An in vivo study on the diuretic activity of Holarrhena antidysenterica

Holarrhena antidysenterica is used as diuretic in traditional medicine. The aim of this study was to evaluate the crude extract of H. antidysentrica seeds (Ha.Cr) and its fractions, n-hexane (Ha.Hx), n-butanol (Ha.Bu) and aqueous (Ha.Aq), for their diuretic effect in Wistar rats and to investigate whether the activity is concentrated in any of the fractions. Wistar rats kept on fasting for 24 h with water ad labium, divided into normal, positive control and treated groups were orally given normal saline (20 ml/kg), hydrochlorothiazide (HCT; 10 mg/kg) and different doses of the plant material, respectively. Immediately after dosing, the rats were housed in the metabolic cages. The urine was collected at 2 h interval for 6 h and volume, pH and electrolytes levels were measured. Ha.Cr caused dose-dependent (30 and 100 mg/kg) increase in urine output, indicating the diuretic effect. In addition, Ha.Cr increased urine contents of Na+ and K+, suggesting that the diuretic effect is mediated through increased electrolyte excretion. Similarly, the reference drug, HCT (10 mg/kg), increased urine volume and Na+ and K+ excretion. None of the resultant fractions exhibited diuretic effect comparable to that of the parent crude extract. Ha.Hx was devoid of diuretic effect, Ha.Bu exhibited a mild diuretic effect at 30 mg/kg, whereas, Ha.Aq caused a significant increase in urine output only at 100 mg/kg, indicating that the diuretic activity is distributed among fractions but in an order of increasing polarity of the solvent. The enhanced diuretic effect in the crude extract as compared to any individual fraction is suggestive of the existence of additive and/or synergistic effect in the crude extract. This study shows the presence of diuretic activity in the H. antidysentrica possibly mediated through its saluretic effect, which rationalizes its medicinal use as diuretic

Antiurolithic activity of Origanum vulgare is mediated through multiple pathways

<p>Abstract</p> <p>Background</p> <p><it>Origanum vulgare </it>Linn has traditionally been used in the treatment of urolithiasis. Therefore, we investigated the crude extract of <it>Origanum vulgare </it>for possible antiurolithic effect, to rationalize its medicinal use.</p> <p>Methods</p> <p>The crude aqueous-methanolic extract of <it>Origanum vulgare </it>(Ov.Cr) was studied using the <it>in vitro </it>and <it>in vivo </it>methods. In the <it>in vitro </it>experiments, supersaturated solution of calcium and oxalate, kidney epithelial cell lines (MDCK) and urinary bladder of rabbits were used, whereas, in the <it>in vivo </it>studies, rat model of urolithiasis was used for the study of preventive and curative effect.</p> <p>Results</p> <p>In the <it>in vitro </it>experiments, Ov.Cr exhibited a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of nucleation and aggregation and also decreased the number of calcium oxalate monohydrate crystals (COM) produced in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against DPPH free radical and lipid peroxidation induced in rat kidney tissue homogenate. Ov.Cr reduced the cell toxicity using MTT assay and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm²) crystals. Ov.Cr relaxed high K⁺(80 mM) induced contraction in rabbit urinary bladder strips, and shifted the calcium concentration-response curves (CRCs) towards right with suppression of the maximum response similar to that of verapamil, a standard calcium channel blocker. In male Wistar rats receiving lithogenic treatment comprising of 0.75% ethylene glycol in drinking water given for 3 weeks along with ammonium chloride (NH₄Cl) for the first 5 days, Ov.Cr treatment (10-30 mg/kg) prevented as well as reversed toxic changes including loss of body weight, polyurea, crystalluria, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls.</p> <p>Conclusion</p> <p>These data indicating the antiurolithic activity in Ov.Cr, possibly mediated through inhibition of CaOx crystallization, antioxidant, renal epithelial cell protective and antispasmodic activities, rationalizes its medicinal use in urolithiasis.</p

Mannich bases derivatives of 2-Phenyl-5-Benzimidazole sulfonic acid; Synthesis, Characterization, Computational studies and Biological evaluation

A new series of N-Mannich bases of 2-Phenyl-5-benzimidazole sulfonic acid have been synthesized through amino methylation reaction with secondary amines. The two moieties were held together through a methylene bridge, which comes from formaldehyde (Formalin Solution 37%) used in the reaction. Chemical structures of the newly synthesized compounds have been confirmed using FT-IR,&nbsp;1HNMR and&nbsp;13CNMR. Different&nbsp;in vitro&nbsp;assays including Anti-oxidant, Enzyme inhibition, Anti-microbial and Cytotoxicity assay were performed to evaluate the biological potential with reference to the standard drug. Among the synthesized library, compound 3a shows maximum alpha-glucosidase inhibition with an IC50&nbsp;value of 66.66 μg/ml, compound 3d was found most toxic with LC50&nbsp;value of 10.17 μg/ml. ADME evaluation studies were performed with the help of Molinspiration online software. Docking calculations were also performed. Given the importance of the nucleus involved, the synthesized compound might find extensive medicinal applications as reported in the literature

Studies on bronchodilator and cardiac stimulant activities of Urginea indica

This study was designed to evaluate bronchodilator and cardio-tonic effects of Urginea indica to provide rational for these medicinal uses. U. indica bulb extract was studied on rabbit tracheal and guinea-pig atrial preparations mounted in tissue baths under simulated physiological conditions. U. indica inhibited carbachol (1 µM) and K+ (80 mM)-induced contractions in rabbit trachea, similar to dicyclomine, suggesting the presence of anticholinergic and calcium channel blocking (CCB) mechanisms in U. indica. Anticholinergic and CCB effects of U. indica were respectively confirmed when it shifted the carbachol and Ca2+ concentration-response curves rightwards, similar to dicyclomine. U. indica (0.01-1 mg/mL) increased force of guinea-pig atrial contractions without significantly affecting the rate. These data, indicating that U. indica possesses the bronchodilator activity possibly mediated through a combination of anticholinergic and Ca2+ antagonist mechanisms together with selective positive inotropic effect, provide rational for medicinal applications of U. indica in airways and cardiac disorders

Comparison of different weed control methods in groundnut (Arachis hypogaea L.) under rainfed conditions

&nbsp;The experiment was carried out at Adaptive Research Farm Bhaun Chakwal during Kharif 2014, 2015 and 2016 successive seasons to evaluate the most appropriate method of weed control in groundnut. Three weed control measures were evaluated&nbsp; &nbsp;i.e. pre emergence application of Ipiflour (trifluralin), Stomp (pendimethaline) and hoeing. A weedy check (Control) was also included in the experiment for comparison purpose. The results showed that both chemicals gave significant better yield than hoeing. Stomp as pre emergence weedicides gave significant yield (710.6 kg/ha) during all tested periods and gave maximum net return of Rs. 17919/- with CBR 5.66 followed by ipiflour with net return of Rs.8773.2/- and CBR 3.77. It is concluded from the experiment that the &nbsp;hand hoeing gave reasonable groundnut yield (680kg/ha) but it was uneconomical due to high labor wages. So it is concluded that weedicides application is most appropriate and economical method of weed control in groundnut

Association of Sociodemographic Factors with Trends of Self-Medication Practice and Its Hazard Perception for Oral Health Problems among Patient

OBJECTIVES: To assess the impact of sociodemographic factors with the trends of self-medication practice and its hazard perception among patients METHODOLOGY: A cross sectional descriptive study was conducted on the patients visiting Sharif Medical and Dental College from June 2019 to June 2020. Data was collected using a validated questionnaire from 142 patients. Chi-square and fisher exact tests were used to find the association of trends of self-medication practice and hazard perception with sociodemographic factors. RESULTS: The patients in the age range of 18 to 29 years practiced self-medication the most. The triggering factor for use of medication was toothache among all ages. The most commonly used drug was reported to be analgesics. The main reason for self-medication was lack of time to visit the doctor. The females practiced self-medication more than the males. The triggering factor for both the genders was toothache and analgesics were mostly used. The patients with tertiary level education and those who were unemployed practiced self- medication the most. The triggering factor was toothache across all levels of education and employed as well as unemployed patients. Drug resistance was stated the main hazard. CONCLUSION: The triggering factor for use of medication was toothache, most commonly used drugs were analgesics and the main reason for self-medication was lack of time across all ages, both the gender, married and unmarried patients, levels of education and employment. Un-employed patients and those with tertiary level of education-practiced self- medicated themselves the most. The highest percentage of patients considered drug resistance to be the biggest hazard

Chiari Malformation with and without Syringomyelia: Surgical Technique and Outcome in 88 Adult Patients

Objective:&nbsp;&nbsp;This study identified the relationship between posterior fossa craniectomy, expansion neuroplasty, and radiological appearances in patients with Chiari malformation with and without clinical syringomyelia with the surgical outcomes in an attempt to correct the lesion. Materials &amp; Methods:&nbsp;&nbsp;Eighty-eight patients with Chiari malformation (CM) were included in the study where 70 had associated syringomyelia. All underwent posterior fossa craniotomy, expansion duroplasty without fiddling with cerebellar tonsils. Patients were evaluated at 1 month, 3 months, and 12 months. The MRI studies were done at 12 months when symptomatic relief and radiological findings were evaluated and matched. Results:&nbsp;&nbsp;Most of the patients were young adults between the age range of 25 – 40 years. The most common complication was pseudomeningocele (5.68%) formation followed by CSF leak (4.54%). Patients with a longer history of Chiari malformation or syrinx-related symptoms and signs had partial relief in symptoms and signs. The poor outcome as expected was seen in patients with atrophic changes in upper limbs and hypertonia in lower limbs, especially in patients with loss of joints position sense and poor balance. Patients showed maximum improvement in headaches both suboccipital as well as generalized. Syringomyelia was decreased in size in 49 patients and remained unchanged in 21.&nbsp; Dysesthesias were improved in 31 patients. Conclusion:&nbsp;&nbsp;Clinical improvement was related to the expansion of the posterior fossa and subarachnoid cistern and reduction in the size of the syrinx. Surgical decompression of the posterior fossa should create adequate space for its contents and reduce the syrinx cavity. The relationship between symptomatic improvement and radiological findings is not always linear. Keywords:&nbsp;&nbsp;Chiari Malformation, Tonsillar Herniation, Syringomyelia, Duroplasty

Assessment of potential dietary toxicity and arsenic accumulation in two contrasting rice genotypes : effect of soil amendments

High concentration of arsenic (As) in rice is a serious problem worldwide. Pot experiments were conducted to assess the potential dietary toxicity of arsenic and effect of various soil amendments on arsenic accumulation in rice grains. Two basmati rice genotypes were used to conduct pot experiments using various levels of arsenic (10, 25, 50 and 100 mg kg-1 29 soil). In addition, plants were exposed to soil collected from a well documented arsenic contaminated site. Contrasting results for growth, yield and grain arsenic concentration were obtained for basmati-385 (Bas-385), exhibiting tolerance (56% yield improvement at 10 mg As kg-1 32 ), while genotype BR-1 showed 18% yield decline under same conditions. Furthermore, application ofsoil amendments such as iron (Fe), phosphate (PO4) and farmyard manure (FYM) at 50 mg kg-1,80 kg ha-1 and 10 t ha-1, respectively improved the plant height and biomass in both genotypes. Accumulation of arsenic in rice grain followed a linear trend in BR-1 whereas a parabolic relationship was observed in Bas-385. Both genotypes exhibited a positive response to iron sulfate amendment with significant reduction in grain arsenic concentrations. Regression analysis gave soil arsenic threshold values of 12 mg kg-1 in Bas-385 and 10 mg kg-1 39 in BR-1 for potential dietary toxicity. This study suggests that genotype Bas-385 can be used for safe rice production in areas with soil arsenic contamination up to 12 mg kg-1 41 and that appropriate dose of iron sulfate for soil amendment can be used effectively to reduce translocation of arsenic to rice grai

Synthesis of Selective CDK2/SPY1 Inhibitors employing Stereochemical Control - An invaluable tool in an Organic Chemist’s belt

The cell cycle of a healthy eukaryotic cell depends on the efficiency of cyclin-dependent kinase (CDKs) checkmarks, to ensure normal cell proliferation. CDK2 is responsible for progression of cells into the S and M phases, and it is critical to the abnormal growth processes of cancer cells. Examination of different kinds of human cancers, for their vulnerability to CDK2 inhibition, has revealed CDK2 as a good therapeutic target. In the past two decades, various CDK2 inhibitors have been designed but have stumbled on the roadblock of selectivity issue, since CDK2 shares 74 and 68% sequence identity and active sites with its family members’ CDK3 and CDK1, respectively. Moreover, it’s not CDK2 alone that needs to be targeted but the activated complex it forms with Spy1, a protein that can activate CDK2 in the same way as cyclin but is highly upregulated in cancer cells. After extensive computational studies, we found some unique yet challenging CDK2/SPY1 inhibitors. In this presentation, I will discuss the importance of stereochemical control in the design and synthesis of novel and selective CDK2/SPY1 inhibitors. The synthesis ensures that the inhibitors are stereochemically pure, and thus the biological activity can be accurately evaluated. These results can then be used to refine our computational models to further improve the selectivity of our drug candidates

Outcomes of Cranioplasty after Craniectomy

Objective:&nbsp;&nbsp;Craniectomy is a widely used procedure in neurosurgery that results in more cranioplasties to repair skull defects. The complication rate after cranioplasties seems to be higher than elective craniotomies so this study was conducted to determine the outcome of cranioplasty after craniectomy. Materials &amp; Methods:&nbsp;&nbsp;The patients included in this study had craniectomy and cranioplasty for any indication. Patients included had variables, such as age, sex, underlying pathology, craniectomy and cranioplasty dates, the material used for cranioplasty (autologous bone or methyl methacrylate), and methods of cranioplasty flap fixation (sutures or titanium plates and screws) follow up period and complications. Results:&nbsp;&nbsp;It was concluded that patients in the age group of 41 – 60 years (5 cases), males (7 cases), cranioplasty performed after 6 months (5cases) with autologous bone graft (8cases) were associated with more complications. Conclusion:&nbsp;&nbsp;The overall rate of complications associated with cranioplasties is not negligible, however, early cranioplasty in young patients with the use of polymethyl methacrylate may be associated with less complication rate. Keywords:&nbsp;&nbsp;Decompressive, Craniectomy, Cranioplasty, Autologous, Polymethyl Methacrylat