Hepatitis after the use of germander,a herbal remedy.

The authors report two cases of hepatic injury associated with the ingestion of germander, a herbal medicine used to facilitate weight loss. In both patients, hepatitis characterized by asthenia, jaundice and a marked increase in serum amino-transferase levels occurred after 5 to 6 months of germander use. The jaundice disappeared within 8 weeks after germander use was stopped, and the overall outcome was favourable. The subsequent resumption of germander therapy by one patient was soon followed by the recurrence of hepatitis. Similar reports from France have led to the banning of germander in that country. Like several other herbal remedies, germander may be hepatotoxic, and many herbal medicines may not be as safe as the public generally assumes.     

IgM antibody against hepatitis B core antigen (IgM anti-HBc): diagnostic and prognostic significance in acute HBsAg positive hepatitis.

IgM antibody against hepatitis B core antigen (IgM anti-HBc), a marker of recent hepatitis B virus infection, was sought by radioimmunoassay in sera diluted 1/4000 from 376 patients presenting to four centres in Italy with acute, apparently type B hepatitis (hepatitis B surface antigen (HBsAg) positive). In 320 patients (85%) a positive IgM anti-HBc test result confirmed that hepatitis was due to primary infection with hepatitis B virus. In the remaining 56 patients absence of the IgM marker indicated that they were previously unrecognised long term carriers of HBsAg. Further serum analysis often showed delta infection and occasionally hepatitis A or cytomegalovirus infection as the true cause of their illness. After six to eight months circulating HBsAg persisted in 38 of 45 patients (84%) without IgM anti-HBc but in only six of 150 patients (4%) with the IgM antibody (p less than 0.0001). A negative IgM anti-HBc test result in patients with acute HBsAg positive hepatitis points to a factor other than hepatitis B virus as the cause of the liver damage and predicts the carriage of HBsAg.     

A specific complement-fixation test for human hepatitis a employing CR326 virus antigen. Diagnosis and epidemiology.

A specific diagnostic complement-fixation test for hepatitis A antibody in human serum was described employing livers of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A CF antibody shortly after the onset of illness and this persisted thereafter. Good agreement was noted in the development of CF and neutralizing antibodies in hepatitis A cases. Hepatitis A was shown to occur in a person with hepatitis B antigenemia and hepatitis B occurred in persons with hepatitis A antibody. Most persons with hepatitis A who were tested, but none of those with hepatitis B, developed increased anticomplementary activity in their sera at the time of onset of illness. At least one patient with hepatitis A developed antibody against normal liver that persisted. The possible inplications of this in relation to pathogenesis and to non-specific diagnostic tests in hepatitis were discussed. A limited epidemiologic study of a family outbreak of hepatitis in Costa Rica and of a group of young adults in our epidemic country acquire their infections at an early age and are immune thereafter; persons in areas of relatively low incidence may proceed into adulthood without experience with hepatitis A. The CF test should provide an excellent tool for diagnosis and for epidemiologic investigation of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture.     

Toxic hepatitis induced by a herbal medicine: Tinospora crispa

Herbal remedies are becoming increasingly popular in many countries. Tinospora species (Menispermaceae) is commonly used as a herbal medicine in South Asia, but very few toxic effects have been described. We report a case of acute hepatitis associated with chronic use of high doses of Tinospora crispa.A 49-year-old male with chronic low back pain bought a herbal medicine at a market in Vietnam that was supposed to be Tinospora crispa, and started to take 10 pellets per day. He had no medical history and did not take any other drugs or toxins. Four weeks later; he developed dark urine and pale stools, associated with asthenia and right hypochondrial pain. Two months after starting treatment, he was referred to the hepatology department with jaundice. Blood tests showed aspartate aminotransferase: 1.169 IU/l, alanine aminotransferase: 2.029 IU/l, total bilirubin: 20.47 mg/dl, direct bilirubin: 13.29 mg/dl, and γ-glutamyltransferase: 243 IU/l. Viral and autoimmune hepatitis were eliminated. Upper abdominal ultrasound was normal. Histopathological findings were consistent with a toxic reaction. The herbal medicine was stopped on admission and the patient fully recovered without treatment, with normal liver function 2 months after the acute episode. Tinospora crispa was clearly identified in the pellets by microscopic analysis of the botanical characters combined with chromatographic fingerprints.The use of herbal medicines containing Tinospora crispa can induce toxic hepatitis. Recovery can be complete after discontinuation. This case highlights the risk associated with traditional herbal remedies.     

Partial nonstructural 3 region analysis of hepatitis C virus genotype 3a

Molecular Biology Reports - The hepatitis C virus (HCV) is a major cause of illness around the world. HCV genotype 3a is the most prevalent genotype in Thailand. Direct-acting antiviral (DAA) drugs...     

The hepatitis B virus and its DNA polymerase: The prototype three-D virus

Summary The hepatitis B virus (HBV), the causal agent of serum hepatitis, has a diameter of 42 nm and is comprised of an outer surface coat and a 27 nm core. A unique DNA-dependent DNA polymerase is associated with the core of the virus. The core also houses a circular DNA that contains both double-stranded and single-stranded regions. In the endogenous reaction, the DNA polymerase repairs the single-stranded gaps of the viral DNA. The surface protein of the virus, called hepatitis B surface antigen, contains both lipid and carbohydrate, and is often present in particulate form in the blood of infected patients. In Asia and Africa HBV infection is associated with subsequent development of primary hepatocellular carcinoma. Although most patients recover completely from acute illness, the hepatitis B virus may cause chronic infection. Recently, a virus similar to human HBV was discovered in woodchucks. HBV has not yet been propagated in a cell culture system and the mode of replication of this unusual virus in hepatocytes is still moot. Although reliable therapy has not yet been provided, the problem of this world-wide infection has led to many interesting approaches to both vaccine production and anti-viral chemotherapy.     

Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research

Seville orange (Citrus aurantium) extracts are being marketed as a safe alternative to ephedra in herbal weight-loss products, but C. aurantium may also have the potential to cause adverse health effects. C. aurantium contains synephrine (oxedrine), which is structurally similar to epinephrine. Although no adverse events have been associated with ingestion of C. aurantium products thus far, synephrine increases blood pressure in humans and other species, and has the potential to increase cardiovascular events. Additionally, C. aurantium contains 6',7'-dihydroxybergamottin and bergapten, both of which inhibit cytochrome P450-3A, and would be expected to increase serum levels of many drugs. There is little evidence that products containing C. aurantium are an effective aid to weight loss. Synephrine has lipolytic effects in human fat cells only at high doses, and octopamine does not have lipolytic effects in human adipocytes.     

Quinine-induced granulomatous hepatitis.

Many adverse reactions to quinine have been reported. A 65 year old woman taking quinine sulphate for nocturnal leg cramps presented for investigation of episodes of malaise, fever, nausea, vomiting, and polyarthralgia. Granulomatous hepatitis was diagnosed, for which no common cause was found. She was challenged with quinine sulphate; within hours her temperature had risen and her symptoms returned; transaminase activities rose within 48 hours, as did erythrocyte sedimentation rate. After withdrawal of the drug symptoms abated and transaminase activities returned to normal. The biochemical response to challenge with quinine implicates the drug as the cause of the liver disturbances. Quinine should be added to the list of drugs known to cause granulomatous hepatitis and should be considered in cases where symptoms are episodic or where no other cause is apparent.     

Production and characterization of the B chains of mistletoe toxic lectins

Mistletoe toxic lectins consist of two polypeptide chains: an enzymatically active A chain, which is a toxic component, and a disulfide-bonded B chain, which confers the lectin properties on the total molecule. Mistletoe leaves contain three toxic lectins encoded by three genes. The B chains of these lectins were overproduced in Escherichia coli in a soluble form. The recombinant proteins bound with asialofetuin, but had substantially lower affinity for simple sugars D-galactose and N-acetyl-D-galactosamine as compared with the natural proteins. The functional properties of the B chains strongly depended on the storage conditions (salt concentration and the presence of galactose); the dependence was explained by structural instability of nonglycosylated recombinant proteins. The lectin activity of one of the recombinant B chains was close to that of the native protein, which was attributed to the lack of N-glycosylation sites in the latter.     

Spatial variation in impacts of brushtail possums on two Loranthaceous mistletoe species

Browsing by introduced brushtail possums is linked to major declines in mistletoe abundance in New Zealand, yet in some areas mistletoes persist, apparently unaffected by the presence of possums. To determine the cause of this spatial variation in impact I investigated the abundance and condition (crown dieback and extent of possum browse) of two mistletoes (Alepis flavida, Peraxilla tetrapetala) and abundance and diet of possums in two mountain beech (Nothofagus solandri var. cliffortioides) forests in the central-eastern South Island of New Zealand. Mistletoe is common and there are long-established uncontrolled possum populations in both forests. Mistletoes were abundant (216?1359 per hectare) and important in possum diet (41?59% of total diet), but possum density was low (c. 2 per hectare) in both areas. Possum impacts were slight with low browse frequencies and intensities over much of the study sites. However, impacts were significantly greater at a forest margin, where possum abundance was highest, and at a high-altitude site where mistletoe density was lowest. Mistletoe crown dieback was inversely proportional to intensity of possum browsing. These results suggest that the persistence of abundant mistletoe populations at these sites is due to mistletoe productivity matching or exceeding consumption by possums in these forests of low possum-carrying capacity, rather than low possum preference for the local mistletoe populations.     

Immune-indian ink method for detection of hepatitis A associated antigen and antibody.

TIndian-ink grains coated with commercial gamma globulin (immune-Indian-ink) were agglutinated by 3 percent of sera from healthy volunteer blood donors; by 4 percent of those from hospital staff in contact with patients suffering from hepatitis; and by 10 percent of those from patients with viral diseases other than hepatitis, In contrast, the rate of positive reactions was 86 percent in the case of sera taken from patients in the acute phase of an illness diagnosed as hepatitis A on the basis of epidemiological and clinical data. Investigation of serum samples taken serially from patients positive in the acute phase of illness revealed that the immune-Indian-ink agglutinating factor does not persist for long in majority of cases. Two months after discharge from the hospital it was present in 18 percent of the patients only. The reaction proved negative when a limited number of cases diagnosed as hepatitis B were investigated. The immune-Indian-ink agglutinating factor was inhibited by all but one of 36 sera taken in the convalescent phase from patients with a diagnosis of hepatitis A. Some sera displaying agglutination with immune-Indian-ink gave a reaction with uncoated Indian-ink, too. Efforts to free the sera from non-specific agglutinating factor by starch-block electrophoresis have led to partial success. Fractionation on Sephadex G-200 columns suggested that in molecular weight (or particle size) the immune-Indian-ink agglutinating factor is smaller than HBsAg and larger than the non-specific agglutinating factor. On the basis of these results it is assumed that the immune-tindian-ink reaction is suitable for detecting an antigen tentatively called IH chi Ag and its antibody (IH chi Ab) specific to hepatitis A.     

Obtaining and characterization of the B-chains of mistletoe toxic lectins

Mistletoe toxic lectins consist of two polypeptide chains: an enzymatic A chain, the toxic component, is joined by disulfide bond to a B chain conferring the lectin properties to the complete molecules. Mistletoe leaves contain three of toxic lectins encoded by three genes. The three B chains were produced in Escherichia coli in a soluble form. The recombinant proteins were found to bind to asialofetuin but in contrast to native proteins could be competed to a less extent by simple sugars D-galactose and N-acetyl-D-galactosamine. The functional properties of the proteins were strongly influenced by storage conditions such as salt concentration and simple sugar presence thus indicating an unstable folding. The lectin activity of one of the recombinant B chains was most close to the native protein that possibly results from the absence of N-glycosylation.     

光合细菌转化槲寄生制剂抗肿瘤活性初步研究

通过急性毒性实验比较各制剂组的毒性,MTT法考查各制剂组对人体外癌细胞的生长抑制率,体内实验考查各制剂组对移植性肿瘤的抗肿瘤作用。结果表明,光合细菌（PSB）制剂组、光合细菌转化槲寄生（PSBT）制剂组无毒,PSBT降低了槲寄生的毒性;PSBT制剂组对人体外癌细胞BGC-803、A2780、KB和小鼠体内S180肉瘤、H22肝癌、Lewis肺癌均具有明显抑制作用,且抗肿瘤活性高于其他制剂组。     

Use of Computer-assisted Model in Diagnosis of Drug Hypersensitivity Jaundice

Of 374 patients with jaundice seen in the liver unit over a four-year period 21 were finally thought to be hypersensitive to one of seven different drugs. The clinical, laboratory, and histological features were often difficult to distinguish from those of viral hepatitis, tumour of the extrahepatic biliary tree, or primary biliary cirrhosis. A computer-assisted diagnostic model made use of minor differences, and made a correct diagnosis in all patients. Even when information about drug ingestion was left out it was still correct in 81% of patients. Sixty-four other patients gave a history of ingestion of potentially hepatotoxic drugs of whom 62 were correctly diagnosed by the computer. In the complete series of 374 patients only two were incorrectly computed to have drug jaundice when there was no history of drug ingestion.Two additional patients became jaundiced after exposure to drugs, but were found to have primary biliary cirrhosis.     

Acute lindane poisoning with development of muscle necrosis.

A 35-year-old man ingested food contaminated with lindane, an insecticide containing almost pure gamma hexachlorocyclohexane. Grand mal seizures and severe acidemia developed rapidly. The seizures recurred for nearly 2 hours, then ceased. In addition, the patient had muscle weakness and pain, headaches, episodic hypertension, myoglobinuria, acute renal failure and anemia. Pancreatitis developed 13 days after the ingestion of lindane. A muscle biopsy on the 15th day of illness demonstrated widespread necrosis and regeneration of muscle fibres. The patient''s condition improved and he was discharged 24 days after the onset of his illness. During the year following the poisoning the patient noted difficulty with recent memory, loss of libido and easy fatigability. One year after lindane ingestion the results of physical examination, including those for muscle power and bulk, were normal.     

Characterization and correlation of DC electrical penetration graph waveforms with feeding behavior of beet leafhopper, Circulifer tenellus

Feeding behavior of beet leafhopper, Circulifer tenellus (Baker) (Homoptera: Cicadellidae), was studied with a DC electrical penetration graph. Nine different electrical penetration graph waveforms associated with feeding were identified and characterized. Waveforms were correlated with specific feeding behaviors using a number of techniques, including high magnification video recording, honeydew analysis, stylectomy, and histological processing. Waveforms were grouped into three phases based on feeding behavior: pathway phase (waveforms A, B1, B2, and C), non-phloem ingestion phase (waveform G), and phloem phase (waveforms D1, D2, D3, and D4). No ingestion was found to occur during waveforms A, B1, B2, and C. Waveform G was associated primarily with ingestion of xylem sap and occasionally with ingestion of mesophyll sap. Stylet tips were located in phloem during waveforms D1, D2, and D3, and waveforms D2 and D3 were correlated with ingestion of phloem sap. Waveform D4 probably also plays a role in phloem ingestion, because D4 is very brief and always occurs embedded in either waveform D2 or D3. In contrast to most other homopteran insects, rate of honeydew production (and hence rate of ingestion) was much lower on phloem than on xylem. More rapid rates of ingestion are expected on phloem, because its high turgor pressure drives sap into the feeding insect whereas the negative pressure of xylem sap is expected to cause a slow rate of ingestion. The very slow ingestion rate of beet leafhopper feeding on phloem suggests that it is not able to exploit the high turgor pressure of phloem to achieve the high rate of ingestion that is typical of phloem ingestion by other insects.     

Factitious diarrhea

The causes of diarrhea are legion. In any diagnostic problem a factitious etiology must be carefully considered. Three cases are presented, in two of which daily ingestion of prunes and prune juice was found to be the cause of chronic diarrhea. In the third case an edible oil product, Coffee Rich, was determined by dietary manipulation to be the cause, carrageenan possibly being the laxative principle.     

Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations.

A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000.     

Nonspecific indices of cellular and humoral immunity in viral hepatitis A and B patients

The article deals with the comparative study of the state of phagocytosis, as manifested by the ingestion of bacterial cells and by the results of the specific lupus erythematosus test, in 65 patients with acute viral hepatitis A and 45 patients with acute viral hepatitis B; these patients were also compared with respect to the presence of the markers of antigenemia and the state of their nonspecific immunity, determined by the level of serum immunoglobulins.     

Magnetic immunoseparation PCR assay (MIPA) for detection of hepatitis a virus (HAV) in American oyster (Crassostrea virginica)

In order to detect the low numbers of hepatitis A viral (HAV) particles which may potentially be present in food and cause a serious illness, an original procedure which combines immunomagnetic separation and PCR is described. The use of streptavidin magnetic beads coated with biotinylated human anti-HAV IgG allows virus capture and the removal of the RT-PCR inhibitory compounds which usually are present in shellfish extracts. Following immunomagnetic capture, the separated HAV were lysed, the beads discarded, and the supernatant containing the viral RNA subjected to the RT-PCR protocol. Levels of HAV ranging from 10 to 10⁵ pfu were successfully detected in artificially contaminated samples of shucked American oyster ( Crassostrea virginica ).