A method for the simultaneous measurement of volatile sulfur compounds (COS, H2S, CS2, CH3SH, DMS) is established with preconcentration and GC-flame photometric detection (FPD). Prior to preconcentration of ambient air, it was necessary to remove SO2, water vapor and atmospheric oxidant. SO2 and water vapor were removed using a glass fiber filter and a cooled PTFE water trap loop, respectively. In order to remove atmospheric oxidant, the efficiency of an ascorbic acid scrubber was examined. It was found that an ascorbic acid scrubber enabled measurement of volatile sulfur compounds without adsorption and reaction loss. The detection limits for COS, H2S, CS2, CH3SH and DMS were 20, 34, 35, 263 and 44 pg of S, respectively.

OBJECTIVE

Terbutaline, a selective beta2-agonist, is a frequently used tocolytic known to affect maternal metabolism. The purpose of this study was to evaluate the effect of oral terbutaline on maternal glucose metabolism and energy expenditure.

METHODS

Six healthy pregnant women with normal glucose tolerance were evaluated between 30 and 34 weeks' gestation. Oral terbutaline was administered to determine the effects on hepatic glucose production with [6-6(2)H2] glucose tracer, insulin sensitivity (hyperinsulinemic-euglycemic clamp), and energy expenditure (indirect calorimetry). Terbutaline, insulin, and glucagon levels were also obtained. Subjects were randomly assigned to either oral terbutaline 5 mg every 6 hours for 24 hours or no medication. Repeat studies were conducted 1 week apart, each subject serving as her own control.

RESULTS

In the basal state terbutaline was associated with a trend toward increased basal glucose levels (81.6 +/- 6.6 vs 93.7 +/- 12.0 mg/dl, p = 0.06) but no significant increase in hepatic glucose production (3.2 +/- 0.3 vs 3.6 +/- 0.4 mg/kg fat-free mass/min, p = 0.23). However, there was a significant increase in basal insulin concentration (17.6 +/- 9.2 vs 25.6 +/- 10.4 microU/ml, p = 0.02). There was a 28% decrease in insulin sensitivity as measured by the glucose infusion rate during the euglycemic clamp plus residual hepatic glucose turnover (5.78 +/- 1.91 vs 4.16 +/- 1.49 mg/kg fat-free mass/min, p = 0.005). Glucagon concentration was significantly decreased both in the basal state (163 +/- 26 vs 144 +/- 27 pg/ml, p = 0.0007) and during the clamp (144 +/- 27 vs 133 +/- 27 pg/ml, p = 0.003). Basal oxygen consumption increased 9% (270 +/- 49 vs 294 +/- 50 ml oxygen/min, p = 0.007) and caloric expenditure 14% (1.32 +/- 0.23 vs 1.50 +/- 0.31 kcal/min, p = 0.025) or 260 kcal/day with terbutaline.

CONCLUSIONS

Decreased peripheral insulin sensitivity, and to a lesser degree increased endogenous glucose production, may represent the pathophysiology of abnormal glucose tolerance observed in many women treated with oral terbutaline. Common side effects such as tremors and tachycardia experienced by many women on a regimen of terbutaline are consistent with our finding of a significant increase in basal energy expenditure.

Exposure of human platelets to U46619, a thromboxane (Tx) A2 mimetic, desensitizes the TxA2/prostaglandin (PG) H2 receptor and sensitizes adenylylcyclase to stimuli, such as PGI2 or PGD2. This phenomenon may occur in vivo in conditions associated with platelet activation. Tx synthase inhibitors produce a rediversion of arachidonic acid metabolism toward the adenylylcyclase stimulators PGD2 and PGI2. We assessed whether the desensitization of the platelet TxA2 receptor affects the antiplatelet activity of drugs acting on the arachidonic acid metabolic cascade. A Tx synthase inhibitor (OKY046), a PGH2/TxA2 receptor antagonist (BM13.505), their combination, two dual Tx synthase inhibitors/receptor antagonists (picotamide and ridogrel) or the cyclooxygenase inhibitor aspirin were studied. OKY046 alone or combined with BM13.505, picotamide and ridogrel, as well as PGD2, but not BM13.505 or aspirin, caused a stronger inhibition of platelet aggregation with desensitized platelets; this effect was potentiated by the phosphodiesterase inhibitor HL725 and was almost abolished by the adenylylcyclase inhibitor SQ22,536. A larger increase in cAMP synthesis was observed in desensitized as compared with control platelets with a Tx synthase inhibitor or with dual Tx synthase inhibition/receptor antagonism. No differences were observed in the degree of TxA2 suppression. Our observations showed that Tx synthase inhibitors exerted a stronger antiaggregatory effect in TxA2 receptor-desensitized platelets due to a stimulation of adenylylcyclase. This can be of relevance in the treatment of thrombotic disorders in which an in vivo desensitization of platelet TxA2 receptors takes place.

Forty-eight patients with erosive reflux esophagitis were allocated to either sucralfate tablets, 4 g/day, or cimetidine, 1.6 g/day, for 8 weeks in a randomized, prospective, single-blind, cross-over therapeutic trial. Pretreatment lower esophageal sphincter (LES) pressure and serum pepsinogen I (PG-I) levels were investigated as possible predictors of healing with either drug. The trial was completed by 41 patients (21 in the sucralfate group and 20 in the cimetidine group); one patient in each group was removed because of side effects. Symptom improvement occurred to a similar extent in both groups. Endoscopic results after 8 weeks of treatment with sucralfate revealed complete healing of esophageal erosions in 48% (cimetidine, 55%) and improvement in an additional 19% (cimetidine, 20%). Neither of these differences was statistically significant. Some patients refractory to one drug had endoscopic healing of esophagitis when treated with the other drug after crossover. LES pressure did not influence outcome in patients treated with sucralfate, whereas significantly (p = 0.024) more patients refractory to cimetidine had an LES pressure less than 7 mm Hg than did those with a good response to the histamine-2 (H2)-receptor blockade. Patients whose esophagitis healed or improved after sucralfate tended to have lower serum PG-I levels than those with treatment failure (104 +/- 35 ng/mL vs 125 +/- 45 ng/mL), whereas the opposite occurred in patients treated with cimetidine (132 +/- 58 ng/mL in responders vs 78 +/- 27 ng/mL in nonresponders, p = 0.048). The results confirm that sucralfate is a valuable alternative to H2-receptor inhibitors for the treatment of reflux esophagitis. They also provide preliminary evidence that LES pressures and serum PG-I levels may have predictive value of the response to one or the other of these two drugs.

A 6-month-old infant had bullous lesions on his posterior neck, upper trunk, and extremities for two months prior to admission for fever and shock. He had an elevated white blood cell count with left shift and normal platelet count, but abnormal coagulation studies. He was treated with intravenous antibiotics, crystalloids, fresh-frozen plasma, and pressor agents. A histamine H2 receptor antagonist was started for guaiac-positive nasogastric tube drainage. The patient recovered after four days of treatment. A skin biopsy confirmed mastocytosis. A week later the child passed grossly bloody stools with blood clots. No source of gastrointestinal bleeding was identified by extensive work-up. Blood histamine level measured one day before gastrointestinal bleeding was 16,400 pg/ml (normal 263 +/- 202 pg/ml). The bleeding resolved spontaneously. The patient was maintained on cimetidine. Results of a subsequent bone scan were normal. Shock or gastrointestinal bleeding associated with unusual skin lesions should alert the pediatrician to the possibility of mastocytosis.

The present study was designed to determine the role of H2-receptors in the postprandial release of somatostatin-like immunoreactivity (SLI) from the gastric fundus and antrum and from the pancreas. In dogs subjected to laparotomy, the pylorus was bisected and a gastric fistula was created, following which 250 ml 20% liver extract (LE) at pH 7 or 2 were instilled intragastrically. In the fundic vein the incremental SLI rise in response to LE at pH 7 was 2423 plus or minus 540 pg/ml during a control infusion of saline and 4780 plus or minus 863 pg/ml during the infusion of cimetidine (1 mg/kg per h) (P less than 0.05). In the antral vein the incremental SLI in response to LE at pH 7 was 2182 plus or minus 530 pg/ml during the saline control but did not rise significantly during cimetidine infusion. In the pancreatic vein the incremental SLI level after LE at pH 7 was 1953 plus or minus 358 pg/ml in the control experiments and 4430 plus or minus 1024 pg/ml during cimetidine infusion (P less than 0.025). The incremental inferior vena cava SLI level was approximately 925 pg/ml in both groups (not significant). The instillation of LE at pH 2 during the saline control lowered fundic vein SLI by 500 pg/ml; this decline was abolished during cimetidine infusion. In the antral vein the incremental SLI level of 15 750 plus or minus 2514 pg/ml during saline was lowered to only 6728 plus or minus 2257 pg/ml during cimetidine (P less than 0.025). After LE at pH 2 the incremental pancreatic vein SLI level of 5641 plus or minus 1175 pg/ml during the control infusion was also significantly reduced to 2392 plus or minus 559 pg/ml by cimetidine (P less than 0.05). The incremental SLI in the inferior vena cava was reduced from 1270 plus or minus 280 pg/ml during saline to 680 plus or minus 190 pg/ml when cimetidine was infused (P less than 0.05). The present data suggest a histaminergic influence via stimulation of H2-receptors upon the regulation of gastric and pancreatic somatostatin release during the gastric phase of a meal.

Histamine has been proposed to be an excitatory transmitter between the carotid body (CB) chemoreceptor (glomus) cells and petrosal ganglion (PG) neurons. The histamine biosynthetic pathway, its storage and release, as well as the presence of histamine H1, H2 and H3 receptors have been found in the CB. However, there is only indirect evidence showing the presence of histamine in glomus cells, or weather its application produces chemosensory excitation. Thus, we studied the histamine immunocytochemical localization in the cat CB, and the effects of histamine, and H1, H2 and H3 receptor blockers on carotid sinus nerve (CSN) discharge, using CB and PG preparations in vitro. We found histamine immunoreactivity in dense-cored vesicles of glomus cells. Histamine induced dose-dependent increases in CSN discharge in the CB, but not in the PG. The H1-antagonist pyrilamine reduced the CB responses induced by histamine, the H2-antagonists cimetidine and ranitidine had no effect, while the H3-antagonist thioperamide enhanced histamine-induced responses. Present data suggests that histamine plays an excitatory modulatory role in the generation of cat CB chemosensory activity.

Real-time PCR methodology can successfully quantitate microchimeric cell populations at a concentration of 100 microchimeric cells/100,000 host cells; however, it has not been successful in quantitating DNA from trace numbers of microchimeric white blood cells which we reported are present in murine peripheral blood at a concentration as low as 2/100,000 host cells. We report methodology using primers for a portion of the H2-k(b) murine histocompatibility sequence, specific for the C57BL/6J mouse. When these primers were used in the presence of 11,000 microM primer, a 20-fold increase in the median manufacturer's recommended concentration, the assay could be optimized to detect 34 pg of C57BL/6J DNA in a background of 2.5 microg of carrier BALB/cJ DNA (1/100,000). These conditions resulted in a detection limit half as sensitive as that found when no carrier DNA was present.

In order to obtain basic information toward the bioremediation of dioxin-polluted soil, microbial communities in farmland soils polluted with high concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were studied by quinone profiling as well as conventional microbiological methods. The concentration of PCDD/Fs in the polluted soils ranged from 36 to 4,980 pg toxicity equivalent quality (TEQ) g(-1) dry weight of soil. There was an inverse relationship between the levels of PCDD/Fs and microbial biomass as measured by direct cell counting and quinone profiling. The most abundant quinone type detected was either MK-6 or Q-10. In addition, MK-8, MK-8(H2), and MK-9(H8) were detected in significant amounts. Numerical analysis of quinone profiles showed that the heavily polluted soils >> or = 1,430 pg TEQ g(-1)) contained different community structures from lightly polluted soils (< or = 56 pg TEQ g(-1)). Cultivation of the microbial populations in the heavily polluted soils with dibenzofuran or 2-chlorodibenzofuran resulted in enrichment of Q-10-containing bacteria. When the heavily polluted soil was incubated in static bottles with autoclaved compost as an organic nutrient additive, the concentrations of PCDD/Fs in the soil were decreased by 22% after 3 months of incubation. These results indicate that dioxin pollution exerted a significant effect on microbial populations in soil in terms of quantity, quality, and activity. The in situ microbial populations in the dioxin-polluted soil were suggested to have a potential for the transformation of PCDD/Fs and oxidative degradation of the lower chlorinated ones thus produced.

How to in situ detect intracellular telomerase activity with high sensitivity still faces many challenges. This paper constructs a new fluorescence biosensing platform for the sensitive detection of intracellular telomerase activity via the combination of nanoflare and hybridization chain reaction (HCR)-based signal amplification on a single patchy gold/carbon nanosphere (PG/CNS), which has two or more distinct parts and allows hybridized-DNA (HS-DNA/Primer-DNA/Flare-DNA) and H1/H2-DNA (a pair of cross complementary DNA hairpins) to bind onto their surfaces via Au-S bond and electrostatic interaction, respectively. In the presence of telomerase, Primer-DNA (telomerase primer) extends at its 3' end to produce a telomeric repeated sequence, resulting in the release of Flare-DNA followed by the recovery of the fluorescence. Subsequently, the released Flare-DNA further initiates cross hybridization of H1 and H2 DNA from mimic-HCR system to amplify the fluorescence signal. The in vivo confocal microscopy studies demonstrate that resulting sensor can enter into the cancer cells such as A549 cells, and lead to the increase in luminescence, which is stronger than the sensor without the HCR-based signal amplification system. A linear relationship between the fluorescence intensity and the amount of A549 cells is observed, and the limit of detection of the sensor reaches about 280 A549 cells.

Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B2 receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H2, respectively, but not thromboxane A2. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH2 has different functionally active isoforms, including PGD2, PGE2, and PGF2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) and the B2 receptor antagonist HOE-140, but not the B1 receptor antagonist des-Arg(9), [Leu(8)]-BK, completely abolished it. In a functional study, PGD2, PGE2, and PGF2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF2α>> PGE2>> PGD2. The cultured PBAECs produced PGD2, PGE2, and PGF2α spontaneously, and BK significantly enhanced the production of PGF2α, but not that of PGD2 and PGE2. The B2, but not B1, antagonist completely abolished the BK-enhanced production of PGF2α. These results suggest that BK induces production of NO and PGF2α simultaneously from PBAECs via B2 receptor activation.

Magnocellular neurons are innervated by an excitatory histaminergic pathway. They also express neuronal NO synthase, interleukin-1beta (IL-1beta) and cyclo-oxygenase (COX). In normally hydrated rats when NO synthase activity is inhibited with N(G)-nitro-L-arginine methyl ester (L-NAME), administered intracerebroventricularly (i.c.v.), OT concentration in plasma increases. In the present study, the increase in hormone after L-NAME is attenuated by indomethacin, an inhibitor of COX, as well as by antagonists of histamine receptors at H1 (pyrilamine) and H2 (cimetidine) subtypes injected i.c.v. Moreover, enhanced OT secretion induced by centrally administered IL-1beta, but not naloxone (opiate receptor antagonist), is prevented by indomethacin. PGE2 and PGD2 (i.c.v.) stimulate OT release, but only PGD2 affects circulating vasopressin levels. Thus, NO inhibits release of OT stimulated by: (1) a COX-dependent mechanism, i.e. NO->>-(COX->>+PG->>+OT release); (2) histamine, i.e. NO->>-(histamine->>H1 and H2 receptors->>+OT release); and possibly (3) IL-1beta, i.e. NO->>-(IL-1beta->>+COX->>+PG->>+OT release). These interactions of NO, cytokine and histamine may be important for management of stress-induced activation of neuroendocrine systems.

The histamine H2-receptor antagonist cimetidine (25-100 mg/kg) caused a partial inhibition of the pronounced blood pressure fall induced by dextran (Macrodex, 40-100 mg/kg) in the rat. The inhibition by cimetidine could not be distinguished from the inhibition achieved by the serotonin D-receptor antagonist bromolysergic acid diethylamide (BOL, 1-4 mg/kg). Doses of cimetidine and BOL that gave submaximum inhibitory effects separately, showed approximately additive effects when combined. The combined effect of these drugs never exceeded the maximum effects of the drugs separately, whereas injection of tranexamic acid (AMCHA, 100-300 mg/kg) together with cimetidine or BOL, increased the total inhibition. Previous works showed that dextran injected intravenously into rats reduced the level of plasminogen (PG) and plasminogen proactivator (pro-PGA) in plasma (Briseid et al. 1979; Berstad 1980a; Berstad & Briseid 1982). High doses of AMCHA (200 mg/kg) did not inhibit these effects, but significantly increased the lowering caused by dextran of the capacity of high molecular weight kininogen (HMWK) to function as a cofactor in the activation of factor XII. BOL (1-4 mg/kg, Berstad 1981) and cimetidine (50-100 mg/kg) also reduced the cofactor capacity of HMWK in the doses that were required to provide a manifest inhibition of the dextran-induced blood pressure fall. It is suggested that the early phase of the state of shock induced by dextran in the rat can be counteracted at different sites, correlated with histamine and serotonin receptors on the one hand, and with an effect antagonized by AMCHA, on the other. The lowest effective doses of cimetidine and BOL were rather high, suggesting a less specific mechanism for their effects than inhibition at selective receptor sites.

The process of follicle rupture has been described as an inflammatory reaction in which prostaglandins (PGs) and/or histamine may be involved. With an in vitro perfused rabbit ovary preparation, experiments were carried out for determination of whether a relationship exists among PGs, histamine, and ovulation. PGF2 alpha alone was capable of inducing ovulation when added to the perfusion fluid at 1, 10, and 100 ng/ ml. Effectiveness in achieving ovulation varied directly with the dosage; however, the ovulatory efficiency of PGF2 alpha-treated ovaries was lower than that of ovaries exposed to human chorionic gonadotropin (hCG, 100 IU). PGF2 alpha-induced ovulation could not be blocked by the H2 receptor antagonist, cimetidine. The PG synthesis inhibitor, indomethacin, did not prevent histamine-induced ovulation. Ovulation induced by hCG was partially blocked by the administration of indomethacin; however, the concomitant administration of cimetidine was not associated with further reduction in ovulation. In all but one experimental group, the majority of ovulated ova did not progress beyond the intact germinal vesicle stage unless the ovaries had been exposed to hCG. On the basis of these experiments, PGs and histamine do not appear to be interdependent in their effects on the ovulatory process in vitro.

Administration of thromboxane A2/prostaglandin H2 (TxA2/PGH2)-receptor agonist U-46619 (2.86 nmol/kg i.v.) to conscious rats increased mean arterial pressure (MAP) by 17 +/- 2 mmHg (n = 6; P < 0.001) and plasma arginine vasopressin (AVP) by 3.5 +/- 1.1 IU/ml (n = 6; P < 0.001). Ifetroban (TxA2/PGH2 antagonist; intracerebroventricularly) prevented both responses. Intracerebroventricular U-46619 increased MAP in Long-Evans rats (n = 6) more than in AVP-deficient Brattleboro rats. AVP V1-receptor antagonist d(CH2)5Tyr(Me)AVP (3 microg/kg i.v.) blocked 67 +/- 5% and 69 +/- 7% of pressor response to intravenous AVP and intracerebroventricular U-46619, respectively. AVP (10 ng/kg i.v.) increased AVP by 4.7 +/- 0.5 pg/ml, comparable to the increase of 3.5 +/- 1.2 pg/ml with intracerebroventricular U-46619 (2.86 nmol/kg), but the rise in MAP was only one-half as great (+8 +/- 3 mmHg for AVP vs. +17 +/- 2 mmHg for U-46619; P < 0.05). In conclusion, U-46619 raises blood pressure and releases AVP by activating brain receptors. AVP explains approximately one-half of the pressor response.

Intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP), induced hyperthermia in guinea-pigs which was not mediated through prostaglandins (PG) or norepinephrine since a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocking agent, phenoxybenzamine did not antagonize the hyperthermia. In contrast, the hyperthermic response to dibutyryl cyclic AMP was attenuated by central administration of a beta-adrenergic receptor antagonist, sotalol, indicating that cyclic AMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production/conservation. Central administration of dibutyryl cyclic GMP (Db-cGMP) produced hypothermia which was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The antagonism of hypothermia induced by dibutyryl cyclic GMP and acetylcholine + physostigmine, by central administration of a cholinergic muscarinic receptor antagonist, atropine, and not by a cholinergic nicotinic receptor antagonist, d-tubocurarine, suggests that cholinoceptive neurons and endogenous cyclic GMP may regulate heat loss through cholinergic muscarinic receptors. These results support a regulatory role in thermoregulation provided by a balance between opposing actions of cyclic AMP and cyclic GMP in guinea-pigs.

BACKGROUND

Macrophages seem to play an important role in the development of glomerulosclerosis. In both human and experimental animal models of focal glomerulosclerosis (FSGS), infiltration of macrophages in the mesangium has been considered key in the development of FSGS.

METHODS

In the present study, we evaluated the effect of vasoactive agents on the migration of monocytes across a filter in a modified Boyden chamber as well as across a cultured glomerular endothelial cell layer (in vitro model of glomerular mesangium). Both light as well as scanning electron microscopic studies were performed. We evaluated the effect of vasoactive agents including histamine, prostaglandin (PG) E2, angiotensin II, endothelin-1, platelet-activating factor, and interleukin-1 (IL) on the migration of monocytes/macrophages across an endothelial cell layer as well as a gelatin-coated filter. In addition, we evaluated the effect of cyclic adenosine 3',5' cyclic monophosphate (cAMP) and PGE2 on vasoactive-induced migration of monocytes.

RESULTS

Histamine increased (P < 0.003) the migration of monocytes across the filter. This effect of histamine was dose-dependent. Histamine at concentrations of 10(-8) to 10(-5) mol/L induced optimal migration across the filter (control, 16.6 +/- 1.1 vs histamine, 10(-8) mol/L, 40.9 +/- 0.9 monocytes/high power field). Cimetidine, an H2 receptor blocker, attenuated (P < 0.001) the effect of histamine on the migration of monocytes. PGE2 inhibited the migration of monocytes in a dose-dependent manner. Histamine increased (P < 0.001) the passage of monocytes across the glomerular endothelial cell layer (control, 1012 +/- 37 vs 1711 +/- 163 cpm/well). Histamine also increased the migration of murine macrophages across the glomerular endothelial cell layer. PGE2 inhibited the migration of monocytes across the endothelial cell layer under basal as well as histamine-stimulated states. Dibutyryl cyclic (DBc) AMP also attenuated the migration of monocytes under basal as well as histamine-stimulated states. Both PGE2 and DBcAMP also attenuated the IL-1 beta-stimulated migration of monocytes. Angiotensin II, endothelin-1, and platelet-activating factor did not modulate the migration of monocytes.

CONCLUSIONS

Vasoactive agents directly modulate the transmigration of monocytes. The present in vitro study provides a basis for a hypothesis that vasoactive agents may also be modulating the migration of monocytes across the glomerular endothelial cell layer (into the mesangium).

Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials.

To investigate the expression of H2 Relaxin (H2RLX) in chronic heart failure (CHF) patients and determine whether H2RLX level can predict cardiovascular events in CHF patients within 180 days after discharge. One hundred forty-six patients were selected for examination from July 2012 to January 2014. The CHF group included a total of 115 patients, while the control group comprised a total of 31 patients without CHF. In the early morning on the first day after admission, patients' blood samples were obtained for measuring levels of brain natriuretic peptide (BNP), LDL-cholesterol, haemoglobin, fasting blood glucose, thyroid stimulating hormone, and creatinine clearance rate (Ccr). Enzyme-linked immunosorbent assay was performed to analyse the plasma concentration of H2RLX, collagen I, and collagen III. Echocardiography was used to estimate left ventricular ejection fraction. We followed patients for 6 months to record cardiovascular events (asymptomatic, symptomatic, re-hospitalisation for heart failure, and cardiac death). Plasma H2RLX in CHF patients was significantly higher than that in the control group (0.593 [0.542-0.644] vs. 0.390 [0.355-0.425] pg/mL; P < 0.01). With elevated cardiac dysfunction, plasma concentrations of both collagen I and H2RLX increased in all patients. Moreover, there was a significant correlation between H2RLX and collagen I (r = 0.890, P < 0.001). The area under the receiver operating characteristic (ROC) curve for prognosis was 0.816 (P < 0.01), suggesting that plasma H2RLX level predicts severe cardiovascular events (re-hospitalisation and cardiac death) within 180 days after discharge. Elevated H2RLX levels in CHF patients may be associated with disease severity, and H2RLX level may predict cardiovascular events in CHF patients within 180 days after discharge.

A novel halophilic, filamentous actinomycete, designated TRM 4064(T), was isolated from a hypersaline habitat in Sichuan Province, China. Phylogenetic analysis based on an almost-complete 16S rRNA gene sequence of strain TRM 4064(T) showed that it was most closely related to Actinopolyspora mortivallis (99.1 % sequence similarity). The sequence similarities between strain TRM 4064(T) and other Actinopolyspora species with validly-published names were <97.0 %. However, it had relatively low mean values for DNA-DNA relatedness with the A. mortivallis DSM 44261(T) (23.2 %). Optimal growth occurred at 37 °C, pH 7.0 and in the presence of 13 % (w/v) NaCl. The whole-cell sugar pattern consists of xylose, glucose, ribose and arabinose. The predominant menaquinones are MK-10(H4) (38.2 %), MK-9(H4) (25.1 %), MK-9(H2) (28.6 %) and MK-8(H4) (7.3 %). The major fatty acids are anteiso-C17:0 (36.9 %) and iso-C17:0 (19.3 %). The diagnostic phospholipids detected were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylcholine (PC), phosphatidylinositol (PI) and two unknown phospholipids. The G+C content of the genomic DNA of the type strain is 66.3 mol%. Strain TRM 4064(T) therefore represents a novel species of the genus Actinopolyspora, for which the name Actinopolyspora dayingensis sp. nov. is proposed. The type strain is TRM 4064(T) (= KCTC 19979(T) = CCTCC AA 2010010(T)).

A novel Gram-staining positive, catalase-positive, oxidase-negative, aerobic, non-motile coccus, designated strain YIM 13062(T), was isolated from a marine sediment sample collected from the Indian Ocean. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 13062(T) belongs to the genus Kocuria, and is closely related to Kocuria polaris NBRC 103063(T) (97.8 % similarity), Kocuria rosea NBRC 3768(T) (97.6 % similarity) and Kocuria carniphila JCM 14118(T) (97.4 % similarity). The strain grew optimally at 28 °C, pH 8.0 and in the presence of 2-4 % (w/v) NaCl. Cell-wall peptidoglycan type was Lys-Ala3 (type A3α). The major isoprenoid quinones were MK-6(H2) and MK-7(H2). The polar lipids of strain YIM 13062(T) consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), one unidentified phospholipid (PL), one unidentified aminophospholipid (APL), two unidentified aminolipids (AL) and four unidentified lipids (L). Major fatty acids of the novel isolate were anteiso-C15:0, iso-C14:0 and C18:1 2OH. The genomic DNA G+C content of strain YIM 13062(T) was 68.0 mol%. The level of DNA-DNA relatedness between strain YIM 13062(T) and K. polaris NBRC 103063(T), K. rosea NBRC 3768(T), K. carniphila JCM 14118(T) were 53.2, 48.8 and 42.6 %, respectively. On the basis of genotypic and phenotypic data, it is apparent that strain YIM 13062(T) represents a novel species of the genus Kocuria, for which the name Kocuria subflava sp. nov. is proposed. The type strain is YIM 13062(T) (=CGMCC 4.7252(T)=KCTC 39547(T)).

Renin inhibitors are an alternative means of blockade of circulating and tissue-based renin-angiotensin systems (RAS). We studied a new renin inhibitor, Ro 42-5892, by low-dose (0.1 mg/kg) intravenous (i.v.) infusion in 10 min (fast) or 6 h (slow) or placebo in a double-blind cross-over study to assess the relationship between drug concentration and response. Fasting salt-replete normotensive male volunteers (n = 9) aged 18-32 years were studied supine. There were no significant changes in blood pressure (BP) or heart rate (HR) between drug and placebo infusion. Drug concentration peaked (482 +/- 140 ng/ml) at the end of the fast infusion or showed a sustained plateau (25.9 +/- 6.1 ng/ml) with the slow infusion (mean time to peak 121 +/- 99 min). Both fast (135.2 +/- 26 ng/ml/h2) and slow (121.0 +/- 31.1 ng/ml/h2) infusions had similar area under the curve (AUC)0-24-values. Plasma renin activity (PRA) was dramatically reduced by both strategies, but AUC0-10 for PRA was significantly less for slow (1.7 +/- 0.6 ngAI/ml/h2) than fast (4.9 +/- 2.5 ngAI/ml/h2) infusions. Mean peak plasma active renin (AR) concentration was increased by both fast (102.2 +/- 65.9 pg/ml) and slow (195.2 +/- 110.5 pg/ml) infusions as compared with placebo (49.9 +/- 18.6 pg/ml). Similarly, AUC0-10 for AR was greater for slow (990.2 +/- 582.1 pg/ml/h) than fast (512.4 +/- 189.4 pg/ml/h) infusions. Plasma angiotensin-converting enzyme (ACE) activity was unaltered. Our results indicate that protracted low concentrations of Ro 42-5892 may provide more effective and long-lasting inhibition of renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Since prostaglandins (PGs) and histamine (HA) seem to be involved in the activation of the hypothalamic-pituitary-adrenal axis following immunochallenges with lipopolysaccharide (LPS) endotoxin and cytokines, we investigated whether the histaminergic and eicosanoid systems in the male rat brain interact in their regulation of ACTH secretion. The PG synthesis inhibitor indomethacin (10 mg/kg i.p.) attenuated the ACTH response to LPS (10 micrograms/kg i.p.) and HA (30 micrograms i.c.v.). Infusion of PGE1, PGE2 or PGF2 alpha (1 and/or 5 micrograms infused intracerebroventricularly) stimulated ACTH secretion. The ACTH response to PGE1 was inhibited by the HA synthesis inhibitor alpha-fluoromethyl-histidine and the H1 receptor antagonist mepyramine (MEP) but not the H2 receptor antagonist cimetidine (CIM). Neither MEP nor CIM affected the ACTH response to PGE2. MEP and CIM attenuated the ACTH response induced by PGF2 alpha. The findings indicate that HA and some PGs in the brain interact in their stimulatory regulation of ACTH secretion. Such an interaction may also be involved in their mediation of the ACTH response to immunochallenges.

Oxytocin appears to play an important role in regulating uterine secretion of prostaglandin F2 alpha (PGF2 alpha) in sheep. Changes in uterine secretion of PGF2 alpha throughout the oestrous cycle and early pregnancy may be due to changes in the intracellular regulatory pathways that control synthesis of PGF2 alpha in response to oxytocin. In this experiment, caruncular endometrial tissue was collected from ewes throughout the oestrous cycle and early pregnancy. Endometrial tissue was incubated in vitro to assess release of PGF2 alpha and activity of phospholipase C (PLC) in response to oxytocin. Release of PGF2 alpha in the presence of arachidonic acid was used to assess the activity of prostaglandin H2 endoperoxide synthase (PGS). In non-pregnant ewes, oxytocin stimulated release of PGF2 alpha from endometrial tissue collected on days 14 and 16, but not on days 4-7, 10 or 12 after oestrus. This coincided with times when oxytocin stimulated the activity of PLC. Release of PGF2 alpha was enhanced by the addition of arachidonic acid to tissues collected on days 12, 14 and 16 after oestrus. As with tissue from nonpregnant ewes, oxytocin could stimulate release of PGF2 alpha on days 14 and 16 of early pregnancy. Yet, oxytocin had no effect on activity of PLC in tissue from pregnant ewes. Release of PGF2 alpha in the presence of arachidonic acid by tissue from pregnant ewes was similar to that in nonpregnant ewes at comparable times after oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)