Association between dexamethasone treatment and alterations in serum concentrations of trace metals.

Previously, a significant elevation in the serum levels of iron (Fe) was observed within a few days after the initiation of cisplatin (CDDP)-based chemotherapy. To clarify the underlying mechanisms, the serum concentration of hepcidin, a negative regulator of Fe release, was determined in the clinical samples obtained from six patients with cancer. The result showed that the serum concentration of hepcidin in patients receiving CDDP-based chemotherapy was significantly increased after 4-6 days of treatment, in comparison to the baseline level, suggesting that aforementioned excessive systemic Fe was not explained by the change of serum hepcidin level. All these patients received antiemetic premedication. We next evaluated of the effects of Pt-containing drugs and prophylactic antiemetic dexamethasone medication on the serum concentration of trace metals in mice, and on the hepatic and renal concentration of trace metals. The serum concentrations of Fe, Cu, and Zn in the CDDP-treated and oxaliplatin-treated mice were not significantly altered in comparison to those of the vehicle-treated control group. The serum concentrations of Fe, Cu, and Zn were increased after 24 h of dexamethasone treatment, compared to those of the control group (P < 0.05). The hepatic concentration of Mn was significantly reduced, whereas those of Fe and Cu inclined to diminish. The present findings suggest that dexamethasone can partly contribute to the changes in the serum concentrations of trace metals during anticancer chemotherapy.

Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists' assessment and intervention based on Screening Tool of Older Persons' Potentially Inappropriate Prescriptions criteria ver.2.

WHAT IS KNOWN AND OBJECTIVES: The Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (stopp) criteria were updated in 2014 (stopp criteria ver.2), but few studies have evaluated the usefulness of stopp criteria in elderly patients. This prospective observational study evaluated the prevalence of potentially inappropriate medications (PIMs), and the efficacy of hospital pharmacists' assessment and intervention based on stopp criteria ver.2. METHODS: The study was conducted at three medical units of Kobe University Hospital between April 2015 and March 2016. Pharmacists assessed and detected PIMs based on stopp criteria ver.2 and considered the patient's intention to change the prescription at the time of admission of each patient. If the pharmacists judged that benefits outweighed risks of prescription change and the patients consented to change the medications, they recommended the doctor to change the prescription. If there was a risk of exacerbation of disease by the change of medications and the pharmacists judged it to be difficult to adjust medications during hospitalization or the patients did not consent to change the medications, they did not recommend to change it. The pharmacists and the doctors discussed and finally decided whether to change the PIMs or not. The number of patients prescribed PIMs, the number and contents of PIMs, and the number of medications changed after pharmacists' intervention were calculated. RESULTS: Totally, 822 new inpatients aged ≥65 years prescribed ≥1 daily medicine were included. Their median (interquartile range) age was 75·0 (71·0-80·0) years, and 54·9% were male. According to the criteria, 346 patients (42·1%) were prescribed ≥1 PIMs. Patients prescribed PIMs took significantly more medications than others: 10·0 (7·0-13·0) vs. 6·0 (4·0-9·0), P < 0·001. The total number of PIMs was 651%, 47·6% of which (n = 310) were recommended the doctors to change, and 292 of 651 PIMs (44·9%) were finally discontinued/changed after pharmacists' assessment and intervention. PIMs related to benzodiazepines, including Z-drugs, were most frequent, with a detailed classifications as follows (changed/total): (i) benzodiazepines for 4 or more weeks (75/205), (ii) drugs that predictably increase the risk of falls in older people (benzodiazepines) (30/67) and (iii) drugs that predictably increase the risk of falls in older people (hypnotic Z-drugs) (15/31). CONCLUSION: Over 40% elderly patients were prescribed PIMs, and pharmacists' assessments and interventions based on stopp criteria ver.2 were useful in detecting and correcting prescription of PIMs.

Speciation in ninespine stickleback: reproductive isolation and phenotypic divergence among cryptic species of Japanese ninespine stickleback.

Although similar patterns of phenotypic diversification are often observed in phylogenetically independent lineages, differences in the magnitude and direction of phenotypic divergence have been also observed among independent lineages, even when exposed to the same ecological gradients. The stickleback family is a good model with which to explore the ecological and genetic basis of parallel and nonparallel patterns of phenotypic evolution, because there are a variety of populations and species that are locally adapted to divergent environments. Although the patterns of phenotypic divergence as well as the genetic and ecological mechanisms have been well characterized in threespine sticklebacks, Gasterosteus aculeatus, we know little about the patterns of phenotypic diversification in other stickleback lineages. In eastern Hokkaido, Japan, there are three species of ninespine sticklebacks, Pungitius tymensis and the freshwater type and the brackish-water type of the P. pungitius-P. sinensis species complex. They utilize divergent habitats along coast-stream gradients of rivers. Here, we investigated genetic, ecological and phenotypic divergence among three species of Japanese ninespine sticklebacks. Divergence in trophic morphology and salinity tolerance occurred in the direction predicted by the patterns observed in threespine sticklebacks. However, the patterns of divergence in armour plate were different from those previously found in threespine sticklebacks. Furthermore, the genetic basis of plate variation may differ from that in threespine sticklebacks. Because threespine sticklebacks are well-established model for evolutionary research, the sympatric trio of ninespine sticklebacks will be an invaluable resource for ecological and genetic studies on both common and lineage-specific patterns of phenotypic diversification.

Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer.

BACKGROUND: We searched for a viral aetiology for non-small cell lung cancer (NSCLC), focusing on Merkel cell polyomavirus (MCPyV). METHODS: We analysed 112 Japanese cases of NSCLC for the presence of the MCPyV genome and the expressions of RNA transcripts and MCPyV-encoded antigen. We also conducted the first analysis of the molecular features of MCPyV in lung cancers. RESULTS: PCR revealed that 9 out of 32 squamous cell carcinomas (SCCs), 9 out of 45 adenocarcinomas (ACs), 1 out of 32 large-cell carcinomas, and 1 out of 3 pleomorphic carcinomas were positive for MCPyV DNA. Some MCPyV DNA-positive cancers expressed large T antigen (LT) RNA transcripts. Immunohistochemistry showed that MCPyV LT antigen was expressed in the tumour cells. The viral integration sites were identified in one SCC and one AC. One had both episomal and integrated/truncated forms. The other carried an integrated MCPyV genome with frameshift mutations in the LT gene. CONCLUSION: We have demonstrated the expression of a viral oncoprotein, the presence of integrated MCPyV, and a truncated LT gene with a preserved retinoblastoma tumour-suppressor protein-binding domain in NSCLCs. Although the viral prevalence was low, the tumour-specific molecular signatures support the possibility that MCPyV is partly associated with the pathogenesis of NSCLC in a subset of patients.

The effect of starting or stopping skin cooling on the thermoregulatory responses during leg exercise in humans.

To assess the effects of starting or stopping leg cooling on the thermoregulatory responses during exercise, 60 min of cycling exercise at 30% of maximal oxygen uptake was performed under 4 conditions using tube trouser perfused with water at 10 °C; no leg cooling (NC), starting of leg cooling after 30 min of exercise (delayed cooling, DC), continuous leg cooling (CC), and stopping of continuous leg cooling after 30 min of exercise (SC) at an environmental temperature of 28.5 °C. During exercise under the DC conditions, an instantaneous increase in the esophageal temperature (Tes), a suppression of the cutaneous vascular conductance at the forearm (%CVC), and a decrease in the mean skin temperature (Tsk) were observed after leg cooling. The total sweat loss (Δm sw,tot) was lower under the DC than the NC condition. In the SC study, however, the Tes remained constant, while the %CVC increased gradually after leg cooling was stopped, and the Δm sw,tot was greater than that under the CC condition. These results suggest that during exercise, rapid skin cooling of the leg may cause an increase in core temperature, while also enhancing thermal stress. However, stopping skin cooling did not significantly affect the core temperature long-term, because the skin blood flow and sweat rate subsequently increased.

The role of microRNA-150 as a tumor suppressor in malignant lymphoma.

MicroRNA (miRNA; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that overexpression of miR-21 and/or miR-155 leads to activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway in malignant lymphomas expressing CD3(-)CD56(+) natural killer (NK) cell antigen. Through expression analysis, we show in this study that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKT(ser473/4) and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 functions as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma.

Ecological divergence and habitat isolation between two migratory forms of Japanese threespine stickleback (Gasterosteus aculeatus).

When two closely related species migrate to divergent spawning sites, divergent use of spawning habitats can directly reduce heterospecific mating. Furthermore, adaptations to divergent spawning habitats can promote speciation as a by-product of ecological divergence. Here, we investigated habitat isolation and ecological divergence between two anadromous forms of threespine stickleback (Gasterosteus aculeatus), the Japan Sea and Pacific Ocean forms. In several coastal regions of eastern Hokkaido, Japan, these forms migrate to the same watershed to spawn. Our field surveys in a single watershed revealed that segregation of distinct spawning sites between the two forms was maintained within the watershed across multiple years. These spawning sites diverged in salinity and predator composition. Morphological and physiological divergence between the forms also occurs in the direction predicted by ecological differences between the spawning sites. Our data indicate that migration into divergent spawning habitats can be an important mechanism contributing to speciation and phenotypic divergence in anadromous fishes.

Clinical evaluation after a notification policy of linezolid use: a case series of 22 patients.

Linezolid exhibits a broad spectrum of activity against Gram-positive cocci, including Methicillin-resistant Staphylococcus aureus (mRSA) and vancomycin-resistant enterococci (VRe). However, recent studies have already reported the emergence of linezolid-resistant mRSA or VRe. the purpose of this study is to evaluate not only the efficacy of linezolid for the treatment of nosocomial mRSA infections but also the effect of a notification policy of linezolid use. the charts of inpatients who had been treated with linezolid were reviewed for clinical outcome. After introduction of the notification policy of linezolid use, the clinical success rate was 73.3%, and the rate of appropriate linezolid use was 80%, whereas the success rate was 14.2% and the appropriate use rate was 14.3% before the policy. in conclusion, appropriate use controlled by a notification policy of antibiotics use is essential for prevention of the emergence and spread of linezolid-resistant bacteria, and for proper demonstration of its antibacterial ability.

Sea-run migratory behaviour in the Japan Sea form of three-spined stickleback Gasterosteus aculeatus in the tidal pool of eastern Hokkaido Island, Japan.

Juveniles in the Japan Sea form of three-spined stickleback Gasterosteus aculeatus collected from a tidal pool in eastern Hokkaido Island, Japan, had a unimodal standard length (L(S)) frequency distribution in each period, ranging from 11.9 to 31.6 mm, and those of sea-run migrating individuals collected from the outlet of this tidal pool ranged from 17.0 to 36.0 mm, suggesting juveniles of this form would migrate towards the sea when they reached >17.0 mm. In general linear models (GLM) for testing the best model, there was a relationship between the number of sea-run migratory individual and precipitation, which suggests that precipitation may trigger migration.

[Consideration of the prognostic factors influencing survival after lung metastasectomy of renal cell carcinoma].

From 1989 to 2002, 9 patients with metastatic renal cell carcinoma to lung underwent lung resections for curative removal of metastatic disease in our department. Disease free interval (DFI), number and size of metastases resected (at first metastasectomy), and number of metastasized regional lymph nodes were studied after resection of pulmonary metastases. DFI were 0 to 60 months with mean value of 23 months. At first operation, single metastases accounted for 4 cases and multiple lesions more than 2 metastases accounted for 5 cases with mean value of 2.1. Maximal diameter of metastases was 10 to 50 mm with mean value of 24 mm. Regional lymph nodes metastases were demonstrated only 1 patient in 2 of No. 12 lymph nodes adjacent to metastases. At subsequent relapse, 1 patient had second-stage metastasectomy, 2 patients went on to a third phase. Four patients were lost, 2 are under treatment for newly relapsed lesions, and 3 are now free of metastases. Analysis was performed by Cox proportional hazards model of survival using these factors. Though lacking the statistical significance, only maximal diameter of metastases was prone to have influencing factor on prognosis. Survival was not related to DFI between 0 to 21 months and more than 21 months and numerous lung metastases between single metastasis and with 2 or more. In general, estimated survival rate of these patients according to Kaplan-Meier was 0% at 67 months. Considering the above results, surgical treatment for patients with metastatic renal cell carcinoma to lung should be planned carefully.

Alternative approach to endoluminal treatment of an anastomotic aneurysm.

Conventional surgical treatment of patients with an anastomotic aneurysm can be a surgical challenge if severe adhesions are present. We report here effective treatment of an anastomotic aneurysm using an endoluminal stent graft. A 71-year-old man had undergone an aorto-bifemoral bypass for Leriche's syndrome in 1989 and partial gastrectomy for cancer in 1996. He was admitted to our department with a pseudoaneurysm of a proximal anastomosis located at the aorta below both renal arteries. Based on his medico-surgical history, we considered that an endovascular stent should be placed. This graft composed of an UBE(UBE-WOVEN GRAFT) graft and self-expandable Z stents were introduced through the right limb of the bifurcated graft previously implanted, then were placed using the delivery system while advancing under fluoroscopic control, using a pusher rod. Endoleakage was not evident and the postoperative course was uneventful. An endovascular graft is one alternative approach for treating patients with an anastomotic aneurysm as it is less invasive. This procedure proved satisfactory for this patient.

Effects of glibenclamide on hydroxyl radical formation in the postischaemic reperfused heart with or without inhalation anaesthetics.

BACKGROUND AND OBJECTIVE: We investigated whether glibenclamide (glyburide) affects myocardial metabolism and hydroxyl radical formation in the rat heart-lung preparation with or without inhalation anaesthetics. METHODS: Thirty-seven male Wistar rats were allocated to four groups: (a) control group (C), received vehicle only; (b) group G, received glibenclamide 10 microM L-1; (c) group I, received glibenclamide 10 microM L-1 and 1.4% isoflurane during perfusion; (d) group S, received glibenclamide 10 microM L-1 and 2.7% sevoflurane during perfusion. Glibenclamide was administered 7 min after the start of perfusion. Ten minutes later, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero, and then the heart was reperfused for 10 min. The formation of hydroxyl radicals in perfusate blood and heart was measured with high performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acids. RESULTS: The recovery time from ischaemia in group G was significantly longer than the other groups. However, there were no differences in myocardial metabolites and dihydroxybenzoic acids concentrations in the perfusate and heart among the four groups. CONCLUSIONS: Glibenclamide prolonged recovery time from ischaemia, but did not affect hydroxyl radical formation in the postischaemic reperfused heart. In addition, isoflurane and sevoflurane shortened this time. These facts suggest that mechanisms other than effects of volatile anaesthetics on hydroxyl radical formation are responsible for their protective effects in this model.

A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases.

We retrospectively analyzed 52 adult patients with hemophagocytic syndrome (HPS). The underlying diseases were heterogeneous, including malignant lymphoma (lymphoma-associated hemophagocytic syndrome [LAHS]) in 26 patients, systemic lupus erythematosus in 3 patients, viral infections in 7 patients, and bacteria] or fungal infections in 6 patients. More than 83% of patients received prednisolone as an initial treatment. Multiple-agent chemotherapies (cyclophosphamide, doxorubicin, and vincristine) were administered to 96% of LAHS patients after a histopathological diagnosis of lymphoma. HPSs were controllable and remissions were achieved except for those patients with LAHS, fulminant Epstein-Barr virus-associated HPS, and an immunosuppressive state. Twenty-one (81%) of the LAHS patients had uncontrollable HPS and died of multiple organ failure and disseminated intravascular coagulation. The median survival time of LAHS patients was 83 days. In contrast, 3 (12%) of the other HPS patients died of multiple organ failure within 44 days.The clinical manifestations and the laboratory findings of LAHS and the other HPSs were too variable to establish the prognosis based only on the findings at the onset of HPS. The prognostic factors of adult HPS were found to be the underlying diseases, notably malignant lymphoma and infections, accompanied by the immunosuppressive state.

Inhibitory effect of prostaglandin E 1 on intimal thickening caused by poor runoff conditions in the canine autologous vein grafts.

The efficacy of ONO-1608, a newly developed liposomal formulation of prostaglandin E 1 prodrug, was evaluated on intimal hyperplasia of experimental canine autologous vein grafts under distal poor runoff conditions. The femoral vein was implanted into the femoral artery, preparing a distal poor runoff canine model. After 4 weeks of preparing the poor runoff model, the femoral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 weeks, the grafts were harvested and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine incorporation 2 weeks after surgery. In addition, the effect of ONO-1608 on the proliferation of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was also investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control group. The bromodeoxyuridine labeling index 2 weeks after grafting was significantly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-stimulated HASMCs in culture. These results demonstrate the efficacy of ONO-1608 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of ONO-1608 may be beneficial in patients who have undergone gone arterial reconstruction.

Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse.

Several gene transfer methods, including viral or nonviral vehicles have been developed, however, efficacy, safety or handling continue to present problems. We developed a nonviral and plasmid-based method for arterial gene transfer by in vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit carotid arteries, we first optimized gene transfer efficiency, and firefly luciferase gene transfer via electronic pulse under 20 voltage (the pulse length: P(on)time 20 ms, the pulse interval: P(off) time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogenous gene expression was detectable for at least up to 14 days. Electroporation-mediated gene transfer of E. coli lacZ with nuclear localizing signal revealed successful gene transfer to luminal endothelial cells and to medial cells. Histological damage was recognized as the voltage was increased but neointima formation 4 weeks after gene transfer was not induced. In vivo electroporation-mediated arterial gene transfer is readily facilitated, is safe and may prove to be an alternative form of gene transfer to the vasculature.

Natural course of the functional and morphological changes in canine autogenous arterial graft.

BACKGROUND: We examined the time course of endothelium-dependent and -independent responses in reversed autogenous arterial grafts during regeneration and tissue repair processes after arterial grafting in dogs. MATERIALS AND METHODS: Autogenous arterial grafts implanted in the canine femoral artery were removed, cut into rings and suspended in organ chambers for isometric tension recording on the 1st, 3rd, 7th, 14th and 28th days after implantation. Electron-microscopic examination on the 1st, 3rd,7th, 14th and 28th days after transplantation was also performed. Control arteries were taken from nonsurgically treated femoral arteries. RESULTS: Acetylcholine (ACh) and A23187 caused endothelium-dependent relaxations in arterial grafts throughout the study. Although endothelium-dependent relaxations to ACh and A23187 on the 3rd day after transplantation were only significantly impaired compared to those of control, they were similar to the control within 1 week after grafting. Smooth muscle relaxations in response to sodium nitroprusside in arterial grafts throughout the study were comparable with those of control arteries. No apparent intimal thickening of the arterial grafts was observed. Electron microscopy scanning revealed mild endothelial cell damage in implanted autogenous arterial grafts on the 1st or 3rd day after grafting. Seven to 14 days after grafting, the endothelial cell layer appeared to be normal. CONCLUSIONS: It was observed that the endothelial function remained intact and there was an absence of intimal thickening in the arterial grafts. These observations may explain the improved patency of autogenous arterial grafts compared to the vein grafts in aortocoronary revascularization.

[The influence of N-nitro-L-arginine methyl ester (L-NAME) on hydroxyl free radical formation in the post-ischemic reperfused heart of anesthetized rats].

N-nitro-L-arginine methyl ester (L-NAME) has been reported to have protective action against hydroxyl free radicals. We have investigated whether L-NAME influences free radical formation in the post-ischemic reperfused heart of anesthetized rats. An isolated rat heart-lung preparation was used. Forty male Wistar rats were allocated into D (D-NAME 100 microMol.l-1), L (L-NAME 100 microMol.l-1), LH (L-NAME 100 microMol.l-1 and 1MAC halothane), LI (L-NAME 100 microMol.l-1 and 1MAC isoflurane), and LS (L-NAME 100 microMol.l-1 and 1MAC sevoflurane) groups. The heart was perfused initially at the cardiac output of 30 ml.min-1 and the atrial pressure of 70 mmHg. Drugs were administered into the reservor 7 min after the start of perfusion. Ten minutes after the start of perfusion, the heart was rendered globally ischemic for 10 min by reducing the preload and afterload to zero and then reperfused for 10 min. At the end of reperfusion, the heart was freeze-dried for 4 days. The perfusate blood was collected just before and after ischemia and at the end of reperfusion. The formation of hydroxyl radicals in the perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acid (DHBA). Before and after ischemia, there were no significant differences among the groups in cardiac output, systolic pressure, heart rate, and right atrial pressure. DHBAs in the heart of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups. The concentrations of DHBA in the perfusate blood after ischemia and reperfusion were significantly higher than those before ischemia in all groups. DHBAs in the perfusate blood after ischemia and reperfusion of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups administered L-NAME. This study indicates that L-NAME reduces hydroxyl free radical formation in the post-ischemic reperfused heart in anesthetized rats and volatile anesthetics do not influence the depressant effect of hydroxyl free radical formation by L-NAME.

Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets.

Heat shock protein (hsp), including hsp70, has been reported to restore the glucose-induced insulin release suppressed by nitric oxide (NO). However, the mechanism underlying this recovery remains unclear. In the present study, we examine the effects, in rat islets, of heat shock on insulin secretion inhibited by a small amount of NO and also on glucose metabolism, the crucial factor in insulin release. Exposure to a higher dose (15 U/ml) of interleukin-1beta (IL-1beta) abolished the insulin release by stimulation of glucose or KCl in both control and heat shocked islets. In rat islets exposed to a lower dose (1.5 U/ml) of IL-1beta, insulin secretion in response to glucose, but not to glyceraldehydes (GA), ketoisocaproate (KIC), or KCl, was selectively impaired, concomitantly with lower ATP concentrations in the presence of 16.7 mM glucose, while such suppression of insulin secretion and ATP content was not observed in heat shock-treated islets. NO production in islets exposed to 1.5 U/ml IL-1beta was significantly, but only partly, decreased by heat shock treatment. The glucose utilization rate measurement using [5-3H]-glucose and [2-3H]-glucose and the glucokinase activity in vitro were reduced in islets treated with 1.5 U/ml IL-1beta. In heat shock-treated islets, glucose utilization and glucokinase activity were not affected by 1.5 U/ml IL-1beta. These data suggest that heat shock restores glucose-induced insulin release inhibited by NO by maintaining glucokinase activity and the glucose utilization rate in islets in addition to reducing endogenous NO production.

Effects of cibenzoline on cardiac function and metabolism in the rat heart--lung preparation.

BACKGROUND AND OBJECTIVE: Although there is concern that cibenzoline, an antidysrhythmic drug for the treatment of ventricular and supraventricular dysrhythmias, may be associated with dose-dependent inhibition of myocardial contractility there are few reports about the relationship between myocardial metabolism and cardiac function when it is used. The present study was designed to investigate the effects of cibenzoline on cardiac function and metabolism. The effects of cibenzoline on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. METHODS: Thirty-two male Wistar-ST rats were divided into four groups: control, and those to receive cibenzoline, either 300, 900 or 3000 ng mL(-1). The cibenzoline was administered into the perfusate 5 min after the start of perfusion. Heart rates in the 3000 ng mL(-1) group were significantly lower than those in the control group. Cardiac output in the 3000 ng mL(-1) group at 15 and 30 min was significantly lower than in the control group. In all groups, values for %LV dP/dt max (the ratio of values at each time to those at 5 min) at 20, 25, 30 min were significantly higher than at 5 min. Myocardial adenosine triphosphate concentration in the 3000 ng mL(-1) group was significantly lower than in controls. There was no difference between groups in the lactate/pyruvate ratio. CONCLUSION: The therapeutic range of cibenzoline has few effects on cardiac function and metabolism, although concentrations 10 times greater may cause a deterioration in myocardial metabolism.