Bariatric surgery in severely obese adolescents improves major comorbidities including hyperuricemia

Objective

Serum uric acid (sUA) is believed to contribute to the pathogenesis of metabolic comorbidities like hypertension, insulin-resistance (IR) and endothelial dysfunction (EDF) in obese children. The present pilot study investigated the association between sUA concentrations and loss of body weight following laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y-gastric bypass (RYGB) in severely obese adolescents.

Materials/Methods

10 severely obese adolescents underwent either LSG (n = 5) or RYGB (n = 5). 17 normal weight, healthy, age- and gender-matched adolescents served as a normal weight peer group (NWPG). Pre- and 12 months postoperatively, sUA and relevant metabolic parameters (glucose homeostasis, transaminases, lipids) were compared.

Results

Preoperatively, sUA was significantly elevated in patients with severe obesity compared to NWPG. Twelve months after LSG and RYGB, a significant decrease in sUA, BMI, CVD risk factors, hepatic transaminases, and HOMA-IR was observed. Reduction in SDS-BMI significantly correlated with changes in sUA.

Conclusions

sUA levels and metabolic comorbidities improved following bariatric surgery in severely obese adolescents. The impact of changes in sUA on long-term clinical complications of childhood obesity deserves further study.     

The future of pharmacological treatment in idiopathic pulmonary fibrosis

The therapeutic approach in idiopathic pulmonary fibrosis has changed substantially over the past 5 years. National and international guidelines for the pharmacological treatment of IPF recommend 2 antifibrotic drugs, nintedanib and pirfenidone. The use of both these drugs is supported by high-level evidence, with benefits including not only slower disease progression but also a reduction in the annual risk of death. Currently, the therapeutic management of these patients prioritizes both the use of drugs that act on the pathogenic mechanisms of the disease, and the positive effect of improving quality of life with integrated multidisciplinary support, including nutrition, physical activity, education, emotional support, and palliation of symptoms. The overall aim is to ensure that the patient remains as well as possible for as long as possible after diagnosis. However, the goal of the new antifibrotic combinations that are currently under evaluation in clinical trials is to use the potential antifibrotic synergy to enhance the therapeutic benefit or completely halt disease progression, by acting simultaneously on different pathogenic pathways. Another line of investigation involves markers that might be useful for identifying patients who may benefit more from certain antifibrotics than from others, which would make it possible to optimize resources and take the first steps toward precision medicine in pulmonary fibrosis. Below, we review the main potential areas for improvement in the pharmacological treatment of idiopathic pulmonary fibrosis in the short, medium, and long term.     

Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin resistance in type 2 diabetic patients

Objectives

To evaluate the effects of vildagliptin compared to glimepiride on glycemic control, insulin resistance and post-prandial lipemia.

Material and Methods

167 type 2 diabetic patients, not adequately controlled by metformin, were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day for 6 months, in a double blind, randomized clinical trial. We evaluated: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma proinsulin (FPPr), glucagon, lipid profile, resistin, retinol binding protein-4 (RBP-4), visfatin and vaspin. Furthermore, at the randomization and at the end of the study all patients underwent an euglycemic hyperinsulinemic clamp to evaluate M value and an oral fat load.

Results

Despite a similar decrease of glycated hemoglobin, there were an increase of body weight with glimepiride + metformin and a decrease with vildagliptin + metformin. Fasting plasma insulin increased with glimepiride + metformin, while it did not change with vildagliptin + metformin. Vildagliptin + metformin improved lipid profile. Regarding insulin sensitivity, vildagliptin + metformin increased M value. Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant. Vildagliptin + metformin reduced post-prandial lipemia and insulinemia compared to glimepiride + metformin.

Conclusion

Vildagliptin, in addition to metformin, was more effective than glimepiride + metformin in reducing insulin resistance and post-prandial lipemia.     

Cortical edema in moderate fluid percussion brain injury is attenuated by vagus nerve stimulation

Development of cerebral edema (intracellular and/or extracellular water accumulation) following traumatic brain injury contributes to mortality and morbidity that accompanies brain injury. Chronic intermittent vagus nerve stimulation (VNS) initiated at either 2 h or 24 h (VNS: 30 s train of 0.5 mA, 20 Hz, biphasic pulses every 30 min) following traumatic brain injury enhances recovery of motor and cognitive function in rats in the weeks following brain injury; however, the mechanisms of facilitated recovery are unknown. The present study examines the effects of VNS on development of acute cerebral edema following unilateral fluid percussion brain injury (FPI) in rats, concomitant with assessment of their behavioral recovery. Two hours following FPI, VNS was initiated. Behavioral testing, using both beam walk and locomotor placing tasks, was conducted at 1 and 2 days following FPI. Edema was measured 48 h post-FPI by the customary method of region-specific brain weights before and after complete dehydration. Results of this study replicated that VNS initiated at 2 h after FPI: 1) effectively facilitated the recovery of vestibulomotor function at 2 days after FPI assessed by beam walk performance (P<0.01); and 2) tended to improve locomotor placing performance at the same time point (P=0.18). Most interestingly, results of this study showed that development of edema within the cerebral cortex ipsilateral to FPI was significantly attenuated at 48 h in FPI rats receiving VNS compared with non-VNS FPI rats (P<0.04). Finally, a correlation analysis between beam walk performance and cerebral edema following FPI revealed a significant inverse correlation between behavior performance and cerebral edema. Together, these results suggest that VNS facilitation of motor recovery following experimental brain injury in rats is associated with VNS-mediated attenuation of cerebral edema.     

NIDDM患者红细胞膜流动性改变与血浆胰岛素和糖化血红蛋白水平的关系

本文观察３６５例非胰岛毒依赖型糖尿病（ＮＩＤＤＭ）人红细胞膜流动性，并探讨了膜流性与空腹血浆胰岛素（ＦＰＩ）、空腹血糖（ＦＢＧ）和糖化血红蛋白（ＨｂＡ１ｃ）水平的关系．结果表明：ＮＩＤＤＭ患者红细胞膜微粘度明显高于同年龄正常对照组，提示其红细胞膜流动性降低。并且患者膜微粘度与ＦＢＧ浓度和ＨｂＡ崐１ｃ水平呈明显正相关，而与ＦＰＩ浓度呈明显负相关，上述结果说明ＮＩＤＤＭ患者红细胞膜流动性改变与病情控制有关。     

Further evaluation of antihyperglycaemic activity of Hunteria umbellata (K. Schum) Hallier f. seed extract in experimental diabetes

Ethnopharmacological relevance

In African traditional medicine, water decoction made from the dry seeds of Hunteria umbellata (K. Schum) Hallier f. is highly valued in the management of diabetes mellitus.

Aim

In the present study, the antihyperglycaemic activity of the seed aqueous extract of Hunteria umbellate (K. Schum) Hallier f. (HU) was investigated in alloxan-induced, high fructose- and dexamethasone-induced hyperglycaemic rats.

Materials and methods

Alloxan-induced, dexamethasone-induced and high fructose-induced hyperglycaemic rats were treated with single, daily oral administration of 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in Groups III, IV, V and VI, for 14 days, 21 days and 8 weeks, respectively. The effects of these drugs on FBG, free plasma insulin levels, HbA_1c, serum TG and TC, and insulin resistance indices were investigated.

Results

Data generated in the current study showed that glibenclamide and graded oral doses of HU caused significant dose related (p < 0.05, <0.01 and <0.001) reductions in FBG when compared to the values obtained for the model control (Group II) rats. Similarly, daily oral administration of 66.7 g/kg fructose to rats for 8 weeks was associated with significant (p < 0.001) hyperglycaemia, elevations in plasma HbA_1c, free insulin, fasting insulin resistance indices, serum TG, and cholesterol. However, concomitant oral treatments with 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg, and 200 mg/kg of HU extract significantly and dose dependently (p < 0.05, <0.01 and <0.001) attenuated development of hyperglycaemia, decreased levels of plasma HbA_1c, free insulin, and serum triglyceride and cholesterol, in the Groups III, IV, V and VI rats, respectively, when compared to fructose-induced hyperglycaemic (Group II) rats. Similar effect was also recorded in the dexamethasone-induced hyperglycaemic rats.

Conclusion

Results of this study suggest that the hypoglycaemic and antihyperlipidaemic effects of HU are mediated via enhanced peripheral glucose uptake and improvements in hyperinsulinaemia.     

Gastric dysmotility in healthy first-degree relatives of patients with schizophrenia

Gastric dysmotility has been reported in patients suffering from major depression or schizophrenia. An increased sympathetic activity modulating the gastric pacemaker located in the antrum of the stomach has been suggested as the underlying pathology. Similar to patients suffering from schizophrenia, their first-degree relatives showed alterations in cardiac autonomic modulation. Here we aimed to investigate gastric myoelectrical activity in healthy relatives of patients suffering from paranoid schizophrenia.     

大鼠脑损伤对移植人胚神经干细胞存活和分化的影响

目的 探讨大鼠脑液压冲击伤(FPI)后对植入的人胚神经干细胞(HNSCs)存活和分化的影响。方法 取8周龄人胎儿大脑皮层细胞，体外培养获得神经干细胞(NSCs)，巢蛋白免疫荧光染色；SD大鼠制作FPI模型．于伤后24h在损伤区移植标有5-溴脱氧脲嘧啶(BrdU)的HNSCs，1周和4周后处死大鼠，邻片行BrdU／微管相关蛋白-2(MAP-2)和BrdU胶质纤维酸性蛋白(GFAP)免疫组织化学双染。结果 HNSCs移植后1周可见BrdU阳性细胞向周围迁移，且BrdU／MAP-2双阳性细胞多于BrdU GFAP双阳性细胞；移植后4周BrdU阳性细胞迁移的范围更广，但细胞数量明显减少，脉络丛和微血管中可见BrdU阳性细胞．BrdU／GFAP双阳性细胞多于BrdU／MAP-2双阳性细胞。结论 HNSCs能存活于损伤区域，移植后逐渐分化为星形胶质细胞．且易被内皮吞噬细胞吞噬。     

A pyrazole curcumin derivative restores membrane homeostasis disrupted after brain trauma

We have assessed potential mechanisms associated with the deleterious effects of TBI on the integrity of plasma membranes in the hippocampus, together with consequences for behavioral function. In addition, we have investigated the efficacy of a dietary intervention based on a pyrazole curcumin derivative with demonstrated bioactivity and brain absorption, to re-establish membrane integrity. We report that moderate fluid percussion injury (FPI) increases levels of 4-Hydroxynonenal (HNE), an intermediary for the harmful effects of lipid peroxidation on neurons. A more direct action of FPI on membrane homeostasis was evidenced by a reduction in calcium-independent phospholipase A2 (iPLA₂) important for metabolism of membrane phospholipids such as DHA, and an increase in the fatty acid transport protein (FATP) involved in translocation of long-chain fatty acids across the membrane. A potential association between membrane disruption and neuronal function was suggested by reduced levels of the NR2B subunit of the transmembrane NMDA receptor, in association with changes in iPLA2 and syntaxin-3 (STX-3, involved in the action of membrane DHA on synaptic membrane expansion). In addition, changes in iPLA2, 4-HNE, and STX-3 were proportional to reduced performance in a spatial learning task. In turn, the dietary supplementation with the curcumin derivative counteracted all the effects of FPI, effectively restoring parameters of membrane homeostasis. Results show the potential of the curcumin derivative to promote membrane homeostasis following TBI, which may foster a new line of non-invasive therapeutic treatments for TBI patients by endogenous up-regulation of molecules important for neural repair and plasticity.