Search

The recent advancement in regional anesthesia (RA) has been largely attributed to ultrasound technology. However, the safety and efficiency of ultrasound-guided nerve blocks depend upon the skill and experience of the performer. Even with adequate training, experience, and knowledge, human-related limitations such as fatigue, failure to recognize the correct anatomical structure, and unintentional needle or probe movement can hinder the overall effectiveness of RA. The amalgamation of artificial intelligence (AI) to RA practice has promised to override these human limitations. Machine learning, an integral part of AI can improve its performance through continuous learning and experience, like the human brain. It enables computers to recognize images and patterns specifically useful in anatomic structure identification during the performance of RA. AI can provide real-time guidance to clinicians by highlighting important anatomical structures on ultrasound images, and it can also assist in needle tracking and accurate deposition of local anesthetics. The future of RA with AI integration appears promising, yet obstacles such as device malfunction, data privacy, regulatory barriers, and cost concerns can deter its clinical implementation. The current mini review deliberates the current application, future direction, and barrier to the application of AI in RA practice., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aim: Spinal anesthesia is the most common type of anesthesia administered for caesarean section and it is frequently associated with hypotension. When post-spinal hypotension is accompanied with bradycardia, the condition may become more complicated. Numerous pharmacological agents have therefore been tried for prevention of hypotension and 5HT3 antagonists are the latest in the armamentarium. However, studies have shown conflicting evidence regardings the effectiveness of 5HT3 inhibitors (ondansetron and granisetron) in preventing spinal hypotension. We have tried to address this controversy and also wanted to explore the adverse effects of granisetron on the foetus, if any., Materials and Methods: Two hundred patients were included in the study and divided into two groups of 100 patients each. Group S patients received 5ml of 0.9% normal saline while Group G patients received IV granisetron 1mg (diluted to 5ml) 10 minutes prior to administration of spinal anesthesia. Analysis of variance (ANOVA) test was used for comparing the data, Student t-test was applied to compare the difference between the two means and Chi-Square test was used to test significance of difference of proportions., Results: The incidence of hypotension in Group S was 69%, whereas it was 37% in Group G (p<0.001), hence patients of Group S required a significantly higher (p=0.001) amount of mephentermine. Haemodynamic parameters were well maintained throughout the study period in patients of Group G. The neonatal outcome was assessed by Apgar score at 0 minutes, one minute, and five minutes after delivery, and it was comparable between the two study groups., Conclusion: Intravenous granisetron 1mg if administered before administering spinal anesthesia can effectively attenuate hypotension in parturients without any adverse effects on the mother and the neonate., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Chatterjee et al.)

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.

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, Ca 2+ -handling abnormalities, increase in the availability of intracellular free Ca 2+ , 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 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 β 1 -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 β 1 -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.

Stroke results more than 4.3 million deaths worldwide per annum and 85% of all strokes are ischaemic in nature. Besides numerous modifiable and non-modifiable known risk factors, microalbuminuria is thought to be an important marker of global endothelial dysfunction and associated with cardiovascular disease including stroke. Fifty ischaemic stroke cases and 50 (age, sex matched) control subjects were subjected to study to compare and evaluate risk stratification of micro-albuminuria, its predictive value and outcome on day 1 and day 7 among admitted ischaemic stroke cases.The result was found that micro-albuminuria was present in 66% of ischaemic stroke cases compared to only 8% of control group (p < 0.001). Most validated National Institute of Health Stroke Scale (NIHSS) score was used for evaluation and calculation of predictive value and outcome of micro-albuminuria positive patient where higher value indicates poor prognosis, and the result was mean NIHSS score 29.12 versus 18.88 between two groups of strokes ie, with and without micro-albuminuria. Out of 50 ischaemic stroke patients 33 (66%) had micro-albuminuria. Among 11 patients who died, 10 (90.9%) had micro-albuminuria and NIHSS score was 33.64 and 25.0 on day 1 and day 7. Among 39 patients who were discharged, 23 patients (58.97%) were MA positive and NIHSS score was much less than death group ie, 23.38 and 16.38 on day 1 and day 7 respectively. So this study reveals micro-albuminuria itself results higher risk for ischaemic stroke compared to control group and it shows good predictive value for early assessment of clinical severity and subsequent fatal outcome. This is also simple, cost effective and affordable.

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.

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.

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.

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.

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.

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.

Polyunsaturated fatty acids (PUFAs) have significant, cardioprotective effects against ischemia. Hempseed contains a high proportion of the PUFAs linoleic acid (LA) and alpha-linolenic acid (ALA), which may have opposing effects on postischemic heart performance. There are no reported data concerning the cardiovascular effects of dietary hempseed intake. A group of 40 male Sprague-Dawley rats were distributed evenly into four groups that were fed for 12 wk a normal rat chow supplemented with hempseed (5% and 10%), palm oil (1%), or a 10% partially delipidated hempseed that served as a control. Plasma ALA and gamma-linolenic acid levels were significantly elevated in the rats that were fed a 5% or 10% hempseed-supplemented diet, but in heart tissue only ALA levels were significantly elevated in the rats fed these diets compared with control. After the dietary interventions were completed, postischemic heart performance was evaluated by measuring developed tension, resting tension, the rates of tension development and relaxation, and the number of extrasystoles. Hearts from rats fed a hempseed-supplemented diet exhibited significantly better postischemic recovery of maximal contractile function and enhanced rates of tension development and relaxation during reperfusion than hearts from the other groups. These hearts, however, were not protected from the occurrence of extrasystoles, nor were the increases in resting tension altered during ischemia or reperfusion as a function of any dietary intervention. Our data demonstrate that dietary hempseed can provide significant cardioprotective effects during postischemic reperfusion. This appears to be due to its highly enriched PUFA content.

Peripheral neuropathies constitute an important group of disorders in neurological practice. Very few systematic studies on peripheral neuropathies are available from India. Hence we conducted a prospective study in two large hospitals from Kolkata, the biggest city of eastern India in order to find out the spectrum of peripheral neuropathy. This prospective study was carried out from June 1998 to January 2003 on admitted patients with symptoms and signs of peripheral neuropathy. Two hundred and twenty-five patients were evaluated (one hundred and twenty-five from an industrial hospital and one hundred from an academic tertiary care institution at Kolkata). Result showed that most of the cases of peripheral neuropathy belonged to fourth decade with men dominance. Common varieties of neuropathy were Guillain-Barré syndrome, diabetes mellitus, hereditary motor sensory neuropathy, chronic inflammatory demyelinating neuropathy, drugs and toxin related. Unusual varieties were Isaacs's syndrome and X-linked hereditary motor-sensory neuropathy. One case of neuropathy due to Plasmodium vivax has received intravenous immunoglobulin therapy. The type of peripheral neuropathy in hospital-based patients in eastern India was similar to other parts of country excepting some sporadic types due to infective or genetic causes and a large number of cases of undetermined aetiology exist despite detailed investigations.

Sodium orthovanadate suspended in a lichee black tea decoction effectively regulates blood glucose levels in rats with insulin-dependent, streptozotocin (STZ)-induced diabetes. The primary advantage of vanadate delivery with the tea decoction over conventional systems that use water suspensions of vanadate is a significant reduction in the toxic side effects of vanadate. It is unknown if the tea alters the bioavailability of vanadate. Male Sprague-Dawley rats were administered an intravenous injection of STZ to induce diabetes. Four days later, the diabetic rats were treated by oral gavage with 40 mg of Na-orthovanadate suspended in double-distilled, deionized water (V/H2O), tea/vanadate (TV) decoction, or were treated with the tea decoction alone. Vanadium concentrations were measured in blood and various tissues at 1 to 24 hours posttreatment using graphite furnace atomic absorption spectrophotometry. With the exception of bone, maximal vanadium concentration in plasma and tissue samples were observed 2 hours after ingestion, but steadily decreased after that. Plasma vanadium levels continued to decrease until 16 hours. In contrast, vanadium steadily accumulated in bone over the 24-hour period. Overall, rats treated with V/H2O contained similar or significantly higher concentrations of vanadium in all tissues compared with TV treatment. The pattern of vanadium accumulation was also similar over time in both treatment groups. Vanadium levels were highest in bone > kidney > liver > pancreas > lung > heart > muscle > brain in both TV- and V/H2O-treated animals. This study demonstrates that the accumulation of vanadium in diabetic rats is reduced when coadministered with a black tea decoction in comparison to administration of vanadium in water. However, this effect is unlikely to be of a magnitude to explain the full capacity of TV to reduce the toxic side effects of vanadate.

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.

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., (Copyright 2005 Wiley-Liss, Inc.)

Background: Since the advent of laparoscopic inguinal hernia repair, the procedure has invited numerous controversies, and although the procedure has some definitive advantages, no definitive indications for its use have been formulated. The objective of this study was to investigate a novel method for inguinal hernia repair (through a small 2 cm to 2.5 cm) single skin incision that combines the time-tested fundamentals of Lichtenstein's tension-free repair with the advantages of laparoscopic assistance., Methods: The study was conducted as a randomized, controlled trial over a 1-year period and included 50 patients. Only patients with simple reducible hernias without associated comorbid conditions were included. The patients were randomized into 2 groups of 25 patients each. One group underwent conventional tension-free meshplasty, while the other group underwent the repair through a single 2-cm to 2.5-cm skin incision with laparoscopic assistance. This repair was carried out with the help of an indigenously designed steel retractor, 10-mm laparoscope, and conventional instruments; the mesh was fixed with the help of endotacks. Univariate analysis of variance techniques using SPSS 7.5 software was used for data analysis., Results: Two groups were compared for time taken for the procedure, size of skin incision, postoperative pain, complications, return to work, and cosmetic appearance. The results showed a significant decrease in postoperative pain and an earlier return to work, along with much improved cosmesis for the new procedure., Conclusions: Although the study was conducted with a limited number of patients and a very short follow-up, it is worth considering this method over laparoscopic and conventional techniques, especially in reducible hernias.

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.

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.

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.

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., (Copyright 2003 Wiley-Liss, Inc.)

Purpose: Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer., Patients and Methods: One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system., Results: Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P =.61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays., Conclusion: This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.

Purpose: To investigate the efficacy of dexamethasone as a prophylactic antiemetic for patients receiving fractionated radiotherapy to the upper abdomen in a randomized controlled trial., Patients and Methods: One hundred fifty-four patients planned to receive fractionated radiotherapy to fields involving the upper abdomen (minimum total dose, 20 Gy; minimum number of fractions, five) were randomized to receive prophylactic dexamethasone (2 mg orally three times a day [tid], starting in the morning of first treatment and continuing until after their fifth treatment) or placebo. The primary end point of the study was the proportion of patients free from emesis during the study period. Secondary end points included a quality-of-life assessment using the core questionnaire of the European Organization for Research and Treatment of Cancer and side effects of dexamethasone therapy in this population of patients., Results: Fifty-four (70%) out of 75 patients receiving dexamethasone had complete protection versus 37 (49%) out of 75 patients on placebo (P = .025). Most emetic episodes occurred during the initial phase of treatment. Although there was no difference in global quality of life between the two sets of patients, patients receiving dexamethasone had less nausea and vomiting and less loss of appetite but more insomnia., Conclusion: Dexamethasone 2 mg tid seems to be an effective prophylactic antiemetic in this situation. Side effects were acceptable, but there seemed to be no overall effect on global quality of life.

Although captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been shown to exert a beneficial effect on cardiac function in heart failure, its effect on the status of sarcoplasmic reticulum (SR) Ca(2+) transport in the failing heart has not been examined previously. In order to determine whether captopril has a protective action on cardiac function, as well as cardiac SR Ca(2+)-pump activity and gene expression, a rat model of heart failure due to myocardial infarction was employed in this study. Sham operated and infarcted rats were given captopril (2 g/l) in drinking water; this treatment was started at either 3 or 21 days and was carried out until 8 weeks after the surgery. The untreated animals with myocardial infarction showed increased heart weight and elevated left ventricular end diastolic pressure, reduced rates of pressure development and pressure fall, as well as depressed SR Ca(2+) uptake and Ca(2+)-stimulated ATPase activities in comparison with the sham control group. These hemodynamic and biochemical changes in the failing hearts were prevented by treatment of the infarcted animals with captopril. Likewise, the observed reductions in the SR Ca(2+) pump and phospholamban protein contents, as well as in the mRNA levels for SR Ca(2+) pump ATPase and phospholamban, in the failing heart were attenuated by captopril treatment. These results suggest that heart failure is associated with a defect in the SR Ca(2+) handling and a depression in the gene expression of SR proteins; the beneficial effect of captopril in heart failure may be due to its ability to prevent remodeling of the cardiac SR membrane., (Copyright 1999 Academic Press.)

Background: There is a well recognized need for a system capable of providing effective support for patients with hepatic failure pending liver regeneration or liver transplantation. Recent attempts of using bioartificial liver containing encapsulated porcine hepatocytes, the deployment of emergency whole liver, or hepatocyte transplantation are complex and not consistently successful. The technique of ex vivo hepatic perfusion developed and used clinically by Abouna in the 1970s, has now been redesigned in a perfusion circuitry that mimics the physiological conditions of a normal liver. Before clinical application of this system, a preclinical trial was carried out in dogs with induced hepatic failure., Methods: Acute hepatic failure was induced in dogs by an end-to-side porto caval shunt, followed 24 hr later, by a 2-hr occlusion of the hepatic artery. All animals (n=18) were medically supported and were divided into three groups. In the control group (n=6) only medical support was used. In the experimental group (n=12) the animals were connected to the ex vivo liver support apparatus during acute hepatic failure via an AV shunt using a dog liver (n=6) or calf liver (n=6) (after a temporary extracorporeal bovine kidney transplant to remove preformed xeno antibody). Hepatic perfusion was carried out at 37 degrees C through the hepatic artery and portal vein at physiological pressures, and blood flow rate for 6-8 hr., Results: All control animals died of progressive hepatic failure at 14-19 hr after clamping the hepatic artery. The animals treated with ex vivo liver showed remarkable clinical and biochemical improvement. Five animals survived for 36-60 hr. Another seven animals recovered completely and became long-term survivors with biochemical and histological evidence of regeneration of their own liver. Biopsy of the allogeneic ex vivo liver at the end of perfusion showed some interstitial edema. Similar biopsy of the xenogeneic calf liver showed only mild and delayed xenograft rejection, which was most likely due to removal of preformed xeno antibody by temporary transplantation of the calf kidney before liver perfusion., Conclusions: The observations and results obtained in this trial strongly confirm that extracorporeal perfusion through a whole liver, using the system described, is very successful and cost effective for the treatment of acute, but reversible hepatic failure, as well as serving as a bridge to liver transplantation. The time has come for this form of liver support technology to be reintroduced and widely used.

Objective: Earlier studies have revealed sarcolemmal (SL) defects in congestive heart failure due to myocardial infarction; however, the mechanisms of SL changes in the failing heart are poorly understood. Since congestive heart failure is associated with various metabolic abnormalities including a deficiency of carnitine, we examined the effects of propionyl L-carnitine, a carnitine derivative, in animals with congestive heart failure., Methods: For this purpose, heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated with 100 mg/kg (i.p. daily) propionyl L-carnitine for 4 weeks. The sham control group received saline injections. The animals were assessed for their left ventricular function. SL membranes were examined for Na(+)-K+ ATPase, Na(+)-Ca2+ exchange and adenylate cyclase activities., Results: A marked improvement in the attenuated left ventricular function of the experimental animals was seen upon treatment with propionyl L-carnitine. The SL adenylyl cyclase activities in control, untreated failing hearts and treated failing hearts were 590 +/- 36, 190 +/- 22 and 320 +/- 21 pmol cAMP/mg/10 min, whereas the SL Na(+)-K+ ATPase activities were 35.7 +/- 2.8, 22.5 +/- 2.4 and 30.1 +/- 2.8 mumol Pi/mg/h, respectively. Furthermore, the SL Na(+)-dependent Ca(2+)-uptake activity, which decreased in the failing hearts (4.6 +/- 0.4 vs. 9.3 +/- 0.7 nmol Ca2+/mg/2 s for control), was improved (6.8 +/- 0.5 nmol Ca2+/mg/2 s) significantly following treatment with propionyl L-carnitine., Conclusion: These results indicate that metabolic therapy with propionyl L-carnitine may attenuate defects in the SL membrane and thus may improve heart function in congestive heart failure due to myocardial infarction.

Eighty-two patients with non-compressive myelopathy have been studied from July 1994 to June 1996 in Bangur Institute of Neurology and S.S.K.M. Hospital, Calcutta, of which 48 patients were men and 34 patients were women. Presentation was acute in 40 patients (48.78%), subacute in 7 (8.53%), chronic in 27 (32.92%) and history of relapse and remission in 8 (9.75%) patients. Preceding as well as simultaneous fever was observed in 16 cases (19.5%); vaccination (anti-rabies) in 1 case (1.21%); drug abuse in 1 case (1.21%); arthralgia-myalgia and rash in 2 cases (2.42%) and history of electrocution in 2 cases (2.42%). Only pyramidal tract involvement was present in 24 cases (29.26%) and remaining 58 cases (70.73%) had pyramidal tract affection with other sites of involvement. CSF study carried out in 60 cases, revealed rise of protein in 31 (37.8%); oligoclonal band had been detected in 6 (7.31%), pleocytosis in 18 cases (21.95%) and increased IgG index greater than 6.66 in 2 cases (2.42%). CT myelogram done in 23 cases revealed no abnormality. MRI study carried out in 59 cases showed myelomalacia in 1 (1.21%); demyelination plaque in 14 cases (17.07%); atrophy of cord in 3 (3.65%); infarction of cord in 1 (1.21%) and in 40 cases (48.78%) no abnormality could be detected. Etiological diagnosis could be established in 59 (71.95%) cases such as transverse myelitis or myelopathy (post infectious) in 24 (29.26%); demyelination in 16 (19.51%); vascular and vasculitis in 3 (3.65%); toxic in 1 (1.21%); physical (electrocution) in 2 cases (2.42%). In the remaining 23 cases (28.04%) no aetiological factors could be found.

The moderately pyridoxine (vitamin B6)-deficient male rat was introduced by us as an animal model (B6DHT) for the study of hypertension. Hypertension in this rat is associated with increased sympathetic stimulation. Arterial segments from B6DHT rats maintained a higher resting tone. The influx of 45calcium into intracellular compartment of the vascular smooth muscle of the caudate artery of B6DHT rats was also enhanced. Administration of pyridoxine attenuated the hypertension in B6DHT rats as well as in genetic or dietary-induced moderately hypertensive conditions such as in the Zucker obese rat and sucrose or low calcium-fed rats. However, pyridoxine did not have any effect on the spontaneously hypertensive rat. All classes of calcium channel blockers were effective in lowering the systolic blood pressure of B6DHT rats. The increased in vitro influx of 45calcium into intracellular compartment of artery segments of B6DHT rats as well as the BAY K 8644-induced influx of 45calcium into artery segments from normal rats were blocked by pyridoxal phosphate as well as by dihydropyridine-sensitive calcium channel blockers (DHP). Pyridoxal phosphate (PLP) in vitro enhances the binding of calcium channel antagonists to membrane preparations from vascular tissue. PLP corrects the membrane abnormality in responsive hypertensive conditions and thus, could be an endogenous modulator of DHP-sensitive calcium channels.

Seventy three patients with myasthenia gravis were studied over 9 years period (1987-1995) in departments of neuromedicine, respiratory care unit, cardiothoracic unit of Institute of Postgraduate Medical Education and Research and Bangur Institute of Neurology, Calcutta, with reference to their clinical presentations, laboratory findings and various modes of treatment. Commonest age of presentation was 5th decade in men and 3rd decade in women. Fifty five percent of patients belong to type 2A myasthenia gravis (Osserman classification). Presentation was insidious (67.2%) and course was slowly progressive (65.7%) in majority of cases. Fatigability and ptosis were commonest clinical presentation and diurnal variation was noticed in 60% of cases. Edrophonium test was positive in 90.4% of cases and repetitive nerve stimulation showed 93.5% positivity in 30 cases. 27 patients (36.9%) underwent thymectomy and out of these, 89% of patients showed hyperplastic change and thymoma in 11% of cases. Mortality rate including both operated and nonoperated patients was recorded to be 9.6%. We observed earlier onset of myasthenia in male, higher incidence of oculo-bulbar involvement and lower incidence of respiratory problem and thymoma.

Full text is available as a scanned copy of the original print version.

Strains of Vibrio parahaemolyticus were isolated from clinical, marine and freshwater fish of Calcutta, West Bengal, India. Drug and metal resistance characteristics were compared for differentiation of clinical and environmental strains. Eighteen out of the twenty environmental isolates were resistant to arsenate, unlike the clinical isolates which were all susceptible. All the thirty-five isolates of V. parahaemolyticus were resistant to ampicillin and streptomycin.

Although congestive heart failure subsequent to myocardial infarction is known to be associated with increased sympathetic activity, very little information regarding changes in the sympathetic nerves in the left and right ventricles at various stages after infarction is available. Male Sprague-Dawley rats were subjected to coronary artery ligation and studied 4 and 8 weeks later; these animals had mild and moderate stages of congestive heart failure. A sham group, without coronary ligation, was used as control. Four weeks after myocardial infarction, plasma and ventricular (left and right) epinephrine (EPI), unlike norepinephrine (NE), were markedly increased. Whereas plasma catecholamine (EPI and NE) levels were increased 8 weeks after infarction, NE concentration in the left ventricle was unchanged but EPI concentration was increased in comparison with sham control. The right ventricle showed an increased level of both NE and EPI 8 weeks after infarction. Measurement of the rate of change in the specific activity of NE (NE turnover) in the left and right ventricles 8 weeks after infarction revealed an increase in NE turnover in the left ventricle, without any changes in the right ventricle. The concentration of EPI, unlike NE, was increased in the kidney, spleen, and brain 8 weeks after coronary occlusion. These results are interpreted to mean that congestive heart failure caused by myocardial infarction is associated with differential changes in the status of sympathetic nerves in the left and right ventricles; sympathetic activity is increased only in the left ventricle, whereas the right ventricle may play an adaptive role by increasing catecholamine stores during the development of heart failure.

Because major cardiovascular disease states are characterized by defects in adenylyl cyclase regulation, it becomes important to understand the mechanisms by which adenylyl cyclase activators affect inotropy and chronotropy in intact conscious animals. Accordingly, we examined the inotropic and chronotropic responses to forskolin in 11 normal conscious, chronically instrumented dogs and 3 dogs with ventricular denervation (VD). Left ventricular first derivative of pressure (LV dP/dt) increased by 96 +/- 7%, P < 0.05, in response to forskolin (50 nmol.kg-1.min-1) in normal dogs and by significantly less, 52 +/- 14%, in VD dogs. Circulating norepinephrine (NE) levels increased similarly in both groups (from 226 +/- 18 to 389 +/- 33 pg/ml in normal dogs, from 177 +/- 23 to 329 +/- 71 pg/ml in VD dogs). In the presence of ganglionic blockade, the increase in LV dP/dt in response to forskolin was reduced (+62 +/- 4%) in normal dogs but was unchanged in VD dogs (+52 +/- 12%). Ganglionic blockade abolished the increase in circulating NE levels in both groups. Increases in heart rate in the presence of ganglionic blockade (+54 +/- 6 beats/min) were less than in the presence of atropine alone (+92 +/- 10 beats/min). Notably, the LV dP/dt and heart rate responses to forskolin were further attenuated by beta-adrenergic receptor blockade in the presence and absence of ganglionic blockade. Morphine also attenuated the increases in both LV dP/dt and plasma NE in response to forskolin. Increases in LV dP/dt in response to NKH-477 (30 micrograms/kg), a water-soluble forskolin derivative, were similar before and after ganglionic blockade (+63 +/- 8 and +51 +/- 10%, respectively). However, in vitro experiments in LV sarcolemmal membrane preparations demonstrated that stimulation of adenylyl cyclase by forskolin and NKH-477 was not affected by beta-adrenergic receptor blockade. These results indicate that in conscious dogs, inotropic and chronotropic effects of forskolin are not only due to direct activation of adenylyl cyclase, but the effects also are mediated by neural mechanisms and potentiated by the prevailing level of sympathetic tone.

Objectives: We examined the possible effect of neuropeptide Y in modulating central sympathetic activity after myocardial infarction in rats., Background: Previous studies have shown the coexistence of neuropeptide Y and norepinephrine in the brain and a possible functional interaction between the two. Neuropeptide Y inhibits the release of norepinephrine at the presynaptic level and can be considered to act as a neuromodulator., Methods: Two groups of rats were examined in this study-an experimental group, defined as those rats undergoing left coronary artery ligation, and a sham group without coronary artery ligation, serving as the control group. The animal in both groups underwent microdialysis in the paraventricular nucleus at 2, 4 and 8 weeks after operation. Microdialysis samples were collected with and without injecting neuropeptide Y in the paraventricular nucleus. The concentration of norepinephrine was determined by injecting purified microdialysate samples during high performance liquid chromatography. To explore the receptor's possible role, autoradiographic localization of neuropeptide Y receptors in the paraventricular nucleus was also carried out in the experimental and sham groups., Results: The concentration of norepinephrine measured in the samples was decreased by 50% with neuropeptide Y in 2- and 4-week old rats after infarction, but by only 20% (p < 0.05) in 8-week old rats after infraction. The diminished inhibitory effects of neuropeptide Y on norepinephrine release was associated with increased sympathetic activity, as reflected by plasma norepinephrine; 8-week old rats after infarction had almost a 100% (p < 0.05) increase in their plasma norepinephrine level compared with the sham group. Autoradiography revealed a significant decrease in density of neuropeptide Y receptors in the paraventricular nucleus in 8-week old rats after infarction (p < 0.05)., Conclusions: The data presented in this report suggest that the reduction of the inhibitory activation of neuropeptide Y on sympathetic release may contribute to elevated norepinephrine levels after myocardial infarction.

Neuropeptide Y has been shown to inhibit contractility in the rat heart. Although the reasons for this effect are not known, it is possible that postsynaptic adrenergic mechanisms involving neuropeptide Y may be responsible. To ascertain whether this neuromodulatory effect is possible for decreasing contractility, we investigated the effect of neuropeptide Y on agonist-stimulated contractility of the isolated rat myocardium. Receptor binding studies of purified cardiac membranes showed that incubating membrane in the presence of neuropeptide Y (10(-7) mol/L) decreased the number of alpha-/beta-adrenoceptor binding sites without affecting the affinity of these receptors. Isolated hearts perfused with phenylephrine (10(-5) to 10(-10) mol/L) or isoproterenol (10(-5) to 10(-10) mol/L) in a nonrecirculating Langendorff setup demonstrated a significant increase in contractility over control values, whereas no change in contractility was observed when the hearts were perfused with neuropeptide Y (10(-7) mol/L). However, in the presence of both agonist and neuropeptide Y the increase in contractility previously seen with agonist alone was not evident. Comparisons made with hearts taken from aortic banded rats yielded similar results. Although neuropeptide Y itself was ineffective in decreasing contractility, it prevented the agonists from stimulating contractility when perfused together. We conclude that neuropeptide Y does not directly decrease contractility but prevents agonist-stimulated increases in contractility through alpha-/beta-adrenoceptor pathways. This neuromodulatory effect of neuropeptide Y is unchanged in situations of increased sympathetic activity, such as hypertension.

In a prospective study, the prognostic value of clinical characteristics and CT scan findings in 50 patients of intracerebral haemorrhage (ICH) has been examined. Follow up has been done over 6 months period. Each patient has been individually followed up for 8 weeks. At the end of the follow up period 34% of the patients died, 36% were dependent on outside help for daily living while 30% were capable of independent existence. Age of more than 60 yrs, Glasgow Coma Scale (GCS) Score of 6 or less (in a modified Scale of 10) at the time of admission, ICH volume greater than 30 ml., midline shift in CT scan of more than 3 mm and presence of intraventricular haemorrhage (IVH) and hydrocephalus had an adverse impact on outcome. Young age, GCS score of more than 8, ICH volume of less than 20 ml, presence of lobar haemorrhage and absence of IVH/hydrocephalus were associated with relatively favourable outcome.

Changes in dopamine neurotransmission in the nucleus accumbens of the spontaneously hypertensive rat (SHR) may be involved in the pathogenesis of hypertension. This investigation tested the hypothesis that the sulfated octapeptide cholecystokinin (CCK8S) induced release of dopamine is greater in the SHR than in its normotensive control, the Wistar-Kyoto rat (WKY). Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were sampled using microdialysis in the caudal half of the nucleus accumbens of 10-week-old anesthetized SHRs and WKYs. Samples were collected in the following order: 3 baseline, 3 CCK8S (10 mumol/l), and 3 postdrug samples. The samples were then analyzed using high pressure liquid chromatography with electrochemical detection. CCK8S increased dopamine and DOPAC levels in both the SHR and WKY with a larger increase in basal dopamine in the SHR (greater than 200%). Perfusion of the nucleus accumbens with 1 mumol/l of CCK8S or the nonsulfated form of CCK8 (CCK8US, 10 mumol/l) produced no significant increase in the release of dopamine in the SHR. These results indicate that CCK8S-induced release of dopamine in the nucleus accumbens is greater in the SHR. Changes in CCK8S neurotransmission/receptor function may be responsible for the alterations in dopaminergic function of the SHR and the pathogenesis of hypertension.

The basolateral region of the amygdala and the lateral hypothalamic area are involved in cardiovascular regulation. The aim of the present investigation was to determine if the terminal field of afferent projections from the basolateral nucleus of the amygdala to the nucleus accumbens overlap with the origin of the efferent projections from the nucleus accumbens to the lateral hypothalamic area. Neurons projecting from the nucleus accumbens to the lateral hypothalamic area were labeled by injecting the retrograde tracer Fluoro-Gold in the lateral hypothalamus of rats. In the same rats, fiber terminals from the amygdala to the nucleus accumbens were labeled by injecting the anterograde tracer Fluoro-Ruby in the basolateral region of the amygdala. Injections of Fluoro-Gold in the lateral hypothalamus labeled neurons in the posteromedial portion of the nucleus accumbens. Injections of Fluoro-Ruby in the basolateral amygdala labeled fibers and terminals in all parts of the nucleus accumbens with the highest density being found in the posteromedial part of the nucleus accumbens where Fluoro-Gold-labeled neurons were located. When regions of the posteromedial nucleus accumbens were examined under high-magnification, Fluoro-Ruby-labeled terminals appeared to make contact on Fluoro-Gold-labeled dendrites and cell bodies. This investigation demonstrates that there is a distinct overlap in the posteromedial region of the nucleus accumbens between the terminal field from neurons originating in the amygdala and neurons which project to the lateral hypothalamus. In addition, neurons in the basolateral amygdala appear to make synaptic contact with neurons in the nucleus accumbens that project to the lateral hypothalamic area.(ABSTRACT TRUNCATED AT 250 WORDS)

We employed receptor autoradiography to test the hypothesis that changes in cholecystokinin neurotransmission in the striatum of the young spontaneously hypertensive rat (SHR) is involved in the development of hypertension. The binding density of 125I-Bolton Hunter labelled cholecystokinin octapeptide (125I-BH-CCK8) in the striatum of 5-week-old prehypertensive SHRs and its normotensive control the Wistar-Kyoto rat (WKY) was determined using computer-assisted densitometry. We found a significant increase in 125I-BH-CCK8 binding density in the nucleus accumbens of the SHR. No difference between the binding density of 125I-BH-CCK8 was found in the caudate-putamen and the prefrontal cortex of SHRs and WKYs. These results suggest that changes in CCK8S neurotransmission or receptor function are not secondary to an increase in arterial blood pressure and, therefore, may be involved in the development of hypertension.

The present study examined the effect of fenoldopam, a known dopamine-1 receptor (DA1) agonist in order to understand its involvement in the cardiac hypertrophic process. Male Sprague-Dawley rats underwent abdominal aortic constriction (AB) with placement of a suprarenal ligature while sham operated animals served as controls. The AB groups showed an increase in their heart wt, left ventricular (LV) wt, heart wt/body wt and LV wt/body ratio. Furthermore, the length of these hearts, as measured from the auriculoventricular border to the apex, LV wall and interventricular (IV) septal thickness were increased from control levels. Treatment with SCH 23390, a DA1 antagonist, on the other hand, was able to partially regress the cardiac hypertrophic changes. All these parameters were also increased in control animals treated with fenoldopam (F). Such changes were more striking in the F+AB group which showed a significant acceleration of the cardiac hypertrophic process on superimposing the two treatments. Plasma dopamine and renin activity were increased in all the groups as compared to control. These results indicate that dopamine receptors are implicated in the development of cardiac hypertrophy.

The colonization ability of a representative epidemic strain of V. cholerae O139 Bengal was studied in the oral rabbit colonization model and the nature of colonization in the ileal and jejunal tissues was examined ultrastructurally. Results of the colonization study and ileal loop assay indicated that the strain proliferates and colonizes the small intestine of the rabbit mucosal surface. Further, the electronmicroscopic study revealed the disruptive effect of the strain on the apical membrane of the epithelial cells. The results of this study suggested that apart from colonization, invasion of the bacteria was important in the pathogenesis of V. cholerae O139 mediated infections.

1. The characteristics of dopamine (D) receptors were studied in kidney using the radiolabelled receptor assay of [3H]-SCH-23390 for D1 and [3H]-sulpiride for D2 receptors during cardiac hypertrophy. Male Sprague-Dawley rats (175-200 g) underwent abdominal aortic constriction above the renal arteries and were studied 28 days thereafter. Sham operated animals without aortic constriction were used as control. 2. Membranes obtained from kidney cortex showed an increase in the number of binding sites (Bmax) of D1 receptors in the aortic banded group. The apparent affinity for the ligand (Kd) was unchanged with D1 receptors, as compared to sham control. Both Bmax and Kd were unchanged for D2 receptors in the aortic banded group. 3. Autoradiographic data further reinforced the findings, showing an increased number of D1 receptors in the kidney at 28 days after abdominal aortic constriction. These changes were associated with an increase in plasma renin activity in the aortic banded group. Further, Na(+)-K(+)-ATPase as measured by fmol of 32Pi released from [gamma-32P]-ATP, was decreased in the kidney cortex of banded animals. 4. Reversal of hypertrophic parameters was observed in the aortic banded group treated for 14 days with SCH 23390 hydrochloride (0.1 mg kg-1 i.p.), a known D1 receptor antagonist. 5. The present study shows an upregulation of renal D1 receptors following abdominal aortic constriction and it is suggested that upregulation of D receptors may be involved in the development of cardiac hypertrophy.

The effect of neuropeptide Y on the number and affinity of catecholamine receptors in the ventricular myocardium was investigated. Receptor binding studies showed that incubation of cardiac membrane in the presence of neuropeptide Y (NPY, 10(-7) M) decreased the number of alpha/beta-adrenoceptor binding sites (Bmax) without affecting the affinity (KD) of these receptors. Although not able to modulate the contractility by itself, NPY was able to decrease the positive inotropic effects of phenylephrine and isoproterenol in the isolated, perfused myocardium. Ca2+/Mg(2+)-ATPase activity, measured from the sarcolemma, sarcoplasmic reticulum and myofibrils, was unaltered whereas the activity of sarcolemmal Na+/K(+)-ATPase was decreased when NPY was included in the media. On the other hand, NPY was shown to increase the phosphoinositide-phospholipase C associated with the sarcolemma. These findings support the hypothesis that NPY modulates postsynaptic adrenergic receptors in the myocardium and can affect the adrenergic-induced, inotropic response.