Special report adds nothing new, say paper authors.
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Cause of Death↗
Biomedical subjects
J Huber
Publications and source records attributed to J Huber.
Ghrelin does not regulate the GH response to insulin-induced hypoglycaemia in children but could be involved in the regulation of cortisol secretion.
OBJECTIVE: Ghrelin activates the growth hormone secretagogue receptor GHS-R. It strongly stimulates GH secretion and has a role in energy homeostasis. The relationship between plasma ghrelin and cortisol levels during insulin-induced hypoglycaemia in prepubertal and pubertal children has not yet been investigated. The aim of the present study was to establish whether insulin-induced hypoglycaemia stimulates ghrelin secretion and whether changes in ghrelin concentrations are related to changes in GH and cortisol in children. DESIGN AND PATIENTS: We studied a group of 20 children and adolescents (five girls, 15 boys, mean age 10.8 +/- 3.7 years) undergoing insulin tolerance tests (ITTs) for clinical investigation of GH deficiency. MEASUREMENTS: Stimulation tests were performed to investigate the relationship between ghrelin, GH, cortisol and glucose levels according to age and pubertal stage by determining the ghrelin profiles during insulin-induced hypoglycaemia (at 0, 60 and 120 min). RESULTS: Ghrelin was significantly and inversely related to body weight, height, body mass index (BMI) and age of children (P < 0.05). Significant changes in ghrelin levels (P = 0.00013) were found after the insulin bolus, with a decline at 60 min and an increase to baseline values at 120 min. Changes in cortisol levels were negatively correlated with changes in ghrelin at 60 min (r = -0.59, P = 0.004) and at 120 min (r = -0.605, P = 0.003). CONCLUSIONS: This study shows that ghrelin might not regulate the GH response to insulin-induced hypoglycaemia in prepubertal and pubertal children. A role for ghrelin in the regulation of cortisol secretion can be hypothesized concerning the negative correlation between changes in ghrelin and cortisol. Furthermore, the results imply that ghrelin secretion is age dependent and is a function of growth.
Adolescent↗
Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids.
OBJECTIVE: Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids (PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue. METHODS AND PROCEDURE: Male obese diabetic (db/db) mice were treated with either a low-fat standard diet (LF), or high-fat diets rich in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) or the latter including marine n-3 PUFA (HF/3). White adipose tissue was analyzed for gene expression, fatty acid composition and by immunofluorescence. RESULTS: HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes. CONCLUSION: N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients.
Adipocytes↗
Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids.
AIMS/HYPOTHESIS: Inflammatory alterations in white adipose tissue appear to underlie complications of obesity including diabetes mellitus. Polyunsaturated fatty acids (PUFA), particularly those of the n-3 series, modulate immune responses and may ameliorate insulin sensitivity. In this study, we investigated how PUFA affect white adipose tissue inflammation and gene expression in obese diabetic animals. MATERIALS AND METHODS: We treated db/db mice as well as lean non-diabetic mice (db/+) with either low-fat standard diet (LF) or high-fat diets rich in (1) saturated/monounsaturated fatty acids (HF/S), (2) n-6 PUFA (HF/6) and (3) the latter including purified marine n-3 PUFA (HF/3). RESULTS: Many genes involved in inflammatory alterations were upregulated in db/db mice on HF/S compared with LF in parallel with phosphorylation of c-Jun N-terminal kinase (JNK). In parallel, adipose tissue infiltration with macrophages was markedly enhanced by HF/S. When compared with HF/S, HF/6 showed only marginal effects on adipose tissue inflammation. However, inclusion of n-3 PUFA in the diet (HF/3) completely prevented macrophage infiltration induced by high-fat diet and changes in inflammatory gene expression, also tending to reduce JNK phosphorylation (p<0.1) in diabetic mice despite unreduced body weight. Moreover, high-fat diets (HF/S, HF/6) downregulated expression and reduced serum concentrations of adiponectin, but this was not the case with n-3 PUFA. CONCLUSIONS/INTERPRETATION: n-3 PUFA prevent adipose tissue inflammation induced by high-fat diet in obese diabetic mice, thereby dissecting obesity from adipose tissue inflammation. These data suggest that beneficial effects of n-3 PUFA on diabetes development could be mediated by their effect on adipose tissue inflammation.
Adiponectin↗
Mode of delivery is associated with maternal and fetal endocrine stress response.
OBJECTIVE: To determine whether mode of delivery is associated with the endocrine stress response in mother and child. DESIGN: Prospective observational study. SETTING: Tertiary care centre, University hospital. POPULATION: A total of 103 nulliparous women with uncomplicated singleton pregnancies at term undergoing either spontaneous labour for vaginal delivery or delivering by caesarean section without labour. Thirty women delivered vaginally without any pain relief, 21 women delivered vaginally with epidural anaesthesia, 23 women had ventouse extraction and 29 women underwent caesarean section with epidural analgesia. METHODS: After delivery, maternal and umbilical cord blood was collected for determination of different stress-associated hormones. MAIN OUTCOME MEASURES: Concentrations of epinephrine (EP), norepinephrine (NOR), adrenocorticotropic hormone (ACTH), cortisol (CORT), prolactin (PRL), corticotropin-releasing factor and beta-endorphin (BE). RESULTS: Caesarean section was associated with significantly lower maternal concentrations of EP, NOR, ACTH, CORT, PRL and BE and lower newborn levels of EP, NOR and CORT compared with all other modes of delivery. Concentrations of EP, ACTH and BE differed significantly in newborns delivered by normal vaginal delivery, vaginal delivery with epidural anaesthesia and ventouse extraction. CONCLUSIONS: The mode of delivery and analgesia used during birth are associated with maternal and fetal endocrine stress responses.
Adrenocorticotropic Hormone↗
The P48T germline mutation and polymorphism in the CDKN2A gene of patients with melanoma.
CDKN2A has been implicated as a melanoma susceptibility gene in some kindreds with a family history of this disease. Mutations in CDKN2A may produce an imbalance between functional p16ink4a and cyclin D causing abnormal cell growth. We searched for germline mutations in this gene in 22 patients with clinical criteria of hereditary cancer (early onset, presence of multiple primary melanoma or 1 or more first- or second-degree relatives affected) by secondary structural content prediction, a mutation scanning method that relies on the propensity for single-strand DNA to take on a three-dimensional structure that is highly sequence dependent, and sequencing the samples with alterations in the electrophoretic mobility. The prevalence of CDKN2A mutation in our study was 4.5% (1/22) and there was a correlation between family history and probability of mutation detection. We found the P48T mutation in 1 patient with 2 melanoma-affected relatives. The patient descends from Italian families and this mutation has been reported previously only in Italian families in two independent studies. This leads us to suggest the presence of a mutational "hotspot" within this gene or a founder mutation. We also detected a high prevalence (59.1%) of polymorphisms, mainly alleles 500 C/G (7/31.8%) or 540 C/T (6/27.3%), in the 3' untranslated region of exon 3. This result reinforces the idea that these rare polymorphic alleles have been significantly associated with the risk of developing melanoma.
Adolescent↗
Oct-4 expression in human endometrium.
The transcription factor Oct-4 is crucial for the maintenance of cell pluripotency and is known to be expressed in embryonic stem cells, germ cells and whole embryos at various stages of development. Oct-4 regulates cell fate in a dose-dependent manner and plays a key role in germ-cell tumours. In the past, several stem-cell markers have been detected, and their role in the pathogenesis of diseases has been discussed frequently. Thus, we investigated the expression of Oct-4 comparing its occurrence in endometrium of healthy and diseased women using immunohistochemistry (IHC) and RT-PCR. IHC demonstrated Oct-4 expression in 25 of 60 sections (42%), respectively in 11 out of 25 patients (44%). Oct-4 mRNA was detected by RT-PCR in all tested samples (9 of 9) of endometrium, although the levels of expression varied. To our knowledge, this is the first study demonstrating Oct-4 expression in human endometrium.
Adult↗
Laparoscopic versus open myomectomy: a double-blind study to evaluate postoperative pain.
The advantages of laparoscopic over open surgery have been documented in nonblinded settings. Our prospective, double-blind setting evaluated pain scores 72 h after surgery by comparing patients who underwent laparoscopic myomectomy or with laparotomy. Forty women referred for conservative myomectomy were included in the study. After stratification (myoma size, number of myomas, and surgeon), patients were randomized to either laparoscopy (n = 19) or laparotomy (n = 21) and received a standardized anesthesia and patient-controlled analgesia for 24 h after surgery. Identical wound dressings were applied to blind the patient and the observer to the surgical approach. The postoperative pain scores were documented on a visual analog scale (VAS; 0 = no and 10 = unbearable pain) at 24, 48, and 72 h after surgery. As the primary outcome variable, we calculated the mean overall VAS-score at these time points. P < 0.05 (t-test and analysis of covariance) was considered statistically significant. There were no differences in patient characteristics among the groups. The mean overall VAS score at 24, 48, and 72 h was statistically significantly lower in the laparoscopic group compared with the laparotomy group (2.28 +/- 1.38 versus 4.03 +/- 1.63; P < 0.01). Our data demonstrate, for the first time in a double-blind setting, that laparoscopic myomectomy reduces postoperative pain for 72 h after surgery compared with laparotomy.
Adult↗
Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition.
AIMS/HYPOTHESIS: Renal accumulation of AGEs may contribute to the progression of diabetic nephropathy. We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes. METHODS: Male Zucker diabetic fatty rats (ZDF, Gmi-fa/fa) rats were treated from age 10 to 37 weeks with ramipril (1 mg.kg(-1).day(-1)), AVE7688 (45 mg.kg(-1).day(-1)) or without drug. Ramipril and AVE7688 reduced albuminuria by 30 and 90%, respectively. RESULTS: ZDF rats showed increased renal accumulation of the AGE subtypes 3-deoxyglucosone-imidazolone, pentosidine and CML by about 40, 55 and 55%, respectively compared with heterozygous, non-diabetic control animals at the age of 37 weeks. AVE7688 but not ramipril attenuated the renal accumulation of 3-deoxyglucosone-imidazolone, pentosidine and CML and improved CML clearance in ZDF rats. During glycation reactions in vitro, AVE7688 also demonstrated potent chelating activity and inhibited metal-catalysed formation of pentosidine and CML. CONCLUSIONS/INTERPRETATION: Improved AGE clearance and direct inhibition of AGE formation by chelation may contribute to reduced accumulation of renal AGEs and to the nephroprotective effects of vasopeptidase inhibition in type 2 diabetes.
Angiotensin-Converting Enzyme Inhibitors↗
Identifying target regions for vigilance improvement under hormone replacement therapy in postmenopausal syndrome patients by means of electroencephalographic tomography (LORETA).
RATIONALE: Daytime fatigue, which at the neurophysiological level is due to vigilance decrements, is a frequent complaint in postmenopausal women. OBJECTIVES: In a three-arm, 2-month, parallel group-design study, vigilance-promoting effects of a novel continuous combination (=Climodien 2/3) of estradiol valerate (EV; 2 mg) and dienogest (DNG; 3 mg) were compared with the effects of both EV alone and placebo in 55 insomniac, postmenopausal syndrome patients. METHODS: Low-resolution brain electromagnetic tomography (LORETA) was undertaken to identify the cerebral target regions of hormone replacement therapy. RESULTS: An omnibus significance test revealed Climodien to increase activity in 882 of 2,394 voxels in the alpha-2 band, followed by 733, 706, and 664 voxels in the beta-2, beta-1, and beta-3 bands, and 509 voxels in the delta band, whereas 2 mg EV alone did not produce a significant suprathreshold activity. Current density increased predominantly in the right hemisphere, which had already been described in the literature as the center of the vigilance system. In the fast alpha range, which plays a major role in the context of vigilance, increased activity was found in the right prefrontal, temporal, and superior parietal cortices, i.e., those brain areas of the right-sided fronto-parietal neuronal network that are responsible for sustained attention. A further activity increase was seen in the anterior cingulate gyrus associated with attentional control and conflict monitoring. The right temporal lobe showed increased current density in all frequency bands. CONCLUSIONS: Electroencephalographic tomography (LORETA) identified the right-hemispheric vigilance system as the target region of Climodien.
Arousal↗
Sudden unexplained infant death in 20 regions in Europe: case control study.
BACKGROUND: After striking changes in rates of sudden unexplained infant death (SIDS) around 1990, four large case-control studies were set up to re-examine the epidemiology of this syndrome. The European Concerted Action on SIDS (ECAS) investigation was planned to bring together data from these and new studies to give an overview of risk factors for the syndrome in Europe. METHODS: We undertook case-control studies in 20 regions. Data for more than 60 variables were extracted from anonymised records of 745 SIDS cases and 2411 live controls. Logistic regression was used to calculate odds ratios (ORs) for every factor in isolation, and to construct multivariate models. FINDINGS: Principal risk factors were largely independent. Multivariately significant ORs showed little evidence of intercentre heterogeneity apart from four outliers, which were eliminated. Highly significant risks were associated with prone sleeping (OR 13.1 [95% CI 8.51-20.2]) and with turning from the side to the prone position (45.4 [23.4-87.9]). About 48% of cases were attributable to sleeping in the side or prone position. If the mother smoked, significant risks were associated with bed-sharing, especially during the first weeks of life (at 2 weeks 27.0 [13.3-54.9]). This OR was partly attributable to mother's consumption of alcohol. Mother's alcohol consumption was significant only when baby bed-shared all night (OR increased by 1.66 [1.16-2.38] per drink). For mothers who did not smoke during pregnancy, OR for bed-sharing was very small (at 2 weeks 2.4 [1.2-4.6]) and only significant during the first 8 weeks of life. About 16% of cases were attributable to bed-sharing and roughly 36% to the baby sleeping in a separate room. INTERPRETATION: Avoidable risk factors such as those associated with inappropriate infants' sleeping position, type of bedding used, and sleeping arrangements strongly suggest a basis for further substantial reductions in SIDS incidence rates.
Alcohol Drinking↗
Cryopreservation of a whole ovary as a strategy for restoring ovarian function.
PURPOSE: To evaluate whether a total ovary can successfully be cryopreserved and thawed under maintenance of high proportions of structurally normal primordial follicles. METHODS: Porcine ovaries were explanted immediately after slaughtery. Ten ovaries were cooled to -196 degrees C using cryoprotective solution and a computer-controlled freezing technique. Five contralateral ovaries were fixed with formalin for histological examination, the five remaining ovaries were directly plunged in liquid nitrogen. After three weeks of storage, frozen ovaries were thawed and examined by light and electron microscopy. Viability was assessed by evaluation of intact primordial follicles with respect to cellular and intracellular structures. RESULTS: Histological viability of primordial follicles in computer-frozen ovaries was 84.4% (76.1-90.6%), as compared to non-frozen control samples (92-100%; mean 97.6%) and to ovaries plunged in liquid nitrogen without cryoprotection 21.1% (4.5-35.0%). CONCLUSIONS: Cryopreservation of whole ovaries may present a feasible way to maintain high numbers of viable primordial follicles in ovarian tissue retransplantation.
Animals↗
Hormone profiles, body mass index and aging male symptoms: results of the Androx Vienna Municipality study.
Aging in the male is accompanied by steroid hormonal decline, and men may develop symptoms associated with hypogonadism. Increased awareness of 'andropause' in recent years has led to greater demand for hormonal assessments, resulting in a rising burden for health economics. We conducted a cross-sectional study to define men at risk for hypogonadism, in whom further hormonal investigation should be performed. We examined 664 blue-collar workers aged 40-60 years at their workplace and determined hormonal status and body mass index (BMI). Men with an abnormal urogenital status and those on medication that might affect endocrine status were excluded from the study. All participants completed the validated Aging Male Symptom (AMS) questionnaire and obtained scores for psychological symptoms, somatovegetative symptoms, and sexual symptoms. Multiple logistic regression analyses revealed a significantly increased risk (represented by the odds ratio) of psychological symptoms for men with low levels of testosterone and/or bioavailable testosterone (BAT). Increased BMI as well as low testosterone levels and/or low BAT levels raised the risk of somatovegetative symptoms. Each decrease of BAT by 1 ng/ml caused an approximately 1.8-fold increase of the risk (odds ratio = 1.832, p = 0.005). Additional independent risk factors were increased age and low luteinizing hormone (LH) level. Men aged 55 years with BMI > 28 kg/m2 and with somatovegetative symptoms and moderate or severe psychological symptoms had a 7.2-fold increase in the risk of a BAT level < 1.5 ng/ml compared to men without these risk factors (p < 0.001). Sensitivity and specificity were 75% and 71%, respectively. The AMS score combined with age and BMI provides an easy and convenient method to identify men with probable androgen deficiency who require hormonal assessment.
Adult↗
Role of progestins with partial antiandrogenic effects.
An experts' meeting on the 'Role of progestins with partial antiandrogenic effects' was held in Berlin from January 19 to 22, 2001. The meeting was chaired by Dr R. Sitruk-Ware (New York, USA) and participants included Ms F. Fruzzetti (Pisa, Italy), J. Hanker (Trier, Germany), J. Huber (Vienna, Austria), F. Husmann (Bad Sassendorf, Germany), S. O. Skouby (Copenhagen, Denmark), J. H. H. Thijssen (Utrecht, The Netherlands), and R. Druckmann (Nice, France). The present paper reports the conclusions of the meeting. However, the publication of the Women's Health Initiative study, which appeared after the meeting, led to additional comments and revisions.
Androgen Antagonists↗
[Is there a lasting effect of functional claw-trimming on claw conditions?].
The influence of regular claw-trimming on the occurrence and prevalence of claw disorders was examined on a total of 164 dairy cows (Simmental, Red Friesian, Holstein Friesian). Ten dairy farms in the Austrian province of Salzburg were used for this study. Three examinations of the claws were carried out with an interval of six months in between to find out claw disorders. The results were recorded according to a claw scoring system. The claw scores were in the range of other studies using the same scoring system. The median of the claw scores at the beginning of the study was 27 in the tied stall group compared with 37 in the loose housing group, remaining at that level in the first group and falling to 25 in the second group. All in all, the positive effect of regular claw trimming was more pronounced in the loose housing group than in the tethered housing group.
Animal Husbandry↗
De novo complex chromosome rearrangement: a study of two patients.
Complex chromosome rearrangements (CCR) involving multiple breaks in two or more chromosomes are rare. We describe a girl with development delay and overgrowth who presents a nine-break apparently balanced de novo rearrangement involving chromosomes 1, 2, 3, 4 and 12, and a boy with developmental delay and seizures with a complex three-chromosome apparently balanced de novo rearrangement involving chromosomes 2, 7 and 13. The relationship between clinical abnormalities and apparently balanced rearrangements is discussed.
Adolescent↗
No free lunch for estrogen.
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Estrogen Replacement Therapy↗
Differential effects of "Advanced glycation endproducts" and beta-amyloid peptide on glucose utilization and ATP levels in the neuronal cell line SH-SY5Y.
Beta-amyloid peptide (Abeta) and "Advanced glycation endproducts" (AGEs) are components of the senile plaques in Alzheimer's disease patients. It has been proposed that both AGEs and Abeta exert many of their effects, which include the upregulation of pro-inflammatory cytokines, through RAGE ("receptor for advanced glycation endproducts"). To investigate whether Abeta and AGEs cause similar or identical effects on cell survival and energy metabolism, we have compared the effects of a model-AGE and Abeta on cell viability, ATP level, glucose consumption and lactate production in the neuroblastoma cell line SH-SY5Y. The results show that AGEs and Abeta increase glucose consumption and decrease ATP levels in a dose dependent manner. Furthermore, both compounds decrease mitochondrial activity measured by the MTT assay. However, only AGEs decrease the number of cells and significantly increase lactate production. These data indicate that both AGEs and Abeta can cause differential disturbances in neuronal metabolism, which may contribute to the pathophysiological findings in Alzheimer's disease. However, their signalling pathways are apparently quite distinct, a fact which should stimulate a more detailed investigation in this field, e.g. for the purpose of a rational design of potential "neuroprotective" RAGE antagonists.
Adenosine Triphosphate↗