Influence of combined intravenous and oral glucose administration on splanchnic glucose uptake in man

Summary. The influence of intravenous plus oral glucose administration on splanchnic glucose handling was examined in healthy young individuals by combining the hepatic vein catheterization technique with the double glucose tracer method. After 1 h of steady state hyperglycaemia (11·7 Itim ) induced by intravenous glucose alone (hyperglycaemic clamp technique), subjects ingested 89 ± 1 g of glucose, and the hyper-glycaemic plateau was maintained for the subsequent 4 h by adjusting the exogenous glucose infusion rate. Over the 4-h absorptive period, only 51 ± 4 g of oral glucose (i.e. 58 ±4% of the ingested load) appeared in the systemic circulation, while 193 ± 15 g (1·072±0·083 mol) of glucose had to be infused exogenously to sustain the hyperglycaemia. Endogenous glucose production was suppressed by over 60%. Net splanchnic glucose balance switched from a positive value (i.e. net uptake) of 506 ± 2–56 uniol min^-1kg^-1with intravenous glucose alone (0·60 min) to a negative one (i.e. net output) of 12·50 ± 2·44 u. mol min^-1kg^-1during 4 h (60–300 min) of intravenous+oral glucose. The mean rate of splanchnic glucose uptake was estimated to be 6·39 ±4·67 ixmol min^-1kg^-1with intravenous glucose alone, and 8·83 ±4·28 u. mol min^-1kg^-1with intravenous+oral glucose. In either case, the large majority (80–90%) of the glucose appearing in the systemic circulation was disposed of by extrasplanchnic tissues. These results indicate that pre-existing hyperglycaemia and/or hyperinsulinaemia inhibit gastrointestinal glucose absorption, and that oral glucose administration does not result in a major redistribution of intravenous glucose between splanchnic and extrasplanchnic tissues.     

The roles of P-glycoprotein and intracellular metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac

Methadone is used as a treatment for opiate detoxification in methadone maintenance programs. Intra- and inter-patient variations in methadone bioavailability have been observed after oral methadone treatment and this makes it difficult to predict a dosing regimen. Intestinal absorption and metabolism could explain these variations. The in vitro gut sac model was used to study the intestinal absorption of methadone, and it confirmed that methadone is a substrate for P-glycoprotein. The transport of methadone was increased in presence of P-gp inhibitors verapamil and quinidine. The appearance of a major metabolite of methadone, 2-ethylidene-1, 5-dimethyl-3, 3-diphenyl pyrrolidine (EDDP) in the gut sac contents also demonstrated the existence of intestinal metabolism of methadone.     

Congenital intestinal malrotation with gastric wall defects causing extensive gut necrosis and short gut syndrome: A case report

BACKGROUNDCongenital intestinal malrotation (CIM) is a common malformation in neonates. Early diagnosis and surgical intervention can improve the prognosis. CIM combined with congenital gastric wall defect is a potentially fatal condition. We present a severe case of CIM with gastric wall defect causing extensive gut necrosis and short gut syndrome. After three operations, the neonate survived and subsequently showed normal growth and development during infancy.CASE SUMMARYA male neonate (age: 4 d) was hospitalized due to bloody stools and vomiting for 2 d, and abdominal distention for 1 d. Emergent exploratory laparotomy revealed black purplish discoloration of the bowel loops. Bowel alignment was abnormal with congestion and dilatation of the entire intestine, and clockwise mesentery volvulus (720°). The posterior wall of the gastric body near the greater curvature showed a defect in the muscularis layer (approximately 5.5 cm), and a circular perforation (approximately 3 cm diameter) at the center of this defect. Ladd’s procedure was performed and gastric wall defect was repaired. Third operation performed 53 d after birth revealed extensive adherence of small intestine and peritoneum, and adhesion angulated between many small intestinal loops. We performed intestinal adhesiolysis, resection of necrotic intestine, and small bowel anastomosis. CONCLUSIONThis case highlights that prolonged medical treatment may help improve intestinal salvage after surgical removal of necrotic intestines, and improve patient prognosis.     

Antidiabetic and antihyperlipidemic activity of p-coumaric acid in diabetic rats,role of pancreatic GLUT 2: In vivo approach

P-coumaric acid (p-CA, 3-[4-hydroxyphenyl]-2-propenoic acid), the major component widely found in nutritious plant foods, has various antioxidant, antiinflammatory and anticancer property. To evaluate the antidiabetic and antihyperlipidemic mechanisms, via the effects on carbohydrate, lipids and lipoproteins responses in adult male albino Wistar rats were examined by treated with p-CA. Rats were injected with streptozotocin (STZ, 40 mg/kg b.w.) by intraperitonially (i.p.) 30 days for the induction of experimental diabetes mellitus. Diabetic rats were treated with p-CA orally at a dose of 100 mg/kg b.w. The potential defending character of p-CA against diabetic rats was evaluated by performing the various biochemical parameters and glucose transporter such as GLUT2 mRNA expression of pancreas. Administration of p-CA significantly lowers the blood glucose level, gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase whereas increases the activities of hexokinase, glucose-6 phosphatase dehydrogenase and GSH via by increasing level of insulin. p-CA reduces the total cholesterol and triglycerides in both plasma and tissues i.e. liver and kidney. p-CA also decreases the LDL-C, VLDL-C and it considerably increase the level of HDL-C. A significant decreased expression of GLUT 2 mRNA in the pancreas was recorded in the supplementation of p-CA treated groups. Taken together, these results suggest that p-CA modulates glucose and lipid metabolism via GLUT 2 activation in the pancreatic and has potentially beneficial effects in improving or treating metabolic disorders.     

Transcatheter arterial infusion chemotherapy and embolization for primary lacrimal sac squamous cell carcinoma: A case report

BACKGROUNDAlthough tumors of the lacrimal sac are rare, they represent a potentially life-threatening situation that can easily be overlooked since patients present with features consistent with chronic dacryocystitis. Lacrimal sac squamous cell carcinoma is the most common lacrimal sac malignancy, but no definitive treatment is currently available. CASE SUMMARYWe describe a 34-year-old unmarried male who presented with a red and swollen right lower eyelid, which gradually developed into a mass of the lower eyelid that obstructed vision in his right eye. He was treated with transcatheter arterial infusion chemotherapy and interventional embolization based on the tumor characteristics, and we also administered intensity-modulated radiotherapy and targeted therapy after tumor shrinkage. The tumor treatment demonstrated good efficacy, and the patient’s condition was stable after 10 mo of follow-up.CONCLUSIONTo our knowledge, this is the first report of lacrimal sac squamous cell carcinoma treated with transcatheter arterial infusion chemotherapy and interventional embolization, which might expand clinical treatment options for lacrimal sac carcinoma.     

Bcl-2的表达及其与急性白血病化疗效果关系的Meta分析

目的系统评价国内有关Bcl-2在急性白血病不同病理状态中的表达及其与化疗效果的关系。方法计算机检索CBMdisc、中文科技期刊全文数据库、万方数据库、中国期刊网专题全文数据库、中国优秀硕士学位论文全文数据库、中国博士学位论文全文数据库,并辅以文献追溯的方法,收集国内公开发表的所有相关病例对照、队列研究。检索年限均为从建库至2010年5月23日。按纳入排除标准筛选文献并评价纳入研究的质量后,采用RevMan 5.0软件进行Meta分析。结果共纳入10个研究,合计545例患者。Meta分析结果显示:Bcl-2阳性的急性白血病患者化疗后完全缓解率低于Bcl-2阴性患者,其差异有统计学意义[OR=0.26,95%CI(0.14,0.46),P<0.0001];急性淋巴细胞白血病与急性非淋巴细胞白血病患者Bcl-2阳性率差异无统计学意义[OR=0.87,95%CI(0.46,1.65),P=0.68];急性白血病患者化疗后完全缓解(CR)患者Bcl-2阳性率明显低于部分缓解者/完全不缓解者,其差异有统计学意义[SMD=–0.87,95%CI(–1.53,–0.20),P=0.01]。结论现有国内证据表明,Bcl-2表达与急性白血病患者缓解率呈显著负相关关系,Bcl-2基因的表达水平可用于急性白血病患者化疗效果考核和预后评价研究。但该结论需要更多高质量的研究进一步证实。     

睾丸内胚窦瘤二例报告及文献复习

目的提高睾丸内胚窦瘤的诊治水平。方法对2010年8月和2011年9月分别收治的2例睾丸内胚窦瘤诊治资料进行分析并结合文献复习。结果 2例均行患侧睾丸肿瘤根治性切除术,术后分别随访3个月和1年,无局部复发及处转移。结论甲胎蛋白结合影像学检查可提高睾丸内胚窦瘤的诊断率;根治术结合放射治疗、化学治疗能提高治愈率;甲胎蛋白可作为观察疗效的指标。     

Hypomagnesaemia and risk for metabolic glucose disorders: a 10-year follow-up study

Background Although several lines of evidence suggest that hypomagnesaemia is a risk factor for developing type 2 diabetes, there are no studies regarding the association between hypomagnesaemia and the risk for developing impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Our objective was to examine the association between serum magnesium levels and the risk for developing IFG, IGT and type 2 diabetes. Materials and methods A total of 1122 individuals (20–65 years of age) were enrolled between 1996 and 1997, and 817 individuals re‐examined about 10 years later. New‐onset IFG (5·6–7·0 mmol L^?1 fasting glucose), IGT (7·8–11·1 mmol L^?1 glucose 2‐h postload), and type 2 diabetes were determined from the number of subjects who had these conditions at the second examination without evidence that they were present at the first one. The relative risk of new‐onset metabolic glucose disorders and diabetes (dependent variables) was computed using Poisson regression model adjusted for age, sex, family history of diabetes, waist circumference and homeostasis model assessment for insulin resistance index. Serum magnesium levels of < 0·74 mmol L^?1 (independent variable) defined the exposed group. Results At baseline, 420 (51·4%) individuals had hypomagnesaemia. New‐onset IFG and IGT was identified in 276 (33·8%) individuals. The relative risk for IFG, IGT and IFG + IGT was 1·11 (95% confidence interval, 0·5–5·1), 1·38 (95% confidence interval, 1·1–6·3) and 1·49 (95% confidence interval, 1·1–4·9), respectively. New‐onset diabetes was identified in 78 (9·5%) individuals (relative risk 2·54; 95% confidence interval, 1·1–4·1). Conclusions Hypomagnesaemia is independently associated with the development of IGT, IFG + IGT and type 2 diabetes, but not with the development of IFG.     

Nigella sativa improves glucose homeostasis and serum lipids in type 2 diabetes: A systematic review and meta-analysis

Background & objective(s)Global prevalence of type 2 diabetes (T2D) is very high and is currently growing alarmingly. With respect to recent researchers' attention to the potential role of herbal medicine in disease prevention and management, the present meta-analysis review investigates the effectiveness of Nigella sativa (N. sativa), a popular herb, in T2D.MethodsLiterature search was conducted covering PubMed/Medline, Scopus, and Cochrane Registry of Clinical Trials up to February 2017 to obtain the relevant published intervention studies. Study selection, quality rating and data extraction of studies were investigated by two independent reviewers. Heterogeneity was assessed using I-squared (I²) statistics test. Subgroup analysis was done to assess type of N. sativa supplement as source of heterogeneity. Effect sizes of eligible studies were pooled using STATA software version 12 (STATA corp, College Station, TX, USA).ResultsSeven trials were included in the meta-analysis of glycemic and serum lipid profile end points. Supplementation with N. sativa significantly improved fasting blood sugar (FBS) [−17.84 mg/dl, 95% CI: −21.19 to −14.49, p < 0.001], HbA1c [−0.71%, 95% CI: −1.04 to −0.39, p < 0.001], total-cholesterol (TC) [WMD: −22.99 mg/dl, 95% CI: −32.16 to −13.83, p < 0.001] and LDL-cholesterol (LDL-c) [−22.38 mg/dl, 95% CI: −33.60 to −11.15, p < 0.001]. The overall effects for triglyceride (TG) [−6.80 mg/dl, 95% CI: −33.59 to 19.99, p = 0.61] and HDL-cholesterol (HDL-c) [0.37 mg/dl, 95% CI: −1.59 to 2.33, p = 0.71] were insignificant. Subgroup analysis revealed significant reduction on TG with N. sativa seed oil [−14.8 mg/dl, 95% CI: −23.1 to −6.5, p < 0.001], while TG was increased with seed powder [29.4 mg/dl, 95% CI: 16.9–42.0, p < 0.001]. All measures, but HbA1c, showed no evidence of publication bias.ConclusionAlthough, the meta-analysis conducted included a few number of studies, but has shown promising results on the effectiveness of N. sativa on glucose homeostasis and serum lipids. Current findings suggest N. sativa supplementation a suitable choice in managing the complications of T2D, although future researches are necessary.     

Thermal Characteristics of Neutralization Therapy and Water Dilution for Strong Acid Ingestion: An In-vivo Canine Model

Objective: To determine whether in-vivo neutralization therapy for acid ingestions will superimpose a thermal injury upon tissue already damaged by acid.
Methods: An in-vivo canine model was used with repeated measures of tissue and luminal temperatures. All dogs were placed under halothane general anesthesia. The stomach was exteriorized and temperature probes were placed in the lumen and mucosa. 25 mL of 0.5 N HC1 (25°C) was placed in the gastric lumen followed 5 minutes later by 75 mL of either 8% NaHCO, neutralization (25°C. n = 10) or water dilution (25°C, n = 10). Temperature measurements were recorded at specified intervals for 5 minutes post HCl acid exposure and for 30 minutes post treatment. Temperature profiles were analyzed by repeated-measures ANOVA. Post treatment changes were evaluated using signed-rank tests.
Results: In both treatment groups, treatment resulted in significant decreases in initial mucosa and intraluminal temperatures. Both the mucosa and intraluminal temperatures decreased immediately after treatment with HCO, by an average of 1.6°C (p = 0.05). In the water dilution treatment group, both temperatures decreased by 1.1°C (p = 0.05). Ensuing post-treatment temperatures increased but did not reach baseline temperatures at any time up to 30 minutes post treatment.
Conclusions: In the in-vivo setting, there is no evidence of hazardous temperature elevation when a weak alkali or dilution therapy is used to neutralize strong acid-induced injury. Contraindication of this form of emergency treatment should not be based on the preconceived idea that a resultant exothermic reaction will cause a superimposed thermal injury. Further clinical study is needed to determine the clinical utility of this emergency therapeutic modality.     

COX-2基因多态性与食管癌易感性关系的Meta分析

目的探讨COX-2基因多态性与食管癌易感性的关系。方法计算机检索PubMed和EMbase数据库,检索时间截至2011年1月1日,获取COX-2基因多态性与食管癌易感性关系的病例-对照研究。以食管癌组与对照组人群基因型分布的OR值及其95%CI为效应指标,在纯合子模型、显性模型和隐性模型中采用固定或随机效应模型进行Meta分析,并进行发表偏倚评估。统计分析采用Stata 11.0软件。结果共纳入5个病例-对照研究。Meta分析结果显示:在COX-2-765G>C多态性位点,显性模型中,与野生基因型GG相比,CC+GC合并的OR值(95%CI)为1.806(1.050,3.106),其余为阴性结果。在COX-2-1195G>A多态性位点中,纯合子模型、显性模型及隐性模型均为阳性结果。结论 COX-2基因多态性与食管癌易感性可能相关。     

不同膳食方案对2型糖尿病患者肠道菌群丰度及血糖的影响研究

目的探讨不同膳食方案对2型糖尿病患者肠道菌群丰度及血糖的影响。方法招募40名2型糖尿病志愿者为研究对象,在刚入组而未经任何干预阶段定义为1期,膳食纤维素干预阶段定义为2期,膳食纤维素联合蛋白质膳食干预定义为3期。在不同干预时段末,对患者的血清白蛋白、血糖、胰岛素、C肽、糖化血红蛋白水平进行重复检测,并检测肠道菌群丰度。结果(1)1~3期患者白蛋白水平分别为(42.3±3.2)g/L、(41.6±2.5)g/L、(47.2±2.8)g/L,白蛋白水平始终在正常范围内。与3期时相比,患者在1期、2期时的白蛋白水平明显较低(P<0.05)。(2)在1期及2期时,患者空腹血糖无明显差异(P>0.05),在3期时空腹血糖明显降低(P<0.05)。与1期时相比,餐后0.5h、1h、2h、3h血糖在2期及3期时均显著降低(P<0.05)。(3)患者在1期、2期、3期时的空腹及0.5h、1h、2h、3h时的胰岛素水平均无明显改善(P>0.05)。(4)与1期相比,2期时患者的0.5h、1h、2h、3hC肽水平即明显下降(P<0.05);3期时空腹1h、2h的C肽水平又出现上升(P<0.05)。(5)PCA主成分分析发现,患者在1期、2期、3期的肠道菌群结构存在显著差异,分别趋于不同的方向。患者在1期时,肠道菌群中丰度较高的菌属包括罗氏菌属、双歧杆菌属、软酸杆菌属、萨特菌属、假单胞菌属、脆弱拟杆菌属。2期时丰度较高的菌属包括副类杆菌属、表皮葡萄球菌属、链球菌属、厌氧梭状杆菌属、巨单胞菌属。3期时丰度较高的菌属包括罗斯菌属、巨单胞菌属、萨特菌属。结论膳食纤维可改善2型糖尿病患者血糖浓度,提高有益菌丰度;蛋白饮食可改善血糖水平,但会加重胰岛素抵抗。     

乳腺癌组织中COX-2表达及临床意义的Meta分析

目的系统评价国内有关乳腺癌组织中COX-2表达及临床意义的研究。方法计算机检索CBM、CNKI、VIP和万方数据库,并辅以文献追溯的方法,收集公开发表的所有关于乳腺癌组织中COX-2表达及其与临床病理特征关系的病例对照研究。检索年限均为从建库至2010年7月25日。按纳入排除标准筛选文献并评价纳入研究质量后,应用RevMan 4.2.10软件进行Meta分析。结果共纳入8个病例对照研究,其中乳腺癌500例,正常乳腺153例。Meta分析结果显示:COX-2在乳腺癌组与正常乳腺对照组[OR=16.36,95%CI(9.18,29.15)]、乳腺癌高分化组与中低分化组[OR=0.34,95%CI(0.18,0.63)]的表达差异均有统计学意义;COX-2在乳腺癌淋巴结转移组与非淋巴结转移组[OR=1.36,95%CI(0.61,3.03)]、临床Ⅰ～Ⅱ期组与临床Ⅲ～Ⅳ期组[OR=0.61,95%CI(0.34,1.10)]的表达差异则无统计学意义。结论目前国内证据证明,COX-2可能参与了乳腺癌发生、发展的全过程,但尚不能作为判定乳腺癌预后的独立因素,有待于进一步深入探讨。     

Etifoxine analgesia in experimental monoarthritis: A combined action that protects spinal inhibition and limits central inflammatory processes

Inflammatory and degenerative diseases of the joint are major causes of chronic pain. Long-lasting pain symptoms are thought to result from a central sensitization of nociceptive circuits. These processes include activation of microglia and spinal disinhibition. Using a monoarthritic rat model of pain, we tried to potentiate neural inhibition by using etifoxine (EFX), a nonbenzodiazepine anxiolytic that acts as an allosteric-positive modulator of gamma-aminobutyric acid type A (GABAA) receptor function. Interestingly, EFX also can bind to the mitochondrial translocator protein (TSPO) complex and stimulate the synthesis of 3α-reduced neurosteroids, the most potent positive allosteric modulator of GABAA receptor function. Here we show that a curative and a preventive treatment with 50 mg/kg of EFX efficiently reduced neuropathic pain symptoms. In the spinal cord, EFX analgesia was accompanied by a reduction in microglial activation and in the levels of proinflammatory mediators. Using electrophysiological tools, we found that EFX treatment not only amplified spinal GABAergic inhibition, but also prevented prostaglandin E2–induced glycinergic disinhibition and restored a “normal” spinal pain processing. Because EFX is already distributed in several countries under the trade name of Stresam for its anxiolytic actions in humans, new clinical trials are now required to further extend its therapeutic indications as pain killer.