Evaluation of anticonvulsant activity of angiotensin receptor antagonists in an animal model

Background: Epilepsy is common chronic disorder in clinical practice and there was some studies which shows brain renin angiotensin system may be involved in upregulation of seizures hence present study was planned to investigate whether angiotensin II AT1 receptor antagonists possess anticonvulsant activity in experimental animals.Methods: The anticonvulsant activity of angiotensin receptor antagonists, losartan (50 mg/kg), telmisartan (30 mg/kg) and candesartan (20 mg/kg), were administered intraperitoneally to the mice and evaluated by using maximum electroshock (MES) and pentylenetetrazol induced seizures (PTZ) seizure methods. The standard was taken as phenytoin for MES and diazepam for PTZ method. Motor impairment of performance was assessed by the inverted screen test and spontaneous motor activity with digital actophotometer.Results: Losartan demonstrated the anticonvulsant efficacy in MES and PTZ models. Telmisartan and candesartan have anticonvulsant activity in MES induced seizures, but did not show protection against pentylenetetrazol induced seizures. Losartan at dose 50 mg/kg prolonged the mean latency to convulsion (p<0.01) and mean number of convulsions also significantly reduced (p<0.05) convulsions in the mice. Telmisartan and candesartan at dose 30 mg/kg and 20 mg/kg respectively showed significant prolongation in mean latency to convulsion (p<0.05). None of the test drugs i.e. angiotensin receptor antagonists showed significant motor impairment.Conclusions: Angiotensin receptor antagonists: losartan, telmisartan and candesartan had showed anticonvulsant activity in PTZ and MES seizure methods. The exact mechanism of action of their anticonvulsant action not precisely known and hence there is more studies need to test it in various other animal anticonvulsant models

Novel Spectrophotometric Method for Estimation of Olmesartan Medoxomil from its Tablet Dosage Form Using Hydrotropic Solubilization

Aim: Quantitative estimation of poorly water-soluble drugs involves use of organic solvents. In the present investigation, hydrotropic solubilization is employed to enhance the aqueous solubilities of poorly water-soluble drugs like Olmesartan Medoxomil in tablet dosage forms. Material and methods: This method utilizes 0.05 M Sodium acetate solution as hydrotropic solubilizing agent Where Olmesartan Medoxomil shows maximum absorbance at 256 nm. The 0.05 M Sodium acetate solution does not show any interference with the sampling wavelength. The hydrotropic agent and additives used in the manufacture of tablets did not interfere in the analysis. Results and Conclusion: The drug obeys the Beer’s Law in the concentration range 2-14 μg/ml with correlation coefficient value of 0.9987. The developed reliable method was validated statistically following ICH Q2B (R1) guidelines. Statistical analysis proved that the method was simple and rapid for the estimation of Olmesartan Medoxomil and can be used for routine analysis of Olmesartan Medoxomil in quality control laboratories. The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 Kg.m.s-2. The in vitro drug release studies revealed that formulation FA8 released 84% and FB16 released 99.01% of drug in 140 min.Objetivo: La estimación cuantitativa de fármacos poco solubles en agua implica el uso de disolventes orgánicos. En la presente investigación, se emplea la solubilización hidrotrópica para mejorar las solubilidades acuosas fármacos poco solubles en agua como el olmesartán medoxomilo dosificado en comprimido. Material y Métodos: Este método emplea acetato sódico 0,05 M como agente solubilizante hidrotrópico, mostrando el olmesartán medoxomilo una absorbancia máxima a 256 nm. La solución de acetato 0.05 M no muestra ninguna interferencia con la longitud de onda de muestreo. El agente hidrotrópico y los aditivos utilizados en la elaboración de los comprimidos no interfieren en el análisis. Resultados y conclusiones: El fármaco obedece a la Ley de Beer en el intervalo de concentraciones 2-14 mg / ml con un de coeficiente de correlación de 0,9987. El método desarrollado fue validado estadísticamente siguiendo las directrices ICH Q2B (R1) . El análisis estadístico demostró que el método era sencillo y rápido para la estimación de olmesartán medoxomilo y se puede utilizar para análisis de rutina de olmesartán medoxomilo en laboratorios de control de calidad

HPLC ANALYSIS OF HUMAN URINE FOR OXALATE CONTENT

Objective: In the present communication, development and validation of reverse phase-high performance liquid chromatography method have been carried out for estimation of oxalate content in the urine of human volunteers with recurrent kidney stone disease and healthy status.Methods: The analysis of oxalic acid has been carried out on KYA TECH HiQ Sil C18HS column using a mobile phase of methanol: 0.001 N acetic acid in water (50:50, v/v) with a flow rate of 1 ml/min and detection wavelength, 237 nm.Results: Analysis of oxalate content was carried out using single point calibration method with retention at 2.705 min with good resolution parameters. Urine sample collected from kidney stone patients and healthy volunteers over the period of 24 h were analyzed and it has been found that concentration of oxalate in healthy volunteers is less than 12 µg/ml whereas that in case of kidney stone patients is in the range of 39-151 µg/ml and this data can be utilized for further interpretations about oxalate content in healthy and kidney stone diseased volunteers. This method was validated as per united states food and drug administration (USFDA) guidelines by the study of accuracy, precision, linearity, range, selectivity, the lower limit of quantitation, extraction recovery studies and stability studies for determining oxalate content in the urine of human volunteers. As relative standard deviations of oxalate content estimated are less than 5 percent, the method can be claimed accurate, precise, sensitive and selective for determining oxalate content in the urine of human volunteers.Conclusion: The results are satisfactory, proving the effectiveness of the method for analysis of oxalate content from other biological fluids with few optimizations

Synthesis, Characterization and Quantification of Simvastatin Metabolites and Impurities

Simvastatin is used in treatment of hypercholesterolemia because it regulates cholesterol synthesis as a result of its β-hydroxy acid acting as an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA). The present communication deals with synthesis, characterization and development of accurate, precise and sensitive Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for simultaneous estimation of simvastatin and its synthetic impurities. The impurities methyl ether and β-hydroxy acid of simvastatin were synthesized in the laboratory and characterized by MS, NMR and FT-IR spectroscopy. The separation of simvastatin and its impurities was carried out on an isocratic JASCO RP-HPLC system using KYA TECH HIQ SIL C18 column (150 × 4.6 mm internal diameter, particle size 5 μm) operating at ambient temperature using acetonitrile:water (80:20 v/v) with 0.1% orthophosphoric acid as mobile phase. The method developed for HPLC analysis of three impurities along with simvastatin was validated using ICH Q2B (R1) guidelines and it complied with these guidelines. The results of analysis were found to be in the range of 98.14% to 101.89% for all analytes with acceptable accuracy and precision. The method can be used for detection and quantification of synthetic impurities in bulk or formulations of simvastatin

Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients

ANALGESIC PROPERTY OF ANGIOTENSIN AT1 RECEPTOR ANTAGONIST: CANDESARTAN IN RATS AND MICE

  Objective: The objective was to evaluate analgesic activity of candesartan in graded dose in tail flick method in rats and acetic acid-induced writhing in mice.Methods: Wistar Albino rats of either sex weighing 200-250 g or Swiss Albino mice of either sex weighing 20-25 g. Analgesic activity of candesartan (5 mg/kg, 10 mg/kg, 15 mg/kg.) was evaluated in graded dose and compared with tramadol (10 mg/kg) and aspirin (100 mg/kg) using tail flick response method and acetic acid-induced writhing of analgesia. Study was conducted after approval from the Institutional Animal Ethics Committee, which is an approved body by Committee for the Purpose of Control and Supervision of Experiments on Animals letter no. 78 dated October 18, 2012.Results: In the present study, oral administration of candesartan showed analgesic activity at high dose compared to the control and less analgesic activity as compared to the standard in analgesic methods. In tail-flick method, after 30-90 minutes of drug administration, tail flick latency of candesartan (15 mg/kg) was significant (p&lt;0.05) compared with control but less than that of tramadol and aspirin. In acetic acid induced writhing method, the analgesic activity of candesartan was significant only at high dose (15 mg/kg) compared to the control.Conclusion: Candesartan possesses analgesic activity only at high dose. However, further studies need to be carried out to see underlying mechanism candesartan in analgesia and to know the extent of analgesia.Keywords: Acetic acid induced writhing method, Angiotensin II receptor blockers, Candesartan, Tail flick metho

IMPLEMENTATIONOF TOTAL PRODUCTIVE MAINTENANCE FOR CAPACITY ENHANCEMENT BY IMPROVING OVERALL EQUIPMENT EFFECTIVENESS OF SLOTTING AND HONING MACHINE

Productivity is a measure of the rate at which outputs of goods and services are produced per unit of input (labour, capital, raw materials, etc.). It is calculated as the ratio of the amount of outputs produced to some measureof the amount of inputs used. Productivity measures are used at the level of firms, industries and entire economies. The goal of the any TPM program is to improve productivity and quality along with increased employee morale and job satisfaction. It is essential requirement for longer life cycle of machines in an industry. In this paper experience of implementing Total Productive Maintenance is shared and investigated for a company manufacturing compressors

Implementationof Total Productive Maintenance for Capacity Enhancement by Improving Overall Equipment Effectiveness of Slotting and Honing Machine

Productivity is a measure of the rate at which outputs of goods and services are produced per unit of input (labour, capital, raw materials, etc.). It is calculated as the ratio of the amount of outputs produced to some measureof the amount of inputs used. Productivity measures are used at the level of firms, industries and entire economies. The goal of the any TPM program is to improve productivity and quality along with increased employee morale and job satisfaction. It is essential requirement for longer life cycle of machines in an industry. In this paper experience of implementing Total Productive Maintenance is shared and investigated for a company manufacturing compressors

Microwave Assisted Synthesis of 2,4-Diphenyl-4H-chromen-5-one Using ZnCl2/Montmorillonite K-10

α, β-Unsaturated carbonyl compounds and 1, 3-cyclohexanedione under microwave irradiation in the presence ZnCl2/montmorillonite K-10 offers the corresponding 2,4-diphenyl-4H-chromen-5-one in excellent yield. Catalyst is recycled and reused for several time