The relationship between ghrelin levels and insulin resistance in men with idiopathic hypogonadotrophic hypogonadism at diagnosis and after therapy

Wstęp: Ostatnio wykazano, że grelina wpływa na bilans energetyczny i czynności rozrodcze, jednak jej rola w patogenezie insulinooporności nadal nie została wyjaśniona. Celem badania jest przede wszystkim ocena zależności między insulinoopornością i stężeniem greliny u mężczyzn z hipogonadyzmem, a następnie wykazanie wpływu leczenia testosteronem na stężenia insuliny i greliny. Materiał i metody: Do badania włączono 24 mężczyzn z nowo rozpoznanym idiopatycznym hipogonadotropowym hipogonadyzmem (IHH, idiopathic hypogonadotropic hypogonadism) i 20 zdrowych mężczyzn. Stężenie greliny, insuliny, glukozy, testosteronu całkowitego i wolnego, wartości wskaźników HOMA-IR i QUICKI oraz procentową zawartość tłuszczu w organizmie określono u wszystkich osób na początku badania, a u mężczyzn z hipogonadyzmem również po zakończeniu terapii. Wyniki: U mężczyzn z hipogonadyzmem stwierdzono istotnie niższe stężenia całkowitego i wolnego testosteronu, greliny i mniejszą wartość wskaźnika QUICKI niż w grupie kontrolnej, natomiast procentowa zawartość tłuszczu w organizmie, i wartość wskaźnika HOMAIR były wyższe u mężczyzn z IHH niż u zdrowych mężczyzn. Po leczeniu testosteronem u mężczyzn z hipogonadyzmem odnotowano istotne zwiększenie stężenia greliny i wskaźnika QUICKI oraz zmniejszenie wartości wskaźnika HOMA-IR i masy tkanki tłuszczowej. Obliczono współczynnik korelacji Pearsona i wykazano, że u mężczyzn z hipogonadyzmem stężenie greliny jest skorelowane dodatnio ze stężeniami całkowitego i wolnego testosteronu i wartością wskaźnika QUICKI oraz ujemnie z zawartością tkanki tłuszczowej i wskaźnikiem HOMA-IR. Po 6 miesiącach terapii testosteronem korelacje te nadal były obecne. Wnioski: Powyższe dane potwierdzają tezę, że grelina może stanowić wspólne ogniwo dla mechanizmów regulujących funkcje rozrodcze i homeostazę metaboliczną. (Endokrynol Pol 2010; 61 (4): 351-358)Introduction: It has recently been shown that ghrelin affects energy balance and reproductive function, but the role of ghrelin in the pathogenesis of insulin resistance is unclear. Firstly to assess the interaction between insulin resistance and ghrelin levels in hypogonadal men, and then to show the effects of testosterone (T) therapy on insulin and ghrelin. Material and methods: Twenty-four male patients newly diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) and 20 healthy male subjects were enrolled in this study. Ghrelin, insulin, glucose, total and free testosterone levels, HOMA-IR and QUICKI, and percentage of body fat mass were determined at baseline in all subjects and after therapy in hypogonadal men. Results: When compared with control subjects, hypogonadal men had significantly lower total and free T concentrations, ghrelin levels, and QUICKI whereas they had significantly higher body fat mass and HOMA-IR score. Following T therapy, a significant increase in ghrelin and QUICKI, and a decrease in HOMA-IR score and body fat mass were demonstrated in hypogonadal men. Calculation of the Pearson coefficient showed that ghrelin concentrations in hypogonadal men were positively correlated with free and total testosterone and QUICKI, whereas they were negatively correlated with body fat mass and HOMA-IR. After six months of T therapy, these correlations were still observed. Conclusions: Our data supports the notion that ghrelin may constitute an important link between the regulation of reproduction and metabolic homeostasis. (Pol J Endocrinol 2010; 61 (4): 351-358

An elderly diabetic case of ochronosis with depression and chronic pain

Alkaptonuria (ochronosis) is a rare autosomal recessive disorder featuring a genetic error in the amino acid metabolism. A defect in the tyrosine metabolism results in the accumulation and deposition of homogentisic acid in connective tissue, causing a blue-black discolouration. Degenerative arthropathy of the spine, knee, and hip are common signs of ochronosis in older age. An association between ochronosis and depression has not previously been discussed in the literature. This case report describes a 69 year-old woman with diabetes mellitus, ochronosis, depression and chronic pain. (Pol J Endocrinol 2010; 61 (6): 710-713)Alkaptoniuria (ochronoza) jest rzadką, dziedziczoną w sposób autosomalny recesywny chorobą metaboliczną, która polega na genetycznym defekcie przemiany aminokwasu, tyrozyny. Defekt ten powoduje gromadzenie się i odkładanie kwasu homogentyzynowego w tkance łącznej powodujące jej niebiesko-czarne zabarwienie. Częstymi objawami ochronozy w starszym wieku są zmiany zwyrodnieniowe stawów kręgosłupa, kolan i bioder. W bibliografii nie znaleziono opracowań dotyczących związku między ochronozą i depresją. Niniejszy opis przedstawia przypadek 69-letniej kobiety cierpiącej z powodu ochronozy, depresji i przewlekłego bólu. (Endokrynol Pol 2010; 61 (6): 710-713

Potential benefits of hyperbaric oxygen therapy on atherosclerosis and glycaemic control in patients with diabetic foot

Wstęp: Celem badania była ocena wpływu leczenia tlenem w komorze hiperbarycznej (HBOT, hyperbaric oxygen therapy) na kontrolę glikemii, czynniki ryzyka miażdżycy, wskaźniki zapalenia oraz inne kliniczne i laboratoryjne parametry u chorych z owrzodzeniem w przebiegu zespołu stopy cukrzycowej poddanych systemowej HBOT. Materiał i metody: Do badania włączono 28 chorych z owrzodzeniem stopy 2-4 stopnia według skali Wagnera. Wszyscy chorzy odbyli 30 sesji terapii 100-procentowym tlenem przy ciśnieniu 2,4 ATA przez około 105 minut, 5 razy w tygodniu. Zmierzono następujące parametry: glikemię na czczo, odsetek HbA1c, wskaźnik insulinooporności HOMA-IR, stężenie wysokoczułego białka C-reaktywnego (hs-CRP, high sensitivity C-reactive protein), stężenie kwasu moczowego, średnią objętość płytek krwi, a ponadto zbadano morfologię krwi i profil lipidowy. Wyniki: Po zakończeniu terapii stwierdzono istotną poprawę średnich wartości wszystkich badanych parametrów. Wnioski: Wykazano, że HBOT wpływa korzystnie na czynniki ryzyka miażdżycy i kontrolę glikemii u chorych na cukrzycę. Potrzebne są dalsze, prowadzone na szeroką skalę badania z randomizacją, aby ocenić ogólnoustrojowe efekty HBOT. (Endokrynol Pol 2010; 61 (3): 275-279)Introduction: The aim of this study was to investigate the effects of hyperbaric oxygen therapy (HBOT) on glycaemic control, atherosclerosis, inflammatory markers, and other clinical and laboratory parameters in patients undergoing systemic HBOT for diabetic foot ulcerations. Material and methods: Twenty-eight patients with Wagner grade 2-4 diabetic foot ulcerations were included. All patients were given 100% oxygen at 2.4 absolute atmosphere (ATA) for about 105 minutes, five times a week for a total of 30 sessions. Fasting blood glucose (FBG), haemoglobin A1c (HbA1c), homeostasis model measurement-insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), uric acid, mean platelet volume (MPV), complete blood count, and lipid profile were tested. Results: Upon completion of treatment, a statistically significant improvement was observed in the mean values of all assessed parameters. Conclusions: HBOT was shown to have beneficial effects on atherosclerosis and glycaemic control in diabetic patients. Further large-scale randomized studies are needed to study the systemic effects of HBOT. (Pol J Endocrinol 2010; 61 (3): 275-279

Case Report:Inactivating PTH/PTHrP Signaling Disorder Type 1 Presenting With PTH Resistance

peer reviewedPTH resistance is characterized by elevated parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia and it is classically associated with GNAS locus genetic or epigenetic defects. Inactivating PTH/PTHrP signaling disorders (iPPSD) define overlapping phenotypes based on their molecular etiology. iPPSD1 is associated with PTH1R variants and variable phenotypes including ossification anomalies and primary failure of tooth eruption but no endocrine disorder. Here we report on a 10-month-old child born from consanguineous parents, who presented with mild neurodevelopmental delay, seizures, enlarged fontanelles, round face, and bilateral clinodactyly. Hand x-rays showed diffuse delayed bone age, osteopenia, short metacarpal bones and cone-shaped distal phalanges. A diagnosis of PTH resistance was made on the basis of severe hypocalcemia, hyperphosphatemia, elevated PTH and normal vitamin D levels on blood sample. The patient was treated with calcium carbonate and alfacalcidol leading to rapid bio-clinical improvement. Follow-up revealed multiple agenesis of primary teeth and delayed teeth eruption, as well as Arnold-Chiari type 1 malformation requiring a ventriculoperitoneal shunt placement. GNAS gene analysis showed no pathogenic variation, but a likely pathogenic homozygous substitution c.723C>G p.(Asp241Glu) in PTH1R gene was found by trio-based whole exome sequencing. We studied the deleterious impact of the variant on the protein conformation with bioinformatics tools. In conclusion, our study reports for the first time PTH resistance in a child with a biallelic PTH1R mutation, extending thereby the clinical spectrum of iPPSD1 phenotypes

Case report:Thirty-year progression of an EMPF1 encephalopathy due to defective mitochondrial and peroxisomal fission caused by a novel de novo heterozygous DNM1L variant

Mutations in DNM1L (DRP1), which encode a key player of mitochondrial and peroxisomal fission, have been reported in patients with the variable phenotypic spectrum, ranging from non-syndromic optic atrophy to lethal infantile encephalopathy. Here, we report a case of an adult female patient presenting with a complex neurological phenotype that associates axonal sensory neuropathy, spasticity, optic atrophy, dysarthria, dysphasia, dystonia, and ataxia, worsening with aging. Whole-exome sequencing revealed a heterozygous de novo variant in the GTPase domain of DNM1L [NM_001278464.1: c.176C>A p.(Thr59Asn)] making her the oldest patient suffering from encephalopathy due to defective mitochondrial and peroxisomal fission-1. In silico analysis suggested a protein destabilization effect of the variant Thr59Asn. Unexpectedly, Western blotting disclosed profound decrease of DNM1L expression, probably related to the degradation of DNM1L complexes. A detailed description of mitochondrial and peroxisomal anomalies in transmission electron and 3D fluorescence microscopy studies confirmed the exceptional phenotype of this patient

Structural and functional alterations in salivary gland chromosomes and enzyme activity of Chironomus riparius Mg. (Diptera, Chironomidae) from anthropogenically polluted sites in Bulgaria and Turkey

The effect of environment contaminants on genome instability and changes in enzyme activity (acetylcholinesterase (AChE), glutathione S-transferase activities (GST), etoxyresorufin O-deethylase (EROD) and metallothionein (MT)) of Chironomus riparius Mg. from Bulgarian and Turkish stations over two years (2009, 2010) as well as laboratory reared larvae were studied. Physicochemical analysis of the sediments from the field stations indicated the presence of heavy metal pollutants (Cr, Cu, Mn, Pb, and Cd) whose concentrations were higher than the reference data. Genome instability was determined by somatic structural and functional alterations of the polytene chromosomes. In the field sites of both countries somatic aberrations occurred at a significantly higher frequency (p < 0.001) compared with control and laboratory material. C. riparius in sediments with higher concentrations of trace metals (Derincay River, Turkey and Chaya River, Bulgaria), was found to possess a high spectrum of somatic chromosome rearrangements with a somatic index of 2.53 and 3.25 respectively. Changes in functional activity included decreased activity of the Balbiani rings (BRs) and nucleolar organizer (NOR). The observed chromosome alterations agree with the high degree of trace metal pollution and high activity of the studied enzymes. However, no correlation between single somatic chromosome rearrangements and concentrations of specific metal ions was defined. The data are discussed in the light of the wide variety of interactions of metals in nature. The results show that the genome response and biochemical markers are sensitive markers of toxicity and provide early warning indicators of contaminants in the environment. © 2012 Dipartimento di Biologia Evoluzionistica

Tonically Active α2 Subunit-Containing Glycine Receptors Regulate the Excitability of Striatal Medium Spiny Neurons

Medium spiny neurons (MSNs) of the dorsal striatum represent the first relay of cortico-striato-thalamic loop, responsible for the initiation of voluntary movements and motor learning. GABAergic transmission exerts the main inhibitory control of MSNs. However, MSNs also express chloride-permeable glycine receptors (GlyRs) although their subunit composition and functional significance in the striatum is unknown. Here, we studied the function of GlyRs in MSNs of young adult mice. We show that MSNs express functional GlyRs, with α2 being the main agonist binding subunit. These receptors are extrasynaptic and depolarizing at resting state. The pharmacological inhibition of GlyRs, as well as inactivation of the GlyR α2 subunit gene hyperpolarize the membrane potential of MSNs and increase their action potential firing offset. Mice lacking GlyR α2 showed impaired motor memory consolidation without any changes in the initial motor performance. Taken together, these results demonstrate that tonically active GlyRs regulate the firing properties of MSNs and may thus affect the function of basal ganglia