Role of catecholamines in the pathogenesis of diabetic cardiomyopathy 1.

Although the sympathetic nervous system plays an important role in the regulation of cardiac function, the overactivation of the sympathetic nervous system under stressful conditions including diabetes has been shown to result in the excessive production of circulating catecholamines as well as an increase in the myocardial concentration of catecholamines. In this brief review, we provide some evidence to suggest that the oxidation products of catecholamines such as aminochrome and oxyradicals, lead to metabolic derangements, Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+, as well as activation of proteases and changes in myocardial gene expression. These alterations due to elevated levels of circulatory catecholamines are associated with oxidative stress, subcellular remodeling, and the development of cardiac dysfunction in chronic diabetes.

An international basic science and clinical research summer program for medical students.

An important part of training the next generation of physicians is ensuring that they are exposed to the integral role that research plays in improving medical treatment. However, medical students often do not have sufficient time to be trained to carry out any projects in biomedical and clinical research. Many medical students also fail to understand and grasp translational research as an important concept today. In addition, since medical training is often an international affair whereby a medical student/resident/fellow will likely train in many different countries during his/her early training years, it is important to provide a learning environment whereby a young medical student experiences the unique challenges and value of an international educational experience. This article describes a program that bridges the gap between the basic and clinical research concepts in a unique international educational experience. After completing two semester curricula at Alfaisal University in Riyadh, Kingdom of Saudi Arabia, six medical students undertook a summer program at St. Boniface Hospital Research Centre, in Winnipeg, MB, Canada. The program lasted for 2 mo and addressed advanced training in basic science research topics in medicine such as cell isolation, functional assessment, and molecular techniques of analysis and manipulation as well as sessions on the conduct of clinical research trials, ethics, and intellectual property management. Programs such as these are essential to provide a base from which medical students can decide if research is an attractive career choice for them during their clinical practice in subsequent years. An innovative international summer research course for medical students is necessary to cater to the needs of the medical students in the 21st century.

Neuropeptide Y level in paraventricular nucleus of experimental diabetic rats: correlation with sympathetic activity and body weight.

Neuropeptide Y (NPY), colocalized with norepinephrine neuron, is known to modulate sympathetic activity and feeding behavior. Although experimental type 1 diabetes has increased sympathetic activity at the early part of the disease process, little effort was made so far to understand the correlation between NPY level in the hypothalamus and sympathetic activity in diabetes. Male Sprague Dawley rats were made diabetic by a single injection of streptozotocin (65 mg/kg body weight, IV). The animals were then studied after 2, 4, and 8 weeks. Control animals received only citrate vehicle. In an effort to clarify the modulatory effect of NPY at the early stage of diabetes, the paraventricular nucleus (PVN) of hypothalamus was sampled by microdialysis for NPY and norepinephrine level. While NPY level was increased immediately within 2 weeks (along with feeding behavior), norepinephrine level was increased only after 8 weeks following injection of streptozotocin. The animals lost significant weight. These results are interpreted to mean that a strong correlation exists between the feeding behavior and NPY level in PVN. Since NPY is known to inhibit sympathetic activity it is possible that NPY receptors are down-regulated following diabetes. The higher level of norepinephrine indicating higher sympathetic activity did not allow the animals to gain weight. In addition, controversy exists regarding pleiotropic activities of NPY related to the feeding behavior of these animals.

Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction.

Diabetes mellitus is associated with abnormal cardiomyocyte Ca(2+) transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP3/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP3/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca(2+) transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP3/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.

Increased homocysteine-induced release of excitatory amino acids in the striatum of spontaneously hypertensive stroke-prone rats.

BACKGROUND AND PURPOSE: Increased plasma [homocysteine] is associated with stroke but its direct effects on the brain during a stroke are unknown. Since excitatory amino acids are important in inducing brain damage, we examined the effect of homocysteine on the release of various amino acids in the striatum of spontaneously hypertensive stroke-prone (SHSP) rats before and after a stroke. METHODS: In vivo microdialysis was carried out in the striatum of anesthetized SHSP rats before and after signs of stroke. Animals were exposed to 20 and 200 muM homocysteine in the microdialysis solution and then the microdialysates were analyzed 30 min later for amino acid content. Brain cryosections were silver-stained to quantify infarcts in the non-ischemic and the damaged tissues in pre-stroke and post-stroke rats. RESULTS: Both pre-stroke and post-stroke animals had similar levels of all amino acids in the striatum. Homocysteine did not alter amino acid release in rats prior to stroke but induced a significant increase in the release of all amino acids tested in the post-stroke rats. However, the increase was significantly greater with the excitatory amino acids glutamate and aspartate, and with tyrosine in post-stroke animals as compared to those in pre-stroke, normal animals. The mean pixel density of the gray matter of post-stroke animals was significantly decreased following homocysteine treatment indicating the presence of neurological damage. CONCLUSIONS: Homocysteine-induced neurological damage in post-infarct SHSP rats was associated with a hypersecretion of excitatory amino acids. Patients with hyperhomocysteinemia may be at risk for augmented brain damage from an ischemic infarct due to a selective activation of neuronal excitatory amino acids.

Evaluation of small-group teaching in human gross anatomy in a Caribbean medical school.

Although there are a number of medical schools in the Caribbean islands, very few reports have come out so far in the literature regarding the efficacy of small-group teaching in them. The introduction of small-group teaching in the gross anatomy laboratory one and a half years ago at St. Matthew's University (SMU) on Grand Cayman appears to have had a significant positive impact on the academic achievement of students in anatomy. This study surveyed the responses of the students to the small-group learning method in gross anatomy at SMU using a structured questionnaire. The results show that our students prefer this small-group learning method over a completely self-directed method in the gross anatomy lab because the study materials were carefully chosen and the study objectives were demonstrated by the resource person. However, teacher-centered teaching was deliberately avoided by fostering problem-solving skills in the anatomy lab sessions. Another aim of the small-group teaching at SMU was to develop the interpersonal and communication skills of the students, which are important in their later education and career.

Assessment of anatomy in a problem-based medical curriculum.

In the problem-based learning (PBL) approach to medical education, students are expected to be trained more by applying processes of reasoning than by memorization of facts. In a PBL curriculum, as with others, it is necessary to match the assessment to the learning process. A detailed description of the testing of anatomical teaching-learning outcomes at the Arabian Gulf University (AGU) is presented. In addition to describing the general principles and guidelines as well as the process of continuous assessment, we have given examples of the multiple-choice questions, patient management problems, and objective-structured practical examinations, which compose our end-of-unit examination and test both vertical and horizontal integration of themes. Students have the opportunity to review the examination after publication of the results. We believe that our approach to the assessment of anatomy tests effective integration of factual knowledge with the principles of problem-solving through the different formats of the components of our examinations.

Structured problem-related anatomy demonstrations: making order of random teaching events.

BACKGROUND: A standardized learning activity called "Structured Problem-Related Anatomy Demonstrations" was recently implemented. This activity is intended to be a substitute to the need-based instruction method in which students schedule appointments in small groups or individually with faculty to discuss issues and difficulties related to anatomy the students have encountered during their tutorial discussions and self-study learning. DESCRIPTION: Students in a given year were divided into 2 groups. Each group was further divided into 4 small groups (n = 10) who rotated through 4 "stations." A faculty member who demonstrated a specific aspect of anatomy related to the weekly health problem staffed each of the stations. EVALUATION: The effect of the new method of instruction on students' performance in end-of-unit examinations was not statistically significant. A 5-point scale questionnaire seeking the perceptions of 3rd- and 4th-year medical students (n = 176), who had experience with both methods, was used. The means +/- standard deviation of students' responses to items related to organization was 3.61 +/- 0.55, to knowledge was 4.29 +/- 0.73, to integration was 3.91 +/- 0.73, and to skills was 3.84 +/- 0.83. The vast majority of students expressed their overall support for continuing the new system (4.54 +/- 0.58). CONCLUSIONS: The new method increased students' satisfaction and confidence while maintaining their level of performance in final assessments. Faculty have more control over their schedules and can devote more quality time to teaching and research.

Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade.

In order to understand the mechanisms of exercise intolerance and muscle fatigue, which are commonly observed in congestive heart failure, we studied sarcoplasmic reticulum (SR) Ca(2+)-transport in the hind-leg skeletal muscle of rats subjected to myocardial infarction (MI). Sham-operated animals were used for comparison. On one hand, the maximal velocities (Vmax) for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities in skeletal muscle of rats at 8 weeks of MI were higher than those of controls. On the other hand, the Vmax values for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca(2+)-transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca(2+)-pump for Ca2+. Furthermore, the stimulation of SR Ca(2+)-stimulated ATPase activity by cyclic AMP-dependent protein kinase was not altered at 8 or 16 weeks of MI when compared with the respective control values. Treatment of 3-week infarcted animals with angiotensin-converting enzyme (ACE) inhibitors such as captopril, imidapril, and enalapril or an angiotensin receptor (AT1R) antagonist, losartan, for a period of 13 weeks not only attenuated changes in left ventricular function but also prevented defects in SR Ca(2+)-pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca(2+)-transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca(2+)-pump activity in skeletal muscle may be compensatory whereas the depression at late stages of MI may play a role in exercise intolerance and muscle fatigue in congestive heart failure. Furthermore, the improvements in the skeletal muscle SR Ca(2+)-transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure.

Evaluation of the teaching strategy of cardiovascular system in a problem-based curriculum: student perception.

It is generally acknowledged that an integrated approach to teaching cardiovascular system (CVS) is clinically relevant. However, very little attention has been paid with respect to student perception of teaching CVS in an integrated problem-based curriculum. A questionnaire on the feedback and perception of medical students (n = 60) to their learning experience of CVS exposed early in the problem-based integrated curriculum at the Arabian Gulf University (AGU) was used. The average percentage scores of positive student responses to items related to knowledge was 62.7%, to integration was 87.3%, and to skills was 77.1%. A significant positive correlation was observed among skills and knowledge (r = 0.408, P = 0.002), skills and integration (r = 0.506, P < 0.000), and integration and knowledge (r = 0.294, P = 0.028). The lowest individual percentage score related to knowledge items was given to the role of resource sessions in understanding difficult concepts (32.7%). Interestingly, 90.7% of the students were aware of the presence of gaps in their knowledge. On the other hand, 92.7% of students expressed their satisfaction with the study experience of CVS in the integrated problem-based approach. These results indicate that students overall achieved satisfactory learning outcome during the study of CVS in the problem-based integrated curriculum at AGU. The study also points out issues where improvement and fine tuning of the educational system can take place.

Influence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarction.

Although it is generally accepted that the efficacy of imidapril, an angiotensin-converting enzyme inhibitor, in congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR) proteins has not been fully understood. In this study, we examined the effects of long-term treatment of imidapril on mortality, cardiac function, and gene expression for SL Na+/K+ ATPase and Na+ -Ca2+ exchanger as well as SR Ca2+ pump ATPase, Ca2+ release channel (ryanodine receptor), phospholamban, and calsequestrin in CHF due to myocardial infarction. Heart failure subsequent to myocardial infarction was induced by occluding the left coronary artery in rats, and treatment with imidapril (1 mg.kg(-1).day(-1)) was started orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed hemodynamically and the heart and lung were examined morphologically. Some hearts were immediately frozen at -70 degrees C for the isolation of RNA as well as SL and SR membranes. The mortality of imidapril-treated animals due to heart failure was 31% whereas that of the untreated heart failure group was 64%. Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced morphological changes in the heart and lung. The depressed SL Na+/K+ ATPase and increased SL Na+-Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing hearts were partially prevented by imidapril. Although changes in gene expression for SL Na+/K+ ATPase isoforms as well as Na+-Ca2+ exchanger and SR phospholamban were attenuated by treatments with imidapril, no alterations in mRNA levels for SR Ca2+ pump proteins and Ca2+ release channels were seen in the untreated or treated rats with heart failure. These results suggest that the beneficial effects of imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression.

Teaching of anatomy in a problem-based curriculum at the Arabian Gulf University: the new face of the museum.

The College of Medicine and Medical Sciences of the Arabian Gulf University has an undergraduate medical curriculum that uses problem-based learning as the principal teaching strategy. Teaching of anatomy comes at various places in the curriculum, and the anatomy museum serves as an important resource and engages the students in self-directed learning. Although the museum had sufficient resource materials, the emphasis on individualized instruction and self-directed learning in anatomy has resulted in the need for an effective approach and a reorganization of the facilities in the museum. Thus, we recently rearranged the museum to create 42 modules or stations (learning carrels) focusing on specific organ systems for self-study by students. Computer-assisted programs, videocassettes, ultrasound, and structured living anatomy sessions in the clinical professional skills program facilitated such an arrangement. An increased utilization by the students was observed in the reorganized museum. Thus, the museum can play an effective role in the study of anatomy through problem-based integrated learning modules.

Stress, sympathetic activity and heart disease: Is there any common mediator?

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