A combination of generated hydrogen sulfide and nitric oxide activity has a potentiated protectant effect against cisplatin induced nephrotoxicity.

Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 µmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine and kidney samples were collected for biochemical assays and histopathological analysis. Results: Cisplatin decreased body weights and increased urinary output, while plasma creatinine and urea levels were elevated, but sodium and potassium concentrations were diminished. The renal function parameters, blood urea nitrogen and creatinine clearance, were raised and decreased respectively. Regarding markers of reactive oxygen species, plasma total superoxide dismutase was reduced, whereas malondiadehyde was augmented.Cisplatin also diminished plasma and urinary H2S as well as plasma NO, while NaHS and L-arginine counteracted this activity on both redox-active molecules. Cisplatin cotreatment with NaHS, and/or L-arginine exhibited a reversal of all other measured parameters. Conclusion: In current study, NaHS and L-arginine as monotherapy protected the rats from cisplatin-induced nephrotoxicity but the combination of both worked more effectively suggesting the augmented anti-inflammatory and antioxidative potential of test treatments when administered together.

Countenance and implication of Β-sitosterol, Β-amyrin and epiafzelechin in nickel exposed Rat: in-silico and in-vivo approach.

The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with ß-sitosterol (100 mg/kg b wt), ß-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds ß-sitosterol, ß-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.

Evaluation of anti-inflammatory and analgesic effects of Hertia intermedia (Boiss.) Kuntze extract.

Hertia intermedia is a traditional medicinal plant of Balochistan, used for pain management and stomach problems. Current research work was intended to evaluate the anti-inflammatory and analgesic activities of crude ethanolic extract of H. intermedia. Anti-inflammatory activity was determined by the carrageenan-induced and histamine-induce Rat paw edema in rats, analgesic activity was determined by acetic acid-Induced writhing test, formalin-induced hind paw licking in mice and Tail immersion test. H. intermedia crude ethanolic extract showed significant (p<0.05) effect in both carrageenan and histamine-induced rat paw edema at both 250 and 500 mg/kg oral doses. There were significant analgesic activities in comparison with standard drug and control (p<0.05). It is concluded that H. intermedia crude ethanolic extract possesses significant anti-inflammatory and analgesic effects. However further studies may be carried out to isolate the phytochemicals responsible for anti-inflammatory and analgesic activities.

Clinical Characteristics, Comorbidities, and Outcome of Critically Sick Patients With COVID-19 Pneumonia Admitted in the Intensive Care Unit of a Tertiary Care Hospital in Lahore, Pakistan: A Retrospective Cohort Study.

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a multisystem disease that primarily involves the respiratory tract. The first case of COVID-19 was identified in late 2019 in the province of Wuhan, China, which was followed by the rapid spread of the disease globally, becoming a present-day pandemic. Objectives The aim of this study is to describe the clinical characteristics, comorbidities, and outcomes of critically sick patients with COVID-19 pneumonia admitted to the intensive care unit (ICU) of Fatima Memorial Hospital, Lahore, from March 2021 to August 2021. A total of 133 patients were chosen for this retrospective cohort study. Results There was a total of 133 patients, out of which 65 (48.9%) were male and 68 (51.1%) were female. Of these 133 patients, 70 (52.6%) were discharged home after recovery and 63 (47.4%) died; 96 (72.2%) patients had diabetes mellitus and of these, 53 (55.2%) patients died and 43 (44.8%) were discharged, 94 (70.7%) patients had hypertension, out of which 53 (56.4%) died and 41 (43.6%) were discharged home, 40 (30.1%) patients had ischemic heart disease (IHD), out of which 28 (70%) died and 12 (30%) were discharged. A total of 48 (36.1%) patients needed invasive positive pressure ventilation (IPPV) and 78 (58.6%) patients required noninvasive positive pressure ventilation (NIPPV). Conclusion Patients with one or more underlying co-morbidities had poor clinical outcomes compared to those with no co-morbidities, with the most vulnerable group being patients with Ischemic heart disease, chronic kidney disease, hypertension, and diabetes mellitus in descending order.

Spectrum of Dyslipidemias in Treatment-Naïve Human Immunodeficiency Virus-Infected Patients Presenting to an HIV Clinic of a Tertiary Care Hospital.

Introduction HIV/AIDS is a major communicable disease worldwide, especially in developing countries where disease prevalence is over 90%. The National AIDS Control Programme of Pakistan reported around 160,000 HIV cases (140,000-190,000) with a 5% prevalence among traditional risks groups. HIV infection is thought to affect lipids metabolism adversely, thus resulting in increased morbidity and mortality. The aim of the study was to find out the frequency and types of dyslipidemia in patients with HIV not taking anti-retroviral therapy, presenting to an HIV clinic at a tertiary care hospital. Methods This cross-sectional study was conducted at the HIV clinic of Jinnah Hospital from January 2020 to July 2020. A total of 280 treatment-naïve patients, fulfilling the inclusion protocol, were included through non-probability consecutive sampling after informed consent. Blood samples of 5 mL were taken using aseptic measures and following standard procedure after ensuring overnight fasting by a nurse and were sent immediately to the pathology laboratory of Allama Iqbal Medical College. The results of the lipid profile were collected the next day and noted in the proforma. Dyslipidemia and type of dyslipidemia were recorded as per operational definition. Data were analyzed by SPSS software, version 27.0 (IBM Corp., Armonk, NY). Cross-tabulation was done to assess the relationship of gender, BMI, and family history on dyslipidemia, and a chi-square test was applied to check statistical significance. Results Among 280 treatment-naïve HIV-infected patients, the majority of patients were females (52%). The mean duration of HIV was 9.31 + 2.13 months. About 55% of patients had a BMI of more than 25 kg m2. A family history of dyslipidemia was found in 62% of the patients. Dyslipidemia was observed in 70% of patients with maximum derangement seen in total cholesterol level (62%). After applying the chi-square test, a significant relation was identified between BMI and family history with dyslipidemia in HIV-infected individuals (p-value = 0.00). Conclusion A considerable proportion of treatment-naïve HIV patients have underlying dyslipidemia with a significant relationship with higher BMI and a family history of dyslipidemia. The findings of this study highlight the importance of early screening for dyslipidemia in HIV patients.

A Comparison of Disease Severity and Outcomes in COVID-19 Cases Taking Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Versus Other Antihypertensive Drugs.

Objective In this study, we aimed to compare the severity and outcomes in hypertensive patients presenting with coronavirus disease 2019 (COVID-19) who were taking angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and those who were on other antihypertensive drugs. Methods This retrospective cohort study involved 182 hypertensive patients who presented with COVID-19 infection. The study population comprised 91 patients who were taking ACEIs/ARBs (group A) and 91 patients who were taking other antihypertensive drugs such as ß-blockers (BBs), calcium channel blockers (CCBs), or thiazides (group B). All patients were provided the same type of treatment for the management of COVID-19. We recorded the data related to demographic and anthropometric variables as well as clinical symptoms during the treatment period. Disease severity and hospital mortality were the primary study endpoints. Results There was no significant difference in COVID-19-related outcomes between the groups except for the severity of lung infiltration on chest X-rays. There were 37 (41.1%) patients having >50% lung infiltration in group A and 53 (58.2%) in group B (p-value: 0.02). Severe disease was diagnosed in 37 (40.7%) patients in group A compared to 39 (42.7%) patients in group B (p-value: 0.76). In-hospital mortality was noted in 17 (18.7%) patients in group A and 22 (24.2%) patients in group B (p-value: 0.36). Conclusion Based on our results, we did not find any significant association between the use of ACEIs/ARBs and either the severity of COVID-19 infection necessitating admission to ICU or in-hospital mortality.

"Tocilizumab-an option for patients with COVID-19 associated cytokine release syndrome: A single center experience", a retrospective study-original article.

BACKGROUND: The first case of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was diagnosed in Wuhan, China in 2019. In the first half of 2020, this disease has already converted into a global pandemic. This study aimed to find that treatment of patients with COVID-19 pneumonia with Tocilizumab or steroids was associated with better outcomes. Objectives: To analyze the effectiveness of Tocilizumab in moderate to severe Covid-19 patients based on predefined assessment criteria . Study Settings: Single-center, Fatima Memorial Hospital, Lahore. STUDY DESIGN: Quasi-experimental. DURATION OF STUDY: From May 12, 2020 to June 12, 2020. PATIENTS & METHODS SAMPLE SIZE AND TECHNIQUE: Sample size was 93; 33 patients were kept in the experimental group, given Tocilizumab, 8 mg/kg intravenously or 162 mg subcutaneously, and the rest of the 60 patients were given corticosteroids, methylprednisolone 80 mg/day. Consecutive sampling. Failure of therapy was labeled when patients were intubated or died, and the endpoints were failure-free survival which was the primary endpoint, and overall survival secondary at the time of discharge. RESULTS: A total of 93 patients were enrolled, the Tocilizumab (TCZ) group (case) and Corticosteroid (CS) group (Control). The median age was 58 years (IQR-21), 37 (39.8%) patients with diabetes mellitus, 11 (11.8%) in the TCZ group, and 26 (28%) in the CS group. On the whole, the total median hospital stay in days was 7 with IQR (4), a total of 83 (89.2%) patients recovered successfully and discharged, 27 (29%) in the TCZ group and 56 (60.2%) in the CS group. Total 10 (10.8%) patients died, out of which 6 (6.5%) belonged to the TCZ group and 4 (4.3%) belonged to the CS group The median Oxygen requirement with IQR was 8 (9) in both the groups and in total as well, p-value (0.714). CONCLUSIONS: Tocilizumab is a quite effective treatment option for critically sick patients of Covid-19 by reducing their oxygen requirement drastically and so the ICU stay, median hospital stay and so the mortality as well. CLINICALS TRIALS REGISTRATION: UIN # NCT04730323.

Characterization of Antileishmanial Compounds from Lawsonia inermis L. Leaves Using Semi-High Resolution Antileishmanial Profiling Combined with HPLC-HRMS-SPE-NMR.

This work describes an analytical platform based on semi-high-resolution antileishmanial profiling combined with hyphenation of high-performance liquid chromatography - high-resolution mass spectrometry - solid-phase extraction - nuclear magnetic resonance spectroscopy, i.e., semiHR-antileishmanial assay/HPLC-HRMS-SPE-NMR. The platform enables fast pinpointing of HPLC peaks representing Leishmania tropica inhibitors in complex matrices, with subsequent structural identification of targeted inhibitors. Active analytes were cumulatively trapped on SPE cartridges and the structures elucidated by analysis of NMR spectra obtained in the HPLC-HRMS-SPE-NMR mode. This led to the identification of six known compounds 2,4,6-trihydroxyacetophenone-2-O-ß-D-glucopyranoside (1), lalioside (2), luteolin-4'-O-ß-D-glucopyranoside (3), apigenin-4'-O-ß-D-glucopyranoside (4), luteolin (5), and apigenin (6). IC50 of the active compounds were determined with luteolin being the most potent inhibitor with an IC50 value of 4.15 µg/ml. The platform proved to be an efficient method for the identification of L. tropica inhibitors.

Assessment of medication adherence among type 2 diabetic patients in Quetta city, Pakistan.

OBJECTIVES: Type 2 diabetes (T2DM) is a growing burden among all countries including Pakistan, with medication adherence very important to improve care. However, little is known about medication adherence in Pakistan and potential predictors among T2DM patients to provide future guidance. This needs to be addressed. Consequently, the present study sought to assess medication adherence among type 2 diabetic patients in Quetta city, Pakistan. METHODS: Questionnaire based, descriptive study among 300 Pakistani patients attending public and private hospitals aged 18 years and above, having a confirmed diagnosis of T2DM, without additional co-morbidities were targeted. Descriptive statistics were used to describe demographic and disease characteristics. The association between socio-demographic data and study variables was compared through the Mann Whitney/Kruskal Wallis test (where applicable). The factors that were significantly associated with medication adherence were further assessed by logistic regression analysis. RESULTS: 55.6% of patients had high adherence although overall patients reported moderate adherence. Age, gender, education, diabetes-related knowledge and treatment satisfaction were significantly associated with medication adherence. Older males with only primary education and with poor diabetes-related knowledge had the lowest adherence. CONCLUSIONS: This study presents a model that is associated with medication adherence among T2DM patients, with disease-related knowledge as a significant predictor of likely adherence. Results of the current study revealed that improved diabetes related knowledge plays a significant role in improving medication adherence. Healthcare practitioners and the system should formalize and acknowledge patient education as a key component to treat patients with T2DM. This should include a greater role for pharmacists and other professionals.

Frequency and evaluation of the perceptions towards caesarean section among pregnant women attending public hospitals in Pakistan and the implications.

OBJECTIVES: There is increasing prevalence of caesarean sections (CS) worldwide; however, there are concerns about their rates in some countries, including potential fears among mothers. Consequently, we aimed to determine the frequency of CS, and explore patient's perception towards CS attending public hospitals in Pakistan, to provide future guidance. METHODS: A two-phased study design (retrospective and cross sectional) was adopted. A retrospective study was conducted to assess the frequency of CS over one year among four public hospitals. A cross sectional study was subsequently conducted to determine patients' perception towards CS attending the four tertiary care public hospitals in Quetta city, Pakistan, which is where most births take place. RESULTS: Overall prevalence of CS was 13.1% across the four hospitals. 728 patients were approached and 717 responded to the survey. Although 78.8% perceived CS as dangerous, influenced by education (p = 0.004), locality (p = 0.001) and employment status (p = 0.001), 74.5% of patients were in agreement that this is the best approach to save mother's and baby's lives if needed. 62% of respondents reported they would like to avoid CS if they could due to post-operative pain, and 58.9% preferred a normal delivery. There was also a significant association with education (p = 0.001) and locality (p = 0.001) where respondents considered normal vaginal delivery as painful. CONCLUSION: The overall frequency of CS approximates to WHO recommendations, although there is appreciable variation among the four hospitals. When it comes to perception towards CS, women had limited information. There is a need to provide mothers with education during the antenatal period, especially those with limited education, to accept CS where needed.

Evaluation of acute toxicity, sedative and analgesic effects of Taverniera glabra methanolic extract on mice.

Present study was conducted on crude methanolic extract of stem and root of Taverniera glabra. In Pakistan T. glabra is found in the region of Balochistan only. T. glabra has numerous therapeutic uses in traditional medicine and it is also used for the pain relief. Current study was carried out to evaluate acute toxicity, analgesic and CNS depressant activity of the plant. Acute toxicity was carried out by oral administration of the T. glabra extract from 250 to 2000mg/kg oral dose. Analgesic activity was carried out by acetic acid induced writhing test and formalin test. Central Nervous System (CNS) depressant activity was carried out by exploratory activities (open field activity, cage crossing activity, rearing test) and forced swimming test. Oral administration of the methanolic extract of T. glabra was nontoxic at the dose of 1500mg/kg in the acute toxicity test. Exploratory behavior of mice treated with the methanolic extract of T. glabra showed sedative effects (P<0.05) in open field, cage crossing, traction and rearing test, particularly at the dose of 500mg as compared with standard drug Diazepam. In forced swimming test, mobility time was significantly (P<0.05) increased at 500mg/kg oral dose, and results were significant as compared with control. Methanolic extract of T. glabra produced significant (P<0.05) analgesic effects at the dose of 500mg/kg in the acetic acid induced writhing test and the formalin test. In conclusion, results show that the crude methanolic extract of T. glabra possess sedative as well as potent analgesic effects. Present pharmacological studies are the first ever studies conducted on the methanolic extract of T. glabra.

Polymorphisms of the ABCB1 Gene in the Pakistani Population.

OBJECTIVE: To investigate the frequency of the single nucleotide polymorphism C1236T in exon 12 of the ABCB1 gene in Pakistani population and to compare it with published data on Asian and Caucasian populations. STUDY DESIGN: Across-sectional observational study. PLACE AND DURATION OF STUDY: Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, from August 2012 to May 2013. METHODOLOGY: C1236T polymorphism was investigated in 426 Pakistani subjects. The frequency was compared with the published data on other Asian and Caucasian populations. RESULTS: The frequencies of ABCB1 C1236T were 16.4% for CC, 44.1% for CT and 39.4% for TT. Pakistanis differed significantly from all the European populations compared in the distribution of the TT genotype of C1236TABCB1 (p < 0.05). The Pakistani population also differed significantly from some of the European populations in the distribution of CC and CT genotype (p < 0.05). CONCLUSION: There was significant difference in the genotype frequency of the ABCB1 gene compared to other populations. This study has provided a framework for future pharmacogenetic and pharmacokinetic studies on this polymorphic variant of ABCB1 gene in the Pakistani population.

Association of Anti-Emetic Efficacy of Ondansetron with G2677T Polymorphism in a Drug Transporter Gene ABCB1 in Pakistani Population.

OBJECTIVE: To determine the association of ABCB1 polymorphism G2677T with anti-emetic efficacy in patients treated with ondansetron for preventing postoperative nausea and vomiting. STUDY DESIGN: A clinical trial. PLACE AND DURATION OF STUDY: Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering, Islamabad, from 2012 to 2013. METHODOLOGY: Four mg ondansetron was administered intravenously 30 minutes before the end of surgery. A total of 246 patients with the complaints of nausea and vomiting and 244 patients without nausea and vomiting were analyzed for G2677T polymorphism using PCR-RFLP method. Results were described as frequency percentages and chi-square test with significance at p < 0.05. RESULTS: The patients with TT genotype had significantly lower incidence of postoperative nausea and vomiting during the first 2 hours (p < 0.001) and between 2 - 24 hours after surgery as compared to other genotypes (p < 0.001). The patients with GG genotypes had significantly higher incidence of this complaint (p=0.014). CONCLUSION: Polymorphism of ABCB1 has an association with responsiveness for ondansetron. There is a role for genetics in the management of PONV.

Hypoglycaemic effects of methanolic extract of Canscora decussata (Schult) whole-plant in normal and alloxan-induced diabetic rabbits.

In present study hypoglycaemic effects of the crude powdered C. decussata and its methanolic extract (ME) in alloxan diabetic rabbits were evaluated. The hypoglycaemic effect was measured by blood glucose, insulin level, HbA1c and his to pathology of pancreas. Glucose lowering effect of the ME was studied in diabetic rabbits. The effects of extract on blood glucose, body weight, food in take, fluid intake, OGTT were also evaluated. The results showed that 0.5,1 and 2g/kg of the powder significantly decreased blood glucose levels in normal rabbits and diabetic rabbits at the intervals checked. Oral intake of pioglitazone also reduced the levels in these rabbits. Synergistic hypoglycaemic effect of 600mg/kg of ME with different doses of insulin (2 & 3unit/kg, s/c) further reduced blood glucose levels of treated alloxan-diabetic rabbits. The oral glucose tolerance test revealed lowered area under curve values in ME treated rabbits. Treatment with ME (400 and 600 mg/kg) for 30 days showed highly significant decrease in blood glucose level by augmenting insulin secretion, HbA1cand significant increase in body weight, serum insulin levels in treated diabetic rabbits. Histopathology study showed regeneration of ß-cells. These studies have, therefore, supported the traditional use of this herb in diabetic patients.

Comparison of diagnostic methods in cutaneous Leishmaniasis (histopathology compared to skin smears).

Present study is carried out to compare laboratory diagnostic methods of Cutaneous leishmaniasis (CL) for the outdoor patients of Bolan Medical College Complex Hospital, Quetta, Balochistan. From November 2005 to December 2007, three hundred cases of CL patients were selected without restriction of age and sex. The lesions were divided into two groups. Early with duration less than 2 months and late duration between 2 to 4 months and were noted as nodules, plaques, ulcers and scarring (in case of relapses). Skin smears were taken on first visit of the patients, followed by skin biopsy for histopathological examination. Result showed that out of 300 cases 163 (54.33%) were positive smears for Leishmania donovani (LD) bodies and 137 (45.67%) were negative smears for LD bodies.. While histological examination of all 300 cases showed that only 83 (27.66%) cases were negative for (LD) bodies and no granuloma seen, except with evidence of acute and chronic inflammation. Further analysis of histological observations of positive cases (72.34%) revealed that 91(30.33%) cases had LD bodies,, 78 (26%) cases had only necrotic sloughs showing polymorph neutrophilic infiltration, and 48(16%) cases were having granulomas composed of, epithelioid cells Langhan's type of giant cells and lymphocytes. It is therefore concluded that histopathological examination as compared to skin smears method is more sensitive method for diagnosis of CL.

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels.

BACKGROUND: Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. METHODS: Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of Morinda citrifolia roots (Mc.Cr). RESULTS: The Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K(+) induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca(++), similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 µM) in normal- Ca(++) and Ca(++)-free kreb solutions and by high K(+), similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 µM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 µM) and removal of endothelium. CONCLUSIONS: These results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of Morinda citrifolia in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant.

Pharmacokinetics of ciprofloxacin in normal rabbits and changes observed in induced dehydrated state.

The pharmacokinetics of ciprofloxacin following oral administration of a single dose of 20 mg/kg body weight was investigated in normal rabbits and changes were observed in water-deprived rabbits. High performance liquid chromatographic method was employed for the determination of plasma concentration of ciprofloxacin. The mean plasma concentration and AUC (0-t) and AUC (0-inf) were significantly different between normal and dehydrated rabbits (P<0.05), but the absorption rate, distribution rate, and elimination rate did not show any statistically significant difference. The results reflect a need for monitoring toxicity of ciprofloxacin in the water-deprived condition.

Some studies on human urine as promoter for the growth of leishmania in vitro.

Leishmaniasis, a parasitic disease caused by the protozoan Leishmania is endemic in many parts of tropic and sub tropic areas of the world. In vitro cultivation of parasite plays an important role in the study and treatment of disease. Traditionally media available do not meet the requirement for the bulk cultivation of Leishmania parasites, it requires fetal calf serum (FCS), that is very expensive and not easily available in the market. It is reported that human urine has stimulatory effect on the growth of Leishmania while cultured in vitro. We undertook a detailed study of such an effect in old world Leishmania isolates causing cutaneous leishmaniasis. Different concentrations of urine are tried and it is found that 1% sterile urine in our undefined medium 1999 supplemented with foetal calf serum gives the maximum growth. It is observed that dated urine has less stimulatory effect on the growth of the parasites as compared to fresh urine. The effect of the urine of different groups is also observed and it is found that the urine of 60 year gives maximum growth.