Search results for: obese mice

Authors: Wen-Yu Lin, Yi-Ching Chung, Tzyy-Rong Jinn

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It is well known that enterovirus 71 (EV71) causes recurring outbreaks of hand, foot and mouth disease (HFMD) and encephalitis leading to complications or death in young children. And, several HFMD of EV71 with high mortalities occurred in Asia countries, such as Malaysia (1997), Taiwan (1998) and China (2008). Thus, more effective antiviral drugs are needed to prevent or reduce EV71-related complications. As reported, interferon-α protects mice from lethal EV71 challenge by the modulation of innate immunity and then degrade enterovirus protease 3Cᵖʳᵒ. On the other side, pleconaril by targeting enterovirus VP1 protein and then block virus entry and attachment. Thus, the aim of this study was to evaluate the synergistic antiviral activity of interferon-α and pleconaril against enterovirus 71 infection. In a preliminary study showed that pleconaril at concentrations of 50, 100 and 300 µg/mL reduced EV71-induced CPE to 52.0 ± 2.5%, 40.2 ± 3.5% and 26.5 ± 1.5%, respectively, of that of the EV71-infected RD control cells (taken as 100%). Notably, 1000 IU/mL of interferon-α in combination with pleconaril at concentrations of 50, 100 and 300µg/mL suppressed EV71-induced CPE by 30.2 ± 3.8%, 16.5 ± 1.3% and 2.8 ± 2.0%, respectively, of that of the pleconaril alone treated with the infected RD cells. These results indicated that interferon-α 1000 IU/mL combination with pleconaril (50, 100 and 300µg/mL) inhibited EV71-induced CPE more effectively than treated with pleconaril alone in the infected RD cells.

Keywords: enterovirus 71, interferon-α, pleconaril, RD cells

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Hailiang Liu, Yan Ni, Jie Zheng, Xiaoyan Jiang, Min Hong

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Allergic contact dermatitis (ACD) is a commonly clinical type IV allergic skin disease, with the pathological features of infiltration by mononuclear cells and tissue necrosis. Traditional Chinese medicine Radix Saposhnikoviae (RS) is traditionally employed to treat exogenous evils, rubella, itching, rheumatism and tetanus. Meanwhile, it is an important component of the commonly used anti-allergy compound. It’s now widely used as an immuno-modulating agent in mixed herbal decoctions to treat inflammation. However, its mechanism of anti-allergy remains unknown. RS was found to reduce ear thickness, as well as the infiltration of eosinophils. The proliferation of T lymphocytes was inhibited significantly by RS, markedly decreased IFN-γ levels in the supernatant of cells cultured and serum were detected with the treatment of RS. RS significantly decreased the amount of DCs in the mouse lymph nodes, and inhibited the expression of CD4 0 and CD86. Meanwhile, T-bet mRNA expression was down remarkably regulated by RS. These results indicate that RS cures Th1-induced allergic skin inflammation by regulating Th1/Th2 balance with decreasing Th1 differentiation, which might be associated with DCs.

Keywords: allergic contact dermatitis, Radix saposhnikoviae, dendritic cells, T-bet, GATA-3, CD4+ CD25+ Foxp3+ treg cells

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Authors: Zhaoguo Liu, Cunsi Shen, Yin Lu

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Growing evidence has shown that menthol has potent anticancer activity in various human cancers. However, its effect on skin cancer remains largely unknown. In the present study, we investigated the chemopreventive potential of menthol against 7, 12-dimethylbenz[a] anthracene(DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin tumorigenesis in ICR mice. Our results showed that menthol significantly inhibited TPA-induced inflammatory responses and pro-inflammatory cytokine release. We also found that menthol treatment significantly inhibited TPA-induced lipid peroxidation (LPO), mouse UDP-glucumno-syltransferase (UGT), mouse NADH Dehydrogenase, Quinone 1 (NQO1) release. Furthermore, we found menthol treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001). Interestingly, we observed that menthol treatment significantly inhibited TPA-induced altered activity of NF-κB in skin tumor. Consistently, menthol-treated tumors also showed significantly suppressed the Ras-Raf-ERK signaling pathway. Thus, our results suggest that menthol inhibits DMBA/TPA-induced skin tumorigenesis by attenuating the Ras and inhibiting NF-κB activity via inhibition of inflammation responses and pro-inflammatory cytokine release.

Keywords: DMBA/TPA, NF-κB, Ras-Raf-ERK, skin tumorigenesis

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Authors: Wenxiao Liu, Kun Zhang, Yongqing Li

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Bovine herpesvirus 1, a member of the genus Variellovirus of the subfamily Alphaherpesvirinae, has caused severe economic cost to the bovine industry. In this study, BoHV-1 glycerol protein gD was expressed in insect cells, and the purified gD was immunized in the Balb/C mice to generate monoclonal antibodies. Based on hybridoma cell fusion techniques, 20 monoclonal antibodies against Bovine herpesvirus 1 have been obtained. Further, mAb 3F8 with neutralizing activity and gD were applied to develop a blocking enzyme-linked immunosorbent assay (Elisa) for detecting neutralizing antibodies against BoHV-1, which shows a significant correlation between the blocking Elisa and VNT. The sensitivity and specificity of the test were estimated to be 94.59% and 93.42%, respectively. Furthermore, antibody pairing tests revealed that mAb 1B6 conjugated to fluorescence microspheres was used as the capture antibody, and mAb 3F9 was used as the detectable antibody to establish the immunochromatographic assay (ICS). The ICS was conducted to detect BoHV-1 in bovine samples with high sensitivity, specificity, and good stability. Clinical sample testing revealed that the results of ICS and real-time PCR have a coincidence rate of 95.42%. Our research confirmed that the ICS is a rapid and reliable method for the diagnosis of BoHV-1. In conclusion, our results lay a solid foundation for the prevention and control of BoHV-1 infection.

Keywords: bovine disease, BoHV-1, ELISA, ICS assay

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Authors: Mohammad Tayefeh Norooz, Amirhossein Kargarzadeh

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Overweight and obesity as an abnormality are health threatening factors. Body mass index (BMI) above 25 is referred to as overweight and above 30 as obese. Apollo Endosurgery, Inc., a pioneering company in endoscopy surgeries, is poised to revolutionize patient care with its minimally invasive treatment options. Some product solutions are designed to improve patient outcomes and redefine the future of healthcare. Weight gain post-weight-loss surgery may stem from an enlarged stomach opening, reducing fullness and increasing food intake. Apollo Endosurgery's OverStitch system, a minimally invasive approach, addresses this by using sutures to reduce stomach opening size. This reflects Apollo's commitment to transformative improvements in healing endoscopy, emphasizing a shift towards minimally invasive options. The system's versatility and precision in full-thickness suturing offer treatment alternatives, exemplified in applications like Endoscopic Sleeve Gastroplasty for reshaping obesity management. Apollo’s dedication to pioneering advancements suggests ongoing breakthroughs in minimally invasive surgery, positioning the OverStitch systems as a testament to innovation in patient care.

Keywords: apollo endosurgery, endoscopic sleeve gastroplasty, weight loss system, overstitch endoscopic suturing system, therapeutic, perforations, fistula

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Authors: Mohamad Nizam Asmuni, Ahmad Naszeri Salleh, Yunus Adam, Azhar Yaacob, Mohd Hafiz Rosli, Muhamad Nazrul Hakim Abdullah

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Athletes at the school should have good physical fitness to participate in tournament. Currently, there are no standards for the level of physical fitness for MARA Junior Science Collage (MJSC). Therefore, this research is to determine the level of physical fitness of rugby player at MJSC. A total of 62 samples (age 16.4 ± 0.75) among rugby players at MJSC were randomly selected to participate in this study. Height, weight, body fat percentage, body mass index (BMI) and other physical testing are measured and recorded. The results showed that the average of body mass index (BMI) for rugby players is 23.4 ± 4:51. Body mass index (BMI) of rugby players can be categorized as pre-obese based on World Health Organization (WHO) guidelines. BMI for rugby players was categorized as healthy based on body fat ranges for standard adults at NY Obesity Research Center. Bleep test results show that the average Bleep test is level 7 and shuttle 5; average VO2max was 37.94 L/min. Physical fitness and performance of rugby players at MJSC is lower compared to the rugby junior athletes in University Putra Malaysia (UPM). Therefore, physical fitness of rugby players must be improved to ensure the rugby players at MJSC could be performs better in the tournament.

Keywords: physical fitness, MARA junior science collage (MJSC), body mass index (BMI), bleep test

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Authors: Karen J. Polvado, Betty Bowles, Jansen Lauren, Gibson Martha, Robin Lockhart

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The purpose of this study was to identify motivation to participate in the Hotter ‘n Hell Hundred (HHH) bicycling event, and the participants’ demographics, health risk factors, and preparation to ride in the event. A convenience sample of adults pre-registered for non-competitive cycling events (N = 7,472) were requested to complete a survey. Of these, 2,645 (35%) responded. Questions identified the participants’ demographics, preparation, previous experience with HHH, and motives for riding. The HHH attracted riders of all ages (18-80), genders, ethnicities, and educational levels. The majority were males, 40-59 years old, married, college graduates, and identified themselves as non-Hispanic whites. The majority (68%) reported no existing medical conditions, and were normal weight (70%), although 52% had been overweight or obese in the past. Preparation to ride in the HHH varied from riding more than five times a week for the last year, to riding 1-2 times per week one month before the event. Most (93%) had ridden in the HHH an average of 5 times. Motivations to ride included: personal challenge (75%); to experience the HHH ride (57%); a chance to ride with family/friends/coworkers (52%); improving health (47%); fun (33%); challenge by others (15%); part of a weight loss plan (11%); training for another event (10%); and raising money for a cause (2%). The motivation to participate appeared to move from extrinsic to intrinsic motivation as age increased. Exploration of the exercise habits and motivations of older adults (70+) is suggested by this study.

Keywords: cycling, motivation, physical activity, training

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Authors: M. S. Mousavi-Daramoroudi, H. Yousefnia, S. Zolghadri, F. Abbasi-Davani

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Dosimetry is an indispensable and precious factor in patient treatment planning; to minimize the absorbed dose in vital tissues. In this study, In accordance with the proper characteristics of DOTATOC and ¹⁷⁷Lu, after preparing ¹⁷⁷Lu-DOTATOC at the optimal conditions for the first time in Iran, radionuclidic and radiochemical purity of the solution was investigated using an HPGe spectrometer and ITLC method, respectively. The biodistribution of the compound was assayed for treatment of adenocarcinoma breast cancer in bearing BALB/c mice. The results have demonstrated that ¹⁷⁷Lu-DOTATOC is a profitable selection for therapy of the tumors. Because of the vital role of internal dosimetry before and during therapy, the effort to improve the accuracy and rapidity of dosimetric calculations is necessary. For this reason, a new method was accomplished to calculate the absorbed dose through mixing between compartmental model, animal dosimetry and extrapolated data from animal to human and using MIRD method. Despite utilization of compartmental model based on the experimental data, it seems this approach may increase the accuracy of dosimetric data, confidently.

Keywords: ¹⁷⁷Lu-DOTATOC, biodistribution modeling, compartmental model, internal dosimetry

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Authors: Lu Yang, Keng Po Lai

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Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

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Authors: Ilma Robo, Saimir Heta, Emela Dalloshi, Nevila Alliu, Vera Ostreni

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The dental whitening process, beyond the fact that it is a mini-invasive dental treatment, has effects on the dental structure, or on the pulp of the tooth, where it is applied. The electronic search was performed using keywords to find articles published within the last 10 years about side effects, assessed as such, of minimally invasive dental bleaching treatment. Methodology: In selected articles, the other aim of the study was to evaluate the side effects of bleaching based on the percentage and type of solution used, where the latter was evaluated on the basic solution used for bleaching. Results: The side effects of bleaching are evaluated in selected articles depending on the method of bleaching application, which means it is carried out with recommended solutions, or with mixtures of alternative solutions or substances based on Internet information. Short conclusion: The dental bleaching process has side effects which have not yet been definitively evaluated, experimentally in large samples of individuals or animals (mice or cattle) to arrive at accurate numerical conclusions. The trend of publications about this topic is increasing in recent years, as long as the trend for aesthetic facial treatments, including dental ones, is increasing.

Keywords: teeth whitening, side effects, permanent teeth, formed dental apex

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.

Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity

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Authors: Saeed S. Al-Sokari, Nasser A. Awadh Ali, Lianet Monzote

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Leishmaniasis (CL) is endemic in at least 82 countries and considered to be a major public-health problem (1). The annual incidence of CL is 1–1.5 million cases of which 90% occur in only seven countries: Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia and Syria (2). In Saudi Arabia, the disease was first described in 1973 by Moursy and Shoura (3). Currently, CL is common in the human population in different localities, including the Eastern Province of Saudi Arabia and in particular the Al-Hassa Oasis that is a known endemic area for CL (4). Five methanolic extracts obtained from Achillea biebersteinii (flower leaf), Euphorbia antiquorm, Solanum incanum (leaf and fruit extracts), collected from Albaha region and selected from ethno-botanical data, were screened for their anti-leishmanial activity against Leishmania amazonensis (6). The cytotoxic activity against normal peritoneal macrophages from normal BALB/c mice was also determined (6). The five extracts had IC50 values ranging from < 12.5 to 37.8 µg/ml against promastigotes. Achillea biebersteinii flower, Euphorbia antiquorm, Solanum incanum leaf extracts showed anti-leishmanial activities with IC50 between < 12.5 - 26.9µg/mL and acceptable selectivity indices of 8 - 5.

Keywords: plant extracts, Albaha, Leishmania amazonensis, Medicinal

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Authors: Sara Boulmai̇z

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In order to study the microbiological quality of chawarma sold in Biskra, a sampling through some fastfoods of the city was done, the parameters studied are highlighted according to the criteria required by the country's trade management. Microbiological analyzes revealed different levels of contamination by microorganisms. The 10 samples were of an overall view of unsatisfactory quality, and according to the standards, no sample was satisfactory. The range of total aerobic mesophilic flora found is between 105 and 1.2 × 10 7 CFU / g, that of fecal coliforms is 104 to 2.4 × 10 5 CFU / g. The suspected pathogenic staphylococci were between 3.103 and 2.7.106 CFU / g. Salmonellae were absent in all samples, whereas sulphite-reducing anaerobes were present in a single sample. The rate of E. cloacae was between 103 and 6.104 CFU / g. As for fungi and safe mice, their rate was 103 to 107 CFU / g. The study of the sensitivity of antibiotics showed multi-resistance to all the antibiotics tested, although there is a sensitivity towards others. All strains of Staphylococcus aureus tested demonstrated resistance against erythromycin, 30% against streptomycin, and 10% against tetracycline. While the strains of E. cloacae were resistant in all strains to amoxicillin, ceftazidime, cefotaxime, and erythromycin, while they were sensitive to fosfomycin, sulfamethoxazole trimethoperine, ciprofloxacin, and tetracycline. While against chlorophenicol and ofloxacin, the sensitivity was dominant, although there was intermediate resistance. In this study demonstrates that foodborne illnesses remain a problem that arises in addition to the increasingly observed bacterial resistance and that, after all, healthy eating is a right.

Keywords: chawarma, microbiological quality, pathogens., street food

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Authors: Kyu Rae Lee

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The aim of the study is to investigate the clinical efficacy of combination therapeutic modalities using liraglutide (1.2mg/d) add on low-dose phentermine (7.5 mg/d)/topiramate (50mg/d) medication on the obese patient in the bariatric clinic. We assessed the retrospective cohort clinical analyses to the clinical efficacy of medication and combination in the patients who visited the bariatric clinic. We measured all participants’ body fat (bioelectric impedance analysis), weight, height, and the cross-sectional areas of adipose tissues (umbilicus level) after keep fasting for 8 hours at 0, 4, 12 weeks. The design of the study was opened, paired t-test and Wilcoxon test were performed using SPSS for windows (ver.18, IL, USA) for comparison of weight, body fat, and adipose tissues. The participants were one hundred twenty-eight subjects aged 44.67 (1.18) years, 28.95 (0.39) kg/m², and female (82.7%). Their body fat was 40.57 (2.23%), and waist to hip ratio was 0.96 (0.01). The mean cross-sectional area of visceral adipose tissue was 142.59 (7.06) mm², and that of subcutaneous adipose was 274.37 (9.18) mm². 73 of them (57.5%) took medication only, 54 of them took medication with liraglutide for 12 weeks. The subjects in the medication group lost 5.4165 kg, 6.8069%, and those of the combination group did 6.2481 kg, 3.564%. The mean cross-sectional areas of visceral, subcutaneous adipose tissue in the medication group significantly decreased (p=.043), even more in the combination group. (p=.028). Further controlled clinical trials should be considered in the future. We conclude that the low dose of phentermine/topiramate with liraglutide therapeutic modalities would be more effective than phentermine/topiramate medication only in obesity treatment for 12 weeks.

Keywords: low dose phentermine, topiramate, liraglutide, obesity, efficacy

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Authors: Alemu Tadesse Feroche

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In this study, some 2, 3 distributed quinazoline -4 (3H) - one derivative were synthesized using a three-step synthetic route. They were obtained in a good yield (59.5-85%) by applying different chemical reactions like cyclization and condensation reactions. The chemical structure of the final compounds was also verified by spectroscopic methods (IR, ¹HNMR) and elemental microanalysis. The in vivo antimalarial activity of these compounds on P. berghei infected mice was found to be moderate to high at an oral dose of 0.04846 mmol/kg /day. This is equal to 25 mg/kg of chloroquine phosphate, which causes 100% inhibition of the parasite. It is worth mentioning that most active compounds (E) -3 Phenyl -2- [2- (pyridine -4- yl) vinyl] -4 (3H) -quinazolinone IVa (64.02%, (E)-2-[2-(4 - Hydroxy-3 - methoxystyryl) - vinyl) -3 - phenyl -4 (3H ) - quinazolinone IVc (77.25%) and (E)-2 –[2 –(Pyridin -4-yl) –vinyl] -3 phenenylamine -4(3H) quinazolinone IVe (73.54%) showed a dose-dependent increase in present suppression in antimalarial activities. Furthermore, the synthesized compounds were screened for their in vitro antileishmanial activity against L. aethiopica isolate (CL/039/09). All tested compounds (IVa (0.03766 ug/ml), IVb (0.00538 ug/ml, IVc (0.00412 ug/ml, IVd (0.00110 ug/ml), IVe (0.03017 ug/ml) and IVf (0.03894 ug/ml)) showed excellent potency that is much better than amphotericin B (IC50 = 0,04359 ug/ml). The results of acute toxicity indicated that all test compounds (IVa –IVf) proved to be nontoxic and well tolerated by the experimental animals up to 300 mg/kg in oral and 140 mg/kg in parental studies.

Keywords: 4(3H)-quinazolinone, in vivo antimalarial activity, in vitro antileishmanial activity, acute toxicity

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Sadia Suri Kashif, Raheeda Fatima, Maqsood Ahmed Khan

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Purpose of the study: The objective of this research was to determine the perception of Pakistani physicians (whether primary care, specialists or residents) in Karachi, being one of the largest and highly populated cities of Pakistan, regarding clinical approaches towards diet, exercise, and therapy in obese patients. This research determines their understanding of obesity and employability of obesity management in their daily practices. Research methodology: This is a questionnaire-based survey. A minimum of 300 questionnaires (N=300) were distributed and filled by practicing physicians in a random selection of medical setups in Karachi. Randomly 246 physicians responded to the survey. The survey tested their views regarding weight management, importance of general awareness and their strategies to control weight. Results: In the first part of survey the physicians responded to almost 66% regarding the seriousness of obesity management with advising diet modification, physical exercise and decreasing calorie intake; 57% failed to employ Body Mass Index and Waist Hip Ratio as weight measurement tools in their daily practice; 50% disagreed on using pharmacotherapy as an option; 67% were not sure about the proper dosage and indication of anti-obesity medication while almost same disagreed on using surgical options for management of obesity; 83.3% physicians agreed on the increased obesity pandemic in Pakistan. Conclusion: The findings indicate that there is a gap between awareness and knowledge among Pakistani practicing physicians regarding pharmacotherapy for obesity. There is a need to frequently update latest guidelines to help manage this condition, which is becoming more prevalent in our country day by day. Physicians should be obligated to use updated knowledge for managing obesity.

Keywords: obesity, physicians, BMI, weight management, obesity awareness

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Authors: Claudia Patricia Beltran Miranda, Mónica López Anaya, Mónica Navarro Meza, Maria Leonor Valderrama Chairez

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Background: Mexico occupies the second world-wide place of morbid obese people (10- 12 million). Factors that predispose the development of MO are genetic, environmental, physiological, psycho-social and behavioral (nourishing habits). Objective: Associate Gln223Arg polymorphism of gene LEPR, levels of leptina and nourishing habits with the presence of morbid obesity in adolescents of the south of Jalisco (México). Methods: In 41 adolescents (18 normal weight and 23 morbid obesity) of 12 to 19 years of age, both sexes that were measure size and weight with tanita scale and stadimeter to determine IMC. Morbid obesity was determined by tables of the WHO and was established with a standard deviation >3. The Gln223Arg polymorphism have been identify by PCR and leptina levels by ELISA. Nourishing habits were evaluate by the questionnaire the Adolescent Food Habits Checklist. The statistical analysis was performed to compare mean scores obtained from the questionnaire when we compare morbid obesity vs. normal weight adolescents with p=0.03 and a significance of 95%. Results: frequencies alellics and genics were not stadistics significatives p= 0,011 and p=0,279 respectly when were compared between normal weight adolescents and morbib obesity Leptin levels and nourishing habits were associated with morbid obesity. The polymorphism not shown significance with morbid obesity. Conclusions: Dietary habits and leptin levels in adolescents are important factor that predisposes the development of obesity in adolescents. The presence of the polymorphism are not associated with morbid obesity in these subjects.

Keywords: leptin, nourishing habits, morbid obesity, polymorphism

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

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The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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Authors: Abdul Rohim Tualeka, Erick Caravan K. Betekeneng, Ramdhoni Zuhro, Reko Triyono, M. Sahri

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It has been widely reported incidence caused by acute and chronic effects of exposure to ammonia in the working environment in Indonesia, but ammonia concentration was found to be below the threshold value. The purpose of this study was to determine the safety limit concentration of ammonia in the working environment through the expression of CD8 as a reference for determining the threshold value of ammonia in the working environment. This research was a laboratory experimental with post test only control group design using experimental animals as subjects experiment. From homogeneity test results indicated that the weight of white rats exposed and control groups had a homogeneous variant with a significant level of p (0.701) > α (0.05). Description of the average breathing rate is 0.0013 m³/h. Average weight rats based group listed exposure is 0.1405 kg. From the calculation IRS CD8, CD8 highest score in the doses contained 0.0154, with the location of the highest dose of ammonia without any effect on the lungs of rats is 0.0154 mg/kg body weight of mice. Safe Human Dose (SHD) ammonia is 0.002 mg/kg body weight workers. The conclusion of this study is the safety limit concentration of ammonia gas in the working environment of 0,025 ppm.

Keywords: ammonia, CD8, rats, safe limits concentration

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Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

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The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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Authors: Preeti Khanna, Bani T. Aeri

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Background: Recent studies have indicated challenges that hamper health and wellbeing of a vast majority of adolescents in developing countries. Many modifiable factors like behavior and temperament related to food intake among adolescents have not been adequately explored. The aim of the proposed research is to study the impact of behavior and temperament on food intake and diet quality of adolescents. Objectives: In the present study data on dietary behavior and anthropometry of adolescent boys & girls (aged 13-16 years) studying in public schools of Delhi will be gathered to ascertain the quality of diet among adolescent boys and girls and to study the effect of behavior and temperament on diet quality of adolescents. Methods: In total, 400 adolescents will participate in this cross-sectional study. Weight and height of adolescents will be measured and BMI will be calculated. Information will be obtained on their socio-demographic profile and various factors influencing their Food Choices and diet quality such as body image perception, Behavior, temperament, locus of control and parental influence. Expected results: Several direct effects of adolescent traits and behavior on food intake will be observed. Maturational patterns and gender differences in behavior traits will be assessed. By profiling of the behavior and temperament traits, we will have a better understanding of impact of these factors on weight and eating behaviors in overweight/obese or even underweight adolescents. Conclusions: The proposed study will highlight the association of behavioral factors with nutritional status of adolescents. It will also serve as a strategic approach for the obesity prevention and health management policies designed for adolescents.

Keywords: behaviour, temperament, food intake, adolescents

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Authors: Seham Alsaif, Susan Wray

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Obesity is a worldwide disorder influencing women’s health and childbearing. There is a close relation between obesity and pregnancy related complications. Dyslipidemia and adipokine dysregulation are core environmental changes that may mechanistically link these complications with obesity in pregnant women. We have previously found that visfatin has a relaxant effect on mouse, rat and human myometrial contractility. We hypothesised that visfatin inhibits mouse myometrial contractility through the NAD+ pathway. This study was designed to examine the mechanism of action of visfatin on myometrial contractility. To examine the NAD+ pathway, FK866 which is a potent inhibitor of NAD+ biosynthesis was used. Methods: Myometrial strips from term pregnant mice were dissected, superfused with physiological saline and the effects of visfatin (10nM) on oxytocin-induced contractions (0.5nM) alone and after the infusion of FK866 (10uM) were studied. After regular contractions were established, contractility was examined for control (100%) and test response at 37 °C for 10 min each. Results: FK866 was found to inhibit the effect of visfatin on myometrial contractility (the AUC increased from 89±2% of control, P=0.0009 for visfatin alone to 97±4% of control, P>0.05 for visfatin combined with FK866, n=8). In conclusion, NAD+ pathway appears to be involved in the mechanism of action of visfatin on mouse myometrium. This could have a role in making new targets to prevent obesity-related complications.

Keywords: myometrium, obesity, oxytocin, pregnancy, visfatin

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Authors: Nuha Alamro

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Besides achieving of weight loss, Bariatric surgery (BS) shown metabolic improvement including reduction of cardiovascular disease, insulin resistance and diabetes. This study aimed to measure BS effects on Framingham Risk Score (FRS) and metabolic syndrome (MetS) among patients who underwent BS. Additionally, to determine the effect of BS on TSH among euthyroid obese patients. A Retrospective follow-up study was conducted in King Abdullah Medical City. A total of 160 participants who underwent BS and completed one year of follow ups. Medical history, biochemical, anthropometric, and hormonal parameters were evaluated at baseline and 3-12 months after BS. International Diabetes Federation (IDF) criteria were used to diagnose MetS pre and postoperative. The mean age of participants was 41.9 ± 10.6 with Body Mass Index (BMI) of 48.8 ± 7.3. After 3 months, Systolic, Diastolic blood pressure (SBP, DBP), glycated haemoglobin (HBA1C), Low-density lipoprotein (LDL), cholesterol, triglycerides and Thyroid stimulating hormone (TSH) were significantly decrease (P < 0.001). Significant decrease was seen in Mets, BMI, FRS, SBP, DBP, HBA1C, LDL, triglycerides, cholesterol, liver enzyme, with significant increase in high-density lipoprotein (HDL) level 12 months post-op (P < 0.001). After 1 year, the prevalence of MetS, DM, HTN, FRS were significantly decrease from 72.5%, 43.1%, 78.1%, 11.4 to 16.3%, 9.4%, 22.5% and 5.4, respectively. Besides achieving substantial weight loss, MetS resolution was linked to improvement in cardiovascular risk profile.

Keywords: bariatric surgery, cardiovascular disease, metabolic syndrome, thyroid stimulating hormone

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Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

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From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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Authors: Tahmineh Hasanzadeh, Afshin Farahbakhsh

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There is some report about the hypoglycemic effect of Juglans rejia L. leaf in alloxan induced diabetic rats and hypoglycemic effect of its fruit peel administered intraperitoneally.In Iranian traditional medicine, septum of walnut shell (SWS) was recommended to reduce blood glucose. For this purpose, 41 male bulb/C mice 25-30 gm were divided into five groups. All the animals received IP injection of streptozotocin (STZ) (220 mg/kg). Two weeks later, the diabetic animals were received daily oral treatment of normal saline and aqueous extract of SWS (200, 400, 600 and 800 mg/kg) respectively for four weeks. Blood samples were taken from retro orbital sinus before the start of the experiment and repeated each two weeks. At the end of the experiment, the animals were sacrificed and the pancreatic tissues were fixed, prepared and stained by Hematoxylin-Eosin for light microscope studies. The results showed that in each group, the SWS extract reduced blood glucose in a long time (p < 0.05). metabolic extract in STZ- induced diabetic rats, which was accompanied by the hypoglycemic effect of leaf extract. However, this effect should be determined with scientific researches. Therefore, the aim of this study is to evaluate the effect of the aqueous extract of SWS on blood glucose and histopathological structure of pancreas.

Keywords: septum of walnut, blood glucose, pancreas, diabetes, walnut leaf, walnut peel, insulin

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Authors: Mohamad Nizam Asmuni, Ahmad Naszeri Salleh, Yunus Adam, Azhar Yaacob, Mohd Hafiz Rosli, Muhamad Nazrul Hakim Abdullah

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Physical Education teacher at the school should have good physical fitness to educate and guide students in the school. Currently, there are no standards for the level of physical fitness for teachers who teaches physical education at the school. Therefore, this research is to determine the level of physical fitness of teacher of Physical Education at Maktab Rendah Sains MARA (MRSM). A total of 28 samples (18 men and 10 women, age 33 ± 4.91), teachers of physical education at MRSM, were randomly selected to participate in this study. Height, weight, body fat percentage, body mass index (BMI) and other physical testing are measured and recorded. The results showed that the average of body mass index (BMI) for teachers of Physical Education is 25.9 ± 4:57. Body mass index (BMI) of teachers can be categorized as pre-obese based on World Health Organization (WHO) guidelines. Body fat percentage for male (age; 34.3 ± 5.13) and female (age; 30.9 ± 3.81) teachers is 24.7% ± 6.54 and 30.6% ± 6.28, respectively. Male teachers were categorized as overfat, however, female teachers were categorized as healthy based on body fat ranges for standard adults at NY Obesity Research Center. Bleep test results show that the average Bleep test is level 4 and shuttle 2; average VO2max was 27.5 ± 5.94 L/min. Physical fitness and performance of physical education teachers at MRSM is much lower compared to the rugby junior athlete in University Putra Malaysia (UPM). Therefore, physical fitness of teachers must be improved to ensure the physical education classes at MRSM could be done better.

Keywords: physical fitness, BMI, bleep test, obesity

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Authors: Eli Maria Forti-Pazzianotto, Carolina Moraes Da Costa, Daniela Faleiros Berteli Merino, Maura Rigoldi Simões Da Rocha, Irineu Rasera-Junior

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There is no conclusive evidence to support the use of one type or brand of incentive espirometry over others. The decision as to which equipment is best, have being based on empirical assessment of patient acceptance, ease of use, and cost. The aim was to evaluate the effects of use of two methodologies of breathing exercises, performed by flow-oriented incentive spirometry, in the reversal of diaphragmatic dysfunction in postoperative bariatric surgery. 38 morbid obese women were selected. Respiratory muscle strength was evaluated through the nasal inspiratory pressure (NIP), and the respiratory muscles endurance, through incremental test by measurement of sustained maximal inspiratory pressure (SMIP). They were randomized in 2 groups: 1- Respiron® Classic (RC) the inspirations were slow, deep and sustained for as long as possible (5 sec). 2- Respiron® Athletic1 (RA1) - the inspirations were explosive, quick and intense, raising balls by the explosive way. 6 sets of 15 repetitions with intervals of 30 to 60 seconds were performed in groups. At the end of the intervention program (second PO), the volunteers were reevaluated. The groups were homogeneous with regard to initial assessment. However on reevaluating there was a significant decline of the variable PIN (p= < 0.0001) and SMIP (p=0.0004) in RC. In the RA1 group there was a maintenance of SMIP (p=0.5076) after surgery. The use of the Respiron Athletic 1, as well as the methodology of application used, can contribute positively to preserve the inspiratory muscle endurance and improve the diaphragmatic dysfunction in postoperative period.

Keywords: bariatric surgery, incentive spirometry, respiratory muscle, physiotherapy

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Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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