Search results for: Liver X receptor (LXR)

Authors: Ruttayaporn Ngasaman, Saowakon Indouang, Usa Chethanond

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Leptospirosis is a public health concern zoonosis in Thailand. Human and animals are often infected by contact with contaminated water. The infected animals play an important role in leptospira infection for both human and other hosts via urine. In humans, it can cause a wide range of symptoms, some of which may present mild flu-like symptoms including fever, vomiting, and jaundice. Without treatment, Leptospirosis can lead to kidney damage, meningitis, liver failure, respiratory distress, and even death. The prevalence of leptospirosis in stray animals in Thailand is unknown. The aim of this study was to investigate leptospira infection in stray animals including dogs and cats in Songkhla province, Thailand. Total of 434 blood samples were collected from 370 stray dogs and 64 stray cats during the population control program from 2014 to 2018. Screening test using latex agglutination for the detection of antibodies against Leptospira interrogans in serum samples shows 29.26% (127/434) positive. There were 120 positive samples of stray dogs and 7 positive samples of stray cats. Detection by polymerase chain reaction specific to LipL32 gene of Leptospira interrogans showed 1.61% (7/434) positive. Stray cats (5/64) show higher prevalence than stray dogs (2/370). Although active infection was low detected, but seroprevalence was high. This result indicated that stray animals were not active infection during sample collection but they use to get infected or in a latent period of infection. They may act as a reservoir for domestic animals and human in which stay in the same environment. In order to prevent and reduce the risk of leptospira infection in a human, stray animals should be done health checking, vaccination, and disease treatment.

Keywords: leptospirosis, stray animals, risk reduction, Thailand

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Authors: Raad Nari, Maura Moriaty, Maha T. Barakat

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Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs with a unique mechanism of action. They are used to improve glycaemic control in adults with type 2 diabetes by enhancing urinary glucose excretion. In the UAE, there has been certainly an increased use of these medications. As with any new medication, there are safety considerations related to their use in patients with type two diabetes. A retrospective study was conducted at the three main centres of the Imperial College London Diabetes Centre. Methodology: All patients in electronic database (Diamond) from October 2014 to October 2017 were included with a minimum of six months usage of sodium glucose co-transporter inhibitors that comprise canagliflozin, dapagliflozin and empagliflozin. There were 15 paired sample biochemical and clinical correlations. The analysis was done at the start of the study, three months and six months apart. SPSS version 24 was used for this study. Conclusion: This study of sodium glucose co-transporter-2 inhibitors used showed significant reductions in weight, glycated haemoglobin A1C, systolic and diastolic blood pressures. As the case with systematic reviews, there were similar changes in liver enzymes, raised total cholesterol, low density lipopoptein and high density lipoprotein. There was slight improvement in estimated glomerular filtration rate too. Our analysis also showed that they increased in the incidence of urinary tract symptoms and incidence of urinary tract infections.

Keywords: SGLT2 inhibitors dapagliflozin empagliflozin canagliflozin, adverse effects, amputation diabetic ketoacidosis DKA, urinary tract infection

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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: Yi Sun, George Ed Rainger, Steve P. Watson

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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: Syed Farooq Adil, Merajuddinkhan, Mujeeb Khan, Hamad Z. Alkhathlan

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Phytochemicals from plant extracts belong to an important source of natural products which have demonstrated excellent cytotoxic activities. However, plants of different origins exhibit diverse chemical compositions and bioactivities. Therefore, the discovery of plants based new anticancer agents from different parts of the world is always challenging. In this study, methanolic extracts of different parts of 11 plants from Saudi Arabia have been tested in vitro for their anticancer potential on human liver cancer cell line (HepG2). Particularly, for this study, plants from Asteraceae, Resedaceae, and Polygonaceae families were chosen on the basis of locally available ethnobotanical data and their medicinal properties. Among 12 tested extract samples, three samples obtained from Artemisia monosperma stem, Ochradenus baccatus aerial parts, and Pulicaria glutinosa stem have demonstrated interesting cytotoxic activities with a cell viability of 29.3%, 28.4% and 24.2%, respectively. Whereas, four plant extracts including Calendula arvensis aerial parts, Scorzonera musilii whole plant, A. monosperma leaves show moderate anticancer properties bearing a cell viability ranging from 11.9 to 16.7%. The remaining extracts have shown poor cytotoxic activities. Subsequently, GC-MS analysis of methanolic extracts of the four most active plants extracts such as C. comosum, O. baccatus, P. glutinosa and A. monosperma detected the presence of 41 phytomolecules. Among which 3-(4-hydroxyphenyl) propionitrile (1), 8,11-octadecadiynoic acid methyl ester (2), 6,7-dimethoxycoumarin (3), and 1-(2-hydroxyphenyl) ethenone (4) were found to be the lead compounds of C. comosum, O. baccatus P. glutinosa and A. monosperma, respectively.

Keywords: medicinal plants, asteraceae, polygonaceae, hepg2

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Authors: Ebtisam A. Benomran, Abdurrauf M. Gusbi, Malak S. Elazarg, M. Sultan, Layla M. Kafu, Arwa M. Matoug, Esra E. Benamara

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Normal pregnancy is associated with metabolic changes leading to decreased insulin sensitivity and reduced glucose tolerance, however, 3-5% of pregnant women proceed to develop gestational diabetes mellitus (GDM). Researcher studied the use of metformin in many fields and the benefit to risk balance of using metformin during pregnancy and the risk of fetotoxic. In this study we examined the use of Metformin to control Glucose in pregnant Women with gestational diabetes mellitus (GDM) and evaluate its safety use during the first trimester of pregnancy.A group of pregnant patients with gestational diabetes mellitus from the first trimester of pregnancy, non smoking with no family history of congenital malformation disease, aged between (20-45 years) and have no liver diseases and who had indicating good compliance at more than one visit over several month until delivery put on Metformin were participated in this trial. Our study shown that all the studied group of pregnant women using metformin 500 mg daily delivered a healthy babies. Meta-analysis by mother risk program showed no increase in incidence of malformations by use Metformin during the first trimester of pregnancy. A hundred outpatients were participated in the survey on the general knowledge and awareness of diabetic patients to their illness and medication used their aged between 20-40 years old. In this survey we realize that 90% of the doctors are not giving the patient full information about their illness and the use of metformin during pregnancy, also about 65% of the patients did not know about the nutritionist in the hospital and the right control diet for diabetes. Courses on first aid, rapid diagnosis of poisoning and follow the written procedures to dealing with such cases.

Keywords: gestational diabetes, malformations, metformin, pregnancy

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Authors: Rabia Ashfaq, Saeed Iqbal, Atiq ur Rehman, Irfanullah Khan

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An extensive series of radiopharmaceuticals have been explored in order to discover a better brain tumour diagnostic agent. Tc99m labelling with cysteine and its derivatives in liposomes shows effective tagging of about 70% to 80 %. Due to microscopic size it successfully crossed the brain barrier in 2 minutes which gradually decreases in 5 to 15 minutes. HMPAO labelled with Tc99m is another important radiopharmaceutical used to study brain perfusion but it comes with a flaw that it’s only functional during epilepsy. 1, 1 ECD is purely used in Tc99m ECD formulation; because it not only tends to cross the blood brain barrier but it can be metabolized which can be easily entrapped in human brain. Radio labelling of Cysteine with Tc99m at room temperature was performed which yielded no good results. Hence cysteine derivatives with salicylaldehyde were prepared that produced about 75 % yield for ligand. In order to perform it’s radio labelling a suitable solvent DMSO was selected and physical parameters were performed. Elemental analyser produced remarkably similar results for ligand as reported in literature. IR spectra of Ligand in DMSO concluded in the absence of SH stretch and presence of N-H vibration. Thermal analysis of the ligand further suggested its decomposition pattern with no distinct curve for a melting point. Radio labelling of ligand was performed which produced excellent results giving up to 88% labelling at pH 5.0. Clinical trials using Rabbit were performed after validating the products reproducibility. The radiopharmaceutical prepared was injected into the rabbit. Dynamic as well as static study was performed under the SPECT. It showed considerable uptake in the kidneys and liver considering it suitable for the Hypatobilliary study.

Keywords: marcapto compounds, 99mTc - radiolabeling, salicylaldicysteine, thiozolidine

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Authors: Mohamad Ahrari, Kayvan Sadri, Mahmoud Reza Jafari

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PEGylated liposomes have a smaller volume of distribution and decreased clearance, consequently, due to their more prolonged presence in bloodstream and maintaining their stability during this period, these liposomes can be applied for imaging tumoral sites. The purpose of this study is to develop an appropriate radiopharmaceutical agent in long-term imaging for improved diagnosis and evaluation of tumors. In this study, liposomal formulations encapsulating albumin is synthesized by solvent evaporation method along with homogenization, and their characteristics were assessed. Then these liposomes labeled by Philips method and the rate of stability of labeled liposomes in serum, and ultimately the rate of biodistribution and gamma scintigraphy in C26-colon carcinoma tumor-bearing mice, were studied. The result of the study of liposomal characteristics displayed that capable of accumulating in tumor sites based of EPR phenomenon. these liposomes also have high stability for maintaining encapsulated albumin in a long time. In the study of biodistribution of these liposomes in mice, they accumulated more in the kidney, liver, spleen, and tumor sites, which, even after clearing formulations in the bloodstream, they existed in high levels in these organs up to 96 hours. In gamma scintigraphy also, organs with high activity accumulation from early hours up to 96 hours were visible in the form of hot spots. concluded that PEGylated liposomal formulation encapsulating albumin can be labeled with In-Oxine, and obtained stabilized formulation for long-term imaging, that have more favorable conditions for the evaluation of tumors and it will cause early diagnosis of tumors.

Keywords: nano liposome, 111In-oxine, imaging, biodistribution, tumor

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Authors: Madhulika Pathak, Polani Seshagiri, Vani Venkatappa

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Blastocyst hatching is an indispensable process for successful implantation. One of the major reasons for implantation failure in IVF clinic is poor quality of embryo, which are not development/hatching-competent. Therefore, attempts are required to develop or enhance the culture system with a molecule recapitulating the autocrine/paracrine factors containing the environment of in-vivo endometrial milieu. We have tried to explore the functional molecules involved in the hamster hatching phenomenon. Blastocyst hatching is governed by several molecules that are entwined and regulate this process, among which cytokines are known to be expressed and are still least explored. Two of such cytokines we have used for our study are IL-1β and its natural antagonist IL-1ra to understand the functional dynamics of cytokines involved in the hatching process. Using hamster, an intriguing experimental model for hatching behavior, we have shown the mRNA (qPCR) and protein (ICC) expression of IL-1β, IL-1ra and IL-1 receptor type 1 throughout all the stages of morula, blastocyst and hatched blastocyst. Post-asserting the expression, the functional role is shown by supplementation studies, where IL-1β supplementation showed enhancement in hatching level (IL-1β treated: 84.1 ± 4.2% vs control: 63.7 ± 3.1 %, N=11), further confirmed by the diminishing effect of IL-1ra on hatching rate (IL-1ra treated: 27.5 ± 11.1% vs control: 67.9 ± 3.1%). The exogenous supplementation of IL-1ra decreased the survival rate of embryos and affected the viability in dose-dependent manner, establishing the importance of IL-1β in blastocyst cell survival. Previously, the cathepsin L and B were established as the proteases that were involved in the hamster hatching process. The inducing effect of IL-1β was correlated with enhanced mRNA level, as analyzed by qPCR, for both CAT L (by 1.9 ± 0.5 fold) and CAT B (by 3.5 ± 0.1) fold which was diminished in presence of IL-1ra (Cat L by 88 percent and Cat B by 94 percent. Moreover, using a specific fluorescent substrate-based assay kit, the enzymatic activity of these proteases was found to be increased in presence of IL-1β (Cat L by 2.1 ± 0.1 fold and CAT B by 2.3 ± 0.7 fold) and was curtailed in presence of IL-1ra. These observations provide functional insights with respect to the involvement of cytokines in the hatching process. This has implications in understanding the hatching biology and improving the embryo development quality in IVF clinics.

Keywords: Blastocyst, Cytokines, Hatching, Interleukin

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Authors: Doaa Hashad, Amany Elyamany, Perihan Salem

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Introduction: Hepatitis C virus infection (HCV) constitutes a serious dilemma that has an impact on the health of millions of Egyptians. Hepatitis C virus related hepatocellular carcinoma (HCV-HCC) is a crucial consequence of HCV that represents the third cause of cancer-related deaths worldwide. Aim of the study: assess the use of mitochondrial DNA (mtDNA) content as a non-invasive molecular biomarker in hepatitis c virus related hepatocellular carcinoma (HCV-HCC). Methods: A total of 135 participants were enrolled in the study. Volunteers were assigned to one of three groups equally; a group of HCV related cirrhosis (HCV-cirrhosis), a group of HCV-HCC and a control group of age- and sex- matched healthy volunteers with no evidence of liver disease. mtDNA was determined using a quantitative real-time PCR technique. Results: mtDNA content was lowest in HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multi-centric hepatic lesions had significantly lower mtDNA content. On using receiver operating characteristic curve analysis, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA was associated with greater HCC risk on using healthy controls, HCV-cirrhosis, or combining both groups as a reference group. Conclusions: mtDNA content might constitute a non-invasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the non significant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the grey zone created by the use of AFP in some cirrhotic patients.

Keywords: DNA copy number, HCC, HCV, mitochondrial

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Authors: Magaya Rutendo P., Mutibvu Tonderai, Nyahangare emmanuel T., Ncube Sharai

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This study aimed to evaluate the effects of phytase and tannase addition in broiler diets on growth performance and meat quality of broilers fed sorghum-based diets. Twelve experimental diets were formulated at three sorghum levels, which include 0, 50, and 100%, and 4 enzyme levels: No enzyme, 5000FTU phytase, 25TU tannase, and a combination of 5000FTU phytase plus 25TU tannase. Data on voluntary feed intake, average weekly weight gain and feed conversion ratio were recorded and used to assess growth performance. Meat technical and nutritional parameters were used to determine meat quality. Broilers fed total sorghum diets with phytase and tannase enzyme combination had the highest feed intake in the first (24.4 ± 0.04g/bird/day) and second weeks of life (23.0 ± 1.06g/bird/day), respectively. Complete sorghum diets with phytase (83.0 ± 0.88g/bird/day) and tannase (122.0 ± 0.88g/bird/day) showed the highest feed intake in the third and fourth weeks, respectively. Broilers fed 50% sorghum diets with tannase (135.3 ± 0.05g/bird/day) and complete maize diets with phytase (158.1 ± 0.88g/bird/day) had the highest feed intake during weeks five and six, respectively. Broilers fed a 50% sorghum diet without enzymes had the highest weight gain in the final week (606.5 ± 32.39g). Comparable feed conversion was observed in birds fed complete maize and 50% sorghum diets. Dietary treatment significantly influences the live body, carcass, liver, kidneys, abdominal fat pad weight, and intestinal length. However, it did not affect Pectoralis major meat nutritional and technical parameters.

Keywords: feed efficiency, sorghum, carcass, exogenous enzymes

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

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Authors: Amberkar Mohanbabu Vittalrao, Avin, Meena Kumari Kamalkishore, Padmanabha Udupa, Vinaykumar Bavimane, Honnegouda

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Objective: To evaluate the hepato-protective activity of Tinospora cordiofolia (Tc) against paracetamol induced hepatic damage in rats. Methods: The plant stem (test drug) was procured locally, shade dried, powdered and extracted with water. Silymarin was used as standard hepatoprotective drugs and 2% gum acacia as a control (vehicle) against paracetamol (PCT) induced hepatotoxicity. Results and Discussion: The hepato-protective activity of aqueous stem extract was assessed by paracetamol induced hepatotoxicity preventive model in rats. Alteration in the levels of biochemical markers of hepatic damage like AST, ALT, ALP and lipid peroxides were tested in both paracetamol treated and untreated groups. Paracetamol (3g/kg) had enhanced the AST, ALT, ALP and the lipid peroxides in the serum. Treatment of silymarin and aqueous stem extract of Tc (200 and 400mg/kg) extract showed significant hepatoprotective activity by altering biochemical marker levels to the near normal. Preliminary phytochemical tests were done. Aqueous Tc extract showed presence of phenolic compound and flavonoids. Our findings suggested that Tc extract possessed hepatoprotective activity in a dose dependent manner. Conclusions: Tc was found to possess significant hepatoprotective property when treated with PCT. This was evident by decreasing the liver enzymes significantly when treated with PCT as compared to PCT only treated group (P < 0.05). Hence Tinospora cardiofolia could be a good, promising, preventive agent against PCT induced hepatotoxicity.

Keywords: Tinospora cardiofolia, hepatoprotection, paracetamol, silymarin

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Authors: Małgorzata Tomczyńska, Joanna Saluk-Bijak

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Background: Graves’ disease is a frequent organ-specific autoimmune thyroid disease, which characterized by the presence of different kind autoantibodies, that, in most cases, act as agonists of the thyrotropin receptor, leading to hyperthyroidism. Role of platelets and lymphocytes can be modulated in the pathophysiology of thyroid autoimmune diseases. Interference in the physiology of platelets can lead to enhanced activity of these cells. Activated platelets can bind to circulating lymphocytes and to affect lymphocyte adhesion. Platelets and lymphocytes can regulate mutual functions. Therefore, the activation of T lymphocytes, as well as blood platelets, is associated with the development of inflammation and oxidative stress within the target tissue. The present study was performed to investigate a platelet-lymphocyte relation by assessing the degree of their mutual aggregation in whole blood of patients with Graves’ disease. Also, the purpose of this study was to examine the impact of platelet interaction on lymphocyte migration capacity. Methods: 30 patients with Graves’ disease were recruited in the study. The matched 30 healthy subjects were served as the control group. Immunophenotyping of lymphocytes was carried out by flow cytometry method. A CytoSelect™ Cell Migration Assay Kit was used to evaluate lymphocyte migration and adhesion to blood platelets. Visual assessment of lymphocyte-platelet aggregate morphology was done using confocal microscope after magnetic cell isolation by Miltenyi Biotec. Results: The migration and functional responses of lymphocytes to blood platelets were greater in the group of Graves’ disease patients compared with healthy controls. The group of Graves’ disease patients exhibited a reduced T lymphocyte and a higher B cell count compared with controls. Based on microscopic analysis, more platelet-lymphocyte aggregates were found in patients than in control. Conclusions: Studies have shown that in Graves' disease, lymphocytes show increased platelet affinity, more strongly migrating toward them, and forming mutual cellular conglomerates. This may be due to the increased activation of blood platelets in this disease.

Keywords: blood platelets, cell migration, Graves’ disease, lymphocytes, lymphocyte-platelet aggregates

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Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

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Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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Authors: Sheng Yu Chen, Shi-Heng Wang

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Aim: Based on human, animal experiments, and genetic studies, cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are inflammatory substances that are metabolized by 5-lipooxygenase from arachidonic acid, and these substances trigger asthma. In addition, the synthetic pathway of cysteinyl leukotriene is relevant to the increase in cardiovascular diseases such as myocardial ischemia and stroke. Given the situation, we aim to investigate whether cysteinyl leukotrienes receptor antagonist (LTRA), montelukast which cures those who have asthma has potential protective effects on cardiovascular diseases. Method: We conducted a cohort study, and enrolled participants which are newly diagnosed with asthma (ICD-9 CM code 493. X) between 2002 to 2011. The data source is from Taiwan National Health Insurance Research Database Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Among the remaining participants, every montelukast user was matched with two randomly non-users by sex, and age. The incident cardiovascular diseases, including myocardial infarction and ischemic stroke, were regarded as outcomes. We followed the participants until outcomes come first or the end of the following period. To explore the protective effect of montelukast on the risk of cardiovascular disease, we use multivariable Cox regression to estimate the hazard ratio with adjustment for potential confounding factors. Result: There are 55876 newly diagnosed asthma patients who had at least one claim of inpatient admission or at least three claims of outpatient records. We enrolled 5350 montelukast users and 10700 non-users in this cohort study. The following mean (±SD) time of the Montelukast group is 5 (±2.19 )years, and the non-users group is 6.2 5.47 (± 2.641) years. By using multivariable Cox regression, our analysis indicated that the risk of incident cardiovascular diseases between montelukast users (n=43, 0.8%) and non-users (n=111, 1.04%) is approximately equal. [adjusted hazard ratio 0.992; P-value:0.9643] Conclusion: In this population-based study, we found that the use of montelukast is not associated with a decrease in incident MI or IS.

Keywords: asthma, inflammation, montelukast, insurance research database, cardiovascular diseases

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Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

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Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

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Authors: Jiangang Shen

Abstract:

Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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Authors: Yong-Hui Zheng

Abstract:

Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Kirsten Wilson, Patrick M. Brauer, Sandra Babic, Diana Golubeva, Jessica Van Eyk, Tinya Wang, Avanti Karkhanis, Tim A. Le Fevre, Andy I. Kokaji, Allen C. Eaves, Sharon A. Louis, , Nooshin Tabatabaei-Zavareh

Abstract:

Long-lived plasma cells are rare, non-proliferative B cells generated from antibody-secreting cells (ASCs) following an immune response to protect the host against pathogen re-exposure. Despite their therapeutic potential, the lack of in vitro protocols in the field makes it challenging to use B cells as a cellular therapeutic tool. As a result, there is a need to establish robust and reproducible methods for the generation of B cells. To address this, we have developed a culture system for generating B cells from hematopoietic stem and/or progenitor cells (HSPCs) derived from human umbilical cord blood (CB) or pluripotent stem cells (PSCs). HSPCs isolated from CB were cultured using the StemSpan™ B Cell Generation Kit and produced CD19+ B cells at a frequency of 23.2 ± 1.5% and 59.6 ± 2.3%, with a yield of 91 ± 11 and 196 ± 37 CD19+ cells per input CD34+ cell on culture days 28 and 35, respectively (n = 50 - 59). CD19+IgM+ cells were detected at a frequency of 31.2 ± 2.6% and were produced at a yield of 113 ± 26 cells per input CD34+ cell on culture day 35 (n = 50 - 59). The B cell receptor loci of CB-derived B cells were sequenced to confirm V(D)J gene rearrangement. ELISpot analysis revealed that ASCs were generated at a frequency of 570 ± 57 per 10,000 day 35 cells, with an average IgM+ ASC yield of 16 ± 2 cells per input CD34+ cell (n = 33 - 42). PSC-derived HSPCs were generated using the STEMdiff™ Hematopoietic - EB reagents and differentiated to CD10+CD19+ B cells with a frequency of 4 ± 0.8% after 28 days of culture (n = 37, 1 embryonic and 3 induced pluripotent stem cell lines tested). Subsequent culture of PSC-derived HSPCs increased CD19+ frequency and generated ASCs from 1 - 2 iPSC lines. This method is the first report of a serum- and feeder-free system for the generation of B cells from CB and PSCs, enabling further B lineage-specific research for potential future clinical applications.

Keywords: stem cells, B cells, immunology, hematopoiesis, PSC, differentiation

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Authors: Leelavinothan Pari , Ayyasamy Rathinam

Abstract:

Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.

Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines

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Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu

Abstract:

Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.

Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.

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Authors: Barry D. Kyle, Jessica Boyd, Robin Pickersgill, Nicole Squires, Cynthia Balion

Abstract:

Background-Aim: Fentanyl is a highly-potent synthetic μ-opioid receptor agonist used for exceptional pain management. Its main metabolite, norfentanyl, is typically present in urine at significantly high concentrations (i.e. ~20%) representing an effective targeting molecule for immunoassay detection. Here, we evaluated the NCS^TM One Step Fentanyl Test Device© and the BTNX Rapid Response^TM Single Drug Test Strip© point of care (POC) test strips targeting norfentanyl (20 ng/ml) and fentanyl (100 ng/ml) molecules for potential risperidone interference. Methods: POC tests calibrated against norfentanyl (20 ng/ml) used [immunochromatographic] lateral flow devices to provide qualitative results within five minutes of urine sample contact. Results were recorded as negative if lines appeared in the test and control regions according to manufacturer’s instructions. Positive results were recorded if no line appeared in the test region (i.e., control line only visible). Pooled patient urine (n=20), that screened negative for drugs of abuse (using NCS One Step Multi-Line Screen) and fentanyl (using BTNX Rapid Response Strip) was used for spiking studies. Urine was spiked with risperidone alone and with combinations of fentanyl, norfentanyl and/or risperidone to evaluate cross-reactivity in each test device. Results: A positive screen result was obtained when 8,000 ng/mL of risperidone was spiked into drug free urine using the NCS test device. Positive screen results were also obtained in spiked urine samples containing fentanyl and norfentanyl combinations below the cut-off concentrations when 4000 ng/mL risperidone was present using the NCS testing device. There were no screen positive test results using the BTNX test strip with up to 8,000 ng/mL alone or in combination with concentrations of fentanyl and norfentanyl below the cut-off. Both devices screened positive when either fentanyl or norfentanyl exceeded the cut-off threshold in the absence and presence of risperidone. Conclusion: We report that urine samples containing risperidone may give a false positive result using the NCS One Step Fentanyl Test Device.

Keywords: fentanyl, interferences, point of care test, Risperidone

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Authors: James Patrick A. Diaz, Raul E. Ramboyong

Abstract:

Background: Hypertensive response during maximal exercise test provides important information on the level of blood pressure control and evaluation of treatment. Method: A single center retrospective descriptive study was conducted among 117 young (aged 20 to 40) and middle age (aged 40 to 65) hypertensive patients, who underwent treadmill stress test. Currently on maintenance frontline medication either monotherapy (Angiotensin-converting enzyme inhibitor/Angiotensin receptor blocker [ACEi/ARB], Calcium channel blocker [CCB], Diuretic - Hydrochlorthiazide [HCTZ]) or combination therapy (ARB+CCB, ARB+HCTZ), who attained a maximal exercise on treadmill stress test (TMST) with hypertensive response (systolic blood pressure: male >210 mm Hg, female >190 mm Hg, diastolic blood pressure >100 mmHg, or increase of >10 mm Hg at any time during the test), on Bruce and Modified Bruce protocol. Exaggerated blood pressure response during exercise (systolic [SBP] and diastolic [DBP]), peak exercise blood pressure (SBP and DBP), recovery period (SBP and DBP) and test for ischemia and their antihypertensive medication/s were investigated. Analysis of variance and chi-square test were used for statistical analysis. Results: Hypertensive responses on maximal exercise test were seen mostly among female population (P < 0.000) and middle age (P < 0.000) patients. Exaggerated diastolic blood pressure responses were significantly lower in patients who were taking CCB (P < 0.004). A longer recovery period that showed a delayed decline in SBP was observed in patients taking ARB+HCTZ (P < 0.036). There were no significant differences in the level of exaggerated systolic blood pressure response and during peak exercise (both systolic and diastolic) in patients using either monotherapy or combination antihypertensives. Conclusion: Calcium channel blockers provided lower exaggerated diastolic BP response during maximal exercise test in hypertensive middle age patients. Patients on combination therapy using ARB+HCTZ exhibited a longer recovery period of systolic blood pressure.

Keywords: antihypertensive, exercise test, hypertension, hyperytensive response

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Authors: Shima Fasahat

Abstract:

This research is an experimental research which was done about microbial fuel cells in order to study them for electricity generating and wastewater treatment. These days, it is very important to find new, clean and sustainable ways for energy supplying. Because of this reason there are many researchers around the world who are studying about new and sustainable energies. There are different ways to produce these kind of energies like: solar cells, wind turbines, geothermal energy, fuel cells and many other ways. Fuel cells have different types one of these types is microbial fuel cell. In this research, an MFC was built in order to study how it can be used for electricity generating and wastewater treatment. The microbial fuel cell which was used in this research is a reactor that has two tanks with a catalyst solution. The chemical reaction in microbial fuel cells is a redox reaction. The microbial fuel cell in this research is a two chamber MFC. Anode chamber is an anaerobic one (ABR reactor) and the other chamber is a cathode chamber. Anode chamber consists of stabilized sludge which is the source of microorganisms that do redox reaction. The main microorganisms here are: Propionibacterium and Clostridium. The electrodes of anode chamber are graphite pages. Cathode chamber consists of graphite page electrodes and catalysts like: O₂, KMnO₄ and C₆N₆FeK₄. The membrane which separates the chambers is Nafion117. The reason of choosing this membrane is explained in the complete paper. The main goal of this research is to generate electricity and treating wastewater. It was found that when you use electron receptor compounds like: O_2, MnO₄, C₆N₆FeK₄ the velocity of electron receiving speeds up and in a less time more current will be achieved. It was found that the best compounds for this purpose are compounds which have iron in their chemical formula. It is also important to pay attention to the amount of nutrients which enters to bacteria chamber. By adding extra nutrients in some cases the result will be reverse.  By using ABR the amount of chemical oxidation demand reduces per day till it arrives to a stable amount.

Keywords: anaerobic baffled reactor, bioenergy, electrode, energy efficient, microbial fuel cell, renewable chemicals, sustainable

Procedia PDF Downloads 199

Authors: Adela Penesova, Zofia Radikova, Boris Bajer, Andrea Havranova, Miroslav Vlcek

Abstract:

Background: The aim of our study was to compare the effect of intensified lifestyle intervention on insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fibroblast growth factor (FGF) 21 after 8 weeks of lifestyle intervention. Methods: A group of 43 obese patients (13M/30F; 43.0±12.4 years; BMI (body mass index) 31.2±6.3 kg/m2 participated in a weight loss interventional program (NCT02325804) following an 8-week hypocaloric diet (-30% energy expenditure) and physical activity 150 minutes/week. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices according to Matsuda and Cederholm were calculated (ISImat and ISIced). Plasma ALT, AST, Fetuin-A, FGF 21, and physical fitness were measured. Results: The average reduction of body weight was 6.8±4.9 kg (0-15 kg; p=0.0006), accompanied with a significant reduction of body fat amount of fat mass (p=0.03), and waist circumference (p=0.02). Insulin sensitivity has been improved (IR HOMA 2.71±3.90 vs 1.24±0.83; p=0.01; ISIMat 6.64±4.38 vs 8.93±5.36 p ≤ 0.001). Total, LDL cholesterol, and triglycerides decreased (p=0.05, p=0.04, p=0.04, respectively). Physical fitness significantly improved after intervention (as measure VO2 max (maximal oxygen uptake) (p ≤ 0.001). ALT decreased significantly (0.44±0.26 vs post 0.33±0.18 ukat/l, p=0.004); however, AST not (pre 0.40±0.15 vs 0.35±0.09 ukat/l, p=0.07). Hepatokine Fetuin-A significantly decreased after intervention (43.1±10.8 vs 32.6±8.6 ng/ml, p < 0.001); however, FGF 21 levels tended to decrease (146±152 vs 132±164 pg/ml, p=0.07). Conclusion: 8-weeks of diet and physical activity intervention program in obese otherwise healthy subjects led to an improvement of insulin resistance parameters and liver marker profiles, as well as increased physical fitness. This study was supported by grants APVV 15-0228; VEGA 2/0161/16.

Keywords: obesity, diet, exercice, insulin sensitivity

Procedia PDF Downloads 174

Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: Dietary supplement may potentially help to fight obesity and other metabolic disorders such as adipogenesis, insulin resistance, and inflammation. The present study aimed to test whether supplementation with African walnuts (Aw) could have an effect on adipogenesis and others dysfunctions associated with obesity in rats. Methods: Wistar rats were fed with standard diet (SD) or high-fat high-sucrose diet (HFS) and HFS with supplemented (HFS-Aw) for eight weeks. Results: HFS diet-induced body weight gain and increased fat mass compared to SD. In addition HFS-fed rats developed fasting hyperglycaemia and insulinaemia as well as insulin resistance. Aw supplementation in HFS rats had a protective effect against adipose tissues weigh gain but slightly against body weight gain and major study related disorders. This could be mainly due to decreased food intake dependently of effect in food intake in central nervous system, which decreased in HFS rats supplemented with African walnut compared to the HFS-diet group. Interestingly, African walnut supplementation induced a slight decrease of fasting glycaemia, insulinaemia and Nitric Oxide which could partially explain its minor protective effect against diet-induced insulin resistance. Additionally a decrease in hepatic TG and transaminases levels suggesting a protective effect against liver injury. Conclusion: Taken together these data suggested that supplementation of African walnut could be used to prevent adipose weight gain and related disorders on the other hand, minimally reduced insulin resistance.

Keywords: African walnut, dietary fiber, insulin resistance, oxidative stress

Procedia PDF Downloads 258

Authors: Zahraa Albasry, Hadeel D. Najim, Anmar Al-Taie

Abstract:

Background: Hypertension is considered as one of the most important causes of cardiovascular complications and one of the leading causes of worldwide mortality. Identifying the potential risk factors associated with this medical health problem plays an important role in minimizing its incidence and related complications. The objective of this study is to explore the prevalence of receptor sensitivity regarding assess and understand the perception of specific predictive confounding factors on the prevalence of hypertension (HT) among a sample of Iraqi population in Baghdad, Iraq. Materials and Methods: A randomized cross sectional study was carried out on 100 adult subjects during their visit to the outpatient clinic at a certain sector of Baghdad Province, Iraq. Demographic, clinical and health records alongside specific screening and laboratory tests of the participants were collected and analyzed to detect the potential of confounding factors on the prevalence of HT. Results: 63% of the study participants suffered from HT, most of them were female patients (P < 0.005). Patients aged between 41-50 years old significantly suffered from HT than other age groups (63.5%, P < 0.001). 88.9% of the participants were obese (P < 0.001) and 47.6% had diabetes with HT. Positive family history and sedentary lifestyle were significantly higher among all hypertensive groups (P < 0.05). High salt and fatty food intake was significantly found among patients suffered from isolated systolic hypertension (ISHT) (P < 0.05). A significant positive correlation between packed cell volume (PCV) and systolic blood pressure (SBP) (r = 0.353, P = 0.048) found among normotensive participants. Among hypertensive patients, a positive significant correlation found between triglycerides (TG) and both SBP (r = 0.484, P = 0.031) and diastolic blood pressure (DBP) (r = 0.463, P = 0.040), while low density lipoprotein-cholesterol (LDL-c) showed a positive significant correlation with DBP (r = 0.443, P = 0.021). Conclusion: The prevalence of HT among Iraqi populations is of major concern. Further consideration is required to detect the impact of potential risk factors and to minimize blood pressure (BP) elevation and reduce the risk of other cardiovascular complications later in life.

Keywords: Correlation, Hypertension, Iraq, Risk factors

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Authors: Kebret Kebede, Anthony Scinta

Abstract:

Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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