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This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23 HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47.8% vs. 15.8%). The longer time on HD, hypercalcemia, hyperphosphatemia and elevated parathyroid hormone level were observed in the HD patients with cinacalcet. Besides, GI adverse events of cinacalcet were observed more frequently in the HD patients with gallstones compared with those without gallstones (odds ratio 13.5, 95% CI: 1.80–101). Therefore, screening for gallstones before dosing cinacalcet may reduce the risk of GI adverse events in SHPT patients.

The number of small boilers using city natural gas, heavy oil (HO), and waste oils has been increasing annually in Japan, and more stringent regulations for nitrogen oxides (NOx) emission are being anticipated to reduce environmental NOx concentration. Taking this into consideration, it is envisioned that a suitable flue gas treatment system for small boilers will be required. The author proposed a plasma–chemical hybrid clean technology, consisting of an indirect nonthermal plasma process and a wet-chemical treatment. The tested flue tube boiler has an original rotary burner for gas and/or oil and is operated using city natural gas, biomass oil, or HO. The boiler has a steam generation rate of 2.5 ton/h, and for the clean technology, two sets of silent discharge-type plasma ozonizers are employed to generate ozone. Using the combination of ozone injection and chemical scrubber for flue gas, NOx can be effectively decomposed to nitrogen and oxygen, thus purifying the resulting effluent. The amount of nitrogen monoxide (NO) removed is almost the same as the amount of the corresponding ozone required to oxidize NO to nitrogen dioxide (NO2) (1:1 stoichiometric ratio). Previously reported experimental data are also discussed in the paper. A NOx removal efficiency of more than 85% was achieved over an operating time of 23 h using city natural gas as fuel. Based on the concept of carbon neutrality, ~80% carbon dioxide (CO2) reduction or fuel saving is also possible using waste vegetable oil (WVO)/HO mixed fuels. This low-emission boiler system can be used in industry.

A super-clean boiler system comprising a multi-fuel boiler and a reactor for plasma-chemical hybrid NOx aftertreatment is developed, and its industrial applications are examined. The purpose of this research is to optimally reduce NOx emission and utilize waste bio-oil as a renewable energy source. First, NO oxidation using indirect plasma at elevated flue gas temperatures is investigated. It is clarified that more than 98% of NO is oxidized when the temperature of the flue gas is less than 130 °C. Three types of waste bio-oils (waste vegetable oil, rice bran oil, and fish oil) are burned in the boiler as fuels with a rotary-type burner for CO2 reduction considering carbon neutrality. NOx in the flue gases of these bio-oils is effectively reduced by the indirect plasma-chemical hybrid treatment. Ultralow NOx emission less than 2 ppm is achieved for 450 min in the firing of city natural gas fuel. The boiler system can be successfully operated automatically according to unsteady steam demand and using an empirical equation for Na2SO3 supply rate, and can be used in industries as an ideal NOx control technology.

Objectives To summarize the basis for and progress with the development of in-vitro–in-silico–in-vivo (IV-IS-IV) relationships for oral dosage forms using physiologically based pharmacokinetic (PBPK) modelling, with the focus on predicting the performance of solid oral dosage forms in humans. Key findings Various approaches to forecasting oral absorption have been reported to date. These range from simple dissolution tests, through biorelevant dissolution testing and laboratory simulations of the gastrointestinal (GI) tract, to the use of PBPK modelling to predict oral drug absorption based on the physicochemical parameters of the drug substance. Although each of these approaches can be useful for qualitative predictions, forecasting oral absorption on a quantitative basis with an individual approach is only possible for selected drug/dosage form combinations. By integrating biorelevant dissolution test results with the PBPK models, it has become possible to achieve quantitatively accurate as well as qualitative predictions of plasma profiles after oral dosing for both immediate and modified release formulations. Summary With further refinement of both the biorelevant dissolution testing methods and the PBPK models, it should be possible to expedite the development and regulatory approval of optimized dosage forms and dosing conditions.

Proton pump inhibitors (PPIs) are widely prescribed as first-line therapy for the treatment of acid-related diseases, such as peptic ulcers and gastro-esophageal reflux disease, and for the eradication of Helicobacter pylori. However, the therapeutic efficacy of conventional PPIs is considered limited because: (1) they are unstable under acidic conditions and require an enteric-coated formulation in clinical use; (2) they show high interindividual variability in pharmacokinetics due to genetic polymorphisms of cytochrome P450 (CYP) 2C19 metabolism; (3) they have a relatively slow onset of pharmacological action and may require several doses to achieve optimal acid suppression and symptom relief; and (4) they often do not provide stable suppression of gastric acid secretion over 24 h. Vonoprazan fumarate (TAK-438, hereinafter referred to as “vonoprazan”) is a new potassium-competitive acid blocker (P-CAB) developed to resolve the above limitations of conventional PPIs. Various physicochemical data have shown that vonoprazan has a high solubility and stability over a broad pH range in aqueous conditions. In addition, vonoprazan has a more potent and longer-lasting acid suppression effect than the conventional PPI, lansoprazole. Preclinical pharmacokinetic studies have shown that vonoprazan is accumulated and retained in the stomach for more than 24 h, even after it is eliminated from the plasma. From these findings, we propose that vonoprazan, which possesses a novel mode of action, can improve on the outcomes seen with conventional PPI-based treatments for acid-related diseases. This review project, including the publication of this article, was funded by Takeda Pharmaceutical Company Limited.

A pilot-scale low-emission boiler system consisting of a bio-fuel boiler and a plasma-chemical hybrid NOx removal system is investigated. This system can achieve carbon neutrality because the bio-fuel boiler uses waste vegetable oil (WVO) as one of the fuels. The plasma-chemical hybrid NOx removal system has two processes: NO oxidation by ozone produced from plasma ozonizers and NO2 removal using a Na2SO3 chemical scrubber. Test demonstrations of the system were carried out for mixed oils (mixture of heavy oil and WVO). A stable combustion was achieved for the mixed oil (20%-50% WVO). The properties of flue gas-e.g., O2, CO2, and NOx -when firing mixed oils were nearly the same as those when firing heavy oil for an average flue gas flow rate of 1000 Nm3/h. The NOx concentrations at the boiler outlet were 90-95 ppm. Furthermore, during a 300-min continuous operation when firing 20% mixed oil, a NOx removal efficiency of more than 90% was confirmed. This is equivalent to less than 10 ppm at the scrubber outlet when the flue gas flow rate was 870 Nm3/h. In addition, CO2 reduction when heavy oil was replaced with WVO was estimated. The system comparison is described between the plasma-chemical hybrid NOx removal and the conventional NOx removal.

The process of removing NOx from the flue gas emitted from a smoke-tube boiler was investigated using an ozonizer, which is used for carrying out the indirect oxidation of NO, and a Na2SO3 chemical scrubber. The flow rate of the flue gas was in the range of 410 - 1480nN·m3/h, its temperature was in the range of 185°C- 325°C, and the concentration of NOx was approximately 40 ppm during the combustion of city gas. Operational and performance data were obtained from the experiments. The efficiency of the NOx removal process was clearly dependent on the oxidation reduction potential (ORP), and it increased with a decrease in the ORP of the scrubbing solution. To effectively remove the requisite amount of NOx, it is essential to maintain the ORP by controlling the injection rates of the Na2SO3 solution and maintaining an ORP of less than 0 mV and the rate of change in ORP to less than 0 mV/min. More than 4 kg/h of Na2SO3 must be added to the scrubber in order to sustain the aforementioned ORP condition of the scrubbing solution. The amount of NOx emitted from the flue gas was maintained as less than 4 ppm at a flue gas flow rate of 410 N ·m3/ h during a 300-min continuous system operation by maintaining an ORP of -30 mV and a pH of more than 7.8 for the scrubbing solution.

NOx removal from the flue gas of a smoke tube boiler using an ozonizer for NO oxidation and a Na2SO3 aqueous solution scrubber (diameter: 0.6 m; height: 3.7 m) was investigated. In this paper, in order to determine the correlation NOx removal performance, the height of the packing material layer in the scrubber was varied from 2.1 to 0 m. The performance tests were carried out using both a compressed natural gas (CNG) and a heavy oil. The flue gas flow rates were in the range of 455-1440 Nm3/h under CNG firing and 675-1330 Nm3/h under heavy oil firing, and the boiler NOx emission concentrations were approximately 40 and 100 ppm, respectively. A total packing height of 0.75 m resulted in NOx removal efficiencies of 70% and 60% for CNG and heavy oil, respectively. Moreover, the Na2SO3 consumption rate at 0.75 m was 10%-20% less than that at 1.2 m, although the NOx removal efficiency was nearly the same. The correlation between the NOx removal performance and the gas retention time in the scrubber was obtained, providing the design information of the scrubber for industrial applications.

NO x removal from an actual boiler flue gas is investigated using an indirect plasma and chemical hybrid system comprising a commercial ozonizer and an Na 2 SO 3 chemical scrubber. A high NO x removal efficiency in the continuous operation of a commercial-scale apparatus is achieved by controlling pH and oxidation reduction potential (ORP) and injecting additional Na 2 SO 3 and NaOH aqueous solutions into the scrubber sump when required. Ozone injection is demonstrated to be extremely effective for NO oxidation. The relation between the ORP and NO x removal efficiency, which is essential for the optimal operation of this system, is obtained.

Background Increased intracellular calcium ([Ca2+]i) in platelets is also proposed as an intermediate phenotype for hypertension in spontaneously hypertensive rats (SHR). Increased [Ca2+]i in platelets is hypothesized to contribute to atherothrombotic events. Platelet hyperactivity is frequently associated with cardiovascular disease. Methods In a genome scan, we performed the quantitative trait loci (QTL) mapping for [Ca2+]i in back-crossed rats derived from SHR and normotensive Fischer 344 rats, which demonstrated a single major QTL for hypertension on chromosome 1. Thrombin-stimulated [Ca2+]i in Ca2+-free and in Ca2+-containing buffers was measured in platelets using the Fura-2 method. Results Among the parental strains, systolic blood pressure and thrombin-stimulated [Ca2+]i were significantly greater in SHR than in Fischer 344 and F1 rats. The sarco(endo)plasmic reticulum Ca2+-dependent ATPase II gene locus (Serca2) between D12Mgh5 and D12Mgh6 showed the significant linkage for thrombin-stimulated [Ca2+]i in Ca2+-free and Ca2+-containing buffers. The peak logarithm of the odds scores were 3.6 and 3.3, respectively. These QTL explained 19.8% and 17.4% of the total variances, respectively. D3Mit13 and DXMgh1 showed suggestive linkage for thrombin-stimulated [Ca2+]i in Ca2+-free and in Ca2+-containing buffers, respectively. The peak logarithm of the odds scores were 2.6 and 2.1, respectively. Conclusions A significant QTL for [Ca2+]i was mapped near Serca2 on chromosome 12, and suggestive QTL were identified near D3Mit13 and DXMgh1 in a genome scan. Genetic abnormalites in platelet [Ca2+]i may contribute to cardiovascular disease via platetet hyperactivity, independent of blood pressure elevation.

Objectives To develop a physiologically based pharmacokinetic (PBPK) model for furosemide immediate release (IR) tablets and modified release (MR) capsules by coupling biorelevant dissolution testing results with pharmacokinetic (PK) and physiologic parameters, and to investigate the key factors influencing furosemide absorption using simulation approaches and the PBPK model. Methods Using solubility, dissolution kinetics, gastrointestinal (GI) parameters and disposition parameters, a PBPK model for furosemide was developed with STELLA software. Solubility and dissolution profiles for both formulations were evaluated in biorelevant and compendial media. The simulated plasma profiles were compared with in-vivo profiles using point estimates of area under plasma concentration-time curve, maximal concentration after the dose and time to maximal concentration after the dose. Key findings Simulated plasma profiles of both furosemide IR tablets and MR capsules were similar to the observed in-vivo profile in terms of PK parameters. Sensitivity analysis of the IR tablet model indicated that both the gastric emptying and absorption rate have an influence on the plasma profile. For the MR capsules, the sensitivity analysis suggested that the release rate in the small intestine, gastric emptying and the absorption rate all have an influence on the plasma profile. Conclusions A predictive model to describe both IR and MR dosage forms containing furosemide was attained. Because sensitivity analysis of the model is able to identify key factors influencing the plasma profile, this in-vitro–in-silico–in-vivo approach could be a useful tool for facilitating formulation development of drug products.

OBJECTIVE: Increased Na+-H+ exchanger activity (NHE) has been reported as an intermediate phenotype in hypertensive subjects, particularly those with insulin resistance. To investigate whether NHE abnormality plays a role in hypertension, Wistar fatty rat (WFR) with overt obesity, hyperglycemia and marked hyperinsulinemia was examined. METHODS: WFR and Wistar lean rats (WLR) as a control (n = 12, each) were fed either with normal (0.38%) or high sodium (4% NaCl) diet for 12 weeks and then sacrificed to examine platelets NHE activity. RESULTS: Mean arterial pressure (MAP) was higher in WFR than in WLR (113 +/- 4 versus 96 +/- 7 mmHg, P < 0.05) under a normal chow. Vmax values of NHE activity were significantly higher in WFR than in WLR. WFR fed with a high sodium diet showed higher MAP than those with a normal chow (128 +/- 3 versus 113 +/- 4 mmHg, P < 0.05). Though Km values were not different between WFR and WLR under a normal chow, both maximal transport rate (Vmax) and half maximal transport (Km) values were significantly higher in WFR with a high salt diet than those with a control diet. Vmax showed significant correlation with MAP, whereas Km values correlated with immunoreactive insulin (IRI) levels. Significant interaction between dietary sodium intake and the strain differences was observed both on blood pressure and on IRI levels by two-way analysis of variance (ANOVA). CONCLUSION: WFR presented salt-sensitive blood pressure elevation. NHE activity was enhanced in WFR in correlation with the blood pressure. These results suggest that augmented NHE activity contributes to the development of salt-sensitive blood pressure elevation in WFR.

Our purpose was to determine the effect of ovariectomy on intracellular Ca2+ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced intracellular Ca2+ mobilization in fura-2 loaded platelets and platelet aggregation. Ovariectomy enhanced the increase of systolic blood pressure and heart to body weight ratio on an 8% NaCl diet. However, thrombin evoked intracellular Ca2+ was not correlated with systolic blood pressure (r = −0.338, P = .17), and was lowered by sodium loading and ovariectomy (360 ± 23 to 285 ± 9, 296 ± 10 nmol/L, P < .05). Furthermore, the ionomycin induced intracellular calcium fraction in the absence of external Ca2+ that reflected internal Ca2+ discharge capacity was reduced in ovariectomized rats compared with sham operated rats on an 8% NaCl diet (648 ± 15 v 768 ± 35 nmol/L, P < .05). The internal Ca2+ discharge capacity was inversely correlated with systolic blood pressure (r = −0.506, P = .03). In addition to the decreased internal Ca2+ discharge capacity, intracellular Ca2+-independent platelet aggregation by phorbol 12-myristate 13-acetate, a protein kinase C activator, was significantly enhanced in hypertensive rats. We concluded that ovariectomy enhanced sodium induced hypertension associated with the decreased internal Ca2+ discharge capacity and increased platelet aggregation in Dahl-Iwai salt-sensitive rats.

Spontaneously hypertensive rats (SHR) are known to be blood pressure sensitive to dietary calcium. The effects of dietary calcium on platelet aggregation and intracellular Ca2+ mobilization were assessed by turbidimetric methods and fura-2 methods, respectively, in washed platelets of SHR. Ca2+ ATPase activity was examined in aortic membrane fractions. Six weeks of dietary calcium supplementation attenuated the increase of systolic blood pressure (SBP 199 +/- 16 v 170 +/- 9 mm Hg, P < .001) and thrombin-induced platelet aggregation (84.5 +/- 3.7 v 73.7 +/- 7.4%, P < .004) at 9 weeks of age. The ionomycin-induced intracellular calcium ([Ca2+]i) peak in the absence of external Ca2+, which reflects [Ca2+]i storage size, and thrombin-evoked [Ca2+]i release from [Ca2+]i storage were decreased by 2.0% Ca diet (472 +/- 55 v 370 +/- 23 nmol/L, P < .001, 339 +/- 29 v 278 +/- 33 nmol/L, P < .002). In addition, SBP was positively correlated with platelet aggregation (r = 0.703, P = .0088), thrombin-evoked [Ca2+]i (r = 0.739, P = .0044), and ionomycin-induced [Ca2+]i (r = 0.591, P = .0415), respectively. However, there was no significant effect of dietary calcium on Ca2+-ATPase activity in aortic membranes. These results suggest that dietary calcium supplementation had a beneficial effect on platelets of SHR by attenuating [Ca2+]i mobilization from [Ca2+]i storage. The hypotensive effect of dietary calcium might be associated with attenuated [Ca2+]i mobilization in SHR.

OBJECTIVES To determine whether insulin sensitivity is impaired in normotensive offspring of essential hypertensives and to investigate how it relates to disturbed calcium metabolism. DESIGN In 10 young lean, normotensive subjects with family histories of essential hypertension and in 10 age-matched controls we investigated insulin sensitivity by the euglycaemic hyperinsulinaemic clamp technique, and 75-g oral glucose tolerance test (GTT). We simultaneously measured calcium-related factors, including the intracellular calcium concentration in platelets. RESULTS Insulin-induced glucose uptake was significantly impaired in subjects with positive compared with in subjects with negative family history of essential hypertension. Intracellular calcium concentration was significantly higher in subjects with positive than in those with negative family history. Insulin sensitivity was inversely correlated with intracellular calcium concentration (r = -0.56; P < 0.05). Those who showed a higher intracellular calcium concentration had impaired insulin sensitivity. Oral GTT results were normal in both groups. CONCLUSION Impaired insulin sensitivity and disturbed calcium metabolism exist before the onset of hypertension. Insulin sensitivity correlates inversely with intracellular calcium concentration. These findings suggest that the association of the impaired insulin sensitivity and disturbed calcium metabolism may contribute to the development of hypertension.

A pilot-scale low emission boiler plant which consists of a multi-fuel boiler and a plasma-chemical hybrid NOx removal system was investigated. This plant can achieve carbon neutrality because the multi-fuel boiler uses waste vegetable oil as one of fuels. The plasma-chemical hybrid NOx removal system has two processes; one is NO oxidation by ozone produced from plasma ozonizers, and the other is NO2 removal using a Na2SO3 chemical scrubber. The operation tests of the plant were carried out for mixed oils (mixture of heavy oil and waste vegetable oil). Stable combustion was achieved for the mixed oil (20%~50% vegetable oil). The flue gas properties, such as O2, CO2 and NOx in firing mixed oils, were nearly the same as those in firing heavy oil when the flue gas flow rate was 1000 Nm3/h on average. NOx concentrations at boiler outlet were 90~95 ppm. Furthermore, it is confirmed that during a 300 min continuous operation in firing 20% mixed oil NOx removal efficiency was attained more than 90%, equivalent to less than 10 ppm at scrubber outlet when the flue gas flow rate was 870 Nm3/h. In addition, the effect of replacing heavy oil by waste vegetable oil on CO2 reduction was estimated.

NO x removal from a smoke tube boiler flue gas was investigated using a commercial ozonizer for indirect NO oxidation and a Na2SO3 chemical scrubber. The flue gas flow rate was in the range of 410 Nm3/h-1480 Nm3/h, the gas temperature of 185°C–325°C, and NO x concentration of around 40 ppm in city gas firing. Operational and performance data were obtained. The NO x removal efficiency was clearly dependent on the ORP and increased inversely as the oxidation reduction potential (ORP) in the liquid decreased. To keep the specified NO x removal performance, it is essential to maintain the ORP properly by controlling additional Na2SO3 and NaOH solution injection. NO x emission of less than 4 ppm was attained at 410 Nm3/h for a 300 minutes system continuous operation by maintaining ORP of-30 mV and pH of more than 7.8.

NOx removal from a smoke tube boiler flue gas was investigated using a commercial ozonizer for indirect NO oxidation and a Na2SO3 chemical scrubber. The flue gas flow rate was in the range of 410~1,480 Nm3/h, the gas temperature of 185~325degC, and NOx concentration of around 40 ppm in city gas firing. Operational and performance data were obtained. The NOx removal efficiency was clearly dependent on the ORP, and increased inversely as the oxidation reduction potential (ORP) in the liquid decreased. To keep the specified NOx removal performance, it is essential to maintain the ORP properly by controlling additional Na2SO3 and NaOH solution injection, and to keep the ORP of less than 0 mV and the ORP change rate of less than 0 mV/min. At least, more than 4 kg/h of Na2SO3 added to the scrubber should be necessary to sustain the condition. NOx emission of less than 4 ppm was attained at 410 Nm3/h for a 300 minutes system continuous operation by maintaining ORP of -30 mV and pH of more than 7.8.

The regeneration of nicotinamide-adenine dinucleotide (reduced form, NADH) by the reaction of NAD with hydrogen gas was carried out in the presence of the hydrogenase from Alcaligenes eutrophus. And the formations of alcohol, CO2, and 6-phospho-gluconate were observed by a combination of the above system and corresponding dehydrogenases. NADH was regenerated by hydrogen gas with the hydrogenase and recycled in these reactions.

Objective To investigate the effects of oestrogen supplementation after ovariectomy on systolic blood pressure and platelet aggregation on different sodium content diet in the female Dahl salt-sensitive rats. Methods At 12 weeks of age, rats were ovariectomized or sham-operated and were fed either a high NaCI (8%) or low NaCI (0.3%) diet Ovariectomized rats were treated with either 17β-oestradiol or placebo for 8 weeks, whereas sham-operated rats received placebo alone. After 8 weeks, the systolic blood pressure and platelet aggregation were measured and analysed by two-way analysis of variance. Results The systolic blood pressure of ovariectomized rats was significantly higher than that of sham-operated rats, and this increase in systolic blood pressure was suppressed by oestrogen supplementation. Systolic blood pressure was inversely correlated with plasma 17β-oestradiol levels (r = - 0.77, P < 0.01) and with the uterus weight to body weight ratio (r = - 0.47, P < 0.01). Platelet aggregation was significantly enhanced by salt loading. Salt loading and female hormonal manipulation significantly interacted on platelet aggregation. Only in Dahl salt-sensitive rats fed a low sodium diet, ovariectomy increased platelet aggregation, whereas hormone replacement did not improve it. In Dahl salt-sensitive rats fed a high sodium diet, hormone replacement reduced platelet aggregation. Conclusions Oestrogen replacement suppresses the development of hypertension and attenuates platelet aggregatory function in the salt-loaded ovariectomized Dahl salt-sensitive rats. It has a potential to inhibit the atherosclerotic process in postmenopausal hypertension.

Epistasis used to be considered an obstacle in mapping quantitative trait loci (QTL) despite its significance. Numerous epistases have proved to be involved in quantitative genetics. We established a backcross model that demonstrates a major QTL for hypertension (Ht). Seventy-eight backcrossed rats (BC), derived from spontaneously hypertensive rats (SHR) and normotensive Fischer 344 rats, showed bimodal distribution of systolic blood pressure (BP) values and a phenotypic segregation ratio consistent with 1:1. In this backcross analysis, sarco(endo)plasmic reticulum Ca2+-dependent ATPase (Serca) II heterozygotes showed widespread bimodality in frequency distribution of BP values and obviously demonstrated Ht. First, in genome-wide screening, Mapmaker/QTL analysis mapped Ht at a locus between D1Mgh8 and D1Mit4 near Sa in all 78 BC. The peak logarithm of the odds (LOD) score reached 5.3. Second, Serca II heterozygous and homozygous BC were analyzed separately using Mapmaker/QTL. In the 35 Serca II heterozygous BC, the peak LOD score was 3.8 at the same locus whereas it did not reach statistical significance in the 43 Serca II homozygotes. Third, to map Ht efficiently, we selected 18 Serca II heterozygous BC with 9 highest and 9 lowest BP values. In these 18 BC, the peak LOD score reached 8.1. In 17 of the 18, D1Mgh8 genotypes (homo or hetero) qualitatively cosegregated with BP phenotypes (high or low) (P < 0.0001, by chi-square analysis). In conclusion, selective genotyping with epistasis can be utilized for a major QTL mapping near Sa on chromosome 1 in SHR.

Objectives Carboxyl methylation is a reversible posttranslational event which regulates the function of several cellular proteins. Because the human Na + -H + antiporter (NHE-1) possesses a C-terminal consensus sequence for carboxyl methylation, we examined the role of protein carboxyl methylation in the regulation of intracellular pH homeostasis. Design Experiments were conducted using human platelets and N-acetyl-S-trans,trans-farnesyl-L cysteine (AFC), a specific prenylcysteine methyltransferase inhibitor. The effect of AFC on both basal intracellular pH (pH i ) and on the kinetic properties of the Na + -H + antiporter was characterized. Materials and methods pH i was determined in cell suspensions using 2,7-biscarboxyethyl-5(6)-carboxy-fluorescein tetraacetoxymethyl ester, a fluorescent pH indicator. The kinetics properties of the Na + -H + antiporter activity were determined using platelets acidified with nigericin and challenged with varying extracellular concentrations of Na + . Results AFC (20 μmol/l) decreased basal pH i significantly (7.047 ± 0.011 versus 7.133 ± 0.012 for control, P< 0.001). The acidification was dose-dependent and reached steady state 3 min after AFC addition. In the absence of extracellular Na + , the platelets were acidified to the same extent with AFC or with ethanol (control): 6.530 ± 0.031 versus 6.532 ± 0.031 (P = 0.97). However, upon addition of Na + , the platelets treated with AFC showed a significant decrease in the maximal value for initial pH i recovery compared with controls: 0.788 ± 0.041 versus 0.983 ± 0.047 pH/min (P< 0.02). AFC also increased the Hill coefficient (2.89 ± 0.22 versus 2.14 ± 0.16, P

Background Previous studies have shown that farnesol, a 15-carbon nonsterol derivative of mevalonic acid, inhibits vasoconstriction. Because of its lipophilic properties, we hypothesized that farnesol increased membrane dynamics, thus reducing uptake of Ca 2+ and contraction. Objective To characterize the effect of farnesol on cell membrane fluidity. Design The study was conducted using A7r5 cells, a rat aortic vascular smooth muscle cell line. Inhibition of Ca 2+ uptake by farnesol was first established in these cells. Then, the effect of farnesol on membrane dynamics was determined. Finally, to ascertain that activation of Ca 2+ extrusion and reuptake processes by farnesol did not occur, Ca 2+ -ATPase activity was examined. Methods Membrane fluidity in cell homogenates was estimated using two fluorescent dyes (1,6-diphenyl-1,3,5-hexatriene) and (1-[-(trimethylamino)-phenyll-6-phenyl-1,3,5-hexatriene). Ca 2+ uptake was determined by monitoring the changes in cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in fura-2-loaded cells after addition of KCI. Ca 2+ -ATPase activity was measured in 100 000 x g cell fractions. Results Farnesol reduced KCI-induced [Ca 2) ] i transients significantly (P< 0.001), but did not modify membrane dynamic properties [0.214 ± 0.007 versus 0.218 ± 0.007 (n = 10) and 0.142 ± 0.002 versus 0.146 ± 0.003 (n = 5) for 1-[-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene anisotropies, respectively; NS]. Administration of up to 30 μmol/l farnesol did not affect Ca 2+ -ATPase activity. Conclusion Farnesol inhibits KCI-dependent rise of [Ca 2+ ] i in A7r5 cells. This effect of farnesol is not related to a global change in plasma membrane lipid organization or to activation of Ca 2+ pumps. Other mechanisms such as direct inhibition of voltage-dependent Ca 2+ channels could therefore explain the biologic action of farnesol in the vascular tissue.

A pilot-scale low-emission boiler system consisting of a bio-fuel boiler and plasma-chemical hybrid NOx removal system is investigated. This system can achieve carbon neutrality because the bio-fuel boiler uses waste vegetable oil as one of the fuels. The plasma-chemical hybrid NOx removal system has two processes: NO oxidation by ozone produced from plasma ozonizers and NO2 removal using a Na2SO3 chemical scrubber. Test demonstrations of the system are carried out for mixed oils (mixture of A-heavy oil and waste vegetable oil). Stable combustion is achieved for the mixed oil (20 – 50% waste vegetable oil). Properties of flue gas—e.g., O2, CO2 and NOx—when firing mixed oils are nearly the same as those when firing heavy oil for an average flue gas flow rate of 1000 Nm3/h. NOx concentrations at the boiler outlet are 90 – 95 ppm. Furthermore, during a 300-min continuous operation when firing 20% mixed oil, NOx removal efficiency of more than 90% (less than 10 ppm NOx emission) is confirmed. In addition, the CO2 reduction when heavy oil is replaced with waste vegetable oil is estimated. The system comparison is described between the plasma-chemical hybrid NOx removal and the conventional technology.

Abstract Our objective was to determine whether increased salt sensitivity after menopause precedes the development of overt hypertension. We investigated the effect of ovariectomy on pressure natriuresis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats by in vivo perfusion studies. Differences in the neural and hormonal backgrounds of the kidney were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. The pressure-natriuresis relationship was blunted in DS rats compared with DR rats (slope, 0.30 versus 0.63 μmol·min −1 ·g kidney wt −1 ·mm Hg −1 , P −1 ·g kidney wt −1 ·mm Hg −1 , P

The regeneration of nicotinamide-adenine dinucleotide (reduced form, NADH) by the reduction of NAD with hydrogen gas was carried out in the presence of the hydrogenase from Alcaligenes eutrophus, and ketone hydrogenationwas attempted by a combination of the above system and alcohol dehydrogenase. Ketones such as 2-butanone, 2-pentanone, 2-hexanone and cyclohexanone were easily hydrogenated by hydrogen gas. After 65 h, the conversion of 2-butanone was 87% and the turnover number of NAD was 64 for 2-butanone, showing regeneration of NAD by hydrogen gas.

The dehydrogenation of 2, 3-dimethylbutane, 3-methylpentane and methylcyclopentane over Pt-C catalyst was studied at low conversion levels and temperatures ranging from 400 to 480°C, under the hydrogen atmospheric pressure.The dehydrogenated products included all possible alkenes and cycloalkenes possessing the same skeletal structures as raw materials and were approximately in thermodynamic equilibrium at conversions as low as 8%. The compositions of these product mixtures observed at 460°C were: 43% 2, 3-dimethyl-1-butene and 57% 2, 3-dimethyl-2-butene; 9% 3-methyl-1-pentene, 11% 2-ethyl-1-butene, 31% 3-methyl-cis-2-pentene and 49% 3-methyl-trans-2-pentene; 68% 1-methylcyclopentene, 20% 3-methylcyclopentene, 10% 4-methylcyclopentene and 2% methylenecyclopentane in each skeletal hydrocarbons, respectively.At the initial step of the reaction, however, it was shown that 2, 3-dimethyl-1-butene, 3-methyl-1-pentene and 3-methylcyclopentene were formed beyond their thermodynamic equilibrium compositions, respectively.It was found that the rate of the dehydrogenation was influenced by the ratio of hydrogen to hydrocarbon and that in the absence of hydrogen the reaction did not proceed at all. The reaction rate increased with the molar ratios, being constant at the molar ratio of one and above.These results suggested that the hydrogen played an important role on the dehydrogenation mechanism over Pt catalyst used in the present study.

To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium ( P < 0.001), elevated parathyroid hormone levels ( P < 0.001), reduced calcitonin levels ( P < 0.05), unchanged 1,25(OH)2D3levels, and elevated skull ( P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced ( P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals ( P = 0.057). However, mean arterial pressure was elevated ( P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism ( P < 0.001), as well as BP ( P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets ( P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

The regeneration of nicotinamide-adenine dinucleotide (reduced form, NADH) by the reduction of NAD with hydrogen gas was carried out in the presence of the hydrogenase from Alcaligenes eutrophus, and ketone hydrogenation was tried by the combination of the above system and alcohol dehydrogenase (ALDH). The ketones such as 2-butanone, 2-pentanone, and 2-hexanone were easily hydrogenated by hydrogen gas. After 65 h, the turnover number of NAD was 64 for 2-butanone showing a recurrence of NAD by hydrogen gas.