Search results for: systemic inflammatory response syndrome

Authors: Leila Karshenas, Hamidreza Khodaei, Behnaz Mahdavi

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Ovulation is a physiologic process with an inflammatory response that depends on a coordinated activity of gonadotropins and steroid hormones, as well as inflammatory mediators such as cytokines, prostaglandins, leptin, nitric oxide (NO), etc. Conjugated linoleic acid (CLA) is composed of polyunsaturated fatty acids (PUFA) found in dairy products, beef and lamb. There is strong evidence that dietary CLA affects mediators involved in ovulation. The aim of this study was to determine the effects of different doses of dietary CLA on systemic and local hormones and factors involved in ovulation. In this case-control study, 80 (50±2-day old) female mice were randomly divided into four groups (C as the controls and T1, T2 and T3 as the treatment groups). There were four replicates in each group and there were five mice in every replicate (20 mice, in total). The mice in the control group were fed with no CLA in their diet but the ones in the treatment group received 0.1, 0.3 and 0.5g/kg of CLA (replacing corn oil in the diet), respectively for 120 days. Later on, blood samples were obtained from the tails of animals that displayed estrus signs and estradiol (E2), progesterone (P4), LH, FSH, NO, leptin and TNFα were measured. Furthermore, the effects of CLA on the ovarian production of prostaglandins (PGs) and NO were investigated. The data were analyzed by SAS software.CLA significantly decreased serum levels of FSH (p<0.05), LH, estradiol, NO, leptin and TNFα (p<0.01). In addition, CLA decreased progesterone levels but this effect was statistically insignificant. The significantly negative effects of CLA were seen on the ovarian production of PGE2 and PGF2α (p<0.01).It seems that CLA may play an effective role in reducing the ovulation rate in mice as CLA adversely affected female reproduction and it had negative effects on systemic and local hormones involved in ovulation.

Keywords: conjugated linoleic acid, nitric oxide, ovary, ovulation, prostaglandin, gonadotropin

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Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

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Authors: Rachna Agarwal, R. Naveen, Darpan Thakre, Rohit Shahi, Maryam Abbasi, Upendra Rathore, Latika Gupta

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Aim: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and juvenile IIM patients visiting a tertiary care centre in 2021 satisfying the International Myositis Classification Criteria were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6% vs. 4.3%, p <0.001), AV nicking (14% vs. 2.2%, p=0.053), and vascular tortuosity (18.6% vs. 2.2%, p=0.012), besides decreased visual acuity (53.5% vs. 10.9%, p<0.001) and immature cataracts (34.9% vs. 2.2%, p<0.001). Attenuation of vessels [OR 10.9 (1.7-71), p=0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p=0.068], especially attenuation of vessels [14(38%) vs. 0(0), p=0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-third to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Keywords: idiopathic inflammatory myopathies, vascular health, retinal microvasculopathy, arterial attenuation

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Authors: Hamidreza Khodaei, Ali Daryabeigi Zand

Abstract:

Ovulation is a physiologic process with an inflammatory response that depends on a coordinated activity of gonadotropins and steroid hormones, and inflammatory mediators such as cytokines, prostaglandins, leptin, nitric oxide (NO), etc. Conjugated linoleic acid (CLA) is composed of polyunsaturated fatty acids (PUFA) found in dairy products, beef, and lamb. There is strong evidence that dietary CLA affects mediators involved in ovulation. The objective of this study is to evaluate the impacts of various doses of dietary CLA on systemic and local hormones and parameters involved in ovulation. In this case-control research, 80 (50 ± 2-day old) female mice were randomly divided into 4 groups (C as control treatment and T1, T2 and T3 are considered as the treatment groups). There were four replicates in each group, and there were five mice in every replicate (20 mice, in total). The mice in the control group were fed with no CLA in their diet, but the ones in the treatment group received 0.1, 0.3 and 0.5g/kg of CLA (replacing corn oil in the diet), respectively for four months. After that, blood samples were obtained from the tails of animals that displayed estrus signs and estradiol (E2), progesterone (P4), LH, FSH, NO, leptin and TNFα were measured. In addition, the impacts of CLA on the ovarian production of prostaglandins (PGs) and NO were studied. The data were analyzed by SAS software. CLA considerably decreased serum levels of FSH (p < 0.05), LH, estradiol, NO, leptin and TNFα (p < 0.01). In addition, CLA decreased progesterone levels, but this effect was statistically not significant. The significantly adverse effects of CLA were observed in the ovarian production of PGE2 and PGF2α (p < 0.01). It seems that CLA may play an important role in reducing the ovulation rate in mice as CLA negatively affected female reproduction and it had adverse effects on systemic and local hormones involved in ovulation.

Keywords: conjugated linoleic acid, nitric oxide, ovary, ovulation, prostaglandin, gonadotropin

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Authors: Mohammad Alqattan, Tala Alkhunani, Reema Al, Aldawish, Felwa Almurshard, Abdullah Alzahrani

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: Poland’s Syndrome is a congenital anomaly with two clinical features : unilateral agenesis of the pectoralis major and ipsilateral hand symbrachydactyly. Case presentation: We report a rare case of bilateral Poland’s syndrome with several unique features. Discussion: Poland’s syndrome is thought to be due to a vascular insult to the subclavian axis around the 6th week of gestation. Our patient has multiple rare and unique features of Poland’s syndrome. Conclusion: To our best knowledge, for the first time in the literature we associate Poland’s syndrome with cone-shaped epiphysis of the metacarpals of all fingers. Bilaterality, cleft hand deformity, and dextrocardia, were also rare features in our patient.

Keywords: Poland's syndrome, cleft hand deformity, bilaterality, dextrocardia, cone-shaped epiphysis

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Authors: Sourav Ghosh, Antony Gomes

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Since 1894 anti-snake venom serum (ASVS) is the only available treatment against snake envenomation, although there are many side effects and limitations. The need for a supportive treatment was felt for a long time to overcome the side effects and limitations of ASVS. Andrographolide conjugated with gold nanoparticle (A-GNP) has been found to antagonize viper venom-induced local damages. The present study was aimed to study the protective efficacy of A-GNP against Viper venom-induced inflammatory response and organ toxicity in animal model. Ethical clearance was obtained from animal experiments. Physico-chemical characterization of A-GNP was done by DLS (diameter and zeta potential), FE-SEM and XRD. Swiss albino male mice were divided into 4 groups: Gr.1-Sham control, Gr.2- Russell’s Viper venom (RVV) control, Gr.3- andrographolide treated and Gr.4- A-GNP treated. The 1/5th minimum lethal dose of RVV (500µg/kg, s.c.) was induced in animals of group 2, 3 & 4 animals, followed by treatment with andrographolide (100mg/kg, i.p.) and A-GNP (100mg/kg, i.v.) in group 3 & 4 animals, respectively. Blood was collected after 18 h, serum was prepared, and inflammatory markers (IL 1β, 6, 17a, 10, TNF α) and biochemical markers (AST, ACP, LDH, urea, creatinine) were assessed. Values were expressed as mean±SEM (n=4), one way ANOVA was done, P<0.05 was considered as statistically significant. DLS size showed the hydrodynamic diameter of A-GNP to be 230-260nm with polydispersity index of 0.103 and zeta potential was -18.32mV. XRD data confirmed the presence of crystalline gold in A-GNP, and FESEM indicated the presence of nearly spherical particle with size18-24nm.Treatment with A-GNP significantly decreased viper venom-induced proinflammatory markers (IL 1β, 6, 17, TNF α) increased anti-inflammatory markers (IL 10) and decreased organ toxicity markers (AST, ACP, LDH, urea, creatinine) in animal model. Venom neutralization efficacy of A-GNP was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation. Venom neutralization by A-GNP was due to anti-oxidant/anti-inflammatory activity of andrographolide, which showed increased efficacy after gold nanoparticle tagging. Thus, A-GNP may serve as a supportive therapy in snake-bite (against inflammatory response and organ toxicity) subject to further detail studies.

Keywords: andrographolide, gold nanoparticle, inflammatory response, organ toxicity, snake venom, snake venom neutralization, viper venom

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Authors: Obinna Afamefuna Echi

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Background: The global increase in the elderly population is anticipated to reach significant levels by 2050, presenting extensive economic, social, and healthcare challenges. Age-related cognitive decline, alterations in brain anatomy, and systemic inflammation are profound concerns that diminish the quality of life and increase susceptibility to diseases like Alzheimer's and cardiovascular diseases. Resistance training is presently studied for its potential neuroprotective and anti-inflammatory benefits in older adults. Objectives: This study aimed to explore the effects of different resistance training modalities on neurotrophic factors, inflammatory markers, and cognitive functions in the elderly. Methods: A controlled trial was conducted with 60 male participants aged 60-75, assigned to either 12 weeks of high-intensity blood flow restriction training (BFRT), muscle damaging resistance training (MDRT), or a non-exercising control group. Cognitive function, neurotrophic factors such as BDNF, and inflammatory markers including IL-6 and TNF were measured before and after the intervention period. Setting: Participants were recruited from Kaunas, Lithuania, with sessions facilitated at the Lithuanian Sports University and health assessments conducted at the Lithuanian University of Health Sciences. Results: Preliminary data suggested did not show significant improvements in BDNF levels and cognitive functions in the BFRT and MDRT groups compared to controls. However, there was a notable reduction in inflammatory markers, indicating potential health benefits beyond cognitive enhancement. Conclusion: The incorporation of resistance training can be a strategic intervention to mitigate age-associated cognitive decline and systemic inflammation, thereby enhancing overall health and quality of life in older adults. The results advocate for wider adoption and further study of resistance training as a preventive measure in ageing populations. Funding: The Lithuanian Sports University, the Research Council of Lithuania and the Lithuanian University of Health Sciences.

Keywords: ageing, resistance training, BDNF, cognitive function

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Authors: Dyna Ann C. Sevilles, Noel J. Belonguel, Jarungchai Anton S. Vatanagul, Mary Jeanne O. Flordelis, Grace G. Anota

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Guillain Barre syndrome is an acute inflammatory polyradiculoneuropathy causing progressive symmetrical weakness which can be debilitating to the patient. Early diagnosis is important especially in the acute phase when treatment favors good outcome and reduces the incidence of the need for mechanical ventilation. Electrodiagnostic studies aid in the evaluation of patients suspected with GBS. However, the characteristic electrical changes may not be evident until after several weeks. Thus, studies performed early in the course may give unclear results. The aim of this study is to associate the symptom onset of patients diagnosed with Guillain Barre syndrome with the EMG NCV results and determine the earliest time when there is evident findings supporting the diagnosis. This is a retrospective descriptive chart review study involving patients of >/= 18 years of age with GBS written on their charts in a Tertiaty hospital in Cebu City, Philippines from January 2000 to July 2014. Twenty patients showed electrodiagnostic findings suggestive of GBS. The mean day of illness when EMG NCV was carried out was 7 days. The earliest with suggestive findings was done on day 2 (10%) of illness. Moreover, the highest frequency with positive results was done on day 3 (20%) of illness. Based on the Dutch Guillain Barre Study group criteria, the most frequent variables noted were: prolonged distal motor latency in both median and ulnar nerves(65%) and both peroneal and tibial nerves (71%); and reduced CMAP in both median and ulnar nerves (65%) and both tibial and peroneal nerves (71%). The EMG NCV findings showed majority of demyelinating type (59%). Electrodiagnostic studies are helpful in aiding the physician in the diagnosis and treatment of the disease in the early stage. Based on this study, neurophysiologic evidence of GBS can be seen in as early as day 2 of clinical illness.

Keywords: Acute Inflammatory Demyelinating Polyneuropathy, electrophysiologic study, EMG NCV, Guillain Barre Syndrome

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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Authors: Surbhi Aggarwal, Jaishree Paul

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Background: Role of GABA has been implicated in autoimmune diseases like multiple sclerosis, type1 diabetes and rheumatoid arthritis where they modulate the immune response but role in gut inflammation has not been defined. Ulcerative colitis (UC) and diarrhoeal predominant irritable bowel syndrome (IBS-D) both involve inflammation of gastrointestinal tract. UC is a chronic, relapsing and idiopathic inflammation of gut. IBS is a common functional gastrointestinal disorder characterised by abdominal pain, discomfort and alternating bowel habits. Mild inflammation is known to occur in IBS-D. Aim: Aim of this study was to investigate the role of GABA in UC as well as in IBS-D. Materials and methods: Blood and biopsy samples from UC, IBS-D and controls were collected. ELISA was used for measuring level of GABA in serum of UC, IBS-D and controls. RT-PCR analysis was done to determine GABAergic signal system in colon biopsy of UC, IBS-D and controls. RT-PCR was done to check the expression of proinflammatory cytokines. CurveExpert 1.4, Graphpad prism-6 software were used for data analysis. Statistical analysis was done by unpaired, two-way student`s t-test. All sets of data were represented as mean± SEM. A probability level of p < 0.05 was considered statistically significant. Results and conclusion: Significantly decreased level of GABA and altered GABAergic signal system was detected in UC and IBS-D as compared to controls. Significantly increased expression of proinflammatory cytokines was also determined in UC and IBS-D as compared to controls. Hence we conclude that insufficient level of GABA in UC and IBS-D leads to overproduction of proinflammatory cytokines which further contributes to inflammation. GABA may be used as a promising therapeutic target for treatment of gut inflammation or other inflammatory diseases.

Keywords: diarrheal predominant irritable bowel syndrome, γ-aminobutyric acid (GABA), inflammation, ulcerative colitis

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Authors: Leyla Sattarzadeh, Shahin Fathi Molk Kian, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6), vascular inflammatory markers as adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of different patterns of resistance exercise training on these inflammatory markers, present study aimed to examine the effect of different patterns of eight week resistance exercise training on CRP, IL-6, ICAM-1 and VCAM-1 levels in healthy untrained women. 56 healthy volunteered untrained female university students (aged: 21 ± 3 yr., Body Mass Index: 21.5 ± 3.5 kg/m²) were selected purposefully and divided into four groups. At the end of training protocol and after subject drop during the protocol, upper body exercise training (n=11), lower body (n=12) and whole body resistance exercise training group (n=11) completed the eight weeks of training period although the control group (n=7) did anything. Blood samples gathered pre and post-experimental period and CRP, IL-6, ICAM-1 and VCAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one-way analysis of variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP, ICAM-1 and VCAM-1 showed no significant changes due to the exercise training, but there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper, lower and whole body exercise training by involving the different amounts of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP, ICAM-1 and VCAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: resistance training, C-reactive protein, interleukin-6, intracellular adhesion molecule-1, vascular cell adhesion molecule-1

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Authors: Anna D. Kotrova, Alexandr N. Shishkin, Elena I. Ermolenko

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The aim. To study the quantitative and qualitative colon bacteria ratio from patients with metabolic syndrome. Materials and methods. Fecal samples from patients of 2 groups were identified and analyzed: the first group was formed by patients with metabolic syndrome, the second one - by healthy individuals. The metagenomics method was used with the analysis of 16S rRNA gene sequences. The libraries of the variable sites (V3 and V4) gene 16S RNA were analyzed using the MiSeq device (Illumina). To prepare the libraries was used the standard recommended by Illumina, a method based on two rounds of PCR. Results. At the phylum level in the microbiota of patients with metabolic syndrome compared to healthy individuals, the proportion of Tenericutes was reduced, the proportion of Actinobacteria was increased. At the genus level, in the group with metabolic syndrome, relative to the second group was increased the proportion of Lachnospira. Conclusion. Changes in the colon bacteria ratio in the gut microbiota of patients with metabolic syndrome were found both at the type and the genus level. In the metabolic syndrome group, there is a decrease in the proportion of bacteria that do not have a cell wall. To confirm the revealed microbiota features in patients with metabolic syndrome, further study with a larger number of samples is required.

Keywords: gut microbiota, metabolic syndrome, metagenomics, tenericutes

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Authors: Armaghan Moravej Aleali, Hajieh Shahbazian, Seyed Mahmoud Latifi, Leila Yazdanpanah

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Objective: Metabolic syndrome or insulin resistance syndrome or syndrome X is a collection of abdominal obesity, hypertension, glucose intolerance and lipid abnormalities (elevated triglycerides, elevated LDL, and decrease the amount of HDL). That increases the incidence of diabetes and risk of cardiovascular disease. The aim of this study is to investigate the prevalence of metabolic syndrome in people over 20 years of Ahvaz according to IDF, ATPIII, Harmonized I and Harmonized II. Material & Methods: A cross-sectional study with a random cluster sampling in six health centers in Ahvaz was done. After obtaining informed consent, questionnaire for each person filled up including demographic data and examinations, including blood pressure in sitting position, weight, height, waist circumference, and waist circumference measurement. Results: From all participating 912 people, (434 (2/47%) male and 478 (2/52%) female) were evaluated. Mean age was 42/27± 14years (44/2±14/26 for male and 40/5±13/5 for female). Prevalence of metabolic syndrome was 22/8%, 28/4%, 30/9% and 16/9% according to ATPIII, IDF, Harmonized I and Harmonized II criteria respectively and increased with age in both sexes. IDF and Harmonized I had most kappa coordination (0/94). Conclusion: The results show a high prevalence of metabolic syndrome in Ahvaz. So, identification of the risk factors should be attempted to prevent metabolic syndrome.

Keywords: metabolic syndrome, IDF, ATP III, prevalence

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Authors: Sahar Iqrar, Malik Adeel Anwar, Zain Akram, Maria Noor

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Introduction: Oral lichen planus is a chronic inflammatory condition of unknown etiology. Oral lichen planus may be related with several other diseases. Grinspan's Syndrome is characterized by a triad of oral lichen planus, hypertension, and diabetes mellitus. Other associations reported in the literature are with chronic liver disease and, with dyslipidemia. The nature of these associations is still not fully understood. Material and methods: Study was conducted in Department of Oral Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan. A total of n=89 clinically diagnosed patients of oral lichen planus of both gender and all age groups were recruited and detailed history were recorded in the designed performs. Results: A total of n=89 patients were taken with male to female ratio of 3:8 in which 24 were male and 65 females. Mean age was 48.8 ± 13.8 years. Age range of 10-74 years was seen. Among these patients suffering from oral lichen planus, 41.6% (n=37) had a positive history for hypertension with 59.5% (n=22) of these patients were taking different medication for their condition. Whereas Diabetes Mellitus was found in 24.7% (n=22) patients with 72.7% (n=16) of these patients using the hypoglycemic drug (oral or injectable) to control their blood glucose levels. Out of these n=89 lichen planus patients 21.3% had both hypertension and diabetes mellitus (fulfilling the criteria for Grinspan's Syndrome). Out of this Grinspan's Syndrome pool 94.7% (n=19) were taking drug atleast for one of the two conditions. Conclusion: As noticed form the medical history of the patients, most of them were using hypoglycemic drugs for diabetes mellitus and beta blockers, diuretics and calcium channel blockers for hypertension. These drugs are known for lichenoid reaction. Therefore, it should be ruled out at histopathological/ immunological and molecular level whether these patients are suffering from lichen planus or lichenoid drug reaction to truly declare them as patients with Grinspan’s Syndrome.

Keywords: diabetes mellitus, grinspan's syndrome, lichenoid drug reaction, oral lichen planus

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Authors: Deepa Gandhi, Pravin K. Naoghare, Amit Bafana, Krishnamurthi Kannan, Saravanadevi Sivanesana

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Oxidative stress is known to depreciate normal functioning of osteoblast cells. Present study reports oxidative/inflammatory signatures in fluoride exposed human osteosarcoma (HOS) cells and its possible association with the genes involved in bone developmental pathway. Microarray analysis was performed to understand the possible molecular mechanisms of stress-mediated bone lose in HOS cells. Cells were chronically exposed with sub-lethal concentration of fluoride. Global gene expression is profiling revealed 34 up regulated and 2598 down-regulated genes, which were associated with several biological processes including bone development, osteoblast differentiation, stress response, inflammatory response, apoptosis, regulation of cell proliferation. Microarray data were further validated through qRT-PCR and western blot analyses using key representative genes. Based on these findings, it can be proposed that chronic exposure of fluoride may impair bone development via oxidative and inflammatory stress. The present finding also provides important biological clues, which will be helpful for the development of therapeutic targets against diseases related bone.

Keywords: bone, HOS cells, microarray, stress

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Authors: Olha Yarova

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This study is a collaborative project between the American University of Central Asia and parent association of children with Down syndrome ‘Sunterra’ that took place in Bishkek, Kyrgyzstan. The purpose of the study was to explore whether principles and techniques of applied behavior analysis (ABA) could be used to teach children with Down syndrome socially significant behaviors. ABA is considered to be one of the most effective treatment for children with autism, but little research is done on the particularity of using ABA to children with Down syndrome. The data for the study was received during clinical observations; work with children with Down syndrome and interviews with their mothers. The results show that many ABA principles make the work with children with Down syndrome more effective. Although such children very rarely demonstrate aggressive behavior, they show a lot of escape-driven and attention seeking behaviors that are reinforced by their parents and educators. Thus functional assessment can be done to assess the function of problem behavior and to determine appropriate treatment. Prompting and prompting fading should be used to develop receptive and expressive language skills, and enhance motor development. Even though many children with Down syndrome work for praise, it is still relevant to use tangible reinforcement and to know how to remove them. Based on the results of the study, the training for parents of children with Down syndrome will be developed in Kyrgyzstan, country, where children with Down syndrome are not accepted to regular kindergartens and where doctors in maternity hospitals tell parents that their child will never talk, walk and recognize them

Keywords: down syndrome, applied behavior analysis, functional assessment, problem behavior, reinforcement

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Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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Authors: Sandip Tambare, Revati Ghadge

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Alcohol withdrawal syndrome continue to be concerning health issue worldwide in alcoholics. Many current option for treating alcohol withdrawal signs are habit forming causing dependency of sedatives. The divine science of Ayurveda recommends Nasya for improvement of alcohol withdrawal signs. As per the latest reports 1/3 of the Indian population is using alcohol in an unhealthy manner, the complication being wide and varied among which, the Alcohol Withdrawal Syndrome is the dominant one. The presentation varies from mild sleep loss or anxiety to delirium. Ayurveda has given utmost in the context of Madatyaya(Alcoholism). Various protocols based on the identification of the status of tridoshas are explained which includes sodhana, samana and satwavachaya chikitsa. Various medications are being used, with appreciated effects in the clinical practice. As per reports, the panchakarma procedure nasya seems highly effective, in managing of the alcohol withdrawal syndrome. Nasya with Ksheerabala Taila is given for 7 days in the condition of Alcohol Withdrawal syndrome and it was the non Randomized trial with 30 subjects satisfying the DSM V criteria for alcohol withdrawl and the assessment was done using the Clinical Institute Withdrawal Assessment for Alcohol Scale revised (CIWA-Ar). Conclusion: Among the symptoms which were studied after the interventions, it was found that there was high significant response in almost all the symptoms in the given subjects. The eternal science of Ayurveda is able to answer the existing problem of alcohol and its abuse in the society.

Keywords: nasya, alcohol withdrawal, madatyaya, ksheerabala taila

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Authors: Gema Gómez-Casado, Alba Rodríguez-Muñoz, Virginia Mela-Rivas, Pallavi Kompella, Francisco José Tinahones-Madueña, Isabel Moreno-Indias, Almudena Ortega-Gómez

Abstract:

Obesity is a high-priority health problem worldwide due to its high prevalence. The proportion of obese and overweight subjects in industrialized countries exceeds half of the population in most cases. Beyond the metabolic problem, obesity boosts inflammation levels in the organism. The gut microbiota, considered an organ by itself, controls a high variety of processes at a systemic level. In fact, the microbiota interacts closely with the immune system, being crucial in determining the maturation state of neutrophils, key effectors of the innate immune response. It is known that changes in the diet exert strong effects on the variety and activity of the gut microbiota. The effect that those changes have on the axis microbiota-immune response is an unexplored field. In this study, 10 patients with obesity (weight 114,3 ± 14,5Kg, BMI 40,47±3,66) followed a Mediterranean-hypocaloric diet for 3 months, reducing their initial weight by 12,71 ± 3%. A transplant of microbiota from these patients before and after the diet was performed into wild type “germ-free” mice (n=10/group), treated with antibiotics. Six weeks after the transplant, mice were euthanized, and the presence of cells from the innate immune system were analysed in different organs (bone marrow, blood, spleen, visceral adipose tissue, and intestine) by flow cytometry. No differences were observed in the number of myeloid cells in bone marrow, blood, spleen, or visceral adipose tissue of mice transplanted with patient’s microbiota before and after following the Mediterranean diet. However, the intestine of mice that received post-diet microbiota presented a marked decrease in the number of neutrophils (whose presence is associated with tissue inflammation), as well as macrophages. In line with these findings, intestine monocytes from mice with post-diet microbiota showed a less inflammatory profile (lower Ly6Gˡᵒʷ proportion of cells). These results point toward a decrease in the inflammatory state of the intestinal tissue, derived from changes in the gut microbiota, which occurred after a 3-month Mediterranean diet.

Keywords: obesity, nutrition, Mediterranean diet, gut microbiota, immune system

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Authors: Dessy Laksyana Utami

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The sick building syndrome comprises of various nonspecific symptoms that occur in the occupants of a building. It is commonly increases sickness absenteeism and causes a decrease in productivity of the workers. Evidence suggests that what is called the Sick Building Syndrome are at least three separate entities, which has at least one cause. The following are some of the factors that might be primarily responsible for Sick Building Syndrome such as: Chemical contaminants, Biological contaminants, Inadequate ventilation and Electromagnetic radiation. In many cases it is due to insufficient maintenance of the HVAC (heating, ventilation, air conditioning) system in the building. As this syndrome is increasingly becoming a major occupational hazard. It was used the analytic cross-sectional design. Based on data obtained 80% of respondents reported significant ongoing health problems in the eyes, head, and the nose. 60% had bad symptoms in the throat, the stomach and cough, 50% had gastrointestinal disorders, 40% fatigue and 25% occurred all symptoms sick building syndrome. The 40 respondents were recruited to the study, with a mean age of 35 years (range 20-55). To support the evidence of Sick Building Syndrome, further checks are needed for some of the factors in next research, i.e. measurement of Chemical contaminants, Biological contaminants, inadequate ventilation & Electromagnetic radiation.

Keywords: indoor air pollution, sick building syndrome, indoor air quality, oil gas polution

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Authors: Hossam M. Abdallah, Ali M. El-Halawany, Gamal A. Mohamed, Khalid Z. Alshali, Zainy M. Banjar, Hany A. El-Bassossy

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Hypertension and vascular dysfunction are major components and complications of many diseases like metabolic syndrome. In addition, vascular dysfunction is considered the initial step in diabetic atherosclerosis, the main etiology for mortality and a great percent of morbidity in diabetic patients. In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Herbal drugs are prescribed widely in treatment of different aliment because of their effectiveness, fewer side effects and relatively low cost. Nine plants belong to five different families grown in Kingdom of Saudi Arabia were evaluated for their effect on exaggerated vasoconstriction and impaired relaxation in aortae isolated from metabolic syndrome rats. The aerial parts of Onopordum ambiguum Fresen. (OA), Astragalus abyssinicus Steud. (AA), Pulicaria Arabica Cass. (PA), Echinops sheilae Kit Tan (ES), Aizoon canariense L. (AC), Cleome viscosa L. (CV), Chrozophora oblongifolia (Delile) A.Juss. ex Spreng (CO), Centaurea pseudosinaica Mouterde (CP) and Tephrosia nubica Baker (TN) were dried and extracted with methanol. The effect of thirty minute incubation with the total extracts (10-330 µg/ml) or their fractions on the exaggerated vasoconstriction response to phenylephrine (10nM to 10microM) and impaired vasodilation to acetylcholine (10-330 µg /ml) of aortae isolated from metabolic syndrome animals was studied. Incubating aortae isolated from metabolic syndrome animals with total methanol extract of OA, AA, PA, AC, CV, and TN at concentrations (10-330 microgram/ml) in the organ bath led to concentration dependent alleviation of exaggerated vasoconstriction response to phenylephrine without having beneficial effect on impaired vasodilation to acetylcholine. In conclusion, addition of OA, AA, PA, AC, CV and TN to the standard therapies may provide superior means to alleviate the associated vascular complications.

Keywords: vascular dysfunction, exaggerated vasoconstriction, metabolic syndrome, Saudi plants

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Authors: Armaghan Moravej Aleali, Seyed Bahman Ghaderian, Homeira Rashidi, Mahmoud Mapar

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Background and Objective The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. The aim of this study was finding an association between metabolic syndrome and hypogonadism in Khouzestan, Iran. Subjects and Methods: In this study, 60 patients divided into two groups consisted of 30 cases (with metabolic syndrome) and 30 controls. Total and free Serum Testosterone and FBS in all of them were measured. Data was analyzed with SPSS20 program. Results: There was a significant difference between two groups about free Testosterone (P=0.01), FBS (P=0.002) and LH (P=0.03). Conclusion: According to this finding, it is thought the prevalence of hypogonadism in men with metabolic syndrome is more than the general population.

Keywords: metabolic syndrome, fasting blood sugar, hypogonadism, testosterone

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Authors: Recep Kesli, Onur Turkyilmaz, Cengiz Demir

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Objective: Autoimmune collagen diseases occur with the immune reactions against the body’s own cell or tissues which cause inflammation and damage the tissues and organs. In this study, it was aimed to compare seropositivity rates and patterns of the anti-nuclear antibodies (ANA) in the diagnosis of four different autoimmune collagen tissue diseases (Rheumatoid Arthritis-RA, Systemic Lupus Erythematous-SLE, Scleroderma-SSc and Sjogren Syndrome-SS) with each other. Methods: One hundred eighty-eight patients applied to different clinics in Afyon Kocatepe University ANS Practice and Research Hospital between 11.07.2014 and 14.07.2015 that thought the different collagen disease such as RA, SLE, SSc and SS have participated in the study retrospectively. All the data obtained from the patients participated in the study were evaluated according to the included criteria. The historical archives belonging to the patients have been screened, assessed in terms of ANA positivity. The obtained data was analysed by using the descriptive statistics; chi-squared, Fischer's exact test. The evaluations were performed by SPSS 20.0 version and p < 0.05 level was considered as significant. Results: Distribution rates of the totally one hundred eighty-eight patients according to the diagnosis were found as follows: 82 (43.6%) were RA, 38 (20.2%) were SLE, 22 (11.7%) were SSc, and 46 (24.5%) were SS. Distribution of ANA positivity rates according to the collagen tissue diseases were found as follows; for RA were 54 (65,9 %), for SLE were 36 (94,7 %), for SSc were 18 (81,8 %), and for SS were 43 (93,5 %). Rheumatoid arthritis should be evaluated and classified as a different class among all the other investigated three autoimmune illnesses. ANA positivity rates were found as differently higher (91.5 %) in the SLE, SSc, and SS, from the RA (65.9 %). Differences at ANA positivity rates for RA and the other three diseases were found as statistically significant (p=0.015). Conclusions: Systemic autoimmune illnesses show broad spectrum. ANA positivity was found as an important predictor marker in the diagnosis of the rheumatologic illnesses. ANA positivity should be evaluated as more valuable and sensitive a predictor diagnostic marker in the laboratory findings of the SLE, SSc, and SS according to RA.

Keywords: antinuclear antibody (ANA), rheumatoid arthritis, scleroderma, Sjogren syndrome, systemic lupus Erythemotosus

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Authors: Ben Clapperton, Daniel Stahl, Kimberley Goldsmith, Trudie Chalder

Abstract:

Chronic fatigue syndrome (CFS) is a condition characterised by chronic disabling fatigue and other symptoms that currently can't be explained by any underlying medical condition. Although clinical trials support the effectiveness of cognitive behaviour therapy (CBT), the success rate for individual patients is modest. Patients vary in their response and little is known which factors predict or moderate treatment outcomes. The aim of the project is to develop a prediction model from baseline characteristics of patients, such as demographics, clinical and psychological variables, which may predict likely treatment outcome and provide guidance for clinical decision making and help clinicians to recommend the best treatment. The project is aimed at identifying subgroups of patients with similar baseline characteristics that are predictive of treatment effects using modern cluster analyses and data mining machine learning algorithms. The characteristics of these groups will then be used to inform the types of individuals who benefit from a specific treatment. In addition, results will provide a better understanding of for whom the treatment works. The suitability of different clustering methods to identify subgroups and their response to different treatments of CFS patients is compared.

Keywords: chronic fatigue syndrome, latent class analysis, prediction modelling, self-organizing maps

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Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

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The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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Authors: Mandob Enyegue Damaris, Oko Ndjollo Viviane

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The prevalence of Metabolic Syndrome is increasing throughout the world. The etiology of the metabolic syndrome is dependent on different factors such as ethnic group. This study aimed to evaluate the metabolic syndrome among Mbo ethnic group people leaving in Yaounde, Cameroon. The study conducted on the hundred and thirty two people 40 men and 92 women aged between 18-60 years who were referred to the Andre Fouda Medical Fundation in Yaounde. Metabolic syndrome was diagnosed using Adult Treatment Panel-III (A.T.P-III) 2001 guidelines. The mean of age, high fasting blood glucose, triglycerides levels and total cholesterol levels were significantly (P<0.05) higher in women with metabolic syndrome. High blood pressure level (56.80%), high fasting glucose (20.45%) and high waist circumference (10.60%) were respectively the most frequent characteristics in comparison to others metabolic components. The overall prevalence of MetS was (4.55%) and higher in women (3.03%) than in men (1.52%). The prevalence of MetS is low in originates of Mbo ethnic group of Yaounde. High blood pressure is the most common abnormality.

Keywords: individual components, metabolic syndrome, Mbo ethnic group, Yaounde-Cameroon

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Authors: Priyanka Sharma, Niti Puri

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Anemia develops when blood lacks enough healthy erythrocytes. Past studies indicated that anemia, inflammatory process, and oxidative stress are interconnected. Erythrocytes are continuously exposed to reactive oxygen species (ROS) during circulation, due to normal aerobic cellular metabolism and also pathology of inflammatory diseases. Systemic mastocytosis and genetic depletion of mast cells have been shown to affect anaemia. In the present study, we attempted to reveal whether mast cells have a direct role in clearance or erythrophagocytosis of normal or oxidatively damaged erythrocytes. Murine erythrocytes were treated with tert-butyl hydroperoxidase (t-BHP), an agent that induces oxidative damage and mimics in vivo oxidative stress. Normal and oxidatively damaged erythrocytes were labeled with carboxyfluorescein succinimidyl ester (CFSE) to track erythrophagocytosis. We show, for the first time, direct erythrophagocytosis of oxidatively damaged erythrocytes in vitro by RBL-2H3 mast cells as well as in vivo by murine peritoneal mast cells. Also, activated mast cells, as may be present in inflammatory conditions, showed a significant increase in the uptake of oxidatively damaged erythrocytes than resting mast cells. This suggests the involvement of mast cells in erythrocyte clearance during oxidative stress or inflammatory disorders. Partial inhibition of phagocytosis by various inhibitors indicated that this process may be controlled by several pathways. Hence, our study provides important evidence for involvement of mast cells in severe anemia due to inflammation and oxidative stress and might be helpful to circumvent the adverse anemic disorders.

Keywords: mast cells, anemia, erythrophagocytosis, oxidatively damaged erythrocytes

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Authors: Muslim Idan Mohsin, Mohammed Jasim Al-Shamarti, Rusul Idan Mohsin, Ali A. Majeed

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One of the causative agents of the lower respiratory tract (LRT) is Pseudomonas aeruginosa, which can lead to severe infection associated with a lung infection. There are many cytokines that are secreted in response to bacterial infection, in particular interleukin IL-36 cytokine in response to P. aeruginosa infection. The involvement of IL-36 in the P. aeruginosa infection could be a clue to find a specific way for treatments of different inflammatory and degenerative lung diseases. IL36 promotes primary immune response via binding to the IL-36 receptor (IL-36R). Indeed, an overactivity of IL-36 might be an initiating factor for many immunopathologic sceneries in pneumonia. Here we demonstrate if the IL-36 cytokine increases in response P. aeruginosa infection that is isolated from lower respiratory tract infection (LRT). We demonstrated that IL-36 expression significantly unregulated in human lung epithelial (A549) cells after infected by P. aeruginosa at mRNA level.

Keywords: IL36, Pseudomonas aeruginosa, LRT infection, A549 cells

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Authors: S. Ibrahim, D. Salilew-Wondim, M. Hoelker, C. Looft, E. Tholen, C. Grosse-Brinkhaus, K. Schellander, C. Neuhoff, D. Tesfaye

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Bovine endometrial cells appear to have a key role in innate immune defense of the female genital tract. A better understanding of molecular changes in microRNAs (miRNAs) and their target genes expression may identify reliable prognostic indicators for cows that will resolve inflammation and resume cyclicity. In the current study, we hypothesized that let-7 miRNAs family has a primary role in the innate immune defence of the endometrium tissue against bacterial infection, which is partly achieved via regulating mRNA stability of pro-inflammatory cytokines at the post-transcriptional level. Therefore, we conducted two experiments. In the first experiment, primary bovine endometrial cells were challenged with clinical (3.0 μg/ml) and sub-clinical (0.5 μg/ml) doses of lipopolysaccharide (LPS) for 24h. In the 2nd experiment, we have investigated the potential role of let-7 miRNAs (let-7a and let-7f) using gain and loss of function approaches. Additionally, tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 induced transcript 1 (TGFB1I1) and serum deprivation response (SDPR) genes were validated using reporter assay. Here we addressed for the first time that let-7 miRNAs have a precise role in bovine endometrium, where LPS dysregulated let-7 miRNAs family expression was associated with an increased pro-inflammatory cytokine level by directly/indirectly targeting the TNFα, interleukin 6 (IL6), nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), TGFβ1I1 and SDPR genes. To our knowledge, this is the first study showing that TNFα, TGFβ1I1 and SDPR were identified and validated as novel let-7 miRNAs targets and could have a distinct role in inflammatory immune response of LPS challenged bovine endometrial cells. Our data represent a new finding by which uterine homeostasis is maintained through functional regulation of let-7a by down-regulation of pro-inflammatory cytokines expression (TNFα and IL6) at the mRNA and protein levels. These findings suggest that LPS serves as a negative regulator of let-7 miRNAs expression and provides a mechanism for the persistent pro-inflammatory phenotype, which is a hallmark of bovine subclinical endometritis.

Keywords: bovine endometrial cells, let-7, lipopolysaccharide, pro-inflammatory cytokines

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