A combination of phenobarbital and the bumetanide derivative bumepamine prevents neonatal seizures and subsequent hippocampal neurodegeneration in a rat model of birth asphyxia.

OBJECTIVES: Bumetanide was suggested as an adjunct to phenobarbital for suppression of neonatal seizures. This suggestion was based on the idea that bumetanide, by reducing intraneuronal chloride accumulation through inhibition of the Na-K-2Cl cotransporter NKCC1, may attenuate or abolish depolarizing γ-aminobutyric acid (GABA) responses caused by birth asphyxia. However, a first proof-of-concept clinical trial failed. This could have had several reasons, including bumetanide's poor brain penetration, the wide cellular NKCC1 expression pattern in the brain, and problems with the general concept of NKCC1's role in neonatal seizures. We recently replicated the clinical failure of bumetanide to potentiate phenobarbital's effect in a novel rat model of birth asphyxia. In this study, a clinically relevant dose (0.3 mg/kg) of bumetanide was used that does not lead to NKCC1-inhibitory brain levels. The aim of the present experiments was to examine whether a much higher dose (10 mg/kg) of bumetanide is capable of potentiating phenobarbital in this rat model. Furthermore, the effects of the two lipophilic bumetanide derivatives, the ester prodrug N,N-dimethylaminoethylester of bumetanide (DIMAEB) and the benzylamine derivative bumepamine, were examined at equimolar doses. METHODS: Intermittent asphyxia was induced for 30 min by exposing male and female P11 rat pups to three 7 + 3 min cycles of 9% and 5% O2 at constant 20% CO2 . All control pups exhibited neonatal seizures after the asphyxia. RESULTS: Even at 10 mg/kg, bumetanide did not potentiate the effect of a submaximal dose (15 mg/kg) of phenobarbital on seizure incidence, whereas a significant suppression of neonatal seizures was determined for combinations of phenobarbital with DIMAEB or, more effectively, bumepamine, which, however, does not inhibit NKCC1. Of interest, the bumepamine/phenobarbital combination prevented the neurodegenerative consequences of asphyxia and seizures in the hippocampus. SIGNIFICANCE: Both bumepamine and DIMAEB are promising tools that may help to develop more effective lead compounds for clinical trials.

Hydrolytic biotransformation of the bumetanide ester prodrug DIMAEB to bumetanide by esterases in neonatal human and rat serum and neonatal rat brain-A new treatment strategy for neonatal seizures?

OBJECTIVES: The loop diuretic bumetanide has been proposed previously as an adjunct treatment for neonatal seizures because bumetanide is thought to potentiate the action of γ-aminobutyric acid (GABA)ergic drugs such as phenobarbital by preventing abnormal intracellular accumulation of chloride and the subsequent "GABA shift." However, a clinical trial in neonates failed to demonstrate such a synergistic effect of bumetanide, most likely because this drug only poorly penetrates into the brain. This prompted us to develop lipophilic prodrugs of bumetanide, such as the N,N-dimethylaminoethyl ester of bumetanide (DIMAEB), which rapidly enter the brain where they are hydrolyzed by esterases to the parent compound, as demonstrated previously by us in adult rodents. However, it is not known whether esterase activity in neonates is sufficient to hydrolyze ester prodrugs such as DIMAEB. METHODS: In the present study, we examined whether esterases in neonatal serum of healthy term infants are capable of hydrolyzing DIMAEB to bumetanide and whether this activity is different from the serum of adults. Furthermore, to extrapolate the findings to brain tissue, we performed experiments with brain tissue and serum of neonatal and adult rats. RESULTS: Serum from 1- to 2-day-old infants was capable of hydrolyzing DIMAEB to bumetanide at a rate similar to that of serum from adult individuals. Similarly, serum and brain tissue of neonatal rats rapidly hydrolyzed DIMAEB to bumetanide. SIGNIFICANCE: These data provide a prerequisite for further evaluating the potential of bumetanide prodrugs as add-on therapy to phenobarbital and other antiseizure drugs as a new strategy for improving pharmacotherapy of neonatal seizures.

Meta-analysis of platelet-rich plasma in repairing burn wounds / 中国组织工程研究

BACKGROUND: At present, platelet-rich plasma has been used in bums, plastic surgery, surgery and orthopedics. However, due to the different standards for platelet-rich plasma preparation, the results of research on bums are controversial. OBJECTIVE: To systematically evaluate the effectiveness of platelet-rich plasma in the repair of burn wounds. METHODS: A computer-based online search of CNKI, VIP, WanFang, CBMdisc, PubMed, Embase, CochraneLibrary, Web of Science databases to retrieve randomized controlled trials regarding platelet-rich plasma repair of bum wounds. In the treatment group, platelet-rich plasma therapy or platelet-rich plasma therapy combined with conventional or other therapies were used. In the control group, conventional therapy, other therapies, or placebo treatment were used. After literature screening, information extraction and quality evaluation, Review Manager 5.3 software was used for meta analysis. RESULTS AND CONCLUSION: Eleven articles were included, involving 837 patients consisting of 420 patients in the treatment group and 417 patients in the control group. Meta analysis results revealed that the wound healing rate in the treatment group was significantly higher than that in the control group [OR=12.61, 95%Cl (6.93,18.29), P<0.000 1], Wound healing time in the treatment group was significantly shorter than that in the control group [OR=-4.64, 95%Cl (-6.21, -3.06), P<0.000 01]. The number of layers of gauze soaked by dressing [OR=-4.01, 95%Cl (-4.91, -3.11), P<0.000 01], the times of changing inner gauze [OR=-3.79, 95%Cl (-5.33, -2.26), P<0.000 01, and the times of dressing change on wound surface [OR=-3.41, 95%Cl (-5.93, -0.88), P=0.008] in the treatment group were significantly less than those in the control group. The positive rate of bacterial culture in wound [OR=0.46, 95%Cl (0.22, 0.94), P=0.03] and the incidence of inflammatory reaction in wound [OR=0.30, 95%Cl (0.17, 0.56), P=0.000 1] in the treatment group were significantly lower than those in the control group. The results suggested that platelet-rich plasma can increase the wound healing rate, shorten wound healing time, reduce the number of layers of gauze soaked by dressing, the times of changing inner gauze, and the times of dressing change on wound surface, and lower the positive rate of bacterial culture and the incidence of inflammatory reaction in wound.

Clinical Research on the Effect of Stellate Ganglion Block on the Stress Ulcer after Bum Injury / 现代生物医学进展

Objective:To investigate the clinical effects of stellate ganglion block(SGB) on the stress ulcer in burn patients and explore the underlying mechanisms.Methods:40 patients with burn injury induced stress ulcer were randomized to two groups:SGB group (n=20) and Control group (n=20).SGB group was treated with conventional symptomatic therapy,SGB group underwent SGB every two days for 1 week on the basis of Control group.And the levels of plasma ET-1 and NO were detected using ELISA before and after therapy.And the clinical efficacy of the two groups was observed after the treatment.Results:Compared with the Control group,the levels of plasma ET-1 and NO were markedly lower in the SGB group (P＜0.05),while the clinical efficacy was higher(P＜0.05).Conclusion:SGB could enhance the clinical efficacy stress ulcer in bum patients,which might be related to the decrease of plasma ET-1 and NO levels.

Protective effects of valproic acid on gut barrier function after major burn injury and its mechanism / 中华危重病急救医学

Objective To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism.Methods Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS),sham + VPA,scald + NS,and scald + VPA groups,with 10 rats in each group.Rat with 55％ total body surface area (TBSA) third-degree severe-bums model was reproduced by immersing into 80 ℃ water,and the rats in sham groups were given sham-bums by immersing into 37 ℃ water.The rats after severebums were immediately treated with 0.25 mL of 300 mg/kg VPA or NS by subcutaneous injection.Rats were sacrificed at 2 hours and 6 hours after injury,and abdominal aortic blood and ileal tissue were harvested.The levels of vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA).The intestinal permeability was evaluated by fluorescein isothiocyanate-dextran (FITC-dextran) determination.The histomorphological changes in gut barrier were evaluated by Chiu grading system.Levels of acetylated lysine at the ninth position of histone 3 protein (Ac-H3K9),hypoxia-inducible factor 1α (HIF-1α),zona occludens 1 (ZO-1) and myosin light chain kinase (MLCK) were determined by immunofluorescence staining and Western Blot.Results Compared with sham + NS group,rats in scald + NS group showed intestinal mucosal damage 2 hours after bum injury,as well as increased mucosal permeability,protein expression levels of HIF-1 α,VEGF,MLCK,and lowered levels of AC-H3K9 and ZO-1.These changes were much more prominent at 6 hours after injury.VPA treatment significantly attenuated the bum-induced intestinal damage.Compared with scald + NS group,the protective effects in scald + VPA group was not evident at 2 hours after injury;however,intestinal damage was much less severe at 6 hours after injury (Chiu score:2.03 ± 0.27 vs.3.12 ± 0.15),intestinal permeability was significantly decreased [FITC-dextran (μg/L):709 ± 76 vs.1138 ± 75],histone acetylation was enhanced [Ac-H3K9 (gray value):1.55 ± 0.12 vs.0.48±0.12],ZO-1 degradation was significantly inhibited (gray value:0.69 ± 0.12 vs.0.43 ± 0.16),the protein expression levels of VEGF and MLCK were significantly down-regulated [VEGF (ng/mg):51.7±3.7 vs.71.2±4.3,MLCK (gray value):1.98±0.20 vs.2.80±0.24],while the HIF-1 α protein expression levels were significantly reduced at both 2 hours and 6 hours after injury (gray value:2.50±0.39 vs.3.88±0.42 at 2 hours,1.83±0.42 vs.4.42±0.41 at 6 hours,all P ＜ 0.05).Conclusions Severe bum injury can induce histone deacetylation,ZO-1 degradation and intestinal barrier dysfunction.VPA can improve the levels of histone acetylation and ZO-1,and protect intestinal epithelial barrier function.These may probably be mediated through inhibiting HIF-1α and its downstream gene VEGF and MLCK.

[Textual research on Han-Chinese formulae collected in Tubo medical manuscript unearthed in 'Bum-pa-Che Tower].

A Tibetan manuscript with title of Sman-dpyad gces-pa grub-pa kun-'dus-pa in the Collection of Practiced Medical Quintessence, was found in the basement of a Buddhist tower named 'Bum-pa-che in Lhokha (Shannan), Tibet. It contains a purgative recipe of TCM with its title "Powder of Han Region" and several ingredients in Chinese transliteration. Based upon the rule of medieval Chinese system of pronunciation with reference of related texts and studies, a textual research identifies it as a kind of Maren (seed of Cannabis sativa L. ) wan in TCM. Although no identical formulae of its kind has been found in extant literature of TCM prior to the Song Dynasty(960 AD), yet its ingredients, pharmaceutical preparation and efficacy are very similar to the Modified maren wan, the variant formulae of Maren wan in Wai tai mi yao (Arcane Essentials from the Imperial Library) of the Tang Dynasty.

Application of Kangxiuke apozem in the treatment of severe burn shock / 国际中医中药杂志

ObjectiveTo observe the clinical effect of Kangxiuke apozem in the treatment of severe bum shock.Methods40 patients of severe burn shock were randomly divided into a treatment group and a control group,with 20 patients in each group.All the patients were treated by the same route of counter-shock therapy,and the treatment group was additionally given Kangxiuke apozem (nasal feeding,qd,150 ml/d).Level of blood lactic acid,heart rate and urinary volume were evaluated by time.Main shock symptoms,including restlessness,hydrodipsia,perspiration and coldness,were observed.ResultsThe treatment group was significantly superior to the control group in the amelioration of blood lactic acid,heart rate and urinary volume ( t =10.485、3.219、7.429,P＜ 0.01 ).The symptomatic extinction of restlessness,hydrodipsia,perspiration and coldness in the extremities in the treatment group were significantly superior to those in the control group (x2=10.16、7.37、5.63、4.29,P＜0.05).ConclusionAt the same time of routine counter-shock therapy,thereby prompt burn patients to smoothly go through shock period and decreas late complications.

The improved application of artificial dermaiin repairing depth of burn wounds / 中国综合临床

ObjectiveTo explore the therapeutic efficacy of artificial dermal in repairing depth of burn wounds.MethodsTwenty-two cases of patients with depth bum who were admitted to our hospital during August of 2008 to August of 2010 were enrolled in this trial for retrospective study.The style of management was evaluated in these patients.Burn wound depth and severity was assessed immediately after patients admission,wound treatment was performed after patients with stable vital signs and wound edema peak period vanished.Artificial dermal was grafted onto the wound tissue after the primary debridement. Then,transplantation of artificial dermal was performed,with moist dressingonto it.After two weeks,the razor thick autoskin was grafted onto the surface of the artificial dermal after the removing of its silicon membrane during the secondary operation.ResultsThe wound healed completely with the survival of skin grafting and satisfactory appearance in all 22 patients. Furthermore,the scar in the donor site exhibited unconspicuous. Conclusion It's an optimal choice to repair deep burn with artificial dermal and thick autoskin.

Up-regulation of Tim-3 Expression Contributes to Development of Burn-induced T Cell Immune Suppression in Mice / 华中科技大学学报（医学）（英德文版）

T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses,but its role in burn-induced T cells immune suppression remains unclear.In the present study,in order to identify the relationship between Tim-3 expression and post-bum T cells immune suppression,C57BL/6 mice were subjected to bum injury or sham injury,and the liver and spleen were harvested at the day 1 after operation.The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3+ T cells were evaluated.It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4+ and CD8+ T cells in contrast with the post-burn depletion of T cells.Furthermore,Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury,including increased expression of anti-inflammatory cytokine IL-10,decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α,reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1.Moreover,Tim-3+ T cells subsets were more prone to spontaneous apoptosis than Tim-3 T cells subsets.Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after bum injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.

Application of zingiberol combined with purple burn ointment in prevention of chemotherapy-induced phlebitis / 中国实用护理杂志

Objective To explore the effect of zingiberol combined with purple burn ointment in prevention of chemotherapy- induced phlebitis. Methods 200 cases of peripheral intravenous chemotherapy were randomly divided into the experimental group and the control group with 100 cases in each. The control group was given conventional infusion chemotherapy drugs, the experimental group used zingiberol combined with purple bum ointment to embrocate the skin around the vein to prevent phlebitis. After chemotherapy, the results were observed and recorded. Results The incidence of phlebitis in the experimental group significantly reduced compared with the control group. Conclusions Embrocation with zingiberol and purple burn ointment can prevent chemotherapy-induced phlebitis, which is simple with significant effect.

Effect of insulin on the apoptosis of vascular endothelial cells induced by burn serum / 中华急诊医学杂志

Objective To investigate the effeets of insulin on the apoptosis of vascular endothelial cells cuinduced by burn$eruln in order to explore its possible mechamsm.Method Cultured human ECV304 cells were randomly divided into 33x)ups:control group,the ECV304 cells hured by 15%(V/V)rat normal,qertlm(t=6);bum semm group,the ECV3()4 cells simulated by 15%(V/V)self-made burn semm collected from rats with 30%TBSA full-thickness burns on the,back(n=6);and burn Serum+insulin group.the ECV304 cells cultared by insulin(10-7mol/L)and 15%(V/V) seIf-made rat bum serum(n=6).The transferase mediated nick end labeling(TUNEL) method was employed to measure the apoptosis of endothelial cells at 6 hours after stimulation.Meanwhile.immanohistochemical technique and Western blotting were used to determine the protein expressions of bcl-2 and eNOS.Data are expressed ills mean ±SEM.Statistical comparison was made using oneway analysis of vtriance.Significance was accepted at P<0.05.Results Compswith the control group,bum$erunl induced the apoptusis(18.5±3.1%)and down-regalated bcl·2(O.36±0.12)and p-eNOS(O.55±0.28)protein expressions of HUVECs(P<0.01).Burn 9AJ'unl+insulin significantly decreased the apoptosis(9.6 4-2.8%)and up-regulated bcl-2(0.944-0.25)and p-eNOS(0.89±0.16)protein expressions ofHU-VECs in comparison with the bum serllm group(P<0.01).eNOS showed no significant differences in three groups.Conclusions Insulin could markedly inhibit the apoptosis and up-regalate bcl-2 protein expression of HUVECs induced by bum serum,and its mec,harfism might involve the protein expression ofphosphorylated eNOS.

Does risk exist in severe burned patients applied with recombinant growth hormone? / 中华临床营养杂志

Effectiveness of recombinant human growth hormone ( rhGH) in treating critically ill or severe burned patients have been demonstrated. Although adverse effects of rhGH have also been identified, they are controllable. The dosage and timing of rhGH must be well designed, and hyperglycemia be controlled. Application of rhGH in critically ill patients should be deliberately considered.

Observation in effect of shuanghuang liquid on burn wound healing / 中国实用护理杂志

Objective To observe the effect of shuanghuang liquid on bum wound healing. Meth-ods 120 cases of patients with moderate bums adopted shuanghuang liquid (the treatment group) and gentamyein (the control group) for wound dressing change, wound pain and wound healing effect were com-pared between the two groups. Results The two groups showed difference in reducing wound pain and shortening time of wound healing. Conclusions Shuanghuang liquid was superior to gentamycin in wound healing and wounds pain.

Effects of four somatropins on blood sugar in severely burned patients / 中华临床营养杂志

ured with different techniques.Standardized application of somatropins will not induce diabetes.

Carbachol alleviates intestinal inflammation during enteral fluid resuscitation of rats with burn shock / 中华急诊医学杂志

Objective To investigate the effect of carbachol on local gut inflammation during entetal resuscitation of rats with bum shock. Method Thirty-eight Wistar rats were subjected to 35%TBSA full thickness scald injury, and enteral fluid was infused into animal intestines via duodenal stomas 30 minutes post bum. The animals were randomly divided into four groups: no resuscitation (Control, n = 8), enteral resuscitation using either a glucose electrolyte solution (GES, n = 10) or GES plus carbachol (60 μg·kg-1,GES/CAR, n = 10), or carbachol alone (CAR, n = 10) .The volumeof GES infusion was based on the Parkland formula (4 ml· 1% TB-SA-1·Kg-1) - All animals were sacrificed 4 hours post bum, and specimens of jejunal tissue were collected to determine the levels of tumor necrosis factor (TNF)-α, nitric oxide (NO), nitric oxide synthase (NOS) and myeloperoxidase (MPO). Serum assays for plasma diamine oxidase (DAO) activities were also performed. Results There were no statistical differences in the intestinal levels of NOS, NO, TNF-α and MPO, and plasma OAO activities, between the GES group and the control group. Compared to the GES group, the GES/CAR group showed significantly lowered levels of intestinal NOS (1.276 ±0.391 vs. 1.818 ±0.436, P＜0.05), NO (0.925 ±0.402 vs. 1.561 ±0.190, P ＜ 0.05, TNF-α (0.87±0.13 vs. 1.94±0.47, P ＜0.01) and MPO (0.465 ±0.092 vs. 0.832±0.214, P＜0.05),and reduction in plasma DAO activites (0.732±0.192 vs. 1.381 ±0.564, P ＜0.05). The CAR group also showed significantly lowered levels of intestinal NOS, NO, TNF-α and MPO and reduced plasma DAO activites, compared to the GES group. Conclusions Theses results suggest that carbachol significantly inhibits the release of proinflammatory mediator and attenuates local inflammation in gut during enteral fluid resuscitation of rats in rats with bum shock. We postulate that carbachol may exert its and-inflammatory effects via the cholinergic anti-inflammatory pathway.

Effects of puerarin on MDA and MPO in myocardial in earlier period of scalded rats / 中华急诊医学杂志

Objective To observe the effect of puerarin on the level of malondialdehyde (MDA) and myeloperoxidase (MPO) in myocardial in scalded rat.Methods Eighty-eight Wistar rats were randomly divided into the recovery group (group R,n=40),the treatment group (group T,n=40) and the control group (group C,n=8) . The rats in the recovery and the treatment groups were subjected to 30% TBSAⅢdegree scald.Myocardial tissue samples from the group R and group T were harvested at 1,3,6,12,24 postburn hours for the determination of MDA and MPO. The morphological change in the myocardial tissue was observed with transmission electronic microscope.Results (1)In group R,MDA、MPO went up 1 hours after burns,and all attaining the top at 12 hours post burn (P＜0.01).(2)In group T,the indexes above had the same trends as group R.But comparing with group R,MPO and MDA were much lower at 1,3,6,12 hours (P＜0.05 or P＜0.01).(3)Comparing with group R,the altrastructural changes were obviously alleviated at 24 hours in group T.Conclusion The production of MDA,MPO in severely burned rats can be inhibited by puerarin,which was beneficial in the management of myocardial injuries after severe burns.

Two Cases of Cement Burn

Wet cement can cause caustic ulcers due to its alkalinity. Besides caustic ulcers frequently called cement burn, allergic and irritant contact dermatitides are common in cement workers. Alkalinity of calcium hydroxide in wet cement combined with the effect of pressure and occlusion against skin may result in cement burn. We report two cases of cement burn due to their occupational exposures.

The Changes of Serum Myocardial Enzymogram in Bum Patients / 第二军医大学学报

The serum myocardial enzymes and isoenzymes activities were measured in 65 bum patients. The results showed that serum CK, CK-MB, LDH and AST activities, and CK-MB/CK and LDH1/LDH2 ratios were markedly elevated after burn injury. The CK-MB/CK ratio in major bum patients was higher than 0.05 1 -3d and 14d postbum. The results suggest that myocardial cells of serious bum patients are significantly injured in both early period and 14 d postbum.