Development of the circadian clockwork in the kidney.

The circadian molecular clock is an internal time-keeping system composed of centrally synchronized tissue-level pacemakers. Here, we explored the ontogeny of the clock machinery in the developing kidney. Pregnant rats were housed at 12-12 h light-dark cycles. Offsprings were killed at 4-h intervals on embryonic day 20 and at postnatal weeks 1, 4, and 12. Canonical clock gene (Clock, Bmal1, Rev-erbα, Cry1, Cry2, Per1, Per2) and kidney-specific clock-controlled gene (αENaC, SGK1, NHE3, AVPR2) expression was profiled by RT-PCR. To investigate the role of nutritional cues, the feeding pattern was modified postpartum. Clock, Rev-erbα, Per2, αENaC, SGK1, NHE3, and AVPR2 showed circadian expression at the end of intrauterine development. By 1 week, all genes oscillated with a distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour withdrawal of mothers induced a 12-hour phase shift of Clock and Bmal1 expression, while disrupting oscillations of the other genes. After weaning, oscillation phases shifted back toward the adult pattern, which was fully expressed at 12 weeks. Thus, functional circadian molecular clockwork evolves in the late fetal and early postnatal kidney. During the nursing period, oscillations are entrained by nutritional cues. The coupling of the circadian expression of tubular regulators of fluid and electrolyte excretion to the feeding-entrained clockwork may be important to maintain homeostasis during this critical period.

Continuous glucose monitoring system (CGMS) in kidney-transplanted children.

NODAT and IGT are well-known complications of immunosuppressive therapy after transplantation being a risk factor for cardiovascular disease affecting patient and graft survival. Therefore, early identification and treatment are of high importance. In this study, we examined the glycemic homeostasis of 20 renal-transplanted children using routine laboratory tests and the continuous glucose monitoring system (CGMS). Six patients (30%) had IGT, and one patient had NODAT (5%). The HOMA index was in an abnormal range in 35% of all patients and was abnormal in 67% of the IGT patients. CGMS analysis showed that IGT patients had higher "lowest glucose" level, and the incidence of hypoglycemic episodes was significantly lower compared with patients with normal OGTT result. In IGT patients, glucose variability tended to be lower. Furthermore, in the whole patient cohort, glucose variability significantly decreased with time after transplantation. Summarizing, these novel data show that "lowest glucose" level and hypoglycemic episodes are significantly influenced and altered in renal-transplanted patients with IGT. Furthermore, there is a decrease in glucose variability with time after transplantation. The mechanism and relevance of these data need further investigations.

Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury.

Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoid-regulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a gender-specific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.

[Phoniatrics in the rehabilitation for head and neck cancer]. / A foniátria feladatai az onkológiai betegek rehabilitálásában.

The aim of treating head and neck cancer is to eliminate the tumor and save functions as much as possible. Despite all efforts the vital (swallowing) and communicative (phonation, articulation) functions can be injured. The treatment of dysphagia is the most important in the rehabilitation, because it can lead to fatal complications: aspiration pneumonia (for example aspiration of saliva), dehydration, malnutrition. According to the localization of the lesion we distinguish oropharyngeal and esophageal dysphagia. The aspiration may be pre-, intra- and post-deglutition. The aspiration without coughing is called silent aspiration which is mainly seen in neurogenic dysphagia, but can also happen in head and neck cancer patients. There are different possibilities to compensate the failing functions in the phoniatric rehabilitation. The swallowing therapy includes causal, compensatory and dietary strategies. In addition to the swallowing therapy the treatment of communicative dysfunctions with articulation exercises will also improve the quality of life of the patients.

Efficacy of conservative voice treatment in male-to-female transsexuals.

A voice assessment was performed before and after conservative voice treatment in 3 male-to-female transsexuals and in 2 nontreated transsexuals serving as control persons. The characteristics studied were voice quality, habitual speaking pitch, vocal pitch range, vocal intensity range, maximum phonation time and 'communicative impairment', a subjective self-estimation by the patient. Based on these parameters the Friedrich dysphonia index (DI) was calculated. The habitual speaking pitch of the 3 transsexuals who had received voice treatment became female, in contrast to that of the nontreated transsexuals, which remained in the so-called 'indifferent pitch range'. The DI of the treated patients was close to the normal value, in contrast to the DI of controls, which continued to be pathological. Even based on this small population, study results reflected the effectiveness of voice therapy in transsexuals.