Elevated Serum Aspartate Aminotransferase Research Articles

Extremely Elevated Lactate Dehydrogenase and Aspartate Aminotransferase Level as an Indicator of Tumor Lysis during Bortezomib Treatment in a Multiple Myeloma Patient: Case Report.

Bortezomib has been shown to increase the response rate, time to disease progression, and overall survival in patients with relapsed-refractory multiple myeloma(MM). We currently treated a refractory MM patient and observed extremely elevated lactate dehydrogenase(LDH) and aspartate aminotransferase (AST) levels during bortezomib treatment, but without the abnormal serum electrolyte concentrations and elevated uric acid level. A 67 years old female was admitted to our hospital. She has been suffered with fatigue, lumbar myalgia, dizziness and difficulty in ambulation since Nov 2005. She was found renal inadequacy and intermediate anemia and was diagnosed with stage III MM, IgG type on bone marrow pathology, immunoglobulin analysis and X-ray examination. The disease was not controllable after 3 cycles of VAD regimen (vincristine, adriamycin and dexamethason). She had severe chest and back pain and was on morphine. Bone marrow morphology showed 32 percent plasma cells and her immunoglobulin G (IgG) level was 85g/L, microglobulin β2 level over 10000 ng/ml and creatinine 310.3mmol/L. She was also with hypercalcinemia and elevated serum LDH and AST transaminase level. Bortezomib therapy was considered with her refractory MM in disease progression and deterioration. Bortezomib at 1.3 mg/m2 IV days 1, 4, 8, 11 were planned to be administered in the first three weeks, in combination with dexamethazone at 40 mg on the same days. And a diphosphonate regimen was administered simultaneously. Hydration and alkalinization were initiated one day before the administering of chemotherapy. She was also given allopurinol prophylactically. She was suffered with severe debilitation and mild diarrhea after the second dosage of bortezomib. Gradually elevated LDH and AST were observed, with an extremely high point at 18666 and 9551 respectively on day 9 (table 1). LDH isoenzymes analysis showed that tumor-derived LDH3 and LDH4 were dramatically increased. AST isoenzyme analysis demonstrated elevated serum AST level, with normal level of mitochondria-derived AST level. Although her serum phosphate level was mild elevated and the calcium level was decreased, but the serum potassium, uric acid levels were normal. This could be the effect of diphosphonate regimen. The third and fourth doses of bortezomib were delayed for one week. Her chest and back pain was relieved shortly after the combination therapy. And only 1 percent of plasma cells were found on bone marrow smear prepared on day 20. Her IgG level decreased steadily and it was 19.5g/L on day 28. The microglobulin β2 level was 7200 ng/ml and creatinine was 173 mmol/L. She was still with elevated serum LDH and AST transaminase levels at 1129 and 324 respectively on day 28. We concluded that combination therapy with bortezomib and dexamethazone is very potent and effective in this refractory MM patient. The response is dramatically prompt with rapid tumor lysis demonstrated by extremely elevated LDH and AST level in this case. Carefully prophylactical measurement is recommended for patients under bortezomib treatment to prevent tumor lysis syndrome, a life-threatening metabolic emergency.Dynamic changes of LDH and AST level during bortezomib treatmentLDH(IU/L)AST(u/L)day 0915529day 21022539day 550323120day 7186669551day 8147066090day 973543575day 1056023704day 1148383324day 1328471220day 142529842

Effects of trapidil on renal ischemia-reperfusion injury

There is increasing evidence to suggest that reactive oxygen and nitrogen species play a role in the pathogenesis of renal ischemia-reperfusion (I/R) injury. This study was designed to determine the possible protective effects of trapidil treatment against oxidative and nitrosative tissue injury of kidney induced by I/R. A renal I/R injury was induced by a left renal pedicle occlusion by ischemia for 45 minutes, followed by 1 hour of reperfusion with contralateral nephrectomy in I/R and I/R + trapidil groups. Trapidil (8 mg/kg intravenously) was administrated immediately before reperfusion phase. At the end of the reperfusion period, rats were killed. Then, renal tissue samples were taken for biochemical analysis and histopathological evaluation, and blood samples were obtained to determinate serum urea, aspartate aminotransferase (AST), and tumor necrosis factor– α (TNF- α) levels. Ischemia-reperfusion injury caused significant increases in myeloperoxidase activity and malondialdehyde and 3-nitrotyrozine levels in renal tissue and elevated serum urea, AST, and TNF- α levels. In addition, severe deterioration of renal morphology was seen in the I/R group. Trapidil treatment significantly reduced in biochemical parameters, as well as serum urea, AST, and TNF- α levels. Furthermore, renal tissue injury was markedly attenuated with trapidil treatment. These data suggest that reactive oxygen species and reactive nitrogen species play a causal role in I/R-induced renal tissue, and trapidil has a renoprotective effect against oxidative and nitrosative kidney damage.

Protective effect of dietary curcumin and capsaicin on induced oxidation of low‐density lipoprotein, iron‐induced hepatotoxicity and carrageenan‐induced inflammation in experimental rats

The beneficial influence of dietary curcumin, capsaicin and their combination on the susceptibility of low-density lipoprotein (LDL) to oxidation was examined in an animal study. Individually, both dietary curcumin and capsaicin significantly inhibited the in vivo iron-induced LDL oxidation, as well as copper-induced oxidation of LDL in vitro. The protective effect of the combination of curcumin and capsaicin on LDL oxidation was greater than that of individual compounds. This protective influence of spice principles was also indicated by the relative anodic electrophoretic mobility of oxidized LDL on agarose gel. In another study, rats injected with iron showed hepatic toxicity as measured by an increase in lipid peroxides and elevated serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase. Dietary curcumin, capsaicin and their combination reduced the activities of these enzymes, and lowered the liver lipid peroxide level, indicating amelioration of the severity of iron-induced hepatotoxicity. In yet another study, a comparison of the extent of carrageenan-induced paw inflammation showed that both dietary curcumin and capsaicin moderately lowered inflammation, while the spice principles in combination were more effective. Dietary curcumin and capsaicin significantly decreased the activity of 5'-lipoxygenase activity in the polymorphonuclear lymphocytes in carrageenan-injected rats, the decrease being even higher in the case of combination of these two spice principles. Results suggest that dietary curcumin and capsaicin individually are protective to LDL oxidation both in vivo and in vitro, to iron-induced hepatotoxicity and to carrageenan-induced inflammation. This beneficial effect was higher when the two compounds were fed in combination.

Acute cough

Acute cough

Toxicokinetic profile of swainsonine following exposure to locoweed (Oxytropis sericea) in naïve and previously-exposed sheep

AIM: To determine the toxicokinetic profiles of swainsonine (SW) in sheep previously (subacute) and not previously (acute) exposed to locoweed. METHODS: Twenty-nine wethers were stratified by body-weight (BW; 68.0 (SE 7.6) kg) and randomly assigned to one of six treatments. Treatments were: 0 (n=5), 0.4 (n=5), and 1.6 (n=5) mg SW/kg BW for Trial 1, and 0 (n=4), 0.2 (n=5), and 0.8 (n=5) mg SW/kg BW for Trial 2. Acute exposure in both trials included adaptation to blue grama (Bouteloua gracilis) hay for 14 days and no previous exposure to locoweed (i.e. SW), followed by administration of a single oral dose of SW prepared from an extract of locoweed, in the doses described above. Subacute exposure comprised ingestion of a blue grama and locoweed (428 μg SW/g locoweed) diet for 21 days in Trial 1 and 28 days in Trial 2, followed by removal from locoweed for 5 days, then an oral dose of SW, as above. Quantities of locoweed fed in the diet were adjusted to achieve the dose rates specified for each treatment. Blood samples were collected via jugular venepuncture twice daily for 3 days prior to initial exposure to SW and then every 7 days for the duration of the trials, to monitor serum alkaline phosphatase (Alk-P) and aspartate aminotransferase (AST) activities. For intensive sampling periods, SW was administered immediately following blood sampling at 0 h, and blood samples were collected at hourly intervals from 0–12 h, 3-h intervals from 15–24 h, 6-h intervals from 30–48 h, and 12-h intervals from 60–168 h. Concentrations of SW in serum and locoweed extract were determined using the α-mannosidase inhibition assay (detection limit = 25 ng/ml). Rates of absorption and elimination of SW from serum were calculated for each animal, using exponential curve fits of the concentration of SW in serum concentration vs time plots. RESULTS: In both trials, SW was detected in serum in all animals exposed to locoweed. Elevated (p<0.05) serum Alk-P and AST activities indicated that subclinical SW intoxication was induced during the subacute exposure phase. Calculated rates of elimination were faster (p<0.001) for the 1.6 vs 0.4 (Trial 1) and 0.8 vs 0.2 (Trial 2) mg SW/kg BW doses. Rates of elimination indicated that, in both trials, SW was removed from serum faster (p<0.06) following acute exposure than subacute exposure. Higher exposure rates to SW resulted in higher concentrations of SW in serum within a trial. CONCLUSIONS: Multiple compartments were involved in the kinetics of SW, and dose and previous exposure altered the toxicokinetics of SW. CLININCAL RELEVANCE: Should the true elimination half-life prove to be as high or higher than the 95 h demonstrated for the treatment using 0.4 mg SW/kg BW in Trial 1, then withdrawal periods for clearing SW from sheep should be >40 days (assuming 10 half-lives to clear the compound).

The Protective Role of Chinese Prescription Kangen-karyu Extract on Diet-Induced Hypercholesterolemia in Rats

This study was carried out to investigate the protective potential of Chinese prescription Kangen-karyu, comprising six crude drugs, on coronary heart disease which is the principal cause of morbidity and mortality worldwide. The diet-induced hypercholesterolemic rat model, which shows an elevation in low density lipoprotein (LDL) cholesterol and atherosclerosis, was employed. The control rats fed a diet of 1% cholesterol and 0.5% cholic acid showed the highest cholesterol levels in serum and feces relative to those fed a normal diet, however, the rats administered Kangen-karyu extract showed reductions in these levels without changes in liver cholesterol, indicating that the reduction of serum total cholesterol by Kangen-karyu extract probably arises from an increase in cholesterol excretion. Furthermore, the administration of Kangen-karyu extract significantly prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase, known as marker enzymes of liver damage. The elevated serum levels of LDL cholesterol were lowered, however, the high density lipoprotein cholesterol level was significantly elevated by Kangen-karyu extract and these were dose-dependent decreases in the atherogenic index to 15.2, 8.8 and 7.5 at oral doses of 50, 100 and 200 mg from the 19.4 control value, respectively. In addition, Kangen-karyu extract inhibited LDL oxidation in a dose-dependent manner, and the elevated level of thiobarbituric acid-reactive substances in control rats showed a decline by the administration of Kangen-karyu extract. The present study suggests that Kangen-karyu could play a protective role against hypercholesterolemia through the regulation of cholesterol levels and inhibition of lipid peroxidation.

Autoimmune Liver Disease in Three Children with Sickle Cell Disease

Autoimmune Liver Disease in Three Children with Sickle Cell Disease

Effect of garlic on isoniazid and rifampicin-induced hepatic injury in rats

To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid (ZNH) and rifampicin (RIF). Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic homogenate was administered orally half an hour before the INH+RIF doses. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation (LPO) as a marker of oxidative stress and non-protein thiols (glutathione) for antioxidant levels were measured in liver homogenate. The treatment of rats with INH+RIF (50 mg/kg per day each) induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis (6/8) and portal triaditis (8/8). Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH+RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH+RIF treated animals. The group which received 0.25 g/kg per day garlic homogenate along with INH+RIF showed higher levels of glutathione (P<0.05) and low levels of LPO (P<0.05) as compared to INH+RIF treated group. Freshly prepared garlic homogenate protects against INH+RIF-induced liver injury in experimental animal model.

Safety and Effectiveness of Rosiglitazone in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease

Background/PurposeNonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD.MethodsTaiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate amino-transferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%.ResultsOut of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 ± 2.4 kg (p<0.001).ConclusionRosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.

Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats.

Mechanism of protective action of bicyclol against CCl4‐induced liver injury in mice

Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis in China. This paper reports the protective action of bicyclol against experimental liver injury in mice and its mechanism of action. Oral administration of bicyclol markedly reduced the elevated serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal lipids and proteins in vitro, and decreased the level of the trichloromethyl free radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver microsomes. On the other hand, bicyclol neither directly inhibited the activity of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These results suggest that bicyclol has remarkable hepatoprotective effects and its mechanism of action may be related to a decrease in free radical-induced damage to hepatocytes.

Clinical Factors and Outcomes in Patients with Acute Mesenteric Ischemia in the Emergency Department

The purpose of this study was to determine the initial clinical characteristics of acute mesenteric ischemia and identify variables associated with adverse outcomes in the emergency department (ED). The charts of 124 consecutive patients with surgically and pathologically identified acute mesenteric ischemia from September 1990 to September 2000 were reviewed retrospectively to obtain data about demographics, initial clinical presentations, predisposing diseases, previous medications, laboratory tests, and common findings on computed tomography scans with contrast. Only patients admitted through the ED and treated on medical or surgical wards were enrolled. Mean patient age was 71.1 years (range, 25-100 years). The overall mortality rate was 50%. There were no significant differences in gender, underlying disease, previous medication, initial signs and symptoms, and causes of mesenteric infarction, between survivors and non-survivors. Univariate analysis demonstrated that older age, bandemia, hepatic and renal impairment, hyperamylasemia, metabolic acidosis, hypoxia, intramural pneumatosis, and septic syndrome, were more frequent in patients who died than in those who survived (p < 0.05). Logistic regression identified the following variables as independent predictors of death: old age (odds ratio, OR, 1.077; 95% confidence interval, Cl, 1.013, 1.146; p = 0.02); bandemia (OR, 3.894; 95% Cl, 1.160, 13.074; p = 0.03); elevated serum aspartate aminotransferase (AST; OR, 4.532; 95% Cl, 1.274, 16.122; p = 0.02); increased blood urea nitrogen (BUN; OR, 7.219; 95% Cl, 1.166, 44.696; p = 0.03); and metabolic acidosis (OR, 6.604; 95% Cl, 1.804, 24.171; p < 0.01). A high index of suspicion and aggressive diagnostic imaging can facilitate early diagnosis and improve outcomes for patients with acute mesenteric ischemia. Risk stratification showed that elderly patients with metabolic acidosis, bandemia, or elevated AST and BUN had a poor prognosis. Greater therapeutic intervention is advocated to reduce mortality in high-risk patients with acute mesenteric ischemia.

Changes in Antithrombin Activity and Platelet Counts in the Late Stage of Twin and Triplet Pregnancies

It is possible that women with triplet pregnancies are more likely to exhibit pregnancy-induced antithrombin deficiency, gestational thrombocytopenia, and perinatal elevation in serum aspartate aminotransferase (AST) than women with twin pregnancies. We retrospectively reviewed changes in antithrombin activity, platelet count, and blood chemistry in 23 twin and seven triplet pregnancies in which the mothers received antenatal care and gave birth in our hospital during 1999 and 2001. Both antithrombin activity and platelet counts gradually decreased until delivery, then promptly increased after delivery in both twin and triplet pregnancies. A significantly larger number of women developed gestational thrombocytopenia of < 100 x 10 (9)/L (43% [three of seven] versus 4.3% [one of 23]; p < 0.01) and pregnancy-induced antithrombin deficiency of < 60% of normal activity (57% [four of seven] versus 17% [four of 23]; p < 0.05) in triplet than in twin pregnancies. Eight women with pregnancy-induced antithrombin deficiency, including three women with gestational thrombocytopenia, were significantly more likely to develop perinatal elevations of AST, lactate dehydrogenase, serum creatinine, fibrin/fibrinogen degradation products, and D-dimer than were those without pregnancy-induced antithrombin deficiency. These findings suggest that women with triplet pregnancies are at an increased risk of the HELLP syndrome and acute fatty liver of pregnancy compared with women with twin pregnancies.

Anti-hyperglycaemic and anti-dyslipidaemic effect of dietary supplement of white Ocimum Sanctum Linnean before and after STZ-induced diabetes mellitus

This study was conducted to elucidate whether dietary treatment of white Ocimum sanctum Linnean. (OS) either before or afterstreptozotocin (STZ) - induced diabetes has anti-hyperglycemic and anti-dyslipidaemic action. Two series of experiments wereperformed. The first involved three groups of rats; one group was fed normal diet for 6 weeks, a second diabetic group receivednormal diet and a third diabetic group received 2 % dietary OS from 3 weeks after induction of diabetes for a period of 3 weeks.The second involved three groups of rats: one group was fed normal diet, a second group received or did not receive 2 % dietarywhite OS before induction of diabetes. Fasting blood glucose was determined before and after induction of diabetes. At the endof the study, arterial blood was collected to evaluate serum triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol,serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and creatinine. The results show that bloodglucose was not significantly altered after 3 weeks of dietary supplement of white OS in diabetic rats. In contrast, elevated bloodglucose after 3 weeks of diabetes was alleviated in diabetic rats pretreated with white OS. STZ-induced diabetes significantlyraised serum triglyceride, total cholesterol, LDL-cholesterol, AST, ALT and creatinine. White OS supplementation, either beforeor after induction of diabetes, normalized lipid profile and creatinine and partially reduced an elevated serum AST and ALT. Itcan be concluded that STZ-induced hyperglycaemia can be ameliorated by pretreatment with white OS. Dietary supplement withOS either before or after diabetic induction reverses dyslipidaemia and renal glomerular filtration function, and partially protectsliver function.

A hepatoprotective effect of an aqueous extract of pomegranate ( Punica granatum L. ) rind against acetaminop hen treated rats

In ancient times Egyptians regarded pomegranate fruit as a symbol of fertility due to the round shape and abundant seeds .They used it to heal many ailments. Pomegranate (El-Ruwmon ) that fruit mentioned in our holy Quran not less than three times, that paid attention for its importance. This investigation aims to evaluate the hepatoprotective activity of an aqueous rind powder extract of pomegranate (Punica granatum L.) in its human therapeutic dose against overdose acetaminophen. Pretreatment of rats with 0.43g/KgB.W.of an aqueous rind extract of Punica granatum for 3 days before intraperitoneally (i. p.) injection of 0.5gm acetaminophen significantly reduced the acute elevation of serum aspartate aminotransferase (AST),serum alanine aminotransferase , lactate dehydrogenase (LDH)and alleviated the degree of liver damage after the i.p. injection of hepatotoxin. The group treated only with 0.5gm acetaminophen displayed significant increase in serum (AST),(ALT), (LHD)and liver displayed congestion of central and hepatic portal veins, vacuolization and ballooning also a lot of pyknotic nuclei were detected with many small necrotic areas of hepatocytes. Inflammatory cells inbetween hepatocytes and around the portal tract were observed. Some fatty droplets were scattered in the hepatocytes. In conclusion aqueous extract of pomegranate peels possess a strong antioxidant capacity could ameliorate the damage occurred in liver by overdose acetaminophen

Hemodynamics, electrolytes, and organ histology of larger-volume liposuction in a porcine model.

Liposuction is a procedure that allows the surgical removal of excess adipose tissue in healthy individuals. Lipoplasty is commonly performed with few clinical side effects. However, with increased lipoaspirate volumes, complications have been reported. In addition, the abnormal appearance of fat cells in other tissues subsequent to lipoplasty has been reported in a small number of cases. The authors examined whether larger-volume lipoplasty, in the porcine model, resulted in disturbances in cardiac or pulmonary output levels, electrolytes, and liver chemistry analyses or alterations in organ histology. Nine adult porcine specimens were subjected to either lipoplasty (n = 6) with the superwet technique or no lipoplasty (n = 3). Using a Swan-Ganz catheter, cardiac output and pulmonary artery pressure measurements were obtained from initial placement before lipoplasty until 48 hours postoperatively. Blood analyte measurements were obtained. Upon euthanization, liver, kidney, and lung specimens were collected and tissue sections were prepared. No significant differences or trends were observed in cardiac parameters or blood analytes between control and experimental groups. Significant elevations in serum aspartate aminotransferase and alanine aminotransferase enzyme levels (p < 0.03) were observed in animals postoperatively (10 to 48 hours) subjected to lipoplasty compared with controls. Upon gross examination, the lung tissues of animals subjected to lipoplasty unexpectedly demonstrated patchy petechial hemorrhages on the pleural surface. Tissue sections revealed marked hemorrhagic congestion and evidence of pulmonary edema. Fat emboli were also identified within the pulmonary and renal systems.

Severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is an infectious disease first recognized in November 2002 in Guangdong Province, China. It spread to many countries all over the world during February to June 2003, with 8098 cases reported. Twenty-one percent of the affected people were health care workers. Because SARS is a new emerging disease, this review describes the current understanding about the etiology, clinical pictures, laboratory and radiological findings of SARS. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was quickly found to be the etiological agent of SARS in April 2003. The transmission of SARS-CoV between human beings is mainly due to close contact. Using barrier precautions, the transmission of SARS-CoV can be prevented. The most common clinical presentations of patients with SARS include fever, cough, and dyspnea. The common laboratory findings include lymphopenia, thrombocytopenia, elevated serum alanine and aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase, and C-reactive protein. The most common radiological finding is pneumonic lesion(s) in the chest radiogram. Many patients experience exacerbation of clinical symptoms in the second week of disease course and some may progress to respiratory failure and need mechanical ventilatory support. The overall case fatality rate is 9.6%. The current method of treatment of SARS is still controversial. SARS is an infectious disease with high contagiousness and a high mortality rate. Early case identification and infection control are two important factors to limit its spread.

Examination of the Rat Model of Liver Injury via Thioacetamide (TAA) or Carbon Tetrachloride (CCl4)

In the present study, a suitable rat model for testing the modifying effect of liver injury on the rat male organ toxicity of endocrine disrupters was researched using thioacetamide (TAA) and carbon tetrachloride (CCl4) as liver toxicants. Male 8-week-old F344 rats were divided into six groups as follows. Animals in groups 1 and 2 were given 200 and 100 mg/kg body weight of TAA with PBS by intraperitoneal injection (ip.) 3 times a week for 4 weeks, respectively. Group 3 was given PBS only. Animals in groups 4 and 5 were given 2 and 1 mg/kg body weight of CCl4 with corn oil by subcutaneous injection (sc.) once a week, for 4 weeks, respectively. Group 6 was given corn oil only. Three rats from each group were sacrificed at week 4 and the rest of groups 1 and 4 were sacrificed after a further 4 weeks of withdrawal period. In the animals administered 200 mg/kg of TAA the findings of apparent liver damage on both histopathological and biochemistrical examinations could be seen: fibrosis, enlargement of Glisson's sheath and infiltration of inflammatory cells in the liver, and apparent elevation of serum aspartate aminotransferase and alanine aminotransferase levels. On the other hand, in the animals administered 2 mg/kg of CCl4 only the histopathological findings of liver damages could be seen: fatty and inflammatory changes in liver. In the animals administered 100 mg/kg of TAA or 1 mg/kg body weight of CCl4 only the histopathological findings of slight inflammatory changes in their liver samples. However these findings of liver damage were almost completely absent after the 4-week withdrawal period.

Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice.

Adiponectin, an adipocytokine, has been identified in adipose tissue, and its receptors are widely distributed in many tissues, including the liver. The present study was performed to clarify the role of adiponectin in lipopolysaccharide (LPS)-induced liver injury using KK-Ay obese mice. We analyzed the effects of adiponectin pretreatment on liver injury induced by D-galactosamine/LPS (GalN/LPS) in KK-Ay obese mice. GalN/LPS treatment induced significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the blood, apoptotic and necrotic changes in hepatocytes, and/or showed a high degree of lethality. The GalN/LPS-induced liver injury was more pronounced in KK-Ay obese mice than in lean controls. Pretreatment with adiponectin ameliorated the GalN/LPS-induced elevation of serum AST and ALT levels and the apoptotic and necrotic changes in hepatocytes, resulting in a reduction in lethality. In addition, pretreatment with adiponectin attenuated the GalN/LPS-induced increases in serum and hepatic tumor necrosis factor alpha (TNF-alpha) levels and increased peroxisome proliferator-activated receptor (PPAR) alpha messenger RNA expression in the liver. Furthermore, abdominal macrophages from KK-Ay obese mice pretreated with adiponectin in vitro exhibited decreased LPS-induced TNF-alpha production compared with controls. Finally, adiponectin pretreatment also ameliorated TNF-alpha-induced liver injury. In conclusion, these findings suggest that adiponectin prevents LPS-induced hepatic injury by inhibiting the synthesis and/or release of TNF-alpha of KK-Ay obese mice.

Connexin 32 dominant-negative mutant transgenic rats are resistant to hepatic damage by chemicals.

Connexins are subunits of gap junction channels, which allow direct transfer of ions, secondary messenger molecules, and other metabolites between contacting cells. Gap junctions are believed to be involved in tissue homeostasis, embryonic development, and control of cell proliferation. Several studies have shown that cell damage signals are transmitted through gap junctions when cells are irradiated or when cells bearing the herpes simplex virus-thymidine kinase (HSV-TK) gene are treated with ganciclovir. We established 2 lines of transgenic rats with a dominant-negative mutant of connexin 32 gene under control of the albumin promoter. In the livers of transgenic rats, membrane localization of normal endogenous connexin 32 protein is disturbed, and gap junction capacity measured by scrape dye-transfer assay in vivo is markedly decreased when compared with wild-type rats. The present investigation concerned susceptibility to the liver-toxic substances D-galactosamine and carbon tetrachloride. These toxicants induced massive liver cell death and elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the wild-type rats; however, much fewer liver cells were damaged and serum enzyme elevation was much lower in the transgenic rats. In conclusion, gap junctional intercellular communication (GJIC) plays an important role in toxic effects of chemicals; damage or death signals may pass through gap junctions in the rat liver in vivo.