Effects of exercise training on excitation-contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats.

Although, several novel forms of intervention aiming at newly identified therapeutic targets are currently being developed for diabetes mellitus (DM), it is well established that physical exercise continues to be one of the most valuable forms of non-pharmacological therapy. The aim of the study was to investigate the effects of exercise training on excitation-contraction coupling and related gene expression in the Goto-Kakizaki (GK) type 2 diabetic rat heart and whether exercise is able to reverse diabetes-induced changes in excitation-contraction coupling and gene expression. Experiments were performed in GK and control rats aged 10-11 months following 2-3 months of treadmill exercise training. Shortening, [Ca(2+)]i and L-type Ca(2+) current were measured in ventricular myocytes with video edge detection, fluorescence photometry and whole cell patch clamp techniques, respectively. Expression of mRNA was assessed in ventricular muscle with real-time RT-PCR. Amplitude of shortening, Ca(2+) transients and L-type Ca(2+) current were not significantly altered in ventricular myocytes from GK sedentary compared to control sedentary rats or by exercise training. Expression of mRNA encoding Tpm2, Gja4, Atp1b1, Cacna1g, Cacnb2, Hcn2, Kcna3 and Kcne1 were up-regulated and Gja1, Kcnj2 and Kcnk3 were down-regulated in hearts of sedentary GK rats compared to sedentary controls. Gja1, Cav3 and Kcnk3 were up-regulated and Hcn2 was down-regulated in hearts of exercise trained GK compared to sedentary GK controls. Ventricular myocyte shortening and Ca(2+) transport were generally well preserved despite alterations in the profile of expression of mRNA encoding a variety of cardiac muscle proteins in the adult exercise trained GK diabetic rat heart.

Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle. The amplitude of ventricular myocyte shortening and the intracellular Ca(2+) transient were unaltered; however, the time-to-peak shortening was prolonged and time-to-half decay of the Ca(2+) transient was shortened in GK myocytes compared with control myocytes. The results of this study demonstrate changes in expression of genes encoding various excitation-contraction coupling proteins that are associated with disturbances in myocyte shortening and intracellular Ca(2+) transport.

Effects of pioglitazone on ventricular myocyte shortening and Ca(2+) transport in the Goto-Kakizaki type 2 diabetic rat.

Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca(2+) current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 microM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 microM PIO reduced the amplitude of the Ca(2+) transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca(2+) release from the sarcoplasmic reticulum and recovery of Ca(2+) transients following application of caffeine and myofilament sensitivity to Ca(2+) were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca(2+) current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca(2+) transient however, the mechanisms remain to be resolved.

Infectious diseases among food handlers.

trichiura was the most common infection in the studied group. Continuous follow up and health education of food handlers have led to avoidance of outbreaks of infections among food consumers in the hospital. This study was carried out to find the prevalence and associated factors of communicable diseases especially parasitic infections among food handlers in King Fahd Hospital, Jeddah, Saudi Arabia, for early detection and proper management. This study was conducted as a preemployment examination on 52 new kitchen male workers with a mean age of 26.77+/-5.03 years. They were subjected to complete medical examination as well as some general and specific laboratory investigations as a food handler. Results of throat swab showed that 12% of the studied group were positive for group A beta haemolytic streptococci. Parasitological examination showed that seven subjects (13.5%) were infected. Out of them 3 only had single parasitic infections and 4 had double infections. Trichuris trichiura was the most common infection in the studied group. Continuous follow up and health education of food handlers have led to avoidance of outbreaks of infections among food consumers in the hospital.

Epidemiology of anemia among attendants of primary health care, Jeddah.

This study was carried out to find the prevalence of anemia, as well as associated factors in the studied group. The material of this study included all reports of diseases that were sent from all PHC, Jeddah city, to the Health Information Systems Unit at the Directorate of PHC, Jeddah during the year of 1415 Hegrian. Data about anemia were collected and analyzed. Results of the study showed that the prevalence of anemia was found to be 1.82% in the studied group, among Saudi population it was found to be 1.84%. The prevalence of anemia among females was found to be 2.39% which was significantly higher than that among males (1.25%). Also, the prevalence of anemia was found to be significantly higher among different age groups compared to those aged 1-4 years. The prevalence of anemia was found also to be affected by geographic distribution of the population.

An outbreak of hepatitis A associated with treated waste water used for irrigation.

Hepatitis A virus (HAV) infection is endemic in developing countries and remains a public health problem elsewhere. This study was conducted to investigate an outbreak of HAV infection, which occurred during a period of almost 5 months (January-May 1996) in the National Guard Iskan (Housing Authority) in Jeddah, Saudi Arabia. Ninety four cases were found to be positive for IgM antibody to HAV. A case control study was done to identify possible risk factors. For every case, 3 controls have been selected from the same household matched for age and sex. Information about reported cases was obtained by attending physicians through an interview questionnaire from adult cases and parents of young cases and controls (<12 y). It included questions regarding symptoms, demographics and possible source of the infection. Results showed that the attack rate of the whole population was 1.03 %, while that for children <10 years was twofold higher (2.05 %) than the total population. The risk of acquiring infection among them was found to be five times that among those aged 40 years and higher (R.R=5.32). There was a lack of association between developing hepatitis A and any of the food items or milk used in the studied area during the time of the outbreak. On the other hand exposure to irrigation water among cases was found to be significantly higher than among controls especially among children below 10 years (O.R=2.26). Analysis of the available data suggests a strong association between illness and exposure to waste water used for irrigation of gardens through playing with it, or through occasional drinking especially among children below 10 years. The prolonged course of the outbreak (5 months) may be attributed to subsequent person to person transmission from index cases to intimate contacts especially among the same household.

Saudi Arabia experience trial of fluvastatin (Lescol) in the treatment of hyperlipidemia.

This study was carried out to assess the efficacy, safety and tolerability of fluvastatin as monotherapy in the treatment of primary hypercholesterolemia. This multicenter study started with 467 patients but only 315 subjects completed 12 weeks treatment. Patients followed a standard lipid-lowering diet for 3 weeks before entering and throughout the study. Every patient received fluvastatin 20 mg once daily with the evening meal for the first 6 weeks, from week 7 to week 12 the daily dose was changed to one capsule 40 mg daily in the evening. Results showed that the mean percent changes in lipid parameters between baseline and endpoint was as follows: LDL-C (-32.7%); total cholesterol (-29.42%), triglycerides (-19.7%) and HDL-C (16.6%). Meanwhile, the mean percent increase in liver enzymes between baseline and endpoint was 17.2% for ASAT and 20.3% for ALAT, respectively, but the mean values of both enzymes at the endpoint were within normal range. The most frequent side effects being gastrointestinal (4.3%) including dyspepsia, nausea, flatulence and diarrhea. In conclusion, fluvastatin as monotherapy in the treatment of hypercholesterolemia among Saudis was found to be safe, well tolerated and produced a significant improvement in the overall lipid parameters.

The effects of a training program on knowledge, attitude and practice of the staff of primary health care centers towards growth monitoring: an intervention study.

This study was carried out aiming at assessing the effects of a training program on the knowledge, attitude and practices (KAP) of health care workers (HCWs) in primary health care centers (PHCCs) regarding growth monitoring (GM). It included 148 health care workers (30 General Practitioners (GPs) and 118 nurses), from 17 PHCCs in Jeddah city, Kingdom of Saudi Arabia (KSA). Tests on KAP were held before and six months following a training program on GM conducted by the investigators. Results showed significant improvements in the KAP of the trained health care workers after training, the 44 trained HCWs obtained higher mean comprehension score (7.9 +/- 1.2), higher mean practice score (11.6 +/- 3.0), and higher mean general scores (32.3 +/- 4.6) compared to the mean scores they obtained in the pre-test (5.7 +/- 1.5; 7.4 +/- 2.2 and 25.7 +/- 4.4, respectively). These differences were statistically significant (P < 0.001). However; the difference in the mean knowledge scores, before and after the GM training program was not significant. The training has also led to the disappearance of the significant knowledge gap between GPs and nurses. And also, the 44 trained HCWs had higher mean comprehension score (7.9 +/- 1.2), mean practice score (11.6 +/- 3.0), and mean general scores (32.3 +/- 4.6) compared to those among untrained group (controls) (6.3 +/- 2.1; 8.5 +/- 3.7, and 27 +/- 6.1, respectively). These differences were statistically significant (P < 0.0005). Nevertheless, the difference in the mean knowledge scores, between the two groups, was not statistically significant. It also has led to some changes in the attitude of the trained HCWs towards GM compared to the untrained group. In conclusion, We credit the significant improvements in KAP of HCWs to the training program and recommend its adoption by the national MCH program in KSA. We also recommend new methods of teaching and training based on sound educational concept of active participation and practical work as well as supportive supervision and evaluation.

Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase.

This study aimed at comparing the effects of atorvastatin and vitamin E on erectile dysfunction in patients initially irresponsive to sildenafil, with investigation into the underlying possible mechanisms. Sixty patients were randomly divided into three groups: the atorvastatin group received 80 mg daily, the vitamin E group received 400 IU daily and the control group received placebo capsules. Patients were examined both before and after 6 weeks of treatment for biochemical tests; Superoxide dismutase (SOD), glutathione peroxidase (GPO), C-reactive protein (CRP), interleukin-6 (IL-6), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) and for erectile function tests; International index of erectile function (IIEF-5) scores and Rigiscan. Both atorvastatin and vitamin E showed a statistically significant GPO increase (P<0.05) and a statistically significant IL-6 decrease (P<0.05). Only atorvastatin showed a statistically significant increase in NO (15.19%, P<0.05), eNOS (20.58%, P<0.01), IIEF-5 score (53.1%, P<0.001) and Rigiscan rigidity parameters (P<0.01), in addition to a statistically significant decrease in CRP (57.9%, P<0.01). However, SOD showed a statistically significant increase only after vitamin E intake (23.1%, P<0.05). Both atorvatstain and vitamin E had antioxidant and anti-inflammatory activities. Although activating eNOS by atorvastatin was the real difference, and expected to be the main mechanism for NO increase and for improving erectile dysfunction. Atorvastatin, but not vitamin E, is a promising drug for sildenafil nonresponders.

The direct effects of streptozotocin and alloxan on contractile function in rat heart.

Streptozotocin (STZ) and alloxan (ALX) are widely used to induce diabetes mellitus in experimental animals. The direct effects of STZ and ALX on the amplitude and time course of ventricular myocyte shortening and on cardiac action potentials were investigated. STZ and ALX (10(-5)M) were dissolved in normal Tyrode (NT), maintained at pH 7.4 and 37 degrees C and stored for either 15 or 60-120min. Both compounds reduced the amplitude of myocyte shortening. Compared to NT the amplitude of shortening was 34.7+/-5.0% and 35.2+/-6.8% with STZ and 41.0+/-5.5% and 37.3+/-5.7% with ALX stored for 15 and 60-120min, respectively. During a 10min NT washout STZ myocytes recovered to 56.2+/-8.3% and 60.5+/-8.2% and ALX myocytes recovered to 88.9+/-10.0% and 83.7+/-9.9% after storage of compounds for 15 and 60-120min, respectively. Perfusion of the whole heart with ALX induced bradycardia but had no effects on the duration of action potential repolarization at 50% and 70% from peak action potential. The negative inotropic effects of STZ and ALX were not altered by storage. The results suggest that some of the effects on heart reported in STZ- and ALX-induced diabetes may be partly attributed to direct action of these compounds.