Evaluation of glucose tolerance and insulin secretion in cystic fibrosis patients.

UNLABELLED: Blood glucose profile and insulin levels during the oral glucose tolerance test were retrospectively analyzed in 52 cystic fibrosis (CF) patients aged 10-33 years (mean 18 years). Thirty-seven subjects (71.1%) had normal glucose tolerance; 6 patients (11.5%) had impaired glucose tolerance and 9 patients (17.3%), with fasting blood glucose levels below 7.2 mmol/l were classified as diabetic, according to WHO diagnostic criteria. No significant differences in the total amount of secreted insulin (expressed as area under the curve) were detected in CF patients with or without glucose intolerance, but a significant delay in the insulin peak time appeared to be related to a compromised nutritional status. Our data indicate a significantly increased risk of glucose metabolism impairment related to poor nutritional condition (RR 5.40; 95% CI: 1.5-19.7) and worse clinical status (RR 4.27; 95% CI: 1.05-17.2). In particular, glucose tolerance abnormalities were found in 50% of CF patients with an unsatisfactory nutritional condition versus 15.6% of CF patients with good nutritional status. CONCLUSIONS: Since CF-related diabetes is often underdiagnosed and associated with deterioration in patients' overall clinical status, it is very important to identify subjects at risk of developing diabetes by strict monitoring of glucose metabolism when deterioration in nutritional and clinical conditions is seen which cannot be otherwise explained.

Ethanol alters monoamines in specific mouse brain regions.

Ethanol (3.5 g/kg 60 min post-IP injection) produced the following changes in regional brain monoamine levels and in the respective metabolite/neurotransmitter ratios: for the noradrenergic system, MHPG was decreased in the amygdala and increased in the hypothalamus, while the MHPG/NE ratio was increased in the prefrontal cortex and the hypothalamus. For the dopaminergic system, DA was decreased in the olfactory tubercle, DOPAC was increased in the prefrontal cortex and septum, and DOPAC/DA was increased in the prefrontal cortex, septum, striatum, and hypothalamus. HVA was increased in the prefrontal cortex and septum, while HVA/DA was increased in the same regions plus the olfactory bulb. 3MT was decreased in the olfactory tubercle and striatum. The serotonergic system was not altered. The results demonstrate that ETOH produces selective regional changes in the concentration and utilization of monoamines in mouse brain with a predominant influence on dopaminergic systems and a lesser effect on noradrenergic activity.

Cocaine and regional brain monoamines in mice.

Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice IP. Thirty minutes later, brains were removed and nine regions were isolated: olfactory bulbs (OB), olfactory tubercles (OT), prefrontal cortex (PC), septum (SP), striatum (ST), amygdala (AMY), hypothalamus (HT), hippocampus (HC), and thalamus (TH). Using high-performance liquid chromatography, concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their major metabolites were determined. At 10 mg/kg cocaine, NE levels were increased in the AMY and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), was decreased in the PC, AMY, and HT. DA levels were also increased in the AMY, while its intracellular metabolite, dihydroxyphenylacetic acid (DOPAC), was decreased in the ST and its extracellular metabolite, homovanillic acid (HVA), was decreased in the PC. 3-Methoxytyramine (3-MT) levels were not altered in any tissue. 5-HT levels were increased in the AMY, HT, and TH, while its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was decreased in the OB and ST. MHPG/NE ratios were decreased in the PC, AMY, and HT as were those for HVA/DA. DOPAC/DA ratios were decreased in the ST and AMY and increased in the SP while those for 3-MT/DA were decreased in the TH and increased in the PC. 5-HIAA/5-HT ratios were decreased in the AMY, HC and TH. At 50 mg/kg cocaine, there was an increase in DA in the TH. There was a decrease in DOPAC, HVA, and 3-MT, as well as the DOPAC/DA ratio in the ST. In the OT, there was a decrease in DOPAC, the DOPAC/DA ratio, 3-MT, and the 3-MT/DA ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Restrictive tissue in the area of perimembranous ventricular septal defect. Cross-sectional and Doppler echocardiographic study.

This study using pulsed and continuous wave Doppler echocardiography was designed to achieve a cross-sectional echocardiographic categorization of the fibrous tissues in the environs of perimembranous ventricular septal defects, to determine the mechanism involved in its formation and for qualitative and quantitative evaluation of the anomalies associated with the entity. A total of 67 patients was studied, 23 presented cross-sectional echocardiographic evidence of perimembranous ventricular septal defect in isolation, 12 associated with tissue 'tags' and 32 combined with 'restrictive' tissue in the area of the defect. Four echocardiographic features of the 'restrictive' tissue were observed. In 23 of these 32 patients, it was possible to identify the exact anatomic origin of the 'restrictive' tissue (in seven complete and, in 15, partial involvement of the septal leaflet of the tricuspid valve; in one, prolapse of the aortic valve with a partial involvement of the tricuspid septal leaflet) while in nine the origin remained undetermined. In 20, the 'restrictive' tissue simultaneously protruded into the right atrium and ventricle; only in 12 did it extend exclusively into the right ventricle. Tricuspid insufficiency was detected by pulsed Doppler in 78% of the patients with 'restrictive' tissue and in 23% of the remaining patients. Tricuspid incompetence was severe in only two patients of the first group. Three patients with 'restrictive' tissue (9%) had obstruction to the outlet of the right ventricle and four (13%) patients presented aortic insufficiency. Five patients (16%) with 'restrictive' tissue closing the defect did not present pulsed Doppler evidence of a shunt at the ventricular level.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional brain monoamine levels and utilization in middle-aged rats.

Significant changes in monoamine levels and utilization were noted in certain brain regions of middle-aged Fisher 344 rats when compared with young adult controls. In the prefrontal cortex and septum, 3,4 dihydroxyphenylglycol (MHPG) and the MHPG/norepinephrine (NE) ratio were decreased. The septum also showed increases in dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) but there was a decrease in the DOPAC/DA ratio. The striatum showed an increase in the MPHG/NE ratio and an increase in DOPAC. The hippocampus and thalamus showed an increase in 5-hydroxyindoleacetic acid (5HIAA). This demonstrates that selected neurotransmitter systems in the brain are altered at an early stage of senescence. This could lead to ensuing neurological deficits.

Caffeine and regional brain monoamine utilization in mice.

Caffeine (100 and 200 mg/kg, 30 min., i.p.) selectively altered the regional utilization of monoamines in the brains of mice. This depended upon the specific neurotransmitter and metabolite studied. Caffeine increased serotonin (5HT) utilization a dramatic ten-fold in the OB but decreased 5HT utilization in the HT. No 5HT changes were seen in other brain regions. Caffeine markedly increased norepinephrine (NE) utilization in the olfactory bulbs (OB), olfactory tubercles (OT), prefrontal cortex (PC), amygdala (AMY), hypothalamus (HT) and hippocampus (HC). Caffeine increased dopamine (DA) utilization in the OB, OT, PC, septum (SP), HT and thalamus (TH) but by various metabolic routes. The selective regional alterations in monoamine utilization produced by caffeine may be relevant to caffeine's central stimulatory effects. Limbic structures are predominantly involved. These changes may have important clinical and research implications. For example, the profound effect of caffeine on OB monoamines indicates that it may serve as a meaningful tool in olfactory research, including the bulbectomy model. Caffeine may also be useful in other limbic system behavioral models.

Isolation-induced fighting in mice and regional brain monoamine utilization.

The utilization of norepinephrine, dopamine and serotonin was measured in ten brain regions of isolated fighting mice and resting control animals. Fighting produced a markedly significant change in the utilization of dopamine (P greater than 0.006), but not in norepinephrine or serotonin. However, important trends were identified in the latter systems which warrant further testing. This study highlights the importance of dopaminergic participation in fighting behavior.

Rimcazole (BW 234 U) and regional monoamine concentrations in mouse brain.

Rimcazole (BW 234 U), a novel agent with antipsychotic potential, was administered i.p. (50 mg/kg) to adult male ICR mice 30 minutes before brain removal. Regional HPLC analysis of central monoamine levels showed no change in the DOPAC/DA ratio for any tissue as compared with values obtained from control saline treated animals. However, the MHPG/NE ratio was increased in the septum, striatum, hypothalamus and thalamus and there was a reciprocal decrease in the 5HIAA/5HT ratio in the septum. The data are consistent with a known lack of rimcazole affinity for dopamine receptors and indicate the involvement of alternate neurotransmitter systems in the actions of this drug.