BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse e...BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse effects.This report aims to highlight a seldom-considered rare side effect of diazoxide.We believe that this brief report is of general interest to World Journal of Clinical Pediatric readership and increase the physicians’awareness of the guideline importance.Moreover,it underlines the importance of stopping immediately the drug if suspected side effects.CASE SUMMARY The manuscript describes a patient diagnosed with congenital hyperinsulinism(CHI)treated with diazoxide not overlapping with diuretic.He resulted in sudden respiratory distress and therefore was transferred to the Neonatal Intensive Care Unit.The cardiological evaluation showed pericardial effusion and left ventricular myocardial hypertrophy,absent before.In suspicion of an iatrogenic effect of diazoxide it was progressively reduced until stop while introducing diuretic treatment,with resolution of symptoms.Once clinically stabilized,an 18 fluoro-diydroxy-phenylalanine positron emission tomography/computed tomography(PET/CT)was performed to differentiate between a focal or diffuse form of CHI.The PET/CT highlighted the presence of a single focal accumulation of the tracer located in the pancreatic tail,consistent with a focal form of hyperin-sulinism.At the age of four months,the patient underwent a distal pancreatectomy with histological confirmation of a focal form of nesidioblastosis,resulting in a curative operation.CONCLUSION Diuretic administration and vigilant monitoring of diazoxide therapy are crucial to prevent and promptly identify potentially life-threatening adverse effects.展开更多
AIM:To evaluate the effects of diazoxide on ischemia/reperfusion(I/R)-injured hepatocytes and further elucidate its underlying mechanisms.METHODS:Male Sprague-Dawley rats were randomized(8 for donor and recipient per ...AIM:To evaluate the effects of diazoxide on ischemia/reperfusion(I/R)-injured hepatocytes and further elucidate its underlying mechanisms.METHODS:Male Sprague-Dawley rats were randomized(8 for donor and recipient per group)into five groups:I/R group(4 h of liver cold ischemia followed by 6 h of reperfusion);heme oxygenase-1(HO-1)small interfering RNA(siRNA)group(injection of siRNA via donor portal vein 48 h prior to harvest);diazoxide(DZ) group(injection of DZ via donor portal vein 10 min prior to harvest);HO-1 siRNA+DZ group;and siRNA control group.Blood and liver samples were collected at 6 h after reperfusion.The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting,and tissue morphology was examined by light and transmission electron microscopy.Serum transaminases level and cytokines concentration were also measured.RESULTS:We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA+DZ group when compared with I/R group,while the increases were prominent in the DZ group.Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA+DZ groups compared with DZ group.Serum alanine aminotransferase,aspartate transaminase,tumor necrosis factor-αand interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA+DZ groups,and decreased in the DZ group.CONCLUSION:The protective effect of DZ may be induced by upregulation of HO-1.By inhibiting expression of HO-1,this protection pretreated with DZ was abolished.展开更多
Mitochondrial K＋-ATP （mito-KATP） channels play an important role in cellular function and survival following ischemic stress. The present results revealed that intervention with diazoxide, a mito-KATP channel opene...Mitochondrial K＋-ATP （mito-KATP） channels play an important role in cellular function and survival following ischemic stress. The present results revealed that intervention with diazoxide, a mito-KATP channel opener, led to an increase in Bcl-2 expression in the cerebral cortex of rats subjected to cerebral ischemia reperfusion injury. In addition, the intervention also led to clear improvements in neuronal mitochondrial morphology and consciousness post-injury. Glibenclamide a mito-KATP channel blocker, exhibited the converse effects. Both diazoxide and glibenclamide exerted dose-dependent effects （in particular, at 18 mg/kg diazoxide and 25 mg/kg glibenclamide）. These findings suggest that diazoxide exerts a neuroprotective effect on cerebral ischemia reperfusion injury by opening mito-KATP channels and upregulating Bcl-2 expression.展开更多
Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular mode of epilepsy by cultur...Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular mode of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate effects of diazoxide preconditioning on the expression of inwardly rectifying potassium channel （Kir） subunits of the ATP-sensitive potassium. We found that neuronal viability was significantly reduced in the epileptic cells, whereas it was enhanced by diazoxide preconditioning. Double immunofluorescence and western blot showed a significant increase in the expression of Kir6.1 and Kir6.2 in epileptic cells, especially at 72 hours after seizures. Diazoxide pretreatment completely reversed this effect at 24 hours after seizures. In addition, Kir6.1 expression was significantly upregulated compared with Kir6.2 in hippocampal neurons after seizures. These findings indicate that diazoxide pretreatment may counteract epileptiform discharge-induced cytotoxicity by suppressing the expression of Kir subunits.展开更多
In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups： the rats in the experimental ...In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups： the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 rain, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group, MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced （P〈0.05）. And the cell ultrastructure was obviously improved, But the activity of SOD had no change （P〉0.05）. It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis.展开更多
The effects of diazoxide treatments on electrophysiologyic properties in guinea pig papillary muscles undergoing ischemia/reperfusion was studied using intracellular microelectrode technique. Twenty-four guinea pigs w...The effects of diazoxide treatments on electrophysiologyic properties in guinea pig papillary muscles undergoing ischemia/reperfusion was studied using intracellular microelectrode technique. Twenty-four guinea pigs were randomly divided into three groups (n=8 in each group). In control group, St.Thomas solution was given. In experimental group, St.Thomas solution with diazoxide (100 mol/L) was given. In pretreatment group, the muscle was treated with diazoxide 20 min before arrested with St.Thomas cardioplegia. The results showed that the APD_50 and APD_90 in experimental and pretreatment groups were significantly shorter after 5 and 10 min reperfusion (P<0.01, P<0.05), but longer after 30 min reperfusion (P<0.01, P<0.05) than in control group. In experimental and pretreatment groups, APA, OS, Vmax recovered more quickly than those in control group. The time to re-systole after reperfusion in control group was longer than that in experimental and pretreatment groups. There was no significant difference in RP among three groups. The time of arrest in pretreatment group was longer than that in experimental and pretreatment group (P<0.05). This study indicates that protective effects of St.Thomas solution with diazoxide is better than that of pretreatment with diazoxide or St.Thomas solution alone.展开更多
Objectives To analyze and identify differentially expressed phosphoproteins associated with mitochondrial KATP channel opening. Methods： Adult rat ventricular myocytes were isolated, cultured, and identified, and pre...Objectives To analyze and identify differentially expressed phosphoproteins associated with mitochondrial KATP channel opening. Methods： Adult rat ventricular myocytes were isolated, cultured, and identified, and pretreated without or with 100 μmol/L diazoxide for 10 min. Phosphoproteins prepared and enriched from the control and diazoxide-pretreated cells were separated by two-dimensional gel electrophoresis （2-DE） followed by sliver staining. The obtained interesting phosphoproteins were further identified by mass spectrometry. Results. Associated with diazoxide preconditioning, the proteins of chaperonin containing TCP-1 and hypothetical protein XP-346548 were phosphorylated significantly （P〈0. 01）, while the 94-kDa glucose-regulated protein, calpactin I heavy chain and ferritin were dephosphorylated markedly （P〈0. 01）. Conclusion： These findings suggest that cardiomyocytes undergo significant posttranslational modification via phosphorylation in a multitude of proteins in order to respond diazoxide preconditioning, and these phosphorylated protein may mediate the downstream signaling of cardioprotection by mitochondrial KATp channel opening induced by ischemic preconditioning.展开更多
BACKGROUND Uterine fibroids are common benign gynecological conditions.Patients who experience excessive menstruation,anemia,and pressure symptoms should be administered medication,and severe cases require a total hys...BACKGROUND Uterine fibroids are common benign gynecological conditions.Patients who experience excessive menstruation,anemia,and pressure symptoms should be administered medication,and severe cases require a total hysterectomy.This procedure is invasive and causes severe postoperative pain,which can affect the patient’s postoperative sleep quality and,thus,the recovery process.AIM To evaluate use of dezocine in patient-controlled epidural analgesia(PCEA)for postoperative pain management in patients undergoing total myomectomy.METHODS We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups:A control group receiving 0.2%ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2%ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA.Outcomes assessed included pain levels,sedation,recovery indices,PCEA usage,stress factors,and sleep quality.RESULTS The observation group showed lower visual analog scale scores,shorter postoperative recovery indices,fewer mean PCEA compressions,lower cortisol and blood glucose levels,and better polysomnographic parameters compared to the control group(P<0.05).The cumulative incidence of adverse reactions was lower in the observation group than in the control group(P<0.05).CONCLUSION Dezocine PCEA can effectively control the pain associated with total myomectomy,reduce the negative impact of stress factors,and have less impact on patients’sleep,consequently resulting in fewer adverse effects.展开更多
Background Cerebral ischemia-reperfusion/hypoxia-reoxygenation insult triggers lots of pathophysiological and biochemical events that separately affect the evolution of cerebral damage. Accordingly, all known effectiv...Background Cerebral ischemia-reperfusion/hypoxia-reoxygenation insult triggers lots of pathophysiological and biochemical events that separately affect the evolution of cerebral damage. Accordingly, all known effective neuroprotective measures should be taken to get the optimal efficacy of therapy. This study was undertaken to investigate whether diazoxide （DZ） preconditioning combined with the following hypothermia could contribute to synergistic neuroprotection compared with either hypothermia or DZ preconditioning alone. Methods Cultured for 9-10 days in vitro, the hippocampal neurons of SD rats were preconditioned with DZ 0 pmol/L or DZ 250 pmol/L for 1 hour per day and this treatment lasted for 3 days. Subsequently, neurons were subjected to deprivation of oxygen for 4 hours at 37°0, 34°C, 30℃ and 22℃, respectively. This experiment consisted of 8 groups （4 temperature groups and 4 combination groups） and each group contained 12-well or 2-dish cells. Survival rate, expression of Bcl-2, fluorescence magnitude of intracellular calcium, and concentration of malondialdehyde （MDA） were determined at 24 hours after reoxygenation. Results The survival rate and expression of Bcl-2 were both increased in individually hypothermic conditions compared with those at 370G （P〈0.05）, whereas intracellular calcium and MDA did the opposite exhibition simultaneously （P〈0.05）. 22℃ contributed to a higher survival rate and greater expression of Bcl-2 in comparison with other hypothermia （P〈0.05）. Preceding administration of 250 pmol/L DZ took the similar effects on the neurons like hypothermia. Moreover, compared with individual hypothermia or DZ preconditioning, the neuronal survival rate and expression of Bcl-2 in the combination group were increased significantly （P〈0.05）, whereas the calcium fluorescence density and concentration of MDA were reduced further （P〈0.05）. 250 Iamol/L DZ preconditioning combined with 22℃ provided a maximal neuroprotection. Conclusions Compared with either individual hypothermia or DZ preconditioning, the combination of both treatments conferred synergistic protection for cultured hippocampal neurons in vitro against hypoxia- reoxygenation insult.展开更多
AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips.METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile...AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips.METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile responses to electrical field stimulation were recorded on a physiograph in an isotonic manner after administration of cumulative concentrations of indomethacin. The effects of indomethacin on the strips pretreated with KATP channel modulators, diazoxide and glybenclamide were studied.RESULTS: Treatment of the transverse strips with indomethacin resulted in a concentration-dependent inhibitory response. In longitudinal strips, biphasic responses were seen, which included a stimulatory response at low concentrations of indomethacin, followed by an inhibitory response at higher concentrations.Diazoxide pre-treatment inhibited the stimulatory response of longitudinal strips. Glybenclamide pre-treatment not only blocked inhibitory effect of the low concentrations of indomethacin on transverse strips, but also increased the amplitude of contractions. Moreover, the drug decreased the amplitude of contractions in longitudinal strips.CONCLUSION: Responses of the isolated longitudinal and transverse rat gastric fundus strips to indomethacin are not similar, and are influenced by KATP channel modulators.展开更多
Backgroud Recent studies in adult hearts have indicated that K ATP channels in the inner mitochondrial membrance are responsible for the protection. And we investigated whether opening of mitochondrial K ATP ...Backgroud Recent studies in adult hearts have indicated that K ATP channels in the inner mitochondrial membrance are responsible for the protection. And we investigated whether opening of mitochondrial K ATP channels (mK ATP ) could provide myocardial protection for immature rabbits and determined its role in cardioprotection Methods Thirty-four 3-4-week-old rabbits, weighing 300-350 g, were divided randomly into five groups: Group Ⅰ (control group, n=8); Group Ⅱ [diazoxide preconditioning group; n=8; the hearts were pretreated with 100 μmol/L diazoxide for 5 minutes followed by 10-minute wash out with Krebs-Henseleit buffer (KHB)]; Group Ⅲ ; Group Ⅲ [diazoxide+5-hydroxydeconate (5-HD) preconditioning group; n=5; the hearts were pretreated with 100 μmol/L diazoxide and 100 μmol/L 5-HD); Group Ⅳ (diazoxide+cardioplegia group; n=8; cardioplegia containing 100 μmol/L diazoxide perfused the hearts for 5 minutes before ischemia); Group Ⅴ (diazoxide+5-HD+cardioplegia group; n=5; the cardioplegia contained 100 μmol/L diazoxide and 100 μmol/L 5-HD) All hearts were excised and connected to langendrff perfusion system and passively perfused with KHB at 38℃ under a pressure of 70 cmH 2O After reperfusion, the recovery rate of left ventricular diastolic pressure (LVDP), ±dp/dt max , coronary flow (CF), the creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) in coronary sinus venous effluent and the tissue ATP were measured Mitochondria were evaluated semiquantitatively by morphology Results After ischemia and reperfusion (I/R), the two groups that were treated by diazoxide only (Groups Ⅱ and Ⅳ) had a significant improvement in LVDP, ±dp/dt max , and CF recovery AST, LDH, and CK were decreased, and the levels of tissue ATP in the two groups were higher Mitochondria was protected better in Group Ⅳ than in other groups Conclusions Activating mK ATP channels before and during ischemia can similarly protect immature rabbit hearts, and the mechanism is related to the direct protective effect on mitochondria Opening of mK ATP channel during ischemia provides a better protection for mitochondria than it does before ischemia展开更多
文摘BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse effects.This report aims to highlight a seldom-considered rare side effect of diazoxide.We believe that this brief report is of general interest to World Journal of Clinical Pediatric readership and increase the physicians’awareness of the guideline importance.Moreover,it underlines the importance of stopping immediately the drug if suspected side effects.CASE SUMMARY The manuscript describes a patient diagnosed with congenital hyperinsulinism(CHI)treated with diazoxide not overlapping with diuretic.He resulted in sudden respiratory distress and therefore was transferred to the Neonatal Intensive Care Unit.The cardiological evaluation showed pericardial effusion and left ventricular myocardial hypertrophy,absent before.In suspicion of an iatrogenic effect of diazoxide it was progressively reduced until stop while introducing diuretic treatment,with resolution of symptoms.Once clinically stabilized,an 18 fluoro-diydroxy-phenylalanine positron emission tomography/computed tomography(PET/CT)was performed to differentiate between a focal or diffuse form of CHI.The PET/CT highlighted the presence of a single focal accumulation of the tracer located in the pancreatic tail,consistent with a focal form of hyperin-sulinism.At the age of four months,the patient underwent a distal pancreatectomy with histological confirmation of a focal form of nesidioblastosis,resulting in a curative operation.CONCLUSION Diuretic administration and vigilant monitoring of diazoxide therapy are crucial to prevent and promptly identify potentially life-threatening adverse effects.
基金Supported by Social Development Projects of Yunnan Province,No.2008CA026
文摘AIM:To evaluate the effects of diazoxide on ischemia/reperfusion(I/R)-injured hepatocytes and further elucidate its underlying mechanisms.METHODS:Male Sprague-Dawley rats were randomized(8 for donor and recipient per group)into five groups:I/R group(4 h of liver cold ischemia followed by 6 h of reperfusion);heme oxygenase-1(HO-1)small interfering RNA(siRNA)group(injection of siRNA via donor portal vein 48 h prior to harvest);diazoxide(DZ) group(injection of DZ via donor portal vein 10 min prior to harvest);HO-1 siRNA+DZ group;and siRNA control group.Blood and liver samples were collected at 6 h after reperfusion.The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting,and tissue morphology was examined by light and transmission electron microscopy.Serum transaminases level and cytokines concentration were also measured.RESULTS:We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA+DZ group when compared with I/R group,while the increases were prominent in the DZ group.Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA+DZ groups compared with DZ group.Serum alanine aminotransferase,aspartate transaminase,tumor necrosis factor-αand interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA+DZ groups,and decreased in the DZ group.CONCLUSION:The protective effect of DZ may be induced by upregulation of HO-1.By inhibiting expression of HO-1,this protection pretreated with DZ was abolished.
文摘Mitochondrial K＋-ATP （mito-KATP） channels play an important role in cellular function and survival following ischemic stress. The present results revealed that intervention with diazoxide, a mito-KATP channel opener, led to an increase in Bcl-2 expression in the cerebral cortex of rats subjected to cerebral ischemia reperfusion injury. In addition, the intervention also led to clear improvements in neuronal mitochondrial morphology and consciousness post-injury. Glibenclamide a mito-KATP channel blocker, exhibited the converse effects. Both diazoxide and glibenclamide exerted dose-dependent effects （in particular, at 18 mg/kg diazoxide and 25 mg/kg glibenclamide）. These findings suggest that diazoxide exerts a neuroprotective effect on cerebral ischemia reperfusion injury by opening mito-KATP channels and upregulating Bcl-2 expression.
基金supported by the Technology Development Plan of Linyi City, No. 201113002
文摘Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular mode of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate effects of diazoxide preconditioning on the expression of inwardly rectifying potassium channel （Kir） subunits of the ATP-sensitive potassium. We found that neuronal viability was significantly reduced in the epileptic cells, whereas it was enhanced by diazoxide preconditioning. Double immunofluorescence and western blot showed a significant increase in the expression of Kir6.1 and Kir6.2 in epileptic cells, especially at 72 hours after seizures. Diazoxide pretreatment completely reversed this effect at 24 hours after seizures. In addition, Kir6.1 expression was significantly upregulated compared with Kir6.2 in hippocampal neurons after seizures. These findings indicate that diazoxide pretreatment may counteract epileptiform discharge-induced cytotoxicity by suppressing the expression of Kir subunits.
文摘In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups： the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 rain, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group, MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced （P〈0.05）. And the cell ultrastructure was obviously improved, But the activity of SOD had no change （P〉0.05）. It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis.
文摘The effects of diazoxide treatments on electrophysiologyic properties in guinea pig papillary muscles undergoing ischemia/reperfusion was studied using intracellular microelectrode technique. Twenty-four guinea pigs were randomly divided into three groups (n=8 in each group). In control group, St.Thomas solution was given. In experimental group, St.Thomas solution with diazoxide (100 mol/L) was given. In pretreatment group, the muscle was treated with diazoxide 20 min before arrested with St.Thomas cardioplegia. The results showed that the APD_50 and APD_90 in experimental and pretreatment groups were significantly shorter after 5 and 10 min reperfusion (P<0.01, P<0.05), but longer after 30 min reperfusion (P<0.01, P<0.05) than in control group. In experimental and pretreatment groups, APA, OS, Vmax recovered more quickly than those in control group. The time to re-systole after reperfusion in control group was longer than that in experimental and pretreatment groups. There was no significant difference in RP among three groups. The time of arrest in pretreatment group was longer than that in experimental and pretreatment group (P<0.05). This study indicates that protective effects of St.Thomas solution with diazoxide is better than that of pretreatment with diazoxide or St.Thomas solution alone.
基金Supported by the National Natural Science Foundation of China (No. 30200089 and No. 30500211)
文摘Objectives To analyze and identify differentially expressed phosphoproteins associated with mitochondrial KATP channel opening. Methods： Adult rat ventricular myocytes were isolated, cultured, and identified, and pretreated without or with 100 μmol/L diazoxide for 10 min. Phosphoproteins prepared and enriched from the control and diazoxide-pretreated cells were separated by two-dimensional gel electrophoresis （2-DE） followed by sliver staining. The obtained interesting phosphoproteins were further identified by mass spectrometry. Results. Associated with diazoxide preconditioning, the proteins of chaperonin containing TCP-1 and hypothetical protein XP-346548 were phosphorylated significantly （P〈0. 01）, while the 94-kDa glucose-regulated protein, calpactin I heavy chain and ferritin were dephosphorylated markedly （P〈0. 01）. Conclusion： These findings suggest that cardiomyocytes undergo significant posttranslational modification via phosphorylation in a multitude of proteins in order to respond diazoxide preconditioning, and these phosphorylated protein may mediate the downstream signaling of cardioprotection by mitochondrial KATp channel opening induced by ischemic preconditioning.
基金Natural Science Foundation of Gansu Provincial Science and Technology Department(Basic Research Program),No.23JRRA1385.
文摘BACKGROUND Uterine fibroids are common benign gynecological conditions.Patients who experience excessive menstruation,anemia,and pressure symptoms should be administered medication,and severe cases require a total hysterectomy.This procedure is invasive and causes severe postoperative pain,which can affect the patient’s postoperative sleep quality and,thus,the recovery process.AIM To evaluate use of dezocine in patient-controlled epidural analgesia(PCEA)for postoperative pain management in patients undergoing total myomectomy.METHODS We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups:A control group receiving 0.2%ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2%ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA.Outcomes assessed included pain levels,sedation,recovery indices,PCEA usage,stress factors,and sleep quality.RESULTS The observation group showed lower visual analog scale scores,shorter postoperative recovery indices,fewer mean PCEA compressions,lower cortisol and blood glucose levels,and better polysomnographic parameters compared to the control group(P<0.05).The cumulative incidence of adverse reactions was lower in the observation group than in the control group(P<0.05).CONCLUSION Dezocine PCEA can effectively control the pain associated with total myomectomy,reduce the negative impact of stress factors,and have less impact on patients’sleep,consequently resulting in fewer adverse effects.
基金This study was supported by a grant from Specialized Research Fund for Doctoral Program of Higher Education, Ministry of Education of China (No. 20030023028).
文摘Background Cerebral ischemia-reperfusion/hypoxia-reoxygenation insult triggers lots of pathophysiological and biochemical events that separately affect the evolution of cerebral damage. Accordingly, all known effective neuroprotective measures should be taken to get the optimal efficacy of therapy. This study was undertaken to investigate whether diazoxide （DZ） preconditioning combined with the following hypothermia could contribute to synergistic neuroprotection compared with either hypothermia or DZ preconditioning alone. Methods Cultured for 9-10 days in vitro, the hippocampal neurons of SD rats were preconditioned with DZ 0 pmol/L or DZ 250 pmol/L for 1 hour per day and this treatment lasted for 3 days. Subsequently, neurons were subjected to deprivation of oxygen for 4 hours at 37°0, 34°C, 30℃ and 22℃, respectively. This experiment consisted of 8 groups （4 temperature groups and 4 combination groups） and each group contained 12-well or 2-dish cells. Survival rate, expression of Bcl-2, fluorescence magnitude of intracellular calcium, and concentration of malondialdehyde （MDA） were determined at 24 hours after reoxygenation. Results The survival rate and expression of Bcl-2 were both increased in individually hypothermic conditions compared with those at 370G （P〈0.05）, whereas intracellular calcium and MDA did the opposite exhibition simultaneously （P〈0.05）. 22℃ contributed to a higher survival rate and greater expression of Bcl-2 in comparison with other hypothermia （P〈0.05）. Preceding administration of 250 pmol/L DZ took the similar effects on the neurons like hypothermia. Moreover, compared with individual hypothermia or DZ preconditioning, the neuronal survival rate and expression of Bcl-2 in the combination group were increased significantly （P〈0.05）, whereas the calcium fluorescence density and concentration of MDA were reduced further （P〈0.05）. 250 Iamol/L DZ preconditioning combined with 22℃ provided a maximal neuroprotection. Conclusions Compared with either individual hypothermia or DZ preconditioning, the combination of both treatments conferred synergistic protection for cultured hippocampal neurons in vitro against hypoxia- reoxygenation insult.
文摘AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips.METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile responses to electrical field stimulation were recorded on a physiograph in an isotonic manner after administration of cumulative concentrations of indomethacin. The effects of indomethacin on the strips pretreated with KATP channel modulators, diazoxide and glybenclamide were studied.RESULTS: Treatment of the transverse strips with indomethacin resulted in a concentration-dependent inhibitory response. In longitudinal strips, biphasic responses were seen, which included a stimulatory response at low concentrations of indomethacin, followed by an inhibitory response at higher concentrations.Diazoxide pre-treatment inhibited the stimulatory response of longitudinal strips. Glybenclamide pre-treatment not only blocked inhibitory effect of the low concentrations of indomethacin on transverse strips, but also increased the amplitude of contractions. Moreover, the drug decreased the amplitude of contractions in longitudinal strips.CONCLUSION: Responses of the isolated longitudinal and transverse rat gastric fundus strips to indomethacin are not similar, and are influenced by KATP channel modulators.
文摘Backgroud Recent studies in adult hearts have indicated that K ATP channels in the inner mitochondrial membrance are responsible for the protection. And we investigated whether opening of mitochondrial K ATP channels (mK ATP ) could provide myocardial protection for immature rabbits and determined its role in cardioprotection Methods Thirty-four 3-4-week-old rabbits, weighing 300-350 g, were divided randomly into five groups: Group Ⅰ (control group, n=8); Group Ⅱ [diazoxide preconditioning group; n=8; the hearts were pretreated with 100 μmol/L diazoxide for 5 minutes followed by 10-minute wash out with Krebs-Henseleit buffer (KHB)]; Group Ⅲ ; Group Ⅲ [diazoxide+5-hydroxydeconate (5-HD) preconditioning group; n=5; the hearts were pretreated with 100 μmol/L diazoxide and 100 μmol/L 5-HD); Group Ⅳ (diazoxide+cardioplegia group; n=8; cardioplegia containing 100 μmol/L diazoxide perfused the hearts for 5 minutes before ischemia); Group Ⅴ (diazoxide+5-HD+cardioplegia group; n=5; the cardioplegia contained 100 μmol/L diazoxide and 100 μmol/L 5-HD) All hearts were excised and connected to langendrff perfusion system and passively perfused with KHB at 38℃ under a pressure of 70 cmH 2O After reperfusion, the recovery rate of left ventricular diastolic pressure (LVDP), ±dp/dt max , coronary flow (CF), the creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) in coronary sinus venous effluent and the tissue ATP were measured Mitochondria were evaluated semiquantitatively by morphology Results After ischemia and reperfusion (I/R), the two groups that were treated by diazoxide only (Groups Ⅱ and Ⅳ) had a significant improvement in LVDP, ±dp/dt max , and CF recovery AST, LDH, and CK were decreased, and the levels of tissue ATP in the two groups were higher Mitochondria was protected better in Group Ⅳ than in other groups Conclusions Activating mK ATP channels before and during ischemia can similarly protect immature rabbit hearts, and the mechanism is related to the direct protective effect on mitochondria Opening of mK ATP channel during ischemia provides a better protection for mitochondria than it does before ischemia
