Microcirculatory basis for nonuniform flow delivery with intravenous nitroprusside.

BACKGROUND: The purpose of this study was to determine the effects of systemic infusions of nitroglycerin and sodium nitroprusside on flow distribution and wall shear stress in the microcirculation. METHODS: With university approval, the cremaster muscle of 28 anesthetized (70 mg/kg pentobarbital given intraperitoneally) hamsters (Harlan Sprague Dawley: Syrian; weight, 121+/-11 g [mean +/- SDD) was observed using in vivo fluorescence microscopy. Arteriolar diameter, erythrocyte flux, and velocity were measured for a feed arteriole and its sequential branches. Observations were made during control (mean arterial pressure, 88+/-4 mm Hg) and after 30 min of intravenous delivery of sodium nitroprusside or nitroglycerin, titrated to decrease mean arterial pressure by 20 mm Hg. RESULTS: Sodium nitroprusside significantly dilated select upstream portions of the network (23+/-2.6 to 29+/-2.6 microm); no arterioles were dilated with nitroglycerin. Erythrocyte flux into the feed (i.e., inflow into the arteriolar network) and into the sequential branches (i.e., distribution within the network) were evaluated. With nitroglycerin, inflow decreased significantly from 1,560+/-335 to 855+/-171 cells/s, and flux into the branches decreased evenly. With sodium nitroprusside, inflow increased significantly to 2,600+/-918 cells/s, yet cells were "stolen" from upstream branches (a decrease from 425+/-67 to 309+/-87 cells/s in the first branch). Excess flow passed into a downstream "thorough-fare channel," significantly increasing flux from 347+/-111 to 761+/-246 cells/s. Wall shear stress decreased uniformly with nitroglycerin infusion, with a decrease in the feed from 8.8+/-2.5 to 6+/-1.7 dyn/cm2. With sodium nitroprusside, variable changes occurred that were location specific within the network. For instance, at the inflow point to the network, wall shear stress changed from 8.3+/-2.5 to 4.2+/-3.3 dyn/cm2. CONCLUSIONS: Nitroglycerin infusion promoted homogeneity of flow. Sodium nitroprusside significantly increased the heterogeneity of flow within this arteriolar network; an anatomic location for steal induced by sodium nitroprusside is identified.     

Inhibitory effect of capsaicin on cholinergic transmission in ovine airways: evidence for non-cholinergic contractions

Electrical stimulation of ovine trachealis smooth muscle and bronchial ring segments induced neurogenic and monophasic atropine-sensitive contractions. Pretreatment of the tissues with capsaicin (100 microM) significantly reduced these contractions indicating a possible contribution of a peptidergic neurotransmitter to the contractions. The effect of capsaicin on electrically induced contractions was significantly inhibited by capsazepin indicating an action on vanilloid receptors. In both preparations, electrically induced contractions were not modified by tachykinin NK(1)- and NK(2)-receptor antagonists singly and in combination. It was therefore concluded that a component of the atropine-sensitive electrically induced contractions of ovine airways smooth muscles involved the release of a peptide neurotransmitter which is probably not a tachykinin. However, an action of capsaicin on prejunctional vanilloid receptors located on cholinergic nerves cannot be ruled out.     

Huge colloid cyst of the third ventricle associated with calcification in the cyst wall

Giant or huge colloid cysts of the third ventricle up to of more than 3 cm in diameter are extremely rare. The patient presented with symptoms of increased intracranial pressure, including headache, vomiting, and papilledema. Computerized tomographic (CT) scan revealed a hypodense, huge colloid cyst of the third ventricle associated with calcification in the cyst wall. Both hypodensity and calcification are uncommon roentgenological findings for colloid cysts of the third ventricle. The patient was operated on by the transcortical/transventricular approach and the colloid cyst was completely excised.     

Dietary antioxidants and the biochemical response to oxidant inhalation. II. Influence of dietary selenium on the biochemical effects of ozone exposure in mouse lung

We examined the influence of dietary selenium (Se) on the pulmonary biochemical response to ozone (O3) exposure. For 11 weeks, weanling female strain A/St mice were fed a test diet containing Se either at 0 ppm (-Se) or 1 ppm (+Se). Each diet contained 55 ppm vitamin E (vit E). Mice from each dietary group were exposed to 0.8 +/- 0.05 ppm (1568 +/- 98 micrograms/m3) O3 continuously for 5 days. After O3 exposure, they were killed along with a matched number of unexposed controls, and their lungs were analyzed for various biochemical parameters. The Se contents of lung tissue and whole blood were determined, and the levels were seven- to eightfold higher in +Se mice than in -Se mice, reflecting the Se intake of the animals. In unexposed control mice, Se deficiency caused a decline in glutathione peroxidase (GP) activity relative to +Se group. After O3 exposure, the GP activity in the -Se group was associated with a lack of stimulation of glutathione reductase (GR) activity and the pentose phosphate cycle (PPC) as assessed by measuring glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities. In contrast, the +Se group after O3 exposure exhibited increases in all four enzyme activities. Other parameters, e.g., lung weight, total lung protein, DNA and nonprotein sulfhydryl contents, and O2 consumption, were not affected by dietary Se in the presence or absence of O3 exposure. The data indicate that dietary Se alters the GP activity, which in turn influences the GR and PPC activities in the lung evidently through a reduced demand for NADPH. The level of vit E in the lung was found to be twofold higher in the -Se group than in the +Se group, suggesting a compensatory relationship between Se and vit E in the lung. With O3 exposure, both Se and vit E contents further increased in the lungs of each dietary group. It is plausible that Se and vit E under oxidant stress are "mobilized" to the lung from other body sites.     

Enhancement of imipramine-induced rat brain β-adrenoreceptor desensitization by subacute co-administration of trazodone,zimelidine, quipazine or 5-hydroxytryptophan

The present work was undertaken to characterize the role of serotonin in the regulation of -adrenoceptors utilizing isoprenaline-induced water drinking in the rat. For this purpose, a serotonin precursor, 5-hydroxytryptophan (24.3 mg/kg/day, PO), the serotonin neuronal uptake blockers, trazodone (18.5 mg/kg/day, PO), or zimelidine (14.6 mg/kg/day, PO) or a serotonin agonist, quipazine (12.6 mg/kg/day, PO) were administered either alone or in combination with imipramine for a period of 4 days. While none of these drugs alone showed any significant effect in attenuating the effects of isoprenaline-induced water drinking, their co- administration with imipramine did produce a significant reduction in isoprenaline-induced drinking. Simultaneous injection of the serotonin synthesis inhibitor,p-chlorophenylalanine (200 mg/kg/day, IP), has resulted in blockade of this acceleration of desensitization of -adrenoceptors produced by the subacute co-administration of trazodone or quipazine with imipramine. The selective 5HT₂ receptor antagonist ketanserin (4 mg/kg/day/ IP) significantly inhibited the attenuation of the isoprenaline-induced drinking attained by the co-administration of quipazine with imipramine, while methysergide (2 mg/kg/day, IP) which blocks both 5HT₁ and 5HT₂ receptors failed to produce a significant effect on this response. These results indicate that the inhibition of the synaptosomal uptake of serotonin by quipazine seems to be more pertinent than its serotoninergic agonistic effect in the desensitization of central -adrenoceptors in the rat. Thus, it can be concluded that noradrenaline and serotonin are both required for the process of the desensitization of central -adrenoceptor systems by antidepressants.Part of this paper was presented at the International Symposium of Serotonin from Cell Biology to Pharmacology and Therapeutics, Florence (Italy), March 29–April 1989     

Matching pain coping strategies to the individual: A prospective validation of the Cognitive Coping Strategy Inventory

The validity of the Cognitive Coping Strategy Inventory (CCSI; Butler et al., 1989) was tested in a prospective fashion. Subjects were randomly assigned to one of three conditions. Some were matched to a strategy for which they received a high CCSI score, some were mismatched to a strategy for which they received a low CCSI score, and some were given a choice of strategies. Those subjects using a matched strategy obtained better threshold and tolerance times on the cold pressor than subjects who used a mismatched strategy. Despite clear differences in exposure to the cold pressor these conditions did not differ from each other in self-reported levels of pain. It was concluded that the CCSI appears to be a valid and useful tool for selecting a coping strategy to help particular individuals manage acute pain. Though the CCSI is relatively easy to administer and score, the comparative costs and benefits of using it must be weighed against the somewhat more efficient approach of simply offering the subject a choice of treatments. Subjects given a choice of strategies performed as well as subjects matched to a strategy on the basis of CCSI scores.     

Gamete development inPlasmodium berghei regulated by ionic exchange mechanisms

Ionic regulation in the induction of exflagellation ofPlasmodium berghei was investigated by culturing the parasites in various isotonic media. Of the salts tested, NaHCO₃ exhibited the highest activity in inducing exflagellation, whereas KHCO₃ showed no activity. In the absence of HCO ₃ ^– , media containing monovalent cation (Na⁺, K⁺, Cs⁺, Rd⁺, choline⁺, lysine⁺, arginine⁺) and Cl^– also induced exflagellation, but their activities were lower than that of NaHCO₃. Anions of Br^– or NO ₃ ^– could be substituted with Cl^–, whereas other anions such as I^–, NO ₂ ^– , SO ₄ ^2– , SCN^–, H₂PO ₄ ^– , or HPO ₄ ^2– failed to induce exflagellation, as did tetramethylammonium-Cl, CaCl₂, MgSO₄, MgCl₂ and sucrose as well. These results suggest that the induction of exflagellation requires the presence of Na⁺ and HCO ₃ ^– or monovalent, membrane-permeable cation and Cl^– in the medium. Measurements of the efflux of H[¹⁴C]O ₃ ^– or Cl^– indicated that these anions were released from the cells into the NaCl or the NaHCO₃ medium, respectively, probably by exchange in HCO ₃ ^– /Cl^–. Determination of intracellular ionic concentrations by electron microscopic X-ray microanalysis of cryopreserved specimens revealed that in the NaHCO₃ medium, external Na⁺ (and probably HCO ₃ ^– ) enters the gametocytes by exchange with internal Cl^– (and probably H⁺), whereas in Cl^–-containing media, external unspecified cation and Cl^– influx by exchange, probably with H⁺ and HCO ₃ ^– . It is therefore suggested that two separate ion exchangers, i.e., Na⁺-dependent HCO ₃ ^– (in)/Cl^–(out) and nonspecific monovalent-cation-dependent Cl^–(in)/HCO ₃ ^– (out) exchangers, are involved in the induction of gametogenesis inP. berghei. Furthermore, the presence of both classes of anion in the medium enhanced exflagellation activity and increased Na⁺ uptake more than did the NaCl or NaHCO₃ medium alone. The apparent synergistic enhancement by two contraactive anion exchangers is consistent with a recycling model of pH_i regulation, in which HCO ₃ ^– and Cl^– are exchanged between the cells and the media, resulting in the acceleration of monovalent cation/H⁺ exchange.This work was supported by a Grant-in-Aid (No. 01570212) from the Ministry of Education, Science and Culture, Japan and the Ohyama Health Foundation, Japan (to FK), and in part by the Medical Research Council, United Kingdom (to RES)     

Louse-borne relapsing fever: II. Combined penicillin and tetracycline therapy in 160 Sudanese patients

One hundred and sixty patients with louse-borne relapsing fever were treated with a combination therapy of procaine penicillin and tetracycline. Fortified procaine penicillin B.P. was given as 400,000 units in the first day. This was followed the next day by 2 g tetracycline orally in divided doses for seven days. A mild rise in temperature was observed in 22 (13·7%) patients within four hours of administering penicillin. Rigors and hypotension occurred in one patient. Relapse occurred in two patients, of whom one had concomitant typhoid and one visceral leishmaniasis. The combined therapy has been found to be effective and safe. It lacks the disadvantages of penicillin (relapses) and tetracycline (severe reaction), when each drug is used alone.The use of the arsenicals (Wolffet al., 1946; Garnhamet al., 1947), penicillin (Taft & Pike, 1945; Ingraham & Lepenta, 1946; Harrison & Whittington, 1951; Knaacket al., 1972) and tetracycline (Brycesonet al., 1970; Knaacket al., 1972) in louse-borne relapsing fever has resulted in a dramatic reduction of the mortality rate from more than 40% in untreated cases (Garnhamet al., 1947) to less than 5%. However, each of these drugs suffers from one drawback or another. The arsenicals are toxic (Wolffet al., 1946). Penicillin is slow in clearing the spirochaetaemia, has a higher rate of relapse and does not clear residual infection in the brain (Harrison & Whittington, 1951). Tetracycline almost invariably induces a distressing Jarisch-Herxheimer reaction (Brycesonet al., 1970; Knaacket al., 1972; Perineet al., 1974). The combined use of penicillin (to reduce reaction) and tetracycline (to prevent relapses) can be a safe and effective alternative in the treatment of this disease. This paper describes the treatment of 160 Sudanese patients with louse-borne relapsing fever, using combined penicillin and tetracycline.