Inhibitory activities of extracts of Rumex dentatus,Commelina benghalensis,Ajuga bracteosa,Ziziphus mauritiana as well as their compounds of gallic acid and emodin against dengue virus

Objective: To investigate the inhibitory effects against dengue virus serotype 2(DENV-2) by five different fractions(extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa and Ziziphus mauritiana, as well as their constituents(gallic acid, emodin, and isovanillic acid). Methods: All the samples were tested for cytotoxicity on baby hamster kidney cells by MTT assay and for anti-DENV-2 activity by plaque reduction neutralization assay using two DENV-2 doses(45 and 90 plaqueforming units or PFU). Results: All the samples except isovanillic acid exhibited significant prophylactic effects against DENV-2 infectivity(without cytotoxicity) when administered to cells before infection, but were not effective when given 6 h post-infection. The methanol extract of Rumex dentatus demonstrated the highest antiviral efficacy by inhibiting DENV-2 replication, with IC_(50) of 0.154 μg/mL and 0.234 μg/mL, when added before infection with 45 and 90 PFU of virus, respectively. Gallic acid also exhibited significant antiviral effects by prophylactic treatment prior to virus adsorption on cells, with IC_(50) of 0.191 μg/mL and 0.522 μg/mL at 45 and 90 PFU of DENV-2 infection, respectively. Conclusions: The highly potent activities of the extracts and constituent compounds of these plants against DENV-2 infectivity highlight their potential as targets for further research to identify novel antiviral agents against dengue.     

Inhibition of dimethylhydrazine-induced aberrant crypt foci and induction of apoptosis in rat colon following oral administration of the glucosinolate sinigrin

Glucosinolates are sulphur compounds that occur as glycosides in brassica vegetables. In response to tissue disruption they are degraded by thioglucosidase, releasing a range of highly reactive breakdown products, including the isothiocyanates, which we have previously shown to be selectively cytotoxic to undifferentiated colorectal tumour cells (HT29). In the present study we explored the effect of sinigrin on the intestinal mucosa of rats previously treated with dimethylhydrazine (DMH). In the first experiment, a semisynthetic feed containing sinigrin (400 microg/g diet) was provided 6 h after the second of two injections of DMH. The level of apoptosis was measured by morphological assessment of intact microdissected crypts obtained at 18, 24, 38, 48 and 72 h after injection, and compared with control groups given DMH only, or a sham-injection. Higher numbers of apoptotic nuclei were present in colonic tissue from both groups of DMH-treated rats compared with the controls, and the level was significantly higher in DMH- treated rats fed sinigrin compared with those given DMH only (P < 0.02). In a second experiment, rats were given sinigrin (400 microg/g diet) 22 h after the second of two injections of DMH; the level of apoptosis was measured after 48 h and the numbers of aberrant crypt foci (ACF) were measured after 42 days. The level of apoptosis was significantly higher in DMH-treated rats given sinigrin compared with controls (P < 0.05), and the numbers of ACF were significantly lower in sinigrin-treated rats (P < 0.001). There was no statistically significant induction of apoptosis in animals fed sinigrin alone. Sinigrin administered after DMH suppresses induction of ACF. This may be due to increased apoptotic deletion of damaged stem cells in the crypts of animals fed sinigrin.      

A carbamazepine trial in chronic, treatment-refractory schizophrenia

Carbamazepine was given to 12 chronic, treatment-refractory schizophrenic patients for 5 weeks. No overall change was found, but four patients significantly improved while eight worsened. Given the paucity of successful treatments for refractory schizophrenia, further study of carbamazepine appears warranted.     

PSYCHIATRIC EFFECTS OF HYSTERECTOMY

An excess of psychiatric symptoms in post-hysterectomy women have been reported by some authors but denied by others. Thirty six women undergoing hysterectomy for non-malignant pathologies were compared with equal number of comparable patients who underwent other gynaecological operations. Patients were assessed pre- and post-operatively by semi-structured psychiatric interview, Sinha''s anxiety scale and Hamilton''s depression rating scale. Patients undergoing hysterectomy were significantly more anxious and depressed both pre- and post-operatively as compared to the control patients. Hysterectomy was not associated with significantly higher psychiatric morbidity.KEY WORDS: Hysterectomy, Depression     

MODIFIED BROMOPHENOL BLUE DYE BINDING METHOD FOR QUANTITATION OF MICROALBUMINURIA IN DIABETES MELLITUS

Albumin excretion in microalbuminuria range is one of the earliest manifestation of nephropathy, specially in diabetes mellitus. The modified dye binding method using bromo-phenol blue was studied in 27 healthy controls and 54 patients of diabetes mellitus, negative for albuminuria by albustix test. The analytical recovery (99.4 to 104.0%), within run coefficient of variation (0.8 to 0.36%) and day-to-day coefficient of variation (2.39 to 0.82%), for low and higher range were within acceptable limits. The values in controls ranged as follows: urinary albumin concentration (mg/L) 7.7 – 28.4 in 2-hour specimen and 10.3 – 29.2 in overnight specimen; albumin excretion rate (µg/min) 7.8 – 29.7 in 2-hour and 9.2 – 29.6 in overnight specimen; and albumin creatinine ratio (mg/g) 10.6 – 29.6 in 2-hour and 11.9 – 29.6 in overnight specimens.Correlation analysis of various albumin excretion parameters revealed excellent correlation between estimations from overnight and 2-hour samples for albumin-creatinine ratio (r = 1.00) and albumin excretion rate (r=0.96). Equally good correlation was observed between 2-hour albumin-creatinine ratio and albumin excretion rate (r=0.95). In 10 of 54 patients excretion rate was more than 200 µg/min and could have been detected by repeat albustix test. Of the 36 positive for microalbuminuria, 21 had one or more target organ involvement. There was no target organ involvement in 8 patients negative for microalbuminuria. Screening for microalbuminuria by this simple and economic method, using 2-hour albumin-excretion rate or albumin-creatinine ratio could be one of the earliest investigations in diabetic patients.KEY WORDS: Microalbuminuria, Spectrophotometeric method, Diabetes mellitus     

Clozapine: an atypical antipsychotic agent

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, dosage, and cost of the atypical antipsychotic drug clozapine are reviewed. Clozapine is a dibenzazepine compound chemically similar to loxapine but with a distinct pharmacologic profile. Unlike currently available medications, clozapine has a low potential for causing extrapyramidal symptoms and does not induce dopamine type 2 receptor hypersensitivity. It shows affinity in vitro not only for dopamine type 1 and 2 receptors but also for histamine type 1, alpha-adrenergic type 1 and 2, serotonin type 2, and muscarinic receptors. Clozapine given orally is nearly completely absorbed and readily metabolized. Urinary excretion is the major route of metabolite elimination. Clozapine has been used to treat schizophrenia, nonschizophrenic psychotic states, depression, neuroses, and behavioral disorders. Double-blind comparative studies have shown clozapine to be superior to haloperidol, chlorpromazine, and placebo in treating the symptoms of schizophrenia, as measured with validated psychiatric rating scales. Adverse effects include orthostatic hypotension, tachycardia, benign hyperthermia, hypertension, seizures, and sedation. Many of these effects are transient. Because of the risk of agranulocytosis, a comprehensive case-management system has been developed. In treating acute psychosis, the optimum dosage of clozapine is 300-450 mg/day given orally in divided doses. The high cost of clozapine may be offset by improved patient response and reduced hospital costs. Clozapine may be superior to other agents in the treatment of refractory schizophrenia and is associated with a negligible incidence of extrapyramidal symptoms.