Oxidative Products of Catecholamines During Heightened Sympathetic Activity Due to Congestive Heart Failure: Possible Role of Antioxidants.

The past several decades have shown the functional status of sympathetic activity in congestive heart failure. The results, particularly through clinical and basic studies in heart failure, indicate an increased sympathetic neural activity. The definitive and compelling evidence of the involvement of catecholamines is the demonstration that many drugs that are therapeutically useful in the treatment of heart failure also affect the sympathetic nervous system at various sites, including its synthesis, release and uptake of catecholamines and a decreased plasma norepinephrine level. Although it is not surprising that the sympathetic system is altered as cardiac function is compromised in heart failure, it now appears that this system may overreact in chronic situations. The detrimental cardiovascular problems result in the production of aminochrome and free radicals. Antioxidant therapy to target the production of aminochrome from autooxidation of catecholamines should provide an insight into the future therapeutic goal in situations like congestive heart failure.

Implementation of structured team-based review enhances knowledge consolidation and academic performance of undergraduate medical students studying neuroscience.

Team-based learning (TBL) provides a systematic approach to teaching and learning and promotes critical thinking and enhances medical educational activities and professional development. TBL-based didactic methodology has proven beneficial in enhancing learning and consolidating key educational concepts throughout educational curricula. Such areas of application include neuroscience, which is traditionally considered to be one of the most difficult disciplines to be taught in undergraduate medical courses to the point where the scientific literature reports "neurophobia" among undergraduate medical students. Herein, we report the design and application of a modified version of TBL, which we termed team-based review (TBR) throughout two cohorts of undergraduate medical students undertaking neuroscience. We show that our TBR methodology enhanced student understanding of neuroscience, increasing average marks and grades achieved in final exams, while also increasing the proportion of students obtaining higher grades. Application of TBR also improved marks obtained by students throughout continuous assessment (midterms, TBL, and problem-based learning grades). In surveys taken following final exams, students strongly felt that TBR enhanced their learning experience and aided knowledge acquisition, consolidation, and exam preparation. Collectively, we show that TBR-based methodology was effective in enhancing the student learning experience and performance in neuroscience and could potentially be successfully used to enhance performance and learning in other subjects in the undergraduate medical curriculum.

Measurement of homocysteine: a historical perspective.

Elevated plasma level of homocysteine is being increasingly associated with many diseases. There is a significant interest in the development of methods to determine the total homocysteine in biologically relevant tissues. Over the years, researchers use various methods to determine the exact concentrations of homocysteine in these tissues. However, the precise method used in many studies earlier was questionable. We have reviewed various methodologies for the measurement of homocysteine. We list the commonly used methodologies currently in use to determine homocysteine levels. Through extensive literature search, we have come up with the most popular as well as the newest measurement modalities and listed them with a brief discussion of each of the methodology. In conclusion, we have presented the historical perspective of homocysteine measurement in biological fluids in this manuscript. Thus, the precise understanding of its concentration in biological fluids coupled with its importance in health and disease should justify a newer but reliable technique in the area of ongoing research in homocysteine.

Medical education dilemma: How can we best accommodate basic sciences in a curriculum for 21st century medical students? 1.

Over the years, the medical curriculum has been changed to accommodate a variety of evolving disciplines and an exploding scientific knowledge of the basic sciences to prepare "a competent physician" of the 21st century. Therefore, we must be innovative in our approach of curricular development if we wish to continue to incorporate new basic sciences knowledge in the face of decreasing contact hours to satisfy the buzz word, "integration". Certainly, the challenges are phenomenal. The question how to best integrate basic sciences, is not easy to answer as the objectives of the courses and outcome vary from one medical school to another and the fact is, one size does not fit all. However, if we believe that basic sciences are the language of medicine and foundation of clinical knowledge, then we must resolve this ongoing dilemma by introducing basic sciences through a better alignment in a given curriculum. The purpose of this review is to evaluate different curricular models for their basic sciences content and address their strengths and weaknesses. In addition, we will introduce a spiral design to integrate basic sciences for senior students. Finally, we will provide some insight as to how learning and retention of basic science content can be sustained.

ß-1 adrenoceptors and AT1 receptors may not be involved in catecholamine-induced lethal arrhythmias 1.

An excessive amount of catecholamines produce arrhythmias, but the exact mechanisms of this action are not fully understood. For this purpose, Sprague-Dawley rats were treated with or without atenolol, a ß1-adrenoceptor blocker (20 mg/kg per day), for 15 days followed by injections of epinephrine for cumulative doses of 4 to 128 µg/kg. Another group of animals were pretreated with losartan, an angiotensin receptor (AT1) blocker (20 mg/kg per day), for comparison. Control animals received saline. Varying degrees of ventricular arrhythmias were seen upon increasing the dose of epinephrine, but the incidence and duration of the rhythm abnormalities as well as the number of episodes and severity of arrhythmias were not affected by treating the animals with atenolol or losartan. The levels of both epinephrine and norepinephrine were increased in the atenolol-treated rats but were unchanged in the losartan-treated animals after the last injection of epinephrine; the severity of arrhythmias did not correlate with the circulating catecholamine levels. These results indicate that both ß1-adrenoceptors and AT1 receptors may not be involved in the pathogenesis of catecholamine-induced arrhythmias and support the view that other mechanisms, such as the oxidation products of catecholamines, may play a crucial role in the occurrence of lethal arrhythmias.

Sarcolemmal Alterations in Unloaded Rat Heart after Heterotopic Transplantation.

Following heterotopic transplantation, the rat heart undergoes atrophy and exhibits delayed cardiac relaxation without any changes in contraction and systolic Ca 2+ transients. Furthermore, the sarcoplasmic reticular Ca 2+ uptake and release activities were reduced and Ca 2+ influx through L-type Ca 2+ channels was increased in the atrophied heart. Since Ca 2+ movements at sarcolemma are intimately involved in the regulation of intracellular Ca 2+ concentration, the present study was undertaken to test if sarcolemma plays any role to maintain cardiac function in the atrophied heart.The characteristics of sarcolemmal Ca 2+ pump and Na + -Ca 2+ exchange activities were examined in 8 weeks heterotopically isotransplanted rat hearts which did not support hemodynamic load and underwent atrophy. Sarcolemmal ATP (adenosine triphosphate)-dependent Ca 2+ uptake and Ca 2+ -stimulated ATPase (adenosine triphosphatase) activities were increased without any changes in Na + -K + ATPase activities in the transplanted hearts. Although no alterations in the Na + -dependent Ca 2+ uptake were evident, Na + -induced Ca 2+ release was increased in the transplanted heart sarcolemmal vesicles. The increase in Na + -induced Ca 2+ release was observed at different times of incubation as well as at 5, 20, and 40 mM Na + . The sarcolemma from transplanted hearts also showed higher contents of phosphatidic acid, sphingomyelin, and cholesterol.These results indicate that increases in the sarcolemmal, Ca 2+ transport activities in unloaded heart may provide an insight into adaptive mechanism to maintain normal contractile behavior of the atrophic heart.

Assessment of first-year medical students' perceptions of teaching and learning through team-based learning sessions.

Team-based learning (TBL) is an emerging teaching and learning strategy being employed in medical schools. The College of Medicine at Alfaisal University has adopted a TBL approach as an instructional method for first-year medical students. The aim of the present study was to describe the TBL method employed at Alfaisal University College of Medicine and to assess first-year medical students' perceptions of this learning modality for the anatomy- and physiology-based blocks/courses in organ systems form of curriculum. A five-point Likert scale questionnaire was structured based on Kirkpatrick's theory and assessed three major domains: reaction, learning, and behavior. Confirmatory factor analysis (CFA) and Cronbach's α-coefficient tests were used to assess the validity and reliability of the construct, respectively. CFA showed an adequate validity of the survey and Cronbach's α revealed an acceptable internal uniformity (0.69). A total of 185 respondents rated reaction, learning, and behavior toward introduction of TBL as 3.53 ± 1.01, 3.59 ± 1.12, and 3.57 ± 1.12, respectively. Excellent students rated TBL highly in all major domains compared with borderline students (reaction, behavior, and learning domains with P values of <0.049, <0.035, and <0.031, respectively). Students who had prior teamwork experience rated TBL higher in terms of their learning experience compared with those who were rarely involved in team work. This study demonstrated that Alfaisal University first-year medical students perceived TBL positively as a teaching and learning strategy for functional anatomy, and prior involvement in teamwork and academic performance correlates with higher ratings of TBL.

The Integrated Clinical Anatomy Program at Alfaisal University: an innovative model of teaching clinically applied functional anatomy in a hybrid curriculum.

Anatomy has historically been a cornerstone in medical education regardless of specialty. It is essential for physicians to be able to perform a variety of tasks, including performing invasive procedures, examining radiological images, performing a physical examination of a patient, etc. Medical students have to be prepared for such tasks, and we can assist this by changing the way that we educate students in medical schools. Thus, newer medical curricula need to be designed according to needs of future physicians. In this report, we describe a unique program called the Integrated Clinical Anatomy Program (ICAP). The ICAP was developed at the College of Medicine of Alfaisal University in the Kingdom of Saudi Arabia. Here, we describe the unique features of this program, including the structure and facilities of the Anatomy Resource Center. The Anatomy Resource Center plays a pivotal role in engaging the students for faculty-directed structured laboratory sessions as well as peer-assisted uniform student-centered learning. The ICAP has shown great promise, as reflected by early results from a nationwide progress test. Students from all years of the Alfaisal University medical school scored significantly higher than the national average on the anatomy and physiology component of the nationwide progress test examination, with P values of 0.0179 and 0.0015, respectively. We believe that the ICAP can be used as a model for teaching clinically applied functional anatomy to medical students in a hybrid curriculum around the world.

Role of homocysteine in the development of cardiovascular disease.

It is well known that neuronal damage following a stroke has been attributed to the over stimulation of excitatory amino acids such as glutamate and aspartate through activation of NMDA receptors. The brain is exposed to most of the constituents of plasma including homocysteine as a result of the disruption of the blood-brain barrier after stroke, head trauma and stress. The question, therefore, arises as to whether or not homocysteine is able to selectively stimulate the release of excitatory amino acids in stroke. This review article will address the importance of homocysteine in nervous system specifically how these amino acids may trigger the release of catecholamines. Our data will thus strengthen the view that a mechanism for the association of hyperhomocysteinemia with increased brain lesion in stroke. As hypothalamus also controls the cardiac function via sympathetic system, the contractility of heart will be compromised. Homocysteine is also known to mediate cardiovascular problems by its adverse effects on cardiovascular endothelium and smooth muscle cells with resultant alterations in subclinical arterial structure and function. The present review will thus summarize both central and peripheral effects of homocysteine and will highlight some of the controversies associated with hyperhomocysteinemia-induced cardiovascular problems.

Hydroxybenzoic acid isomers and the cardiovascular system.

Today we are beginning to understand how phytochemicals can influence metabolism, cellular signaling and gene expression. The hydroxybenzoic acids are related to salicylic acid and salicin, the first compounds isolated that have a pharmacological activity. In this review we examine how a number of hydroxyphenolics have the potential to ameliorate cardiovascular problems related to aging such as hypertension, atherosclerosis and dyslipidemia. The compounds focused upon include 2,3-dihydroxybenzoic acid (Pyrocatechuic acid), 2,5-dihydroxybenzoic acid (Gentisic acid), 3,4-dihydroxybenzoic acid (Protocatechuic acid), 3,5-dihydroxybenzoic acid (α-Resorcylic acid) and 3-monohydroxybenzoic acid. The latter two compounds activate the hydroxycarboxylic acid receptors with a consequence there is a reduction in adipocyte lipolysis with potential improvements of blood lipid profiles. Several of the other compounds can activate the Nrf2 signaling pathway that increases the expression of antioxidant enzymes, thereby decreasing oxidative stress and associated problems such as endothelial dysfunction that leads to hypertension as well as decreasing generalized inflammation that can lead to problems such as atherosclerosis. It has been known for many years that increased consumption of fruits and vegetables promotes health. We are beginning to understand how specific phytochemicals are responsible for such therapeutic effects. Hippocrates' dictum of 'Let food be your medicine and medicine your food' can now be experimentally tested and the results of such experiments will enhance the ability of nutritionists to devise specific health-promoting diets.

What is an objective structured practical examination in anatomy?

Assessing teaching-learning outcomes in anatomical knowledge is a complex task that requires the evaluation of multiple domains: theoretical, practical, and clinical knowledge. In general, theoretical knowledge is tested by a written examination system constituted by multiple choice questions (MCQs) and/or short answer questions (SAQ). The assessment of practical knowledge (three-dimensional anatomical concepts) involves oral, spot, or objective structured practical examinations (OSPE). Finally, the application of anatomical knowledge to patients is tested mainly through objective structured clinical examinations (OSCE). The major focus of this study is the OSPE. Although many schools challenge students using this tool in practical examinations in the early phase of the curriculum, the true meaning of OSPE is frequently forgotten and it becomes, in reality, a spot examination. This article, for the first time, describes how the concept of the OSPE has evolved and is currently being used to assess the practical domain of anatomical knowledge in a problem-based curriculum at Alfaisal University College of Medicine. In addition, it describes the main differences from the spot examination, which is normally used in traditional medical curricula. The authors believe that the OSPE remains the most efficient tool to assess the practical aspects of anatomical knowledge in a system where basic knowledge is integrated with the clinical or functional part of anatomy. However, this contention only holds true if the OSPE process revolves around structured objectives.

How the dissection laboratory facilitates integration of learning: presence of abdominal aortic aneurysm with a large intracardiac thrombus: a rare cadaver finding.

There is a debate among medical education experts on the application of dissection or prosection for learning anatomy. However, the literature reveals that the majority of published articles are in favor of dissection. In this article, we present a case of an abdominal aortic aneurysm (AAA) with intracardiac thrombus in a cadaver on routine dissection. We will discuss possible explanations for such finding and provide some insight into how this finding can support the significance of the cadaver-based teaching of anatomy of the medical students. Initially, the abdomen was dissected and exposed to study the abdominal structures in an anatomy class and later the thoracic region was dissected and all the clinical abnormalities were examined and documented. Autopsy of the clot was obtained for histopathology analysis. The intracardiac thrombus was present in the right atrium characterized by its projection into the superior vena cava, inferior vena cava, and the right ventricle. The AAA was extensive and inferior to the renal arteries constricting the entire inferior vena cava. Moreover, associated findings included presence of numerous collaterals in the thoracic region near the superior vena cava; histological examination of the clot showed extensive population of leukocytes. There were enlarged mediastinal lymph nodes. Our cadaver showed an excellent model for integrating between clinical anatomy and pathology by triggering medical students to think of normal and abnormal structures: often called "thinking outside the box." Such an effort might help them in developing their thought processes and future medical careers.

Student-centered integrated anatomy resource sessions at Alfaisal University.

Alfaisal University is a new medical school in Riyadh, Kingdom of Saudi Arabia that matriculates eligible students directly from high school and requires them to participate in a hybrid problem-based learning (PBL) curriculum. PBL is a well-established student-centered approach, and the authors have sought to examine if a student-centered, integrated approach to learn human structures leads to positive perceptions of learning outcomes. Ten students were divided into four groups to rotate through wet and dry laboratory stations (integrated resource sessions, IRSs) that engaged them in imaging techniques, embryology, histology, gross anatomy (dissections and prosections), surface anatomy, and self-directed learning questions. All IRSs were primarily directed by students. During two second-semester organ system blocks, forty students responded to a structured questionnaire designed to poll students' perceptions of changes in their knowledge, skills, and attitudes as a result of IRS. The majority (60%) of students felt that the student-centered approach to learning enhanced their medical knowledge. Most students also felt that the IRS approach was advantageous for formulating clear learning objectives (55%) and in preparing for examinations (65%). Despite their positive feelings toward IRS, students did not view this learning approach as an adequate replacement for the knowledge gained from lectures and textbooks. Students' performance on objective structured practical examinations improved significantly for the two curricular blocks that included IRS compared with earlier non-IRS blocks. A student-centered approach to teach human structure in a hybrid PBL curriculum may enhance understanding of the basic sciences in first-year medical students.

Persistent bilateral sciatic artery: Report of a rare case.

The sciatic artery - a rare finding on autopsy - and continuation of the inferior gluteal artery has been reported previously. On a routine dissection, bilateral persistent sciatic arteries were found in both thighs of a female cadaver. This provided evidence that the sciatic artery follows the sciatic nerve, supplies the back of the thigh and finally joins the popliteal artery near the knee. The profunda femoris artery was completely absent bilaterally. The present report strengthens the view that the sciatic artery plays a major role in supplying blood to the lower limbs in utero and its existence after birth may have significant clinical importance.