Cytokines dynamics in a wistar rat model infected with Mycobacterium Tuberculosis strain H37Rv.

Background: The immunology characteristics of the rat model of tuberculosis (TB) infection are still unclear. This study aimed to evaluate the dynamics of pathology and cytokines in a rat model infected with Mycobacterium TB (MTB). Methods: Sixty male Wistar rats were divided into four groups, namely the control group (without MTB infection) and the MTB -induced group (observations at week-3, week-6, and week-12 postinfection). Granuloma formation was analyzed by histology procedure. Analysis of the levels of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), IL-17, IL-2, IL-4, and IL-12 was performed using an enzyme-linked immunosorbent assay technique. Results: The number and size of the ganulomas increased proportionally between weeks 6 and 12 postinfection. Several cytokines, namely IL-6, IL-17, IL-2, IL-4, and IL-12 significantly increased in the 6th week compared to the 3rd week after infection (P < 0.05). These cytokines decreased significantly at the 12th week compared to the 6th week (P < 0.05). TNF-α was found to be stable at the third and 6th weeks and then decreased at the twelfth postinfection week. For IL-12, the longer the infection time, the higher the level. Conclusions: It was concluded that there was a typical pattern of TB infection in Wistar rats, namely certain cytokines that peaked at week 6 of infection. Thus, TB infection in rats can be a model for early-phase TB study.

Kinetics of Granuloma, IFN-γ and IP-10 in a Wistar Rat Model Infected with Mycobacterium Tuberculosis.

Background: Improved access and treatment are critical to controlling the problem. Molecular diagnostic tests, although available, are not feasible in developing countries. Where available, these tests require state-of-the-art laboratories and are not cheap. One alternative to molecular diagnostics is the use of acute phase protein values. This protein is a protein whose levels will increase or decrease in plasma in response to injury or inflammation. Objective: This study aimed to analyze the kinetics of granulomas and the role of IFN-γ and IP-10 in the pathology of tuberculosis in a rat model. Methods: Sixty Wistar rats were divided into four groups, namely the control group (without MTB induction) and the MTB-induced group (observations at week-3, week-6, and week-12 post infection). Induce tuberculosis with bacterial strain H37Rv ATCC 27294. Results: The number and size of the granuloma increased to a peak at week 6 and was consistent for weeks 6 and 12 post-infection. The kinetics of granulomas were consistent with IFN-γ and IP-10 levels. Conclusion: It was concluded that the model of tuberculosis infection by the H37Rv ATCC 27294 strain in Wistar rat found granuloma characteristics and IFN-γ and IP-10 patterns in similar kinetics, so that there was involvement of these molecules in TB pathology. Thus, tuberculosis infection of the H37Rv ATCC 27294 strain in rats can serve as a model for rapid tuberculosis study and display a complete pathological phase.

A "safe space" for learning and reflection: one school's design for continuity with a peer group across clinical clerkships.

The value of continuity in medical education, particularly during clerkships, is increasingly recognized. Previous clerkship-based models have described changes that emphasize continuity in patient care, learner supervision, and curriculum. The creation of continuous student peer groups can foster interactions that enhance mutual support through uncomfortable professional transitions during the clerkship years. Here, the authors describe a third-year clerkship model based at the San Francisco Veterans Affairs (VA) Medical Center called VA Longitudinal Rotations (VALOR), designed explicitly to establish a supportive learning environment for small peer groups.Seven groups of medical students (42 total) completed VALOR across three academic years between 2007 and 2009. On clerkships during VALOR, one hour per week was designated for faculty-facilitated sessions amongst peer groups. Students' perceptions of peer group support and overall program satisfaction were determined with immediate post surveys and focus groups at the end of VALOR, and with follow-up surveys 5 to 27 months after completing VALOR. Students strongly valued several elements of VALOR peer groups, including support through clerkship challenges, meeting for facilitated reflection, and appreciating patient experiences across the continuum of care. Students' appreciation for their peer group experiences persisted well after the conclusion of VALOR. VALOR students performed the same as or better than traditional clerkship students on knowledge and skill-based outcomes. The authors demonstrate that their third-year clerkship program using peer groups has built supportive learning networks and facilitated reflection, allowing students to develop critical professional skills. Student communication around patient care was also feasible and highly valued.

Effect of resistance training during hemodialysis on circulating cytokines: a randomized controlled trial.

The purpose of this study was to evaluate the effect of a 12-week intradialytic progressive resistance training (PRT) regimen on circulating pro- and anti-inflammatory cytokines. Forty-nine patients (62.6 ± 14.2 years) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital, Sydney, Australia. Patients were randomized to: PRT + usual care (n = 24) or usual care control (n = 25). The PRT group performed two sets of 10 exercises at high intensity using free-weights, 3 times per week for 12 weeks during dialysis, while the control group did not exercise. Tumor necrosis factor-alpha, interleukin-1b, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10, and interleukin-12 were measured in serum before and after the intervention period. Muscle cross-sectional area (CSA), intramuscular lipid, intermuscular adipose tissue, and subcutaneous and total thigh fat, evaluated via computed tomography of the non-dominant mid-thigh, were also collected at both time points. All cytokines were significantly elevated in the total cohort at baseline compared with normative data. There were no cytokine changes over time or between groups (p > 0.05). In secondary analyses pooling the groups, changes in logIL-6 and IL-8 were inversely related to changes subcutaneous thigh fat (p < 0.05) while changes in logIL-6 were also inversely related to changes in thigh muscle CSA, and total thigh fat (p < 0.03). These data suggest that 12 weeks of intradialytic progressive resistance training does not improve circulating pro- and anti-inflammatory markers. Further research is required to elucidate the implications and mechanisms of the relationships between IL-6 and IL-8 and body composition in ESRD.

Review article: Tackling the survival issue in end-stage renal disease: time to get physical on haemodialysis.

Life expectancy in haemodialysis patients is reduced fourfold on average versus healthy age-matched individuals. The purpose of this review is to present empirical evidence that intradialytic exercise can mitigate primary independent risk factors for early mortality in end-stage renal disease. These risk factors include measures of skeletal muscle wasting, systemic inflammation, cardiovascular functioning and dialysis adequacy. Overall, the available literature provides support for the integration of exercise within the conventional outpatient haemodialysis unit. The amelioration of various physiological risk factors through an appropriate exercise prescription may enhance survival in this vulnerable cohort. Investigations are required to determine the effects of various doses of intradialytic exercise on a broad range of clinical outcomes, and more thoroughly elucidate the relationship between exercise-induced adaptations and survival advantage in end-stage renal disease.

Progressive resistance training and nutrition in renal failure.

Nutrition and exercise are an integral part of the medical management of many chronic and complex conditions. They are interrelated and share many common metabolic pathways that may affect disease processes and their management. In nephrology, nutritional interventions have been relatively well studied and are recommended in many evidence-based clinical practice guidelines for managing people with chronic kidney disease (CKD). Over the past 20 years, growing evidence has suggested that aerobic exercise interventions are efficacious, and that the rationale for progressive resistance training (PRT) is strong, particularly in this population, despite a more limited evidence base to date. In the small number of clinical trials that have included patients with CKD, PRT programs have proved safe, feasible to administer, and efficacious. They have been shown to improve clinical, physical, and functional outcomes.

A rationale for intradialytic exercise training as standard clinical practice in ESRD.

The purpose of this article is to present a rationale for intradialytic exercise training in patients with end-stage renal disease based on the empirical evidence to date and determine whether this evidence has translated into enhanced renal rehabilitation practices throughout the world. According to the published literature, intradialytic exercise improves exercise adoption and adherence in this cohort, is performed safely, and is feasible to administer. Moreover, intradialytic exercise can improve solute removal, dialysis adequacy, intradialytic protein synthesis, muscular strength, peak oxygen consumption, nutritional status, and quality of life. Despite these findings, there currently are no policies or position stands regarding exercise prescription for hemodialysis patients in Australia. According to a telephone survey we conducted, intradialytic exercise programs are essentially nonexistent in this country. However, such programs are being implemented successfully as standard clinical practice in dialysis units in Germany, and there is reason to believe that this practice can be expanded throughout the world. At present, additional research is indicated. There is a lack of large-scale, robustly designed, randomized, controlled trials of intradialytic exercise training. Such research is needed to conclusively show the clinical importance of intradialytic exercise for hemodialysis patients, which may influence current standard clinical practice among nephrologists and, as such, improve the health and quality of life of this vulnerable cohort.