Adverse drug reactions induced by valproic acid

Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity.     

Serum Gamma-Glutamyl Transferase Level Is an Independent Predictor of Incident Hypertension in Korean Adults

The aim of our study was to assess the relationship between serum gamma-glutamyl transferase (GGT) level within the normal range and incident hypertension according to drinking and obesity status in nonhypertensive individuals. We followed up 4783 normotensive adults (mean age = 44 years) who had serum GGT levels within the normal range at baseline for 3 years. Subjects were divided into four GGT quartile groups according to their serum GGT level at baseline. The overall incidence of hypertension was 8.1%, and the incidence increased with increasing GGT quartile (3.8%, 6.9%, 9.0%, and 12.4% in the lowest, second, third, and highest GGT quartiles, respectively; P < .001). In the logistic regression analysis adjusted for age, sex, body mass index, lifestyle factors, glucose, uric acid, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and baseline systolic blood pressure, the odds ratio (ORs) for incident hypertension increased with increasing GGT quartile (P for trend = .030). In the above model, the highest quartile group showed increased ORs compared with those in the lowest quartile group (ORs [95% confidence interval], 2.638 [1.259–5.528]). Subgroup analyses revealed a significant association between GGT quartile and the incidence of hypertension in the drinker and non-overweight groups. Our results indicate that elevated serum GGT levels within the normal range are associated with a higher risk of incident hypertension in Korean adults, particularly, in drinkers and non-overweight individuals, suggesting possible different pathophysiologic mechanisms in the incidence of alcohol- and obesity-related hypertension.     

Tyrphostins reduce chemotherapy-induced intestinal injury in mice: assessment by a biochemical assay

Intestinal injury that results from chemotherapy belongs to the major factors of dose-limitation in tumour therapy. The tyrphostins AG1714 and AG1801 reduce cisplatin and 5-FU-induced small intestinal mucosal damage, using a quantitative biochemical assay. The assay is based on the determination of the enzymatic activity of gamma-glutamyl transpeptidase, a marker of the brush border epithelium of the small intestine.     

Obstetric cholestasis with elevated gamma glutamyl transpeptidase: incidence, presentation and treatment

BACKGROUND: Obstetric cholestasis (OC) may cause severe pruritus in the mother and lead to fetal distress and stillbirth. The etiology of OC is multifactorial, but includes inherited dysfunction of bile canalicular transporters. One of these, multidrug resistant protein 3 (MDR3), a phospholipid transporter, when dysfunctional is associated with elevated levels of gamma glutamyl transpeptidase (GGT). The aim of the present study was to assess the incidence of OC associated with elevated GGT. We compared the natural history of a cholestatic pregnancy and the efficacy of ursodeoxycholic acid (URSO) in OC patients grouped according to a normal or raised GGT level. METHODS: Eighty-one patients with OC were analyzed. OC was diagnosed in patients with pruritus and elevated serum bile acids (SBA). Fifty-seven consenting volunteer patients (70%) were treated with URSO. RESULTS: Elevated GGT at presentation was found in 21 patients (30%) and was associated with significantly higher serum levels of aspartate transaminase (AST), bilirubin (BIL) and SBA. OC presented at approximately the same gestation week in both groups of patients. In patients not treated with URSO, liver function tests (LFT) showed no significant change from the time of diagnosis to delivery. Patients from both groups responded to URSO with significant improvement in their AST and alanine aminotransferase (ALT) levels, but SBA fell significantly only in the normal GGT group. CONCLUSIONS: An elevated GGT occurs in less than one-third of patients with OC in the UK and, when present, is associated with greater impairment of LFT, but no difference in gestational age at onset. Treatment with URSO appears to be safe and significantly improves LFT in patients with OC, with the exception of SBA in the high GGT group.     

Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to alpha-fetoprotein

Serum protein induced by vitamin K absence or antagonist II (PIVKAII), hepatoma-specific band of serum gamma-glutamyl transferase (GGTII), and alpha-fetoprotein (AFP) levels were determined in 120 patients with hepatocellular carcinoma (HCC) and 90 patients with cirrhosis. The mean serum concentration of PIVKAII in HCC patients was higher than that in cirrhotic patients. A total of 53.3% of patients (64 out of 120) with HCC had PIVKAII levels above 40 mAU ml(-1). However, only 13 patients with cirrhosis had higher PIVKA II levels. Of 32 small HCC patients, 13 (40.6%) had PIVKAII values above 40 mAU ml(-1). An increased concentration of AFP (i.e. 20 ng ml(-1)) was observed in 70 out of 120 (58.3%) patients with HCC and in 33 out of 90 (36.7%) patients with cirrhosis. Positive GGTII was found in 74.0% (89 out of 120) cases of HCC (sensitivity), in 16 of 90 cases of cirrhosis, and 14 of 32 (43.8%) small HCC patients had GGTII positive. No significant correlation was found between serum levels of AFP and PIVKAII. Combining the information from PIVKAII, AFP, and GGTII significantly increases the sensitivity over AFP alone. PIVKAII and GGTII are useful tumour markers complementary to AFP for diagnosis of HCC.     

Differentiation between extrahepatic and intrahepatic cholestasis by discriminant analysis

Discriminant analysis was used to differentiate between extrahepatic biliary atresia and intrahepatic cholestasis. Among the ten laboratory variables tested, three (gamma-glutamyl transpeptidase, alkaline phosphatase and total serum bilirubin) were useful in the differential diagnosis. gamma-Glutamyl transpeptidase contributed most to the discrimination (85%). From a population study of 28 babies with extrahepatic biliary atresia and 24 infants with intrahepatic cholestasis, the procedure achieved a diagnostic accuracy and specificity of 92.9% and an efficiency of 92.3%. The jackknife procedure has also confirmed that the mathematical model was robust for discriminant analysis and therefore it may be valid for screening infants with cholestasis for early surgical intervention. Discriminant analysis is a useful adjunct for differentiation between intrahepatic cholestasis and extrahepatic biliary atresia.     

Antiinflammatory profile of Tridax procumbens in animal and fibroblast cell models

The aqueous extract of Tridax procumbens leaves was lyophilized and studied on the excision wound model, rat skin fibroblast and rat paw oedema. Tridax procumbens did not significantly increase the fibroblast count compared with ibuprofen. Wound contraction was comparable in the Tridax and ibuprofen treated groups. Epithelialization was significant in the Tridax group. The aspirin treated group showed significant retardation in both parameters (p < 0.001). The fibroblast cell count, hydroxyproline/DNA ratio and collagen synthesis were insignificant in the control and Tridax treatment, while ibuprofen and aspirin treatment had a significant effect (p < 0.01) on the above mentioned parameters. In the carageenin induced oedema model, inhibition of oedema was comparable in 200 mg/kg Tridax and 50 mg/kg ibuprofen treatment, and the specific activity of the enzyme gamma glutamyl transpeptidase was comparable in the Tridax, ibuprofen and aspirin at 200 mg/kg, groups. © 1998 John Wiley & Sons, Ltd.     

Urinary enzyme excretion in rats due to heavy physical work: Effect of the antioxidant phenosan

Potassium salt of di-tert-butylhydroxyphenylpropionic acid — Translator     

One-year chronic toxicity study of Aloe arborescens Miller var. natalensis Berger in Wistar Hannover rats. A pilot study.

This study was conducted to evaluate the chronic toxicity of Aloe arborescens Miller var. natalensis Berger (ALOE) in the diet at doses of 4.0%, 0.8% or 0.16% to groups of male and female Wistar Hannover rats. No deaths occurred at any dose level throughout the treatment period. Both sexes receiving 4.0% showed diarrhea, with a reduced body weight gain. Increase of WBCs in the male 4.0% group, decrease of Hb in the female 4.0% and 0.8% groups, decrease of IP in the male 4.0% and 0.8% groups and female 4.0% group, and decrease of Ca and ALT in the female 4.0% group were observed. Relative kidney weight showed increase in the female 4.0% group and relative heart and brain weights were decreased in the female 4.0% and 0.8% groups. Histopathologically, both sexes receiving 4.0% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. In conclusion, the no observed adverse effect level (NOAEL) for ALOE was the 0.16% in diet, which is equivalent to 87.7 and 109.7 mg/kg/day in males and females, respectively.     

Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis

OBJECTIVE: To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC).STUDY DESIGN: A retrospective study of all VLBW infants with PNAC who were admitted to a tertiary referral center was conducted. Patients were classified as treatment group (receiving UDCA within 14 days after onset of cholestasis) or control group (no medical treatment). Patients who received abdominal surgery were excluded. RESULTS: A total of 30 patients were recruited, including 12 in the treatment group and 18 in the control group. The demographic data, total fasting duration, onset of cholestasis, age to tolerance of full feeds, and the duration of parenteral nutrition (PN) before the onset of cholestasis were comparable between the two groups. There was a trend in the control group to later onset of cholestasis. The patients who received UDCA therapy with doses of 10 to 30 mg/kg/day had a shorter duration of cholestasis than the control group (62.8 vs 92.4 days, P=.006). Furthermore, the peak serum levels of direct bilirubin also was significantly lower in the treatment group. CONCLUSION: UDCA can improve the course of PNAC in VLBW infants.