Effect of morphine on the mechanical activity of common bile duct isolated from the guinea pig

The contractile response of isolated guinea pigs common bile ducts (CBD) to transmural electrical stimulation and the effects of morphine and naloxone was studied. Contractile responses increased as a function of stimulus frequency. In the absence of naloxone morphine inhibited the contractile response to electrical stimulation in a dose-dependent manner. Naloxone prevented the inhibitory effect of morphine on the contractile response to electrical stimulation. We conclude that smooth muscle of the CBD in guinea pig is functional and can contribute to biliary motility, and that opiate receptors exist in nerve elements in the CBD.     

Inhibition of gastrointestinal motility by MPTP via adrenergic and dopaminergic mechanisms

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in mice and caused an acute inhibition (of over 60%) of gastrointestinal motility, which was measured by the transit of charcoal. This inhibition was not related to conversion of MPTP to MPP⁺. Administration of the -adrenergic blocker propranolol significantly reduced, but did not completely block, the effect of MPTP. The dopaminergic blocker haloperidol also partly reversed the effects of MPTP. When these blockers were administered together, the action of MPTP was fully blocked. The results indicate that the toxin acted by releasing catecholamines (presumably norepinephrine and dopamine), thereby inhibiting motility.Supported by a grant from the Joint Research Fund of the Hebrew University and Hadassah.     

A direct inhibitory effect of erythromycin on rat urinary bladder smooth muscle

Erythromycin (EM) exerts a dual effect on the contractility of smooth muscle. An excitatory effect mediated via motilin receptors is expressed mainly in the smooth muscle of the stomach and duodenum. The other, a direct inhibitory effect mediated via an unknown mechanism, has been described in guinea-pig and human gallbladder, in the longitudinal smooth muscle of the guinea-pig small intestine and in bronchial smooth muscle. In the present study, the effect of EM on the isolated urinary bladder of the rat was examined using isometric force measurements. The muscarinic agonist carbachol evoked contractions that were reduced by EM in a concentration-dependent manner; at 5 x 10(4) M by 46% [from 1.04+/-0.42 gm. to 0.56+/-0.22 gm., (p <0.001)] and at 10(-3) M by 57% [from 1.04+/-0.42 gm. to 0.45+/-0.20 gm., (p <0.001)]. The inhibitory effect of EM was not altered by the nerve blocker tetrodotoxin. Electric field stimulation of 0.5 Hz, 1 Hz, and 2 Hz contracted the urinary bladder. Erythromycin at 5 x 10(-4) M reduced the contractions evoked at 0.5 Hz by 15% [from 0.60+/-0.22 gm. to 0.51+/-0.20 gm., (p = 0.004)] and at 10(-3) M by 23% [from 0.60+/-0.22 gm. to 0.46+/-0.12 gm., (p <0.001)]. Erythromycin failed to affect the contractions evoked by bradykinin, phenylephrine or substance P. It is concluded that EM has a direct inhibitory effect on the rat urinary bladder smooth muscle.     

Linkage to care following a home-based HIV counselling and testing intervention in rural South Africa

Introduction

Efforts to increase awareness of HIV status have led to growing interest in community-based models of HIV testing. Maximizing the benefits of such programmes requires timely linkage to care and treatment. Thus, an understanding of linkage and its potential barriers is imperative for scale-up.

Methods

This study was conducted in rural South Africa. HIV-positive clients (n=492) identified through home-based HIV counselling and testing (HBHCT) were followed up to assess linkage to care, defined as obtaining a CD4 count. Among 359 eligible clients, we calculated the proportion that linked to care within three months. For 226 clients with available data, we calculated the median CD4. To determine factors associated with the rate of linkage, Cox regression was performed on a subsample of 196 clients with additional data on socio-demographic factors and personal characteristics.

Results

We found that 62.1% (95% CI: 55.7 to 68.5%) of clients from the primary sample (n=359) linked to care within three months of HBHCT. Among those who linked, the median CD4 count was 341 cells/mm³ (interquartile range [IQR] 224 to 542 cells/mm³). In the subsample of 196 clients, factors predictive of increased linkage included the following: believing that drugs/supplies were available at the health facility (adjusted hazard ratio [aHR] 1.78; 95% CI: 1.07 to 2.96); experiencing three or more depression symptoms (aHR 2.09; 95% CI: 1.24 to 3.53); being a caregiver for four or more people (aHR 1.93; 95% CI: 1.07 to 3.47); and knowing someone who died of HIV/AIDS (aHR 1.68; 95% CI: 1.13 to 2.49). Factors predictive of decreased linkage included the following: younger age – 15 to 24 years (aHR 0.50; 95% CI: 0.28 to 0.91); living with two or more adults (aHR 0.52; 95% CI: 0.35 to 0.77); not believing or being unsure about the test results (aHR 0.48; 95% CI: 0.30 to 0.77); difficulty finding time to seek health care (aHR 0.40; 95% CI: 0.24 to 0.67); believing that antiretroviral treatment can make you sick (aHR 0.56; 95% CI: 0.35 to 0.89); and drinking alcohol (aHR 0.52; 95% CI: 0.34 to 0.80).

Conclusions

The findings highlight barriers to linkage following an increasingly popular model of HIV testing. Further, they draw attention to ways in which practical interventions and health education strategies could be used to improve linkage to care.     

Innervation of submucosal adipocytes in the human colon

The submucosal plexus regulates various activities of the gastrointestinal mucosa. As the submucosa in the human colon contains adipose tissue we hypothesized that submucosal neurons might also innervate this tissue. We stained submucosal nerves for the enzyme NADPH-diaphorase, which is a marker for nitric oxide synthase-containing nerves. This resulted in the staining of neurons in submucosal ganglia and numerous nerve fibers throughout the submucosa. These fibers were found to be in close contact with adipocytes, and in many cases fine nerve fibers displaying varicosities were found on the surface of these cells. At least some of these fibers originated from submucosal neurons. In addition, cell bodies of submucosal neurons were in close proximity to adipocytes. It is concluded that submucosal nerves innervate adipose tissue in the submucosa, which is a novel role for these nerves, and might have important functional implications.     

O6-methylguanine induces intrachromosomal homologous recombination in human cells

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which alkylatesmany positions in DNA including the O⁶ position of guanine,efficiently induces intrachromosomal homologous recombinationin mouse L-cells. To investigate the role of O⁶-methylguaninein the induction of homologous recombination in human cells,three cell strains containing duplicated copies of the Herpessimplex virus I thymidine kinase (Htk) gene and three cell strainscontaining duplicated copies of the gene coding for hygromycinphosphotransfer-ase (hyg) were treated with MNNG. Neither theHtk genes nor the hyg genes code for a functional enzyme becauseeach contains an insertion mutation at a unique site, i.e. 8-bpXhoI linker insertions in the Htk genes and 10-bp HindIII linkerinsertions in the hyg genes. These cell strains differ in theirlevel of O⁶-alkylguanine-DNA alkyltrans-ferase (AGT), whichspecifically removes the methyl group from the O⁶ position ofguanine. Generation of a functional Htk or hyg gene has beenshown to require intrachromo-somal homologous recombinationbetween the two mutant Htk genes or the two mutant hyg genes.In all six cell strains, MNNG induced a dose-dependent increasein the frequency of homologous recombination. In each set, therewas an inverse correlation between the frequency of MNNG-inducedrecombination and the level of AGT activity. To further studythe role of O⁶-methylguanine in the induction of homologousrecombination, we used O⁶-benzylguanine to inactivate AGT intwo additional human cell strains containing the hyg recombinationsubstrate. After depletion of AGT activity by O⁶-benzylguanine,both cell strains showed a significantly elevated level of MNNG-inducedhomologous recombination. These results indicate that O⁶-methylguanineis the principal lesion responsible for the induction of homologousrecombination in these human cells by this methylating agent.     

Direct inhibitory effect of erythromycin on human alimentary tract smooth muscle

BACKGROUND: Erythromycin was found to stimulate motor activity in the upper gastrointestinal tract. However, in several smooth muscle preparations, it also elicited an inhibitory effect. Our aim was to study the effect of erythromycin in various human alimentary tract smooth muscles. METHODS: Using force measurements, we assessed the effect of erythromycin on electrically and chemically evoked contractions of isolated muscle strips of human gallbladder, small intestine, and colon. RESULTS: The muscarinic receptor agonist carbachol evoked contraction in gallbladder, ileum, and colonic smooth muscle that were reduced by erythromycin at 10(-4) M to 72% +/- 24%, 77% +/- 22%, and 76% +/- 22% of control values, respectively. Erythromycin did not affect contractions evoked by noncholinergic agents. Erythromycin's inhibitory effects were not altered by nerve blockade, indicating a direct muscle effect. Eryrthromycin also reduced contractions evoked by electrical stimulation at frequencies of 5, 10, and 20 Hz in the human gallbladder, ileum, and colon preparations. These contractions were reduced by erythromycin in a reversible and dose-dependent manner. CONCLUSIONS: Erythromycin antagonized direct cholinergic effects on various smooth muscles from the human alimentary tract in a concentration-dependent manner.     

Dye coupling among satellite glial cells in mammalian dorsal root ganglia

Dorsal root ganglia (DRG) are key elements in sensory signaling under physiological and pathological conditions. Little is known about electrical coupling among cells in these ganglia. In this study, we injected the fluorescent dye Lucifer yellow (LY) into single cells to examine dye coupling in DRG. We found no dye coupling between neurons or between neurons and their attendant satellite glial cells (SGCs). In mouse DRG, we observed that in 26.2% of the cases SGCs that surround a given neuron were dye coupled. In only 3.2% of the cases SGCs that make envelopes around different neurons were coupled. The data from mouse ganglia were very similar to those from rat and guinea pig DRG. The results obtained by injection of the tracer biocytin were very similar to those observed with LY. The coupling incidence within the envelopes increased 3.1-fold by high extracellular pH (8.0), but coupling between envelopes was not affected. Acidic pH (6.8) reduced the coupling. High extracellular K+ (9.4 mM) increased the coupling 2.4-fold and 4.7-fold within and between envelopes, respectively. Low extracellular Ca2+ (0.5, 1.0 mM) partly reversed the effect of high K+ on coupling. The results showed that SGCs in mammalian sensory ganglia are connected by gap junctions. This coupling is very sensitive to changes in pH, and can therefore be modulated under various physiological and pathological conditions. The dependence of the coupling on extracellular K+ and Ca2+ suggests that the permeability of gap junctions can be altered by physiological and pharmacological stimuli.