Search

Abstract: Alzheimer’s disease (AD) is a devastating neurodegenerative disease that mostly affects the elderly population. Mechanisms underlying AD pathogenesis are yet to be fully revealed, but there are several hypotheses regarding AD. Even though free radicals and inflammation are likely to be linked with AD pathogenesis, still amyloid-beta (Aβ) cascade is the dominant hypothesis. According to the Aβ hypothesis, a progressive buildup of extracellular and intracellular Aβ aggregates has a significant contribution to the AD-linked neurodegeneration process. Since Aβ plays an important role in the etiology of AD, therefore Aβ-linked pathways are mainly targeted in order to develop potential AD therapies. Accumulation of Aβ plaques in the brains of AD individuals is an important hallmark of AD. These plaques are mainly composed of Aβ (a peptide of 39–42 amino acids) aggregates produced via the proteolytic cleavage of the amyloid precursor protein. Numerous studies have demonstrated that various polyphenols (PPHs), including cyanidins, anthocyanins, curcumin, catechins and their gallate esters were found to markedly suppress Aβ aggregation and prevent the formation of Aβ oligomers and toxicity, which is further suggesting that these PPHs might be regarded as effective therapeutic agents for the AD treatment. This review summarizes the roles of Aβ in AD pathogenesis, the Aβ aggregation pathway, types of PPHs, and distribution of PPHs in dietary sources. Furthermore, we have predominantly focused on the potential of food-derived PPHs as putative anti-amyloid drugs.

Background: Clerodendrum viscosum is one of the most well-known plants in traditional practices. The study aims to explore the antidiabetic, antidiarrheal and sedative effects of methanolic extract of Clerodendrum viscosum roots (MECV) in mice. Methods: For each experiment, four groups of animals were used consisting of three mice per group. Each group was treated individually: group I treated as negative control, Group II received reference drug of each experiment, Group III and IV received MECV at 200 and 400 mg/kg body weight, respectively. Antidiabetic effect of MECV was evaluated by oral glucose tolerance test. Antidiarrheal activity was examined by the method of castor oil induced diarrhea and reduction in amount of diarrheal feces was determined. To assess the sedative activity of MECV, total sleeping time was determined in phenobarbitone induced mice. Results: MECV showed statistically significant (p

Crassocephalum crepidioides belongs to the Asteraceae family and the leaves of the plant were used in the phytochemical screening. The objective of this study was phytochemical analysis of C. crepidioides in order to evaluate its antioxidant, thrombolytic and cytotoxic effects. In this study, DPPH assay and total phenolic content (TPC) were used to evaluate the antioxidant property. Brine shrimp lethality test was performed to find the cytotoxicity. The TPC of methanolic extract of C. crepidioides was 637.22 mg/gm and gallic acid was standard in this procedure. The IC50 value of the plant extract of DPPH assay was 136.016 μg/mL obtained by using ascorbic acid as reference standard. Furthermore, the obtained IC50 value of ascorbic acid was 94.12 μg/mL. In this study, lethal concentrations of vincristine sulfate and the plant extract were 3.064 μg/mL and 69.245 μg/mL respectively. Indeed, the plant exhibited significant antioxidant, cytotoxic and thrombolytic activity.

Selective determination of peptides in mixtures or biological samples requires specific techniques for analysis. Herein, we report 3-methylcatechol (3-MC) as a novel fluorogenic reagent for the selective determination of dipeptides by a simple fluorescence (FL) derivatization reaction. After extensive screening of 31 different catechol analogues, 3-MC was found to generate FL with peptides. The reaction was performed at 100 °C for 10 min in the presence of borate buffer (pH 7) and sodium periodate. The resulting FL intensities were measured by spectrofluorometer at excitation wavelengths of 380 nm and emission wavelengths of 500 nm. Different reaction conditions such as concentration of sodium periodate, reaction time and pH of the borate buffer were studied to determine the optimum reaction conditions. Linearity was obtained between FL intensity and peptide concentrations from 10 to 160 µM with a lower detection limit of 10 µM (S/N = 3). Dipeptides containing Ala, Phe, Leu and Val at the N-termini generated significant FL in comparison to the reagent blank (**p

Fluorescence (FL) derivatization reactions have often been used for the selective determination of bioactive peptides. Herein, a sensitive and selective fluorometric method has been developed for Pro-Gly and Pro-Gly-Pro using a derivatizing reagent 3,4-dihydroxybenzoic acid (3,4-DHBA). In the presence of borate buffer (pH 8.0) and sodium periodate, peptides were reacted with 3,4-DHBA at 37 °C for 30 min. The resulting FL intensity was measured by spectrofluorometer with the excitation wavelength of 450 nm and the emission wavelength of 535 nm. Different reaction conditions such as concentrations of the reagents, reaction time and pH were optimized to develop the method. Under the optimized conditions, a linear relationship was obtained between FL intensity and peptide concentration from 5–30 µM with a lower detection limit of 5 µM. We found that 3,4-DHBA showed strong preference for Pro-Gly and Pro-Gly-Pro amongst all the peptides tested and no other biogenic substances such as amino acids or proteins produced any FL. The reaction is selective, sensitive and simple which can be applied for the determination of peptides as biomarkers in biological samples or for the assay of various protease activities.

OBJECTIVE We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI. RESEARCH DESIGN AND METHODS Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF. RESULTS In the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = −0.56, P < 0.04). CONCLUSIONS Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.

Objective: To assess the serum magnesium level of pregnant women with pre-eclampsia and eclampsia in Mymensingh Medical College & Hospital (MMCH). Materials and Methods: This descriptive cross-sectional study was carried out in the department of Obstetrics and Gynaecology of Mymensingh Medical College & Hospital (MMCH) and “ Prof. Muhammed Hossain Central Laboratory” of Bangladesh Agricultural University (BAU). The serum magnesium level were estimated in 60 study subjects who were pregnant women with pre-eclampsia & eclampsia and of 60 control subjects who were the normotensive pregnant women by photometric test using xylidyl blue. Results: The mean (±SD) serum magnesium of the control and study group were (2.29 ± 0.28 mg/dl) & (1.84 ±0.26 mg/dl) respectively. The difference in serum magnesium level between the two groups was statistically highly significant (p=

Caspases are the key regulatory factors of apoptosis and are also found to be involved in inflammatory cytokinesis. Sensitive and selective determination of caspases has significant importance in evaluation of apoptosis, disease diagnosis, and drug development. Here, we developed an assay method for the determination of caspase activity. This method is based on a novel fluorescence (FL) reaction selective for N-terminal Ser-containing peptides. FL derivatization of peptides requires heating in the presence of catechol, HEPES buffer (pH 7.5), and sodium periodate. Under optimized conditions, the reaction showed a unique sequence preference for N-terminal Ser-containing peptides, and a lower detection limit (signal/noise [S/N] = 3) of approximately 0.1 μM was obtained for SKTS and SSNSF. Acetylated substrates were enzymatically cleaved to produce N-terminal Ser-containing peptides, which were selectively converted to FL compounds. The enzyme activities were simultaneously determined as low as 2 U (4.3 nM) caspase-3 and 2.5 U (3.3 nM) caspase-8 by high-performance liquid chromatography (HPLC) with FL detection. The proposed assay method does not require any labeled substrates and can be applied to evaluate cell-based apoptosis and also to study apoptosis inhibitors or inducers.

A novel fluorescence (FL) reaction for N -terminal Gly-containing peptides has been developed using 3,4-dihydroxyphenylacetic acid (3,4-DHPAA). The reaction of the peptides with 3,4-DHPAA was carried out in borate buffer (pH 8.0) in the presence of sodium periodate at 37 °C for 10 min, and the FL was measured with a spectrofluorimeter at the excitation and emission wavelengths of 370 nm and 465 nm, respectively. The 3,4-DHPAA reagent generated particularly strong FL for peptides containing Gly at their N -termini. When various other bio-substances, such as amino acids, sugars, nucleic bases, nucleotides, and proteins, were reacted with 3,4-DHPAA, no FL was observed. Under optimized reaction conditions, the lower detection limit of 0.25 μmol L −1 was obtained for the N -terminal Gly-containing peptides of Gly-Pro (GP) and Gly-Pro-Pro (GPP), which gave 3 times greater FL intensity than that observed for the reagent blank. The proposed reaction with 3,4-DHPAA as a fluorogenic reagent is selective and sensitive for the detection of N -terminal Gly-containing peptides, and therefore, this method could be a useful tool for the determination of these particular oligopeptides.

The objective of the present study was to investigate three kinds of health behaviors—treatment-seeking behavior during sickness, self-medication, and noncompliance of both prescription and over-the-counter drugs—of 1,809 nonmedical dorm students of Dhaka University and Jahangirnagar University, two public universities located in Dhaka and Savar, respectively, Bangladesh. In this study, decreased treatment cost and short duration of illness strongly correlated with self-medication incidences ( p < .5). Noncompliance was found to be significantly more prevalent among those who were younger and newcomers to the dorms, of male gender, and those who were ill for short durations. Bangladesh government should recognize and enforce the distinction between prescription and nonprescription medicines and ensure that the users of self-medication are well informed and protected from its possible harm or long-term negative effects.

To date, very scant data is available regarding normal diffusion properties of white matter (WM) fibers. The present study aimed to initiate the establishment of a database of normal diffusion tensor metrics of cerebral WM fibers, including the uncinate fasciculus (UF), posterior cingulum (PC), fornix, and corticospinal tract (CST) for healthy adults using tract-specific analysis by diffusion tensor tractography (DTT). We also attempted to clarify whether age and laterality exerted any effects on this study group.DTT of WM fibers were generated for 100 healthy subjects, then mean diffusivity (MD) and fractional anisotropy (FA) of the tracts were measured. Pearson correlation analysis was used to evaluate age relationships. Paired t testing was used to compare hemispheric asymmetry. Interobserver correlation tests were also performed.Our results showed FA values for UF (right, 0.42 +/- 0.03; left, 0.40+/-0.03), PC (0.51 +/- 0.06, 0.52 +/- 0.06), fornix (0.37 +/- 0.06, 0.38 +/- 0.06), CST (0.70 +/- 0.06, 0.69 +/- 0.07), and MD values for UF (0.81 +/- 0.03, 0.82 +/- 0.04), PC (0.72 +/- 0.03, 0.72 +/- 0.04), fornix (1.86 +/- 0.32, 1.94 +/- 0.37), and CST (0.72 +/- 0.03, 0.74 +/- 0.04). We identified a significant positive correlation between age and MD in the right UF and bilateral fornices, and a negative correlation between age and FA in bilateral fornices. Hemispheric asymmetry was observed in FA of UF (rightleft) and MD of CST (leftright).The results constitute a normative dataset for diffusion parameters of four WM tracts that can be used to identify, characterize, and establish the significance of changes in diseases affecting specific tracts.

6-Fluoroindan-1-carboxylic acid (4) was conveniently synthesised from 3-fluorobenzaldehyde in six steps. The structure of this new compound and three other intermediates, 3-fluorophenylcyanoethylacrylate (1), 3-fluorophenyl succinic acid (2) and 6-fluoro-3-oxo-indan-1-carboxylic acid (3) was elucidated by comprehensive spectral data analyses. The analgesic activity of compounds 3 and 4 was assessed by the acetic acid induced writhing in Swiss albino mice.

A novel fluorometric method was developed for the sensitive and selective detection of Pro-Gly (PG) and Pro-Gly-Pro (PGP) using 4-chlorobenzene-1,2-diol (4-CBD) as a fluorogenic reagent. The reaction was performed at 37°C for 30 min in the presence of a borate buffer (pH 7.0) and sodium periodate. The resulting fluorescence intensity was measured using a spectrofluorometer with excitation and emission wavelengths of 450 nm and 535 nm. To obtain a stable fluorescent signal and maximise its intensity, different reaction conditions such as the concentrations of the reagents, the reaction time, and the pH were optimised. Under the optimised conditions, a linear relationship was obtained between fluorescence intensity and peptide concentrations from 1.0–40.0 µmol L−1 with a limit of detection of 1.0 µmol L−1 (S/N = 3). Both PG and PGP generated a strong signal out of all the peptides tested and no other biogenic substances such as amino acids or proteins produced any fluorescence. The reaction thus developed is simple, rapid, selective, and sensitive. It can be applied to the determination of peptides as biomarkers or substrates.

Sensitive and selective assay of collagen is of substantial importance to the diagnostic study of health- and aging-related failures. In this paper, we describe a highly specific and sensitive method for the assay of whole collagens in biological samples using a novel fluorogenic reagent, 3,4- dihydroxyphenylacetic acid (3,4-DHPAA). The 3,4-DHPAA reagent can selectively detectN-terminal Gly-containing peptides (NGPs) in the presence of sodium borate and NaIO4. Under conditions optimized, this assay format for collagen, termed 3,4-DHPAA assay method showed a good linear relationship between the amplified FL signals and the collagen concentrations from 0.18 to 12 μg/ml. Therefore the sensitive determination of intracellular collagens in cheek tissue and HeLa cells was individually possible without any separation protocol. The dual recognitions of the collagens in the samples could be performed by the enzymatic digestion and the FL reaction. The proposed assay method enables the determination facile, specific, sensitive and quantitative for biogenic collagens., Scientific Reports, 4, 4950; 2014

Purpose Tract-specific analysis (TSA) measures diffusion parameters along a specific fiber that has been extracted by fiber tracking using manual regions of interest (ROIs), but TSA is limited by its requirement for manual operation, poor reproducibility, and high time consumption. We aimed to develop a fully automated extraction method for the cingulum bundle (CB) and to apply the method to TSA in neurobehavioral disorders such as Parkinson's disease (PD). Materials and methods We introduce the voxel classification (VC) and auto diffusion tensor fiber-tracking (AFT) methods of extraction. The VC method directly extracts the CB, skipping the fiber-tracking step, whereas the AFT method uses fiber tracking from automatically selected ROIs. We compared the results of VC and AFT to those obtained by manual diffusion tensor fiber tracking (MFT) performed by 3 operators. We quantified the Jaccard similarity index among the 3 methods in data from 20 subjects (10 normal controls [NC] and 10 patients with Parkinson's disease dementia [PDD]). We used all 3 extraction methods (VC, AFT, and MFT) to calculate the fractional anisotropy (FA) values of the anterior and posterior CB for 15 NC subjects, 15 with PD, and 15 with PDD. Results The Jaccard index between results of AFT and MFT, 0.72, was similar to the inter-operator Jaccard index of MFT. However, the Jaccard indices between VC and MFT and between VC and AFT were lower. Consequently, the VC method classified among 3 different groups (NC, PD, and PDD), whereas the others classified only 2 different groups (NC, PD or PDD). Conclusion For TSA in Parkinson's disease, the VC method can be more useful than the AFT and MFT methods for extracting the CB. In addition, the results of patient data analysis suggest that a reduction of FA in the posterior CB may represent a useful biological index for monitoring PD and PDD.

長崎大学学位論文 [学位記番号]博（医歯薬）甲第545号 [学位授与年月日]平成24年9月20日, (2012-09-20)

Indan derivatives, namely, 5-(5',6'-dichloroindan-1'-yl)-tetrazole (12a) and 5-(5',6'-dichloroindan-1'-yl)- methyltetrazole (12b), were synthesized conveniently from 5,6-dichloroindan-1-carboxylic acid (9a) and 5,6- dichloroindan-1-acetic acid (9b), respectively, as potential analgesic and anti-inflammatory agents. The analgesic and anti-inflammatory properties of 9a, 9b, 12a and 12b were evaluated by the acetic acid induced writhing in Swiss albino mice and the carrageenan-induced rat paw edema models, respectively. Compounds 9a and 12a exhibited significant analgesic activity with the doses of 50 and 100 mg/kg body weight, comparable to that of the positive controls, phenylbutazone, indomethacin and aminopyrine. The anti-inflammatory potencies of 9a and 12a were also comparable to that of the positive control, phenylbutazone. Compounds 9b and 12b showed analgesic and anti-inflammatory activities, but were weaker than that of compounds 9a and 12a.

Background To investigate whether interindividual variation in CYP3A levels can partly be explained by genetic polymorphisms, this study was designed to phenotype 200 healthy Bangladeshi subjects by measuring urinary ratio of 6β-hydroxy-cortisol/cortisol and to genotype all the subjects for the presence of CYP3A4*1B, *2, *4, *5, *6, *10 and *18 and CYP3A5*3 alleles. Methods For phenotyping, cortisol and 6β-hydroxy-cortisol were extracted and quantified by HPLC from morning spot urine samples (n = 200). Genotyping was done using the extracted genomic DNA from all the subjects followed by amplification of target alleles by PCR. Amplified DNA was digested by restriction enzymes (MboII, XcmI, BsmAI, ClaI, HinfI, HpyCH4III, HpaII and RsaI) followed by gel electrophoresis and sequencing to identify the targeted alleles. Results The ratio of 6β-hydroxy-cortisol/cortisol ranged from 0.01 to 31.98 with an average of 3.91. No sample (n = 200) was positive for CYP3A4*2, *4, *5, *6, *10 and *18 alleles. Two samples heterozygous for CYP3A4*1B (1.0%) and twenty six samples with the genotype CYP3A5*1/*1 (13.0%) were found to have relatively high 6β-hydroxy-cortisol/cortisol ratios. Conclusion CYP3A4 variant alleles are present at a low frequency in the Bangladeshi population whereas 50% of the Bangladeshi population carrying a CYP3A5*3/*3 genotype appear to show lower 6β-hydroxy-cortisol/cortisol ratios compared with those with a CYP3A5*1/*1 genotype.

Magnetic resonance diffusion tensor imaging is a noninvasive technique that can identify white matter tracts by evaluating bulk diffusion of water in three dimensions and can thus describe the microarchitectural characteristics of local brain tissue. Several recent reports have shown that mapping of diffusion parameters is potentially useful for speculating about the pathology of Alzheimer disease (AD). These reports have employed image-analysis approaches, including region-of-interest measurement, voxel-based analysis, tract-based spatial statistics, and tract-specific analysis (TSA). The present review focuses on TSA to investigate AD. An overview of the changes in diffusion properties of AD measured using TSA is presented and discussed.

We compared different acquisition and reconstruction methods in phantom and human studies in the clinical setting to validate our hypothesis that optimizing the k-space acquisition and reconstruction method could decrease motion artifacts.Diffusion tensor images of a water phantom were obtained with three table displacement magnitudes: 1 mm, 2 mm, and 3 mm. Images were reconstructed using homodyne and zero-fill reconstruction. Overscanning in 8- and 16-k(y) lines was tested. We performed visual assessment of the artifacts using reconstructed coronal images and analyzed them with Wilcoxon signed-ranks test both for phantom and human studies. Also, fractional anisotropy (FA) changes between acquisition methods were compared.Artifacts due to smaller displacement (1 and 2 mm) were significantly reduced in 16-k(y) overscan with zero filling. The Wilcoxon signed-ranks test showed significant differences (P0.031 for reconstruction methods and P0.016 for overscanning methods). FA changes were statistically significant (P0.037; Student's t-test). The Wilcoxon signed-ranks test showed significant reductions (P0.005) in the human study.Motion-induced artifacts can be reduced by optimizing acquisition and reconstruction methods. The techniques described in this study offer an effective method for robust estimation of diffusion tensor in the presence of motion-related artifactual data points.

6-Fluoro-3-oxo-indan-1-acetic acid (5) and 6-fluoroindan-1-acetic acid (6) were conveniently synthesised from 3-fluorobenzaldehyde in four and five steps, respectively. The structures of these new compounds and two other intermediates, 3-fluorobenzylidine-bis-acetoacetate (2) and 3-fluoro-beta-phenyl glutaric acid (3) were elucidated by spectroscopic means, notably, HRMS, 1D and 2D NMR. The analgesic activity of compounds 5 and 6 were assessed by the acetic acid induced writhing in Swiss albino mice.

Our aim was to determine diffusion abnormalities in the uncinate fasciculus (UF) in Alzheimer's disease (AD) by diffusion tensor tractography (DTT) using a new method for measuring the core of the tract.We studied 19 patients with AD and 19 age-matched control subjects who underwent MRI using diffusion tensor imaging (DTI). DTT of the UF was generated. The mean diffusivity (MD) and fractional anisotropy (FA) of the core of the tract were measured after voxelized tract shape processing. Student's t-test was used to compare results between patients with AD and controls. Intraobserver correlation tests were also performed.FA was significantly lower (P0.0001) in the UF of patients with AD than of controls. There was no significant difference in MD along the UF between the two groups. Intraobserver reliability (intraclass correlation coefficient) for the first and second measurement was r0.93 for measured FA and r0.92 for measured MD.Our results suggest that FA reflects progression of AD-related histopathological changes in the UF of the white matter and may represent a useful biological index in monitoring AD. Diffusion tensor tract-specific analysis with voxelized tract shape processing to measure the core of the tract may be a sensitive tool for evaluation of diffusion abnormalities of white matter tracts in AD.

The antibacterial activity of petroleum ether, carbon tetrachloride and chloroform soluble fractions of crude methanol extracts of nine indigenous plant species of Bangladesh was evaluated by the agar diffusion method. Kanamycin (30 μg/disc) was used as a standard antibacterial agent. The results indicated that all the nine plant species (not all partitionates) exhibited moderate to potent antibacterial activity against a wide variety of gram- positive and gram-negative bacteria at a concentration of 400μg/disc. Among them the carbon tetrachloride soluble fraction of whole plant extract of Corriandrum sativum (family-Apiaceae) revealed the highest antibacterial activity against Shigella boydii with zone of inhibition of 29 mm. Key words: Antibacterial activity; Disc diffusion method; Extract; Indigenous plants of Bangladesh. DOI: 10.3329/dujps.v8i1.5337 Dhaka Univ. J. Pharm. Sci. 8(1): 61-65, 2009 (June)

The purpose of the study was to develop a simple, sensitive and rapid RP-HPLC method for the determination of desloratadine in marketed products. Chromatographic determination was performed in a reverse phase C18 column (250 mm × 3.3 mm I.D. , 5?m particle size) using a mixture of acetonitrile ? n-pentane sulphonic acid sodium salt monohydrate, adjusted to pH 3.0± 0.05 with phosphoric acid (60? 40 v/v) as mobile phase and delivered at a flow rate of 1 ml/min. The UV detection was set at 254 nm. The calibration range was from 2.0 to 40 ?g/ml. The method was validated in term of linearity (r2>0.98, RSD= 1.958%), precision (RSD=3.757 %) and accuracy (deviation>2.653%, RSD> 2.203%). The limit of quantification was 2 ?g/ml and the limit of detection was 0.1 ?g/ml. The linear ranges of desloratadine were 20.23 ± 0.368 ?g/ml and 6.545 ± 0.0495 ?g/ml in tablet (potency = 99.175 ± 0.718 %) and syrup (potency = 101.15 ± 1.838 %) respectively. The potency of desloratadine in marketed products was determined by this method with acceptable precision and reproducibility. Keywords: Desloratadine, marketed products, RP-HPLC, development of a method Dhaka Univ. J. Pharm. Sci. Vol.5(1-2) 2006 The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website