toxicities. The leading worldwide cause of inflammation of the liver or hepatitis is viral in origin. A common misperception is that one virus causes hepatitis actually there is a diverse group of hepatitis viruses lettered A through G, except the letter F hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), hepatitis E (HEV), and hepatitis G (HGV-C). All of the hepatitis viruses have different size, genetic structure, routes of transmission, and ability to produce chronic infection. Despite these differences, hepatitis viruses have the propensity to produce acute symptoms of fatigue, loss of appetite, intermittent nausea, abdominal pain, fever, jaundice, dark-colored urine, chills, and liver enlargement. Several of the hepatitis viruses can evade the elaborate defenses of...

The Implementation Dilemma

Patients suffering from most of the infectious diseases should be quarantined for treatment. Work units employing more than 200 floating people should report to the health department of the local government and implement hygiene measures as required to prevent and control infectious diseases (Article 20). Water, goods, or excrement polluted by diseases such as typhoid, bacillary dysentery, and hepatitis should be strictly treated. The responsible epidemic reporters are personnel working in hospitals and disease control centers. They should report the diseases of plague, cholera, lung anthrax or AIDS to the local health department with a fastest communicating means no later than 6 hours in towns and 12 hours in countryside from the first discovery of the disease (Article 35). The epidemic situation in the military is to be reported to the State Council by the military health department in accordance with relevant regulations (Article 39). The emergency measures under Article 25 of the...

Weaknesses Facilitating Emergence And Re Emergence

The weakening of the public health infrastructure for infectious disease control is evidenced by failures such as in mosquito control in Latin America and Asia with the re-emergence of dengue now causing major epidemics in the vaccination programs in eastern Europe during the 1990s, which contributed to the re-emergence of epidemic diphtheria and polio and in yellow fever vaccination, facilitating yellow fever outbreaks in Latin America and sub-Saharan Africa, including a large urban outbreak that occurred in Cote d'lvoire in 2001. It is also clearly demonstrated by the high levels of hepatitis B and the nosocomial transmission of other pathogens such as HIV in the former USSR and Romania, and the nosocomial amplification of outbreaks of Ebola in Zaire, where syringes and failed barrier nursing drove outbreaks into major epidemics.

Rash on the Soles of the Feet

His past medical history is significant for HIV, which was diagnosed 24 years earlier, idiopathic thrombocytopenic purpura resulting in a splenectomy 16 years earlier, and bipolar disorder diagnosed 18 years earlier with a suicide attempt 5 years ago. He has been on intermittent HAART therapy and his infectious disease history is positive for hepatitis B, gonorrhea, HPV (human papilloma virus) with anal warts, and herpes simplex virus 1 and 2. His most recent PPD skin test (purified protein derivative) for tuberculosis was negative.

Answers and Discussion

Q1. (Answer b) Adriamycin, in common with virtually all chemotherapeutic agents, has high potential toxicity. In the case of this drug, the limiting toxicity is cardiac. More drug might have been beneficial in attacking the tumor but it would likely have been cardiotoxic. There was no mention in his history of chemical abnormalities nor of myocardial infarction during his treatment for the angiosarcoma. Q2. (Answer c) Alcohol is responsible for a range of liver pathology. Heavy drinking causes fatty liver that may progress to hepatitis that may progress to cirrhosis. Some small number of alcoholics develop liver cancer. The specific pathology resulting from alcohol is not predictable but it is certain that alcoholism correlates with risk of hepatic cancer. A history of alcohol abuse puts this patient in a higher risk category. Whether this is merely additive to the risk that arises from vinyl chloride exposure or whether it is greater than the additive risk predicted from each factor...

Biological Characterization of Pegylated Interferons

Type I interferon-a (IFN-a) has proven to be a clinically effective antiviral and antineoplastic drug for 20 yr (1). Recently, pegylated forms of IFN-a have been commercially produced and have shown superior clinical efficacy to unpegylated IFN-a for reducing HCV viral load with less frequent dosing required for the patient (2,3). The superior clinical efficacy is probably derived from the enhanced serum half-life of the pegylated IFN-a in patients. However, pegylation also reduces the in vitro activity of the core IFN-a protein (4,5). Understanding the structural implications of pegylation on IFN-a activity is critical for biologically characterizing the commercial drug product. In vitro characterization provides a basis for establishing consistency in the manufacturing process for the precursor IFN-a and the final pegylated product. The better characterized the product is, the higher the confidence is for assessing and demonstrating comparability between pegylated products when...

Porphyria Cutanea Tarda

Porphyria cutanea tarda (PCT) is a defect of uroporphyrinogen decarboxylase that can be acquired or inherited through autosomal dominant transmission. This disorder becomes active only after additional liver-specific precipitating factors, such as alcohol, drugs, or viral infections (hepatitis, HIV) are present. Among the precipitating factors of hepatic porphyria, estrogens also play an important role estrogen-containing contraceptives have been implicated in the manifestation of PCT in young women. It is known that all of these factors either inhibit uroporphyrinogen decarboxylase or lead to liver damage as a result of direct or indirect deposition of iron in the liver. Perimenstrual improvement of PCT has been explained by menstrual bleeding, which, similar to therapeutic bloodletting, leads to a reduction of iron (36).

Lambda Legal Defense and Education Fund

Lamivudine A nucleoside reverse transcriptase inhibitor (NRTI) from GlaxoSmithKline. It is used in the treatment of HIV and hepatitis B. It was the first drug to be approved for the treatment of hepatitis B. It has been one of the longest used drugs against HIV and has proved durable for many people. It is used in the combination pills combivir and trizivir. 3TC works well in combination with AZT and has shown to decrease mutations causing resistance that can arise in taking AzT. It is available in both a liquid and a pill formulation. It is taken twice daily. The most common side effects are nausea, vomiting, fatigue, and headaches. 3TC does not work well with zalcitabine. (Also known as 3TC and Epivir.)

Endotoxininduced liver injury

Endotoxin-induced fulminant hepatitis is a common clinical complication during sepsis and accounts for a high percentage of sepsis-associated mortality. In comparison to humans, rodents are highly resistant to LPS. However, after treatment with heat-killed P. acnes, mice become highly susceptible to LPS challenge. P. acnes leads to a recruitment of macrophages and dendritic cells into the liver and a differentiation of hepatic T-helper lymphocytes into type 1 T-helper cells. The sensitization by P. acnes in the liver depends on IFN-y, IL-12 and IL-18 59-61 . TLRs are involved in both the P. acnes-priming phase and the LPS challenge phase. Indeed, hepatic granulomas, consisting of macrophages, dendritic cells and lymphocytes, were not found in MyD88-deficient mice after P. acnes administration and liver injury was blunted (Seki, unpublished data). P. acnes sensitizes towards TLR4-, but not TLR2 ligands, and upregulates the hepatic levels of TLR4 and its co-receptor MD-2 62 . Whereas...

Viral Foodborne Pathogens

Viral agents are considered to be an increasingly important cause of food-borne illness. A number of different viral agents have been associated with food-borne disease and cause a variety of illnesses, varying from a simple gastroenteritis to major systemic upset, such as hepatitis. Food and water are vehicles for viruses, but viruses do not reproduce in food and nor do they produce toxins in food. Some viruses, such as Norwalk, cause large outbreaks others seem to be more frequently associated with sporadic disease. Overall, the difficulty in diagnosing viral illness has precluded the development of large amounts of epi-demiological data. However, the advent of rapid tests (e.g. enzyme immunoassays for the detection of rotavirus) is beginning to change this, and will eventually lead to a better understanding of the epidemiology and disease burden caused by the various food-borne viral pathogens.

Collaboration With Governmental Public Health Agencies

States mandate the reporting of various infectious diseases (e.g., AIDS, hepatitis B, measles, rabies, and tuberculosis) and submit data to federal disease surveillance systems (CDC, 1999). Governmental public health agencies also depend on astute clinicians to inform them of sentinel cases of recognized diseases that represent a special threat to the public's health and of unusual cases, sometimes without a confirmed diagnosis, that may represent a newly emerging infection, such as Legionnaires' disease or West Nile virus in North America. Other types of public health surveillance activities,

Audit of volunteer screening procedures

The audit was of the rejection rate and stage at which rejection took place in 831 subjects all volunteering for the same study. The screening procedure at this unit was in three stages first, the volunteers filled out a questionnaire with personal, social and medical details at this stage 117 of the 831 were rejected. Second, a medical history was taken, and a physical examination performed with clinical chemistry and haematology investigations and serology for Hepatitis B and HIV. A urine sample was tested for protein, glucose, blood and bilirubin, and also for drugs of abuse. At this stage 45 volunteers were rejected. Stage three consisted of obtaining information from the GP of each of the volunteers. The questionnaire the GP was asked to complete asked about disorders of the central nervous system, cardiovascular disorders, disorders of the respiratory system, disorders and diseases of the alimentary system and the genito-urinary system, psychiatric...

Differential Induction Of Proinflammatory Cytokines In Primary Mouse Astrocytes And Microglia By Coronavirus Infection

Mouse hepatitis virus (MHV) can infect rodents and cause digestive and central nervous system (CNS) diseases. The severity of the diseases is influenced by both viral and host factors. The strain JHM is highly neurovirulent while A59 is low neurovirulent, although both strains cause encephalitis and demyelination. By contrast, strain MHV-2 is non-neurovirulent, causing only mild meningitis but no encephalitis and demyelination.1 Studies have shown that the viral spike protein is the major determinant for neuro virulence. Recombinant A59 JHM-S, which contains the JHM spike gene in the A59 genomic background, exhibited a neurovirulent phenotype in C57BL 6 mice similar to that of JHM2 while A59 MHV2-S (Penn-98-1), which contains the spike of MHV-2, caused acute encephalitis but did not cause demyelination.3 Thus, the spike can modulate the viral pathogenic phenotype. The host immune system also plays a critical role in the onset and progression of the CNS disease. There is clear evidence...

Other cellular sensors of viral dsRNA

The RNA-binding activity of RIG-I has been mapped to its helicase domain, which has intrinsic ATPase activity. Critically, the RIG-I helicase domain bound the HCV 5' and 3' nontranslated regions 41 . Thus, the interaction of RIG-I with these highly structured regions of the HCV genome represents an affinity of RIG-I for a natural dsRNA-like viral PAMP. Unstructured single-stranded RNA from HCV was not recognised by RIG-I, confirming the specificity of RIG-I for dsRNA. Melanoma differentiation associated gene-5 (Mda-5), a closely related CARD domain containing DExD H box RNA helicase, similarly enhanced IRF-3 activation in response to

Recovery of IHNVfrom cDNAs

Fig. 5 Construction of the full-length infectious clone. Four overlapping fragments covering the full-length IHNV RNA genome were generated and ligated into the pBluescriptplasmidbackbone using restriction sites indicated. T7prom, T7 RNA polymerase transcription promoter T70, T7 RNA polymerase transcription terminator 6, antigenome hepatitis delta virus ribozyme sequence Fig. 5 Construction of the full-length infectious clone. Four overlapping fragments covering the full-length IHNV RNA genome were generated and ligated into the pBluescriptplasmidbackbone using restriction sites indicated. T7prom, T7 RNA polymerase transcription promoter T70, T7 RNA polymerase transcription terminator 6, antigenome hepatitis delta virus ribozyme sequence

Complications of Hemophilia

The wide availability of commercial factor VIII and IX concentrates in the 1970s reduced the severity and frequency of bleeding complications, but came at the cost of hepatitis C and HIV infections. There have been no new cases of HIV infection linked to plasma-derived factor concentrates since 1986, due to effective screening of plasma donors and viral inactivation procedures during the manufacturing process. Similar success has been achieved in prevention of hepatitis C transmission. However, there are many hemophilics still coping with HIV infection and progressive liver disease due to chronic hepatitis C infection.

Exacerbation Of Autoantibodymediated Diseases In Ldvinfected Mice

The pathogenicity of polyclonal rabbit anti-mouse platelet antibody was strongly exacerbated in mice acutely infected with LDV.7,8 This led to severe thrombocytopenia and to the development of purpuric lesions reminiscent of human thrombocytopenic purpura.7 A similar enhancement of antibody pathogenicity was observed in LDV-infected mice that received monoclonal anti-mouse platelet autoantibodies, derived either from (NZB x BXSB)F1 mice or from animals that developed an autoimmune anti-platelet response after immunization with rat platelets.9 Infection with mouse hepatitis virus (MHV) resulted in the same enhancing effect of autoantibody pathogenicity.7 Moreover, anemia induced by an anti-erythrocyte monoclonal antibody was also strongly exacerbated in mice infected with LDV.10 Interestingly, this consequence of LDV infection was found with an IgG2a autoantibody that induces anemia through phagocytosis, but not with an IgG1 autoantibody that lead to a similar disease through distinct...

Viral activation of IRF3 through TLRs

The IFN-P promoter and furthermore, IRF-3 could be co-immunoprecipitated with TRIF 80 . Consistent with this, a requirement for TRIF in LPS-induced IRF-3 activation has been demonstrated 81 . There are, however, key differences between TLR3- and TLR4-mediated IRF-3 activation, suggesting that TRIF function may differ in these two pathways. The TIR adaptor TRAM was shown to play a role in TLR4 but not in TLR3-induced IRF-3 activation 78, 81 . Moreover, poly(I C) treatment led to phosphorylation of the critical C-terminal serine residue 396 (Ser-396) in IRF-3 while LPS was unable to induce phosphorylation at this site 82 . Thus, the exact mechanism of IRF-3 activation by TRIF on engagement of TLR3 and TLR4 remains to be elucidated. Furthermore, the discovery of a critical role for RIG-I in the activation of IRF-3 and type I IFNs in response to some viruses, including, SeV, NDV and HCV 40, 41 questions the relative role of TRIF-induced IRF-3 in the antiviral response. Nevertheless, given...

Justification For Using Cell Culture And In Vitro Assays

The purpose of short-term in vitro genotoxicity assays is to predict if a chemical may have a potential to cause cancer and to offer information regarding chemical mechanisms of DNA damage. These tests do not prove that something causes cancer, nor is there one single test that provides an unequivocal ruling that a given substance is a carcinogen. A carcinogen is generally accepted as an agent that induces neoplasms in humans or animals, increases the incidence of tumors, or speeds up the time for tumor development. Cancer is currently the second leading cause of death in the United States after heart disease. Established human carcinogens include physical agents such as UV light 35 , x-radiation, and gamma radiation 36 , infectious agents such as hepatitis B and C viruses 37 , human papilloma viruses 38 , and helicobacter pylori bacterium 39 , and many chemical agents including alcohol 40 , aflatoxin 41 , Cr6+ 42 , and polycyclic aromatic hydrocarbons 43 .

Targeted viral evasion of TLRmediated immunity

Some virally encoded proteins specifically target components of TLR signalling pathways to inhibit TLR-induced innate immune responses. VV encodes two such proteins (A46R and A52R) which block distinct arms of TLR-mediated signalling cascades. Thus, VV expresses two functionally independent proteins which inhibit TLRs by different mechanisms, emphasising the importance of TLR signalling in the host innate immune response to viral infection. HCV, Hepatitis C virus VV, Vaccinia virus Some virally encoded proteins specifically target components of TLR signalling pathways to inhibit TLR-induced innate immune responses. VV encodes two such proteins (A46R and A52R) which block distinct arms of TLR-mediated signalling cascades. Thus, VV expresses two functionally independent proteins which inhibit TLRs by different mechanisms, emphasising the importance of TLR signalling in the host innate immune response to viral infection. HCV, Hepatitis C virus VV, Vaccinia virus HCV provides us with a...

Results For Chromiumiii Nicotinate

Chromium nicotinate has demonstrated a low toxicity. For example, to date only one adverse clinical case report exists, describing chromium polynicotinate-induced hepatitis 84 . It is also less active in cell culture assays. Chromium nicotinate did not produce cell death at concentrations up to 1 mM Cr3+, nor did it produce chromosomal aberrations in CHO cells after 24 hours of exposure 85 . One study reported that CrNic produced less oxidative stress and DNA damage than CrPic 86 however, that work included co-authors from the company that manufactures CrNic (Interhealth), and data presented in the text of the report showed that both CrPic and CrNic actually produced equivalent levels of cytochrome c reduction, formation of 2,3- and 2,5-dihydroxybenzoic acids, and DNA fragmentation in J774A.1 macrophages that were above untreated controls after 24 hours of exposure. At this time there are no published reports on mutagenicity testing of CrNic.

Liver cancer and masses

Primary liver cancer (hepatoma) is rare, except in chronic liver disease and cirrhosis, particularly when the liver disease is caused by hepatitis B virus infection. People with primary sclerosing cholangitis (PSC) are particularly prone to develop cancer of the biliary epithelium, cholan-giocarcinoma. Non-malignant hepatic adenoma is associated with the use of the oral contraceptive pill. The most commonly occurring cancers in the liver are metastatic deposits from cancer of the stomach, colon, pancreas and breast.

Definition of Porphyria Cutanea Tarda

Sporadic type PCT (type I) accounts for 80 of cases. It is more common in males, with no family history of disease. In sporadic PCT, deficiency of UROD occurs by inac-tivation of this enzyme in the liver, which may be triggered by alcohol use, estrogen excess, iron overload, hepatitis C viral infection, and or HIV infection.1,3 The enzyme deficiency in this subtype of PCT is characterized by 50 reduction in enzymatic activity during full active disease, observed only in hepatocytes, with apparently normal enzymatic activity in erythrocytes and all other tissues. Mutations of the UROD locus have been excluded in sporadic type I PCT.

Pyridoxine hydrochloride

Pyrimethamine An antibiotic used to treat toxoplasmosis, usually in combination with a sulfa drug such as sulfadiazine or clindamycin. The major side effect after prolonged use is anemia. other side effects include gastric intolerance, allergic reactions, and hepatitis, some of which are attributable to the sulfa drug that is taken with it. To avoid anemia, another drug, leucovorin, is given at the same time.

Noninsecticidal Organohalide Pesticides

Although the toxic effects of 2,4,5-T may even be somewhat less than those of 2,4-D, observations of 2,4,5-T toxicity have been complicated by the presence of manufacturing by-product TCDD. Experimental animals dosed with 2,4,5-T have exhibited mild spasticity. Some fatal poisonings of sheep have been caused by 2,4,5-T herbicide. Autopsied carcasses revealed nephritis, hepatitis, and enteritis. Humans absorb 2,4,5-T rapidly and excrete it largely unchanged through the urine.

Agents targeting Tcellantigenpresenting cell interaction

Alefacept is a human fusion protein where the CD2 binding domain of LFA3 has been linked to the Fc portion of human IgG1, leading to functional blockade of the LFA3 CD2 pathway. Thus alefacept by binding to CD2 inhibits the function of CD4+ and CD8+ T-cells and selectively reduces memory-effector CD45RO + T cells (Ormerod, 2003). Treatment with alefacept (12 wk) significantly improved psoriasis in comparison to placebo and a second course of alefacept after 12 wk was found to provide additional benefit. Ale-facept has been shown to provide long-lasting periods of remission. It was well tolerated without any serious short-term side effects (Krueger and Ellis, 2003 Lebwohl et al., 2003). The safety and tolerability of alefacept was corroborated in two patients with psoriasis and hepatitis C. In these patients liver enzymes remained stable during the 12 wk therapy with alefacept (Thaci et al., 2005). An open-label single-centre study of 20 patients with chronic plague psoriasis in which...

Silybum marianum See silymarin

Silymarin The seeds of milk thistle (Silybum mari-anum) have been cultivated for centuries as a medicinal remedy, and are considered by some to have liver-protecting properties. An extract is available under the name silymarin proponents suggest that it is useful for liver-based problems, including cirrhosis, jaundice, chronic hepatitis, and damage due to drugs, alcohol, and poisoning from chemicals and diarrhea. Some reports have suggested that silymarin may stimulate certain immune functions and may protect the liver during hepatitis. To date, no studies of silymarin in pwas have been conducted. No toxic effects of sily-marin have been reported, although it is possible that because of its purported effect on the liver and kidneys, the compound may effect the absorption of other medications. Silymarin concentrations vary in milk thistle capsules, pills, and teas, and

Genetic Engineering of Rhabdoviruses

With efficient reverse genetics systems for rhabdoviruses and other NSVs available, the high degree of amenability of these viruses to genetic engineering and their ability to express foreign genes were rapidly verified. Indeed, the initial report on recovery of recombinant rabies viruses from cDNA included the description of a rabies virus expressing an additional, artificial mRNA from the recombinant genome (Schnell et al. 1994). The potential to express foreign genes was obvious and predicted from the modular genome organization. Since rhabdovirus genomes represent a succession of individual cistrons defined by conserved gene start and gene end signals, and since rhabdoviruses with more than the five basic genes were known, the introduction of additional, and maybe multiple genes appeared easy. This is in contrast to positive-strand RNA viruses such as poliovirus or hepatitis C virus whose genome is translated into a polyprotein-precursor, which is cleaved

Immunology relevant to vaccines

Significant association between particular HLA genes and responsiveness to measles and hepatitis B vaccine has been shown and forms the genetic basis for variation in antibody response to vaccines.25 The MHC proteins are of three different generic types determined by their structures and functions, and the most relevant regions are represented by class I and II proteins. The majority of the cellular MHC antigens are transmembrane glycoproteins found in the plasma membrane. Different MHC antigens are recognized by different T-cell types. Most virally infected cells display viral antigens on the surface of their plasma membranes these antigens are recognized by T-cyto-toxic cells. Helper and cytotoxic T cells do not bind free antigen. It seems that they recognize antigen only in association with MHC products expressed on cell membranes. Cytotoxic T cells usually recognize antigen in association with class I products, which are expressed on all nucleated cells. Helper T cells recognize...

Immune responses to vaccines

Standard vaccines based on killed pathogens or antigens do not enter the cells and thus mainly produce humoral responses. The protection often wears off after some time, and thus booster shots are required. Recombinant protein vaccines stimulate primarily Th2 cells, which are defined by their secretion of the cytokines IL-4, IL-5, and IL-10. Needle injection of such antigens delivers them into the extracellular fluid, which leads to antigen processing via the endosomal pathway and presentation in association with MHC class II molecules. Attenuated live vaccines such as viruses do enter the cells and thus also activate killer T cells, resulting in lifelong immunity, such as with measles, mumps, rubella, oral polio, and smallpox vaccines. Similarly, DNA vaccines have the potential to induce similar immunity. If successfully commercialized, they would be advantageous because, unlike live vaccines, they do not have the risk of potentially producing illness in people whose immune systems...

Routes of administration

Traditionally, vaccines have been administered by intramuscular or subcutaneous needlesticks. The reuse and improper disposal of needles can result in spread of disease and needlestick injuries. Widespread reuse of nonsterile syringes is common in developing countries and is a major source of hepatitis B infections. Compliance also becomes an issue with parenteral administra Mucosal immunization and the development of novel vaccine delivery systems have received increasing attention. The mucosa lining various cavities is protected by a secretary immune system under a complex regulatory control, with stimulation in one area potentially producing immunological responses in some other areas as well. There are also efforts under way to introduce antigens into food products. This strategy, if successful, can potentially provide a novel oral immunization method that would be very easy and economical to administer on a mass scale. As discussed in the introductory chapter to this book,...

Tat gene inhibitor See tat inhibitor

Tattoo An indelible body marking produced by injecting minute amounts of pigments into the skin. When tattooing is done commercially, sterile procedures should be used. Still, there is a risk that infectious hepatitis or HIV or both may be transmitted. Tattoos are usually done for decorative purposes, by those who find it attractive, but they may also be used cosmetically, to conceal a corneal leukoma, to mask pigmented areas of skin, or to color skin to look like the areola in mammoplasty.

Materials And Methods

E peptides corresponding to the human coronavirus 229E (HCoV-229E) E protein NVYHIYQSYMHIDPFPKRVIDF), GenBank accession number NP_073554, mouse hepatitis virus (MHV)-A59 E protein (MFNLFLTDTVWYVGQIIFIFAVCLMVT GenBank accession number NP_068673, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) full-length E protein (MYSFVSEETGTLIVNSVLLFLAFVVF SARS -CoV N-terminal E protein (MYSFVSEETGTLIVNSVLLFLAFVVFLLVTLAIL TALRLC), GenBank accession number NC004718, and infectious bronchitis virus (IBV) Beaudette strain E protein (MTNLLNKSLDENGSFLTALYIFVGFLALYLLGRA NGWKQ), GenBank accession number CAC39303, were chemically synthesized and purified, as described previously.13,14 The peptides were shown to contain full-length products by a variety of methods including, Western blot analysis with E protein specific antibodies, and mass spectral analysis.13,14

Thiazide diuretic 477

When antibiotics were introduced in the late 1940s. However, therapeutic vaccination today remains the standard of care for those believed to be infected with rabies and for babies born to mothers infected with hepatitis B virus. In diseases against which therapeutic vaccination does work, the vaccine retards early infection before the development of a natural immune response.

Top mentality See top

Topical microbicide An antibacterial or antifun-gal compound that can be applied directly to the lining of the vagina before intercourse to thwart sexually transmitted microbes that cause diseases such as gonorrhea, syphilis, genital herpes, chlamydia, hepatitis B, and HIV infections. Today, the development of safe, effective, female-controlled topical microbicides that will block the transmission of HIV and other STD agents is a global priority and a central focus of the STD research program of the National Institute of Allergy and Infectious Diseases (NIAID). The goal is to develop safe antimicrobial products that effectively fight a combination of infectious agents, whether they are viral, bacterial, or protozoan.

Vulvovaginal candidiasis See candidiasis

It is in phase ii trials for treatment of hepatitis c. It has been shown also to have effects on the overproduction of lymphocytes and their migration. This effect is believed to lower the inflammatory response of the liver. It is also being considered for use in immunosuppressive operations such as transplantation.

Pathophysiology of Porphyria Cutanea Tarda

The causes of iron overload in PCT are heterogeneous. Exogenous factors such as alcohol, diet, and viral hepatitis have been shown to increase hepatic iron deposition. Another important causative factor of iron overload in PCT is HH, a genetically inherited autosomal recessive disease of increased iron absorption.

Can Hiv Destroy Your Speech

Vaccine A suspension of infectious agents, or some part of them, given for the purpose of establishing resistance to an infectious disease. Vaccines stimulate an immune response in the body by creating antibodies or activated T lymphocytes (see t cell) capable of controlling the organism. The result is more or less permanent protection against a disease. There are four general classes of vaccines those containing living attenuated infectious organisms those containing infectious agents killed by physical or chemical means those containing living fully virulent organisms or those containing soluble parts of microorganisms. Vaccines are given by mouth or by injection. BCG (bacillus of Calmette and Guerin), cholera, DPT (diphtheria, pertussis, tetanus), hemophilus influenza B, hepatitis B, influenza, measles, mumps, plague, pneumococcal vaccine, polio, rabies, Rh immune globulin rubella (German measles), smallpox, typhoid, and yellow fever are examples of vaccines. The age administered...

Plantibiotics and Pharmaceutical Farming

Other transgenic plants have been used as well. Strains of GM corn produced the first commercially important plant-derived recombinant products, avidin and b-glucuronidase (both useful in diagnostic biochemical tests). Under experimentation or development are GM turnips and rice engineered to produce human interferon for treatment of hepatitis and some cancers transgenic potatoes to produce human lactoferrin, an antimicrobial agent GM corn altered to produce human aprotinin, a protein that might prove useful in transplantation surgery and GM canola plants to produce hirudin, an anticoagulant used to treat blood clots. Additional therapeutic proteins produced by GM plants include, among others, serum albumins, erythropoietin, and antitrypsin (of therapeutic potential in cystic fibrosis, liver diseases, and hemorrhages).

Liver function tests 287

Liver cancer is not commonly found in any population, but it is increased in HIV positive people. Particularly with the advent of haart, people are living longer and they must also handle the infections that can lead to liver cancer, such as hepatitis B or hepatitis C. Up to one-third of people with Kaposi's sarcoma will have some involvement in the liver, but this generally remains asymptomatic, being found only at autopsy. In lymphoma, the gastrointestinal tract and liver are the most common sites of involvement outside of the lymph nodes. Since the liver processes toxic compounds absorbed by the body, its cells are particularly sensitive to the side effects of medications. Many drugs used in AIDS therapy induce changes in liver enzymes or cause other impairments of liver function. Some common ones that may cause hepato-toxicity are Bactrim, Efavirenz, tuberculosis drugs, NNRTIs, and protease inhibitors. Various tests are available for liver disorders. These include tests for liver...

Glucose6phosphate dehydrogenase G6PD deficiency 201

Globulins Simple proteins found in the blood serum that contain various molecules central to immune system function. Immune globulins (IGs) make up preparations used for passive immunization vaccines for the prevention of several illnesses, including chicken pox (varicella zoster), hepatitis a, hepatitis b, rabies, tetanus, and measles. HIV glove In medical care gloves are used to prevent the contamination of an operative site with organisms from the person wearing the glove and to prevent pathogens from the patient from contaminating the health care worker. These factors are particularly important when the patient has a disease such as hepatitis b or AIDS. Medical gloves are generally made of latex. For those allergic to latex, gloves made of polyurethane are also manufactured for these purposes.

Targeting TLRs with specific ligands

Herpes Genitalis Discharge

Topical imiquimod therapy is used for the treatment of external genital and perianal warts caused by Papilloma virus infection 17 . The FDA has recently approved imiquimod for the treatment of actinic keratoses, and there is mounting evidence that imiquimod is an effective treatment of certain types of skin cancer 47, 48 . Resiquimod is a more potent analogue of imiquimod, and trials are under way to assess its use in treatment of genital herpes and hepatitis C virus 49 . Multiple Phase I human clinical trials have been designed to explore the safety and immunostimulatory properties of CpG ODNs administered alone, or in combination with vaccines, antibodies or allergens. Several Phase II studies are also underway to evaluate the therapeutic potential of CpG ODNs in the treatment of cancer, allergy and asthma, or as vaccine adjuvants. Studies have investigated the use of CpG ODNs to reduce allergic rhinitis and immunization of allergen mixed with CpG ODN,...

Microbiological Terrorism

Attention when the British government fined the Imperial College of London for failing to follow research guidelines and compromising public safety in its attempts to speed development of vaccines and drugs against the hepatitis C virus, which infects about 200 million people worldwide. Using recombinant DNA methods, researchers at the college had spliced key genes from dengue fever virus into the hepatitis virus, thereby creating a potentially deadly hybrid type of microbe. Thankfully, nothing bad came of this genetic faux pas.

Penicillinaseresistant Penicillins

In Australia, cholestatic hepatitis women predominate, age 65, rx mean 2 weeks, onset 3 weeks Irom starting rx (Ln Supplied in vials ticarciilin 3 gm, clavutanato Q I grtipeivial 4.5 5 mEqNa per gm Diarrhea due to clavulanale Rare reversible cholestatic hepatitis secondary lo clavulanale (AilM 156 1 327. 1990)_

Minigenome Constructs for Salmonid Rhabdoviruses

Increase Amount Plasmid

Thus, as a first step towards establishing a reverse genetics system for salmonid rhabdoviruses, an IHNV-derived cDNA plasmid construct, pIHNV-CAT(-), in which all the IHNV coding regions were deleted and replaced by the chloramphenicol acetyltransferase (CAT) reporter gene in negative sense, was engineered. As shown in Fig. 1A, a T7 promoter sequence and a hepatitis 6 virus antigenome ribozyme sequence (Perrota and Been 1991) were fused to the IHNV trailer L-gene end and leader N-gene start sequences, respectively The use of a hepatitis 6 virus antigenome ribozyme sequence allowed the generation of an RNA minigenome ending at the authentic extreme nucleotide of the 3' end IHNV genomic RNA, through the autocatalytic activity of the ribozyme. The use of a ribozyme sequence to generate the exact terminus of an RNA genome was first reported for Nodavirus and VSV RNAs (Ball 1992 Pattnaik et al. 1992). Through in vitro RNA polymerase-driven transcription of the pIHN-CAT(-) plasmid...

Deterministic Patterns

We discussed an enzyme of major pharmacological interest in the Introduction, the protease from the hepatitis C virus. The identification of its function was possible because of the observation that its sequence contains a deterministic pattern, and this observation provided the impetus for years of study directed toward inhibiting the activity of the hepatitis C virus, which might, in the future, provide a cure for hepatitis C. Proteases, as we mentioned, are enzymes that catalyze the cleavage of peptide bonds. The hepatitis C virus NS3 protein belongs to a class of proteases in which the amino acid that performs the catalysis is a serine they are collectively known as serine proteases. A large evolutionarily related family of these enzymes is designated chymotrypsin-like, from the name of one of its members, and is very well studied. Several sequences, structures, and biochemical characterizations are available for members of this family. They are distinguished by the presence of...

Envelope Switching Flexibility of Rhabdovirus Envelopes

HCVE1E2p7 HCVE2a HCVE1 orE2a(tsO45)'d HCV E1c'd HCVE1 or E2aandb,E1 andE2b HCV C E1 E2a gous surface glycoprotein was not only incorporated into the virions but was active in receptor binding and subsequent membrane fusion. HIV-1 gp160 surrogate VSV and RV able to amplify only on cells expressing the HIV-1 receptor confirmed the potential of rhabdoviruses in retargeting (Johnson et al. 1997 Foleyet al. 2002). An increasing number ofVSV and RV pseudotype and surrogate viruses carrying glycoproteins from a variety of viruses, including, for example, Ebola virus or hepatitis C virus (HCV), have been used in the following for purposes of retargeting and for presentation of antigen on the surface of virus particles (Table 2).

Principles of Human Tumor Virology

Viruses containing either RNA or DNA genomes can cause tumors, and studies of tumor viruses have provided important insights into basic molecular and cellular processes. Retroviruses are the only class of RNA viruses that are known to cause tumors in animals, whereas several different families of DNA viruses can cause tumors. Four DNA viruses are known to cause or contribute to the development of cancer in humans Epstein-Barr virus, high-risk types of human papillomaviruses, hepatitis B virus, and human herpesvirus-8, which is also known as Kaposi's sarcoma herpesvirus (KSHV). Two RNA viruses are etiologically involved in human cancer human T lymphotropic virus type 1 and hepatitis C virus. The identification of human tumor viruses has generated optimism that it will be possible to develop improved methods to prevent and treat certain cancers in humans. Vaccination and other public health measures that prevent infection or transmission can be expected to reduce the incidence of the...

Virucidal Effect Of A Newly Developed Nickel Alloy On Mouse Coronavirus

A newly recognized disease, severe acute respiratory syndrome (SARS), was first reported in China in February 2003. A few months after the first outbreak of SARS, the disease was transmitted worldwide in more than 20 countries of Asia, Europe, and North America. A novel coronavirus (CoV) was detected in patients with SARS and identified as causative agent. Civet cats have been suspected as natural host of SARS CoV, which infects human beings by oral or intranasal route the infected hosts sheds the virus into air through respiratory route and or feces from intestinal tract. The routes of entry and shedding of SARS CoV is similar to those of mouse hepatitis virus (MHV mouse CoV), which causes a variety of diseases such as diarrhea, hepatitis, encephalitis, and wasting syndrome of nude mice.

Asymptomatic infection

Asymptomatic infection An early stage of an infection in which the patient has no physical symptoms. Long-term asymptomatic HIV infection has been associated with high levels of antibodies to HIV core proteins and the absence of hepatitis b markers. No association with unsafe sex has been found. Additionally, no association between psychological coping skills and slower disease progression has been found. Known side effects of atazanavir include diarrhea and elevated levels of bilirubin, a liver enzyme. Diarrhea was experienced by about 30 percent of research subjects. Bilirubin is the liver enzyme that causes jaundice. A person with high levels of bilirubin may experience a yellowing of the eyes, nails, and skin. The high bilirubin levels were not associated with any liver damage in patients. Research has shown that patients with HBV or HCV coinfection did not suffer liver problems from the rise in bilirubin levels. In some studies hyperbilirubinemia was experienced by 50 percent of...

Civil Rights Act of 1991 105

Infection progresses to cirrhosis in 20 percent of patients. In some persons with chronic HCV infection liver cancer develops. The effect of HIV on HCV is a two to three times more rapid progression to cirrhosis than in HIV-negative individuals. More HIV-positive persons also have cirrhosis and higher mortality rates than their HIV-negative counterparts. The ability to lower HIV viral load to undetectable levels has no effect on HCV, and protease inhibitors are not active against HCV. Treatment for HCV may have potential impact on the coinfected state. To date there is no vaccination for HCV. The gold standard treatment at the present time for HCV is combination therapy. See hepatitis.

Alveolar proteinosis See pulmonary alveolar

Amebiasis A parasitic intestinal infection caused by tiny unicellular microorganisms called amoe-bas, especially Entamoeba histolytica. Many patients remain asymptomatic, but the disease is generally characterized by dysentery with diarrhea, weakness, prostration, nausea, vomiting, and pain. one serious complication is amebic hepatitis. amebic hepatitis Amebic abscess of the liver caused by infection with Entamoeba histolytica.

Treatment of PCT and HH

In general, all patients with PCT should have their underlying disease treated (HCV, HIV), and should avoid precipitating factors such as alcohol, medications drugs, and iron supplementation. Avoidance of excess sunlight is advised until clinical remission is achieved. Phlebotomy remains a primary treatment, even in cases in which the serum iron or ferritin is not necessarily elevated. Urine porphyrins should be monitored until biologic remission is achieved, typically within a 6-month period of treatment. In cases where phlebotomy may be contraindicated, low-dose chloroquine therapy can be used in addition to or in lieu of phlebotomy.1 Chloroquine complexes with porphyrins, assisting in their mobilization from the liver.3 A low dosage of chloroquine is important in these patients because of the risk for transient but occasionally severe hepatitis, and the possibility for worsening photosensitivity in PCT patients. In patients with PCT and with mutations of HH, treatment guidelines...

Young Girl with a Bloody Knee Effusion

Based on a factor VIII activity of 4 and a normal von Willebrand factor (vWF) activity, a diagnosis of moderate hemophilia A was made. She was treated with whole-blood replacement therapy from private donors and recovered. At age 4, she experienced a severe bleed into the right ankle joint and was treated with a commercial factor VIII concentrate prior to the era of mandatory testing of plasma for pathogens and viral inactivation treatment of concentrates. Approximately one month later, she presented with lethargy, nausea, vomiting, and icteric sclerae. A diagnosis of non-A, non-B viral hepatitis was made and she was given a guarded prognosis for recovery. Over the course of the As an adult, the patient and her parents underwent genetic testing for factor VIII mutations. She was heterozygous for an intron 22 inversion that was not detected in either parent. Routine laboratory studies at the time revealed immunity to hepatitis C with undetectable viral load by polymerase chain...

Diagnostic investigations

Diagnosis of MC syndrome is based on both clinical and laboratory findings. Given its clinical polymorphism, a single manifestation (skin vascu-litis, hepatitis, nephritis, peripheral neuropathy, etc.) is often the only apparent or clinically predominant feature, so that a correct diagnosis might be delayed or overlooked entirely (Ferri et al., 2002a, 2004). other minor features can be used to classify those patients with 'incomplete' MC syndrome (Ferri et al., 2002a). Finally, MC can be classified as 'essential' or 'secondary' with regard to the presence absence of well-known triggering factor(s) following the striking association between MC and HCV infection, the term 'essential' can be referred to only a minority of patients (

Middle Aged Alcoholic with Jaundice and Ascites

A 51-year-old white male came to the Emergency Department complaining of weakness, lack of appetite, shortness of breath, and abdominal distension. He was a known alcoholic who had failed detoxification programs several times in the past and continued to drink approximately one pint of vodka or gin per day. Eight months before presentation he had been admitted to another hospital with alcoholic hepatitis and at that time had suffered severe withdrawal symptoms. Soon after discharge, however, he resumed drinking. Two weeks prior to the current presentation, he developed a cold and lost his appetite. He began taking over-the-counter ibuprofen for non-specific pains and continued to drink. When he experienced profound weakness, shortness of breath, and abdominal bloating, he asked his girlfriend to take him to the hospital. Anti-hepatitis C Ab

Novel therapeutics targeting the trail cell death pathway

The absence of detectable apoptosis activity in normal cells after treatment with soluble TRAIL has been shown for primary cells from the lung, bone, liver, endothelium breast, brain, and kidney (12,47). Importantly, short-term treatment of mouse, monkey, and chimpanzee with soluble, recombinant, Zn2+-stabilized TRAIL has demonstrated the tolerabil-ity of the ligand. No detectable toxicities were observed in these nonclinical safety studies. Earlier forms of TRAIL were generated with epitope tags (126). These epitope tagged forms also enhanced the toxicity of TRAIL on normal cells. HIS-tagged, leucine-zipper or antibody crosslinked forms of TRAIL have demonstrated the ability to induce apoptosis in normal hepatocytes in vitro (49,127). TRAIL can induce apoptosis in bacterially activated hepatocytes, in stellate cells from the liver and pancreas, or in mouse models of hepatitis or pancreatitis (50,128). Membrane-bound TRAIL has been shown to induce liver damage in...

Heterologous Gene Expression in Yeast

In recent years, there has been a trend to move from S. cerevisiae to P. pastoris for production of recombinant proteins. This trend is caused by the preference of P. pastoris for respiratory growth and the extremely high level of expression obtained when heterologous gene expression is driven by the alcohol oxidase gene (AOX1) promoter (2). Over 100 heterologous proteins from bacteria to humans have been successfully expressed in P. pastoris examples include human insulin (3), human amyloid precursor protein (APP 4), hepatitis B surface antigen (5) and human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120 (ENV 6). In considering expression strategies using either yeast species, we begin with a general consideration of heterologous gene expression in these organisms before moving on to the procedures for their introduction, maintenance, and expression. Finally, we suggest methods for efficient recovery of the recombinant protein and its concentration prior to...

Universal precautions In 1985 the centers for

Likely to be contaminated with blood. The precautions recommend that because the unpredictable nature of exposures encountered by emergency and public safety workers may make differentiation between hazardous and nonhazardous body fluids difficult or impossible, these workers should treat all body fluids as potentially hazardous when they encounter them. Part I of the CDC's published Guidelines for Prevention of Transmission of Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) to Health-Care and Public-Safety Workers addresses disinfection (of equipment and surfaces), decontamination (of hands, soiled linen, protective clothing), and disposal (of needles and sharps, infective waste). Fire and emergency medical procedures and equipment are also addressed (gloves, masks, eyewear, gowns, resuscitation equipment), as are other considerations, such as handling bodies, autopsies, and forensic requirements. Part II, Recommendations for Preventing Transmission of Human...

Exogenous TLR ligands implicated in the progression of atherosclerosis

A number of infectious agents have been associated with atherosclerotic cardiovascular disorders, including Chlamydia pneumoniae 47 , Helicobacter pylori 48 , cytomegalovirus (CMV) 49 , Epstein-Barr virus 50 , human immunodeficiency virus 51 , herpes simplex viruses (HSV)1 52 , HSV2 53 , and hepatitis B 54 and C 55 . More recent models emphasize the relationship of atherosclerosis to total infectious burden rather than specific pathogens 56 . The above mentioned infectious agents or derived PAMPs have been shown to signal through one or more TLRs (Fig. 2). Furthermore, the recently identified cytoplasmatic PRR NOD1 (nucleotide-binding oligomerization domain) has been proposed to be involved in Chlamydia and Helicobacter induced signal transduction 57, 58 . It is intriguing to

Obese Woman with Persistently Abnormal Liver Enzymes

The patient denied jaundice, pruritus, and change in appetite, but reported a 6-7-lb weight gain. Additionally, she denied a history of hepatitis and any other liver or gallbladder disease in the past. The patient never smoked, used alcohol, or illicit drugs. There was no history of blood transfusions, tattoos placed, or multiple sexual partners. She had not been recently exposed to anyone with known viral hepatitis. Her family history was positive for hypertension, heart disease, and diabetes mellitus, but negative for liver and biliary tract disease. Her current medications included metformin, glipizide, losartan, metoclo-pramide, and aspirin. She used no over-the-counter medications, including herbal or dietary supplements. Anti-hepatitis C Ab

Aflatoxins and how they cause cancer

At high doses the interaction with protein can cause immediate damage to the liver (acute hepatitis). At lower doses interaction with DNA will lead to mutations in the genetic code which can cause cancer. Laboratory studies in experimental animals like rats have revealed that aflatoxin Bj can cause liver cancer, and the products of the reactive metabolites of aflatoxin can be detected in the blood of these animals. Furthermore the same metabolites have also been detected in the blood and urine of humans eating fungus-contaminated food in China, for example. Most recently a correlation has been shown between exposure to these fungal toxins, as indicated by metabolites of aflatoxins bound to protein in blood samples, and liver cancer in humans in China. A specific mutation in the genetic material has been detected in people exposed to aflatoxin. An important factor in determining susceptibility may be individual variation in the metabolism of aflatoxin. A significant risk factor in...

Immune system abnormality

Immune-based therapies Treatments intended to have their effect by enhancing the general activity of the immune system or by specifically modulating the activity of some of its components. They may be used to help restore a person's general immune responsiveness, suppress specific viral infections, or counteract the bone marrow toxicity of some of the drugs used for HIV-related conditions. Hope is placed in these substances because they promise to reduce the pill burden of HIV patients. Drugs used in such therapies include preparations of antibodies and drugs that stimulate production of red and white blood cells, cytokines, and other immune modulators. Vaccines are also immune therapy drugs. Specific drugs used in immune-based therapies include cyclosporine, cytomegalovirus immune globulin, hepatitis B immunoglobulin, interleukin-2 (IL-2 or Proleukin), HIV-1 immunogen (Salk Vaccine or

Clinical manifestations

Cryoglobulinemia and chronic hepatitis C infection have been associated with chronic relapsing CSVV (Martinez-Taboada et al., 1997). The prognosis of isolated CSVV is generally quite good. A case series performed in a private practice by Ekenstam and Callen (1984) reported on 82 patients with CSVV, 51 of which had systemic