Immunosuppressant drugs have contributed significantly to the success of organ transplantation. Therapeutic drug monitoring is an integral part of transplant protocols. Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant variability in blood concentrations between individuals. The variability in blood concentrations can be because of factors like drug-nutrient interactions, gender influence and polymorphism. Drug monitoring is widely practised especially for cyclosporine, tacrolimus, sirolimus and mycophenolic acid. The accuracy and specificity of the drug measurements are fundamental to the clinical interpretation of the concentration data. The issues surrounding the measurement and interpretation of immunosuppressant drug levels such as body fluids used for drug estimation, protein binding, sampling time and method for assay of the drug are discussed in detail in the article.

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Acute poisoning with organophosphorous (OP) pesticides frequently causes ill-health and death all over the world. The treatment of OP poisoning is primarily aimed at reversing the effects of the compound by administration of atropine. A second class of compounds-oximes, capable of regenerating the active enzyme from the OP-cholinesterase complex, is also available to treat OP poisoning. Pralidoxime is the oxime most often used worldwide. The low propensity to aging with diethyl organophosphorous poisoning may allow reactivation of the acetylcholinesterase after several days, when the poison concentration drops. The usefulness of oximes has however been challenged over the past 20 years by physicians in many parts of the world who have failed to see any benefit in their clinical practice. We have carried out a systematic search to find clinical trials, both randomized and nonrandomized involving the management of OP poisoning. The clinical benefits of oximes in OP poisoning is not clear, being limited by the type of OP, poison load, time to start therapy and dose of oximes. Hence, one is left with a doubt as to whether one could use oximes at all in OP poisoning? A high-quality randomized clinical trial on a large number of subjects comparing the current World Health Organization-recommended regimen with a placebo to assess the value of pralidoxime in acute OP poisoning, may answer the above question.

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Neuroleptic drugs used in the treatment of schizophrenia and other affective disorders are known to produce extrapyramidal side effects. Catalepsy induced by these drugs in animals has been used as a model for the extrapyramidal side effects associated with antipsychotic agents in human beings. In the present study, we have attempted to evaluate the protective effect of the ethanolic leaf extractof Ocimum sanctum (OS) on haloperidol (1.0 mg/kg, intraperitoneal administration)-induced catalepsy in mice by employing the standard bar test. Mice were allocated to seven groups, each group containing six animals. The effects of the test drug OS (at 1.75, 4.25 and 8.5 mg/kg doses) and the standard drugs, scopolamine (1.0 mg/kg) and ondansetron (0.5 and 1.0 mg/kg doses) were assessed after single and repeat dose administration for seven days, 30 minutes prior to the haloperidol. The results suggest that OS has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drugs used for the same purpose. Our study indicates that OS could be used to prevent drug-induced extrapyramidal side effects.

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Objective : The present study describes the effect of selenium either alone or in combination with meso-2, 3-dimercaptosuccinic acid (DMSA) against chronic arsenic poisoning in rats. Materials and Methods : Male Wistar rats were exposed to 100 ppm sodium arsenite in drinking water for eight months and treated thereafter with DMSA (0.3 mmol/kg orally) either individually or in combination with selenium (Se, 6.3 or 12.6 µmol/kg, intraperitoneally) once daily for five days. The effects of these treatments in influencing the arsenic (As)-induced changes in heme synthesis, hepatic, renal or brain oxidative stress were evaluated along with the As concentration in blood and soft tissues. Results : Exposure to As significantly altered biochemical parameters related to the heme synthesis pathway, blood and organ (liver, kidney and brain) oxidative stress while increasing body As burden in animals. Treatment with DMSA alone significantly reduced the adverse effects related to most of these biochemical parameters as well as the As concentration in blood and tissues. On the other hand, co-administration of Se with DMSA had only limited additional beneficial effects (particularly tissue oxidative stress) over the individual effect of DMSA. Conclusion : The above results suggest that Se administration during chelation affected by other agents had some beneficial effects on oxidative stress with no major additional beneficial effect on arsenic depletion.

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Objective : The study was undertaken to assess the organ directed toxicity of halquinol in female wistar albino rats. Materials and Methods : Halquinol was administered orally by gavage at the dose of 0 (control), 150 (low), 450 (intermediate) and 1000 (high) mg/kg body weight daily for a period of 28 days to four groups of rats (n=6). Each rat was weighed at the beginning and at weekly intervals thereafter till the end of the study. Blood and serum samples were analyzed on Day 0, 14 and 28 for haematological parameters viz, Hb, Hct, TEC, MCV, MCH, MCHC, TLC and DLC and serum biochemical parameters viz, ALP, ALT, AST, TSP, TA, BUN and Creatinine respectively. At the end of the study organs were weighed and organ to body weight ratios were calculated. The representative tissue samples were processed for histopathological examination. Results : The body weight in the intermediate and high dose group was significantly (P<0.01) lower than the control group. The Hb, TEC and MCHC decreased significantly (P<0.01) whereas MCV increased significantly (P<0.01) in high dose group. Serum biochemical parameters viz, ALP, ALT, BUN and creatinine significantly (P<0.01) increased in intermediate and high dose groups. Organ to body weight ratio in case of liver and kidney was also significantly (P<0.01) higher in high dose group. Histopathology of liver and kidney from intermediate and high dose groups revealed marked pathological alterations. Conclusion : From the present study it was concluded that at intermediate and high dose, halquinol was hepatotoxic and nephrotoxic in female rats.

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Objective : To evaluate the antiimplantation activity of the ethanolic root extract of Momordica cymbalaria Fenzl. Materials and Methods : The acute oral toxicity study was performed according to the OPPTS guidelines. The ethanolic root extract was investigated for antiimplantation, estrogenic and progestrogenic activities at doses of 250 and 500 mg/kg body weight. Antiimplantation activity was studied on successive stages of embryogenesis. Estrogenic studies were carried out by examining uterine weight, histoarchitecture of uterus, vaginal cornification, uterine content of glucose, cholesterol and alkaline phosphatase levels in immature rats. Progestrogenic activity assay was performed by pregnancy maintenance in rats and Clauberg's test (endometrial proliferation assay) in immature rabbits. Results : Both doses of the ethanolic root extract exhibited highly significant (P < 0.001) antiimplantation activity. However, an investigation of the estrogenic activity did not show any increase in uterine weight or vaginal cornification. The histoarchitecture (uterotrophic changes) such as thickness of endometrium and height of endometrial epithelium was unaltered in treated rats. There were no increases in the uterine content of glucose, cholesterol or alkaline phosphatase levels when compared with the control group. Pregnancy was not maintained in the pregnancy maintenance test for progestrogenic activity. Uterine proliferation was not seen in Clauberg's test (endometrial proliferation assay) for progestrogenic activity in immature rabbits. Conclusion : The ethanolic root extract of Momordica cymbalaria Fenzl exhibited antiimplantation activity but this is not due to estrogenic or progestrogenic activities.

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Background : Osteoporosis is conventionally treated with synthetic estrogens. However, the serious side effects of hormone replacement therapy (HRT) hampers the clinical use of estrogens. Hence, alternatives for estrogens are being explored, one of which is the isoflavone, genistein. Many studies show that genistein may exert positive effects on bone. However, there are also studies which report no overall association between genistein intake and bone marrow density (BMD) and fracture rates. The effect of genistein on bone loss is still controversial. Aims : In this study, we evaluated both in vivo and in vitro pharmacological effects of genistein in osteoporosis. Materials and Methods : MTT and ALP activity assays were performed to evaluate genistein's in vitro activity on MC3T3-E1 cells. The OVX rat model was used to test genistein's in vivo effects by determination of BMD and bone calcium and phosphorus content after treatment for 12 weeks. Results and Conclusions : The data showed that 10 ^-6 M genistein both increased the number of MC3T3-E1 cells and elevated ALP activity significantly. In vivo, 9 or 18 mg/kg doses of genistein were found to prevent osteoporosis after 12 weeks treatment. Thus, our results indicated that genistein may be an alternative for HRT in prevention of postmenopausal osteoporosis.

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Objective : We examined the involvement of 5-HT neurotransmission on the antidepressant-like effect of the dichloromethane (DcM) fraction of an extract from Kielmeyera coriacea stems. Materials and Methods : Male Wistar rats treated chronically (45 days, gavage) with the DcM fraction received an intradorsal raphe nucleus (DRN) microinjection of saline or 5-HT _1A receptor ligands and were evaluated in the forced swimming test (FST) and in the open-field test (OFT). Results : The DcM fraction (5.0 mg/kg) reduced immobility time in the FST without altering locomotion in the OFT. IntraDRN microinjection of the 5-HT _1A receptor agonist, (+)-8-OH-DPAT (0.10; 0.20 or 0.33 µg) increased immobility time and reduced locomotion at the higher dose whereas the 5-HT1A antagonists, (-)-pindolol (0.10; 0.20 or 0.40 µg) or WAY100635 (0.11; 0.22 or 0.43 µg) did not produce any effect in the behavioral tests. IntraDRN (+)-8-OH-DPAT (0.20 or 0.33 µg) in rats treated with the DcM fraction (5.0 mg/kg) blocked the changes in the immobility time or in locomotion produced by each drug. Intra-DRN (-)-pindolol (0.10 µg) or WAY100635 (0.43 µg) in rats treated with a subactive dose of the DcM fraction (4.0 mg/kg) synergistically reduced immobility time in the FST. Conclusion : The DcM fraction of Kielmeyera coriacea produced an antidepressant-like effect in the FST and interacted with 5-HT _1A receptor ligands. Activation of 5-HT _1A receptors into DRN by (+) 8-OH-DPAT produced detectable changes in the FST or in the OFT.

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Objectives : To determine the effects of β -adrenoceptor and muscarinic agonists on the contractile rate of isolated right atria of rats fed a high fructose diet with or without rosiglitazone (RSG). Materials and Methods : Male Sprague Dawley rats were assigned to four groups and given ad libitum access to one of the following diets: standard chow, standard chow supplemented with 4 mg/kg/day RSG, a high fructose diet and a high fructose diet with 4 mg/kg/day RSG. All the groups were maintained on these regimens for three weeks with weekly measurements of systolic blood pressure and body weight. At the end of the three weeks, the rats were exsanguinated and the hearts were rapidly removed following which blood glucose, insulin and lipid profiles were estimated. The right atria were isolated from the heart and their responsiveness to sympathetic and parasympathetic agonists was studied. Results : Basal, spontaneous, isolated atrial pacemaker rate was diminished in fructose-fed rats. The maximum pacemaker rate to isoproterenol or norepinephrine was unchanged in fructose-fed rats. Further, the increase in atrial rate and half maximal effective concentration values for each agent were also unaffected. The sensitivity to negative chronotropic action of acetylcholine was enhanced in fructose fed rats, whereas the response to carbachol was unchanged. The increased sensitivity to acetylcholine was restored by RSG treatment. Conclusion : High fructose diet induced insulin resistance and hypertension with alterations in basal spontaneous pacemaker, enhanced sensitivity to cholinergic agonist without any changes in the response to adrenergic and cholinergic receptor activation. Treatment with insulin sensitizer rosiglitazone was able to prevent all these changes. The present study suggests that rosiglitazone may have effect on the cardiovascular system in addition to the insulin sensitising action.

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A 60 year-old male was initiated on azathioprine 50 mg/day for airborne contact dermatitis. As the patient showed a satisfactory response to this initial therapy, azathioprine dose was escalated to 100 mg/day after two weeks. However, the patient started feeling unwell from that day onwards and developed features of azathioprine-induced shock leading to discontinuation of azathioprine. Within the next 24 hours, there was complete resolution of nausea, malaise, abdominal pain, hypotensive episodes, fever and diarrhea in a pattern similar to that in which they had appeared. Rechallenge with a single dose of azathioprine (50 mg), resulted in the recurrence of nausea, vomiting and the characteristic fever spike four hours later. His blood pressure showed a marginal fall from 130/80 to 100/70 mm Hg. However, a clinically manifest episode of hypotension did not develop. This case is being reported for its rarity and clinical interest.

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