A fully human IgG1 antibody targeting connexin 32 extracellular domain blocks CMTX1 hemichannel dysfunction in an in vitro model.

Connexins (Cxs) are fundamental in cell-cell communication, functioning as gap junction channels (GJCs) that facilitate solute exchange between adjacent cells and as hemichannels (HCs) that mediate solute exchange between the cytoplasm and the extracellular environment. Mutations in the GJB1 gene, which encodes Cx32, lead to X-linked Charcot-Marie-Tooth type 1 (CMTX1), a rare hereditary demyelinating disorder of the peripheral nervous system (PNS) without an effective cure or treatment. In Schwann cells, Cx32 HCs are thought to play a role in myelination by enhancing intracellular and intercellular Ca signaling, which is crucial for proper PNS myelination.

Starvation ketoacidosis and refeeding syndrome.

Starvation ketoacidosis (SKA) is a rarer cause of ketoacidosis. Most patients will only have a mild acidosis, but if exacerbated by stress can result in a severe acidosis. We describe a 66-year-old man admitted with reduced consciousness and found to have a severe metabolic acidosis with raised anion gap.

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

Background: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown.

Bone metastasis as primary presentation of pancreatic ductal adenocarcinoma: A case report and literature review.

PDAC bone metastases represent a clinical challenge characterized by multifaceted biological entity.

Analysis and modelling of cholesterol and high-density lipoprotein cholesterol changes across the range of C-reactive protein levels in clinical practice as an aid to better understanding of inflammation-lipid interactions.

Objectives: Raised total cholesterol (TC) and reduced high-density lipoprotein (HDL) cholesterol levels are established cardiovascular disease (CVD) risk factors. However, in autoimmune conditions the lipid-CVD association appears paradoxical, with inflammation as a potential confounding factor. We therefore sought to model the relationship between systemic inflammatory illness and lipid levels using C-reactive protein (CRP) as the prototypical marker of inflammation.

A comparison of the effect of two types of vibration exercise on the endocrine and musculoskeletal system.

Background: Whole body vibration (WBV) is a novel training intervention but a comparison of different methods of WBV has rarely been performed.

Aim: To compare the short and medium term effects of two regimens of WBV on endocrine status, muscle function and markers of bone turnover.

Patients And Methods: Over a period of 16 weeks, 10 men with a median age of 33 yrs (range, 29,49), were randomised to stand on the Galileo platform (GP) or Juvent1000 platform (JP) 3 times/wk.

Resistance to thyroid hormone--an incidental finding.

A 16-year-old female with mild hirsutism was noted to have a small, smooth, non-tender goitre. A resting peripheral tremor, but no other symptoms or signs of thyroid dysfunction were present. Her only medication was the contraceptive pill.

Use of cetrorelix in the investigation of testosterone excess in a postmenopausal woman.

A 65-year-old woman presented to the endocrine clinic with increasing facial hirsutism over the past 6 months. She was noted to have excess hair on forearms, back and abdomen, along with some frontal balding. There were no abnormalities of the external genitalia, blood pressure was satisfactory and weight was stable.

Diagnosing unsuspected hypopituitarism in adults from suggestive thyroid function test results.

Background: The typical pattern of thyroid function tests (TFTs) associated with hypopituitarism consists of subnormal free T4 (fT4) or total T4 and normal or marginally elevated thyroid-stimulating hormone (TSH). A previous study calculated an incidence of hypopituitarism of 3.2 cases/100,000/year by following up abnormal TFTs.

Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease.

HMG-CoA reductase inhibitors (statins) block the mevalonate pathway, preventing biosynthesis of cholesterol and isoprenoids. We investigated the effect of simvastatin on lymphocytes from normal human subjects and cardiovascular disease patients in order to provide a model for the in vivo actions of statins. Thirteen healthy volunteers were treated with 40 mg per day of simvastatin following which mean total cholesterol was reduced by 23% (S.

Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy?

Background: Calcific aortic stenosis may have common etiological factors with atherosclerosis.

Hypothesis: In this retrospective, case-control study, we aimed to determine whether there is an association between hypercholesterolemia and calcific aortic valve stenosis.

Methods: Consecutive patients undergoing single aortic or mitral valve replacement in a regional cardiothoracic surgical center were reviewed and preoperative patient characteristics were recorded: demographics, comorbidity (including coronary artery disease and associated risk factors), serum total cholesterol, lipid-lowering therapy, and serum creatinine.

[Albumin mRNA and pCEA in the histopathologic diagnosis of hepatocellular carcinoma].

Extrahepatic neoplasms metastatic to the liver histologically are often indistinguishable from hepatocellular carcinoma (HCC). The differential diagnosis between HCC and metastatic liver tumours can be even more difficult in ultrasound guided fine-needle biopsies. Purpose of the present study was to investigate the utility of immunohistochemical staining with polyclonal anticarcinoembryonic antigen (pCEA) antibody and of in situ hybridization (ISH) revealing human albumin mRNA, with emphasis on tissues obtained via fine-needle procedure.

Glucocorticoid receptor polymorphism in genetic hypertension.

The Milan hypertensive strain of rat (MHS) displays abnormalities in both renal function and adrenocortical activity. While the pressor role of the former has been studied in detail, the role of the latter has not yet been clearly evaluated. In the present study, glucocorticoid receptor (GR) binding characteristics in liver cytosol from adult MHS and Milan normotensive controls (MNS) have been investigated.

Glucocorticoid receptor polymorphism, skin vasoconstriction, and other metabolic intermediate phenotypes in normal human subjects.

Genetic variation of the glucocorticoid receptor (GR) locus is associated with differences in blood pressure. To define the intermediate phenotypes associated with this variation, we investigated the biochemical and clinical significance of a BclI restriction fragment length polymorphism of the GR locus in 64 normal male volunteers. Blood samples were genotyped as either AA (homozygous large allele; n = 6), Aa (heterozygous; n = 51), or aa (homozygous small allele, n = 7).

Simplified detection of a mutation causing familial hypercholesterolaemia throughout Britain: evidence for an origin in a common distant ancestor.

Familial hypercholesterolaemia (FH) is an inherited autosomal codominant disorder caused by many different mutations in the low-density lipoprotein receptor (LDLR) gene. The one described most frequently in patients with FH from England, arises from a G-->A transition at the first nucleotide of codon 80, resulting in the substitution of lysine for glutamic acid at residue 80 of the mature protein, FH E80K. We describe a simple method to detect this mutation in genomic DNA using the polymerase chain reaction (PCR).

Increased glucocorticoid activity in men with cardiovascular risk factors.

The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension.

Impaired cortisol binding to glucocorticoid receptors in hypertensive patients.

We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension.

In vivo and in vitro effects of carbenoxolone on glucocorticoid receptor binding and glucocorticoid activity.

Carbenoxolone potentiates the mineralocorticoid activity of endogenous glucocorticoid hormones by inhibiting the enzyme 11 beta-hydroxysteroid dehydrogenase, which converts cortisol and corticosterone to inactive 11-oxo-derivatives. We addressed the question of whether glucocorticoid activity is also affected by carbenoxolone. Using a rat model involving low dose corticosterone treatment, we found that carbenoxolone neither potentiated nor inhibited the modest increases in blood pressure or reductions in weight gain caused by steroid treatment.