Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

The electroencephalographic aspects in stress epistaxis

The nasal haemorrhage is a symptom whose significance is seldom completely investigated. In this paper we present the results that we have obtained in two groups of patients: a pediatric population who presented for repeated episodes of nasal haemorrhage and a group of first trimester pregnant women who also have noticed the appearance of this symptom. Beside the clinical examination, a paraclinical assessment has been performed, which included a laboratory profile (hematology and biochemistry) and electroencephalography (EEG), in which we found significant changes. We conclude that EEG is a valuable investigation technique for diagnosis and monitoring purposes in nasal hemorrhage. Also, the clinical management of the stress-related nasal hemorrhage must address multiple issues for becoming efficient.     

EEG patterns in alcohol withdrawal syndrome

The cerebral motor and cognitive behavior is obviously altered by chronic alcoholism, which generates significant morphological and biochemical changes. In turn, alcoholic withdrawal improves the cerebral blood supply, the psychological and motor behavior and the EEG appearance, especially in young alcoholics. Our study also underlines that alcoholic women develop a late improvement of the clinical and bioelectrical condition during the alcoholic withdrawal.     

Influence of the punch diameter and curvature on the yield pressure of MCC-compacts during Heckel analysis.

The volume reduction behaviour of powders has been quantified by means of the 'in-die' yield pressure (YP) using Heckel analysis. However, because different YPs are reported for the same material, the experimental conditions influencing this material-constant were investigated. Silicified microcrystalline cellulose was compressed into flat-faced and convex tablets using a compaction simulator instrumented with load and displacement transducers. During compression, upper and lower punch force and displacement data were recorded and corrected for punch deformation. A symmetrical triangle wave compression profile was used and the instantaneous punch velocity was kept constant (5mm/s). Individual tablet height and weight were used for Heckel analysis. The influence of the 'effective compression pressure' (P(EFF)) (ranging from 10 to 350 MPa), punch diameter (PD) (4, 9.5 and 12 mm) and filling depth (FD) (4.5, 7.5 and 10.5mm) on YP was statistically evaluated using Response Surface Modelling software. A quadratic surface response equation, describing the relationship between P(EFF), PD, FD and YP, was proposed for concave (Adj R(2): 0.8424; S.D.: 14.60 MPa) and flat-faced (Adj R(2): 0.8409; S.D.: 4.49 MPa) punches. YP and tensile strength were mainly determined by P(EFF), irrespective of punch curvature. FD and PD had only a minor influence on the YP, although more pronounced for the concave punches. The method used resulted in reproducible P(EFF) and tensile strength values and the flat-faced tablets showed less weight variation. Flat-faced punches are preferred over punches with a concave surface when investigating the volume reduction behaviour of a powder by means of Heckel analysis and the experimental parameters should be reported.     

A High-Sugar Diet Consumption,Metabolism and Health Impacts with a Focus on the Development of Substance Use Disorder: A Narrative Review

Carbohydrates are important macronutrients in human and rodent diet patterns that play a key role in crucial metabolic pathways and provide the necessary energy for proper body functioning. Sugar homeostasis and intake require complex hormonal and nervous control to proper body energy balance. Added sugar in processed food results in metabolic, cardiovascular, and nervous disorders. Epidemiological reports have shown enhanced consumption of sweet products in children and adults, especially in reproductive age and in pregnant women, which can lead to the susceptibility of offspring’s health to diseases in early life or in adulthood and proneness to mental disorders. In this review, we discuss the impacts of high-sugar diet (HSD) or sugar intake during the perinatal and/or postnatal periods on neural and behavioural disturbances as well as on the development of substance use disorder (SUD). Since several emotional behavioural disturbances are recognized as predictors of SUD, we also present how HSD enhances impulsive behaviour, stress, anxiety and depression. Apart from the influence of HSD on these mood disturbances, added sugar can render food addiction. Both food and addictive substances change the sensitivity of the brain rewarding neurotransmission signalling. The results of the collected studies could be important in assessing sugar intake, especially via maternal dietary patterns, from the clinical perspective of SUD prevention or pre-existing emotional disorders. Methodology: This narrative review focuses on the roles of a high-sugar diet (HSD) and added sugar in foods and on the impacts of glucose and fructose on the development of substance use disorder (SUD) and on the behavioural predictors of drugs abuse. The literature was reviewed by two authors independently according to the topic of the review. We searched the PubMed and Scopus databases and Multidisciplinary Digital Publishing Institute open access scientific journals using the following keyword search strategy depending on the theme of the chapter: “high-sugar diet” OR “high-carbohydrate diet” OR “sugar” OR “glucose” OR “fructose” OR “added sugar” AND keywords. We excluded inaccessible or pay-walled articles, abstracts, conference papers, editorials, letters, commentary, and short notes. Reviews, experimental studies, and epidemiological data, published since 1990s, were searched and collected depending on the chapter structure. After the search, all duplicates are thrown out and full texts were read, and findings were rescreened. After the selection process, appropriate papers were included to present in this review.     

The role of miRNA-210 in pre-eclampsia development

MicroRNAs (miRNAs) are a class of small non-coding, single-stranded RNAs (ribonucleic acids) that play important roles in many vital processes through their impact on gene expression. One such miRNA, miR210, represents a hypoxia-induced cellular miRNA group that hold a variety of functions. This review article highlights the importance of miR-210 in the development of pre-eclampsia.

KEY MESSAGE

• miR-210 is a promising biomarker for monitoring pregnancy with pre-eclampsia. Overexpression of miR-210 had a negative impact on the process of cell migration and trophoblast invasion.

     

The blood enzymatic antioxidative potential in bronchial asthma patients

This study aims at assessing the ability of asthma patients to defend themselves against the noxious effects of oxidative stress, known being the inflammatory nature of this disorder. As the anti-radical defence ability of the body is reflected by the antioxidative potential of blood and tissues, our study was based on the determination of the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and CAT/SOD and GPx/SOD ratios in the blood. Except for SOD, the activity of which was lower in asthma patients by -34.08%, CAT and GPx had values increased by +32.18%, respectively, with a resulting increase of CAT/SOD and GPx/SOD ratios. Our data, demonstrating a change in per-oxidants/antioxidants balance in favour of the first ones, seem to suggest that in the treatment of bronchial asthma the association of some compounds with antioxidants effects would be beneficial.     

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

Background

Growing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.

Methods

Semen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.

Results

Zn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).

Conclusions

This report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.