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   Table of Contents - Current issue
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October-December 2016
Volume 8 | Issue 4
Page Nos. 265-348

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REVIEW ARTICLE  

Averrhoa bilimbi Linn.: A review of its ethnomedicinal uses, phytochemistry, and pharmacology p. 265
Alhassan Muhammad Alhassan, Qamar Uddin Ahmed
DOI:10.4103/0975-7406.199342  
Averrhoa bilimbi Linn. is principally cultivated for medicinal purposes in many tropical and subtropical countries of the world. Literature survey about this plant shows that A. bilimbi is mainly used as a folk medicine in the treatment of diabetes mellitus, hypertension, and as an antimicrobial agent. The prime objective of this review is to accumulate and organize literature based on traditional claims and correlate those with current findings on the use of A. bilimbi in the management of different ailments. Through interpreting already published scientific manuscripts (1995 through 2015) retrieved from the different scientific search engines, namely Medline, PubMed, EMBASE, and Science Direct databases, published articles and reports covering traditional and scientific literature related to A. bilimbi's potential role against various ailments have been thoroughly evaluated, interpreted, and discussed. Several pharmacological studies have demonstrated the ability of this plant to act as antidiabetic, antihypertensive, thrombolytic, antimicrobial, antioxidant, hepatoprotective, and hypolipidemic agent. A. bilimbi holds great value in the complementary and alternative medicine as evidenced by the substantial amount of research on it. Therefore, we aimed to compile an up-to-date and comprehensive review of A. bilimbi that covers its traditional and folk medicine uses, phytochemistry, and pharmacology. Hence, this paper presents an up-to-date and comprehensive review of the ethnomedicinal uses, different chemical constituents, and pharmacological activities of A. bilimbi. So far, the biologically active agents have not been isolated from this plant and this can be a good scientific study for the future antidiabetic, antihypertensive, and antimicrobial implications. Hence, this review targets at emphasizing the diverse traditional claims and pharmacological activities of A. bilimbi with respect to carrying out more scientific studies to isolate active principles through advanced technology.
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ORIGINAL ARTICLES Top

In vitro evaluation of bioremediation capacity of a commercial probiotic, Bacillus coagulans, for chromium (VI) and lead (II) toxicity p. 272
Pranoti Belapurkar, Pragya Goyal, Anand Kar
DOI:10.4103/0975-7406.199344  
Introduction: The bioaccumulation of heavy metals including chromium (VI) (Cr (VI)) and lead (II) (Pb (II)) causes fatal toxicity in humans. Some naturally occurring bacterial genera such as Bacillus and Pseudomonas help in bioremediation of these heavy metals and some of the species of Bacillus are proven probiotics. However, no study has been conducted on Bacillus coagulans, which is a proven probiotic species of genus Bacillus. Objectives: The primary objective of the present study was to assess the potential of a proven probiotic, B. coagulans, marketed as “Sporlac-DS,” to survive in the presence of Cr (VI) and Pb (II) and its ability to reduce its concentration in vitro. Materials and Methods: The Minimum inhibitory concentration (MIC) of the organism for Cr (VI) and Pb (II) was determined followed by its biochemical and morphological characterization. Its antibiotic sensitivity and probiotic efficacy were assessed. Further, its bioremediation capacity was observed in vitro by determining the residual Cr (VI) and Pb (II) concentration after 72 h. Results: B. coagulans could tolerate up to 512 ppm concentration of Cr (VI) and had an MIC of 128 ppm for Pb (II). After 72 h, the organism reduced 32 ppm Cr (VI) and 64 ppm Pb (II) by 93% and 89%, respectively. When B. coagulans was studied before and after growing on Cr (VI) and Pb (II) for 24 h, an increase was seen in sensitivity toward the tested antibiotics whereas no change was observed in morphological and biochemical characters. It also showed no change in their bile and acid tolerance, indicating that it retains its probiotic efficacy. Conclusion: The tested probiotic B. coagulans may have a potential role in bioremediation of Cr (VI) and Pb (II), in vivo.
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Thymol, a monoterpene, inhibits aldose reductase and high-glucose-induced cataract on isolated goat lens p. 277
Divya M Kanchan, Smita S Kale, Gauresh S Somani, Aakruti A Kaikini, Sadhana Sathaye
DOI:10.4103/0975-7406.199348  
Background: Overactivation of aldose reductase (AR) enzyme has been implicated in the development of various diabetic complications. In the present study, the inhibitory effect of thymol was investigated on AR enzyme and its anti-cataract activity was also examined on isolated goat lens. Materials and Methods: Various concentrations of thymol were incubated with AR enzyme prepared from isolated goat lens. Molecular docking studies were carried out using Schrodinger software to verify the binding of thymol with AR as well as to understand their binding pattern. Further, thymol was evaluated for its anti-cataract activity in high-glucose-induced cataract in isolated goat lens in vitro. Quercetin was maintained as standard (positive control) throughout the study. Results: Thymol showed potent inhibitory activity against goat lens AR enzyme with an IC50value of 0.65 μg/ml. Docking studies revealed that thymol binds with AR in similar binding pattern as that of quercetin. The high–glucose-induced cataract in isolated goat lens was also improved by thymol treatment. Thymol was also able to significantly (P < 0.001) reduce the oxidative stress associated with cataract. Conclusion: The results suggest that thymol may be a potential therapeutic approach in the prevention of diabetic complications through its AR inhibitory and antioxidant activities.
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A qualitative insight on complementary and alternative medicines used by hypertensive patients p. 284
Inas Rifaat Ibrahim, Mohamed Azmi Hassali, Fahad Saleem, Haydar F Al Tukmagi
DOI:10.4103/0975-7406.199349  
Background: The self-treatment with complementary and alternative medicines (CAMs) in chronic diseases is portraying an expanding trend worldwide. Yet, little is known concerning patients' motives to use CAM in the control of blood pressure. Objective: This study aims to explore the self-use of CAM in the management of hypertension and explore patients' attitudes, perceived benefits, and disclosure to the physician. Materials and Methods: A qualitative technique was adopted and face-to-face interviews, using a validated interview guide, were carried out among twenty hypertensive patients. A purposive sampling method was used to recruit patients at Al-Karama Teaching Hospital in Baghdad; the capital of Iraq; from January to April 2015. All the interviews were audio-recorded, then transcribed verbatim and examined for thematic relationships. Results: Three major themes were identified through thematic content analysis of the interviews. These encompassed patients' understanding of CAM; experience and perceived benefits; and communication with the doctors. The use of CAM was prevalent among the majority of the respondents. The most commonly used therapies were biological-based practices (herbal remedies, special diet, vitamins, and dietary supplements); traditional therapies (Al-Hijama or cupping); and to a less extent of manipulative body-based therapies (reflexology). Factors influencing the use of CAM were traditions, social relationships, religious beliefs, low-cost therapy, and safety of natural products. Conclusion: The use of CAM was common as a practice of self-treatment among hypertensive patients in Iraq. This was underpinned by the cultural effects, social relationships, religious beliefs, and the perception that natural products are effective and safe. Understanding patients' usage of CAM is of great importance as long as patient's safety and interaction with the standard prescribed treatment are major concerns.
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Risk factors for developing drug-related problems in patients with cardiovascular diseases attending Gondar University Hospital, Ethiopia p. 289
Ousman Abubeker Abdela, Akshaya Srikanth Bhagavathula, Henok Getachew, Yohannes Kelifa
DOI:10.4103/0975-7406.199335  
Background: Cardiovascular diseases (CVDs) are often accompanied with comoribidities and complications leading to taking multiple drugs and thus are more liable to be exposed to drug-related problems (DRPs). DRPs can occur at any stages of medication process from prescription to follow-up treatment. However, a few studies have assessed the specific risk factors for occurrence of at least one potential DRP per patient with CVDs in sub-Saharan African region. Aim: We aim to assess the risk factors for developing potential DRPs in patients with CVDs attending Gondar University Referral Hospital (GUH). Methodology: This was a cross-sectional study. A structured systematic data review was designed focusing on patients with CVDs (both out and inpatients) with age >18 years of both genders attending GUH from April to June 2015. All DRPs were assessed using drugs.com and Medscape. The causes of DRPs were classified using Pharmaceutical Care Network Europe version 6.2. Risk factors that could cause DRPs were assessed using binary logistic regression showing odds ratio with 95% confidential interval. Statistical significance was set at P< 0.05. Results: A total of 227 patients with CVDs were reviewed with a mean age of 52.0 ± 1.7 years. Majority were females (143, 63%), outpatients (133, 58.6%), and diagnosed with heart failure (71, 31.3%). Diuretics (199, 29.5%) were the most commonly prescribed drugs. A total of 265 DRPs were identified, 63.4% of patients have at least one DRP (1.17 ± 1.1). The most common DRPs were found to be an inappropriate selection of drug (36.1%) and dose (24.8%). The most identified risk factors causing DRPs were: Need of additional drug therapy and lack of therapeutic monitoring. Conclusion: The most identified risk factors for developing DRPs were the need of additional drug therapy and lack of therapeutic monitoring. There is a need for clinical pharmacist interventions to monitor and prevent the risk of developing DRPs and contribute to improve the clinical outcome in patients with CVDs.
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Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats p. 296
Lalita Mehra, Yasha Hasija, Gaurav Mittal
DOI:10.4103/0975-7406.199345  
Objective: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control): Normal Saline, Group II (APAP): A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG): APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) with oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05) reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats.
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Optimization, characterization, and efficacy evaluation of 2% chitosan scaffold for tissue engineering and wound healing p. 300
Priyanka Chhabra, Priyanka Tyagi, Aseem Bhatnagar, Gaurav Mittal, Amit Kumar
DOI:10.4103/0975-7406.199346  
Objective: To develop a chitosan-based scaffold and carry out a complete comprehensive study encompassing optimization of exact chitosan strength, product characterization, toxicity evaluation, in vitro validation in cell culture experiments, and finally in vivo efficacy in animal excision wound model. Materials and Methods: Developed chitosan scaffolds (CSs) were optimized for tissue engineering and wound healing efficacy by means of microstructure, toxicity, and biocompatibility evaluation. Results: Scanning electron microscope (SEM) studies revealed that porosity of CS decreased with increase in chitosan concentration. Chemical stability and integrity of scaffolds were confirmed by Fourier transform infrared studies. Highest swelling percentage (SP) of 500% was observed in 2%, while lowest (200%) was observed in 1% CS. Reabsorption and noncytotoxic property of optimized scaffold were established by enzymatic degradation and MTT assay. Enzymatic degradation suggested 20–45% of weight loss (WL) within 14 days of incubation. Cytotoxicity analysis showed that scaffolds were noncytotoxic against normal human dermal fibroblast human dermal fibroblast cell lines. Significant cellular adherence over the scaffold surface with normal cellular morphology was confirmed using SEM analysis. In vivo efficacy evaluation was carried out by means of reduction in wound size on Sprague-Dawley rats. Sprague-Dawley rats treated with optimized scaffold showed ~ 100% wound healing in comparison to ~80% healing in betadine-treated animals within 14 days. Histological examination depicted advance re-epithelization with better organization of collagen bundle in wound area treated with 2% CS in comparison to conventional treatment or no treatment. Conclusion: This study, thus, reveals that 2% CSs were found to have a great potential in wound healing.
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Patterns of prescription drugs use among pregnant women at Sultan Qaboos University Hospital and Sultan Qaboos University Hospital Family and Community Medicine Clinic, Oman p. 309
JZ Al-Hamimi, KA Al Balushi
DOI:10.4103/0975-7406.199347  
Objective: This study evaluates the patterns of prescription drugs use among women attending antenatal clinic at Sultan Qaboos University Hospital (SQUH) and SQUH Family and Community Medicine clinic (FAMCO), Oman. Methods: The study was a descriptive retrospective cross-sectional study on pregnant women who attended the antenatal clinic at SQUH and FAMCO from February to April 2014 and received a prescription containing at least one drug. Patients' information was extracted from SQUH electronic records. Results: A total of 105 pregnant women were included in the study. Among the recruited pregnant women, 35 (33.3%) had at least one chronic disease. The average number of drugs prescribed per patient per prescription during the period of pregnancy was 2.33 ± 1.43. Vitamins and minerals were the most frequently prescribed class of drugs (30.60%) followed by analgesics (11.19%) and antidiabetic drugs (10.13%). According to the Food and Drug Administration risk classification, most of the prescribed drugs were from category B (30.0%) and C (27.14%). No drug was prescribed from category X. There was a significant decrease in prescribing category A drugs over the three trimesters (20.7%, 12.7%, and 9.3%, respectively) (P < 0.047). Conclusion: The study gives an overview of the extent of drug prescription during pregnancy and increases the awareness of health-care providers and women about the potential risks of drug use during pregnancy.
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Assessment of cost of illness for diabetic patients in South Indian tertiary care hospital p. 314
Leelavathi D Acharya, NR Rau, N Udupa, M Surulivel Rajan, K Vijayanarayana
DOI:10.4103/0975-7406.199336  
Background: The impact of diabetes on health-care expenditures has been increasingly recognized. To formulate an effective health planning and resource allocation, it is important to determine economic burden. Objective: The objective of this study is to assess the cost of illness (COI) for diabetic inpatients with or without complications. Methodology: The study was conducted in the medicine wards of tertiary care hospital after ethical approval by the Institutional Ethical Committee. A total of 116 each diabetic with or without complications were selected and relevant data were collected using COI questionnaire and data were analyzed using SPSS version 20. Mann–Whitney U test is used to assess the statistical significant difference in the cost of treatment of diabetes alone and with complications'. P ≤ 0.05 was considered statistically significant. Results: Total COI includes the cost of treatment, investigation, consultation fee, intervention cost, transportation, days lost due to work, and hospitalization. The median of total COI for diabetic care without any complication was Rs. 22,456.97/- per patient per annum and with complication was Rs. 30,634.45/-. Patients on dialysis had to spend 7.3 times higher, and patients with cardiac intervention had to spend 7.4 times higher than diabetic patients without any complication. Conclusion: Treatment costs were many times higher in patients with complications and with cardiac and renal interventions. Complications in diabetic patients will increase the economic burden to family and also to the society.
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Synthesis of some novel pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives as potential antimicrobial agent p. 321
Dipen K Sureja, Sandip P Dholakia, Kantilal R Vadalia
DOI:10.4103/0975-7406.199337  
Objectives: The aim of the present work was to synthesize a novel series of pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives and evaluate their in vitro antimicrobial activity. Methods: Cyclization of an ortho-amino ester of 1-(2,4-dinitrophenyl)pyrazole with various aliphatic/aromatic nitriles under different reaction conditions such as conventional and microwave assisted synthesis, provided pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives. All the synthesized compounds were evaluated in vitro for their antimicrobial activity against selected bacteria and fungi by agar well diffusion method. Results: All newly synthesized compounds were characterized using spectral and elemental analysis. Compounds 2e, 2f, and 2g showed significant antimicrobial activity as compared to standard drugs used. Conclusion: The newly synthesized compounds could be useful templates for the design and optimization of more active analogs as a possible antimicrobial agent.
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1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats p. 327
Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar
DOI:10.4103/0975-7406.199339  
Introduction: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group): control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR) spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a) increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b) decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a) decreased TCA cycle activity and enhanced fatty acid oxidation, (b) dysfunction of lipid and amino acid metabolism and (c) oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new drug-formulations.
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Prescription patterns and appropriateness of antibiotics in the management of cough/cold and diarrhea in a rural tertiary care teaching hospital p. 335
Akram Ahmad, Muhammad Umair Khan, Sadiqa Malik, Guru Prasad Mohanta, S Parimalakrishnan, Isha Patel, Sameer Dhingra
DOI:10.4103/0975-7406.199340  
Background: Acute gastroenteritis and respiratory illnesses are the major causes of morbidity and mortality in children under 5 years of age. The objective of this study was to evaluate the prescription pattern of antibiotic utilization during the treatment of cough/cold and/or diarrhea in pediatric patients. Methods: A descriptive, cross-sectional study was conducted for 6 months in pediatric units of a tertiary care hospital in South India. Children under 5 years of age presenting with illness related to diarrhea and/or cough/cold were included in this study. Data were collected by reviewing patient files and then assessed for its appropriateness against the criteria developed in view of the Medication Appropriateness Index and Guidelines of the Indian Academy of Pediatrics. The results were expressed in frequencies and percentages. Chi-square test was used to analyze the data. A P < 0.05 was considered statistically significant. Results: A total of 303 patients were studied during the study period. The mean age of the patients was 3.5 ± 0.6 years. The majority of children were admitted mainly due to chief complaint of fever (63%) and cough and cold (56.4%). The appropriateness of antibiotic prescriptions was higher in bloody and watery diarrhea (83.3% and 82.6%; P< 0.05). Cephalosporins (46.2%) and penicillins (39.9%) were the most commonly prescribed antibiotics, though the generic prescriptions of these drugs were the lowest (13.5% and 10%, respectively). The seniority of prescriber was significantly associated with the appropriateness of prescriptions (P < 0.05). Antibiotics prescription was higher in cold/cough and diarrhea (93.5%) in comparison to cough/cold (85%) or diarrhea (75%) alone. Conclusions: The study observed high rates of antibiotic utilization in Chidambaram during the treatment of cough/cold and/or diarrhea in pediatric patients. The findings highlight the need for combined interventions using education and expert counseling, targeted to the clinical conditions and classes of antibiotic for which inappropriate usage is most common.
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SHORT COMMUNICATION Top

Pharmacological evaluation of Apium leptophyllum (Pers.) on bronchial asthma p. 341
Himanshu Bhusan Sahoo, Rakesh Sagar, Ganesh Patro, Madhulita Panda, Saroj Kumar Sahoo, D Priyadarshini
DOI:10.4103/0975-7406.199343  
Objective: The present study was to investigate the antiasthmatic potential from the flavonoid fraction of Apium leptophyllum fruit (FFALF) to validate its traditional claim. Materials and Methods: The antiasthmatic activity of FFALF was evaluated by histamine or acetylcholine-induced bronchospasm model in guinea pigs, compound 48/80 induced mast cell degranulation in albino rats and histamine-induced tracheal contraction in guinea pig. The preconvulsion dyspnea time at 0th and 7th day at the dose of 100 and 200 mg/kg in guinea pig's bronchospasm model, the percentage of granulated and degranulated mast cell at the dose of 500, 750, and 1000 μg/ml in rats and tracheal contraction at the dose of 500, 750, and 1000 μg/ml in guinea pig were measured and compared with respective control groups. Results: The treatments of FFALF were significantly (P < 0.001) decreased the histamine/acetylcholine-induced bronchospasm, mast cell degranulation, and histamine-induced tracheal contraction as compared to inducer group. In addition, FFALF showed dose-dependent antiasthmatic activity in all the animals. Conclusion: Hence, this study suggested that the FFALF showed antiasthmatic activity probably by membrane stabilizing property as well as suppressing antibody production and inhibiting of antigen induced by histamine and acetylcholine.
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LETTERS Top

Menopausal symptoms and obesity: Is there a relationship? p. 346
Maria Fernanda Naufel, Cristina Frange, Sérgio Tufik, Helena Hachul
DOI:10.4103/0975-7406.199338  
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Electronic cigarette experimentation in the Malaysian city of Kuantan: Was there an association with the smoking status? p. 347
Konstantinos E Farsalinos, Jacques Le Houezec
DOI:10.4103/0975-7406.199341  
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