Comparison of soft tissue calcium levels throughout the life spans of normal and myopathic hamsters

Comparisons of calcium levels in heart, skeletal muscle, brain, liver and plasma were made throughout the life spans of normal and genetically myopathic hamsters. A large calcium accumulation occurred in, and was restricted to, myopathic tissues (heart and skeletal muscle). Calcium elevation in myopathic tissues corresponded to documented lesion appearance, and persisted throughout the remainder of the life span. Calcium buildup in heart and skeletal muscle, as a central feature of the myopathic process, does not reflect a general failure of calcium homeostasis; nonmyopathic tissues are unaffected. Calcium increased moderately in some normal tissues late in life.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

     

Up-regulation of adenylylcyclases I and II induced by long-term adaptation of rats to morphine fades away 20 days after morphine withdrawal

Background

Activation of adenylyl cyclase (AC) by prolonged exposure of mammalian organism to morphine was demonstrated in previous studies of mechanism of action of this drug. However, expression level of individual AC isoforms was not analyzed in crucial cell structure, plasma membrane (PM).

Methods

Rats were adapted to morphine for 10 days and sacrificed 24 h (group + M10) or 20 days (+ M10/−M20) after the last dose. Control animals were sacrificed in parallel with morphine-treated (groups − M10 and (− M10/−M20)). Percoll®-purified PM were isolated from brain cortex and analyzed by immunoblotting and specific radioligand binding.

Results

ACI (ACII) was increased 8× (2.5×) in morphine-adapted rats (+ M10) when compared with controls (− M10). Increase of ACI and II by long-term adaptation to increasing doses of morphine represented a specific effect as the amount of ACIII–ACIX, of prototypical PM marker, Na, K-ATPase and of trimeric G protein α and β subunits was unchanged. Increase of ACI and II was not detected in PM isolated from group (+ M10/−M20). Thus, the marked increase of ACI and ACII faded away 20 days since the last dose of morphine.

Conclusions

We assume that the specific increase in expression level of ACI and ACII in brain cortex of morphine-adapted rats proceeds as a compensatory, homeostatic response to prolonged exposure to inhibitory drug, morphine.

General significance

Our findings demonstrate that the dramatic and specific change of the crucial component of the opioid receptor cascade in brain cortex, manifested as an increase in PM level of ACI and II, is reversible.     

Atrial natriuretic factor in taurine-treated normal and cardiomyopathic hamsters

Diuretic and natriuretic activities of atrial extracts from BIO 14.6 (cardiomyopathic) and F1B (normal) hamsters at 180 days of age were measured by rat bioassay. Both activities were lower in BIO 14.6 extracts. Because of the reported protective action of taurine in the cardiomyopathic hamster, we tested the effect of 0.1 M taurine drinking upon the activity of atrial extracts. Urine flow and Na+ excretion were increased in both BIO 14.6 and F1B; however, comparatively larger increases in BIO 14.6 taurine drinkers abolished strain differences that were observed in water drinkers. Taurine drinking BIO 14.6 hamsters exhibited an increased plasma sodium concentration. Drinking of 0.6% NaCl also produced an elevated plasma sodium concentration in BIO 14.6. Extracts from hamsters with increased salt intake had diuretic and natriuretic activities that were not different from those of water drinkers. These findings confirm that ANF activity is deficient in BIO 14.6 hamsters, and this suggests a role for taurine in its production, release, and/or activation.     

Age-dependent differences in the effect of atrial natriuretic factor

Replacement of drinking water by 1.8% NaCl solution produces a severe hypernatremia in prepubertal rats and only a moderate elevation of the plasma sodium concentration (pNa) in adults. Hypernatremia in prepubertal rats was reduced by infusion of blood from adult rats, whereas blood from young rats was without this effect. The aim of this study was to find out if the natriuretic factor containing atrial extracts from prepubertal (AEP) and adult (AEA) rats also differ in their ability to reduce hypernatremia in prepubertal rats. A decrease of pNa was observed 10 min after the administration of AEA (delta = -5.43 mmol/l). AEP failed to show this effect (delta = +0.92 mmol/l). No significant effect of AEA on pNa was observed in adult rats with moderate hypernatremia (delta = -1.88 mmol/l). Natriuretic and diuretic effects of AEP were also significantly lower than those of AEA if they were tested in prepubertal recipients, whereas no difference in activities of AEP and AEA was found in adult recipients. Possible mechanisms of the hypernatremia suppressing activity of AEA, causes of the differences in activities between AEA and AEP, and consequences of the low AEP activity for prepubertal rats are discussed.