Probiotic treatment of inflammatory bowel disease: Its extent and intensity

Free radicals (reactive oxygen species, superoxides and hydroxyl radicals) lead to the development of oxidative stress because of imbalance in the amount of antioxidants. Continued development of oxidative stress leads to chronic diseases in humans. The instability in the antioxidant activities and accumulation of oxidative stress due to free radicals may occur in diseases like inflammatory bowel disease (IBD). Antioxidants are substances that inhibit or delay the mechanism of oxidation of molecules mediated by free radicals and also transform into lesser-active derivatives. Probiotics are defined as live microorganisms that show beneficial effects on inflamed intestine and balance the inflammatory immune responses in the gut. Probiotic strains have been reported to scavenge hydroxyl radicals and superoxide anions that are abundantly produced during oxidative stress. The most widely studied probiotic strains are Streptococcus, Bifidobacterium and Lactobacillus. Probiotics cultured in broth have shown some amount of antioxidant activities. Fermented milk and soy milk, which possess starter microorganisms (probiotics), tends to increase the antioxidant activities many-fold. This review aims to discuss the in vivo and in vitro antioxidant activities of specific probiotics with various assays with respect to IBD.     

DJ-1 Variants in Indian Parkinson’s Disease Patients

Parkinson’s disease (PD) is a common neurodegenerative movement disorder. Among the candidate genes, DJ-1 accounts for about 1% of the cases in different populations. We aim to find the contribution of the gene towards PD among Indians. By screening DJ-1 in 308 PD patients of eastern India and 248 ethnically matched controls, a total of 21 nucleotide variants – including two nonsynonymous changes – were detected. p.Arg98Gln was identified in 6 unrelated patients and 2 controls while p.Val35Ile, a novel change, was found only in 2 unrelated patients. A SNP (rs7517357) was observed to be moderately associated with increased risk of PD (p < 0.05). The deletion allele (g.168–185del) of a known 18 bp del/ins/dup polymorphism was found to be over represented (p < 0.05) among older patients (> 40 years) compared to the controls (> 45 years). Two of the patients, also heterozygotes for PINK1 mutation, had more severe disease phenotypes, consistent with the reported interaction between PINK1 and DJ-1 gene products [19]. Our results demonstrate that up to 3.9% (12/308) of PD patients of eastern India harbor DJ-1 variants that should be explored further for any causal relationship with PD.     

Alveolar Soft Part Sarcoma: A Rare Diagnosis

Alveolar soft-part sarcoma (ASPS) is an extremely rare disease arising from connective tissues with a propensity for recurrence and metastasis. Clinically, it can be confused with hemangioma or arterio-venous malformations. Thus, a high index of suspicion and histopathological examination are required to make a definitive diagnosis. We report a case of recurrent ASPS in a young female with multiple sites involvement without any features of metastasis who has been treated with excision of the symptomatic lesions followed by chemotherapy.     

Eye wall resections for intraocular tumors: Our experience

We conducted a retrospective review of 11 eyes undergoing eye wall resection between October 1998 and October 2009. The median age of 11 patients was 29 years. Decreased vision (eight) was the most common presenting symptom. Ciliary body medulloepithelioma was the most common clinical diagnosis (six). Medulloepithelioma was the most common histopathological diagnosis (four). The duration of follow-up ranged from 0.5 to 67 months (median 11 months). Three eyes needed to be enucleated in the postoperative period (margin involvement two eyes, recurrence one eye). Postoperative complications among others included retinal detachment (three), vitreous hemorrhage (three), cataract (two), and suprachoroidal hemorrhage (two). To conclude, prognosis of this procedure continues to be guarded needing close postoperative follow-up.     

Pharmacokinetics-Pharmacodynamics of the Helicase-Primase Inhibitor Pritelivir following Treatment of Wild-Type or Pritelivir-Resistant Virus Infection in a Murine Herpes Simplex Virus 1 Infection Model

Herpes simplex virus (HSV) infections can cause considerable morbidity. Transmission of HSV-2 has become a major health concern, since it has been shown to promote transmission of other sexually transmitted diseases. Pritelivir (AIC316, BAY 57-1293) belongs to a new class of HSV antiviral compounds, the helicase-primase inhibitors, which have a mode of action that is distinct from that of antiviral nucleoside analogues currently in clinical use. Analysis of pharmacokinetic-pharmacodynamic parameters is a useful tool for the selection of appropriate doses in clinical trials, especially for compounds belonging to new classes for which no or only limited data on therapeutic profiles are available. For this purpose, the effective dose of pritelivir was determined in a comprehensive mouse model of HSV infection. Corresponding plasma concentrations were measured, and exposures were compared with efficacious concentrations derived from cell cultures. The administration of pritelivir at 10 mg/kg of body weight once daily for 4 days completely suppressed any signs of HSV infection in the animals. Associated plasma concentrations adjusted for protein binding stayed above the cell culture 90% effective concentration (EC₉₀) for HSV-1 for almost the entire dosing interval. Interestingly, by increasing the dose 6-fold and prolonging the treatment duration to 8 days, it was possible to treat mice infected with an approximately 30-fold pritelivir-resistant but fully pathogenic HSV-1 virus. Corresponding plasma concentrations exceeded the EC₉₀ of this mutant for <8 h, indicating that even suboptimal exposure to pritelivir is sufficient to achieve antiviral efficacy, possibly augmented by other factors such as the immune system.