Catecholamines and pancreatic hormones during autonomic blockade in exercising man

The importance of autonomic nervous activity for the pancreatic hormonal response to exercise in man was studied. 7 men ran at 58% of V(O2)max (determined without administration of drugs) to exhaustion during alpha-adrenergic blockade with phentolamine (P), during parasympathetic blockade with atropine (A), or without drugs (C). At rest phentolamine increased the plasma concentrations of both insulin and norepinephrine. During exercise norepinephrine concentrations increased and were in P experiments 3 times the concentrations in C experiments. Insulin always declined during exercise but in P experiments never decreased below basal levels. At identical times neither glucagon nor glucose differed significantly in the different expts. Thus during exercise alpha-adrenergic blockade increased insulin concentrations but did not diminish the glucagon response. Nor was this response increased when beta-receptor stimulation in P experiments was intensified by the particularly high catecholamine concentrations. The concentrations of FFA, glycerol and lactate were highest in P experiments and identical in A and C experiments. These findings indicate that during prolonged moderate exercise in man insulin secretion is depressed by stimulation of alpha-adrenergic receptors whereas glucagon secretion is not influenced by adrenergic receptors. Stimulation of beta-adrenergic receptors enhances lipolysis but neither lipolysis nor pancreatic hormonal secretion is influenced by cholinergic activity during exercise.     

Molecular epidemiology of hepatitis B virus infections in Denmark.

BACKGROUND: Denmark has a low incidence of acute hepatitis B (HBV) infections but the impact of an increasing number of immigrants with chronic HBV infection on HBV transmission is unknown. OBJECTIVES: To characterise individuals with chronic and acute HBV infection in a defined region and to examine the importance of different risk groups for the current HBV transmission. METHODS: During 2000-2001 all consecutive HBV infected individuals routinely diagnosed through the regional HBV serology laboratory in the County of Funen were classified according to ethnicity, presumed route of transmission and stage of infection based on clinical data mainly supplied by the requesting physician. HBV DNA was sequenced and subjected to phylogenetic analysis. RESULTS: Of 309 identified cases, 91 (29%) were classified as acute infection. HBV DNA sequencing was possible in 54 (59%) of these cases. Phylogenetic analysis showed that HBV isolated from injecting drug users (IDUs) was identical or closely related. Among acute cases acquired in Denmark 89% (74/83) were seen in IDUs (65) or in individuals presumably exposed to IDUs (nine) and phylogenetic analysis corroborated the assumption of IDU related transmission in every case with available sequence data. Among 83 ethnic Danes who acquired their HBV infection in Denmark, no new cases of transmission from immigrants were detected. CONCLUSION: Injecting drug use was the single most important factor for hepatitis B transmission in Denmark. The current Danish vaccination strategy is unable to protect IDUs from HBV infection and IDUs pose a greater risk of HBV transmission to the general population than immigrants.     

Distribution of neurons of origin of zinc-containing projections in the amygdala of the rat

The present study describes the distribution of neurons of origin of zinc-containing pathways in the amygdaloid complex of the rat, using the selenium method for simultaneous retrograde labeling of all zinc-containing neurons. With this method, vesicular ionic zinc is precipitated intravitally with selenium compounds and transported retrogradely to the parent neurons, where it can be visualized by silver amplification. Neurons labeled retrogradely with silver-amplified precipitate were observed in all amygdaloid nuclei except for the lateral olfactory tract nucleus, the accessory olfactory tract nucleus and the central nucleus. Very few labeled cell bodies were seen in the anterior amygdaloid area and the medial nucleus. The amygdalo-hippocampal area and the amygdalo-piriform transition area both showed a substantial number of labeled somata throughout their rostrocaudal extent. In the anterior cortical nucleus, very few labeled cell bodies were found in the rostral pole, whereas they were abundant in the caudal quarter of the nucleus. In the posterolateral cortical nucleus, the number of labeled cell bodies increased gradually; there were none in the rostral pole, but most of the neurons in the caudal part were labeled. The posteromedial cortical nucleus contained a great number of labeled somata, but with some variation in the rostrocaudal extent of the nucleus. Considerable numbers of labeled neurons were observed throughout the lateral nucleus. In the basolateral nucleus, a small number of labeled cell bodies was present in the rostral half, but a gradual increase was observed in the caudal direction. Finally, in the basomedial nucleus, very few labeled cell bodies were present in the rostral two-thirds, whilst a considerable number was encountered in the caudal one-third. Possible functional implications of neuronal zinc are considered. The distribution of neurons of origin of zinc-containing projections has been compared with previously described intrinsic connections of the rat amygdala, and tracts that may possibly be zinc-containing are outlined and discussed. It is concluded that in all probability a substantial proportion of the intrinsic connectivity of the rat amygdaloid complex is zinc-containing.The authors thank Ms. M. Sørensen, Mrs. A. Lyhr, Mr. A. Meier and Mrs. K. Wiedemann for excellent technical help.     

Effect of subthreshold voltage-dependent conductances on the transfer function of branched excitable cells and the conduction of synaptic potentials

1. Impulse response functions were determined from complex point impedance and transfer functions from cultured NG-108 cells to simulate the propagation of a synaptic potential in response to the release of transmitter. In general, the flow of synaptic current has a much shorter duration than the normal membrane time constant, thereby making the use of impulse response functions useful approximations to synaptic events. 2. The resonance observed during the activation of the potassium conductance was reflected in the impulse response function as a pronounced damped oscillation. A comparison of the impulse response functions calculated from point impedance and transfer functions showed similar results for current injections in the growth cone. 3. In addition to the resonance effects of the voltage-dependent conductances on transfer and impulse response functions due principally to the activation of conductances for outward currents, transfer functions were measured during the activation of a steady-state negative conductance. Under these conditions the phase function approaches 180 degrees, indicating that the voltage response is out of phase with the current. 4. In the steady state, the effect of a negative conductance is to algebraically add to the positive conductances and generally decrease the absolute conductance unless there is a net negative current. The decreased conductance enhances the impulse response and the DC space constant, thus leading to a better propagation of slow potentials. This effect can be seen as a decrease in the electrotonic length, L, with intermediate depolarizations. At large depolarizations the steady-state activation of the K conductance generally dominates and leads to a greatly increased electrotonic length. 5. Both the net conductances and the associated kinetics play a role in shaping the potential changes during a synaptic current. This is especially critical if there is a net negative steady-state conductance. Under these conditions there is a surprising reduction in the impulse response function. 6. Thus, during a subthreshold activation of the voltage-dependent negative conductances, the observable synaptic potentials would be either large potential responses due to an apparent increase in the impedance (algebraic summation of positive and negative conductances with a net positive conductance) or a minimal response because of the phasic cancellation due to a net negative conductance. The latter condition could exist near the synaptic reversal potential due to a large synaptic drive and would appear experimentally as a form of inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)     

Noninvasive,automatic 24-h ambulatory blood pressure monitoring in normotensive subjects

Summary The reliability of noninvasive, automatic blood pressure monitoring is not yet clearly established. A 24-h ambulatory blood pressure profile was obtained in 9 healthy, normotensive subjects with an automatic, noninvasive device. The blood pressure profile showed the typical circadian pattern with lower systolic and diastolic values during sleep, although pulse pressure was fairly constant (about 40 mm Hg). The systolic blood pressure rose steeply in the early morning hours — before waking up. The results were compared with simultaneous hourly readings using the auscultatory method. There were no statistically significant differences between the automatic and auscultatory readings, 13 of the 18 mean values at. different time points being within 2 mm Hg of each other. All the auscultatory means fell within the 95% confidence limits of those measured hourly by the automatic method. Although the automatic method seemed to be reliable compared with the auscultatory method, its sensitivity to motion artifacts is a disadvantage in a truly ambulatory setting.     

Effects of lithium on water intake and renal concentrating ability in rats with vasopressin-deficient diabetes insipidus (Brattleboro strain)

Male and female Long Evan rats and Brattleboro rats with ADH-deficient diabetes insipidus were treated with lithium administered in the diet for 12 weeks. The plasma lithium level was about 1 mmol/l in all groups. Lithium caused polydipsia and polyuria and lowering of renal concentrating ability in normal rats. In rats with ADH deficiency lithium tended to increase water intake, but did not influence spontaneous urine osmolality or maximal urine osmolality during water deprivation. The results indicate that the renal concentrating defect caused by lithium in rats can be explained by ADH-blockade as the only mechanism. However, there is circumstantial evidence that lithium in addition may stimulate thirst mechanisms by an ADH-independent action.     

Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL).

It has previously been reported that the expression of the complement receptors CR1 (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with the expression on normal B cells, while deposition of complement C3 fragments, as a consequence of alternative pathway (AP) activation of complement, is observed on mononuclear cells from patients with B CLL. Following our demonstration that normal B cells are capable of activating the AP of complement in a CR2-dependent fashion, we have chosen to re-examine the complement-activating ability of B CLL cells in relation to their altered phenotype with respect to CR2 and the complement regulatory membrane proteins, CR1, decay accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to measure expression of complement receptors and regulatory proteins on CD5+ B cells from CLL patients, as well as the deposition of C3 fragments occurring both in vivo and after in vitro AP activation. We have confirmed the reduced expression of CR1 and CR2 on CLL cells and have shown that AP activation in the presence of homologous, normal serum was reduced on B CLL cells compared with normal B cells. The degree of AP activation correlated directly with CR2 expression. In addition, we observed that CLL cells bear in vivo-deposited C3d,g, although at a significantly lower level than normal B cells.     

Gluthatione-S-transferase P1 polymorphism I105V in familial and sporadic prostate cancer

Several reports suggest that the glutathione-S-transferase (GST) family of enzymes is involved in a variety of cancers, due to their carcinogen-detoxification properties. A polymorphism in codon 105 of the pi variant (GSTP1 I105V), which affects the enzymatic activity of the enzyme, has been linked to the incidence of cancers from different organs. However, the published data in prostate cancer (PCa) is controversial. Some studies report an association with the GSTP1 I105V polymorphism and sporadic PCa, whereas other studies report no association. Recently, one study showed a positive correlation between the GSTP1 I105V polymorphism and familial PCa in a Japanese population. In the present study, we assessed the correlation of the GSTP1 I105V polymorphism with familial and sporadic PCa in an American population. We analyzed DNA samples from 438 patients with familial PCa, 499 patients with sporadic PCa, and 510 controls. We found no significant association between the GSTP1 I105V polymorphism and familial or sporadic PCa when compared to the control group [odds ratio (OR) =1.0 (0.74-1.37); P=0.58]. Moreover, no association was found after stratification for age of diagnosis, Gleason grade, or lymph node involvement [OR =0.84 (0.65-1.09), P=0.37]. These data indicate that there is no associated risk for sporadic or familial PCa in American families containing the GSTP1 I105V polymorphism.     

Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces.

Slime production is not a generally recognized feature of Staphylococcus epidermidis. In a recent outbreak of S. epidermidis intravascular catheter-associated sepsis, we noted that 63% of clinically implicated strains grew as a slimy film coating the culture tube walls when propagated in tryptic soy broth. Only 37% of randomly collected blood culture contaminants and skin isolates demonstrated a similar phenomenon (p less than 0.05). Transmission electron micrographs of these coating bacteria showed them to be encased in an extracellular matrix that stained with alcian blue. Slime production was most evident in autoclaved media containing Casamino Acids and glucose supplementation (0.25% wt/vol). There were strain and media preparation variability of slime production in the presence of other carbohydrates. Some strains were not able to produce slime under any of the tested conditions. The production or nonproduction of slime did not influence growth rate. When grown in vitro, slime producers accumulated on the surface of intravascular catheters as macrocolonies, whereas non-slime, producers did not. Transmission and scanning electron micrographs showed slime producers to be encased in an adhesive layer on the catheter surface, whereas nonproducers were not encased. These results suggest that slime-mediated adherence may be a critical factor in the pathogenesis of S. epidermidis infections of medical devices.     

COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders

In a community sample of 2,327 Caucasians, we tested the hypotheses that polymorphisms in the COMT and DRD3 genes are associated with personality traits conferring vulnerability to anxiety, depression, or alcohol misuse, or with current symptoms of these; and that the association is stronger in persons who also have been exposed to stressor experiences. To conserve resources and to allow replication, the genetic analysis was undertaken in two stages. For the COMT polymorphism, no statistically significant associations were found in the first sample of 862 persons. The remainder of the sample was therefore not analysed for that gene. For the DRD3 polymorphism, those in the first sample with at least one of the Ser(9) alleles had significantly higher scores in neuroticism (p=0.006) and behavioral inhibition (p=0.003). There was a trend, failing to meet the 1% significance criterion, for those with this genotype also to have higher depression and anxiety. The groups did not differ in alcohol use. In persons with the Ser(9) allele who were also exposed to stressors, there was a higher level of depression at the 5% level; and the depression level was higher in homozygotes. But when the remainder of the sample (1,465) was analysed, none of the associations reached statistical significance. We conclude that neither the COMT nor DRD3 polymorphisms are associated with anxiety, depression, or alcohol abuse. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:102-107, 2000 Copyright 2000 Wiley-Liss, Inc.