MTHFR c.677C>T polymorphism as an independent predictor of peak bone mass in Danish men--results from the Odense Androgen Study

The MTHFR c.677C>T polymorphism has been shown to have significant effects on skeletal health in middle-aged to elderly women and men. Despite an accumulating amount of data on MTHFR genetics and the association between homocysteine levels and fracture, it remains unknown if MTHFR c.677C>T genotype affects bone mineral accretion in youth or bone loss in adulthood. The purpose of this cross-sectional study was to examine the effects of this common allelic polymorphism on peak bone mass and bone turnover. We performed MTHFR genotyping in 780 healthy Danish men, aged 20 to 29 years, participating in the Odense Androgen Study. BMD at the spine, hip and whole-body was measured using a Hologic QDR-4500 densitometer. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. Spine BMD was significantly associated with genotype, with a decrease in BMD of 0.20 SD for each copy of the T-allele. Effects were independent of age, BMI, smoking and serum levels of vitamin D and IGF-I. Associations with BMD of the hip and whole body were short of statistical significance. MTHFR genotype showed no association with the bone turnover markers 1-CTP, bone specific alkaline phosphatase or osteocalcin. In conclusion, significant skeletal effects of this common polymorphism were present at the lumbar spine in men at the age of 25 years.     

Influence of Short‐term Confinement and Exercise on Tibia Development in Growing Pigs

The influence of short‐term confinement and moderate exercise on tibia development was investigated in growing pigs (36–41 kg, 10 weeks at the beginning of the study). Animals were kept for 2 weeks either in individual crates of 0.8 m² (‘confinement’, n = 4) or kept in groups of four animals in large crates of 5.6 m² without (‘control’) or with additional exercise (30 min walking at 5 days/week; ‘exercise’). Bone density and morphological parameters were evaluated by computer tomography (CT). Periosteal apposition and longitudinal growth were determined after polychrome sequential labelling in weekly intervals. Cortical areas of the cross sections at the mid‐shaft and at 75% of the length of the bone measured distal to the carpus by CT were significantly correlated to each other (r = 0.70) and revealed a significant reduction in confined animals. This difference was explained by lower periosteal apposition rates in these animals compared with exercised and group‐housed pigs. Similarly longitudinal growth and the formation and calcification of spongiosa of the tibiae were inhibited by confinement. Thus, 2 weeks of confinement led to significant differences in bone growth and metabolism in young growing piglets when compared with animals with moderate activity.     

Glycemia Determines the Effect of Type 2 Diabetes Risk Genes on Insulin Secretion

OBJECTIVE

Several single nucleotide polymorphisms (SNPs) in diabetes risk genes reduce glucose- and/or incretin-induced insulin secretion. Here, we investigated interactions between glycemia and such diabetes risk polymorphisms.

RESEARCH DESIGN AND METHODS

Insulin secretion was assessed by insulinogenic index and areas under the curve of C-peptide/glucose in 1,576 subjects using an oral glucose tolerance test (OGTT). Participants were genotyped for 10 diabetes risk SNPs associated with β-cell dysfunction: rs5215 (KCNJ11), rs13266634 (SLC30A8), rs7754840 (CDKAL1), rs10811661 (CDKN2A/2B), rs10830963 (MTNR1B), rs7903146 (TCF7L2), rs10010131 (WFS1), rs7923837 (HHEX), rs151290 (KCNQ1), and rs4402960 (IGF2BP2).Furthermore, the impact of the interaction between genetic variation in TCF7L2 and glycemia on changes in insulin secretion was tested in 315 individuals taking part in a lifestyle intervention study.

RESULTS

For the SNPs in TCF7L2 and WFS1, we found a significant interaction between glucose control and insulin secretion (all P ≤ 0.0018 for glucose × genotype). When plotting insulin secretion against glucose at 120 min OGTT, the compromising SNP effects on insulin secretion are most apparent under high glucose. In the longitudinal study, rs7903146 in TCF7L2 showed a significant interaction with baseline glucose tolerance upon change in insulin secretion (P = 0.0027). Increased glucose levels at baseline predicted an increase in insulin secretion upon improvement of glycemia by lifestyle intervention only in carriers of the risk alleles.

CONCLUSIONS

For the diabetes risk genes TCF7L2 and WFS1, which are associated with impaired incretin signaling, the level of glycemia determines SNP effects on insulin secretion. This indicates the increasing relevance of these SNPs during the progression of prediabetes stages toward clinically overt type 2 diabetes.Type 2 diabetes is a disorder characterized by chronically elevated blood glucose levels due to insulin resistance and a relative lack of compensatory pancreatic insulin secretion. Environmental triggers such as a sedentary lifestyle, physical inactivity, and increased body weight play an important role in the development of the disease. In this regard, genetics and especially gene-environment interactions play an important role. Recent research revealed more than 25 gene variants leading to a higher risk for the development of type 2 diabetes (1). Interestingly, most of the diabetes risk genes alter β-cell function (1). This supports the hypothesis that the main genetic effect in the development of type 2 diabetes could be impaired insulin secretion. Neither environmental triggers nor genetics alone can explain the multifactorial disease type 2 diabetes, thus a close interaction between both is presumed (2–4). Hence, environmental influences may determine an individual''s susceptibility for single nucleotide polymorphism (SNP) effects, or vice versa genotype may designate a person''s susceptibility toward environmental factors.One “environmental” factor that plays a role early in the pathogenesis of type 2 diabetes is elevated glucose. It is well known that years before type 2 diabetes occurs, glucose control is altered, as reflected by higher fasting glucose and/or higher postprandial glucose (5). High glucose exerts unfavorable effects on insulin sensitivity and secretion, known as glucotoxicity (6,7). On the other hand, elevated glucose levels are needed for the incretin effect. Glucagon-like peptide 1–induced insulin secretion becomes fully active only in the hyperglycemic range (8,9). Incretin-dependent insulin secretion might therefore be of particular importance when compensatory insulin hypersecretion is required.The aim of this study was to investigate whether glycemia influences the effects of genetic variation associated with type 2 diabetes on insulin secretion. We therefore studied 10 genome-wide association study–derived variants that were furthermore found to influence β-cell function in subsequent studies (rev. in 1,10). Of these, 2 (in the TCF7L2 and WFS1 loci) are associated with incretin-stimulated insulin secretion (1). As the magnitude of incretin-stimulated insulin secretion is dependent on elevated glucose levels (8,9), we hypothesized that glucose levels specifically interact with the effect of those SNPs on insulin secretion both in cross-sectional and longitudinal intervention studies.     

Balneophotochemotherapie des Lichen ruber Eigene Ergebnisse und Vergleich mit bisher angewandten Photochemotherapiemodalitäten

Zusammenfassung 12 Patienten mit ausgedehntem, therapieresistentem Lichen ruber wurden mittels Balneophotochemotherapie mit 8-Methoxypsoralen (8-MOP, Konzentration im Badewasser 0,5 mg/l) behandelt. Bei 11 der 12 Patienten kam es innerhalb von 6 Wochen zu einer deutlichen Besserung bzw. zur Abheilung lange bestehender Hautver?nderungen eines Lichen ruber. Lediglich bei einer Patientin zeigte sich nur eine geringgradige Befundbesserung. Durchschnittlich wurden 19,1 (SD±3,6) PUVA-Badbehandlungen durchgeführt. Die mittlere kumulative UV-A-Dosis bis zur Abheilung der Effloreszenzen betrug 16,7 (SD±4,8) J/cm². Au?er verst?rkten phototoxischen Reaktionen bei 2 Patienten kam es zu keinen weiteren Nebenwirkungen. Die Ergebnisse dieser Untersuchung zeigen, da? die Balneophotochemotherapie mit 8-MOP eine effiziente und nebenwirkungsarme therapeutische Alternative in der Behandlung des ausgepr?gten exanthematischen wie auch des hypertrophisch-hyperkeratotischen Lichen ruber darstellt. Im Vergleich mit der peroralen PUVA-Therapie sowie der PUVA-Badtherapie mit Trimethylpsoralen weist die Balneophotochemotherapie mit 8-MOP eine sehr gute Wirkungs- zu Nebenwirkungsrelation auf. Das Abheilen der Hautver?nderungen auch bei Patienten, die auf intensive topische und systemische Therapie nicht ansprachen, weist darauf hin, da? die Balneophotochemotherapie in ihrer Wirkung sogar anderen therapeutischen Verfahren überlegen sein kann. Eingegangen am 20. April 1996 Angenommen am 20. November 1996     

Meningioma and associated cavernous hemangioma as a parasellar tumor

A case of meningioma and associated cavernous hemangioma is described as a parasellar tumor. The meningioma was completely removed. The cavernous hemangioma was subtotally removed because of the high risk.     

Resistance to ischaemic nerve-fibre block in diabetes mellitus and in mitochondrial encephalomyopathies

Thermal thresholds were measured during ischaemic compression block in the left forearms of 26 healthy subjects, 10 patients with diabetes mellitus and 6 patients suffering from different kinds of mitochondrial disorders. Cold and warm thresholds in the 6 patients with deficiencies in the respiratory chain increased earlier than in normals. When cold perception was impaired, cold stimuli were perceived as warmth and pinprick perception attenuated. In diabetics cold thresholds were less elevated during ischaemic block than in controls. This was paralleled by tingling paraesthesiae in all groups. The findings show that higher resistance to ischaemic nerve-fibre block in diabetes mellitus is not exclusively based on increased anaerobic metabolism.     

Urinary disease in 2 Dogon populations with different exposure to Schistosoma haematobium infection: progression of bladder and kidney diseases in children and adults

BACKGROUND: Schistosoma haematobium infection causes severe urinary disease and considerable mortality. The factors that determine disease progression from mild to severe stages are not fully understood. METHODS: Here we describe a cross-sectional epidemiological study of kidney and bladder diseases in 2 Dogon populations with different exposure to S. haematobium infection. RESULTS: Early and high exposure resulted in more-severe disease, especially among young subjects, without clear evidence of a more-rapid development of immunity. Nevertheless, 50%-60% of subjects of all age classes in both villages showed no evidence of disease. Kidney and bladder disease peaked biphasically among young subjects and adults >25 years old. The first peak corresponded with infections of maximum intensity, whereas the second peak occurred among adults with infections of very low intensity. Kidney disease was correlated with circulating anodic antigen concentration in serum, whereas bladder disease was correlated with egg count and eosinophil cationic protein concentration in urine. Kidney and bladder disease did not correlate. Severe kidney disease was more frequent in certain families. CONCLUSIONS: The frequency of urinary disease is increased by infections acquired early during life, is regulated by strong clinical immunity in certain subjects, and may be dependent on hereditary factors. Kidney and bladder disease may involve different mechanisms of pathogenesis, which may differ between children and adults.