The effects simultaneous inhibition of dipeptidyl peptidase-4 and P2X7 purinoceptors in an in vivo Parkinson’s disease model

Metabolic Brain Disease - Loss of dopaminergic neurons following Parkinson’s disease (PD) diminishes quality of life in patients. The present study was carried out to investigate the...     

Back Muscle Function in Older Women With Age-Related Hyperkyphosis: A Comparative Study

ObjectiveThe purpose of this study was to compare static maximal back extensor muscle force, endurance, and characteristics of flexion relaxation phenomenon (FRP) in older women with and without age-related hyperkyphosis.MethodsMaximum back extensor force and endurance measured in a sitting position with a designed load cell setup; appearance, onset, and offset angles of FRP; and extension relaxation ratio (ERR) during a dynamic flexion-extension task were compared between 24 older women with hyperkyphosis (thoracic kyphosis angle ≥50°), mean age 65 ± 4.4 years, and 24 older women without hyperkyphosis (thoracic kyphosis angle ?50°), mean age 63 ± 4.3 years. Variables of force, endurance, angles of FRP, and ERR were analyzed using an independent sample t test. A χ² test was used to identify differences between groups in FRP appearance.ResultsStatic back extensor force and endurance were significantly lower among those with versus those without hyperkyphosis (P ? .001). Although the 2 groups did not differ in FRP appearance and ERR in the superficial erector spinal muscles (P ? .05), FRP in the hyperkyphosis group started sooner and ended later than in the group without hyperkyphosis (P ? .05).ConclusionOur study indicates that women with age-related hyperkyphosis had decreased static maximal force and endurance of the back extensor muscles and prolonged myoelectrical silence of the superficial erector spinal muscles. Reduced endurance of the superficial erector spinal muscles may trigger early onset of FRP and prolonged relaxation of these muscles.     

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats

Background and objective: Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Materials and methods: Male diabetic rats received C3G (10 mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. Results: It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Conclusion: Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors.     

Effect of different doses of furazolidone with amoxicillin and omeprazole on eradication of Helicobacter pylori

BACKGROUND: Resistance to metronidazole is one of the most common reasons for Helicobacter pylori treatment failure with classic triple therapy. In contrast, the clarithromycin-based regimen is not cost-effective for developing countries. Furazolidone is a very good substitute for metronidazole and clarithromycin, but its many side-effects limit widespread use. The aim of the present study was to assess the efficacy of two different doses of furazolidone in combination with amoxycillin and omeprazole. METHODS: A total of 123 patients with duodenal ulcer were randomized and received the following medications for two weeks. Group A: furazolidone 2 x 200 mg + amoxycillin 2 x 1 g + omeprazole 2 x 20 mg/day. Group B: furazolidone 2 x 50 mg + amoxycillin 2 x 1 g + omeprazole 2 x 20 mg/day. Control endoscopy was performed after 6 weeks and two biopsy specimens from the antrum and two from the corpus were taken for a urease test and histology. Eradication was concluded if all tests were negative for H. pylori. RESULTS: In total, 110 patients completed the study. Four patients in group A did not tolerate the regimen on day 8 of therapy and were excluded from the study. Serious complications such as fever, and fatigue and dizziness, which occurred in the beginning of the second week of treatment (days 8-10), were more common in group A than in group B (19%, 15.9% and 14.3%, respectively, in group A vs 0% in group B). The eradication rate by per protocol analysis was significantly higher in group A than in group B (88.9%vs 67.9%, respectively, P = 0.008). However, this difference was low and not statistically significant by intention-to-treat analysis (76.2% in group A and 62.3% in group B, P = 0.09). CONCLUSION: The regimen with a non-reduced dose of furazolidone in combination with amoxycillin and omeprazole was effective when the patients tolerated the drugs and completed the study.     

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke – a randomized,double‐blind,placebo‐controlled trial

Lokk J, Salman Roghani R, Delbari A. Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke – a randomized, double‐blind, placebo‐controlled trial.
Acta Neurol Scand: 2011: 123: 266–273.
© 2010 John Wiley & Sons A/S. Objective – Amphetamine‐like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. Material and methods – A randomized, double‐blind, placebo‐controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl‐Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. Results – All participants showed recovery of motor function and ADL during treatment and at 6‐month follow‐up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6‐month follow‐up. Conclusion – Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most.     

Thymoquinone Attenuates Astrogliosis, Neurodegeneration, Mossy Fiber Sprouting, and Oxidative Stress in a Model of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a rather common and difficult-to-treat variant of epilepsy. Nearly one third of people with epilepsy do not respond effectively to currently available anticonvulsants. In this study, we evaluated the protective effect of thymoquinone (TQ), the main constituent of black seed with antioxidant and anti-inflammatory effects, in the intrahippocampal kainate model of TLE in rat. Following kainate injection, seizure activity was observed that was significantly diminished by TQ pretreatment at a dose of 10 mg/kg, p.o. Intrahippocampal kainate also increased malondialdehyde (MDA), nitrite, and nitrate levels and decreased activity of superoxide dismutase and TQ only significantly attenuated MDA. In addition, intrahippocampal kainate caused a significant reduction of neurons in CA1, CA3 and the hilar regions, and TQ significantly attenuated these changes. Timm histochemistry showed a marked mossy fiber sprouting (MFS) in the dentate gyrus of kainate-lesioned rats, and TQ significantly lowered MFS intensity. Meanwhile, a number of reactive astrocytes (astrogliosis) increased significantly in the kainate group, and TQ pretreatment significantly decreased it. These data suggest that TQ pretreatment could attenuate seizure activity and lipid peroxidation, lower hippocampal neuronal loss and MFS, and mitigate astrogliosis in kainate model of TLE.     

Lumbar trabecular bone mineral density distribution in patients with and without vertebral fractures: a case–control study

Purpose

The proportion of load transmitted through the lumbar neural arch increases with aging, spinal degeneration, and lordosis, effectively shielding the lumbar vertebral bodies from load. This stress shielding may contribute to bone loss in the vertebral body, leading to increased fracture risk. To test his hypothesis, we performed a study to determine if vertebral body fractures were associated with a higher neural arch/vertebral body volumetric bone mineral density (vBMD) ratio.

Methods

Trabecular vBMD was calculated by quantitative CT in the L3 vertebral body and neural arch (pars interarticularis) of 36 women with vertebral compression fractures and 39 controls. Neural arch/vertebral body vBMD ratio was calculated, and its relationship to fracture status was determined using linear regression models adjusted for age and body mass index.

Results

Vertebral body trabecular vBMD was lower in fracture cases as compared to controls (mean ± SD, 49.0 ± 36.0 vs. 87.5 ± 36.8 mg/cm³, respectively; P < 0.001), whereas trabecular vBMD of the neural arch was similar (96.1 ± 57.6 in cases vs. 118.2 ± 57.4 mg/cm³ in controls; P = 0.182). The neural arch/vertebral body vBMD ratio was significantly greater in the fracture group than in controls (2.31 ± 1.07 vs. 1.44 ± 0.57, respectively; P < 0.001).

Conclusion

These results support the hypothesis that stress shielding is a contributor to vertebral body bone loss and may increase fracture risk. Although further studies are needed, there may be a role for interventions that can shift vertebral loading in the spine to help prevent fracture.     

Evaluating the efficacy of commonly used topical anesthetics.

PURPOSE: This study compared the efficacy of commonly used topical anesthetics using an objective measuring scale. METHODS: The following were tested: 5% EMLA cream, 10% cocaine, 10% lidocaine, 10% benzocaine, 1% dyclonine, and a placebo. A special instrument was designed to serve the purpose of pressure application on the gingiva to obtain a threshold discomfort level in grams before and after the topical delivery. The medicaments, in the quantity of 20 microL (2-3 drops) were placed on the maxillary anterior region using Beckman paper wicks in the form of discs. The topical anesthetics were left on the gingiva for 3 min and off for another 3 min. The instrument applied pressure progressively, and the pressure application was stopped when the subjects reported the initial feeling of discomfort. RESULTS: 5% EMLA cream significantly reduced the pain threshold level followed by 1% dyclonine and 10% benzocaine. However, there was no significant difference between 10% cocaine, 10% lidocaine, and the placebo. The placebo effect was observed. CONCLUSIONS: 5% EMLA cream was superior in performance to all other topical anesthetics. The remainder of the agents had no statistically different effect than the saline.     

Evidence of enzymatic degradation of insulin-like growth factor-binding proteins in the 150K complex during pregnancy.

Western ligand blot analysis of the different molecular forms of insulin-like growth factor-binding protein IGF-BP) in serum and plasma samples from 89 pregnant women has revealed a marked decrease, after the second month of pregnancy, in the 41.5 and 38.5K species (which are the binding units of the 150K complex) as well as in the 24K form. There was also a slight decrease in the 34K form, the 30K form was unaffected, and additional 21.5 and 20K bands appeared. Cross-linking experiments demonstrated the disapperance of a 49K band which is characteristic of the 150K complex. The alterations of the electrophoretic profile of the BPs were accompanied by a decrease in binding activity of up to 90%. Gel filtration at pH 7.4 confirmed that the decrease was essentially attributable to changes in the 150K complex BPs: 1) material eluting in the 150K zone contained only one third of the binding activity, as opposed to three quarters in reference material; 2) radiocompetition experiments illustrated the loss of affinity for IGF-I and IGF-II of the BPs extracted from the 150K complex; 3) ligand blot analysis revealed, in contrast with the virtual disappearance of the 41.5 and 38.5K forms, the appearance of a broad indistinct band at 30K and additional bands at 21.5 and 20K. With immunoblotting, the anti-IGF-BP-3 antibody, which specifically recognizes the 41.5 and 38.5K species, cross-reacted with this 30K material. The alterations of the BPs appeared to be enzymatic. When pregnancy serum was mixed with reference serum, the 41.5, 38.5, and 24K forms contributed by the reference serum were markedly reduced after 30 min of incubation at 37 C. However, these alterations could be prevented by incubation at either 0 or at 37 C in the presence of EDTA or aprotinin and could be curbed in the presence of high concentrations of phenylmethylsulfonylfluoride. Unmixed reference serum incubated at 37 C yielded an unchanged BP profile. Incubation of pregnancy serum with hypopituitary serum, which has elevated levels of the 34 and 30K BPs, resulted in a marked decrease in the 41.5 and 38.5K forms, a slight alteration of the 34K form, and no change in the 30K form. These findings suggest that during pregnancy, enzymatic (probably protease) activity either appears or is significantly increased in the circulation, which specifically degrades some of the IGF-BPs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat

The effect of chronic silymarin (SM) treatment on hyperalgesia, sciatic motor nerve conduction velocity (MNCV) and oxidative stress in streptozotocin (STZ)‐diabetic neuropathic rat was evaluated. Rats were divided into control, diabetic, SM‐treated control and diabetic, and sodium salisylate (SS)‐treated control and diabetic. SM was administered daily at a dose of 100 mg/kg for two months. Finally, hyperalgesia and sciatic MNCV and oxidative stress markers were assessed. Diabetic rats showed a significant deficit in MNCV and markedly exhibited chemical and thermal hyperalgesia, indicating development of diabetic neuropathy. Antioxidant enzyme superoxide dismutase (SOD) level significantly reduced and malondialdehyde (MDA) level significantly increased in diabetic rats compared to control rats; SM treatment significantly ameliorated the alteration in MNCV, hyperalgesia, MDA level and antioxidant enzyme SOD in diabetic rats. These results clearly suggest the potential effect of SM in prevention and treatment of diabetic neuropathy. Copyright © 2009 John Wiley & Sons, Ltd.