Circadian activity associated with spatial learning and memory in aging rhesus monkeys.

In rodents, spatial learning and memory tests require navigation, whereas in nonhuman primates these tests generally do not involve a navigational component, thus assessing nonhomologous neural systems. To allow closer parallels between rodent and primate studies, we developed a navigational spatial learning and memory task for nonhuman primates and assessed the performance of elderly (19-25 years) female rhesus monkeys (Macaca mulatta). The animals were allowed to navigate in a room containing a series of food ports. After they learned to retrieve food from the ports, a single port was repeatedly baited and the animals were tested until they learned the correct location. The location of the baited port was then changed (shift position). We also determined whether test performance was associated with circadian activity measured with accelerometers. Performance measures included trials to criterion, search strategies, and several indices of circadian activity. Animals learned the task as reflected in their search strategies. Correlations were found between the number of initial or shift trials and circadian activity parameters including day activity, dark:light activity ratio, sleep latency, and wake bouts. Thus, disruptions in circadian rhythms in nonhuman primates are associated with poorer performance on this novel test. These data support the usefulness of this spatial navigational test to assess spatial learning and memory in rhesus monkeys and the importance of circadian activity in performance.

Intrarenal resistance index for the assessment of early renal function impairment in patients with liver cirrhosis.

BACKGROUND: Renovascular vasoconstriction in patients with hepatorenal syndrome can be quantified by the renal arterial resistance index (RI). We investigated the value of RI measurement in detection of renal function impairment in patients with different stages of chronic liver disease. METHODS: Subjects were divided into 4 groups containing 21 patients with liver cirrhosis and ascites, 25 patients with liver cirrhosis without ascites, 35 patients with fatty liver disease and 78 control subjects. All patients underwent abdominal ultrasound examination with renal RI measurement and correlation with laboratory results for renal function. RESULTS: RI was significantly higher in ascitic patients compared to non-ascitic patients (0.74 vs. 0.67, p<0.01) and in non-ascitic patients with liver cirrhosis than in control subjects (0.67 vs. 0.62, p<0.01). 48% (19/40) of patients with liver cirrhosis and normal serum creatinine concentration showed elevated RI levels. There were no significant differences in RI levels between patients with fatty liver disease and controls (0.63 vs. 0.62). CONCLUSIONS: Intrarenal RI measurement is a predictor of renal vasoconstriction and serves to detect early renal function impairment in cirrhotic patients. The diagnosis of elevated RI may be taken into account in the clinical management of these patients.

Age dependency of intrarenal resistance index (RI) in healthy adults and patients with fatty liver disease.

BACKGROUND: Our aim was to investigate the influence of age and gender on intrarenal resistance index (RI) measurements in 78 healthy subjects (46 males, 32 females; group 1) and 35 subjects (group 2) with fatty liver disease (28 males and 7 females). SUBJECTS AND METHODS: First, each subject underwent a conventional abdominal ultrasound examination. Then, intrarenal RI values were determined from three distinct interlobar and cortical arteries respectively on both kidneys. The correlation of intrarenal RI with age and gender as a variable was statistically evaluated by linear regression. RESULTS: In group 1, the variables gender, kidney region and comparison of right versus left kidney had no significant effect on intrarenal RI (p>0.05). The variable age, on the other hand, showed a significant positive correlation on all four defined measuring points (p<0.01) with linear correlation coefficients of r = 0.26 (left kidney, central) to r = 0.37 (right kidney, cortical). Therefore normal RI values at ages 25, 45, 65 years could be defined as 0.59, 0.61 and 0.63, respectively. Age dependency can thus be expressed as a function with the formula y = 0.565 + 0.001.x. Patients with fatty liver disease showed age dependency on renal RI (p<0.01) as well. CONCLUSION: In accordance with other studies, the influence of age on intrarenal RI measurement is significant in healthy subjects. Intrarenal RI values from subjects with a fatty liver disease showed age dependency as well. Therefore it is necessary to consider the age of the examined person to interpret RI values correctly.

Heat-shock protein HSP70-2 genotypes in patients with Crohn's disease: a more severe clinical course with intestinal complications in presence of the PstI-polymorphism.

BACKGROUND: 70 kDa Heat shock proteins are involved in mucosal protecting reactions in the gut of patients with inflammatory bowel disease. Recently, a single nucleotide polymorphism (PstI, nucleotide 1267) was associated with intestinal perforations and formation of abscesses and fistulas in Japanese patients with Crohn's disease. Our purpose was to evaluate this phenomenon in Caucasian patients with Crohn's disease and to verify the clinical importance of this polymorphism. PATIENTS AND METHODS: 61 consecutive patients with Crohn's disease and 61 healthy control persons were examined. After DNA extraction and PCR amplification spanning the PstI-site, restriction fragment length polymorphism analyses (RFLP) were performed. Homozygous and heterozygous genotypes (AA, AB, BB) were then correlated with the clinical characteristics of the patients, especially with their intestinal complications. RESULTS: Intestinal perforations and formation of fistulas, abscesses and conglomerate tumors were significantly associated with allele B (p = 0.04). Patients with genotype BB showed the highest prevalence for surgical interventions (82%), whereas patients with genotype AA had the lowest prevalence (56%). Onset of disease, the need for immunosuppressive therapy and the occurrence of extraintestinal manifestations did not differ between the three genotypes. Allele A was significantly associated with combined involvement of ileum and colon. CONCLUSION: Caucasian patients carrying the HSP70-2 PstI-polymorphism seem to have a more severe form of Crohn's disease (perforations, abscesses, fistulas, conglomerate tumors). Especially, the homozygous genotype (BB) predisposes for a clinical course with high risk of surgical intervention.

[Disorders of lipid and glucose metabolism. Long-term adverse effects of antiretroviral therapy]. / Störungen des Lipid- und Glukosestoffwechsels. Langzeitnebenwirkungen antiretroviraler Therapie.

In addition to readily controllable short-term side effects, highly active antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis remains uncertain although various hypotheses have been advanced. A number of approaches for the treatment of lipodystrophy are available, the effects of which, however, have not been confirmed by study results. Hyperlipoproteinemia probably means an increased cardiovascular risk, but a final pronouncement on this is not yet possible. Fibrates and statins are currently applied for treatment, but interactions with HAART medicaments have to be considered. HAART-induced diabetes mellitus presents clinically as type 2 diabetes, and is treated accordingly.