Neural and Local Regulation of Blood Flow and Synovial Fluid PO2 in the Rabbit Knee Joint

Synovial fluid, in addition to its lubricating action of moving structures, provides nutrients to avascular structures such as articular cartilage (McKibbin & Maroudas, 1979), and also to the knee ligaments (Renzoni et aL, 1984), within the joint. As synovial fluid formation is critically dependent on synovial blood flow (Levick, 1987), those factors which regulate flow in the synovial vascular bed are clearly important in this process. The first objective of this research was to measure knee joint blood flow quantitatively and also assess the effect of sympathetic nerves in the regulation of joint blood flow. Secondly, to investigate and characterize the type of adrenoceptors mediating the sympathetic control of joint blood flow, and other mediators involved in nerve mediated changes in articular blood flow. Thirdly, to assess the possible role of the endothelium in regulation of joint blood flow and modulation of sympathetic nerve-mediated changes in joint blood flow. Finally to perform all the mentioned procedures in an experimentally induced acutely inflamed knee joints to determine the effect of inflammation on these regulatory mechanisms and factors. The second objective of this study was to measure, in both normal and inflamed knee joints, the synovial PO2 directly in its place; and also assess the correlation between the joint blood flow and oxygen tension in the synovial fluid and the extent to which this correlation may be affected by the process of inflammation. Experiments were performed on rabbits. Acute inflammation was induced by intra-articular injection of carrageenan. Quantitative measurement of joint blood flow was conducted by the radiolabelled microsphere technique. Relative changes in blood flow were assessed by laser Doppler flowmetry, and a polarographic oxygen elecrode (and oxygen meter) was used to measure synovial PO2 and its changes during the course of experiments. The results of this investigation indicate that: 1). The microsphere technique and laser Doppler flowmetry are suitable methods for quantitative and continuous measurement of joint blood flow respectively, and the process of inflammation increases joint blood flow significantly. Despite this increase in blood flow, synovial PO2 which in normal joint is much lower than the arterial PO2, even decreases more in the inflamed joints. 2). Sympathetic nerves innervate the blood vessels of the posterior capsule of the knee joint and play an important role in regulation of joint blood flow. alpha2 adrenoceptors predominate in this vascular bed and mediate vasoconstrictor responses to nerve stimulation. No evidence of pimergic co-transmission was obtained. The process of inflammation reduced the effectiveness of sympathetic nervous system in regulation of joint blood flow. 3). Nerve-mediated vasodilator responses appeared to have two components, a beta-adrenoceptor component which is mediated by postjunctional beta1 adrenoceptors which found to predominate in this vascular bed, and a substance P mediated component which is produced by the release of neuropeptide, substance P, presumably from the unmyelinated sensory nerve endings. 4). Vascular endothelium keeps the joint blood vessels of both normal and inflamed joints in a state of active dilatation by release of nitric oxide (NO) and therefore plays a major role in local regulation of joint blood flow. NO also counteracts the sympathetic vasoconstrictor responses, but it showed no modulatory effect on nerve-mediated vasodilator responses. 5). Prostaglandins are important local factors in regulation of joint blood flow in both normal and inflamed joints. They seemed to have no modulatory effect on sympathetic regulation of blood flow to this vascular bed. PGE2 receptors are present on knee joint blood vessels but they down regulate during the process of inflammation. 6). A polarographic oxygen electrode provided a new and suitable method for quantitative and continuous measurement of oxygen partial pressure in the synovial fluid of both normal and inflamed knee joints. A high correlation between changes in joint blood flow and synovial PO2 was found in both joints

Inadequate control of diabetes and metabolic indices among diabetic patients: A population based study from the Kerman Coronary Artery Disease Risk Study (KERCADRS)

Background: The goal of diabetes control should be feasible in order to minimize the risk of its adverse events and to reduce its burden and cost on patients. The current study aimed to assess the status of glycemic control in male and female patients with Type 2 Diabetes Mellitus (T2DM) in Kerman, Iran. Methods: In the present study, 500 T2DM (300 women and 200 men) from the Kerman Coronary Artery Disease Risk Study (KERCADRS), a population-based study from 2009 to 2011, were selected. Patients were >18 years old, had Fasting Blood Sugar (FBS) higher than 126 mg/dl, and had been through treatment for their diagnosed disease. All participants underwent Glycosylated Hemoglobin (HbA1c) analysis. HbA1c less than 7% was considered as good glucose control. Other metabolic indices based on American Diabetes Association (ADA) target recommendations were considered. Results: The mean level of HbA1c in total subjects was 8.56 ± 4.72% that only 31.66% of men and 26.00% of women had controlled level of HbA1c. Total cholesterol less than 200 mg/dl was reported in 64.50% of men and 44.00% of women, High Density Lipoprotein (HDL) more than 40 mg/dl was revealed in 20.50% of men and 34.67% of women, and Low Density Lipoprotein (LDL) less than 100 mg/dl was reported in 41.50% of men and 25.33% of women. In multivariate logistic regression model, longer duration of disease and higher Waist Circumference (WC) were positively associated with uncontrolled diabetes status. Conclusion: The findings of the present study revealed that diabetes control in T2DM was inadequate. Changing the policy of treatment in individual patient and establishing better diabetes clinic to decrease the frequency of uncontrolled T2DM are crucial. Paying attention to other affecting metabolic components such as WC in the process of T2DM management is important

The effect of opium addiction on serum adiponectin and leptin levels in male subjects

Serum adiponectin and leptin levels have been shown to be related to obesity, insulin resistance and cardiovascular diseases (CVD). Opium addiction has a positive association with endocrine system disorders. The relationship between adipokines and opium addiction is unclear. In the present study, we aimed to determine serum adiponectin and leptin levels in opium addicted subjects. Methods: 176 men, 88 opium addicts and 88 non-addicts were randomly selected from subjects who participated in Kerman Coronary Artery Disease Risk factors Study (KERCADRS); a population-based study. Serum adiponectin and leptin levels were measured using ELISA and compared between two groups. We adjusted the effect of some confounding factors such as the patients’ demographic, clinical and medical history in multivariate analysis model. Results: The serum level of adiponectin in opium addicts was significantly lower than control group (6.5±3.6 vs. 9.8±8.1 μg/ml, P<0.001). There was no significant difference in serum leptin level between two groups (11.8±10.3 ng/ml in control group vs. 11.5±10.8 ng/ml in opium addicts, p = 0.80). In the multivariate analysis, after adjusting for age, cigarette smoking, body mass index, type 2 diabetes, hypertension, cholesterol, triglyceride and high and low density lipoproteins, the negative association between opium addiction and decreased adiponectin level was still present (β = -0.144, P value = 0.005). Conclusions: The results showed that opium addiction reduces serum adiponectin level. Since adiponectin has been shown to have anti-diabetic and anti-atherogenic effects, its reduction may account for increase in the risk of metabolic disorders such as insulin resistance and CVD amongst opium addicted patients

Ameliorative effect of black tea on nicotine induced cardiovascular pathogenesis in rat

Regarding the role of nicotine in the development of cardiovascular complications of smoking, we investigated whether black tea has a modulatory effect on cardiovascular pathogenesis of nicotine in rat. Animals were randomized to control, tea, nicotine and tea plus nicotine groups. Test groups received black tea brewed (adding 400 ml boiling water to 10 g Lipton black tea for 5 min) orally alone or with nicotine 2 mg/kg/day, s.c. separately or combined for four weeks. On 28th day, lipids profile of blood and also malondialdehyde (MDA) level, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) of heart tissue were measured. Nicotine administration caused a significant increase in total cholesterol, TG and HDL-C and also atherogenic index of plasma (log TG/HDL-C). Moreover, nicotine increased MDA level of heart. Black tea alone increased the antioxidant capacity of heart tissue without significant effect on lipid profile and MDA levels. Concomitant use of black tea and nicotine significantly attenuated the hyperlipidemic and atherogenic effects of nicotine but was unable to attenuate the MDA. Our findings suggest that black tea consumption reduces hyperlipidemia and atherogenesis as two cardiovascular risk factors and complications of nicotine, in rat. If these results can be extrapolated to human, smokers who daily drink black tea may be less at risk of cardiovascular disease

SIRT1 and Klotho expression in the heart and kidneys of rats with acute and chronic renovascular hypertension

Aim To evaluate Klotho and SIRT1 expression in the heart and kidneys of rats with acute and chronic renovascular hypertension. Methods Four and sixteen weeks after the induction of renovascular hypertension by clipping the left renal artery, systemic blood pressure, serum angiotensin II level, and the expression of Klotho and SIRT1 proteins and oxidative stress indices in the heart and kidneys were assessed. Results SIRT1 level was significantly reduced in the ischemic (left) kidney in acute and chronic phases of hypertension. In the heart, it decreased in the acute phase, but increased in the chronic phase. Klotho levels in the heart and kidneys did not change significantly in either hypertension phase. Superoxide dismutase (SOD) activity in the heart significantly decreased, and SOD, total antioxidant capacity, and malondialdehyde in the ischemic kidney significantly increased during the development of hypertension. Serum angiotensin II level significantly increased in the acute phase of hypertension. Conclusion Development of renovascular hypertension was associated with a reduction of SIRT1 expression in the heart and ischemic kidney. As angiotensin II and SIRT1 counteract each other’s expression, a SIRT1 reduction in the heart and kidney, along with the influence of systemic/ local angiotensin II, seems to be partly responsible for hypertension development. A combination of SIRT1 agonists and angiotensin II antagonists may be considered for use in the treatment of renovascular hypertension

Potential Effect of Opium Consumption on Controlling Diabetes and Some Cardiovascular Risk Factors in Diabetic Patients

Background: Due to this belief that opium may have beneficial effects on diabetes or cardiovascular risk factors, the present study aimed to assess the potential and possible effects of opium consumption on diabetes control and some cardiovascular risk factors in diabetic patients. Methods: This study enrolled 374 diabetic subjects from diabetes care centers in Kerman, Iran including opium user group (n = 179) and a non opium user group (n = 195). The data were collected through a questionnaire completed by interviewing, physical examination and laboratory assessment. Findings: Opium did not show any statistically significant effect on blood glucose, glycated hemoglobin (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL) and diastolic blood pressure. However, systolic blood pressure and prevalence of high systolic blood pressure were significantly higher in opium user group (P < 0.050). In addition, lower serum high-density lipoprotein (HDL) and frequency of lower HDL was significantly higher in opium user group (P < 0.001). Conclusion: According to this study, opium does not seem to have beneficial effects on diabetes control or cardiovascular risk factors. Therefore, it would not be advisable to consume opium as an anti-diabetes or cardioprotective agent

Modulatory effect of semelil (ANGIPARS™) on isoproterenol induced cardiac injury

Administration of semelil (ANGIPARS™) has been successful in the treatment of diabetic foot ulcer. Considering the improvement of blood flow and anti-inflammatory effect that are attributed to this drug, we investigated its effect on cardiovascular performance in rabbits with isoproterenol (ISO) induced myocardial injury. Animal groups included: control group; ISO group, received ISO 50 mg/kg s.c. for two consecutive days; S1+ISO, S5+ISO and S10+ISO groups, received semelil 1, 5, and 10 mg/kg/day i.p. respectively, 30 min before ISO. On the 3rd day, electrocardiogram (ECG) and hemodynamic parameters were recorded; blood samples were taken and hearts were removed for lab investigations. ISO induced heart injury, ECG disturbance, raise of cardiac troponin I and significant decrease in LVSP (p<0.05), +dp/dt max (p<0.01), -dp/dt max (p<0.05) along with increase of LVEDP (p<0.01). Semelil had no significant effects on ECG and plasma cardiac troponin I. Impairment of +dp/dt max and -dp/dt max was significantly improved in S5+ISO and S10+ISO groups (P<0.05 versus ISO). In addition, LVSP and LVEDP was somewhat recovered in these groups, although semelil (1 mg/kg/day) to some extent exacerbated the myocardial lesions induced by ISO (P<0.05). Therefore, in stressful conditions, semelil may improve myocardial contractility; however, it may aggravate the severity of injury

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

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 level

Oral Health Determinants among Opium Users in Kerman, Iran

Background: Promoting oral health is a complicated issue among drug abusers and opium is the most frequent drug abused in Iran. This study aims to find the oral health determinants of opium users in Kerman, Iran.Methods: This cross-sectional study was a part of the second phase of Kerman coronary artery disease risk factors study (KERCADRS, 2014-2018). In this survey, the data of 1140 opium users were analyzed. The information about using a toothbrush, dental floss, number of dental visits at last year, age of first use of opium, duration, and opium consumption frequency was recorded. The total number of decayed, missing, and filled teeth (DMFT) index and Community Periodontal Index (CPI) was recorded by an oral examination. Poisson and logistic regressions analyses were used for assessing the relationship among variables.Findings: The mean age of participants was 52 ± 12 years. 74.4% were men and 24.6% were women. The average DMFT index was 15.7 ± 7.6 and the prevalence of a healthy CPI score was 18.5%. Educational level (P < 0.001), brushing (P < 0.001), flossing (P < 0.001), dental visit (P < 0.001), first age of using opium (P < 0.001), frequency of consumption (P < 0.001), and age (P < 0.001) were associated with DMFT index. Only using floss (P < 0.001), dental visit [odds ratio (OR) = 1.80, P = 0.030], frequency of consumption (OR = 2.92, P < 0.001), and age (P = 0.001) were associated with CPI score.Conclusion: The frequency of opium consumption has the same effect on caries incidence as oral hygiene habits. Moreover, using dental floss has a more significant effect on the periodontal health of participants