Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy

The mechanism of IgA deposition in the kidneys in IgA nephropathy is unknown, Mesangial IgA is of the IgA I subclass, and since no consistent antigenic target for the IgA I has been described, we have investigated the glycosylation of the molecule, as a potential non-immunological abnormality which may contribute to its deposition. IgA 1 is rich in carbohydrate, carrying N-linked moieties in common with IgG, but also O-linked sugars, which are rare in serum proteins, and not expressed by IgG or lgA2, Lectin binding assays were designed to examine the expression of terminal galactose on the N-linked carbohydrate chains of purified serum IgG and IgAI, and the O-linked sugars of IgAI and C1 inhibitor (one of the very few other serum proteins with O-linked glycosylation). No evidence was found for abnormalities of N-linked glycosylation of either isotype in IgA nephropathy compared with matched controls. However, in IgA nephropathy, reduced terminal galactosylation of the hinge region O-linked moieties was demonstrated; this was not seen in C1 inhibitor, which showed normal or increased galactosylation of the O-linked sugars. This abnormality of IgA1 has considerable implications for the pathogenesis of IgA nephropathy, since the O-linked sugars lie in an important functional location within the IgA1 molecule, close to the ligand of Fc receptors. Changes in the carbohydrates in this site may therefore affect interactions with receptors and extracellular proteins, leading to anomalous handling of the IgA1 protein in this condition, including failure of normal clearance mechanisms, and mesangial deposition.     

N-乙酰半胱氨酸和亚硒酸钠对镉亚慢性毒性的影响

目的探讨N-乙酰半胱氨酸(N-acetyl cysteine,NAC)和亚硒酸钠(Na2SeO3)对亚慢性染镉大鼠肝肾毒性的影响及其机制。方法32只Wistart大鼠随机分为4组,每组8只,第1组为对照组,第2组为单位染镉组,第3、4组为干预组。大鼠连续6周皮下注射7μmol/kg氯化镉,然后干预组分别腹腔注射1 mmol/kg NAC和10μmol/kg Na2SeO3,共2周;测定大鼠尿N-乙酰-β-苷酶(NAG)、碱性磷酸酶活力(ALP)和肝、肾皮质谷胱甘肽(GSH)、丙二醛(MDA)含量及谷胱甘肽过氧化物酶(GSH-Px)活力。结果亚慢性染镉使大鼠肝、肾皮质和尿镉含量显著升高,尿ALP、NAG和蛋白含量显著升高,肝、肾皮质GSH含量显著升高,GSH-Px活力显著降低。与单纯染镉组比较,NAC处理组尿镉、NAG和蛋白含量显著下降,肝、肾皮质GSH显著降低;Na2SeO3处理组尿镉、ALP及肝、肾皮质GSH含量显著下降,GSH-Px活力显著升高。结论NAC和Na2SeO3对镉致肾损伤的恢复具有促进作用,其机制可能与NAC或Na2SeO3改变体内GSH含量和GSH-Px活力有关。     

Instrumental,clinical and subjective evaluation of the efficacy of a cosmetic treatment for home use

Background: In the last few years, there has been increasing demand for aesthetic procedures to improve the effects of skin aging.

Aim: To evaluate the anti-aging efficacy, tolerability and skin changes induced by the topical products containing hyaluronic acid, N-acetyl glucosamine and gamma-amino butyric acid through instrumental techniques, clinical and subjective evaluation.

Patients/Method: Twenty female enrolled applied a day and night cream after applying a serum, once week applied a mask, for 2 months. A clinical assessment of smoothness, expression wrinkles, fine wrinkles and measurements of the parameters using Reveal Imager, X-Rite, Corneometer, Dermalab, Moisture Meter EpiD were taken at day 0, 15, 30 and 60 of study period. A final assessment questionnaire was submitted.

Results: The products were accepted by all the volunteers. The hydration (Corneometer: T0 49.17 vs T60 61.11, average variation 24.28%) (Moisture Meter EpiD: T0 45.73 vs T60 61.10, average variation 33.60%), elasticity (Dermalab: T0 56.06 vs T60 62.78, average variation 11.98%) and lightening of the skin (X-Rite: T0 60.23 vs T60 63.36, average variation 5.26%) improved. All changes were statistically significant (p < 0.05).

Conclusion: The efficacy of the topical products is confirmed by subjective, clinical and instrumental assessment. This should be a routine approach in dermatologic practice.     

Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease

Aim:

Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington''s disease (HD) and explored the mechanisms of action.

Methods:

Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2–5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting.

Results:

3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC.

Conclusion:

Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.     

糖尿病微血管病变患者血清CysC、RBP及尿NAG的变化与糖尿病肾病发展的关系

目的 探讨糖尿病肾微血管病变患者血清胱抑素C(cystatin C,CysC)、视黄醇结合蛋白(retinol binding protein,RBP)及尿N-乙酰-β-D氨基葡萄糖苷酶(N-acetyl beta-D Glucosaminidase,NAG)的水平变化与糖尿病肾病病变程度的关系.方法 本研究选取30例2型糖尿病肾病患者(尿微量白蛋白＜ 14.29mg/L)作为A组、选取30例2型糖尿病肾病患者(尿微量白蛋白≥14.29mg/L)作为B组、30例2型糖尿病肾病引发尿毒症患者作为C组、30例体检正常研究对象作为D组,比较四组患者血清中CysC、RBP、NAG的差异.结果 A、B、C、D四组研究对象的CysC、RBP及尿NAG水平差异均具有统计学意义(P＜0.01);组间比较,A、B、C组CysC、RBP及尿NAG与D组比较均显著的高于D组,差异均具有统计学意义(P＜0.05);A、B组患者的CysC、RBP及尿NAG与C组比较显著低于C组,差异具有统计学意义(P＜0.05);A组患者的CysC、RBP及尿NAG与B组比较显著低于B组,差异具有统计学意义(P＜0.05).结论 糖尿病肾病患者随着病变程度不断加重,CysC、RBP及尿NAG水平呈明显的上升趋势.     

Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl βeta-cyclodextrin (HPβ-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer–Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.     

A proton magnetic resonance spectroscopy study of metabolites in the occipital lobes in epilepsy

PURPOSE: gamma-Amino butyric acid (GABA) and glutamate, respectively the principal inhibitory and excitatory neurochemicals in the brain, are visible to proton magnetic resonance spectroscopy (MRS). We report a study of GABA+ (GABA plus homocarnosine) and GLX (glutamate plus glutamine) concentrations in the occipital lobes in patients with idiopathic generalised epilepsy (IGE) and in patients with occipital lobe epilepsy (OLE). METHODS: Fifteen patients with IGE, 15 patients with OLE, and 15 healthy volunteers were studied. A single voxel was prescribed in the occipital lobes for each subject. PRESS localised short-echo-time MRS was performed to measure GLX by using LCModel. A double quantum GABA filter was used to measure GABA+. Segmented T1-weighted images gave the tissue composition of the prescribed voxel. RESULTS: Grey-matter proportion, GLX, and GABA+ were all elevated in IGE. However, analysis using grey-matter proportion as a covariable showed no significant group differences. No correlation was observed between GABA+ concentration and either seizure frequency or time since last seizure. CONCLUSIONS: GLX and GABA+ were elevated in IGE. Elevated grey-matter content in the IGE group despite normal MRI appearance can be expected to account for some or all of this observed elevation of GLX and GABA+. GABA+ concentration did not correlate with seizure control or duration since most recent seizure.     

Stimulation by intragastrically administered E2 prostaglandins of human gastric mucus output

Abstract. Prostaglandin E₂ and 15(R)15 methyl prostaglandin E₂ were instilled intragastrically to study gastric mucus output in healthy male subjects during an infusion of pentagastrin. Mucus was measured by determining total, free, and bound N-acetyl neuraminic acid (NANA) in gastric recoveries. NANA is a sialic acid located at the end terminals on the carbohydrate chains of mucus glycoprotein. It contributes to viscosity and prevents enzymatic degradation of mucus.
The methyl analogue of prostaglandin E₂ increased the gastric output of NANA and inhibited gastric acid secretion in a dose-dependent fashion. NANA produced in response to the analogue was bound to mucus glycoprotein. Prostaglandin E₂ increased the output of NANA without affecting the gastric acid secretion. Both prostaglandin E₂ and its methyl analogue increased volumes, pH, and NANA content of gastric aspirates withdrawn prior to start of the pentagastrin infusion, indicating a stimulation of the alkaline gastric secretion.
The results show that oral E₂ prostaglandins have dual effects on gastric secretion, and that their ability to stimulate mucus production is not secondary to gastric acid inhibition. Further studies are needed to examine whether their effect is mainly to increase the incorporation of NANA into mucus glycoproteins, or to stimulate the release and/or production of gastric mucus, and also to quantitate the gastric nonparietal secretion.
The stimulatory properties of E₂ prostaglandins on gastric mucus and alkaline secretion may be one mechanism by which they protect the gastric mucosa against experimentally induced damage.