Characterization of Pregnancy Induced Changes in Glucose Metabolism

Many reports indicate that pregnancy is a diabetogenic state in which there is both insulin resistance and an exaggerated maternal glucose and insulin response to food ingestion. However, the magnitude of these aberrations and their temporal relationship have not been adequately characterized. This study utilizes the hyperglycemic clamp technique to investigate the insulin secretory response and tissue sensitivity to insulin under hyperglycemic conditions in normal and gestational diabetic pregnancies. Our results indicate that third trimester normal pregnancy is characterized by an increased first phase (108.81+/-13.03 uU/ml) and second phase (228.57+/-43.40 microunits/ml) insulin secretory response as compared to non-pregnant controls (72.93+/-15.76, 103.02+8/-12.43 ) (p\u3c0.05). However, C-peptide values did not mirror those of insulin in that normal pregnant women during the third trimester of pregnancy demonstrated a significantly lower C-peptide to insulin ratio than either non-pregnant controls or gestational diabetic women in their third trimester (p\u3c0.05). In contrast to normal pregnant women, gestational diabetic women in their third trimester of pregnancy showed no increase in insulin secretion. Glucose uptake under hyperglycemic conditions tended to decrease progressively through pregnancy and was significantly lower than non-pregnant controls (10. 60+/-1. 19 mg/kg/min) in the third trimester of normal pregnancy (7.20+/-0.79 mg/kg/min) and gestational diabetic pregnancy (5.87+/-0.27 mg/kg/min) (p\u3c0.05). Furthermore, there was a significantly lower tissue sensitivity to insulin (defined by the ratio of the glucose uptake to the circulating insulin level during the final sixty minutes of the study) in normal third trimester pregnancies (0.03+/-0.01 mg/kg/min per uU/ml) and gestational diabetic pregnancies (0. 04+/-0. 01 mg/kg/min per uU/ml) as compared to non-pregnant controls (0.11+/-0.02 mg/kg/min per uU/ml) (p\u3c0.05). Neither glucagon nor growth hormone were found to be significantly different between the normal pregnant or gestational diabetic groups. These studies suggest that normal pregnancy is indeed characterized by a tissue insensitivity to insulin and that glucose tolerance (defined in this study as the rate of glucose uptake) in normal pregnancy is primarily related to the degree of compensatory hyperinsulinism. However, this increased compensatory insulin secretion appears to be absent in gestational diabetic women, thereby contributing to the deterioration of glucose tolerance observed in these women

Rechnergesteuerte Leistungsvermögensanalyse mit ABBA in der beruflichen Rehabilitation (Computer-controlled ana-lysis of capability with ABBA in occupational rehabilitation)

"ABBA, job inspection and strain analysis (ArbeitsplatzBegehungs- und BelastungsAnalyse), is a new software-supported expert system (PARADOX database with DELPHI programming system for Windows applications) based on the Ergonomic investigation system for the analysis of activities (Arbeitswissenschaftliches Erhebungssystem zur Tätigkeitsanalyse (AET)) which has been established for over 20 years. This new system makes it possible to compare job requirements with performance possibilities of disabled people in an objective, reliable and valid way and to interpret the results of occupational choice and work trials systematically and to evaluate them. Ergonomic information and the possibility of implementing measurements based on industrial physiology and industrial medicine improve diagnosis, occupational support, the arrangement of a working environment suitable for the disabled as well as placing, targeting these aspects at occupational integration." (Author's abstract, IAB-Doku) ((en))Behinderte, Leistungsfähigkeit - Messung, EDV-Anwendung, Anforderungsprofil, berufliche Rehabilitation, Berufsfindung, Arbeitserprobung

Semiquantitative analysis of intrahepatic CC-chemokine mRNas in chronic hepatitis C.

BACKGROUND: The mechanisms leading to hepatic injury in chronic hepatitis C virus (HCV) infection are only incompletely understood. Recent data propose a correlation of the intrahepatic expression of the CC chemokine RANTES and the degree of periportal and portal inflammatory liver damage. AIM: Here, we have studied the intrahepatic mRNA levels of CC chemokines RANTES together with that of other members of this chemokine family (MIP-1beta, MCP-1, and MCP-2) in chronic hepatitis C as compared with healthy controls. METHODS: Liver samples from 22 HCV-infected patients, nine individuals with primary biliary cirrhosis and from 12 normal controls were included into this study. Intrahepatic mRNA levels of CC chemokines RANTES, MIP-1beta, MCP-1, and MCP-2 were analyzed by a semi-quantitative reverse transcription/real-time polymerase chain reaction assay. RESULTS: In chronic HCV infection, intrahepatic RANTES mRNA levels were significantly higher than in non-infected controls (7.2-fold, p < 0.001) or in the disease control group (2.8-fold, p < 0.001) and higher levels of RANTES mRNA levels were observed in livers with an advanced stage of liver cell injury (histologic activity index > or = 6), although this difference was not statistically significant (p = 0.08). In contrast, mRNA levels of MIP-1beta (p = 0.021) and MCP-1 (p = 0.021) were significantly lower in HCV liver samples while MCP-2 expression was similar in all groups analyzed. CONCLUSION: The data support the concept of chemokines as mediators of liver cell injury in chronic hepatitis C

The Sphingosine-1-Phosphate (S1P) Lysophospholipid Receptor S1P3 Regulates MAdCAM-1+ Endothelial Cells in Splenic Marginal Sinus Organization

Marginal zones (MZs) are microdomains in the spleen that contain various types of immune cells, including MZ B cells, MOMA1+ metallophilic macrophages, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1)+ endothelial cells. MAdCAM-1+ and MOMA1+ cells line the sinus, that separates MZs from splenic follicles. Here we show that a receptor for the lysophospholipid sphingosine-1-phosphate (S1P), S1P3, is required for normal numbers of splenic immature and MZ B cells, and for S1P-induced chemotaxis of MZ B cells. S1P3 is also essential for proper alignment of MOMA1+ macrophages and MAdCAM-1+ endothelial cells along the marginal sinus. The lack of cohesion of the marginal sinus in S1P3−/− mice affects MZ B cell functions, as wild-type (WT) MZ B cells migrate more into S1P3−/− follicles than into WT follicles after treatment with lipopolysaccharide. Additionally, short-term homing experiments demonstrate that WT MZ B cells home to the S1P3−/− spleen in increased numbers, suggesting a role for the marginal sinus in regulating MZ B cells numbers. Moreover, S1P3−/− mice are defective in mounting immune responses to thymus-independent antigen type 2 due to defects in radiation-resistant cells in the spleen. These data identify lysophospholipids and the S1P3 receptor as essential regulators of the MZ sinus and its role as a barrier to the follicle

Fungal phytochrome chromophore biosynthesis at mitochondria

Mitochondria are essential organelles because of their function in energy conservation. Here, we show an involvement of mitochondria in phytochrome-dependent light sensing in fungi. Phytochrome photoreceptors are found in plants, bacteria, and fungi and contain a linear, heme-derived tetrapyrrole as chromophore. Linearization of heme requires heme oxygenases (HOs) which reside inside chloroplasts in planta. Despite the poor degree of conservation of HOs, we identified two candidates in the fungus Alternaria alternata. Deletion of either one phenocopied phytochrome deletion. The two enzymes had a cooperative effect and physically interacted with phytochrome, suggesting metabolon formation. The metabolon was attached to the surface of mitochondria with a C-terminal anchor (CTA) sequence in HoxA. The CTA was necessary and sufficient for mitochondrial targeting. The affinity of phytochrome apoprotein to HoxA was 57,000-fold higher than the affinity of the holoprotein, suggesting a “kiss-and-go” mechanism for chromophore loading and a function of mitochondria as assembly platforms for functional phytochrome. Hence, two alternative approaches for chromophore biosynthesis and insertion into phytochrome evolved in plants and fungi

Nova Geminorum 1912 and the Origin of the Idea of Gravitational Lensing

Einstein's early calculations of gravitational lensing, contained in a scratch notebook and dated to the spring of 1912, are reexamined. A hitherto unknown letter by Einstein suggests that he entertained the idea of explaining the phenomenon of new stars by gravitational lensing in the fall of 1915 much more seriously than was previously assumed. A reexamination of the relevant calculations by Einstein shows that, indeed, at least some of them most likely date from early October 1915. But in support of earlier historical interpretation of Einstein's notes, it is argued that the appearance of Nova Geminorum 1912 (DN Gem) in March 1912 may, in fact, provide a relevant context and motivation for Einstein's lensing calculations on the occasion of his first meeting with Erwin Freundlich during a visit in Berlin in April 1912. We also comment on the significance of Einstein's consideration of gravitational lensing in the fall of 1915 for the reconstruction of Einstein's final steps in his path towards general relativity.Comment: 31 p