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Background: Dillenia indica (Family: Dilleniaceae) is an antioxidant-rich edible fruitbearing medicinal plant. The fruit of this plant (known as elephant apple) has many uses in traditional medicine. Objective: By considering its antioxidant content and ameliorating effects, this study aimed to evaluate the anti-adipogenic effects of D. indica fruit extract (DIFE) on high-fat diet (HFD) fed obese rats. Methods: Male Wistar rats were fed with a standard diet (SD), or high-fat diet (HFD), or HFD with 100 mg/kg or 200 mg/kg or 400 mg/kg DIFE for 8 weeks. The fruit extract was given orally by feeding gavage. The body weight, liver weight, visceral fat weight, plasma lipids, and oxidative stress-related parameters were measured. The mRNA level of different adipogenesis related transcription factors, lipogenic and lipolytic enzymes was also evaluated. Results: Consumption of DIFE daily (400 mg/kg) for 8 weeks resulted in a significant reduction of high-fat diet-induced body weight, liver weight, visceral fat weight, total cholesterol, and LDL-cholesterol level. High-fat diet-mediated elevation of oxidative stress markers was also lowered, with a parallel augmentation of the activities of antioxidant enzymes, due to 400 mg/kg DIFE feeding. DIFE also down-regulated the mRNA level of important pro-adipogenic factors like PPARγ, LXRα, and SREBP1c which consequently downregulated the transcript levels of lipogenic enzymes: ACC, FAS, HMGCR, and DGAT. The transcript level of lipolytic enzyme, HSL was also down-regulated in 400 mg/kg DIFE-fed rats. Conclusion: These findings indicate that the antioxidant-rich ethanolic extract of D. indica fruit can down-regulate the gene expression of pro-adipogenic transcription factors and lipid metabolizing enzymes and thus can suppress diet-induced obesity in Wistar rat.

Background Different parts of the medicinal plant Tamarindus indica L. are full of phytochemicals that are able to reduce elevated blood pressure, blood sugar and lipids. These pharmacological effects are due to the presence of antioxidant type compounds in those parts of the plant. This study was aimed to explore the molecular mechanism of anti-obesity effects of ethanolic extract of T. indica L. leaves (TILE) through the evaluation of biochemical parameters and gene expression analysis in high-fat diet (HFD) consuming Wistar rats. Methods Male Wistar rats were supplied with a standard diet (SD), or HFD, or HFD with 100 mg/kg or 200 mg/kg or 400 mg/kg TILE for 8 weeks. The body weight, liver weight, fat weight, plasma lipids, and oxidative stress-related parameters were measured. The transcript levels of different adipogenesis related transcription factors, lipogenic enzymes, and lipolytic enzymes were also evaluated by quantitative real-time PCR. Result Phytochemical analysis demonstrated that TILE is enriched with a substantial level of polyphenols (287.20 ± 9.21 mg GAE/g extract) and flavonoids (107.52 ± 11.12 mg QE/g extract) which might be the reason of significant antioxidant and radical scavenging activities. Feeding of TILE (400 mg/kg/day) to HFD-fed rats increased activity of superoxide dismutase and catalase which is reflected as a significant reduction of oxidative stress markers like nitric oxide and malondialdehyde. TILE (400 mg/kg/day) feeding also down-regulated the mRNA levels of proadipogenic transcription factors including liver X receptor alpha (LXRα), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein 1c (SREBP1c) in diet-induced obese rats. As a consequence of this, the mRNA level of lipogenic enzymes like acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), diacylglycerol acyltransferase (DGAT), and HMG-CoA reductase was down-regulated with a parallel up-regulation of the transcript level of lipolytic enzyme, hormone-sensitive lipase (HSL). Conclusion Observations from this study indicate that antioxidant-rich TILE can reduce HFD-induced body weight, fat weight and liver weight as well as blood lipids through down-regulating the gene expression of proadipogenic transcription factors and lipogenic enzymes with a concerted diminution of the gene expression of lipolytic enzyme, HSL.

The lower drug retention to the eye's anterior portion is a prime concern in the ocular drug delivery system. To improve the drug retention capacity, we aimed to develop drug–containing nanoparticles using Quality by Design (QbD) approach. The current study describes the development of resveratrol-loaded mucoadhesive lecithin/chitosan nanoparticles (RMLCNs) to be instilled on eyes. The initial risk assessments were carried out using a fishbone diagram followed by final risks assessment using the risk assessment matrix (RAM). A definitive screening design (DSD) study was performed for the CMAs/CPPs (critical material attributes/critical process parameters) on CQAs (critical quality attributes). The identified central composite design (CCD) with a design space showed an optimal desire formulation value of 0.913. The optimized formulation had a particle size of 163.3 nm, PDI (polydispersity index) of 0.254, zeta potential of 46.4 mV, entrapment efficiency of 97.03%, the release of 96.87, and R2 of the zero-order release kinetics of 0.9897, that were within the predictive range at an alpha level of ±0.05 with a bias percentage of ≤3.422. Finally, the AUC0-6 and MRT of the optimized formulation were found to be 6.44 and 2.458 times higher than those of resveratrol solution, respectively, demonstrating the adaptation efficiency of QbD to the development of RMLCNs.

A novel method called kinase-interacting substrate screening based on affinity beads coated with the kinase of interest identifies phosphorylation sites for Rho-kinase and others, which reveals that Rho-kinase substrate Scrib plays a crucial role in the regulation of subcellular contractility by assembling with Rho-kinase and Shroom2., Protein kinases play pivotal roles in numerous cellular functions; however, the specific substrates of each protein kinase have not been fully elucidated. We have developed a novel method called kinase-interacting substrate screening (KISS). Using this method, 356 phosphorylation sites of 140 proteins were identified as candidate substrates for Rho-associated kinase (Rho-kinase/ROCK2), including known substrates. The KISS method was also applied to additional kinases, including PKA, MAPK1, CDK5, CaMK1, PAK7, PKN, LYN, and FYN, and a lot of candidate substrates and their phosphorylation sites were determined, most of which have not been reported previously. Among the candidate substrates for Rho-kinase, several functional clusters were identified, including the polarity-associated proteins, such as Scrib. We found that Scrib plays a crucial role in the regulation of subcellular contractility by assembling into a ternary complex with Rho-kinase and Shroom2 in a phosphorylation-dependent manner. We propose that the KISS method is a comprehensive and useful substrate screen for various kinases.

Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography. First, we examined protein phosphorylation by extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), which has been relatively well studied in cardiomyocytes. The KISS method showed that ERK and PKA mediated the phosphorylation of known cardiac-substrates of each kinase such as Rps6ka1 and cTnI, respectively. Using this method, we found about 330 proteins as Rho-kinase-mediated substrates, whose substrate in cardiomyocytes is unknown. Among them, CARP/Ankrd1, a muscle ankyrin repeat protein, was confirmed as a novel Rho-kinase-mediated substrate. We also found that non-phosphorylatable form of CARP repressed cardiac hypertrophy-related gene Myosin light chain-2v (MLC-2v) promoter activity, and decreased cell size of heart derived H9c2 myoblasts more efficiently than wild type-CARP. Thus, focused proteomics enable us to reveal a novel signaling pathway in the heart.

Trimetazidine is an effective and well-tolerated antianginal drug. In the present study, a simple, sensitive and specific liquid chromatography (HPLC) method with UV detection was developed and validated for the quantification of trimetazidine in human serum samples using caffeine as internal standard. Protein precipitation method with methanol was employed in the extraction of trimetazidine and caffeine from biological matrix. The chromatographic separation was accomplished on Xterra C18 Column with a mobile phase consisting 0.01 M potassium dihydrogen phosphate buffer (pH 4.16 ± 0.01 adjusted with orthophosphoric acid, with a solvent system of triethanolamine and acetonitrile (90:10) at a flow rate of 1.0 ml/min. The chromatogram was monitored at a wavelength of 207 nm. The method was validated over a linear concentration range of 5-200 ng/ml and limit of quantification (LOQ) was 5.0 ng/ml with a coefficient of correlation (r2) ? 0.996. The intra-day and inter-day precision expressed as relative standard deviation was 3.40%-11.63% and 1.30%-10.21%, respectively. The average recovery of trimetazidine from serum was 97.44%. The method was successfully applied to a pharmacokinetic study after oral administration of modified release trimetazidine hydrochloride tablet (35 mg) in healthy Bangladeshi volunteers. DOI: http://dx.doi.org/10.3329/dujps.v10i2.11783 Dhaka Univ. J. Pharm. Sci. 10(2): 71-78, 2011 (December)

Objective Although several generic oral formulations of azithromycin (AZT; CAS 83905-01-5) are available in Bangladesh, information regarding the bioavailability of these formulations in the Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of 2 formulations of AZT 500 mg tablet, namely Azomac® (General Pharmaceutical Ltd., Bangladesh) (Test formulation) and Zithromax® (Pfizer, Rome, Italy) (Reference product) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi volunteers. Materials and methods A randomized, single-dose, two-way, cross-over, open-label pharmacokinetic study was performed in 24 healthy volunteers after administration of single dose of AZT 500 mg tablet under fasting condition following a washout period of 3 weeks. Blood samples were collected at pre-determined time points and analyzed for serum AZT concentration using a validated liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were determined by a noncompartmental method. Results From serum data, the obtained values given as mean (SD) for test and reference products were 382.41 (21.96), 392.31 (18.77) ng/ml for Cmax; 4.83(1.03), 4.83(1.03) h for tmax; 5,646.29 (912.19), 6,293.30 (966.76) h×ng/ml for AUC0-120; and 6,307.50 (863.40), 7,022.54 (961.28) h×ng/ml for AUC0-∞, respectively. The mean t1/2 was 41.44 (7.01), 41.16 (6.38) h for Test formulation and Reference product, respectively. The analysis of variance revealed no period or sequence effect for any pharmacokinetic property; however, a significant formulation effect was observed for Cmax, AUC0-120, AUC0-∞ and AUMC0-120. The 90% confidence intervals of the test/ reference mean ratios of the ln-transformed Cmax, AUC0-120 and AUC0-∞ were 87.89 - 89.36%, 87.40 - 91.70% and 87.47 - 92.07%, respectively, which fell within the predetermined FDA bioequivalence range. Conclusion It can be concluded that the test formulation met the regulatory criteria for bioequivalence to the Reference tablet formulation in terms of both rate and extent of absorption.

In the present study serum Malondialdehyde (MDA) and Vitamin C profiles of conversion disorder patients were compared with control and evaluated the correlation between MDA and vitamin C level was evaluated with their socioeconomic factors. Conversion disorder patients (n=45), age ranging from 17 to 41 years, were randomly recruited from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh for this study. Control group also included 45 healthy individuals matched by the socio-demographic status to that of the patients. Blood samples were analyzed for determining MDA and vitamin C using Ultraviolet-Visible (UV-VIS) spectroscopy. Serum concentrations of MDA and vitamin C of conversion disorder patients were 2.19 ± 1.47 and 19.23 ± 5.59 μmol/L respectively while these were 2.11 ± 0.88 and 21.00 ±4.96 μmol/L in control subjects respectively. Socioeconomic data revealed that most of the patients were young female and unmarried. The mean BMI of patients (21.05 ± 3.39) were not significantly different (P > 0.05) from the control subjects (20.86 ± 1.86). Moreover, statistical analysis revealed that there were no significant correlation between MDA, vitamin C concentrations and socioeconomic factors. The results of our study have shown higher oxygen free radical production, evidenced by increased levels of MDA and decreased levels of ascorbic acid which supports the oxidative stress in conversion disorder patients. DOI: http://dx.doi.org/10.3329/dujps.v10i1.10017 DUJPS 2011; 10(1): 59-64

The purpose of the present study was to evaluate the status of serum trace elements: zinc, copper, manganese, iron, calcium, and magnesium concentrations in obsessive–compulsive disorder patients. Forty-eight obsessive–compulsive disorder patients and 48 healthy volunteers were included in this study. Patients were recruited from Bangabandhu Sheikh Mujib Medical University by random sampling. Serum trace element concentrations were determined using flame atomic absorption spectroscopy (for zinc, copper, iron, calcium, and magnesium) as well as graphite furnace atomic absorption spectroscopy (for manganese). Data were analyzed using independent t test, Pearson's correlation analysis, regression analysis, and ANOVA. Statistical analysis of these data showed a definite pattern of variation among certain elements in patients with obsessive–compulsive disorder compared to controls. In patients' serum, zinc, iron, and magnesium concentrations decreased significantly (p < 0.05) compared to the controls. Serum manganese and calcium concentrations were significantly higher (p < 0.05) in patients compared to the controls. These data showed a definite imbalance in the interelement relations in obsessive–compulsive disorder patients compared to controls and therefore suggest a disturbance in the element homeostasis.

Protein phosphorylation plays a key role in regulating nearly all intracellular biological events. However, poorly developed phospho-specific antibodies and low phosphoprotein abundance make it difficult to study phosphoproteins. Cellular protein phosphorylation data have been obtained using phosphoproteomic approaches, but the detection of low-abundance or fast-cycling phosphorylation sites remains a challenge. Enrichment of phosphoproteins together with phosphopeptides may greatly enhance the spectrum of low-abundance but biologically important phosphoproteins. Previously, we used 14-3-3ζ to selectively enrich for HeLa cell lysate phosphoproteins. However, because 14-3-3 does not isolate phosphoproteins lacking the 14-3-3-binding motif, we looked for other domains that could complementarily enrich for phosphoproteins. We here assessed and characterized the phosphoprotein binding domains Pin1-WW, CHEK2-FHA, and DLG1-GK. Using a strategy based on affinity chromatography, phosphoproteins were collected from the lysates of HeLa cells treated with phosphatase inhibitor or cAMP activator. We identified different subsets of phosphoproteins associated with WW or FHA after calyculin A, okadaic acid, or forskolin treatment. Our Kinase-Oriented Substrate Screening (KiOSS) method, which used phosphoprotein-binding domains, showed that WW and FHA are applicable and useful for the identification of novel phospho-substrates for kinases and can therefore be used as biological filters for comprehensive phosphoproteome analysis.

Protein phosphorylation is a major and essential post-translational modification in eukaryotic cells that plays a critical role in various cellular processes. Recent progresses in mass spectrometry techniques have enabled the effective identification and analysis of protein phosphorylation. Mass spectrometry-based approaches in investigating protein phosphorylation are very powerful and informative and can further improve our understanding of protein phosphorylation as a whole, but they cannot determine the upstream kinases involved. We introduce several studies that attempted to uncover the relationships between various kinases of interest and substrates, including two methods we developed: an in vitro approach termed the kinase-interacting substrate screening (KISS) method and an in vivo approach termed the phosphatase inhibitor and kinase inhibitor substrate screening (PIKISS) method. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.

Azithromycin (AZT; CAS 83905-01-5) is an efficient antibiotic and is widely prescribed in Bangladesh. The taste of uncoated AZT suspension is bitter. Although several taste masked oral suspensions of AZT are available in Bangladesh, information regarding the bioavailability of these formulations in Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of two oral formulation of AZT (200 mg/5 ml) suspensions, the uncoated reference product and coated test product (Tridosil 200 mg/5 ml) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi male volunteers. A randomized, single-dose, two-way cross-over, open-label pharmacokinetic study was conducted in 24 healthy male volunteers after administration of a single dose of 500 mg AZT suspension under fasting condition following a washout period of three weeks. Blood samples were collected in different time intervals and analyzed for serum AZT concentration using a validated LC/MS/MS method. The pharmacokinetic parameters were determined by the non-compartmental method. From serum data, the obtained values for test and reference products were 383.21 +/- 11.59 and 432.28 +/- 7.22 ng/ ml for Cmax; 5677.47 +/- 1229.53 and 6144.56 +/- 1098.70 h x ng/ml for AUC(0-120); and 6085.29 +/- 1267.53 and 6694.15 +/- 1222.50 h x ng/ml for AUC(0-infinity), respectively. On analysis of variance, no period or sequence effects were observed for any pharmacokinetic property; however, a significant formulation effect was observed for Cmax and AUMC(0-infinity). The 90% confidence intervals of the test formulation/reference mean ratios of the Intransformed Cmax, AUC(0-120) and AUC(0-infinity) mean values were found to be 87.89% to 89.36%, 87.96% to 95.71% and 86.77% to 94.29% respectively. In this single-dose study of AZT, it was found that the test formulation met the regulatory criteria for bioequivalence to the reference suspension formulation.

Objective Omeprazole 20 mg enteric coated capsule formulation is generally prepared either with omeprazole 8.5% or omeprazole 7.5% enteric coated pellets to accommodate in capsule Shell 2, but the use of omeprazole 22.5% enteric coated pellets in capsule Shell 5 for the same amount of omeprazole is a new concept and for the first time in the Bangladesh market. This study was conducted to compare the relative bioavailability and pharmacokinetic properties of two omeprazole 20 mg capsule formulations namely Xeldrin®20 (ACI Ltd., Bangladesh) encapsulated with omeprazole 22.5% enteric coated pellets, as test product and Losec®20 (AstraZeneca, Wilmington, DE, USA) as reference product and to assess whether these formulations meet the FDA requirement for bioequivalence. Materials and methods 24 non-smoking healthy Bangladeshi male subjects participated in this open-label, randomized-sequence, single- dose, two-way crossover study. Subjects were randomly assigned to receive test formulation, followed by reference formulation or vice versa, as a single dose of 20 mg capsule after 12 h overnight fasting. A washout period of 1 week was maintained between the treatments. Blood samples were collected before study drug administration (baseline) and at 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 9.0, and 12.0 h after study drug administration. Serum omeprazole concentrations were determined using a validated HPLC method with UV detection. The pharmacokinetic parameters were determined by the non-compartmental method. The two formulations were to be considered bioequivalent if the 90% confidence intervals (CI) for the ln-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80 - 125% according to the guidelines of the US Food and Drug Administration (FDA). Tolerability was assessed on the basis of adverse effects, monitoring vital signs, ECG and laboratory tests at baseline and after completion of the study with the assistance of registered physicians. Results All 24 subjects completed the study without any adverse effect reported. After administering a single dose of 20 mg of each omeprazole formulation, the obtained mean (SD) values for the test and reference products were 608.40 (116.37) and 588.56 (98.36) ng/ml for Cmax; 1.83 (0.25) and 2.00 (0.30) h for tmax; 1,635.77 (581.25) and 1,639.58 (652.54) h-ng/ml for AUC0-12; and 1,721.12 (572.07) and 1,805.58 (856.39) h-ng/ml for AUC(0-∞) respectively. The mean t(1/2) was 3.33 (1.61) and 3.57 (1.24) h for test and reference product respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. The point estimates (90% CI) for the test/reference ratios of the ln-transformed AUC(0-12), AUC(0-∞) and C(max) mean values were 100.73% (91.40 -111.01%), 98.29% (88.45 -109.24%) and 103.06% (99.05 - 07.24%) respectively, which fell within the predetermined FDA bioequivalence range of 80 - 125%. Conclusion This single-dose study found that the test (Xeldrin®20) and reference (Losec®20) 20 mg capsule formulations of omeprazole in these fasting healthy male Bangladeshi subjects met the FDA regulatory criteria for bioequivalence.

Bioequivalence study of two esomeprazole 20 mg capsule formulations namely Esolok ® 20 (Test product) and Nexium 20 (Reference product) was carried out in the present study. 24 healthy male volunteers were enrolled into this randomized, single-dose, two-period, crossover, open-label pharmacokinetic study with one week washout period. After administering a single dose of 20 mg of each formulation, blood samples were collected at different time intervals and analyzed for esomeprazole concentrations using a validated HPLC method. Non-compartmental method was used to determine different pharmacokinetic parameters. Obtained mean (SD) values for the test and reference products were 1.45 (0.53) and 1.53 (0.47) μg/ml for C max ; 2.25 (0.57) and 2.21 (0.71) hr for T max ; 4.38 (2.04) and 4.37 (2.35) hr-μg/ml for AUC 0-12 ; and 4.59 (1.99) and 4.62 (2.39) hr-μg/ml for AUC 0-∞ , respectively. The 90% CIs of the test/reference mean ratios of the ln-transformed AUC 0-12 , AUC 0-∞ and C max mean values were 102.51% (88.10% – 119.27%), 101.92% (87.32% – 118.96%) and 92.56% (85.73% – 99.93%) respectively, which were within the predetermined FDA bioequivalence range of 80% – 125%. In conclusion, the test and reference formulations of esomeprazole meet the regulatory criteria for bioequivalence both in terms of rate and extent of absorption.

In Bangladesh, a number of generic oral formulations of esomeprazole are marketed. Study of the relative bioavailability of these generic formulations has yet to be conducted in a Bangladeshi population.The aims of this study were to assess the relative bioavailability and pharmacokinetic properties of 2 formulations (test and reference) of esomeprazole 40 mg.This open-label, randomized, 2-way crossover study was conducted in healthy Bangladeshi male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, as a single dose of esomeprazole 40 mg after a 12-hour overnight fast. A washout period of 1 week was maintained between treatments. Following oral administration, blood samples were collected at 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 7, 9, and 12 hour(s) after dosing and analyzed for esomeprazole concentrations using a validated HPLC method. Pharmacokinetic parameters, including C(max), AUC(0-12), and AUC(0-infinity), were determined with a non-compartmental method. The formulations were to be considered bioequivalent if the natural log (ln)-transformed ratios of the pharmacokinetic parameters were within the predetermined bioequivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement. The within- and between-group differences were examined using ANOVA. Tolerability was assessed by monitoring vital signs and conducting subject interviews regarding adverse events. Interviewers were not blinded to study design.A total of 24 nonsmoking, healthy, Bangladeshi male subjects (mean [SD] age, 22.8 [2.22] years [range, 20-29 years]; weight, 64.7 [6.9] kg [range, 55-79 kg]; height, 1.69 [0.05] m [range, 1.63-1.82 m]; and body mass index, 22.39 [2.16] kg/m(2) [range, 18.99-27.34 kg/m(2)]) were enrolled. From serum data, the mean (SD) values for the test and reference products were as follows: 5.26 (1.57) and 5.54 (2.94) micromol/L for C(max); 2.53 (0.67) and 2.07 (0.65) hours for T(max); 15.74 (6.50) and 16.68 (6.77) micromol/L/h for AUC(0-12); and 17.15 (7.58) and 18.26 (7.31) micromol/L/h for AUC(0-infinity), respectively. The mean T(max) was found to be significantly different between the test and reference formulations (2.53 [0.67] vs 2.07 [0.65] hours, respectively; P0.05). The point estimates (90% CI) for the test/reference ratios of the In-transformed AUC(0-infinity) and C(max) were 92.92% (84.02%-102.76%) and 102.36% (85.96%-121.90%), respectively, which were within the FDA-accepted limits for assuming bioequivalence. No adverse events were reported by the volunteers during the study.This single-dose study found that the test and reference formulations of esomeprazole 40 mg met the FDA regulatory criteria for assuming bioequivalence in these healthy, fasting Bangladeshi male volunteers. A significant difference was found in T(max) between the 2 formulations. Both formulations were well tolerated in the studied population.

The aim of the study was to determine the concentration of serum Ca, Mg, Cu, Fe, Zn and Mn in Bangladeshi conversion disorder patients compared to control subjects and to correlate the changes, if any, with different socio-demographic factors and nutritional status. Forty five conversion disorder patients were randomly recruited. Forty five healthy control subjects were also recruited by matching the socio-demographic status to that of the patients. Blood samples were analyzed to determine the concentration of serum Ca, Mg, Cu, Fe, Zn and Mn using atomic absorption spectroscopy. Except for Mg, the concentrations of the other elements (Cu, Fe, Zn, Ca, and Mn) decreased in patients compared to control, but the changes were not statistically significant (p > 0.05). Serum Mg level increased insignificantly in patients (p > 0.05). No significant relationship was found between the sociodemographic variables and serum Ca, Mg, Cu, Zn and Mn levels, except for serum Fe, where a significant negative correlation was found between serum Fe level and BMI (r = –0.428; p = 0.023). Key words: Conversion disorder patients; serum elements; socio-economic status DOI: http://dx.doi.org/10.3329/dujps.v9i2.7896 Dhaka Univ. J. Pharm. Sci. 9(2): 119-124, 2010 (December)

Vitiligo is a common pigmentary disorder characterized by depigmented patches or macules caused by the destruction of melanocytes. The pathogenetic mechanisms involved in vitiligo have not been completely clarified. Oxidative stress and reduced circulating antioxidants could be important phenomena in the pathophysiology of vitiligo. We measured serum malondialdehyde (MDA) as an indicator of oxidative stress and serum zinc and vitamin C to check antioxidant status in thirty Vitiligo patients. Thirty healthy control subjects were also recruited by matching the socio-demographic status to that of the patients. Blood samples were analyzed for determining the serum levels of Zn (by atomic absorption spectroscopy), Vitamin C and MDA (by UV-VIS spectroscopy). Serum level of MDA increased in vitiligo patients significantly (p < 0.05) in the present study, where as serum level of Zn increased and serum Vit-C decreased in patients compared to control but the changes were not statistically significant (p > 0.05). Our study reveals the presence of an imbalance in the oxidant/antioxidant system in vitiligo patients which supports a free radical-mediated damage in the pathogenesis of vitiligo. Key words: Vitiligo; Oxidative stress; Antioxidant status; MDA; Vitamin C; Zinc DOI: http://dx.doi.org/10.3329/dujps.v9i2.7894 Dhaka Univ. J. Pharm. Sci. 9(2): 103-108, 2010 (December)

Protein kinase A (PKA) is a serine/threonine kinase whose activity depends on the levels of cyclic AMP (cAMP). PKA plays essential roles in numerous cell types such as myocytes and neurons. Numerous substrate screens have been attempted to clarify the entire scope of the PKA signaling cascade, but it is still underway. Here, we performed a comprehensive screen that consisted of immunoprecipitation and mass spectrometry, with a focus on the identification of PKA substrates. The lysate of HeLa cells treated with Forskolin (FSK)/3-isobutyl methyl xanthine (IBMX) and/or H-89 was subjected to immunoprecipitation using anti-phospho-PKA substrate antibody. The identity of the phosophoproteins and phosphorylation sites in the precipitants was determined using liquid chromatography tandem mass spectrometry (LC/MS/MS). We obtained 112 proteins as candidate substrates and 65 candidate sites overall. Among the candidate substrates, Rho-kinase/ROCK2 was confirmed to be a novel substrate of PKA both in vitro and in vivo. In addition to Rho-kinase, we found more than a hundred of novel candidate substrates of PKA using this screen, and these discoveries provide us with new insights into PKA signaling.