Activation of large-conductance potassium channels in pregnant human myometrium by pinacidil

OBJECTIVE: The aim was to investigate the effects of the potassium-channel opener pinacidil on single uterine potassium channels and the contribution of the latter to pinacidil-induced myometrial relaxation. STUDY DESIGN: Myometrial strips and freshly dispersed uterine myocytes were prepared from the myometrial biopsy samples of women undergoing elective, nonlabor caesarean section at term gestation. RESULTS: In isometric tension experiments pinacidil potently relaxed pregnant nonlabor human myometrial strips, with an agonist concentration yielding the half maximal response of 0.4 +/- 0.1 micromol/L. This effect was antagonized by 500 nmol/L charybdotoxin. Application of 10 micromol/L glibenclamide also inhibited the pinacidil-induced relaxation. Coapplication of charybdotoxin (500 nmol/L) and glibenclamide (10 micromol/L) produced a biphasic curve, which was fitted to a two-site model with values for agonist concentration yielding the half maximal response of 0.6 +/- 0.2 micromol/L and 189.7 +/- 0.8 micromol/L. Large-conductance calcium-dependent potassium channel activity was dramatically increased after application of pinacidil (between 10 and 100 micromol/L) to both inside-out and outside-out patches. The activation required the presence of calcium ions at the intracellular aspect of the membrane. Charybdotoxin but not glibenclamide blocked pinacidil-induced unitary large-conductance calcium-dependent potassium channel activity. CONCLUSION: Pinacidil-mediated relaxation of human pregnant myometrial strips may be partially attributable to the opening of uterine large-conductance calcium-dependent potassium channels in addition to adenosine triphosphate potassium channel activation. Drugs with specific potassium channel-activating properties may have important clinical application as novel tocolytics in the treatment of preterm labor.     

Increased incidence of spina bifida occulta in fluorosis prone areas

Spina bifida, a congenital deformity of the posterior wall of vertebrae of the spine, is a midline defect of skin, vertebral arches and neural tube, usually in the lumbosacral region. Its incidence is reported to be 0.2 to 0.4 per 1000 live births. Various hypotheses have been put forward as etiological factors for spina bifida including consumption of potato affected by blight and hardness of drinking water but these have not been proven. Two groups of 50 randomly chosen children were established. The study group consisted of children aged 5 to 12 years, weighing 15 to 30 kg, consuming fluoride rich drinking water (4.5 and 8.5 ppm fluoride; WHO permissible limit is 1.5 ppm fluoride), and manifesting either clinical, dental and/or skeletal fluorosis. The control group consisted of age and weight-matched children, consuming less than or equal to 1.5 ppm fluoride in drinking water and not showing any evidence of fluoride toxicity. These children were evaluated for antenatal history, general clinical examination (especially for dimples, tufts of hair, haemangioma on skin throughout the length of spine), other congenital abnormalities, evidence of fluoride toxicity, biochemical estimation for fluoride levels in blood and serum and by skiagrams of the spine to examine for the presence of spina bifida occulta. A total of 22 (44%) of the 50 children in group A, the study group, and 6 (12%) of the 50 children in group B, the control group, revealed spina bifida occulta in the lumbosacral region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of fine needle capillary sampling in superficial and deep-seated lesions. An analysis of 670 cases

The gene rafY from the plasmid pRSD2, which enables Escherichia coli to grow on raffinose, was transferred into expression plasmid pUSL77. The protein was expressed in the porin-deficient Escherichia coli strain KS26 and was isolated and purified to homogeneity. The pure protein was reconstituted into lipid bilayer membranes. It formed an ion-permeable channel with a single-channel conductance of 2.9 nS of the open state in 1 M KCl, which is approximately twice of that of the general diffusion pores OmpF and OmpC of E. coli outer membrane. At lower pH the channel exhibited rapid flickering between three substates of the open channel. The RafY channel appears to be wide and water filled and has a small selectivity for cations over anions. Although RafY is part of an uptake and fermentation system for raffinose it does not contain a binding site for carbohydrates. Our results suggest that RafY is a general diffusion pore with a diameter, larger than that of the general diffusion porins OmpF and OmpC, that allows the diffusion of high-molecular-mass carbohydrates through the outer membrane.     

Synthesis of 6-aziridinylbenzimidazole derivatives and their in vitro antitumor activities

In search for new antitumor agents, twelve 6-aziridinylbenzimidazole derivatives were synthesized and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia P388 and B16, and human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtained by Phillips reaction. These benzimidazoles were then reacted with Fremy's salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and four 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4,7-diones (11a-d). Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 10d and 13e-h were prepared by the sequential reactions of esterification and addition. The synthesized compounds show potent cytotoxicity against all of three cell lines tested. The cytotoxicities of 10a-d or 11a-d against SNU-16 were superior to those of 13e-h, and were equal to or slightly higher than that of mitomycin C. Compounds 11a-d were slightly more cytotoxic than 10a-d in all cell lines tested.     

Attitudes toward production pressure and patient safety: a survey of anesthesia residents

The detection and measurement of somatic cell mutation in vivo is an important subject of research for the assessment of human cancer risk induced by various environmental genotoxic factors. The possible mechanisms which influence the persistence of mutant cells of the hematoimmune system in the peripheral blood are presented. The erythroid system is a system which accumulates mutational lesions and so stably generates red blood cells with various phenotypic changes.     

Histomorphometric, physical, and mechanical effects of spaceflight and insulin-like growth factor-I on rat long bones

Pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide belong to the same neuropeptide family. Both peptides are present in nerve fibers in the gastric wall and are thought to be involved in the regulation of inflammatory processes. Experimental ulcers were induced in the rat gastric mucosa by local application of acetic acid. During the healing process we examined the PACAP and VIP innervation by means of immunohistochemistry and in situ hybridization. The ulcer area was examined from day 1 to day 15 after ulcer induction. There was a marked depletion of PACAP in nerve fibers at the ulcer margin from day 1 and onwards. On day 10 and day 15, PACAP-immunoreactive nerve fibers could again be visualized at the ulcer margin. In contrast, VIP immunoreactive nerve fibers were present at the ulcer margin at all time points studied. From day 10 following ulcer induction PACAP- and VIP- immunoreactive nerve fibers were increased in frequency in the smooth muscle beneath the ulcer. An upregulation of VIP and PACAP mRNA was also demonstrated in the myenteric ganglia adjacent to ulcer. The present results indicate that neuronal PACAP and VIP react differently to the inflammation at the ulcer margin but similarly in the smooth muscle during the ulcer healing.     

Mobilization of lead by calcium versenate and dimercaptosuccinate in the rat

1. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) individually and in permutation-combination in various doses (0.1, 0.2 and 0.4 mmol/kg bodyweight) were investigated for their efficacy to mobilize lead from vital tissues into urine and faeces and to restore the lead-sensitive biochemical parameters in lead pre-exposed rats with a view to develop the most acceptable treatment regimen for lead poisoning with a minimal loss of endogenous essential elements. 2. The combined therapy was more effective than a single chelator treatment. 3. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA caused a lower depletion of zinc, calcium and iron but possessed almost equal capability to that of 0.4 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA to produce urinary as well as faecal excretion of lead, to reduce the tissue burden of lead, including that of the brain, and to reverse lead-induced biochemical alterations. 4. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA has shown a definite improvement over previously reported combinations in terms of removal of lead from tissues, particularly the brain, restoration of urinary delta-aminolevulinic acid levels and a decrease in the loss of body zinc and is, therefore, recommended for the treatment of lead intoxication.