TRH acts as a multifunctional hypophysiotropic factor in vertebrates

Thyrotropin-releasing hormone (TRH) is the first hypothalamic hypophysiotropic neuropeptide whose sequence has been chemically characterized. The primary structure of TRH (pGlu-His-Pro-NH₂) has been fully conserved across the vertebrate phylum. TRH is generated from a large precursor protein that contains multiple repeats of the TRH progenitor tetrapeptide Gln-His-Pro-Gly. In all tetrapods, TRH-expressing neurons located in the hypothalamus project towards the external zone of the median eminence while in teleosts they directly innervate the pars distalis of the pituitary. In addition, in frogs and teleosts, a bundle of TRH-containing fibers terminate in the neurointermediate lobe of the pituitary gland. Although TRH was originally named for its ability to trigger the release of thyroid-stimulating hormone (TSH) in mammals, it later became apparent that it exerts multiple, species-dependent hypophysiotropic activities. Thus, in fish TRH stimulates growth hormone (GH) and prolactin (PRL) release but does not affect TSH secretion. In amphibians, TRH is a marginal stimulator of TSH release in adult frogs, not in tadpoles, and a major releasing factor for GH and PRL. In birds, TRH triggers TSH and GH secretion. In mammals, TRH stimulates TSH, GH and PRL release. In fish and amphibians, TRH is also a very potent stimulator of α-melanocyte-stimulating hormone release. Because the intermediate lobe of the pituitary of amphibians is composed by a single type of hormone-producing cells, the melanotrope cells, it is a suitable model in which to investigate the mechanism of action of TRH at the cellular and molecular level. The occurrence of large amounts of TRH in the frog skin and high concentrations of TRH in frog plasma suggests that, in amphibians, skin-derived TRH may exert hypophysiotropic functions.     

Bone mineral densities in individuals with Gilbert’s syndrome: A cross-sectional,case-control pilot study

BACKGROUND

Unconjugated bilirubin inhibits osteoblastic proliferative activity in vitro, raising the possibility that Gilbert’s syndrome (GS) patients are at increased risk of osteoporosis.

OBJECTIVES

To compare bone mineral density (BMD), serum parathyroid hormone (PTH), C-telopeptide (CTX) and osteocalcin levels in GS subjects versus matched controls in a cross-sectional, case-control study.

METHODS

BMD determinations were obtained with central dual-energy x-ray absorptiometry. Serum PTH, CTX and osteocalcin levels were measured by enzyme immunoassay.

RESULTS

A total of 17 GS and 30 control subjects were studied. Overall, there were no significant differences in BMD, PTH, CTX or osteocalcin levels between the two groups. However, when older (older than 40 years of age) and younger (40 years of age and younger) cohorts were considered separately, the older GS cohort had significantly decreased total hip BMD, T scores and Z scores, and femoral neck BMD, T scores and Z scores (P<0.005 for each parameter, respectively) compared with older control subjects. Serum osteocalcin levels were lower in the older versus younger GS cohort (P=0.006). An inverse correlation existed between all subjects’ serum unconjugated bilirubin levels and total body BMD determinations (r=−0.42; P=0.04). On univariate analysis, the association between serum unconjugated bilirubin and total body BMD was not significant (P=0.066), nor was serum unconjugated bilirubin identified as a risk factor for low BMD when entered into multivariate analyses.

CONCLUSIONS

The results of the present pilot study warrant further research involving larger numbers of subjects and longitudinal measurements to determine whether GS is associated with decreased BMD, particularly in older GS subjects.     

Human immunodeficiency virus infection in patients with leukemia

Eighteen human immunodeficiency virus (HIV)-seropositive patients were found among 211 previously treated adult patients with a variety of leukemias who had been multiply transfused before April 1985. Patients known to be homosexual or intravenous drug users were excluded from this study. The spouse of one HIV-seropositive patient became HIV infected and subsequently developed the acquired immune deficiency syndrome. Patients with leukemia who were multiply transfused before the availability of screening of blood products for HIV antibody should be counseled regarding their individual risks of HIV infection and the risk to sexual contacts.     

Age,Creatinine and Ejection Fraction Score in Brazil: Comparison with InsCor and the EuroSCORE

Background

Risk scores for cardiac surgery cannot continue to be neglected.

Objective

To assess the performance of “Age, Creatinine and Ejection Fraction Score” (ACEF Score) to predict mortality in patients submitted to elective coronary artery bypass graft and/or heart valve surgery, and to compare it to other scores.

Methods

A prospective cohort study was carried out with the database of a Brazilian tertiary care center. A total of 2,565 patients submitted to elective surgeries between May 2007 and July 2009 were assessed. For a more detailed analysis, the ACEF Score performance was compared to the InsCor’s and EuroSCORE’s performance through correlation, calibration and discrimination tests.

Results

Patients were stratified into mild, moderate and severe for all models. Calibration was inadequate for ACEF Score (p = 0.046) and adequate for InsCor (p = 0.460) and EuroSCORE (p = 0.750). As for discrimination, the area under the ROC curve was questionable for the ACEF Score (0.625) and adequate for InsCor (0.744) and EuroSCORE (0.763).

Conclusion

Although simple to use and practical, the ACEF Score, unlike InsCor and EuroSCORE, was not accurate for predicting mortality in patients submitted to elective coronary artery bypass graft and/or heart valve surgery in a Brazilian tertiary care center.     

Post-cardiotomy ECMO in pediatric and congenital heart surgery: impact of team training and equipment in the results

Introduction

Post-cardiotomy myocardial dysfunction requiring mechanical circulatory support occurs in about 0.5% of cases. In our environment, the use of extracorporeal membrane oxygenation has been increasing in recent years.

Objective

To evaluate the impact of investment in professional training and improvement of equipment in the rate of weaning from extracorporeal membrane oxygenation and survival.

Methods

A retrospective study. Fifty-six pediatric and/or congenital heart patients underwent post-cardiotomy extracorporeal membrane oxygenation at our institution between November 1999 and July 2014. We divided this period into two phases: phase I, 36 cases (before the structuring of the extracorporeal membrane oxygenation program) and phase II, 20 cases (after the extracorporeal membrane oxygenation program implementation) with investment in training and equipment). Were considered as primary outcomes: extracorporeal membrane oxygenation weaning and survival to hospital discharge. The results in both phases were compared using Chi-square test. To identify the impact of the different variables we used binary logistic regression analysis.

Results

Groups were comparable. In phase I, 9 patients (25%) were weaned from extracorporeal membrane oxygenation, but only 2 (5.5%) were discharged. In phase II, extracorporeal membrane oxygenation was used in 20 patients, weaning was possible in 17 (85%), with 9 (45%) hospital discharges (P<0.01). When the impact of several variables on discharge and weaning of extracorporeal membrane oxygenation was analyzed, we observe that phase II was an independent predictor of better results (P<0.001) and need for left cavities drainage was associated with worse survival (P=0.045).

Conclusion

The investment in professional training and improvement of equipment significantly increased extracorporeal membrane oxygenation results.     

Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation

Oral Diseases (2010) 16 , 351–359 Objectives: To investigate the changes in the muscarinic receptor signaling pathway with submandibular gland (SMG) transplantation and whether carbachol improves secretion in transplanted SMGs. Materials and methods: SMG autotransplantation was performed in a rabbit model. Carbachol (1 μM) was infused into the transplanted glands from postoperative day 1–7. The expression of the M1 and M3 muscarinic receptors, aquaporin‐5 (AQP5), and phosphorylated extracellular signal‐regulated kinase 1/2 (p‐ERK1/2) was measured by RT‐PCR, immunoblotting or immunofluorescence. The content of inositol 1, 4, 5‐trisphosphate (IP₃) was measured by radioimmunoassay. Results: Salivary flow of the transplanted SMGs was decreased after transplantation. As well, the expressions of M1 and M3 receptors and their downstream signaling molecules, IP₃, p‐ERK1/2 and AQP5, were all reduced. Atrophy of acinar cells was shown in transplanted glands. However, all these alterations were reversed after carbachol treatment for 7 days. Furthermore, carbachol directly increased the mRNA expression of AQP5 and phosphorylation of ERK1/2 in cultured neonatal rabbit SMG cells. Conclusion: A lack of acetylcholine and downregulation of the muscarinic receptor signaling pathway is involved in the early hypofunction of transplanted SMGs. Carbachol treatment could be a new therapeutic strategy to improve secretion and prevent the obstruction of Wharton’s duct in the early phase after SMG transplantation.     

Aortic valve calcification in 499 consecutive patients referred for computed tomography

Introduction

Aortic valve calcification (AVC) is the most common cause of aortic stenosis. The aim of the study was to assess the prevalence of aortic valve, coronary artery and aortic calcifications and to evaluate the correlation between calcification of the aortic valve, coronary arteries and aorta.

Material and methods

The study included 499 patients aged 60 years and over who underwent coronary computed tomography because of chest pain. Beside coronary artery calcium score (CAC), we evaluated AVC and ascending aorta calcifications (AAC).

Results

Aortic valve calcification was found in 144 subjects (28.9% of the whole study population). Prevalence of CAC and AAC was higher than AVC and amounted to 73.8% and 54.0%. Prevalence of AVC, CAC and AAC was significantly lower in the group of patients ≤ 70 years than in the group of patients > 70 years of age (p = 0.0002, p < 0.0001, p < 0.0001). Aortic valve calcification was more often observed in men than women (34.7% vs. 25.4%, p = 0.02). Degree of aortic valve calcification was also significantly higher among men than women (median score 4 vs. 0, p = 0.01). Similar observations were true for CAC and AAC, where both prevalence and degree of calcification was higher among men than women. In the whole study population no correlation was noted between AVC and CAC or AAC (p = 0.34, p = 0.85). There was a significant correlation between AAC and CAC (p < 0.0001).

Conclusions

Despite some similarities in pathological mechanism and risk factors, a degenerative defect of the aortic valve could be independent of atheromatous lesions in the coronary arteries and aorta.