Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin

Sex hormone-binding globulin (SHBG) production in humans has been thought to be stimulated by estrogens and thyroid hormone and inhibited by androgens. However, recent data indicate that SHBG production in vitro is stimulated by both androgens and estrogens. This study was designed to determine what other hormonal factors regulate SHBG production. Since hyperinsulinemia and hyperprolactinemia both occur in disease states in which low serum SHBG levels are found, the effects of insulin and PRL were compared to and/or studied in combination with estradiol (E2), T4, and testosterone (T) in a human hepatoma cell line (Hep G2). Hep G2 cells were grown to near confluence in medium including 10% fetal calf serum, and then 72-h experimental incubations were carried out which used only fetal calf serum-free medium. Compared to control incubations, both insulin (10(-8) mol/L) and PRL (10(-8) mol/L) decreased SHBG production from 65.0 +/- 0.6 (+/- SE) to 46.8 +/- 1.1 and 46.8 +/- 1.2 nmol/10(6) cells, respectively (P less than 0.01). Insulin also inhibited both E2 and T4-stimulated SHBG production. T stimulated SHBG production to the same degree as E2. Finally, both E2 and insulin significantly increased cell number, an important consideration when expressing the effect of a hormone on SHBG production in cultured cells. We conclude that insulin and PRL inhibit SHBG production and confirm that T4, T, and E2 stimulate SHBG production in vitro. These findings suggest that insulin and PRL may be important factors in the regulation of SHBG production in vivo.     

HLA antigens and the antibody response after vaccination to hepatitis B

The aim of our work was the search for immunogenetic factors that influence the antibody response to HBs antigen. We analyzed the HLA-A, -B, and -DR antigen frequencies in 19 seropositive to HBs and 28 seronegative to HBs healthy persons finding an elevated frequency of B5 in the seropositive group (p value 0.037). After vaccination with Hevac B Pasteur vaccine of the seronegative persons, the low antibody response was associated with B13 (p value 0.041). An association between local side reactions to the vaccine and HLA A3 and B35 were also found (p values 0.042 and 0.022 respectively). The presented p values are not significant after correction for the number of antigens tested and for this reason our findings require confirmation in an independent study.     

Complex Osteochondral Lesions of the Talus Treated With a Novel Bi-Phasic Aragonite-based Implant

To present initial results of a novel, bi-phasic, porous, biodegrade, and cell-free aragonite-based scaffold for treating complex osteochondral lesions of the talus (OLT). Four subjects (2 males and 2 females; 34-61 years old) were operated on their ankles due to chronic and deep OLT-Hepple grades 4 or 5 (1.8-2.2 cm²). Three subjects had OLT on the medial central trochlea, and 1 had a combined medial and lateral lesions. OLT were exposed through medial malleolus osteotomy, with an additional lateral arthrotomy in the combined lesions. Bi-phasic porous osteochondral scaffolds (single implant or 2 implants) were implanted in a press-fit manner using a designated surgical toolset. Treatment outcome was followed clinically (Foot and Ankle Outcome Score, EQ-5D 3L, Tegner activity scale) and by medical imaging (radiographs, magnetic resonance imaging) from 18 to 32 months. All Foot and Ankle Outcome Score values increased from preoperative to final follow-up values (Symptoms 62 to 71, Pain 53 to 84, ADL 60 to 89, Sport 19 to 65, and QoL 18 to 47). EQ-5D 3L increased from 0.59 to 0.76, and Tegner activity values increased from 1.5 to 3. Kellgren-Lawrence ankle radiographic scores remained stable (2 to 2). Postoperative MR evaluation demonstrated cartilage defect fill of 75% to 100% respect to the native cartilage in 3 subjects (4 OLTs), while 1 lesion was filled 25% to 50%. No graft related serious adverse events or graft failures were reported. The use of a bi-phasic osteochondral biodegradable aragonite-based scaffold in the treatment of complex OLT during the reported period presented positive and promising clinical and radiologic outcome, without serious adverse events or graft failures.     

Lithium and venlafaxine poisoning — a case report

In treatment of manic-depressive conditions long-term lithium therapy may be combined with an effective and relatively safe antidepressant venlafaxine. Combined overdose may increase the risk of early toxicity of both drugs and of delayed lithium intoxication, responding to symptomatic and renal replacement therapy. We present a patient with combined lithium and venlafaxine self-poisoning with nothing but delayed signs of lithium intoxication with the emphasis on early and late treatment. 41-year old woman attempted suicide by large amount of lithium and venlafaxine. On admission she was asymptomatic, but with increased serum lithium over 5mmol/L. After gastric lavage, active charcoal and laxative administration she was receiving IV fluids. After a delay of 63 hours she deteriorated acutely by disorientation, confusion, fasciculation and tremor and was readmitted to Intensive care unit. In spite serum lithium decreased to 2mmol/L clinical signs were attributed to delayed lithium intoxication. After symptomatic and renal replacement therapy the patient’s condition improved after few days. We conclude that decontamination procedures are effective in particular for venlafaxine poisoning. If increased serum lithium levels are noted renal replacement therapy may be started even in asymptomatic patients as delayed lithium intoxication is most likely after few days.     

Synemin is expressed in reactive astrocytes and Rosenthal fibers in Alexander disease

Alexander disease (AxD) is a neurodegenerative disorder with prominent white matter degeneration and the presence of Rosenthal fibers containing aggregates of glial fibrillary acidic protein (GFAP), and small stress proteins HSP27 and αB‐crystallin, and widespread reactive gliosis. AxD is caused by mutations in GFAP, the main astrocyte intermediate filament protein. We previously showed that intermediate filament protein synemin is upregulated in reactive astrocytes after neurotrauma. Here, we examined immunohistochemically the presence of synemin in reactive astrocytes and Rosenthal fibers in two patients with AxD. There was an abundance of GFAP‐positive Rosenthal fibers and widespread reactive gliosis in the white matter and subpial regions. Many of the GFAP‐positive reactive astrocytes were positive for synemin, and synemin was also present in Rosenthal fibers. We show that synemin is expressed in reactive astrocytes in AxD, and is also present in Rosenthal fibers. The potential role of synemin in AxD pathogenesis remains to be investigated.     

Electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells

It has been reported previously that electric pulses of sufficiently high voltage and short duration can permeabilize the membranes of various organelles inside living cells. In this article, we describe electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. The cells were exposed to short, high-voltage electric pulses (from 1 to 20 pulses, 60 ns, 50 kV/cm, repetition frequency 1 kHz). We observed that 10 and 20 such pulses induced permeabilization of membranes of endocytotic vesicles, detected by release of lucifer yellow from the vesicles into the cytosol. Simultaneously, we detected uptake of propidium iodide through plasma membrane in the same cells. With higher number of pulses permeabilization of the membranes of endocytotic vesicles by pulses of given parameters is accompanied by permeabilization of plasma membrane. However, with lower number of pulses only permeabilization of the plasma membrane was detected.     

Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy

Vascular endothelial growth factor (VEGF)-B is poorly angiogenic but prominently expressed in metabolically highly active tissues, including the heart. We produced mice expressing a cardiac-specific VEGF-B transgene via the alpha-myosin heavy chain promoter. Surprisingly, the hearts of the VEGF-B transgenic mice showed concentric cardiac hypertrophy without significant changes in heart function. The cardiac hypertrophy was attributable to an increased size of the cardiomyocytes. Blood capillary size was increased, whereas the number of blood vessels per cell nucleus remained unchanged. Despite the cardiac hypertrophy, the transgenic mice had lower heart rate and blood pressure than their littermates, and they responded similarly to angiotensin II-induced hypertension, confirming that the hypertrophy does not compromise heart function. Interestingly, the isolated transgenic hearts had less cardiomyocyte damage after ischemia. Significantly increased ceramide and decreased triglyceride levels were found in the transgenic hearts. This was associated with structural changes and eventual lysis of mitochondria, resulting in accumulation of intracellular vacuoles in cardiomyocytes and increased death of the transgenic mice, apparently because of mitochondrial lipotoxicity in the heart. These results suggest that VEGF-B regulates lipid metabolism, an unexpected function for an angiogenic growth factor.     

Effect of selective and nonselective β-blockers on resting energy production rate and total body substrate utilization in chronic heart failure

Background: In chronic heart failure (CHF) β-blockers reduce myocardial oxygen consumption and improve myocardial efficiency by shifting myocardial substrate utilization from increased free fatty acid oxidation to increased glucose oxidation. The effect of selective and nonselective β-blockers on total body resting energy production rate (EPR) and substrate utilization is not known. Methods: Twenty-six noncachectic patients with moderately severe heart failure (New York Heart Association class II or III, left ventricular ejection fraction < 0.40) were treated with carvedilol (37.5 ± 13.5 mg/12 h) or bisoprolol (5.4 ± 3.0 mg/d) for 6 months. Indirect calorimetry was performed before and after 6 months of treatment. Results: Resting EPR was decreased in carvedilol (5.021 ± 0.803 to 4.552 ± 0.615 kJ/min, P < .001) and bisoprolol group (5.230 ± 0.828 to 4.978 ± 0.640 kJ/min, P < .05; nonsignificant difference between groups). Lipid oxidation rate decreased in carvedilol and remained unchanged in bisoprolol group (2.4 ± 1.4 to 1.5 ± 0.9 mg m²/kg min versus 2.7 ± 1.1 to 2.5 ± 1.1 mg m²/kg min, P < .05). Glucose oxidation rate was increased only in carvedilol (2.6 ± 1.4 to 4.4 ± 1.6 mg m²/kg min, P < .05), but did not change in bisoprolol group. Conclusions: Both selective and nonselective β-blockers reduce total body resting EPR in noncachectic CHF patients. Carvedilol compared to bisoprolol shifts total body substrate utilization from lipid to glucose oxidation.     

Role of sex in post-transplant diabetes mellitus development: Are men and women equal?

Introduction

Sex differences are defined as biology-linked differences between women and men that occur through the sex chromosomes and their effects on organ systems.