Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat

The efficacy of various drugs used to treat ulcerative colitis, (sulfasalazine, 5-aminosalicylate, hydrocortisone) was investigated in a model of acetic acid-induced colitis in the rat. Subsequently, we tested the ability of antioxidant/5-lipoxygenase inhibitors (gossypol and nordihydroguiaretic acid [NDGA]) and a cyclooxygenase inhibitor (indomethacin) to attenuate the macroscopic colonic damage and/or neutrophil influx (myeloperoxidase activity [MPO]) associated with this model of colitis. Oral pretreatment with either sulfasalazine, gossypol, or NDGA significantly decreased colonic MPO activity induced by acetic acid. Intrarectal administration of such drugs resulted in an even larger reduction of the colonic inflammation, with gossypol being the most potent compound. Oral or intrarectal administration of corticosteroids (dexamethasone, hydrocortisone) also attenuated the parameters of acetic acid induced colitis. In contrast, pretreatment with indomethacin was ineffective, or when administered daily after colitis induction, indomethacin actually increased colonic neutrophil influx significantly. Our data suggest that both the route of drug administration and dosing regimen employed affect the antiinflammatory potency and/or efficacy of compounds on colitis induced by acetic acid in the rat. Drugs which were effective against this colitis may act by scavenging of oxygen derived free radicals.     

Initial evaluation of123|-5-|-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT₂ receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150 or¹²³I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT_2A receptors. This study reports on preliminary¹²³I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT_2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT_2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that¹²³I-5-I-R91150 may be used for the imaging of 5-HT_2A receptors in the living human brain with SPET.     

Spiral laminar flow in the abdominal aorta: a predictor of renal impairment deterioration in patients with renal artery stenosis?

BACKGROUND: Spiral or helical arterial blood flow patterns have been widely observed in both animals and humans. The absence of spiral flow has been associated with carotid arterial disease. The aim of this study was to detect the presence of aortic spiral flow using magnetic resonance imaging (MRI) and to evaluate the relationship of the presence of spiral aortic flow with renal arterial disease and renal function in the follow-up of patients with suspected renal atheromatous disease. METHODS: Prospective study of 100 patients with suspected renal arterial disease and 44 patient controls. Using a 1.5 T MRI unit (Siemens Symphony), phase contrast flow quantification and three-dimensional contrast enhanced MR angiography of the abdominal aorta were performed. Renal arterial stenoses (RAS) were classified minimal, moderate or severe. Renal function was followed at 3 months before and 6 months after MRI. RESULTS: Non-spiral flow was more prevalent in patients with more severe RAS. Renal impairment progressed significantly in severe RAS without spiral flow (P = 0.0065), but did not progress significantly in severe RAS with spiral flow (P = 0.12). In minimal or moderate RAS with or without spiral flow there was no significant progression (P = 0.16, 0.13, 0.47, 0.092, respectively). CONCLUSIONS: Aortic spiral blood flow can be assessed with MRI. Lack of aortic spiral blood flow in patients with severe RAS is associated with significant short-term renal function deterioration. Determination of blood flow patterns may be a useful indicator of renal impairment progression in patients with suspected renal artery stenosis.     

International cancer patterns in men: geographical and temporal variations in cancer risk and the role of gender

The comparison of disease risk in populations stratified by certain demographic variables provides important clues as to the underlying causes of disease. There are fundamental variations in the risk of occurrence of different cancers by gender, area of residence, and time of diagnosis. Men are, for instance, at considerably higher risk of developing most of the common cancers that occur in both sexes, and there are substantial variations in the occurrence of particular cancers in different regions of the World. This paper attempts to highlight some of these remarkable variations using cancer incidence data by sex, area of residence and year of diagnosis, emphasising the strong evidence that many of the contrasts can be appropriated to a number of modifiable “environmental” factors.Rates of cancer occurrence in the developed world are double that of less developed regions, although risk patterns are of very different magnitude and direction depending on the cancer site examined. Lung cancer is the most common neoplasm in men globally, but is overshadowed by prostate cancer in certain westernised countries, notably in the U.S. Cancers of the colon and rectum are important in the developed world, whereas stomach and liver cancer are common in developing areas.Men have systematically higher rates than women for the vast majority of the tumours that develop in both sexes, with the exception of thyroid cancer. There are also huge variations in the extent of the inequality: men have notably elevated risks, relative to women, of developing tumours of the head and neck, bladder, lung, oral cavity and liver.In Europe, incidence trends of lung cancer tend to be declining in men, although there is substantial between-country variation. In women, lung cancer rates are systematically on the increase in most Western, Southern and European countries. Trends in prostate cancer are increasing, as are trends in colorectal cancer (in both sexes), although more noticeably in Southern and Eastern Europe. Stomach cancer continues to fall in most European areas. Bladder cancer is decreasing in both men and women, apart from in Eastern Europe, whereas cancers of the kidney and non-Hodgkin lymphoma are steadily increasing in both sexes.We have estimated that men have better and more readily achievable prospects of avoiding death from cancer since they have lower rates of gender specific cancers, that are probably hormonal in origin, then women. Tobacco consumption plays a dominating role in the excess risk of cancer in men but it is apparent that the male excess disease burden can be effectively reduced by various prevention measures. As well as avoiding (or quitting) smoking, these include, moderating alcohol consumption, avoiding obesity, undertaking regular physical exercise, and maintaining a diet high in fruit and vegetables. The adoption of a healthier lifestyle will be of considerable benefit to the general health of both men and women, with an expectation of a major reduction in the burden of cancer, as well as other major diseases.     

Embedding Medical Student Computer Tutorials into a Busy Emergency Department

Objectives
To explore medical students' use of computer tutorials embedded in a busy clinical setting; to demonstrate that such tutorials can increase knowledge gain over and above that attributable to the clinical rotation itself.
Methods
Six tutorials were installed on a computer placed in a central area in an emergency department. Each tutorial was made up of between 33 and 85 screens of information that include text, graphics, animations, and questions. They were designed to be brief (10 minutes), focused, interactive, and immediately relevant. The authors evaluated the intervention using quantitative research methods, including usage tracking, surveys of faculty and students, and a randomized pretest-posttest study.
Results
Over 46 weeks, 95 medical students used the tutorials 544 times, for an overall average of 1.7 times a day. The median time spent on completed tutorials was 11 minutes (average [SD], 14 [±12] minutes). Seventy-four students completed the randomized study. They completed 65% of the assigned tutorials, resulting in improved examination scores compared with the control (effect size, 0.39; 95% confidence interval = 0.15 to 0.62). Students were positively disposed to the tutorials, ranking them as "valuable." Fifty-four percent preferred the tutorials to small group teaching sessions with a preceptor. The faculty was also positive about the tutorials, although they did not appear to integrate the tutorials directly into their teaching.
Conclusions
Medical students on rotation in a busy clinical setting can and will use appropriately presented computer tutorials. The tutorials are effective in raising examination scores.     

Regulation of neurotransmitter enzyme by quisqualate subtype glutamate receptors in cultured cerebellar and hippocampal neurons

The possible involvement of ionotropic and metabotropic quisqualate (QA) receptors in neuronal plasticity was studied in cultured glutamtergic cerebellar or hippocampal cells in terms of the specific activity of phosphate-activated glutaminase, an enzyme important in the synthesis of the putative neurotransmitter pool of glutamate. When cerebellar of hippocampal neurons were treated with QA, it elevated the specific activity of glutaminase in a dose-dependent manner. The half-maximal effect was obtained at about 0.1 μM, the maximum increase was at about 1 μM, but levels higher than 10 μM QA produced progressive reduction in glutaminase activity. In contrast, QA had little effects on the activities of lactate dehydrogenase and aspartate aminotransferase and the amount of protein, indicating that the increase in glutaminase was relatively specific. The QA-mediated increase in glutaminase was mimicked by the ionotropic QA receptor agonist -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; EC₅₀, about 0.5 μM), but not by the metabotropic QA receptor agonist trans-(±)-1-aino-cyclopentyl-1,3,dicarboxyalte (t-ACPD; up to 0.5 mM). The specific ionotropic QA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited QA- and AMPA-mediated increases in glutaminase activity in a dose-dependent manner, whereas other glutamate receptor antagonists, -2-amino-5-phosphonovalerate, γ- -glutamyl aminomethyl sulphonic acid and γ- -glutamyl diethyl ester were ineffective. The elevation of neurotransmitter enzyme was Ca²⁺-dependent. The increase in Ca²⁺ influx essentially through the activation of L-type voltage-operated Ca²⁺ channels, and not the mobilization of internal Ca²⁺ stores, was responsible for these QA receptor-mediated long-term plastic changes in hippocampal and cerebellar neurons.     

Prospective study of bacterial and viral contamination of exercise equipment.

OBJECTIVE: Transmission of bacterial and viral pathogens is known to occur by hand contact with fomites. Exercise equipment in public facilities may serve as such fomites. It is not known whether equipment disinfection might reduce microorganism colonization. We performed studies to address these issues. DESIGN: Observational study of bacterial and viral culture results from hand-contact surfaces of exercise equipment, pre-exercise and postexercise; prospective study of viral culture results before and after intervention with disinfection solution. SETTING: Two fitness centers in a military community. INTERVENTION: One week trial of twice-a-day equipment disinfection. MAIN OUTCOME MEASURES: Type and number of bacteria and type of viruses present on equipment before and after exercise; prevalence of viral culture positivity on equipment before and after intervention. RESULTS: Bacterial cultures of body contact surfaces on equipment revealed benign bacterial species (coagulase-negative staphylococci, diphtheroids, and so forth) but no pathogenic bacteria whether obtained pre-exercise or postexercise, or whether from aerobic versus weight training equipment. Viral cultures revealed the presence of viruses (generally rhinoviruses) on 63 of 100 (63%) hand-contact surfaces of equipment. Weight equipment was significantly more often contaminated than aerobic equipment (73% vs. 51%; P = 0.026). Disinfection of equipment did not lower the prevalence of virus isolation (48% positive before cleaning; 86% positive after cleaning). CONCLUSIONS: There is little risk of exposure to pathogenic bacteria on exercise equipment. Such equipment may commonly serve as fomites for the transmission of viruses. These data do not suggest that disinfection of exercise equipment will offer significant protective effects against virus exposure.