孕康糖浆治疗黄体功能不全性不孕患者临床观察

目的:观察孕康糖浆治疗黄体功能不全性不孕患者的临床疗效。方法:将84例黄体功能不全性不孕(肾虚型)患者按随机数字表法随机分为对照组和治疗组(n=42)。对照组予氯米芬治疗,治疗组加服孕康糖浆。测量基础体温、血清雌二醇(E2)、孕酮(P),B超观察排卵情况及子宫内膜厚度;进行黄体HPS评分,评价临床疗效。结果:治疗组临床总有效率85.7%,优于对照组;基础体温的高温相持续时间长于对照组;E2、P水平均高于对照组;优势卵泡最大直径、子宫内膜厚度和HPS评分均大于对照组(P<0.05或P<0.01)。结论:孕康糖浆对黄体功能不全性不孕具有肯定疗效,值得推广。     

Acute effects of phenylbutyrate on glutamine,branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Phenylbutyrate (PB) acts as chemical chaperone and histone deacetylase inhibitor, which is used to decrease ammonia in urea cycle disorders and has been investigated for use in the treatment of a number of lethal illnesses. We performed in vivo and in vitro experiments to examine the effects of PB on glutamine (GLN), branched‐chain amino acid (BCAA; valine, leucine and isoleucine) and protein metabolism in rats. In the first study, animals were sacrificed one hour after three injections of PB (300mg/kg b.w.) or saline. In the second study, soleus (SOL, slow twitch) and extensor digitorum longus (EDL, fast twitch) muscles were incubated in a medium with or without PB (5 mM). L‐[1‐¹⁴C] leucine was used to estimate protein synthesis and leucine oxidation, and 3‐methylhistidine release was used to evaluate myofibrillar protein breakdown. PB treatment decreased GLN, BCAA and branched‐chain keto acids (BCKAs) in blood plasma, decreased BCAA and increased GLN concentrations in muscles, and increased GLN synthetase activities in muscles. Addition of PB to incubation medium increased leucine oxidation (55% in EDL, 29% in SOL), decreased BCKA and increased GLN in medium of both muscles, increased GLN in muscles, decreased protein synthesis in SOL and increased proteolysis in EDL. It is concluded that PB decreases BCAA, BCKA and GLN in blood plasma, activates BCAA catabolism and GLN synthesis in muscle and exerts adverse effects on protein metabolism. The results indicate that BCAA and GLN supplementation is needed when PB is used therapeutically and that PB may be a useful prospective agent which could be effective in management of maple syrup urine disease.     

Full-driving soft robotic colonoscope in compliant colon tissue

Robotic colonoscopy is an efficient examination method for finding malignant tumour in its early stage. This research developed a novel robotic endoscope with 13?mm diameter, 105?mm length and 22.3?g weight. A contact biomechanical model is proposed to increase the locomotion safety and efficiency in the soft tissue. The model shows that the friction difference between the robot and the tissue is a key factor to locomotion capability. A soft, full bellow with excellent compatibility was designed to package the robot body. The bellow increased the static friction and decreased the kinetic friction given the change in the contact state. The bellow is divided into three segments. Each segment is composed of a linear locomotor with micromotor, turbine-worm and wire wrapping–sliding mechanism. The robot is tested in in vivo pig colon, which revealed an excellent locomotion capability and safety in soft tissues.     

Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake

The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonyl–CoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl–CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl–CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl–CoA hypothesis.     

Earthworm biomarker responses on exposure to commercial cypermethrin

Cypermethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, disease vector control, and food safety. It accumulates in soil. Therefore, traces of cypermethrin may frequently appear in vegetables grown in contaminated soil. There is a push now to develop biomarkers as early warning indicators of environmental pollution. In this study, DNA damage (tail DNA%, tail length, and olive tail moment), the micronucleus, neutral red retention (NRR) time, and pinocytic adherence ability of coelomocytes were investigated in Pheretima peguana earthworms exposed to cypermethrin in filter paper tests. The NRR time of earthworm coelomocytes decreased significantly at a concentration of 3.5 × 10^?3 µg · cm^?2 (1/100 LC₅₀) after 48 h exposure, with a highly negative correlation with cypermethrin concentration. Pinocytic adherence ability of coelomocytes also declined significantly at a cypermethrin concentration of 3.5 × 10^?2 µg · cm^?2 (1/10 LC₅₀). The DNA damage to earthworm coelomocytes (tail DNA%, tail length, and olive tail moment) increased considerably at the highest concentration (3.5 × 10^?1 µg · cm^?2) although the correlation between tail DNA% and cypermethrin concentration was low. Thus, physiological biomarkers were more sensitive than the genotoxic effects in earthworms exposed to commercial cypermethrin. Although a suite of earthworm biomarkers could be used to evaluate cypermethrin terrestrial pollution, the NRR test is easier to conduct and a more sensitive indicator. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 597–606, 2015.     

Successful living domino liver transplantation in a child with protein C deficiency

PC is produced in the liver and inhibits blood coagulation by catalyzing active factors V and VIII. PC deficiency causes abnormal blood clotting that is difficult to regulate by anticoagulative treatments. Four reports of PC deficiency treated with LTx have been published; however, no report of DLT as a therapy for PC deficiency is available. We describe a case of a 23‐month‐old girl who received DLT for compound heterozygous PC deficiency. Her PC activity was below 5%. She developed intracranial lesion and frequent refractory purpura fulminans. Both her parents had heterozygous mutations of PC genes and were excluded as living donors. Furthermore, she was a low priority on the waiting list of deceased‐donor transplantation. We performed living DLT using the liver from a patient with MSUD. Activated PC concentrate safely supported the perioperative period. After DLT, she maintained normal PC activities and BCAA levels. This is the first case of PC deficiency successfully treated by living DLT with MSUD. We propose that DLT using liver from patients with MSUD is a treatment option for PC deficiency.     

The Effect of a Low Fructose and Low Glycemic Index/Load (FRAGILE) Dietary Intervention on Indices of Liver Function,Cardiometabolic Risk Factors,and Body Composition in Children and Adolescents With Nonalcoholic Fatty Liver Disease (NAFLD)

Background: Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in obese children. Diets high in added fructose (high fructose corn syrup; HFCS) and glycemic index (GI)/glycemic load (GL) are associated with increased risk of NAFLD. Lifestyle modification is the main treatment, but no guidelines regarding specific dietary interventions for childhood NAFLD exist. We hypothesized that reductions in dietary fructose (total, free, and HFCS)/GI/GL over 6 months would result in improvements in body composition and markers of liver dysfunction and cardiometabolic risk in childhood NAFLD. Methods: Children and adolescents with NAFLD (n = 12) and healthy controls (n = 14) 7–18 years were studied at baseline and 3 and 6 months post–dietary intervention. Plasma markers of liver dysfunction (ALT, AST, γGT), cardiometabolic risk (TG, total cholesterol, LDL‐HDL cholesterol, Apo‐B100, Apo‐B48, Apo‐CIII, insulin, homeostasis model of assessment of insulin resistance [HOMA‐IR]), inflammation (TNF‐α, IL‐6, IL‐10), anthropometric, and blood pressure (BP) were studied using validated methodologies. Results: Significant reductions in systolic BP (SBP), percentage body fat (BF), and plasma concentrations of ALT (P = .04), Apo‐B100 (P < .001), and HOMA‐IR were observed in children with NAFLD at 3 and 6 months (P < .05). Dietary reductions in total/free fructose/HFCS and GL were related to reductions in SBP (P = .01), ALT (P = .004), HOMA‐IR (P = .03), and percentage BF in children with NAFLD. Reductions in dietary GI were associated with reduced plasma Apo‐B100 (P = .02) in both groups. With the exception of Apo‐B100, no changes in laboratory variables were observed in the control group. Conclusion: Modest reductions in fructose (total/free, HFCS) and GI/GL intake result in improvements of plasma markers of liver dysfunction and cardiometabolic risk in childhood NAFLD.     

Randomised comparative trial of the efficacy of paracetamol syrup and dispersible tablets for the treatment of fever in children

ObjectiveFever is the most common reason for the presentation of children in the outpatient department. Paracetamol is marketed in different formulations for ease of administration to the paediatric population. These include syrups, dispersible tablets and rectal inserts. Dispersible tablets disintegrate rapidly in liquid and are subsequently taken orally, providing another oral formulation. We determined if there is a difference in the antipyretic efficacy of the syrup and the dispersible formulation of paracetamol, thereby prompting the development of the latter (another oral formulation) for use in children.MethodsA randomised, controlled, double-blind intervention of a single dose of both formulations was given to febrile children, and their temperatures were documented twice in 30-minute intervals. Temperature changes were compared statistically.ResultsThe mean temperatures at recruitment were 38.2 ± 0.5°C and 38.3 ± 0.6°C for the dispersible and syrup group, respectively. There was no significant difference between the temperature changes at T2 (30 minutes) and T3 (60 minutes) between the two study arms. However, the temperature was significantly different at T1 (baseline), T2 and T3 within the dispersible and syrup groups.ConclusionThe decreasing trend in temperature was similar in both groups. Both preparations produced statistically similar antipyretic effects with no reported adverse drug reaction.     

Immobilization of amyloglucosidase onto macroporous cryogels for continuous glucose production from starch

Poly(methyl methacrylate-glycidyl methacrylate) [Poly(MMA-GMA)] cryogels were synthesized using monomers of methylmethacrylic acid and epoxy group bearing GMA via radical cryopolymerization technique. Synthesized cryogels were used for the immobilization of amyloglucosidase to the cryogel surface using epoxy chemistry. Characterizations of the free and immobilized amyloglucosidase were carried out by comparing the optimum and kinetic parameters of enzymes. For this, pH and temperature profiles of free and immobilized preparation were studied and, it was found that, optimum pH of enzyme was not change upon immobilization (pH 5.0), while optimum temperature of the enzyme shifted 10 °C to warmer region after immobilization (optimum temperatures for free and immobilized enzyme were 55 and 65 °C, respectively). Kinetic parameters of free and immobilized enzyme were also investigated and K_m values of free and immobilized amyloglucosidase were found to be 2.743 and 0.865 mg/mL, respectively. V_max of immobilized amyloglucosidase was found to be (0.496 µmol/min) about four times less than that of free enzyme (2.020 µmol/min). Storage and operational stabilities of immobilized amyloglucosidase were also studied and it was showed that immobilized preparation had much more stability than free preparation. In the present work, amyloglucosidase immobilized poly(MMA-GMA) cryogels were used for continuous glucose syrup production from starch for the first time. Efficiency of immobilized enzyme was investigated and released amount of glucose was found to be 2.54 mg/mL at the end of the 5 min of hydrolysis. The results indicate that the epoxy functionalized cryogels offer a good alternative for amyloglucosidase immobilization applications with increased operational and thermal stability, and reusability. Also, these cryogels can be used for immobilization of other industrially valuable enzymes beyond amyloglucosidase.     

A Novel Regulatory Defect in the Branched‐Chain α‐Keto Acid Dehydrogenase Complex Due to a Mutation in the PPM1K Gene Causes a Mild Variant Phenotype of Maple Syrup Urine Disease

This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched‐chain α‐keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease‐causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array‐based genotyping showed a copy‐neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild‐type PPM1K in PP2Cm‐deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm‐deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress‐signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype—and perhaps others.