World Academy of Science, Engineering and Technology

Authors: G. Raviraja Shetty, K. G. Poojitha, Pranay Kumar

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Biodiversity refers to the numbers, variety and variability of living organisms and ecosystem. The climatic and altitudinal variations, coupled with varied ecological habitats of this country, have contributed to the development of immensely rich vegetation with a unique diversity in medicinal plants which provides an important source of medicinal raw materials for traditional medicine systems as well as for pharmaceutical industries in the country and abroad. World Health Organization has listed over 21000 plant species used around the world for medicinal purpose. In India, about 2500 plant species are being used in indigenous system of medicine. The red data book lists 427 Indian Medicinal plant entries on endangered species, of which 28 are considered extinct, 124 endangered, 81 rare, and 34 insufficiently known. It is abundantly clear from the experience of all govt agencies that on their own they cannot efficiently conserve the biodiversity. Participatory Approach with the involvement of local people in conservation is found to be more effective these days. Involvement of local people reduces the cost involved in conservation. Local communities have long tradition of resource use in particular area, hold in depth knowledge and experience of plant which can be invaluable for conservation efforts.Medicinal plants occupy a vital sector of health care system in India and represent a major national resource.There is an immense need for conservation of diversity of medicinal plant wealth for the present and fore coming generations, by adapting the suitable strategy with most appropriate method of conservation.

Keywords: conservation, biodiversity, participatory, medicinal plants

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Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

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Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

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Authors: Richa Sinha, Mohammad Irfan Javed, Sanjay Singh

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Introduction: Good antimicrobial prescribing reduces length of stay in hospital, risk of adverse events, antimicrobial resistance, and unnecessary hospital expenditure. The aim of this prospective audit was to identify any problems with antimicrobial prescribing including documentation of the relevant aspects as well as appropriateness of antibiotics use. The audit was conducted on the surgical wards in a teaching hospital in the UK. Methods: Standards included the indication, duration, choice, and prescription of antibiotic should be in line with current Regional Guidelines and should be clearly documented on the prescription chart. There should be an entry in each patients’ medical record of the diagnosis and indication for each acute antibiotic prescription issued. All prescriptions should clearly document the route, frequency and dose of antibiotic. Data collection was done for 2 weeks in the month of March 2014. A proforma including all the questions above was completed for all the patients. The results were analysed using Excel. Results: 35 patients in total were selected for the audit. 85.7% of patients had indication of antibiotic documented on the prescription chart and 68.5% of patients had indication documented in the notes. The antibiotic used was in line with hospital guidelines in 45.7% of patients, however, in a further 28.5% of patients the reason for the antibiotic prescription was microbiology approved. Therefore, in total 74.2% of patients had been prescribed appropriate antibiotics. The duration of antibiotic was documented in 68.6% of patients and the antibiotic was reviewed in 37.1% of patients. The dose, frequency and route was documented clearly in 100% of patients. Conclusion: Overall, prescribing can be improved on the surgical wards in this hospital. Only 37.1% of patients had clear documentation of a review of antibiotics. It may be that antibiotics have been reviewed but this should be clearly highlighted on the prescription chart or the notes. Failure to review antibiotics can lead to poor patient care and antimicrobial resistance and therefore it is important to address this. It is also important to address the appropriateness of antibiotics as inappropriate antibiotic prescription can lead to failure of treatment as well as antimicrobial resistance. The good points from the audit was that all patients had clear documentation of dose, route and frequency which is extremely important in the administration of antibiotics. Recommendations from this audit included to emphasize good antimicrobial prescribing at induction (twice yearly), an antimicrobial handbook for junior doctors, and re-audit in 6 months time.

Keywords: prescribing, antimicrobial, indication, duration

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Authors: Jyoti Manandhar Shrestha, Saurab Raj Joshi, Maya Shrestha, Prashanna Shrestha, Kshitij Chaulagain

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Background: The widespread use of non-steroidal anti-inflammatory drugs has increased the incidence of ulcer and serious complications, such as perforation and bleeding. Although, the H2 receptor blockers and proton pump inhibitors decrease the acid secretion and promote healing of ulcer, their value in preventing relapse, recurrence, “acid rebound” after cessation of therapy and associated long term adverse effects limit their utility. So to minimize this, the herbal plant Aloe vera having anti-oxidant, anti-inflammatory, mucus secreting, cyto-protective and healing property is believed to cure the peptic ulcer. Objectives: To observe whether oral treatment with Aloe vera gel can prevent peptic ulcer. Indomethacin and ethanol were used to induce gastric ulcers. Thirty six albino rats of either sex were randomly allotted to six groups of six animals each. The negative control was pretreated with normal saline, the positive controls received ranitidine (20 mg/kg) and the test group received Aloe vera gel (300 mg/kg) orally for eight days. Then, after a 24 hour fast Indomethacin (20 mg/kg) or 80% ethanol (2ml) was administered orally to induce ulceration. At the end of the study, the rats were sacrificed, their stomachs opened, the ulcer index studied and tissues sent for histopathological examination. Results: It was observed that, in indomethacin treated group, the ulcer index in control group was 8.167 ± 1.72.In the Aloe vera pretreated animals, the ulcer index was 2.83 ± 1.72 and the standard ranitidine pretreated group ulcer index was 1.67 ± 1.36. In ethanol treated group, the ulcer index in control group was 7.5 ± 2.73. In the Aloe vera pretreated animals, the ulcer index was 2.67 ± 1.75 and the standard ranitidine pretreated group ulcer index was 1.33±1.21. Both ranitidine and Aloe vera gel significantly prevented stomach from gastric ulceration induced by indomethacin and ethanol. Conclusion: The results indicated that Aloe vera gel is effective against indomethacin and ethanol mediated gastric ulcer.

Keywords: Aloe vera gel, ethanol, indomethacin, peptic ulcer, ranitidine

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Authors: Mahdeb Nadia, Ghadjati Nadhra, Bettihi Sara, Daamouche Z. El Youm, Bouzidi Abdelouahab

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The effects of subacute administration of total alkaloids of seeds Peganum harmala were studied in female Albino-Wistar rats. After intraperitoneal administration of dose 50 mg/kg for 10 days and 40 mg/kg for 7 days of total alkaloids to the seeds of Peganum harmala (animal treatment lasted 17 days), there were remarkable changes in general appearance and deaths occurred in experimental group. After 17 days a significant reduction was observed in the surviving animals treated with total alkaloid seeds.The Red Blood Cells (RBC), Hematocrit (HCT), Hemoglobin (HGB) and White blood cells (WBCs), show significant reduction in the treated groups. There were no statistical differences in Glutamic-Oxaloacetic Transaminase (GOT), Glutamic-pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP), total protein, glucose and creatinine observed between groups. However the urea was significantly higher in the treated female rats than the control group. Histological examination of liver showed no histopathological changes. Alkaloids of Peganum harmala showed significant toxicity in female rats.

Keywords: Peganum harmala, rat, liver, kidney, alkaloids, toxicity

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Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

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The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

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Authors: F. Belkhiri, A. Baghiani, S. Boumerfeg, N. Charef, S. Khennouf, L. Arrar

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The present study was conducted to evaluate the in vitro antioxidant and antibacterial properties of methanolic extracts from roots of Tamus communis L. (TCRE), which is a plant used in traditional medicine in Algeria. The antioxidant potential of pattern was evaluated using tow complementary techniques, inhibition of free radical DPPH and the test of β-Carotene/linoleic acid. The antioxidant test indicates that non-polar fractions of TCRE (chloroform and ethyl acetate fractions) were more active than the polar fractions. Among these fractions, the chloroform extract appear in the DPPH test an IC50 of (18.89 µg/ml) comparable to that of BHT (18.6 µg/ml). This fraction was able to inhibiting the oxidation of β-Carotene with a percentage of inhibition (89.84 %). In antibacterial test, non-polar fractions showed antibacterial activity very important compared with the polar fractions. These fractions have inhibited the growth of four from nine bacterial strains, causing zones of inhibition from 08 to 23 mm of diameter.

Keywords: antioxidant activity, antibacterial activity, Tamus communis L., polar fractions

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Authors: Hamdi Belfeki, Belgacem Chandoul, Mnasser Hassouna, Mondher Mejri

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Aqueous and ethanolic extracts of eight Tunisian aromatic and medicinal plants (TAMP) were characterized by studying their composition in polyphenols and also their antiradical and antioxidant capacities. In absence and in the presence of the various extracts, α-amylase from Bacillus subtlis activity, was measured in order to detect a potential inhibition. The total contents of polyphenols and flavonoid vary in function of TAMP and the mobile phase used for the extraction (distilled water or ethanol). The ethanolic extracts showed the most significant antiradical and antioxidant activities. Only the extracts from Coriandrum sativum showed a significant inhibiting effect on the α-amylase activity. This inhibiting capacity could be correlated with the chemical profile of the two extracts, due to the fact that they have the greatest amount of total flavonoid. The ethanolic extract has the most important antioxidant and anti-radicalizing activities among the sixteen extracts studied. The inhibition kinetics of the two coriander extracts were evaluated by pre-incubation method, using Lineweaver-Burk’s equation, obtained by linearization of Michaeilis-Menten’s expression. The results showed that both extracts exercised a competitive inhibition mechanism.

Keywords: α-amylase, antioxidant activity, aromatic and medicinal plants, inhibition

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Authors: Abdelouahab Dehimati, Fatiha Bedjou

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This study focused on the antioxidant and antimicrobial activity of four extracts from the plant Matricaria pubscens (Asteraceae) harvest in the region of Ghardaia, the northern Sahara of Algeria. The different extracts were analyzed for their content of phenolic compounds and their biological activities. The ethanol extract expresses a better extraction yield (44.22%). We have first performed the quantitative colorimetric methods for total polyphenols. Wherein the aqueous extract shows the highest total polyphenol content and total flavonoid (216.66±2.58 mg Eq GA/g and 111.04±0.49 mg Eq Q/g E, respectively) and ethanol extract 50% total tannins content (68.88±2.72 mg Eq AT/g E). The evaluation of the antioxidant activity of extracts of Matricaria pubscens by the arbitrary value IC50. The ethanol 50% extract is expressed strong activity with an IC50 14.19±1.25 mg/m against the DPPH radical and 11.66±0.53 mg/ml against the ABTS radical). In addition, the aqueous extract showed strong reducing power with an IC50 (48.61±1.14 mg/ml). However, the results obtained by the reducing power of phosphomolybdat the test are calculated by the iron maximum absorbance where ethanol extract 50% gives an absorbance of about 1.641 ± 0.01nm. Otherwise, methanol 70% and butanol 80% extracts gave a very large chelating effect of iron with an IC50 (38.38±0.01 μg/ml and 38.58±0.04 μg/ml respectively). By the method of disc Diffuson, the results of the antimicrobial activity are achieved butanolic extract 80% shows high activity towards MRSA (MIC: 3.51mg/ml; BMC>100 mg/ml). Their shares, the extracts were the most active for the antifungal test, the butanol 80% extract was the most active against A. niger (MIC: 12.5 mg/ml; FMC>100 mg/ml). These preliminary results could be used to justify the traditional use of this plant and their phenolic compounds could be exploited for therapeutic purposes, such as antioxidants and antimicrobial effects.

Keywords: Matricaria pubscens, phenolic compounds, antioxidant activity, antimicrobial activity, IC50, MIC

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Authors: Assia Amri, Naima Layachi, Ali Ladjama

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The characterization of some Algerian honey was carried out on the basis of their physico-chemical properties: moisture,hydroxy methyl furfural, diastase activity, pH,free, total and lactonic acidity, electrical conductivity, minerals and proline content. Studied samples are found to be low in moisture and therefore safe from fermentation, low in HMF level and high in diastase activity. Additionally the diastase activity and the HMF content are widely recognized parameters indicating the freshness of honey. Phenolic compounds present in honey are classified into two groups - simple phenols and polyphenols. The simple phenols in honey are various phenol acids, but polyphenols are various flavonoids and flavonides. The aim of our work was to determine antioxidant properties of various Algerian honey samples–the total phenol content, total flavonoids content, as well as honey anti radical activity.The quality of honey samples differs on account of various factors such as season, packaging and processing conditions, floral source, geographical origin and storage period. It is important that precautions should be taken to ensure standardization and rationalization of beekeeping techniques, manufacturing procedures and storing processes to improve honey quality.

Keywords: honey, physico-chemical characterization, phenolic coumpound, HMF, diastase activity

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Authors: Amel Bouaziz, Seddik Khennouf, Mussa Abu Zarga, Shtayway Abdalla, Saliha Djidel, Assia Bentahar, Saliha Dahamna, Smain Amira

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The present study aimed to evaluate the hypotensive and the in vitro antioxidant activities of Crataegus azarolus L. (Rosaceae), a plant widely used as natural remedy for hypertension in folk medicine. The antioxidant potential of methanolic extract (ME)and its three fractions of Chloroform (CHE), ethyl acetate (EAE)and water (AqE) have been investigated using several assays, including the DPPH scavenging, ABTS scavenging, hydroxyl radical scavenging. Inhibition of lipid peroxidation was performed by the β-carotene bleaching assay, ferric thiocyanate method and thiobarburic acid method. Total phenolic and total flavonoid contents of the extracts were estimated using Folin-Chiocalteu reagent and AlCl3, respectively. EAE extract showed the highest polyphenolic and flavonoids contents (396,04±1.20 mg GAE/g of dry extract and 32,73 ± 0.03mg QE/g of dry extract) respectively. Similarly, this extract possessed the highest scavenging activity for DPPH radical (IC 50 = 0,006±0,0001mg /ml), ABTS radical (IC50=0.0035±0,0007 mg/ml) and hydroxyl radical(IC 50=0,283± 0.01 mg/ml). In addition, the EAE exhibited the highest antioxidant activity in the inhibition of linoleic acid/ß-carotene coupled oxidation (89,21%), lipid peroxidation in the ferric thiocyanate(FTC) method (90.13%), and thio-barbituric acid (TBA) method (74.23%). Intravenous administration of Me and EAE decreased mean arterial blood pressure, systolic and diastolic blood pressure in anesthetized rats dose-dependently, at the dose range of 0.4 to 12 mg/kg. The mean arterial blood pressure dropped by 27.58 and 39.37% for ME and EAE, respectively. In conclusion, The present study supported the significant potential to use C. azarolus by-products as a source of natural antioxidants and provides scientific justification for its traditional uses as cardio-protective and anti-hypertensive remedy.

Keywords: Crataegus azarolus, polyphenols, flavonoids, hypertension, antioxidant activity, free radicals, peroxidation

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Authors: Sihana Ahmeti Lika, Merita Dauti, Ledjan Malaj

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The objective of this study is to analyze the prophylactic usage of low molecular weight heparine (LMWH) along pregnancy and the correlation between their usage and month/week of pregnancy, in the Department of Gynecology and Obstetrics, at Clinical Hospital in Tetovo. A retrospective study was undertaken during 01 January–31 December 2012. Over of one year, the total number of patients was 4636. Among the 1447 (32.21%) pregnant women, 298 (20.59%) of them were prescribed LMWH. The majority of patients given LMWH, 119 (39.93%) were diagnosed hypercoagulable. The age group with the highest attendance was 25-35, 141 patients (47.32%). For 195 (65.44%) patients, this was their first pregnancy. Earliest stage of using LMWH was the second month of pregnancy 4 (1.34%) cases. The most common patients, were 70 women along the seventh month (23.49%), followed by 68 in the ninth month of pregnancy (22.81%). Women in the 28th gestational week, were found to be the most affected, a total of 55 (78.57%) were in that week. Clexane 2000 and Fraxiparine 0.3 were the most common for which low molecular weight heparine was prescribed. The number of patients which received Clexane 2000 was 84 (28.19%), followed by those with Fraxiparine 0.3 81 (27.18%). The administration of LMWH is associated with long hospitalization (median 14,6 days).

Keywords: hypercoagulable state, low moleculare weight heparine, month of pregnancy, pregnant women

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Authors: Mohamed A. Etman, Mona G. Abd-Elnasser, Mohamed A. Shams-Eldin, Aly H. Nada

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Orally disintegrating tablets (ODTs) are gaining importance as new drug delivery systems and emerged as one of the popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. Their advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bed-ridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market. These dosage forms dissolve or disintegrate in the oral cavity within a matter of seconds without the need of water or chewing. Desloratadine is a tricyclic antihistaminic, which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. Desloratadine is the major metabolite of loratadine. Twelve different placebos ODT were prepared (F1-F12) using different functional excipients. They were evaluated for their compressibility, hardness and disintegration time. All formulations were non sticky except four formulations; namely (F8, F9, F10, F11). All formulations were compressible with the exception of (F2). Variable disintegration times were found ranging between 20 and 120 seconds. It was found that (F12) showed the least disintegration time (20 secs) without showing any sticking which could be due to the use of high percentage of superdisintegrants. Desloratadine showed bitter taste when formulated as ODT without any treatment. Therefore, different techniques were tried in order to mask its bitter taste. Using Eudragit EPO resulted in complete masking of the bitter taste of the drug and increased the acceptability to volunteers. The compressible non sticky formulations (F1, F3, F4, F5, F6, F7 and F12) were subjected to further evaluation tests after addition of coated desloratadine, including weight uniformity, wetting time, and friability testing.. Fairly good weight uniformity values were observed in all the tested formulations. F12 exhibiting the shortest wetting time (14.7 seconds) and consequently the lowest (20 seconds) disintegration time. Dissolution profile showed that 100% desloratadine release was attained after only 2.5 minutes from the prepared ODT (F12) with dissolution efficiency of 95%.

Keywords: Desloratadine, orally disintegrating tablets (ODTs), formulations, taste masking

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Authors: Merita Dauti, Edita Alili-Idrizi, Sihana Ahmeti –Lika, Ledjan Malaj

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The extermination and proper disposal of pharmaceutical wastes from expired and unused medications remains a disputable issue due to their specific nature and characteristics. Even though the hazards from these wastes are already well known in terms of environment and human health, people still treat them as usual wastes. At a national level, in many countries the management of pharmaceutical and medical wastes has been one of the main objectives in order to protect people’s health and the environment. Even though many legal regulations exist in this respect, there has not been a single law that would clearly explain the procedures of returning medicines, ways of selection, treatment and extermination of pharmaceutical wastes. This paper aims at analyzing the practices of pharmaceutical waste management and treatment in some European countries as well as a review of the legislation and official guidelines in managing these kinds of wastes and protecting the environment and human health. A suitable treatment and management of expired medications and other similar wastes would be in the interest of public health in the first place, as well as in the interest of healthcare institutions and other bodies engaged in environment protection.

Keywords: pharmaceutical waste, legal regulation, proper disposal, environment pollution

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Authors: Suhera M. Aburawi, Habiba A. El Jaafari, Soad A. Treesh, Abdulssalam M. Abu-Aisha, Faisal S. Alwaer, Reda A. Eltubuly, Medeha Elghedamsi

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Introduction: Infertility is a source of psychological, and sometimes social, stress on parents who desire to have children. Formaldehyde is used chiefly as disinfectant, preservative and in the chemical synthesis. The medical uses of formaldehyde are limited, but focused especially on laboratory use. Selenium is an essential trace mineral element for human; it is essential for sperm function and male fertility. Selenium deficiency has been linked to reproductive problems in animals. Objectives: To investigate the prophylactic and curative effect of selenium on male infertility induced by formaldehyde using male albino mice. Method: Forty male albino mice were used, weight 25-30 gm. Five groups of male mice (n=8) were used. Group 1 was daily administered water for injection (5ml/kg) for five days, group 2 was daily administered selenium (100 μg/kg) for five days, group 3 was daily administered formaldehyde (30mg/kg) for five days, group 4 (prophylaxis) was daily administered a combination of formaldehyde and selenium for five days, while group 5 (curative) was daily administered formaldehyde for five days followed by daily administration of selenium for the next five days. Intraperitoneal administration was adopted. At the end of the administration, seminal fluid was collected from vas deferens. Sperm count, morphology and motility were scored; histopathological screening of genital system was carried out. SPSS was applied for comparing groups. Results and conclusion: It was found that formaldehyde toxicity did not change the sperm count and percentage of motile sperm; unhealthy sperm was increased, while healthy sperm was decreased. Formaldehyde produces degeneration/damage to the male mice genital system. Selenium alone produce an increase in sperm count, volume of seminal fluid and the percentage of motile sperm. Selenium has prophylactic and curative effects against formaldehyde-induce genital system toxicity. Future work is recommended to find out if selenium protective effect is through antioxidant or other mechanisms.

Keywords: infertility, formaldehyde, selenium, male mice

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Authors: Patchara Pedpradab, Kietisak Yoksang, Kosin Pattanamanee

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In our ongoing search for pharmacological significant of compounds from marine organisms, we investigated the active constituents of two sponges (Xestospongia sp., Halichondria sp.) and a gorgonian coral (Juncella sp.) from the Andaman Sea, Thailand. Several compounds were isolated from those of marine organisms. A marine sponge, Xestospongia sp. contained an isoqinoline compound namely aureol and cytotoxic thiophenen sesterterpene while Halichondria sp. produced C-28 sterols. The white gorgonian coral, Juncella sp. contained anti-tuberculosis diterpenes namely, junceellin and praelolide. All of the isolated compounds were analyzed by spectroscopic methods, extensively.

Keywords: Xestospongia sp., Halichondria sp., gorgonian, Juncella sp. biological activity

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Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

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Authors: Baljinder Singh, Navneet Sharma

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Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. It influences glucose metabolism by potentiating the action as taking part in insulin signal amplification mechanism. A placebo-controlled single blind, prospective study was carried out to investigate the effect of chromium supplementation on blood glucose, HbA1C and lipid profile in newly onset patients with type-2 diabetes. Total 40 newly onset type-2 diabetics were selected and after one month stabilization further randomly divided into two groups viz. study group and placebo group. The study group received 9 gm brewer’s yeast (42 μ Cr) daily and the other placebo group received yeast devoid of chromium for 3 months. Subjects were instructed not to change their normal eating and living habits. Fasting blood glucose, HbA1C and lipid profile were analyzed at beginning and completion of the study. Results revealed that fasting blood glucose level significantly reduced in the subjects consuming yeast supplemented with chromium (197.65±6.68 to 103.68±6.64 mg/dl; p<0.001). HbA1C values improved significantly from 9.51±0.26% to 6.86±0.28%; p<0.001 indicating better glycaemic control. In experimental group total cholesterol, TG and LDL levels were also significantly reduced from 199.66±3.11 to 189.26±3.01 mg/dl; p<0.02, 144.94±8.31 to 126.01±8.26; p<0.05 and 119.19±1.71 to 99.58±1.10; p<0.001 respectively. These data demonstrate beneficial effect of chromium supplementation on glycaemic control and lipid variables in subjects with newly onset type-2 diabetes.

Keywords: type-2 diabetes, chromium, glucose, HbA1C

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Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

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Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

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Authors: Singh Baljinder, Sharma Navneet

Abstract:

Microalbuminuria is the earliest detectable marker of diabetic nephropathy. We planned to evaluate the prevalence of microalbuminuria in type 1 diabetics and correlate with various risk factor. We randomly selected 100 type 1 diabetic patients after inclusion and exclusion criteria from DCRC, S. P. Medical College, Bikaner. Clinical examinations for anthropometeric parameters, hypertension, retinopathy, glycaemic status, lipid profile were done and microalbuminuria was estimated by micral test. Microalbuminuria was seen in 38% patients. The mean urinary albumin concentration was 96.61 mg/l in microalbuminuria positive cases, 134 mg/L in hypertensive patients while 74.5 mg/L in normal patients. Mean diabetic duration was 6.43 years in microalbuminurics. Albumin excretion increased significantly with age at onset of 10-18 years and declined thereafter. Microalbuminuria cases exhibited mean cholesterol 181.63 mg%, TG 130.94 mg%, LDL 109.87 mg%, HDL 57.5 mg% and VLDL 30.64 mg%. Mean urinary albumin concentration in patients with retinopathy was 160.52 mg/L while 78.66 mg/L without retinopathy. In multiple stepwise logistic regression analysis, a strong positive association was seen between microalbuminuria and hypertension (OR=5.087, CI=2.1319-12.101), fasting blood sugar (OR=3. 491, CI=1.138-10.70), duration of diabetes (OR=3.41, CI=1.360-8.55) and HbA1c (OR=2.381, CI-=1.1-5.64). The present study indicates that microalbuminuria is a common complication of type 1 diabetes mellitus and can be prevented by careful management of risk factors.

Keywords: type 1 diabetes, microalbuminuria, diabetic nephropathy, retinopathy, hypertension

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Authors: Nadali Babaeian Jelodar, Chan Lai Keng, Arvind Bhatt, Laleh Bordbar, Leow E Shuen, Kamaruzaman Mohamed

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Recently artemisinin (the endoperoxide sesquiterpene lactone) has received considerable attention because of its antimalarial activity. It is isolated from the aerial part of the Artemisia annua L. Artemisinin is very difficult to synthesise also its production by mean of cell, tissue or organ cultures is very low. Presently, only its extraction from A. annua L. plants remains the only source of the drug. The reported yield of artemisinin from leaves of A. annua L. is very low and unstable, with yields typically less than 1% of leaf dry weight. To increase the percentage of artemisinin, researchers have been engaged in developing new varieties. A review concerning the breeding of A. annua L. is presented. The aim of this review is to bring together most of the available scientific research papers about the breeding conducted on the genus A. annua L., which is currently scattered across various publications. Through this review the authors hope to attract the attention of breeders throughout the world to focus on the unexplored potential of A. annua L. species. Also the future scope of this plant has been emphasized with a view of the importance of breeding of A. annua L. for increasing of artemisinin content. By releasing of new cultivar of A. annua L. and cultivation of this plant offers the opportunity to optimize yield and achieve a uniform, high quality product.

Keywords: Artemisia annua L., breeding, artemisinin, cultivation, medicinal plant

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Authors: Y. A. Shettima, M. A. Tijjani, S. Modu, F. I. Abdulrahman, B. M. Abubakar

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The toxicity profile of the methanolic extract of Punica granatum L. fruit rind was studied in normal rats. The rats were administered orally by intubating graded doses of 150, 250, 500 and 750 mg/kg body weight of the extract for 28 days and the effects on biochemical parameters and histology of the liver and kidney were evaluated. There was a significant increase (P<0.05) in the levels of liver enzymes of the rats that received the highest dose of 750 mg/kg body weight. The AST and ALT levels were 41.59±0.18 ALP and 9.25±0.29 IU/L, respectively, while the ALP level was 15.68±10 IU/L.There was a significant difference in the albumin and globulin levels; 3.72±0.05 and 4.05±0.13 g/dl, respectively. Serum urea and creatinine levels remained normal, as well as the electrolyte levels. The increase in sodium concentration observed was not statistically significant (P≥0.05) when the control group (131.50±3.11) was compared with the experimental groups (132.25±3.86, 132.75±3.86, 133.50±3.11 and 134.00±1.83). The increase in potassium concentration was not statistically significant (P≥0.05) when the control group with a value of 95.50±3.51 mmol/L was compared with the experimental groups 98.00±3.16, 99.25±2.22, 99.79±0.36 and 99.99±0.02 mmol/L. The increase observed in bicarbonate concentration was not statistically significant (P≥0.05) when the control group with a value of 20.75±1.71 mmol/L was compared with the experimental groups 21.68±0.62, 24.25±2.99, 24.50±3.42, 25.50±2.65 mmol/L.

Keywords: punical granatum, methanolic, ALT, AST, electrolytes, histology

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Authors: Omid Gholipoor Bashiri, Ghafur Mosavi, Aliasghar Behnamghader, Seyed Mahmood Rabiee

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Objective: To determine the effect of selected bone graft on the compression properties of radial bone in rabbit. Design-Experimental in vivo study. Animals: A total of 45 adult male New Zealand white rabbits. Procedures: The rabbits were anesthetized and a one-cm-full thickness piece of radial bone was removed using oscillating saw in the all rabbit. The rabbits were divided into 5 groups on the basis of the material used to fill the bone defect: group 1: the paste of bone cement calcium phosphate; group II: the paste of calcium phosphate mixture with type I collagen; group III: tricalcium phosphate mixed with hydroxyapatite (TCP & HP) with 5% porosity; group IV: the same scaffold as group III with 10% porosity; and group V: the same scaffold as group III and IV with 20% porosity, with 9 rabbits in each group. Subsequently subdivided into 3 subgroups of 3 rabbits each. Results: There was a significant increase in compression properties of radial bone in the group II and V in 2nd and 3rd months as compared with groups I, III and IV. The mean endurable crack-strength in group II and V were slightly higher than that of normal radius (P<0.05). Conclusion and clinical relevance: Application of calcium phosphate paste with type I collagen and scaffold of tricalcium phosphate with hydroxyapatite having 20% porosity indicated to have positive effect in integral formation of qualitative callus at the site of fracture and early re-organization of callus to regain mechanical strength too.

Keywords: calcium phosphate, tricalcium phosphate, hydroxyapatite, radial bone, compressive properties, porosity, type i collagen, rabbit

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

Abstract:

Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Vandana T. Gawande, Kailash G. Bothara, Chandani O. Satija

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The present research work was aimed to determine stability of cefprozil monohydrate (CEFZ) as per various stress degradation conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). Forced degradation studies were carried out for hydrolytic, oxidative, photolytic and thermal stress conditions. The drug was found susceptible for degradation under all stress conditions. Separation was carried out by using High Performance Thin Layer Chromatographic System (HPTLC). Aluminum plates pre-coated with silica gel 60F254 were used as the stationary phase. The mobile phase consisted of ethyl acetate: acetone: methanol: water: glacial acetic acid (7.5:2.5:2.5:1.5:0.5v/v). Densitometric analysis was carried out at 280 nm. The system was found to give compact spot for cefprozil monohydrate (0.45 Rf). The linear regression analysis data showed good linear relationship in the concentration range 200-5.000 ng/band for cefprozil monohydrate. Percent recovery for the drug was found to be in the range of 98.78-101.24. Method was found to be reproducible with % relative standard deviation (%RSD) for intra- and inter-day precision to be < 1.5% over the said concentration range. The method was validated for precision, accuracy, specificity and robustness. The method has been successfully applied in the analysis of drug in tablet dosage form. Three unknown degradation products formed under various stress conditions were isolated by preparative HPTLC and characterized by mass spectroscopic studies.

Keywords: cefprozil monohydrate, degradation products, HPTLC, stress study, stability indicating method

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Authors: Bo Keun Lee, Doo Yeon Kwon, Ji Hoon Park, Gun Hee Lee, Ji Hye Baek, Heung Jae Chun, Young Joo Koh, Moon Suk Kim

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Thermo-responsive materials are viscoelastic materials that undergo a sol-to-gel phase transition at a specific temperature and many materials have been developed. MPEG-b-PCL (MPC) as a thermo-responsive material contained hydrophilic and hydrophobic segments and it formed an ordered crystalline structure of hydrophobic PCL segments in aqueous solutions. The ordered crystalline structure packed tightly or aggregated and finally induced an aggregated gel through intra- and inter-molecular interactions as a function of temperature. Thus, we introduced anionic and cationic groups into the end positions of the PCL chain to alter the hydrophobicity of the PCL segment. Introducing anionic and cationic groups into the PCL end position altered their solubility by changing the crystallinity and hydrophobicity of the PCL block domains. These results indicated that the properties of the end group in the hydrophobic PCL blockand the balance between hydrophobicity and hydrophilicity affect thermo-responsivebehavior of the copolymers in aqueous solutions. Thus, we concluded that determinant of the temperature-dependent thermo-responsive behavior of MPC depend on the ionic end group in the PCL block. So, we introduced zwitterionic end groups to investigate the thermo-responsive behavior of MPC. Methoxypoly(ethylene oxide) and ε-caprolactone (CL) were randomly copolymerized that introduced varying hydrophobic PCL lengths and an MPC featuring a zwitterionic sulfobetaine (MPC-ZW) at the chain end of the PCL segment. The MPC and MPC-ZW copolymers were obtained formed sol-state at room temperature when prepared as 20-wt% aqueous solutions. The solubility of MPC decreased when the PCL block was increased from molecular weight. The solubilization time of MPC-2.4k was around 20 min and MPC-2.8k, MPC-3.0k increased to 30 min and 1 h, respectively. MPC-3.6k was not solubilized. In case of MPC-ZW 3.6k, However, the zwitterion-modified MPC copolymers were solubilized in 3–5 min. This result indicates that the zwitterionic end group of the MPC-ZW diblock copolymer increased the aqueous solubility of the diblock copolymer even when the length of the hydrophobic PCL segment was increased. MPC and MPC-ZW diblock copolymers that featuring zwitterionic end groups were synthesized successfully. The sol-to-gel phase-transition was formed that specific temperature depend on the length of the PCL hydrophobic segments introduced and on the zwitterion groups attached to the MPC chain end. This result indicated that the zwitterionic end groups reduced the hydrophobicity in the PCL block and changed the solubilization. The MPC-ZW diblock copolymer can be utilized as a potential injectable drug and cell carrier.

Keywords: thermo-responsive material, zwitterionic, hydrophobic, crystallization, phase transition

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Authors: A. Reum Son, Jin Seon Kwon, Seung Hun Park, Hai Bang Lee, Moon Suk Kim

Abstract:

These days, stem cell therapy is focused on for promising source of treatment in clinical human disease. As a supporter of stem cells, in situ-forming hydrogels with growth factors and cells appear to be a promising approach in tissue engineering. To examine osteogenic differentiation of hTMSCs which is one of mesenchymal stem cells in vivo in an injectable hydrogel, we use a methoxy polyethylene glycol-polycaprolactone blockcopolymer (MPEG-PCL) solution with osteogenic factors. We synthesized MPEG-PCL hydrogel and measured viscosity to check sol-gel transition. In order to demonstrate osteogenic ability of hTMSCs, we conducted in vitro osteogenesis experiment. Then, to confirm the cell cytotoxicity, we performed WST-1 with hTMSCs and MPEG-PCL. As the result of in vitro experiment, we implanted cell and hydrogel mixture into animal model and checked degree of osteogenesis with histological analysis and amount of expression genes. Through these experimental data, MPEG-PCL hydrogel has sol-gel transition in temperature change and is biocompatible with stem cells. In histological analysis and gene expression, hTMSCs are very good source of osteogenesis with hydrogel and will use it to tissue engineering as important treatment method. hTMSCs could be a good adult stem cell source for usability of isolation and high proliferation. When hTMSCs are used as cell therapy method with in situ-formed hydrogel, they may provide various benefits like a noninvasive alternative for bone tissue engineering applications.

Keywords: injectable hydrogel, stem cell, osteogenic differentiation, tissue engineering

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Authors: Paras Gupta, Rohit Goyal, Yamini Chauhan, Pyare Lal Sharma

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Background: Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Methods: Male Wistar albino rats weighing 180–220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week. Results: Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil. Conclusion: On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol.

Keywords: obesity, Bombax ceiba, free fatty acid, protein tyrosine phosphatase-1B, fatty acid synthase

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Authors: Wan Azuati Wan Omar, Selva Rani John Jasudass, Siti Rohaiza Md. Saad

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Introduction & objective: The objectives of this study were to assess patient’s knowledge of appropriate sublingual glyceryl trinitrate (GTN) use as well as to investigate how patients commonly store and carry their sublingual GTN tablets. Methodology: This was a cross-sectional survey, using a validated researcher-administered questionnaire. The study involved cardiac patients receiving sublingual GTN attending the outpatient and inpatient departments of Taiping Hospital, a non-academic public care hospital. The minimum calculated sample size was 92, but 100 patients were conveniently sampled. Respondents were interviewed on 3 areas, including demographic data, knowledge and use of sublingual GTN. Eight items were used to calculate each subject’s knowledge score and six items were used to calculate use score. Results: Of the 96 patients who consented to participate, majority (96.9%) were well aware of the indication of sublingual GTN. With regards to the mechanism of action of sublingual GTN, 73 (76%) patients did not know how the medication works. Majority of the patients (66.7%) knew about the proper storage of the tablet. In relation to the maximum number of sublingual GTN tablets that can be taken during each angina episode, 36.5% did not know that up to 3 tablets of sublingual GTN can be taken during each episode of angina. Fifty four (56.2%) patients were not aware that they need to replace sublingual GTN every 8 weeks after receiving the tablets. Majority (69.8%) of the patients demonstrated lack of knowledge with regards to the use of sublingual GTN as prevention of chest pain. Conclusion: Overall, patients’ knowledge regarding the self administration of sublingual GTN is still inadequate. The findings support the need for more frequent reinforcement of patient education, especially in the areas of preventive use, storage and drug stability.

Keywords: glyceryl trinitrate, knowledge, adherence, patient education

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Authors: Swanand Pathak, Kiran R. Giri, Reena R. Giri, Kamlesh Palandurkar, Sangita Totade, Rajesh Jha, S. S. Patel

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Background: Population burden, illiteracy, availability of few doctors for larger group of population leads to many unanswered questions left in a patient’s mind. Incomplete information results into noncompliance, therapeutic failure, and adverse drug reactions (ADR). It is very important to establish a system which will provide noncommercial, independent, unbiased source of medicine information. Medicines Info OPD is a concept and step towards safe and appropriate use of medicines. Objective: (1) to assess the present status of knowledge about the medicines in the patients and its correlation with education; (2) to assess the medicine information dispensing modalities, their use and sufficiency from the patients view point; (3) to assess the overall need for Medicines Information OPD in present scenario. Materials and Methods: A pre-validated questionnaire based study was conducted amongst 500 patients of tertiary health care hospital. The questionnaire consisted of specific questions regarding understanding of prescription, knowledge about adverse drug reaction, view about self-medication and opinion regarding the need of Medicines Info OPD. Results: Significantly large proportion of patients opined that doctors do not have sufficient time in current Indian healthcare to explain the prescription and they are not aware of adverse drug reactions, expiry date or use the package inserts etc. Conclusion: Clinically relevant, up to date, user specific, independent, objective and unbiased Medicines Info OPD is essential for appropriate drug use and can help in a big way to common public to address many problems faced by them.

Keywords: information, prescription, unbiased, clinically relevant

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