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Grewia asiatica L. is a potential medicinal plant used for various diseases in traditional medicine. Current study was aimed to evaluate the cardio protective, anti-inflammatory, analgesic and CNS depressant activities of Grewia asiatica L. fruit extract. In cardio protective activity myocardial injury was produced by injection of Isoproterenol (200 mg/kg, s.c), G. asiatica 250 and 500mg/kg treated groups significantly (p<0.05) decreased the level of serum AST, ALT, LDH and CKMB, hence produced cardio protective effect. In analgesic activities G. asiatica produced significant (p<0.05) analgesic effects in acetic acid induced writhing, formalin, paw pressure and tail immersion test. G. asiatica at 250 and 500mg/kg oral dose, significantly (p<0.05) reduced the rat paw edema in carrageen an induced rat paw edema test. G. asiatica extract also produced significant CNS depressant effects in open field, hole board and thiopental sodium induced sleeping time. Findings of the current study suggest that G. asiatica fruit extract showed potential pharmacological effects and can be utilized in alternative medicine. [ABSTRACT FROM AUTHOR]

In skin disorders such as microbial and fungal infections, plants and their parts are used. However, there have been very few scientific reports of herbal extracts of the plant Pinus gerardiana to be administered transdermally. The antifungal activity was assessed using poisoned food method against the strains of three pathogenic fungi, namely Alternaria alternata, Curvularia lunata and Bipolaris specifera. Ointment was prepared according to British pharmacopeia and physiochemical evaluation tests were performed. The GCMS was used to determine the chemical composition of the essential oil of Pinus gerardiana. 27 components were obtained. Monoterpenes= 89.97%, Oxygenated monoterpenes = 8.75%, Sesquiterpenes = 2.21% out of 100% of the total composition. The extract of pinus gerardiana showed a zone of inhibition on organism Bipolaris specifera 2.98±0.1µg/ml, Alternaria alternate 3.48±0.21µ/ml and Curvularia lunata 5.04±0.24µg/ml. Ointment was prepared with pH 5.9, conductivity 0.1, viscosity 22.24 and tested for stability. Franz cells were used in vitro, and release was determined from 30 minutes to 12 hours. [ABSTRACT FROM AUTHOR]

Controlled release" in drug release kinetics denotes reproducibility and predictability, implying that drug release from delivery devices follows a kinetically predictable and repeatable rate profile from dose to dose. In the current study controlled release tablets of famotidine were prepared by direct compression technique using Eudragit RL 100 polymer. Four different formulations of controlled release tablets of famotidine as (F1, F2, F3 and F4) were prepared by adding different drug to polymer ratio. The pre compression and the post compression of the formulation, characteristics were compared. All results obtained were within the specified standard limits. FTIR studies showed that both the drug and the polymer were compatible. In vitro dissolution study were conducted by Method II (Paddle Method) in phosphate buffer (pH 7.4), at 100rpm. Power law kinetic model was applied for drug release mechanism. The difference similarity of the dissolution profile was determined. The formulation F1 and F2 were released 97 and 96 % in 24 hours and other formulations F3 and F4 were released subsequently 93% and 90% in 24 hours. The results showed that incorporation of Eudragit RL 100 in the formulation of controlled release tablets prolong the drug release rates for 24 hours. The release mechanism was Non-Fickian diffusion mechanism. It was deducted from the current study that the Eudragit RL 100 can be efficiently incorporated in the formulation of controlled release dosage forms with predictable kinetics. [ABSTRACT FROM AUTHOR]

Piroxicam (PC) is a non-steroidal anti-inflammatory drug characterized by poor aqueous solubility and reported to cause and impart crucial GIT irritation, bleeding, peptic and duodenal ulcer. Engineering of PC loaded microcapsules and its surface modification using different polymers has become the popular approach to address the said issues. The purpose of the study was to develop new PC loaded gastro-protective polymer hybrid microspheres (PHM) with subsequent conversion to tablet dosage form having modified dissolution rate and improved bioavailability. The crystallinity of the PC loaded PHM were established through powder X-ray diffraction. The optimised microspheres, PCM1 with particle size 32±3.0μm, entrapment efficiency 83.78±2.5% and in vitro drug release 87.1±2.6% were further subjected to tablets development and in vivo evaluation. The in vitro drug release study conducted for PHM at pH media 1.2 and 6.8 demonstrated retarded and enhanced drug release rates (P<0.001) respectively. Both accelerated and real time stability studies confirmed stability of the PC loaded PHM based tablets. A substantial improvement in the drug plasma concentration 12.6±2.36 (P<0.001) was observed for the produced tablets compared to the marketed formulations. [ABSTRACT FROM AUTHOR]

Bovine serum albumin (BSA) is usually employed as a model protein because of being homologous with human serum albumin. Cysteine-34 of BSA has been oxidised with Ellman's reagent to produce BSA labelled with an Ellman's moiety (BSA-SE). The BSA-SE was then reacted with glutathione, N-acetylcysteine and D-penicillamine (Dpen). The two were able to release the Ellman's moiety bound at cysteine-34 while D-pen did not. Albumin labeled using Ellman's reagent was used to demonstrate the cleavage of a protein mixed disulphide. The kinetics of thiol disulfide interchange reactions involving formation of a chromophoric thiolate were determined by UV-visible spectroscopy. The reaction of thiolates with excess Ellman's reagent is used for quantitative estimation of thiol by measuring the absorption at λ, 412 nm. The disulfide exchange reactions occurring at Cys-34 of BSA was determined and the reduction of oxidized Cys-34 was studied in order to understand the reverse reaction. Spectroscopic evidence suggested that glutathione and N-acetylcysteine remove the label and produce BSA in a disulfide form. In contrast, D-pen reaction returned BSA to its thiolate form via mediation. It was observed that thio-disulfide exchange occurred at cysteine-34 labelled with Ellman's moiety. The implications to the redox status of plasma are discussed. [ABSTRACT FROM AUTHOR]

Controlled release formulations are administered once a day and reduce frequency of dose and ensuring patient's compliance. In the current research controlled release matrices of losartan potassium formulated with polymeric combinations of ethocel grade 7 with carbopol 934P NF using different concentrations of polymers. In some polymeric tablets, Co-excipients like CMC, Starch, HPMC was added by replacing of 10% of filler in formulations at 10:5. Tablets were prepared by direct compression method and evaluated for physicochemical characteristics. USP Method-1 (rotating basket method) was used to carry out dissolution study in phosphate buffer pH 6.8. Drug release kinetics determined and comparison of dissolution patterns was done with reference tablets. The polymeric combinations well retarded drug release and drug was released by anamolous non-fickian diffusion mechanism. Dissolution profiles of tested tablets and reference tablets were found not similar. Drug release rate was increased by co-excipients. It was concluded from this research work that this polymeric combination can be used efficiently in designing of controlled release martices. [ABSTRACT FROM AUTHOR]

Berberis lycium (family Berberidaceae) grows in district Sherani, Balochistan, Pakistan. It is used for the treatment of various disorders by the people of Balochistan. The present work was carried out to explore analgesic and neuropharamcological activities of crude methanolic extracts of B. lyceum. The analgesic activity was carried out by acetic acid induced writhing test and formalin test. Open field test, cage crossing test, rearing test, traction test and forced swimming test were carried out in neuropharmacological activities. The results reveal that crude methanolic extracts of B. lyceum showed significant (P<0.05) analgesic activity in acetic acid induced pain as well as with formalin test. In neuropharmacological activities, crude methanolic extracts of B. lyceum showed significant (P<0.05) central nervous system depressant activity and in forced swimming test it showed anxiolytic effects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to prepare topical formulations of micro emulsion, gel and ointment containing the Hedera helix L. extracts against asthma and to evaluate the physicochemical characteristics. A validated HPLC method was used for the analysis of blood plasma. In-vivo studies of the drugs were compared in rabbit plasma with oral dosing. Stability studies were performed for 3 months. The results showed that formulations were stable. No Skin irritation observed on rabbits. The optimized micro emulsion and gel showed fast absorption. Maximal plasma concentration (cmax) and the maximal time to reach cmax (tmax) were 70.226μg/mL, 75.26μg/mL and 2 hours for the micro emulsion and gel, 90.11μg/mL and 1 hour for the oral drug syrup respectively. Pharmacokinetic parameters such as tmax, cmax and AUC of the selected formulations and oral dosing were significantly different (P < 0.01). [ABSTRACT FROM AUTHOR]

Herbal remedies like the Thymus serpyllum L. is useful in traditional medicine for the treatment of many diseases especially congestion, and bronchitis. The purpose of this study was to formulate a micro-emulsion, a gel and an ointment containing the plant hydro distilled thymus oil extracted from Thymus serpyllum L. collected from Ziarat, Balochistan. The prepared formulations were subjected to in-vitro and ex vivo study release, High performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC), to justify their suitability for topical use. The in-vitro and ex-Vivo release was studied using Franz Cells and using two different kinds of membrane synthetic dialysis cellulose membrane and natural rabbit skin, and the amount of drug released was determined by HPLC at λ 274nm. The three formulations result obtained through dialysis cellulose membrane showed the faster release than the natural rabbit skin. However, the micro-emulsion, gel formulation showed the same release except ointment. The release from the above mentioned formulation can be arranged in the following descending order. micro-emulsion > Gel > Ointment. The best fit of release kinetics was achieved by Krosmeyer- Peppas, the TLC and HPLC identifies the Thymol, isolation and quantification of the marker. This study demonstrates that it is necessary to assess the impact of release and permeability pattern of different formulations. In vitro and ex-vivo diffusion cell experiments can be utilized to develop formulations of traditional medicines identifies. [ABSTRACT FROM AUTHOR]

Thallium has been shown to significantly influence various tissues of living organisms; Exposure to Thallium can disturb mitochondrial function, degenerate neurons, and interfere with the function of critical metabolic enzymes and co-enzymes. Glutathione (GSH) an essential biomarker is considered a key factor in harnessing the thallium toxicity. In the present study the interaction of Thallium (Thallium Chloride) and glutathione was investigated spectro-photo-metrically in aqueous media. The renowned Elman's experimental protocol was followed at a wavelength of 412nm for Glutathione quantification in each sample. The pH of each sample was maintained at 7.6 using Phosphate buffer during the entire course of the experiment. A concentration as well as time dependent depletion of glutathione after exposure to various concentration of Thallium metal was observed, revealing chemical interaction between the metal and glutathione. The exact mechanism of interaction of Thallium and glutathione is still to be investigated. However, this piece of research suggests that a decrease in the concentration of Glutathione may be due to Thallium-GSH abduct or oxidize glutathione (GSSG) formation. This study was performed in-vitro as a model of in vivo. [ABSTRACT FROM AUTHOR]

Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity. Angiotensin II Receptor Antagonists/Blockers (ARBs) compete with angiotensin II at the receptor site and block the contractile effect of angiotensin II in all vascular smooth muscles. Among all Angiotensin II Receptor Antagonists/Blockers (ARBs), Telmisartan, Milfasartan and many others have benzimidazole ring in their structure. In this study Angiotensin II Receptor Antagonists/Blockers (ARBs) have been prepared. Synthesized compounds were characterized by physical data and FTIR spectroscopic technique. Synthesized compounds studied were finally screened for their antihypertensive activity by tail cuff method of measurement of blood pressure by NIBP apparatus (None Invasive Blood Pressure) using Chart 5.0 software. The compounds synthesized were 2-(3-nitrophenyl)-1Hbenzimidazole (1a), 3-(1H benzimidazol-2-yl)aniline (1b) and 5-(1H-benzimidazol-2-yl)-2-methoxyphenol (1c). The synthesized compounds have shown antihypertensive activity by taking Losartan as lead compound. [ABSTRACT FROM AUTHOR]

A new high performance liquid chromatography (HPLC) method for the quantitative determination of sitagliptin in human plasma was developed and validated for pharmacokinetics study. The plasma was spiked with the internal standard (Salbutamol, IS), extracted with trichloro acetic acid. The extracted analyte was injected into a Symmetry® ODS C18 column (250mm×4.5mm, 5m) and the flourometric detector was operated at 267nm for excitation and 575nm for emission. The mobile phase consisting of Potassium dihydrogen phosphate buffer pH (4.9)-Acetonitrile- Methanol (30:50:20 v/v) at flow rate of 1.0mL/min. The method showed high specificity. Calibration curves of the peak area ratio of each analyte/IS versus sitagliptin concentration were linear in the range of 0.122-31.25μg/mL (r>0.989) for plasma and 0.012-25ug/ml for QC solution(r>0.995). The lower limit of quantification (LLOQ) was 0.122μg/mL in plasma and 0.012 in QC solution. The intraday and interday coefficient of variation was lower than 10%. The accuracy (relative recovery) at three levels was 100.95%, 101.03% and 97.79% respectively. The extraction recovery was 97.6%, 92.2% and 91.96% at the concentrations of 6.25, 25 and 100μg/mL, respectively. Short term and long term, freeze thaw stability of standard solutions and plasma samples were satisfactory. The optimized HPLC method was validated and proved to be specific, robust and accurate for determination of Sitagliptin in human plasma. [ABSTRACT FROM AUTHOR]

Glutathione is an essential antioxidant of living organism that provides a primary protection against metals toxicity. A significant amount of glutathione is present in blood erythrocytes, plasma and liver hepatocytes to protect them from oxidative damage from both external and internal oxidants. Metalo-element palladium has numerous pharmacological, clinical and toxicological compensations, like palladium is used as anti-viral, anti-bacterial, neuro- protective and anti-tumor agent. However studies have also indicated some mild to serious toxic effects of palladium metallo-elements. In the presence study the interaction of palladium inorganic salt and organic complex with glutathione (GSH) content of liver homogenate was examined spectro-photometrically. 20% (w/v) liver homogenate was prepared of the collected liver of rabbit in 5% TCA (tri-chloro-acetic acid) solution and 1mm EDTA, using a potter-eveljhem homogenizer with motor driven Teflon pestle. The GSH content quantification was carried out by Elman's method. Our finding showed that there was a depletion of GSH content by both palladium inorganic salts and organic complexes, concentrations wise as well as with time elapse as level of GSH content decrease from (43.6% to 72.62%) with Palladium Nitrate and from (24.09 to 59.5%) with Bis-benzonitrile Palladium II Chloride as compared to control, and further dropped with time incubation from 0-90 minutes from (49.7 to 87.1%), with Palladium Nitrate and from (29.3% to 67.6%) respectively. The result showed that the effect of both inorganic salt of palladium was more enhanced as compare to its organic complex. It was suggested from our finding that the depletion in the glutathione content of liver homogenate may be due to oxidation of glutathione or due to glutathione metal abduct formation by both inorganic salt and organic complex of palladium. This study in situ is a model of in vivo. [ABSTRACT FROM AUTHOR]

Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance. In present study, controlled release co-precipitates of Metoprolol Tartrate and Losartan Potassium were prepared by solvent evaporation method using polymers such as Eudragit RL 100 and Carbopol 974PNF and controlled release tablets were directly compressed into tablets. In-vitro dissolution of controlled release coprecipitates were performed by USP Method-II (paddle method) and tablets were evaluated by USP Method-I (rotating basket method) in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature was maintained constant at 37±1.0 0C and the rotation speed of paddle and basket was kept constant at 100rpm. Drug release mechanisms were determined by applying Power Law kinetic model. The difference and similarity of dissolution profiles test formulations with reference standards were also determined by applying difference factor (f1) and similarity factor (f2). The results showed that the controlled release co-precipitates with polymer Eudragit RL 100 of both the drug extended the drug release rates for 10 hours and those having polymer Carbopol 974P NF extended the drug release rates for 12 hours. The controlled release tablets prepared from controlled release co-precipitates extended the drugs release up to 24 hours with both the polymers. The drug was released by all tests anomalous non fickian mechanism except F1 and F5 do not follow Power Law. The f1 and f2 values obtained were not in acceptable limits except F15 whose values were in acceptable limits. It is concluded from the present study that polymers (Eudragit RL 100 and Carbopol 974P NF) can be efficiently used in development of controlled release dosage forms having predictable kinetics. [ABSTRACT FROM AUTHOR]

The metalloelement Palladium has a number of potential Pharmaco-clinical advantages. Palladium compounds have antiviral, antibacterial, neuroprotective and antitumor properties. However studies have also indicated some mild to serious toxic effects of Palladium metalloelements. Biothiols are important antioxidants that provide protection against metals toxicity. The interaction of metalloelements with biothiols can provide valuable information about the level of toxicity of the metalloelements and about the protective role of biothiols thereof. In this piece of work the effect of salt and complexes of Palladium on the status of different thiols (GSH, NAC, and D-Pen) in aqueous medium, were examined, The thiol quantification was carried out using Elman's method through UV-visible spectrophotometry and 1HNMR. Results of the study performed in aqueous medium showed that level of different thiols depleted after the addition of the inorganic salts and organic complexes of Palladium. The mechanism of interaction of Palladium with thiols was examined using H-NMR. The results indicate that the depletion in the level of thiols may be due to 1:1 or 1:2 conjugation of Palladium with thiols. These conjugation reactions further suggest that the Palladium have xenobiotic nature causing oxidative stress and thiols play their role in detoxification and biotransformation of these metalloelements. [ABSTRACT FROM AUTHOR]

Thiol groups are extensively present across biological systems being found in range of small molecules (e.g. Glutathione, Homo-cysteine) and proteins (e.g. albumin, haemo-globin). Albumin is considered to be a major thiol containing protein present in circulating Plasma. Albumin contains a single thiolate group located at cysteine-34(cys-34) at its active site. Albumin also binds a wide variety of metals and metals complexes at various sites around the protein. Usually heavy metals are preferentially attached with the thiol group of albumin. The binding of heavy metals at cys-34 provides a mechanism by which the residence time of potentially toxic species in the body can be increased. In this research we have assessed the oxidative modification of and metal binding capacity of cys-34 with heavy metals Palladium and Vanadium to investigate the ease with which it is possible to effect disulfide-thiol exchange at this sites/or remove a metal bound at this position. Both the metals were treated with albumin and then the albumin metals (Pd and V) complexes were treated with small thoil molecules like Glutathione, Cysteine and D-Penicillamine. Our finding showed that the albumin thiol group retained the metals with itself by forming some strong bonding with the Thiols group, it is concluded from this finding that if by chance both the metals enter the living system; strongly disturb the chemistry and physiological function of this bio-molecule. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the antioxidant activity, screening the phytogenic chemical compounds, and to assess the alkaloids present in the E. intermedia to prove its uses in Pakistani folk medicines for the treatment of asthma and bronchitis. Antioxidant activity was analyzed by using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay. Standard methods were used for the identification of cardiac glycosides, phenolic compounds, flavonoids, anthraquinones, and alkaloids. High performance liquid chromatography (HPLC) was used for quantitative purpose of ephedrine alkaloids in E. intermedia. The quantitative separation was confirmed on Shimadzu 10AVP column (Shampack) of internal diameter (id) 3.0 mm and 50 mm in length. The extract of the solute in flow rate of 1 ml/min at the wavelength 210 nm and methanolic extract showed the antioxidant activity and powerful oxygen free radicals scavenging activities and the IC50 for the E. intermedia plant was near to the reference standard ascorbic acid. The HPLC method was useful for the quantitative purpose of ephedrine (E) and pseudoephedrine (PE) used for 45 samples of one species collected from central habitat in three districts (Ziarat, Shairani, and Kalat) of Balochistan. Results showed that average alkaloid substance in E. intermedia was as follows: PE (0.209%, 0.238%, and 0.22%) and E (0.0538%, 0.0666%, and 0.0514%). [ABSTRACT FROM AUTHOR]

The functional receptor for type III interferons (IFNs) is a heterodimer of IFNLR1 and IL10R2. IFNLR1 is expressed in a highly tissue specific manner, with epithelial and liver tissue as the prime expressing tissues in humans. However, knowledge about the molecular pathways responsible for regulating the expression of IFNLR1 is yet unknown. In this study, various bioinformatics tools were used to predict the scores of signal peptides of IFNλR1 and IFNαR1, which was considered as an important difference in the expression of both receptors or participation in regulating the IFNLR1 gene. In silico study revealed that the signal peptide of IFNαR1 had more potential than the signal peptide of IFNλR1 but changing the signal peptide of wild type IFNλR1 with the signal peptide of IFNαR1 in wet lab had barely shown any differences. Selective expression of IFNλR1 was considered to be a plus point towards the targeted anti-viral activity of IFNλs but artificial control on its expression will surely make IFNλs a better drug with enhanced activity. The results of this study may help us in contributing some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities involved. [ABSTRACT FROM AUTHOR]

Investigation of toxicological effect of various metals is the field of interest for toxicological scientists since four to five decades and especially the toxicological effect of those drugs containing metals and there use is common because there is no other choice except to use these metal containing drugs. Inorganic as well as organic salts of lithium are commonly used in prophylaxis and treatments of many psychiatric disorders. The aim of the present study was to see the difference between the effect of organic and inorganic salt of lithium commonly used in psychiatric disorders on the GSH of human blood plasma. It is the scientific fact that ionic dissociation of organic and inorganic salts of any metal is always quite different hence to prove this fact, the effect of lithium citrate (organic salt of lithium) and lithium carbonate (inorganic salt of lithium) was investigated on human blood plasma GSH to find the difference between the effect of two. Ellman's method was used for the quantification of glutathione contents in plasma. It was found that lithium citrate decrease plasma GSH contents less than lithium carbonate indicating that organic salts of lithium are safe than inorganic salts of lithium when are used in psychiatric disorders. Further to analyze the effect of organic and inorganic salt of lithium on blood plasma GSH with the increase in incubation time was also evaluated and was found that both concentration and time dependent effect of organic salt of lithium shows that this salt has decreased plasma GSH contents of human blood less than inorganic salt of lithium either by promoting oxidation of GSH into GSSG or by lithium glutathione complex formation. These results suggest the physicians that the use of organic lithium salts is much safer than inorganic salts of lithium in terms of depletion of blood plasma GSH contents. [ABSTRACT FROM AUTHOR]

Toxicities of heavy metals is a burning issue and a topic of interest among the toxicologists throughout the world. Metals are always in use of man since long but in recent years the use of cadmium has increased in the form of various cadmium compounds such as cadmium compounds as stabilizers in plastic pipe industries and in the preparations of different alloys etc. Cadmium is even used in phosphate fertilizers and thus comes directly or indirectly in contact with human eatables like crops, vegetables and fruits. Once it is absorbed it affects almost all the organs and systems of human body especially blood components and kidneys. Always the chemical reactions of different chemicals are dependent on some influential factors, among these factors the effect of pH and temperature of the media in which these chemicals interact with each other are very much important. Keeping in view this fact we have evaluated the effect of cadmium nitrate tetra hydrate on GSH of human plasma and cytosolic fraction. Estimation of thiol was done by Ellman's modified method and was found that the interaction of cadmium nitrate tetra hydrate and GSH of these blood components was more at a pH and temperature, which were near to physiological pH and temperature of human body. This fact was proved as the estimated thiol concentration left after the interaction of cadmium nitrate tetra hydrate and thiol of these blood components was minimum at pH and temperature near to human blood pH and temperature. We concluded that the possible reason for depletion of GSH of these blood components was conversion of GSH into Cd(SG)2 and/or GSSG formation. [ABSTRACT FROM AUTHOR]

Cadmium intake is associated with oxidative stress that causes depletion of intracellular as well as extra cellular reduced glutathione. There is strong evidence indicating that reactive oxygen species and reactive nitrogen species generated in the presence of cadmium could be responsible for its toxic effects in many cells and tissues. Depletion of reduced glutathione in various cells, especially in T and B-lymphocytes, causes extreme damage to the antioxidant defense system of body. The aim of this research work was to investigate the metabolic changes that occur in T and B lymphocytes after their incubation with organ cadmium diacetate by using Ellman's spectrophotometric method of thiol quantification. The results of the present study indicate that cadmium depleted T and B lymphocytes GSH to a harmful extent. It is proposed that this depletion is due to the bivalent cadmium glutathione complex formation, oxidation of reduced glutathione (GSH) to its oxidized form, or both. [ABSTRACT FROM AUTHOR]

IL-28Ra and IL1 OR(3 collectively construct a fully functional hetero-dimeric receptor for type III interferons (IFNs). IL-28Ra is the private chain for type III IFNs since their involvement in any other pathway has not been reported yet and they are highly expressed in response to certain viral attack or cancers. IL-28Ra is specific in their expression pattern and it expresses within few cell types only. The regulatory mechanisms governing the expression of IL-28Ra at the molecular level are not completely known yet and need to be scrutinized at primary levels. In the present study, various in-silico techniques were applied and it was observed that API-2, STAT 1-6, P-53, LyF-1 (lymphoid transcription factor), c-Jun, PU. 1, CREB (cAMP response element-binding), PLAG (pleotropic adenoma gene), MYOD (myoblast determination protein 1), NOFL and KLFS as transcription factors that are selected with preference. Interestingly AP-2, c-Jun, LyF-1, STAT, NF-Y and P53 have also been reported in literature recently as some of the key regulatory elements as well. Based on the fact that interlinking between different interferon stimulation genes (ISGs) is also not very clear and induction of one type of interferon can affect the efficacy of the other, we found that IFN-A4 induction can increase the expression of IL-28Ra, similar to IFN-A3 but contrary to type I IFNs, which has either no effect on the expression of IL-28Ra or can down regulate its expression at higher concentrations (data not published). [ABSTRACT FROM AUTHOR]

Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity. [ABSTRACT FROM AUTHOR]

Background: Environmental pollution of transition metals especially of mercury is of great concern to the researchers in medical field since long. Mercury causes oxidative stress in all the cells including lymphocytes of the human immune system. Effect of inorganic compound of mercury was compare with our own report of effect of organic compound of mercury on T and B lymphocytes in human blood. Material & Methods: The present experimental work was design to analyze the concentration and time dependent effect of mercuric chloride on the chemical modulation of T and B-lymphocytes GSH of human blood. Terasaki technique for lymphocytes isolation and then subsequently separation of T and B-cells was used. Quantification of thiol in T and B-cells was done by Ellman's method. Results: The lowest used concentration of mercuric chloride depleted T and B-cells GSH level 2.115 µM (27.34%) and 2.019 µM (32.41%) respectively which was significant (p<0.001) decrease in both T and B-cells GSH level. This effect of mercury was dose and time dependent. Conclusion: This study suggests that depletion of GSH due to inorganic mercury in T and B-lymphocytes is more severe as compared to its organic form. [ABSTRACT FROM AUTHOR]

Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-l), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (p<0.05) in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (p<0.05) exhibited peaks plasma concentration (Cmax =237.66±l .98) and extended the peak time (tmax=4.63±0.24). Good in-vitro in vivo correlation was found (R² =0.9883) against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium. [ABSTRACT FROM AUTHOR]

Current study was carried out on Rhazya stricta. Plant material was collected from Jhalmagsi Dist. Balochistan, Pakistan. Methanolic extract of Rhazya stricta was tested for anti-dermatitis, analgesic, anxiolytic effects, insecticidal activity and Brine shrimp Bioassay. Crude extract showed significant anti-dermatitis activity, as the results of intensity score showed mild Excoriation or erosion, moderate Edema or populations and absence of Erythema or hemorrhage, Scratching time was decreased to 1.45 and histological observations of mice treated with crude extract showed mild changes and few inflammatory cells in several microscopic fields. The results of analgesic activity were significant and the percentage inhibition of writhes were 73.54% and 69.38% at 300mg/kg and 500mg/kg respectively. The overall response of crude extract in anxiolytic activities were depressive and crude extract showed sedative effects. In Brine shrimp (Artemsia salina) lethality bioassay crude extract showed dose depended significant activity, and showed positive lethality with LD50 3.3004μg/ml. Insecticidal activity was positive against Callosbruchus analis, the percent mortality was 40%. [ABSTRACT FROM AUTHOR]

Interferon Lambda (IFN-λ) is a type III interferon which belongs to a novel family of cytokines and possesses antiviral and antitumor properties. It is unique in its own class of cytokines; because of the specificity towards its heterodimer receptors and its structural similarities with cytokines of other classes. This renders IFN- λ a better choice for the treatment against many diseases including viral hepatitis and human coronavirus (HCoV-EMC). The present study describes a computational approach known as relative synonymous codon usage (RSCU); used to enhance the expression of IFN- λ protein in a eukaryotic expression system. Manually designed and commercially synthesized IFN- λ gene was cloned into pET-22b expression plasmid under the control of inducible T7-lac promoter. Maximum levels of IFN- λ expression was observed with 0.4 mM IPTG in transformed E. coli incubated for 4 hours in LB medium. Higher concentrations of IPTG had no or negative effect on the expression of IFN- λ This synthetically over expressed IFN- λ can be tested as a targeted treatment option for viral hepatitis after purification. [ABSTRACT FROM AUTHOR]

To prepare and evaluate three novels functionalized polymers (PGA, PGA-co-caprolactone & PGA-co-pentadecalactone) for the development of nanoparticles which were further used in the development of a novel polymeric prodrug using lbuprofen as a model drug. The Ibuprofen-polymer prodrug was developed by coupling the drug to one of the three prepared polyester polymers via ester linkage. A hydrolytic enzyme was used to prepare two polymer monomers, glycerol and polyvinyl adipate, which are non toxic, ester linked biological monomers. The polymers and their prodrug were characterized using NMR, GPC, UV-spectrophotometer and DSC. In vitro drug release study of Ibuprofen-polymer conjugate was performed in phosphate buffer PH 7.4 using a roller (Stuart STR 1) placed in an incubator (Stuart S1 60) and the temperature was kept constant at 37 ± I°C. Among the three polymers, glycerol-adipateco-pentadecalactone was observed to give a burst release following slow release in the medium. These characteristics suggest that these polymers can be successfully used in sustained release drug formulations. [ABSTRACT FROM AUTHOR]

Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermal and transdermal products. The use of penetration enhancers could provide a success till mean for this purpose. The aim of this study was to develop Clotrimazole gel and to evaluate the effect of almond oil and tween 80 (in different concentrations), on the permeation of drug through rabbit skin in vitro. In order to investigate the effect of penetration enhancers used in this study on the permeation of Clotrimazole through sections of excised rabbit skin, Franz diffusion cell was employed. Sample solution was withdrawn at specific time interval tip to 24 h. Significant difference in permeation among the eight formulations was seen in the study. The permeation profile of various formulations also showed that the added enhancers in individual batches affected the permeation of the drug. Drug permeation increased with increased concentration of Tween 80 and decreased concentration of almond oil. Furthermore, almond oil combined with tween 80 showed synergistic effect. The clotrimazole gels were successfully formulated and could be beneficial for topical use. [ABSTRACT FROM AUTHOR]

Dimercaptosuccinic acid (DMSA) has been evaluated and used with technetium 99m (99mTc) in imaging of kidneys. DMSA lyophilized kits were prepared and radiolabelled with 99mTc. Paper and thin-layer chromatography have been employed using various eluent systems for the radiochemical analysis, percentage labeling and binding capacity of 99mTc-DMSA. Female albino rabbits were used for this study. Biological data obtained after intravenous injection of radiolabelled DMSA to female albino rabbits revealed 32.42% uptake and long retention time in the kidneys. On the basis of animal biodistribution data, it is suggested that DMSA when labeled with 99mTc is useful complex for renal imaging and can be successfully applied as a diagnostic tool in nuclear medicine. Clinical biodistribution and radiation dosimetry studies are planned in future. [ABSTRACT FROM AUTHOR]