Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: A randomized controlled clinical trial

Objectives

Multiple sclerosis is a neurodegenerative and demyelinating disease of central nervous system. High levels of oxidative stress are associated with inflammation and play an important role in pathogenesis of multiple sclerosis. This double-blind, randomized controlled clinical study was carried out to determine the effect of daily consumption of lipoic acid on oxidative stress among multiple sclerosis patients.

Methods

A total of 52 relapsing-remitting multiple sclerosis patients, aged 18–50 years with Expanded Disability Status Scale ≤5.5 were assigned to consume either lipoic acid (1200 mg/day) or placebo capsules for 12 weeks. Fasting blood samples were collected before the first dose taken and 12 hours after the last. Dietary intakes were obtained by using 3-day dietary records.

Results

Consumption of lipoic acid resulted in a significant improvement of total antioxidant capacity (TAC) in comparison to the placebo group (P = 0.004). Although a significant change of TAC (?1511 mmol/L, P = 0.001) was found within lipoic acid group, other markers of oxidative stress including superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde levels were not affected by lipoic acid consumption.

Discussion

These results suggest that 1200 mg of lipoic acid improves serum TAC among multiple sclerosis patients but does not affect other markers of oxidative stress.     

Personalized antiplatelet treatment after percutaneous coronary intervention: The MADONNA study

Background and objectives

Clopidogrel non-responsiveness is associated with adverse clinical outcome. We aimed to investigate whether individualized antiplatelet treatment in clopidogrel non-responders is an effective and safe strategy.

Methods

This was a prospective non-randomized non-blinded study comparing two cohorts (guided and non-guided treatment) with a follow-up of 1-month. Responsiveness to clopidogrel was assessed by multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). In the guided group (n = 403) clopidogrel non-responders received repeated loading doses of clopidogrel or prasugrel, in the non-guided group (n = 395) clopidogrel non-responders did not undergo any change in treatment.

Results

Stent thrombosis occurred significantly less often in the guided group than in the non-guided group (0.2% vs. 1.9%; p = 0.027). The multivariate Cox regression analysis showed that patients in the non-guided group were at a 7.9-fold higher risk to develop stent thrombosis compared to the guided group (OR: 7.9; 95% CI: 1.08–69.2; p = 0.048). In line with this, acute coronary syndrome occurred significantly less often in the guided group than in the non-guided group (0% vs. 2.5%; p = 0.001) whereas there was no difference in the event rates of cardiac death (2% vs. 1.3%; p = 0.422) or major bleedings (1% vs. 0.3%; p = 0.186).

Conclusion

Personalized antiplatelet treatment according to the platelet function testing with MEA resulted in an improved efficacy with an equal safety compared to the standard treatment.     

Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT → TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O⁶-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20 % in the reference group and 19 % (4/21 patients) in the cilengitide group. Compared with TMZ/RT → TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma.     

Anatomical distribution of colorectal carcinoma in Iran: a retrospective 15-yr study to evaluate rightward shift

Background: Although more than two third of colorectal cancers are localized on the left side, recentstudies suggest a right ward shift in anatomical distribution with increase in proximal colon cancers. The aimof the present study was to determine the anatomical distribution of colorectal cancer in a referral center overa 15 year period. Method: Records of patients who underwent colectomy in the Cancer Institute of Iran from1994 to 2009 were retrieved. Data including anatomical localization, year of diagnosis, patient age and gender,tumor histology and differentiation, and disease stage were extracted. Tumors located from the cecum to thedistal transverse colon were classified as right side and those occurring from the splenic flexure to the descendingcolon as left-sided. Cancer of rectum and recto-sigmoid junction were considered as rectal cancers. Results: Atotal of 442 patients including 220 (49/8%) men and 222 (50/2%) women with mean age 53 were included. Mostpatients were in stage II &III (47.1% and 33% respectively). There were 157 (35.5 %) colon cancers and 285(64.5%) rectal cancers. 43.3% of the colon cancers were right sided and 56.7% were left sided. There was nostatistically significant increase in right sided cancer during the period of the study. There were no significantdifferences in age at diagnosis, gender, grade and stage of tumor between the right and the left sided cancers.Conclusion: No proximal shift over time was identified in our study.     

The Impact of Vitamin D Supplementation on Neurodegeneration,TNF-α Concentration in Hypothalamus,and CSF-to-Plasma Ratio of Insulin in High-Fat-Diet-Induced Obese Rats

There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats. At the first phase of the study, the rats were divided into two groups: (1) normal diet (ND, 10% fat) and (2) high-fat diet (HFD, 59% fat) and were fed for 16 weeks. In the second phase, each group was subdivided into four groups including the following: ND, normal diet + vitamin D, HFD, and HFD + vitamin D. Weight was measured and recorded weekly. Vitamin D supplementation for 5 weeks at 500 IU/kg dosage was used. One week after vitamin D supplementation, daily food intake was recorded. At week 22, blood was collected to determine fasting serum glucose, vitamin D, and insulin concentrations, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. CSF samples were also collected to measure insulin concentrations, and the hypothalamus was dissected to determine TNF-α concentration. HFD significantly increased TNF-α concentrations and degenerated neurons in the hypothalamus (P = 0.02). We also observed a significant reduction of CSF-to-serum ratio of insulin in HFD group (P = 0.03). The HOMA-IR test indicated significant increment of insulin resistance in HFD-fed rats (P = 0.006). Vitamin D supplementation in HFD group significantly reduced weight (P = 0.001) and food intake (P = 0.008) and increased CSF-to-serum ratio of insulin (P = 0.01). Furthermore, vitamin D decreased insulin resistance in the HFD group (P = 0.008). Vitamin D had no significant effect on degenerated neurons and TNF-α concentration in the hypothalamus. According to our findings, vitamin D improved brain insulin homeostasis and modulated food intake and body weight in high-fat-diet-induced obese rats. Further studies are needed to better clarify the underlying mechanisms.