Longitudinal study of daily variation of rats' behavior in the elevated plus-maze

We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1). a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2). light/dark phases differences in EPM exploration were present at all developmental stages, (3). older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4). behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm.     

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil

IntroductionLiver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics.MethodsWe reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients’ clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups.ResultsAlmost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795).DiscussionThe new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.     

Acute and nongenomic effects of testosterone on isolated and perfused rat heart

Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.     

Thyroid carcinoma with lung metastasis

Thyroid carcinoma is a rare disease in children. Much rare its presentation with pulmonary metastases is. We here report a recent case in 12 years-old girl. We make a review of recommended treatment and the prognosis.     

Pulmonary cystic adenomatoid malformation with anomalous vascularization with systemic origin

We report an infant with the diagnosis of Congenital Cystic Adenomatoid Malformation. He was operated and we found an abnormal systemic blood supply associated in that lobe. We make a review of the literature, and we make a distinction between this rare combination and others like pseudo pulmonary sequestration, or Congenital Cystic Adenomatoid Malformation associated to pulmonary sequestration.     

Guiding axes for drug safety management of pharmacovigilance centres during the COVID-19 era

International Journal of Clinical Pharmacy - The COVID-19 pandemic presents several challenges to the organisation and workflow of pharmacovigilance centres as a result of the massive increase in...     

Preclinical Study of a Biodegradable Polymer-based Stent with Abluminal Sirolimus Release

Background

Bioabsorbable polymer stents with drug elution only on the abluminal surface may be safer than durable polymer drug-eluting stents.

Objective

To report the experimental findings with the Inspiron^TM stent - a bioabsorbable polymer-coated stent with sirolimus release from the abluminal surface only, recently approved for clinical use.

Methods

45 stents were implanted in the coronary arteries of 15 pigs. On day 28 after implantation, angiographic, intracoronary ultrasonographic and histomorphological data were collected. Five groups were analyzed: Group I (nine bare-metal stents); Group II (nine coated with bioabsorbable polymer on the luminal and abluminal surfaces); Group III (eight stents coated with bioabsorbable polymer on the abluminal surface); Group IV (nine stents with bioabsorbable polymer and sirolimus on the luminal and abluminal surfaces); and Group V (ten stents with bioabsorbable polymer and sirolimus only on the abluminal surface).

Results

The following results were observed for Groups I, II, III, IV and V, respectively: percentage stenosis of 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 and 26 ± 15 (p = 0.443); late lumen loss (in mm) of 1.02 ± 0.60; 1.24 ± 0.48; 1.11 ± 0.54; 0.72 ± 0.44 and 0.78 ± 0.39 (p = 0.253); neointimal area (in mm²) of 2.60 ± 1.99; 2.74 ± 1.51; 2.74 ± 1.30; 1.30 ± 1.14 and 0.97 ± 0.84 (p = 0.001; Groups IV and V versus Groups I, II and III); and percentage neointimal area of 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 and 15 ± 12 (p = 0.001; Groups IV and V versus Groups I, II and III). Injury and inflammation scores were low and with no differences between the groups.

Conclusion

The Inspiron^TM stent proved to be safe and was able to significantly inhibit the neointimal hyperplasia observed on day 28 after implantation in porcine coronary arteries.     

Differential Response of Heat Shock Proteins to Uphill and Downhill Exercise in Heart,Skeletal Muscle,Lung and Kidney Tissues

Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP), but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric) and downhill (predominantly eccentric) muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7%) and downhill (-7% of inclination). At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK) and lactate dehydrogenase (LDH) were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal). When the contraction was concentric (uphill) and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL⁻¹) in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively). The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus.

Key Points

• Exercise can induce increases in HSP70 in the lung, kidney and heart, and in the soleus and gastrocnemius muscles, probably due to systemic alterations such as hypoxia, increase in temperature and the production of free radicals.
• Predominantly concentric contractions (running uphill), seem to be the most efficient way of increasing the HSP70 concentrations in the different tissues, followed by eccentric contraction (downhill) and lastly the concentric-eccentric cycle (horizontal).
• The energy demand, already known to influence HSP70, appears not to be the only factor responsible for the response of these proteins, considering that for the kidney and the soleus muscle, downhill running was more efficient in raising the HSP70 response than horizontal running.
• Future research should explore the mechanisms by which the eccentric, concentric and eccentric-concentric contractions are capable of influencing the responses of the heat shock proteins, opening possibilities for increasing the levels of these proteins in desirable situations, such as to protect against excess free radicals or injuries.

Key words: HSP70, stress, concentric exercise, eccentric exercise, metabolic stress     

Lactobacillus fermentum,a pathogen in documented cholecystitis

INTRODUCTIONLactobacillus species are probiotics proven to exhibit various preventative as well as therapeutic properties. While lactobacillus species have been implicated in the formation of dental caries, endocarditis and bacteremia, their role as pathogens in cholecystitis has not been reported. We present a rare case of Lactobacillus fermentum working as a pathogen in cholecystitis.PRESENTATION OF CASEAn 81-year old male was admitted with right upper quadrant abdominal pain. His signs, symptoms, laboratory values and imaging were consistent with a diagnosis of cholecystitis with ascending cholangitis. In view of his co-morbidity and severe sepsis, the patient was treated non-operatively with antibiotics and cholecystostomy. L. fermentum, which was vancomycin resistant, was identified from the cholecystostomy aspirate and from anaerobic blood culture. The patient went into septic shock, developed multi-organ dysfunction syndrome and eventually died.DISCUSSIONCommensal bacteria such as L. fermentum are known to modulate immunity, reduce the pathogenicity of gastrointestinal organisms and play a therapeutic role in various disease processes. We isolated L. fermentum as a pathogen in a documented case of cholecystitis with ascending cholangitis.CONCLUSIONWhile the routine use lactobacillus species as a probiotic is supported in the literature, understanding its potential role as a pathogen may allow more judicious use of these bacteria and encourage research to elucidate the pathogenicity of lactobacillus species.     

Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children

Background

Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor β1 (U-TGF-β1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin–angiotensin–aldosterone system (RAAS).

Methods

The was a cross-sectional evaluation of 302 children aged 8–9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-β1 and U-AGT levels were determined by immunoenzymatic methods.

Results

Obese children presented with the lowest levels of U-ET-1 and U-TGF-β1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-β1 tended to increase across tertiles (T1–T3) of U-AGT (U-ET-1: T1, 19.9 (14.2–26.3); T2, 32.5 (23.3–141.6); T3, 24.8 (18.7–51.5) ng/g creatinine, p?=?0.007; U-TGF-β1: T1, 2.2 (1.8–4.0); T2, 4.3 (2.7–11.7); T3, 4.9 (3.8–10.1) ng/g creatinine, p?=?0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-β1 was associated with U-AGT levels and 24 h-systolic BP.

Conclusions

Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-β1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury.