Publications by authors named "Hamid Najafipour"

86 Publications

The effect of demographic characteristics on the relationship between smoking and xerostomia: a cross sectional, case-control study.

Epidemiol Health 2021 Feb 28:e2021017. Epub 2021 Feb 28.

Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Objectives: The effect of age, gender and other demographic factors on relationship between smoking and dry mouth remained unknown. The aim of this study was to measure the relationship between dry mouth and smoking specifically by considering demographic characteristics.

Methods: In this case-control study, 5640 subjects who were randomly selected from 10000 participants of the second phase of Kerman coronary artery disease risk factors study (KERCADRS) during 2014-2018, were included. Demographic characteristics and smoking frequency in the participants were recorded by a checklist. Six-item Fox questionnaire was filled out by the participants to determine dry mouth as a dependent variable. The interaction terms of daily cigarette smoking with sex, age, educational level, and marital status were entered to the model and non-significant terms were removed by the hierarchical model selection.

Results: It was revealed that 3429 (60.8%) of controls had not dry mouth and 2211 (39.2%) of cases had xerostomia. Statistical analysis revealed that smokers are more likely to have dry mouth in all ages and both sexes (p<0.001). As men get older, the chance of having dry mouth increases more rapidly among them than female smokers (p<0.001). In addition, female smokers have more chance to have dry mouth compared to male smokers (p<0.001).

Conclusion: Age, sex, and daily cigarette smoking affect the prevalence of dry mouth in the very complex way. Cigarette smoking was associated with more chance of having dry mouth especially in female smokers.
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http://dx.doi.org/10.4178/epih.e2021017DOI Listing
February 2021

Prevalence and risk factors of urinary incontinence among Iranian women.

Neurourol Urodyn 2021 02 7;40(2):642-652. Epub 2021 Jan 7.

Department of Urology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Background: Urinary incontinence is a common condition among women. Although it is not a life-threatening condition, it dramatically influences the quality of life. This study aimed to estimate the prevalence of urinary incontinence and its risk factors among Iranian women in Kerman, Iran.

Methods: This cross-sectional, population-based study was conducted on 3100 Iranian women aged 15-80 years in 2017 in Kerman, Iran. The participants were selected via cluster sampling and were invited to complete the questionnaires. Their demographic information and medical history were assessed, the urinary incontinence questionnaire was completed, and the associated risk factors were also recorded. Quantitative variables are reported as mean ± SD, while qualitative and ranked variables are expressed in percentage. All analyses were conducted in Stata version 12 (Stata Corp.).

Results: The mean age of the participants was 46 years, and the overall prevalence of urinary incontinence was estimated to be 63%. The highest and lowest prevalence rates of urinary incontinence were reported in the elderly and the youth, respectively (79% and 41%, respectively). Age, increase of body mass index (BMI), pregnancy, diabetes, anxiety, and depression were the associated risk factors.

Conclusion: We found that the prevalence of urinary incontinence is high in Iran. Therefore, to control this condition and improve women's quality of life, effective plans are needed.
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http://dx.doi.org/10.1002/nau.24597DOI Listing
February 2021

Perillyl alcohol suppresses monocrotaline-induced pulmonary arterial hypertension in rats via anti-remodeling, anti-oxidant, and anti-inflammatory effects.

Clin Exp Hypertens 2021 Apr 15;43(3):270-280. Epub 2020 Dec 15.

Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences , Kerman, Iran.

: Pulmonary arterial hypertension (PAH) is a disastrous disease that current treatments cannot prevent its progression. The present study investigated the effects of perillyl alcohol (PA), a natural monoterpene, on the experimental PAH in male Wistar rats. : Rats divided into eight groups of control, Monocrotaline (MCT), MCT+vehicle, and MCT+PA with doses of 20, 30, 40, 50, and 60 mg/kg. PAH was induced by a single injection of monocrotaline (60 mg/kg) on day 0. The animals in the groups of MCT+vehicle and MCT+PA received the vehicle or PA from day 22 to 42 once a day. On day 43, under general anesthesia, right ventricular systolic pressure (RVSP), as an index of pulmonary artery systolic pressure, and the ratio of the right ventricle to the left ventricle plus septum weight, as the right ventricular hypertrophy index (RVHI), were measured. Also, some histological and biochemical indices were assessed in the lung tissue. : MCT significantly ( < .001) enhanced the RVSP and RVHI compared to the control group (89.4 ± 8.2 vs 23 ± 3.3 mmHg & 0.63 ± 0.08 vs 0.26 ± 0.04 respectively). It also increased oxidative stress and inflammatory cytokines and reduced Bax/Bcl2 ratio. Treatment with PA significantly recovered RVSP and hypertrophy index and suppressed vascular cell proliferation, oxidant production, and inflammatory processes. : PA exerted noticeable protective and curative effects against MCT-induced PAH and pulmonary vascular remodeling through inhibiting cellular proliferation, oxidative stress, and inflammation. Therefore, PA can be considered as a new therapeutic goal for the treatment of PAH.
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http://dx.doi.org/10.1080/10641963.2020.1860080DOI Listing
April 2021

Improvement of Cardiac Function in Rats With Myocardial Infarction by Low-Intensity to Moderate-Intensity Endurance Exercise Is Associated With Normalization of Klotho and SIRT1.

J Cardiovasc Pharmacol 2021 Jan;77(1):79-86

Neuroscience Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Abstract: Exercise training (Ex) has beneficial effects on cardiovascular diseases by increasing Klotho and SIRT1. This study aimed to investigate whether the beneficial impact of Ex on myocardial infarction (MI) is mediated through Klotho and SIRT1. Fifty-six Wistar rats were divided into 4 main groups of Sham, MI, Ex, and MI + Ex. MI was induced by the closure of the left anterior descending. Animals were trained by endurance exercise for 4 weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of Klotho and SIRT1 in the serum and heart were measured by enzyme-linked immunosorbent assay and Western blot, respectively. The ADAM17 level in the heart and kidneys was assessed by enzyme-linked immunosorbent assay. The infarct size and fibrosis area were assessed by triphenyltetrazolium chloride and Masson trichrome staining, respectively. Ex recovered the reduction of dp/dt max and dp/dt min and decreased myocardial infarct size and fibrotic area in the MI group. Ex normalized the increase in heart rate, systolic blood pressure, left ventricular systolic pressure, and left ventricular end diastolic pressure in the MI group. Ex also normalized the reduction of the levels of Klotho and SIRT1 in serum and heart in the MI group. The changes of Klotho and SIRT1 in serum were positively correlated. Ex also restored ADAM17 levels in the MI group. Ex improved cardiac function in the MI group and is associated with reduction of the infarct size and normalization of Klotho and SIRT1 levels. Regarding unidirectional changes in Klotho and SIRT1, these proteins may play a role in beneficial effects of Ex on MI recovery.
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http://dx.doi.org/10.1097/FJC.0000000000000935DOI Listing
January 2021

Prevalence and incidence of pre-hypertension and hypertension (awareness/control) in Iran: findings from Kerman coronary artery diseases risk factors study 2 (KERCADRS).

J Hum Hypertens 2020 Sep 14. Epub 2020 Sep 14.

Institute for Health Policy Studies, University of California, San Francisco, CA, USA.

Hypertension (HTN) is an important cause of cardiovascular-related morbidity and mortality. The present study was conducted to investigate the prevalence and incidence rate of pre-HTN, diagnosed and undiagnosed HTN, as well as its control and associated factors in adult population in southeast Iran. In a randomized household survey, 9987 participants aged 15-80 years were recruited into the study. HTN was confirmed through examination or using antihypertensive drug(s). Pre-HTN and HTN were defined as 120-139/80-89 and ≥140/90 mmHg for systolic and diastolic BP, respectively. The prevalence of pre-HTN was 28.5%. The prevalence of HTN was 19.2% (13.9% diagnosed and 5.3% undiagnosed). HTN increased with age (from 4% in 15-24 to 67.8% in 75-80 years). Men had higher pre-HTN (35.6% vs. 23.4%) and undiagnosed HTN (7.5% vs. 3.8%) than women. Of those diagnosed, 46.5% had uncontrolled BP, in which, women had better conditions than men (45.6% vs. 47.4%). Obesity, positive family history of HTN, anxiety, and low physical activity were the most significant predictors of HTN. The prevalence of pre-HTN decreased but there was no change in the prevalence of HTN during the last 5 years. The 5-year incidence rate/100 person-years of pre-HTN and HTN was 6.6 and 3.7, respectively. Although there are some promising signs of reducing pre-HTN and slowing HTN rise, currently, almost one-fifth of the adult population suffers from HTN. Given the poor BP control in patients with diagnosed HTN, especially in men, alarms that more effective interventions and strategies are needed to reduce deleterious consequences of HTN.
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http://dx.doi.org/10.1038/s41371-020-00392-5DOI Listing
September 2020

A review on plants and herbal components with antiarrhythmic activities and their interaction with current cardiac drugs.

J Tradit Complement Med 2020 May 6;10(3):275-287. Epub 2020 Apr 6.

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

This paper aimed to compile information on plants or their compounds which have experimentally shown antiarrhythmic effect and to scrutinize the efficacy and potency of them and their potential interaction with conventional cardiac drugs. Literature searches were accomplished by using numerous electronic databases, and the available knowledge on different parts of herbs and their ingredients with antiarrhythmic effects up to 2019 were identified and collected. The results indicate that 36 herbs or their derivatives can be effective in the treatment of arrhythmias, especially in animal and cellular models. They affect various ionic channels in different action potential phases. The alterations in ionic currents lead to changing in the amplitude and duration of the action potential, effective refractory period, maximum velocity, resting membrane potential, channel trafficking, or intracellular calcium concentration. The agents that prolong action potential duration and effective refractory period such as dauricine and sophocarpine seem to be more beneficial if more comprehensive studies confirm their efficacy and safety. It is noteworthy that the consumption of some herbal agents for cardiovascular (e.g. Hawthorn and Ginseng) or other (e.g. Ginseng and Licorice) therapeutic purposes may boost the pro-arrhythmogenic effect of current cardiovascular drugs such as cardiac glycosides. This study accentuates known plants or their derivatives with anti-arrhythmic effects, potential interaction with other cardiac drugs, and the possible mechanisms involved. It can assist clinicians and scientists in research and therapeutic approaches to the management of cardiac arrhythmias.
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http://dx.doi.org/10.1016/j.jtcme.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340875PMC
May 2020

Perillyle alcohol and Quercetin ameliorate monocrotaline-induced pulmonary artery hypertension in rats through PARP1-mediated miR-204 down-regulation and its downstream pathway.

BMC Complement Med Ther 2020 Jul 13;20(1):218. Epub 2020 Jul 13.

Researcher, Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Background: Pulmonary artery hypertension (PAH) is a vascular disease in the lung characterized by elevated pulmonary arterial pressure (PAP). Many miRNAs play a role in the pathophysiology of PAH. Perillyle alcohol (PA) and Quercetin (QS) are plant derivatives with antioxidant and anti-proliferative properties. We investigated the effect of PA and QS on PAP, expression of PARP1, miR-204, and their targets, HIF1α and NFATc2, in experimental PAH.

Methods: Thirty rats were divided into control, MCT, MCT + Veh, MCT + PA and MCT + QS groups. MCT (60 mg/kg) was injected subcutaneously to induce PAH. PA (50 mg/kg daily) and QS (30 mg/kg daily) were administered for 3 weeks after inducing PAH. PAP, lung pathology, expression of miRNA and mRNA, and target proteins were evaluated through right ventricle cannulation, H&E staining, real-time qPCR, and western blotting, respectively.

Results: Inflammation and lung arteriole thickness in the MCT group increased compared to control group. PA and QS ameliorated inflammation and reduced arteriole thickness significantly. miR-204 expression decreased in PAH rats (p < 0.001). PA (p < 0.001) and QS (p < 0.01) significantly increased miR-204 expression. Expression of PARP1, HIF1α, NFATc2, and α-SMA mRNA increased significantly in MCT + veh rats (all p < 0.001), and these were reduced after treatment with PA and QS (both p < 0.01). PA and QS also decreased the expression of PARP1, HIF1α, and NFATc2 proteins that had increased in MCT + Veh group.

Conclusion: PA and QS improved PAH possibly by affecting the expression of PARP1 and miR-204 and their downstream targets, HIF1a and NFATc2. PA and QS may be therapeutic goals in the treatment of PAH.
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http://dx.doi.org/10.1186/s12906-020-03015-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359282PMC
July 2020

Anti-Inflammatory and Anti-Oxidative Effects of Myrtenol in the Rats with Allergic Asthma.

Iran J Pharm Res 2019 ;18(3):1488-1498

Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

The aim of the present study was to investigate the effect of Myrtenol, the active ingredient of Myrtle on the oxidant and anti-oxidant indices and cytokines in the allergic asthma. Allergic asthma was induced by ovalbumin (OVA) sensitization and inhalation in four groups of rats; Control, Asthma, Asthma + Dexamethasone and Asthma + Myrtenol. Myrtenol (50mg/kg) or Dexamethasone (2.5mg/kg) was administered intraperitoneally for 7 consecutive days after OVA inhalation. At the end, histopathological parameters, and interleukins (Interleukin-10 (IL10), Interferon gamma (IFN-γ) , interleukin-1β (IL-1β), Tumor Necrosis Factor α (TNF-α)), and oxidative stress biomarkers, Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the lung and serum were measured by hematoxylin and eosin staining and ELISA method, respectively. Myrtenol reduced the pathological changes in the lungs and airway endothelium ( < 0.01), ( < 0.5). The level of IL-1β ( < 0.05) and MDA in the serum and lung tissue ( < 0.01), ( < 0.05), and also the level of TNF-α ( < 0.05) in the lung tissue decreased in the Myrtenol group compared to the asthma group. Myrtenol increased the level of IL-10 ( < 0.05) and the activity of GPX in the lung tissue and serum ( < 0.001). Myrtenol may improve asthma by increasing the ratio of antioxidants to oxidants and reducing the ratio of pro-inflammatory to anti-inflammatory interleukins in the lung. Myrtenol is presented as a potent herbal medicine ingredient for the treatment of asthma.
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http://dx.doi.org/10.22037/ijpr.2019.1100749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934952PMC
January 2019

Effects of Baneh () Gum on Human Breast Cancer Cell Line (MCF-7) and Its Interaction with Anticancer Drug Doxorubicin.

Iran J Pharm Res 2019 ;18(4):1959-1966

Department of Hematology and Oncology, Baqiyatallah University of Medical Sciences, Tehran, Iran.

is one of the species of that grows in the wild in different regions of Iran. Traditionally, family has antibacterial, fungicidal, and cytotoxic properties. Therefore, the present study was designed to investigate the possible cytotoxic and anti-proliferative properties of Baneh gum. Cytotoxicity of the plant gum was determined using MTT assay on MCF-7 human breast cancer cells. The cellular makers of apoptosis (caspase3 and P53) and cell proliferation (Cyclin-D1) were evaluated by western blotting. Doxorubicin was used as anticancer control drug in combination treatment. The result showed that Baneh gum (100 µg/mL) significantly induced cell damage, activated caspase3, and increased P53 protein level. In addition, Cyclin-D1 was significantly decreased in gum-incubated cells. Furthermore, combination treatment of cells with Baneh gum (25 µg/mL) and doxorubicin (200 nM) produced a significant cytotoxic effect as compared to each drug alone. In conclusion, Baneh gum (100 µg/mL) has a potential pro-apoptotic/anti-proliferative property against human breast cancer cells and its combination with doxorubicin in low doses may induce cell death effectively and be a potent modality to treat this type of cancer.
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http://dx.doi.org/10.22037/ijpr.2019.1100853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059076PMC
January 2019

The Prevalence and 5-Year Incidence Rate of Low Physical Activity in an Urban Population of 10,000 in Southeastern Iran: Relationship With Other Cardiovascular Risk Factors.

J Phys Act Health 2020 04 1;17(4):435-442. Epub 2020 Apr 1.

Background: Because of high prevalence of coronary artery diseases (CADs) in Iran and their relationship with low physical activity (LPA), this study aimed to measure the epidemic size of LPA, its incidence rate, and its relationship with other CAD risk factors in Kerman, Iran.

Methods: About 10,000 adults were randomly recruited through single-stage cluster sampling. Demographic characteristics, biochemical variables, smoking, opium use, mental status, and physical activities were assessed. The relationship between LPA and 7 other CAD risk factors was measured. Five-year incidence rate of LPA was calculated according to the data from the physically active participants in the first phase of the study (n = 3416) who attended the second phase after 5 years.

Results: The prevalence of low, moderate, and intense physical activity was 47.2%, 34.8%, and 18.0%, respectively. LPA rose from 45.1% to 62.2% after the age of 25 years. Women had higher LPA than men. Participants with LPA had significantly higher chance of cigarette smoking, diabetes, overweight/obesity, hypertension, and opium addiction. Five-year incidence rate of LPA was 5.1 persons/100 person-years among physically active population.

Conclusion: Almost half of the studied population suffering from LPA was at risk of CAD. Such risky lifestyle pattern while worsened in the last 5 years makes the emerging of CAD epidemic unavoidable, if appropriate timely interventions not being in place accordingly.
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http://dx.doi.org/10.1123/jpah.2019-0426DOI Listing
April 2020

The Effect of Candesartan Alone and Its Combination With Estrogen on Post-traumatic Brain Injury Outcomes in Female Rats.

Front Neurosci 2019 3;13:1043. Epub 2019 Dec 3.

Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

The aim of this study was to evaluate the effect of candesartan (angiotensin II type I receptor blocker) alone and its combination with estrogen on the changes in brain edema, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) following diffuse traumatic brain injury (TBI) in female rats. TBI was induced in ovariectomized female rats using Marmarou's method. The treatment groups received low-dose (LC) and high-dose (HC) candesartan, estrogen (E2), a combination of estrogen vehicle and candesartan vehicle (oil + vehicle), or a combination of estrogen with low-dose (E2 + LC), or with high-dose (E2 + HC) candesartan. ICP and CPP were measured before and several times after TBI, and the brain water content (brain edema) was measured 24 h after TBI. After the TBI, brain edema and ICP in the estrogen group were lower than in the vehicle and TBI groups. Brain edema and ICP in the HC group were lower than in the vehicle group after TBI. Although there was no significant difference in brain edema and ICP between the LC and vehicle groups, significant differences in these variables were observed when the E2 + LC and E2 + HC groups were compared with the oil + vehicle group after TBI. A significant increase in CPP was observed in the estrogen group 4 and 24 h post-TBI, while this increase was found in the HC and E2 + LC groups 24 h post-TBI. A low dose of candesartan did not exert a protective effect on TBI outcomes, but such an effect did appear after combination with estrogen. This finding suggests that interaction between low-dose candesartan and estrogen improves TBI-induced consequences.
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http://dx.doi.org/10.3389/fnins.2019.01043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901902PMC
December 2019

Chronic treatment with apelin, losartan and their combination reduces myocardial infarct size and improves cardiac mechanical function.

Clin Exp Pharmacol Physiol 2020 03 17;47(3):393-402. Epub 2019 Dec 17.

Physiology Research Center, Semnan University of Medical Sciences, Semnan, Iran.

The renin-angiotensin system (RAS) has a deleterious and apelin/APJ system has protective effect on the ischaemic heart. The collaboration between these systems in the pathophysiology of myocardial infarction is not clear. We determined the effect of chronic pretreatment with apelin, losartan and their combination on ischaemia-reperfusion (IR) injury in the isolated perfused rat heart and on the expression of apelin-13 receptor (APJ) and angiotensin type 1 receptor (AT1R) in the myocardium. During 5 days before the induction of IR, saline (vehicle), apelin-13 (Apl), F13A (apelin antagonist), losartan (Los, AT1R antagonist) and the combination of Apl and Los were administered intraperitoneally in rats. Ischaemia was induced by left anterior descending (LAD) artery occlusion for 30 minutes followed by reperfusion for 55 minutes in the Langendorff isolated heart perfusion system. Pretreatment with Apl, Los and the combination of Apl + Los significantly reduced infarct size by about 30, 33 and 48 percent respectively; and significantly improved the left ventricular function indices such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and rate pressure product (RPP). IR increased AT1R protein level but it did not change APJ significantly. AT1R expression was reduced in groups treated with Apl, Los and Apl + Los. Findings showed that chronic pretreatment with apelin along with AT1R antagonist had more protective effects against IR injury. Combination therapy may diminish the risk of IR-induced heart damage, by reducing AT1R expression, in the heart of patients with coronary artery disease that are at the risk of MI and reperfusion injury.
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http://dx.doi.org/10.1111/1440-1681.13195DOI Listing
March 2020

B12 and Folate Concentrations in Opium Addicts Compared to Healthy Subjects: A Case Control Study from Kerman Coronary Artery Disease Risk Study.

Addict Health 2018 Jul;10(3):198-204

Professor, Physiology Research Center AND Department of Physiology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Background: Opium addiction is a global problem which has implicated many societies. Opium addiction and drug abuse is related to harmful consequences which affect life style, biochemical factors, and vitamins values, and also is considered as a risk for heart diseases. Folate and B12 levels are related to homocysteine and studies about their levels in opium addicts are controversial; therefore, we designed this study to evaluate B12 and folate values in opium addicts.

Methods: From the Kerman Coronary Artery Disease Risk Study (KERCADRS) which is a population-based study, we randomly selected 340 men and entered them into two groups: case (n = 170) and control group (n = 170). Then vitamin B12 and folate levels were measured.

Findings: Opium addiction did not change B12 and folate levels significantly in opium addicts compared to non-addict control subjects. However, only some variables including blood pressure (BP) and diabetes positively and cigarette smoking, triglyceride (TG), alcohol, and cardiovascular disease (CVD) history negatively affected folate, and none of clinical and demographic variables influenced the B12 levels (P > 0.050). TG had significant effects on B12 and folate levels although opium addiction did not show any impact.

Conclusion: High TG levels were accompanied by low levels of B12 and folate. Reduced B12 and folate values are accompanied by serum homocysteine elevation. As TG elevates in opium addicts, it can be considered as an important factor which affects vitamins levels and reduces their absorption. Opium addiction elevates homocysteine level, since we can conclude that homocysteine elevation in opium addicts is independent of B12 and folate levels.
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http://dx.doi.org/10.22122/ahj.v10i3.547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511400PMC
July 2018

The effect of sodium valproate on differentiation of human adipose-derived stem cells into cardiomyocyte-like cells in two-dimensional culture and fibrin scaffold conditions.

Cell Tissue Res 2019 Oct 2;378(1):127-141. Epub 2019 May 2.

Department of Medical Microbiology, and Physiology Research Center, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran.

Differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes is a complex phenomenon, and attempts to find an effective inducing agent are still ongoing. We studied the effect of fibrin scaffold and sodium valproate (VPA, as a histone deacetylase inhibitor) on the differentiation of human adipose-derived stem cells (hADSCs) into cardiomyocyte-like cells. The cells were cultured in culture flask (2D) and in fibrin scaffold (3D), fabricated of human plasma fibrinogen, with and without VPA (1 mM). QRT-PCR, Western blot, and immunochemistry assays were used to evaluate the expression of cardiac markers at gene and protein levels. High levels of CD44, CD90, CD73, and CD105 were expressed on the surface of hADSCs. Treated encapsulated hADSCs (3D) presented significantly higher mRNA expression of HAND1 (1.54-fold), HAND2 (1.59-fold), cTnI (1.76-fold), MLC2v (1.4-fold), Cx43 (1.38-fold), βMHC (1.34-fold), GATA4 (1.48-fold), and NKX2.5 (1.66-fold) in comparison to 2D conditions at four weeks after induction. The protein expressions of NKX2.5 (0.78 vs 0.65), cTnI (1.04 vs 0.81), and Cx43 (1.11 vs 1.08) were observed in the differentiated cells both in 3D and 2D groups, while control cells were absolutely negative for these proteins. The frequency of cTnI and Cx43-positive cells was significantly higher in 3D (24.2 ± 15 and 12 ± 3%) than 2D conditions (19.8 ± 3 and 10 ± 2%). Overall, the results showed that VPA can increase cardiomyogenesis in hADSCs and that fibrin scaffold enhances the inductive effect of VPA. Results of this study may improve cell-based protocols for implementation of more successful cardiac repair strategies.
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http://dx.doi.org/10.1007/s00441-019-03027-5DOI Listing
October 2019

Anxiety, depression, and oral health: A population-based study in Southeast of Iran.

Dent Res J (Isfahan) 2019 May-Jun;16(3):139-144

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Background: Depression and anxiety are two psychosocial illnesses that mostly are comorbid. The prevalence of these diseases is increasing worldwide. Both can affect general health also oral and dental health. The effects can be physiological and behavioral. Patients with these disorders are not willing to keep oral hygiene. The purpose of this study was to investigate the association between depression/anxiety and oral health indices in the 15-75-year-old population of Kerman.

Materials And Methods: This cross-sectional study recruited 5900 people aged 15-75 years through one-stage cluster sampling (Kerman coronary artery disease risk factors study, KERCADRS). Data were collected through beck questionnaires for anxiety and depression and clinical examinations. Oral health indices including decayed, missing, filled teeth, gingival index (GI), and community periodontal index (CPI) were also measured. Data were analyzed by SPSS 21 software. Chi-square, -test and regression analysis were used to determine the relationship between the variables. ≤0.05 was considered as the level of statistical significance.

Results: In the study, 1975 (33.6%) of patients showed moderate-to-severe anxiety and 3502 (59.5%) got the scores as depressed. There was a significant difference between GI and CPI indices of the normal and depressed group ( < 0.01), but the difference in the anxious and normal group was not statistically significant ( > 0.05).

Conclusion: The results of the study showed a significant relationship between depression and oral health indices but not with anxiety. Therefore, the present study suggests that more attention should be paid to the oral health of people with a history of depression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474177PMC
May 2019

Comparison of Lipid Ratios to Identify Metabolic Syndrome.

Arch Iran Med 2018 12 1;21(12):572-577. Epub 2018 Dec 1.

Endorinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Background: The objective of this study was to compare various lipid ratios for detection of metabolic syndrome (MetS) in the Iranian general population.

Methods: This cross-sectional study involved 5677 subjects aged ≥18 years from the general population in Kerman, Iran. Associations between lipid ratio quartiles and MetS were analyzed using logistic regression models. The areas under receiver operating characteristic (ROC) was calculated to determine the accuracy of lipid ratios in predicting MetS.

Results: The adjusted chance of having MetS across quartiles of all lipid ratios had an increasing significant pattern (P < 0.0001). The area under the curves of triglyceride/high-density-lipoprotein-cholesterol (TG/HDL-C) ratio was 0.85 (95% CI = 0.84-0.87) in men and 0.85 (95% CI = 0.84-0.86) in women, of total cholesterol (TC)/HDL-C ratio was 0.79 (95% CI = 0.77-0.81) in men and 0.79 (95% CI = 0.77-0.81) in women and of low-density-lipoprotein cholesterol (LDL-C)/HDL-C ratio was 0.73 (95% CI = 0.71-0.75) in men and 0.74 (95% CI = 0.72-0.76) in women.

Conclusion: Our results indicate that the TG/HDL-C Ratio is a better marker than the LDL-C/HDL-C ratio and the TC/HDL-C ratio for identifying MetS in the Iranian population and could be used in clinical practice.
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December 2018

Effect of apelin on cardiac contractility in acute reno-vascular hypertension: The role of apelin receptor and kappa opioid receptor heterodimerization.

Iran J Basic Med Sci 2018 Dec;21(12):1305-1315

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Objectives: Apelin/APJ system plays an important role in the regulation of myocardial contractility (MC) and blood pressure. Opioid receptors (OPRs) are also important cardiovascular regulators and exert many of their effects through modulating the function of other systems. This study analyzed the interaction between APJ and kappa OPRs (KOR) in cardiac responsiveness to apelin in acute reno-vascular hypertension (2K1C).

Materials And Methods: MC studies were carried out on 2K1C rats. F13A (APJ blocker), Naloxone (OPR inhibitor), nor-Binaltorphiminedihydrochloride (nor-BNI; kappa OPR inhibitor), PTX (Gi path inhibitor) and chelerytrine (protein kinase C; PKC inhibitor) were administered prior to apelin 20 and 40 μg/kg. The phosphorylation of extracellular signal-regulated kinases (ERK1/2) (PERK) was also assessed. Dimerization of APJ and KOR was evaluated by immunoprecipitation.

Results: Both doses of apelin reduced blood pressure. Apelin 40 exerted a negative inotropic effect, which was inhibited by nor-BNI, but apelin 20 showed a positive inotropic effect, which was resistant to this inhibition. Hypertension increased heterodimerization of the APJ and KOR and this was reduced by apelin 20. F13A, naloxone and PTX significantly reduced PERK in apelin 40 group, but F13A, naloxone, and chelerytrine significantly increased PERK in the apelin 20 group.

Conclusion: The lowering effect of apelin 40 on MC and its non-effectiveness on APJ/KOR dimerization, while augmenting the contractility and reducing the dimerization by apelin 20 implies the APJ/KOR-related effects of apelin on the MC under acute reno-vascular hypertension. This may have potential clinical applications as apelin has been introduced as a potential therapeutic agent in heart failure and opioids are being currently used in the treatment of myocardial infarction.
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http://dx.doi.org/10.22038/IJBMS.2018.31361.7555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312676PMC
December 2018

Therapeutic effects of tamoxifen on metabolic parameters and cytokines modulation in rat model of postmenopausal diabetic cardiovascular dysfunction: Role of classic estrogen receptors.

Int Immunopharmacol 2018 Dec 11;65:190-198. Epub 2018 Oct 11.

Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

In postmenopausal women, the risk of diabetic cardiovascular disease drastically increases compared with that of premenopausal women. In the present study we surveyed the effects of Tamoxifen (TAM) and 17-β-estradiol (E2) on diabetic cardiovascular dysfunction. Female wistar rats were divided into six groups: sham-control, Diabetes, Ovariectomized (OVX) + Diabetes, OVX + Diabetes + Vehicle, OVX + Diabetes + E2, OVX + Diabetes + TAM. Type 2 diabetes was induced by High Fat Diet and low doses of STZ. E2 and TAM were administrated every four days for four weeks. Results show that, TAM or E2 reduces cardiac weight, atherogenic and cardiac risk indices. Mean arterial blood pressure (MABP) increased in diabetes group, while TAM and E2 prevented MABP increment. Also, fasting blood glucose was decreased by TAM and E2. Significant decrement in the level of IL-10 was observed in diabetes group and this effect was abolished by TAM and E2. Also, treatment with TAM and E2 resulted in improved inflammatory balance in favor of anti-inflammation. Although diabetes resulted in, increment of TC and LDL, TAM and E2 reduced lipids profile. Furthermore, treatment with TAM prevented the reduction of estrogen receptors (ERs) α and β protein levels, but its effect on the ERβ protein level was higher. Our results indicated that TAM protects against diabetic cardiovascular dysfunction and is a good candidate for E2 substitution.
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http://dx.doi.org/10.1016/j.intimp.2018.10.009DOI Listing
December 2018

The study of the serum level of IL-4, TGF-β, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension.

J Cell Biochem 2019 03 27;120(3):4147-4157. Epub 2018 Sep 27.

Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Background: Obesity increases the risk of diabetes mellitus (DM) and hypertension. We aimed to analyze the serum levels of cytokines that have relevance to the pathologies including, interleukin-4 (IL-4), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), and IL-6 cytokines of overweight men with DM and/or hypertension.

Methods: The study collected serum from 164 men. The sample population contained, 54 overweight men without DM or hypertension (control [CTL] group), 36 men with both DM and hypertension (DH group), 20 men with DM but no hypertension (D group), and 54 had hypertension without DM (H).

Results: The main results showed that the concentration of IFN-γ in the DH group was significantly higher than the D, H, and CTL groups, IL-6 in DH and D groups was significantly lower than the CTL group. The serum level of TGF-β and IL-4 cytokines did not show any significant differences across the four groups. Serum levels of IL-6 were also significantly lower in untreated patients in D group than controls and in DH when compared with H groups.

Conclusion: In conclusion, it appears that the proinflammatory and anti-inflammatory cytokines either play a significant role in the pathogenesis of hypertension and DM or serve as markers for these pathologies. Accordingly, increased serum levels of IFN-γ may participate in the pathogenesis of hypertension in the diabetic patients and decreased IL-6 is associated with type 2 DM.
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http://dx.doi.org/10.1002/jcb.27700DOI Listing
March 2019

Downregulation of IL-22 can be considered as a risk factor for onset of type 2 diabetes.

J Cell Biochem 2018 11 28;119(11):9254-9260. Epub 2018 Jun 28.

Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

There is some controversy as for the roles played by tumor growth factor-β (TGF-β), interleukin-1β (IL-1β), and IL-22 in the onset process of type 2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF-β, IL-1β, and IL-22 in the new cases and long period T2D patients as well as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D patients who have suffered from the disease more than 2 years (group 2), and 104 healthy controls have been selected from 6240 (3619 females) patients who were under study population from Kerman Coronary Artery Disease Risk Factor Study. Serum levels of TGF-β, IL-1β, and IL-22 have been evaluated using commercial kits. Serum levels of TGF-β and IL-1β significantly increased, while IL-22 decreased in 2 groups in comparison to healthy controls. Serum levels of IL-22, but not TGF-β and IL-1β, were significantly decreased in group 1 in comparison to healthy controls. There were no significant differences between groups 1 and 2 as for the cytokine levels. Serum levels of IL-22 increased in the females in group 2 when compared to females in group 1. It appears that TGF-β and IL-1β participate in the induction of inflammation after establishment of T2D, while decrease in IL-22 may be considered as a key factor for onset of the disease. Gender can also be considered as the main risk factor for variation in cytokine levels.
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http://dx.doi.org/10.1002/jcb.27194DOI Listing
November 2018

Prevalence of Multiple Coronary Artery Disease Risk Factors in Kerman: A Population-Based Study in Southeast Iran.

Iran J Med Sci 2018 Mar;43(2):140-149

Physiology Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology, Kerman University of Medical Sciences, Kerman, Iran.

Background: The risk of disease with 1 risk factor is increased by the presence of additional risk factors. The goal of this study was to assess the prevalence of multiple coronary artery disease (CAD) risk factors among adults in Kerman, Iran, to identify the population groups most at risk.

Methods: The present study included 5900 adults aged between 15 and 75 years in 2011 in Kerman, Iran. They were selected by 1-stage cluster sampling. Blood pressure, fasting blood glucose, lipids, and 6 CAD risk factors were assessed in the study population. Standardized prevalence rates were compared between the genders and age groups using the χ test. A P<0.05 was considered statistically significant. All the analyses were performed using Stata, version 14.1.

Results: Overall 93.1%, 57.8%, and 26.2% of the patients had at least 1, 2, and 3 risk factors, respectively. The most frequent combinations of risk factors were dyslipidemia plus low physical activity (37.9%), metabolic syndrome (27.7%), dyslipidemia plus abdominal obesity (14.1%), dyslipidemia plus hypertension (HTN) (10%), dyslipidemia plus smoking (8.6%), and HTN plus abdominal obesity (6.3%). The rate of diabetes mellitus plus HTN plus dyslipidemia was 2.8%. Both prevalence and multiplicity of the risk factors increased by age, and they were mostly higher in the women.

Conclusion: Almost 60% of the patients had at least 2 CAD risk factors and only 7% were risk-factor-free. Given that the population is ageing, community health authorities should seek to lessen the burden of these risk factors, almost all of which are preventable.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936845PMC
March 2018

miR-33 inhibition attenuates the effect of liver X receptor agonist T0901317 on expression of liver X receptor alpha in mice liver.

ARYA Atheroscler 2017 Nov;13(6):257-263

Professor, Physiology Research Center AND Department of Physiology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Background: microRNAs play pivotal roles in metabolism and other aspects of cell biology. microRNA-33 and liver X receptor (LXR) affect lipid metabolism and cholesterol trafficking. In this study, we evaluated effects of co-administration of miR-33 inhibitor and LXR activator on LXR-α and adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression in mice liver.

Methods: Twenty-four mice were randomly allocated into four groups (n = 6). Group 1 mice received standard chow diet without any treatment, group 2 received 30 mg/kg/48 hour LXR agonist (T0901317), group 3 received 1 mg/kg/48 hour in vivo locked nucleic acids (LNA) anti-miR-33 and group 4 received both T0901317 and in vivo LNA anti-miR-33. All treatments were administrated through intraperitoneal injection (IP). After 7 days and at the end of the study, mice were sacrificed, liver tissues were excised and blood samples were collected. LXR-α and ABCA1 genes and protein expression were quantified by real-time polymerase chain reaction (PCR) and western blotting, respectively.

Results: LXR activation caused LXR-α and ABCA1 mRNA (P < 0.050) and protein elevation as compared to control (P < 0.001). miR-33 inhibition attenuates T0901317 effect on LXR-α expression in group IV. Co-administration of T0901317 and anti-miR-33 remarkably elevated high-density lipoprotein cholesterol (HDL-C) levels, compared to control group (P = 0.001). Separate administration of T0901317 and anti-miR-33 also elevated HDL-C levels (P < 0.010).

Conclusion: Co-administration of T0901317 and anti-miR-33 can be considered as a good therapeutic alternative for atherosclerosis because miR-33 inhibition reduced lipogenic effects of LXR-α activator and also helps LXR-α agonist to increase reverse cholesterol transport (RCT) and also HDL-C as antiatherogenic effects.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889916PMC
November 2017

Mild aerobic training with blood flow restriction increases the hypertrophy index and MuSK in both slow and fast muscles of old rats: Role of PGC-1α.

Life Sci 2018 Jun 28;202:103-109. Epub 2018 Mar 28.

Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.

Aims: Existing evidence emphasize the role of mitochondrial dysfunction in sarcopenia which is revealed as loss of skeletal muscle mass and neuromuscular junction remodeling. We assessed the effect of low-intensity aerobic training along with blood flow restriction on muscle hypertrophy index, muscle-specific kinase (MuSK), a pivotal protein of the neuromuscular junction and Peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) in aged male rats.

Main Methods: Animals groups were control (CTL), sham (Sh), leg blood flow restriction (BFR), exercise (Ex), sham + exercise (Sh + Ex), and BFR plus exercise (BFR + Ex) groups. The exercise groups were trained with low intensity exercise for 10 weeks. 48 h after the last training session, animals were sacrificed under anesthesia. Soleus and EDL muscles were isolated, hypertrophy index was estimated and MuSK and PGC-1α were measured by western blot method.

Key Findings: Hypertrophy index enhanced in soleus and Extensor digitorum longus (EDL) muscles of BFR + Ex group (P < 0.01 versus CTL and Sh groups, and P < 0.001 versus other groups). The MuSK protein of soleus and EDL muscles increased in BFR + Ex group (P < 0.01 and P < 0.001, respectively) in comparison with CTL and Sh groups. In BFR + Ex group, the PGC-1α protein increased in both soleus and EDL (P < 0.001 compared to other groups). Also the PGC-1α of soleus muscle was higher in Ex and Sh + Ex groups versus CTL and Sh groups (P < 0.05).

Significance: Findings suggest that low endurance exercise plus BFR improves the MuSK and hypertrophy index of both slow and fast muscles of elderly rats probably through the rise of PGC-1α expression.
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http://dx.doi.org/10.1016/j.lfs.2018.03.051DOI Listing
June 2018

Expression of IGF-1, IL-27 and IL-35 Receptors in Adjuvant Induced Rheumatoid Arthritis Model.

Iran J Immunol 2018 Mar;15(1):14-27

Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Background: IGF-1 and certain other cytokines have been shown to exert inflammatory/anti-inflammatory roles in chronic joint diseases.

Objective: To assess the effect of IGF-1, IL-27 and IL-35, their interaction and their receptor expression in a rheumatoid arthritis model.

Methods: Freund's adjuvant-induced chronic joint inflammation was operated on 160 male rats. Animals were divided into histopathology and receptor expression groups, each composed of 10 subgroups including; control, vehicle, IGF-1, IL-27, IL-35, their antagonists, IGF-1+IL-27 antagonist and IGF-1+IL-35 antagonist. After two weeks, vehicle or agonist/antagonists were injected into the joint space every other day until day 28 where joint histopathology was performed. The expression of IGF-1, IL-27 and IL-35 receptors were assessed by western blot analysis.

Results: IGF-1 did not show pro- or anti- inflammatory functions; endogenous IL-27 and IL-35, on the other hand, exerted inflammatory effects. IL-27 and IL-35 antagonists exerted the highest anti-inflammatory effects. The total inflammation scores were 0.55 ± 0.06, 4.63 ± 0.40, 3.63 ± 0.60, 2.50 ± 0.38 and 1.63 ± 0.40 regarding control, vehicle, IGF-1 Ant., IL-27 Ant. and IL-35 Ant., respectively. IGF-1 receptor expression was reduced in chronic joint inflammation and all three antagonists augmented the IGF-1 receptor expression. IL-27 and IL-35 receptors were up-regulated by chronic joint inflammation.

Conclusion: Overall, the results demonstrated the pro-inflammatory role of endogenous IL-27 and IL-35 along with the over expression of their receptors in chronic joint inflammation. IL-27 and IL-35 antagonists exerted the most anti-inflammatory effects and increased IGF-1 receptor expression. These two antagonists may be potential agents for new treatment strategies in chronic joint inflammatory diseases.
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http://dx.doi.org/IJIv15i1A2DOI Listing
March 2018

The relationship between food insecurity with cardiovascular risk markers and metabolic syndrome components in patients with diabetes: A population-based study from Kerman coronary artery disease risk study.

J Res Med Sci 2017 31;22:118. Epub 2017 Oct 31.

Department of Nutrition, Nutrition and Food Security Research Center, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background: We sought the prevalence of food insecurity and whether cardiovascular risk markers and metabolic syndrome components are significantly different in categories of food insecurity in patients with type 2 diabetes.

Materials And Methods: In this cross-sectional study, 520 patients with type 2 diabetes from the Kerman coronary artery disease risk study aged between 23 and 87 years (60.8 ± 11.4) who selected by one-stage cluster sampling were assigned into four groups of "food secure" and "mild," "moderate," and "severe" food insecure. Household food insecurity was assessed by a 9-item household food insecurity access scale questionnaire.

Results: The prevalence of food security and mild, moderate, and severe food insecurity in patients with diabetes was 24.4%, 33.1%, 28.9%, and 13.6%, respectively. There was a significant difference among the food-secure/insecure sex groups ( = 0.001). The prevalence of food insecurity and risk factors such as total cholesterol, high low-density lipoprotein cholesterol, and visceral obesity in mild food-insecure females was significantly higher than males ( < 0.001, 0.001, and 0.001, respectively). The fasting blood sugar significantly increased ( = 0.020) in diabetic females with food security than the other female groups. Diastolic blood pressure significantly increased ( = 0.028) in diabetic females with severe food insecurity than the other female groups. The glycosylated hemoglobin significantly increased ( = 0.013) in diabetic males with severe food insecurity than the other male groups. Food insecurity odds ratio in females was 1.74 (95% confidence interval [CI]: 1.10-2.70), 2.39 (95% CI: 1.48-3.88), and 2.73 (95% CI: 1.49-5.01) times higher than in males for mild, moderate, and severe food insecurity, respectively.

Conclusion: Food insecurity may deteriorate some cardiometabolic biomarkers in type 2 diabetes. Improving food security in patients with diabetes may help reduce cardiovascular disease.
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http://dx.doi.org/10.4103/jrms.JRMS_12_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680660PMC
October 2017

Long-term Low-Intensity Endurance Exercise along with Blood-Flow Restriction Improves Muscle Mass and Neuromuscular Junction Compartments in Old Rats.

Iran J Med Sci 2017 Nov;42(6):569-576

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Science, Kerman, Iran.

Background: During the aging process, muscle atrophy and neuromuscular junction remodeling are inevitable. The present study aimed to clarify whether low-intensity aerobic exercise along with limb blood-flow restriction (BFR) could improve aging-induced muscle atrophy and nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.

Methods: Forty-eight male Wistar rats, aged 23-24 months, were randomly divided into control, sham (Sh: subjected to surgery without BFR), BFR (subjected to BFR), exercise (Ex: subjected to 10 weeks of low-intensity exercise), Sh+Ex, and BFR+Ex groups. Forty-eight hours after the last training session, the animals were sacrificed and their soleus and extensor digitorum longus (EDL) muscles were removed. The hypertrophy index was calculated, and molecular parameters were measured using western blotting. Statistical analysis was done with ANOVA using SPSS (version 20), with a P<0.05 as the level of significance.

Results: The control and Sh groups showed weight gain (P=0.001), whereas the Ex, Sh+Ex, and BFR+Ex groups had significant weight loss (P<0.001). The hypertrophy index of the soleus was significantly higher in the BFR+Ex group than in the control, Sh, and BFR groups (P<0.001). BFR+Ex induced significant hypertrophic effects on the EDL (P<0.001 vs. the control, Sh, Ex, and Sh+Ex groups, and P=0.006 vs. the BFR group). BFR+Ex also increased nAChRs in the soleus (P=0.02 vs. the control and Sh groups) and the EDL (P=0.008 vs. the control and Sh groups).

Conclusion: BFR plus mild exercise is a safe method with potential beneficial effects in protecting and augmenting muscle mass and nAChR clustering at the neuromuscular junction in old rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684378PMC
November 2017

Heterodimerization of apelin and opioid receptors and cardiac inotropic and lusitropic effects of apelin in 2K1C hypertension: Role of pERK1/2 and PKC.

Life Sci 2017 Dec 4;191:24-33. Epub 2017 Oct 4.

Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Aims: Kappa Opioid receptors (KORs) change the impact of apelin on the phosphorylated ERK1/2 (pERK1/2). However, the role of interaction between KOR and apelin receptors (APJ) on the cardiac contractility effects of apelin and in regulation of pERK1/2 and PKC in the heart of renovascular hypertensive (2K1C) rats is unknown.

Main Methods: Hemodynamic factors, the heterodimerization of KOR and APJ, the expression of KOR mRNA and protein and pERK1/2 in the left ventricle of 2K1C rats were measured following APJ, KOR, PKC and Gi path inhibition by F13A, nor-BNI, chelerythrine and PTX respectively.

Key Findings: Apelin in 40 and 60μg/kg doses increased cardiac contractility, and reduced mean arterial pressure. The cardiac impacts in both doses were reduced by F13A, nor-BNI and chelerytrine and blocked by PTX. Hypertension increased the expression of KORs and heterodimerization of APJ and KOR, and reduced pERK1/2 in the left ventricle. Apelin, in both doses reduced (normalized) heterodimerization and recovered the reduction in pERK1/2. The recovery of ERK1/2 phosphorylation was accompanied by reduction of KOR and APJ heterodimerization.

Significance: 2K1C hypertension increased the expression of KORs and heterodimerization of APJ and KORs. The heterodimerization was associated by reduction of ERK phosphorylation and altered the cardiac inotropic and lusitropic effects of apelin. These changes may participate in pathophysiology of cardiac dysfunction in renovascular hypertension that is associated with subnormal level of serum apelin. Apelin- induced recovery of ERK1/2 phosphorylation and KOR-APJ dimerization may nominate apelin as a therapeutic goal in treatment of this kind of hypertension.
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http://dx.doi.org/10.1016/j.lfs.2017.09.044DOI Listing
December 2017

Opioid receptors mediate inotropic and depressor effects of apelin in rats with 2K1C-induced chronic renovascular hypertension.

Clin Exp Pharmacol Physiol 2018 02 28;45(2):187-197. Epub 2017 Nov 28.

Physiology Research Center, Institute of Neuropharmacology and Department of Physiology and pharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Apelin receptors (APJ) cross-talk with other G-protein-coupled receptors. However, the role of APJ interaction with opioid receptors (OPR) on the cardiovascular effects of apelin in hypertension is not clear. Renovascular hypertension was induced by placing a Plexiglas clip on the left kidney of rats. After 16 weeks, F13A (an APJ antagonist), naloxone (a general OPR inhibitor), and nor-binaltorphimine dihydrochloride (nor-BNI; a selective inhibitor of KOR) were given prior to injections of apelin at doses of 40 and 60 μg/kg. The arterial systolic/diastolic blood pressure and left ventricular contractility responses were then evaluated. The arterial systolic/diastolic blood pressure in sham and 2K1C rats was 110/71 mm Hg and 171/124 mm Hg, respectively. The hypotensive effects of apelin at both doses were inhibited by F13A and naloxone. Nor-BNI completely inhibited the effects of apelin 40 on arterial pressure, and decreased the effects of 60 μg/kg. KOR inhibition also prevented the compensation for the decrease in the left ventricle +dp/dt max and -dp/dt max caused by apelin 60. The simultaneous inhibition of OPR and APJ reduced arterial pressure and increased cardiac contractility. Findings showed that the OPR, particularly KOR, mediate the inotropic, lusitropic, and depressor effects of apelin. The interaction of the OPR and APJ augments the inotropic and vasodepressor effects of apelin. This interaction may have potential clinical applications in cardiac failure since opioids are currently used in the treatment of myocardial infarction and stroke, and apelin has been introduced as a potential therapeutic agent in cardiovascular complications.
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http://dx.doi.org/10.1111/1440-1681.12860DOI Listing
February 2018

Association between Tooth Loss and Opium Addiction: Results of a Community-Based Study on 5900 Adult Individuals in South East of Iran in 2015.

J Int Soc Prev Community Dent 2017 Jul-Aug;7(4):186-190. Epub 2017 Jul 31.

Kerman Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Background: Like any other drug abuse, opium use is known to have detrimental effects on oral health. Oral hygiene neglect in opium users can lead to tooth loss resulting in further functional, esthetic, and dieting problems. Therefore, the aim of this study was to assess the association between tooth loss and opium addiction in a large-scale population.

Materials And Methods: This study was part of an extensive study related to the risk factors of cardiovascular disease and conducted by the center for physiological research during 2012-2015 in Kerman. A total of 5900, 15-75-year-old individuals, were recruited by a single-stage random cluster sampling method. Factors including opium and smoking consumption, factors related to oral health, hygiene, and the number of missing teeth were examined. Data were collected through questionnaires, interviews, and physical examination.

Results: Of 5900 individuals, 2662 (45.1%) were men and the rest were women, which 1011 individuals (17.1%) consumed opium. The prevalence of opium abuse was significantly higher in men. Regarding the oral dental indicators, the numbers of missing teeth ( < 0.001), decayed ( = 0.01), and the total index of decayed, missing, and filled teeth ( < 0.001) were significantly higher in addicts as compared to nonaddicts. The gingival index and community periodontal index scores were significantly lower in addicts. Addicted women had a higher prevalence of tooth loss.

Conclusions: Opium addiction is associated with higher tooth loss, especially, in women opium users. Dental practitioners and health politicians should pay special attention to the oral health of addicts before tooth loss occurs.
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http://dx.doi.org/10.4103/jispcd.JISPCD_189_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558252PMC
July 2017

Comparing indices of median nerve among diabetic patients with or without metabolic syndrome.

Diabetes Metab Syndr 2017 Dec 18;11 Suppl 2:S669-S673. Epub 2017 May 18.

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Background: Metabolic syndrome is highly prevalent among patients with type II diabetes and is reported as a strong risk factor for cardiovascular diseases as well as carpal tunnel syndrome (CTS). The aim of the current study was to compare median nerve indices among diabetic patients with and without metabolic syndrome.

Methods: This cross-sectional study was conducted on 105 patients with type II diabetes whom participated in the coronary artery disease risk factor study in Kerman, Iran (KERCARDS). Patients with type II diabetes were called and those with clinical symptoms of CTS were included in the study, and median nerve indices were measured according to standard electro diagnosis tests. GEE statistical model was used to compare median nerve indices among diabetic patients with and without metabolic syndrome. All statistical analysis was done using SPSS 20.0.

Results: The mean age of participants was 57.57±9.53. There was no significant difference between the left and right hand regarding median nerve indices except median nerve motor amplitude (MA). Furthermore, components of metabolic syndrome including BMI and LDL were determined as risk factors for CTS according to several indices.

Conclusion: Components of metabolic syndrome had more influence on sensory indices than motor indices and primary control of these components might prevent dysfunction of sensory neurons and also motor neurons in advanced stages among diabetic patients.
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http://dx.doi.org/10.1016/j.dsx.2017.04.023DOI Listing
December 2017