Aortic intima-media thickness measured by trans-abdominal ultrasound as an early life marker of subclinical atherosclerosis

Atherosclerosis is a chronic inflammatory process that begins in early life. Improved identification of markers of early atherosclerosis via neonatal aortic intima-media thickness (aIMT) measurement may allow the development of interventions to prevent or reduce later cardiovascular disease.

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

Astrocytic and microglial response and histopathological changes in the brain of horses with experimental chronic Trypanosoma evansi infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunohistochemical characterization of mononuclear cells and MHC II expression in the brain of horses with experimental chronic Trypanosoma evansi infection

Este estudo objetivou caracterizar a resposta imune celular no sistema nervoso central (SNC) de eqüinos com infecção crônica experimental por Trypanosoma evansi. Para este propósito, foram utilizados os métodos histoquímicos (HE) e imunoistoquímicos do complexo avidina-biotina peroxidase (ABC). O fenótipo do infiltrado celular foi caracterizado com o auxílio de anticorpos anti - CD3, para linfócitos T e antiBLA36 para linfócitos B. Os macrófagos foram marcados com anticorpo antiantígenos da linhagem mielóide/histiócitos (Clone Mac387). A lesão no sistema nervoso central (SNC) dos eqüinos infectados com T. evansi foi caracterizada como meningoencefalite e meningomielite não supurativa. A gravidade das lesões variou em diferentes segmentos do SNC, refletindo distribuição irregular das alterações vasculares. A distribuição de células T e B e antígenos do complexo maior de histocompatibilidade classe II foram avaliados dentro do SNC de eqüinos cronicamente infectados com T. evansi. O infiltrado perivascular e meníngeo eram constituídos predominantemente por células T e B. Macrófagos foram raramente visualizados. T.evansi não foi identificado no parênquima do SNC dos eqüinos.

Inflammation, Diabetes, and Chronic Kidney Disease: Role of Aerobic Capacity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Er : YAG laser: Antimicrobial effects in the root canals of dogs' teeth with pulp necrosis and chronic periapical lesions

Objective: Our goal in this study was to evaluate the antimicrobial effect of Er:YAG laser applied after biomechanical preparation of the root canals of dog's teeth with apical periodontitis. Background Data: Various in vitro studies have reported effective bacterial reduction in infected root canals using Er:YAG laser. However, there is no in vivo research to support these results. Methods: Forty root canals of dogs' premolar teeth with pulp necrosis and chronic periapical lesions were used. An initial microbiological sample was taken, and after biomechanical preparation was carried out, a second microbiological sample was taken. The teeth were divided into two groups: Group I-biomechanical preparation was taken of root canals without Er:YAG laser application; Group II-biomechanical preparation was taken of root canals with Er:YAG laser application using 140-mj input, 63-mJ output/15 Hz. After coronal sealing, the root canals were left empty for 7 days at which time a third microbiological sample was taken. The collected material was removed from the root canal with a #40 K file and placed in transport media. It was serially diluted and seeded on culture dishes selective for anaerobes, aerobes, and total streptococci. Colony-forming units per milliliter (CFU/mL) were counted. Results: Groups I and II showed an increase of CFU/mL for all microorganisms 7 days after treatment, being statistically significant for anaerobes in Group I and for anaerobes and total streptococci in Group II. When comparing CFU/mL of Groups I and II, there was a statistically significant increase after 7 d for total streptococci in Group II. Conclusion: Er:YAG laser applied after biomechanical preparation did not reduce microorganisms in the root canal system.

Isolation of Malassezia pachydermatis and M. sympodialis from the external ear canal of cats with and without otitis externa

The objective of this study was to determine the presence of Malassezia spp. in the external ear canal of cats with and without otitis. Forty-five animals were studied, 20 with and 25 without otitis externa (OE). Cerumen or secretion from external ear canal samples was cultured on modified Mycosel agar and sterile olive oil was added to the surface of the medium before specimen seeding. The isolates were analysed for macro- and micromorphology and identified by catalase tests and on the basis of growth on Tween 20, 40, 60 and 80. Malassezia spp. were isolated from 15 out of 20 (75%) animals with otitis and from 7 out of 25 (28%) cats without OE; the difference between the two groups was statistically significant (P <= 0.05). Malassezia pachydermatis and M. sympodialis were isolated from 60% (12/20) and 40% (8/20) of cats with otitis, respectively, with no significant difference in the frequency of isolation between the two species. In the microflora of the healthy ear canal M pachydermatis was significantly more common (6/25, 24%) than M sympodialis (1/25, 4%). The present investigation confirms that M sympodialis can also act as an actiological agent of feline OE, and if commercial veterinary laboratories do not use media with added lipids for the isolation of Malassezia spp., this might lead to false-negative results.

Associations between bioelectrical impedance parameters and cardiovascular events in chronic dialysis patients

Purpose: Malnutrition and fluid overload contribute to the poor cardiovascular prognosis of dialysis patients. Since bioelectrical impedance analysis is an option for the evaluation of body composition and for the monitoring of hydration state, it may assist in the identification of subjects at high cardiovascular risk. The objective of this study was to evaluate the association between bioelectrical impedance parameters and cardiovascular events. Methods: The association between bioelectrical impedance parameters and fatal and non-fatal cardiovascular outcome was evaluated in 145 dialysis patients. Results: The mean age of the population studied was 54.9 ± 15.4 years, 49.7 % were males, and 35.9 % had diabetes. Forty (27.6 %) patients developed cardiovascular events during the 16 months (8; 32) of follow-up. Comparison of patients with and without cardiovascular events revealed higher extracellular mass/body cell mass (ECM/BCM) and extracellular water/total body water ratios and higher C-reactive protein levels in the former. Survival analysis showed that an ECM/BCM ratio >1.2 and a phase angle <6° were associated with poor cardiovascular prognosis. Among nondiabetic patients, these parameters and capacitance were independently associated with cardiovascular events, suggesting that poor nutritional status and fluid overload are associated with the occurrence of these events. Conclusions: Phase angle, capacitance and ECM/BCM ratio are valuable parameters for the evaluation of cardiovascular prognosis, supporting the use of bioelectrical impedance for the clinical assessment of dialysis patients. © 2012 Springer Science+Business Media Dordrecht.

Validity of malnutrition scores for predicting mortality in chronic hemodialysis patients

Purpose: Malnutrition is a strong predictor of mortality in hemodialysis patients. Several scoring systems for evaluating nutritional status have been proposed. However, they rely on different sets of anthropometric and laboratory markers to make a diagnosis of malnutrition and assess its impact on prognosis. To validate them, nutritional scores should be compared with clinical outcomes. Thus, the purpose of this study was to assess malnutrition by three different nutrition scoring systems and determine which best predicts mortality in hemodialysis patients. Methods: This prospective study included 106 adult chronic hemodialysis patients. Their mean age was 56.3 ± 14.9 years and mean body mass index 24.8 (21.8-28.9); 52 % were men and they had been on dialysis for 24 (5-55) months. Nutritional status was classified according to the diagnostic systems proposed by Wolfson et al. (Am J Clin Nutr 39(4):547-555, 1984), International Society of Renal Nutrition and Metabolism (ISRNM) (Fouque et al. in Kidney Int 73(4):391-398, 2008), and Beberashvili et al. (Nephrol Dial Transplant 25(8):2662-2671, 2010). During about 2 years of follow-up, mortality was assessed by Kaplan-Meier curves, log-rank, and Cox's models adjusted for diabetes, sex, C-reactive protein, time on dialysis, age, and fractional urea clearance. Results: Twenty-three deaths (21.5 %) occurred during the study period. According to the systems of Wolfson, Beberashvili, and the ISRNM, 54, 32, and 20 % of patients, respectively, had malnutrition. Both univariate and multivariate analyses showed that the ISRNM system was the only one that predicted poorer survival (fourfold higher death risk) in malnourished patients. Conclusions: The scoring system proposed by the ISRNM most accurately identifies patients at higher risk of death. © 2013 Springer Science+Business Media Dordrecht.

Antimicrobial susceptibility to b-lactams and metronidazole of microorganisms isolated from chronic and aggressive periodontitis

The objective of this study was to evaluate the microbial susceptibility to ß-lactams and metronidazole, and evaluate the production of ß-lactamases by microorganisms isolated from patients with chronic or aggressive periodontitis. The samples were obtained from 50 patients with periodontitis and microorganisms were isolated onto selective and nonselective culture media, identified by biochemical methods and tested for susceptibility to antimicrobial agents (amoxicillin, amoxicillin/clavulanate, cefoxitin, imipenem, metronidazole, penicillin G). The isolates were resistant to at least 1 mg/ml of any drug tested were evaluated to verify the production of ß-lactamases by the method of double layer (or biological) and chromogenic cephalosporin using nitrocefin. The results evidenced resistance to amoxicillin and penicillin G, while the susceptibility to association amoxicillin/clavulanate, imipenem and cefoxitin was widely disseminated among the organisms. Resistance to these drugs showed a clear correlation with the production of ß-lactamase in the majority of microbial groups.

N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity

The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC). Male Wistar rats were submitted to 5/6 nephrectomy (Nx) to induced CRF. An ionic - cyclic Gd (Gadoterate Meglumine) was administrated (1.5 mM/KgBW, intravenously) 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd-chelate administration: 1 - Nx (n = 7); 2 - Nx+NAC (n = 6); 3 - Nx+Gd (n = 7); 4 - Nx+NAC+Gd (4.8 g/L in drinking water), initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6). This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW), proteinuria (mg/24 hs), serum iron (mu g/dL); serum ferritin (ng/mL); transferrin saturation (%), TIBC (mu g/dL) and TBARS (nmles/ml). Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

Functional independence in patients with chronic kidney disease being treated with haemodialysis

Purpose: This study has described and analysed the functional independence of the patients served in the haemodialysis services of a countryside town in the State of Sao Paulo, Brazil, using the Functional Independence Measure (FIM). Method: The population considered was that of 214 patients being treated with haemodialysis, assessed in 2011, by means of a social, demographic and clinical report, a Mini-Mental State Examination (MMSE) and also the FIM. Results: The mean age of the population under study was 58.01 years, while the mean FIM point score was 118.38 points, showing a level of complete or modified independence within this population. Even though the level of dependence found has been low, this can be highlighted, within the locomotion domain, in the activity of going up and down stairs (10.28%). Age, complications arising from haemodialysis, and comorbidities show a negative correlation with FIM. Conclusion: Awareness of the level of functional independence of the patients being subjected to treatment with haemodialysis is essential in order to back up intervention for the improvement of nursing assistance provided to this population.

Searching for chronic hepatitis B patients in a low prevalence area – role of racial origin

Abstract Background Clinical studies for testing new drugs against hepatitis B ought to be carried out in low prevalence areas despite difficulties on patient recruitment. In such areas, relatives of chronic hepatitis B patients are considered to be at risk of acquiring the hepatitis B virus (HBV). The aim of this study was to evaluate the prevalence of HBV markers (anti-HBc, HBsAg and anti-HBs) in familial members of chronic hepatitis B (CHB) patients according to their origin (Asian or Western) in a low prevalence area, the city of São Paulo, Brazil. Methods Twenty three Asian CHB probands and their 313 relatives plus 31 CHB probands of Western origin and their 211 relatives were screened for HBV serological markers; the study was carried out in the outpatient clinic of the University of São Paulo School of Medicine. Results Mother to child transmission was greater in the Asian group whereas sexual transmission was more frequent in the Western group (p < 0.0001). Anti-HBc was positive in 90% and 57% of the Asian and Western parents (p = 0.0432) and in 97% and 33% of the Asian and Western brothers (p = 0.0001), respectively. HBsAg was more frequent among the Asian (66%) than the Western (15%) mothers (p = 0.0260) as well as among the Asian (81%) than the Western (19%) brothers (p = 0.0001). We could detect 110 new HBsAg-positive subjects related to the 54 index patients, being the majority (81%) of Asian origin. Conclusion In low prevalence area of hepatitis B, family members and household contacts of chronic HBV carriers are at high risk for acquiring hepatitis B.

Tenocytes of chronic rotator cuff tendon tears can be stimulated by platelet-released growth factors

BACKGROUND Bone-to-tendon healing after rotator cuff repairs is mainly impaired by poor tissue quality. The tenocytes of chronic rotator cuff tendon tears are not able to synthesize normal fibrocartilaginous extracellular matrix (ECM). We hypothesized that in the presence of platelet-released growth factors (PRGF), tenocytes from chronically retracted rotator cuff tendons proliferate and synthesize the appropriate ECM proteins. MATERIALS AND METHODS Tenocytes from 8 patients with chronic rotator cuff tears were cultured for 4 weeks in 2 different media: standard medium (Iscove's Modified Dulbecco's Media + 10% fetal calf serum + 1% nonessential amino acids + 0.5 μg/mL ascorbic acid) and media with an additional 10% PRGF. Cell proliferation was assessed at 7, 14, 21, and 28 days. Messenger (m)RNA levels of collagens I, II, and X, decorin, biglycan, and aggrecan were analyzed using real time reverse-transcription polymerase chain reaction. Immunocytochemistry was also performed. RESULTS The proliferation rate of tenocytes was significantly higher at all time points when cultured with PRGF. At 21 days, the mRNA levels for collagens I, II, and X, decorin, aggrecan, and biglycan were significantly higher in the PRGF group. The mRNA data were confirmed at protein level by immunocytochemistry. CONCLUSIONS PRGFs enhance tenocyte proliferation in vitro and promote synthesis of ECM to levels similar to those found with insertion of the normal human rotator cuffs. CLINICAL RELEVANCE Biologic augmentation of repaired rotator cuffs with PRGF may enhance the properties of the repair tissue. However, further studies are needed to determine if application of PRGF remains safe and effective in long-term clinical studies. LEVEL OF EVIDENCE Basic Science Study, Cell Biology.

Chronic stress promotes tumor growth through increased BDNF production and neo-innervation

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor growth. Results: First, I examined whether sympathetic nerves are present in human ovarian cancer samples as well as orthotopic ovarian cancer models. Immunohistochemical (IHC) staining for neurofilament revealed that catecholaminergic neurons are present within tumor tissue. In order to determine whether chronic stress affects the density of nerves in the tumor, I utilized an orthotopic mouse model of ovarian cancer that was exposed to daily restraint stress. IHC analysis revealed that nerve density in tumors increased by more than three-fold in stressed animals versus non-stressed controls. IHC analysis suggested that this results from both recruitment of existing neurons (axonogenesis) as well as new neuron formation (neurogenesis) within the tumor. To determine how tumors are recruiting nerve growth, I utilized a PCR array analysis of 84 nerve growth related genes and their receptors, which showed that stimulation of the SKOV3 ovarian cancer cell line with norepinephrine (NE) leads to increased expression of several neurotrophins, including brain-derived neurotrophic factor (BDNF). Neurite extension assays showed that media conditioned by ovarian cancer cell lines is capable of inducing neurite outgrowth in differentiated neuron-like PC12 cells, and NE treatment of cancer cells potentiates this effect. Norepinephrine-induced neurite extension was abolished after BDNF silencing by siRNA, suggesting that BDNF is critical to tumor cell-induced nerve growth. in vivo BDNF inhibition resulted in complete abrogation of stress-induced increases in tumor weight and nerve density, as well as downstream markers of stress. Discussion: These studies indicate that adrenergic signalling induced by chronic stress promotes neo-innervation in the tumor microenvironment. This results in a mutually beneficial relationship between the tumor cells and neurons. This work is crucial for providing a link between chronic stress and its effects on the tumor and its microenvironment. The data shown here aims to open new venues that can be used in development of therapies designed to block the stress effects on tumor growth.