Pituitary binding of vasopressin is altered by experimental manipulations of the hypothalamo-pituitary-adrenocortical axis in normal as well as homozygous (di/di) Brattleboro rats

In the present study we report the properties of vasopressin (VP) receptors in the anterior pituitary gland and show that the number of these receptors is markedly affected by adrenalectomy and hypothalamic lesions. VP-binding activity was assayed in particulate fractions of rat anterior pituitary glands using tritium-labeled arginine VP ([3H] AVP) as tracer. In the presence of Mg2+ the radioligand interacted with a single class of high affinity, low capacity binding sites. Magnesium ions modulated the affinity of the receptors but had no effect on binding capacity. Guanine nucleotides decreased the amount of tracer bound in a dose-dependent manner by increasing the dissociation constant (Kd) of the binding reaction by approximately 2-fold. Increasing the concentration of Mg2+ did not prevent this effect. Bilateral adrenalectomy (ADX) decreased pituitary AVP-binding activity: binding fell by 30% 4 h after surgery and declined further to 10% or less of control at 4 days. The decrease in binding was primarily due to a reduction in the number of receptors. Daily administration of corticosterone inhibited the reduction of binding activity at 4 days in a dose-dependent manner. Destruction of hypophyseotropic VP neurons by means of surgical lesioning of the hypothalamic paraventricular nucleus or the medial basal hypothalamus abolished the effect of ADX on pituitary AVP binding at 24 h but only attenuated the degree of receptor loss at 4 days. Furthermore, the lesions themselves caused a significant (approximately 30%) reduction in receptor number 4-7 days after hypothalamic surgery. Adrenalectomy reduced pituitary AVP-binding activity in homozygous (di/di) Brattleboro rats. The extent as well as the time course of the loss of receptor activity resembled that in normal rats. Rat anterior pituitary segments were exposed to synthetic CRF, AVP, or oxytocin (all 10(-7) M) for 4 h in vitro, and [3H] AVP-binding activity was subsequently determined. Both AVP and oxytocin reduced the amount of radioligand bound, while CRF had no effect. These observations allow the following conclusions: Magnesium ions and guanine nucleotides modulate the affinity of pituitary AVP receptors by different mechanisms and have no effect on binding capacity; Pituitary receptors for AVP are regulated by the amount of AVP released by paraventricular nucleus neurons as well as through a mechanism that requires the presence of corticosterone; Homozygous Brattleboro rats may respond to ADX by increased hypothalamic release of an endogenous ligand for pituitary AVP receptors.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Reconstruction of cervical esophageal anastomosis using median sternotomy

We performed cervical oesophageal anastomosis in 153 patients in 10 years. In 11 patients reconstruction or delayed anastomosis was performed through median sternotomy because cervical approach was not suitable. Reoperations were the following: 7 oesophageal stenosis which couldn't be dilated, 2 necrosis of the transplanted organ and 2 because of delayed anastomosis. 8 patients had oesophageal tumors and 3 erosive fluid reflux. During median sternotomy the transplanted organ was injured twice. In 9 patients after reconstruction dysphagia disappeared, in one pharyngo-ileostomy stenosis was noticed and one of the patients died because of ARDS after a leak.     

Differences in the vascular tree of the femoral trochlear growth cartilage at osteochondrosis‐susceptible sites in foals revealed by SWI 3T MRI

Focal ischemic chondronecrosis of epiphyseal growth cartilage (EGC) during endochondral ossification is believed to be a key early event on the pathway to osteochondrosis (OC) in both animals and humans. The lateral ridge of the equine trochlea is a site where severe osteochondritis dissecans lesions frequently arise and is a model for the study of naturally occurring disease. Non‐invasive imaging to investigate EGC vascularity may help elucidate why focal ischemia occurs. 3T MRI susceptibility‐weighted imaging (SWI) of femoral trochlea of OC predisposed (n = 10) and control (n = 6) day‐old foals, with minimal joint loading after birth, was performed. SWI and 3D images revealed the EGC vascular architecture without a contrast agent, and matched histologic observations. No vascular lesions were identified. There was no difference in the vascular density and architecture between control and OC specimens, but a striking difference in vascular pattern was seen at the OC‐predilected site in the lateral ridge of the trochlea in all specimens, when compared to the medial ridge of the trochlea, where OC lesions are rarely observed. This site was less ossified with more perichondrial vessels not yet bridging with the subchondral bone. Furthermore, the mean vascular density of all specimens was significantly higher at this site. We speculate that joint morphology and focal internal trauma on this site with a unique vascular architecture may trigger ischemic events at this site. SWI permitted visualization of EGC in young foals with a clinical 3T MRI and paves the way for non‐destructive longitudinal studies to improve understanding of OC in all species. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1539–1546, 2016.     

Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated gamma-aminobutyric acid-positive interneurons

BACKGROUND: Recent laboratory studies showed that exposure to supraclinical concentrations of propofol can induce cell death of immature neurons. However, no data are available regarding the effects of clinically relevant concentrations of this agent on neuronal development. The authors addressed this issue by evaluating the effect of propofol on dendritic growth and arbor expansion of developing gamma-aminobutyric acid-positive (GABAergic) interneurons. METHODS: Immature neuroblasts were isolated from the newborn rat subventricular zone and differentiated into GABAergic interneurons in culture. In addition to cell death, the effects of increasing concentrations and durations of propofol exposure on neuronal dendritic development were evaluated using the following morphologic parameters: total dendritic length, primary dendrites, branching point, and Scholl analysis. RESULTS: The authors demonstrate that propofol induced cell death of GABAergic neurons at concentrations of 50 microg/ml or greater. As little as 1 microg/ml propofol significantly altered several aspects of dendritic development, and as little as 4 h of exposure to this agent resulted in a persistent decrease in dendritic growth. In contrast, application of midazolam did not affect neuronal development. CONCLUSION: Short-term exposure of immature developing GABAergic neurons to clinically relevant concentrations of propofol can induce long-term changes in dendritic arbor development. These results suggest that propofol anesthesia during central nervous system development could interfere with the molecular mechanisms driving the differentiation of GABAergic neurons and thus could potentially lead to impairment of neural networks.     

Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials.

AIMS: To compare interferon monotherapy with its combination with lamivudine for hepatitis B e antigen (HBeAg)-positive hepatitis B treatment. METHODS: Two independent researchers identified pertinent randomized controlled trials. The trials were evaluated for methodological quality and heterogeneity. Rates of sustained virological and biochemical responses, and HBeAg clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. RESULTS: Greater sustained virological, biochemical and seroconversion rates were observed with addition of lamivudine to conventional [odds ratio (OR)=3.1, 95% confidence intervals (CI) (1.7-5.5), P<0.0001, OR=1.8, 95% CI (1.2-2.7), P=0.007 and OR=1.8, 95% CI (1.1-2.8), P=0.01 respectively], although not pegylated [OR=1.1, 95% CI (0.5-2.3), P=0.8, OR=1.0, 95% CI (0.7-1.3), P=0.94, and OR=0.9, 95% CI (0.6-1.2), P=0.34 respectively] interferon-alpha, with no significant affect on HBeAg clearance rates [OR=1.6, 95% CI (0.9-2.7), P=0.09, and OR=0.8, 95% CI (0.6-1.1), P=0.26 respectively]. Excluding virological response (P<0.001), pegylated interferon monotherapy and conventional interferon and lamivudine combination therapy were similarly efficacious (P>0.05), with the former studied in harder to treat patients, as evidenced by the superior virological response observed with conventional as compared with pegylated interferon monotherapy (P<0.0001). CONCLUSION: In comparable populations, pegylated interferon monotherapy is likely to be equally or more efficacious than conventional interferon and lamivudine combination therapy, thus constituting the treatment of choice, with no added benefit with lamivudine addition. However, when conventional interferon is used, its combination with lamivudine should be considered.     

Characterization of chemotherapy-induced morphonuclear modifications in the P388 leukaemia and the MXT mammary tumour models of the mouse

Chemotherapy-induced morphonuclear modifications were monitored in vivo by means of the digital cell image analysis of Feulgen-stained nuclei. Two experimental models were used, i.e. the P388 mouse leukaemia and the MXT mouse mammary carcinoma. The drugs used were doxorubicin, etoposide and cyclophosphamide. The results indicate that the chemotherrapy induced a significant decrease in the MXT tumour growth and a significant increase in the survival of the P388 leukaemic mice. These effects were accompanied at the morphonuclear level by an increase in the nuclear area, by modifications in the DNA content in accordance with the effects of the drugs on the cells cycle and by several modifications in the chromatin texture in accordance with the effects of the drugs on the cells cycle and by several modifications in the chromatin texture in accordance with the model or drugs studied. While there were neither homogeneous morphonuclear changes in all treatment groups nor clearcut correlations between the morphonuclear changes and tumour growth or the survival of the animals, the present study nertherless shows that it is possible, at least partly, to monitor in vivo certain chemotherapy-induced effects occurring at the morphonuclear level, and subsequently to obtain information on the mode of action of the drugs.