Protective effect of Barringtonia racemosa Ethyl Acetate Fraction against Cisplatin-induced Nephrotoxicity in Rats

Cisplatin is a major antineoplastic drug for the treatment of solid tumors. Nephrotoxicity is dose- limiting side effect associated with clinical use of cisplatin. The present study was executed to determine whether bartogenic acid containing fraction of Barringtonia racemosa fruits (BREAF) possesses a nephroprotective effect against cisplatin-induced nephrotoxicity in rats. Furthermore, the study was also aimed to explore the mechanisms underlying this effect of BREAF. The BREAF was orally administered at the doses of (2, 5 and 10 mg/kg) for five consecutive days following single dose administration of cisplatin (5 mg/kg, i.p.). Treatment of animals with cisplatin resulted into the significant body weight changes, oxidative stress, elevated levels of serum biomarkers and histological alterations in the kidney architecture. The BREAF administration reduced relative body weight and organ weight changes in cisplatin-treated rats. The BREAF exhibited nephroprotective effect through the significant reduction of cisplatin-induced rise in the serum creatinine, and blood urea nitrogen levels as well as renal levels of malondialdehyde (MDA) the makers of lipid peroxidation. Additionally, the treatment with BREAF resulted into the increased renal levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase activity. Histopathological examination established the nephroprotective effect of BREAF. In conclusion, the anti-oxidant, and anti-inflammatory effects of BREAF has important role underlying its nephroprotective effect.

Mechanistic Investigation On Anti-Nociceptive Potential Of Bartogenic Acid Containing Barringtonia Racemosa Fraction In Experimental Models Of Pain

Barringtonia racemosa (B. racemosa) is a tropical medicinal plant possessing interesting biological activities. B. racemosa fruits are traditionally used in India for the treatment of pain, inflammation, and rheumatic conditions. Earlier, we have reported anti-inflammatory activity of ethyl acetate fraction (BREAF) obtained from B. racemosa fruits in animal models of inflammation and delayed-type hypersensitivity. The present study aimed to assess the anti-nociceptive activity of BREAF. Acetic acid-induced writhing test, and hot plate and tail immersion tests were employed to study the effect of BREAF on peripheral and central pain mechanisms, respectively. The involvement of opioid system was confirmed through naloxone antagonism. Formalin induced pain test was performed to assess the effect of BREAF on neurogenic and inflammatory pain components. Capsaicin induced pain models were used to investigate the involvement of transient receptor potential vanilloid 1 receptor. The BREAF reduced writhing episodes and delayed the onset of acetic acid-induced writhings. The raised percentage maximum protective effects by BREAF in hot plate and tail immersion tests suggest the efficacy of BREAF in pain alleviation. A reversal of the analgesic effect of BREAF following naloxone treatment indicates the involvement of opioid receptors. The BREAF also inhibited inflammatory and neurogenic components of formalin-induced pain. The inhibition of capasaicin induced pain to some extent by the BREAF indicates the possibility of involvement of TRPV1 receptors. This study reinforces the traditional use of B. racemosa in the treatment of painful conditions. However, further studies are reasonable to explore the detailed mechanism(s) of the anti-nociceptive action of BREAF.

Structural studies on Mycobacterium tuberculosis RecA: Molecular plasticity and interspecies variability.

Structures of crystals of Mycobacterium tuberculosis RecA, grown and analysed under different conditions, provide insights into hitherto underappreciated details of molecular structure and plasticity. In particular, they yield information on the invariant and variable features of the geometry of the P-loop, whose binding to ATP is central for all the biochemical activities of RecA. The strengths of interaction of the ligands with the P-loop reveal significant differences. This in turn affects the magnitude of the motion of the ‘switch’ residue, Gln195 in M. tuberculosis RecA, which triggers the transmission of ATP-mediated allosteric information to the DNA binding region. M. tuberculosis RecA is substantially rigid compared with its counterparts from M. smegmatis and E. coli, which exhibit concerted internal molecular mobility. The interspecies variability in the plasticity of the two mycobacterial proteins is particularly surprising as they have similar sequence and 3D structure. Details of the interactions of ligands with the protein, characterized in the structures reported here, could be useful for design of inhibitors against M. tuberculosis RecA.

Antiviral drug profile of human influenza A & B viruses circulating in India: 2004-2011.

background & objectives: Recent influenza antiviral resistance studies in South East Asia, Europe and the United States reveal adamantane and neuraminidase inhibitor (NAIs) resistance. This study was undertaken to evaluate antiviral resistance in influenza viruses isolated from various parts of India, during 2004 to 2011. methods: Influenza viruses were analyzed genetically for known resistance markers by M2 and NA gene sequencing. Influenza A/H1N1 (n=206), A/H3N2 (n=371) viruses for amantadine resistance and A/H1N1 (n=206), A/H3N2 (n=272) and type B (n=326) for oseltamivir resistance were sequenced. Pandemic (H1N1) (n= 493) isolates were tested for H274Y mutation by real time reverse transcription (rRT)-PCR. Randomly selected resistant and sensitive influenza A/H1N1 and A/H3N2 viruses were confirmed by phenotypic assay. results: Serine to asparagine (S3IN) mutation was detected in six isolates of 2007-2008.One dual-resistant A/H1N1 was detected for the first time in India with leucine to phenylalanine (L26F) mutation in Mm2 gene and H274Y mutation in NA gene. A/H3N2 viruses showed an increase in resistance to amantadine from 22.5 per cent in 2005 to 100 per cent in 2008 onwards with S3IN mutation. Fifty of the 61 (82%) A/H1N1 viruses tested in 2008-2009 were oseltamivir resistant with H274Y mutation, while all A/H3N2, pandemic A/H1N1 and type B isolates remained sensitive. Genetic results were also confirmed by phenotypic analysis of randomly selected 50 resistant A/H1N1 and 40 sensitive A/H3N2 isolates. Interpretation & conclusions: Emergence of influenza viruses resistant to amantadine and oseltamivir in spite of negligible usage of antivirals emphasizes the need for continuous monitoring of antiviral resistance.

Active pharmaceutical ingredient (api) from an estuarine fungus, Microdochium nivale (Fr.).

Various marine habitats sustain variety of bio-sources of ecological and biotech potentials. Pharmaceutical potential compound Cyclosporine A was reported from marine fungus Microdochium nivale associated with Porteresia coarctata, a marine salt marsh grass from mangrove environment distributed along the Central West Coast (CWC) of India. This study involves association of M. nivale with P. coarctata plant, fermentation conditions, purification of Cyclosporine A, chemical characterization etc. Its antifungal inhibition and MIC (Minimum inhibitory concentration) against Aspergillus strains (A. niger, A. japonicus, A. fresenii), yeasts and dermatophytes (Candida sp., Cryptococcus neoformans, Trichophyton mentagrophytes, T. tonsurans, T. violaceum, Microsporium gypsum and Fusarium sp.) were evaluated. However, the MIC against A. japonicus, C. neoformans, Candida sp. and T. tonsurans were confirmed to be as low as 12.5-25 mg disc-1. The antifungal properties of Cyclosporine A against Aspergillus species, yeast and dermatophytes revealed that Cyclosporine A would be a potential compound for life threatening diseases caused by above fungi in both human and animals. Furthermore, we have reported herewith another source of Cyclosporin A derived from filamentous fungus, M. nivale. occurring in marine environment.

White spongy nevus: a nonhereditary presentation.

White spongy nevus (WSN) is a rare hereditary dyskeratotic hyperplasia of the mucous membranes. It is an autosomal dominant disorder with variable penetrance. A few cases of WSN occur due to de novo mutations. We report a case of WSN in a 12-year-old female child, with none of her family members having similar lesions.

Burkitt's lymphoma in an Indian girl: a case report.

Burkitt's lymphoma (BL) is a rare monoclonal proliferation of B-lymphocytes and is classified as a poorly differentiated lymphocytic lymphoma. This tumor was first noted in Africans. The cause of this tumor is debatable, but strong evidence implicates Epstein-Barr virus in its development. This tumor predominantly affects children and is probably the fastest growing tumor in humans, with exuberant proliferation. It is a very rare malignancy accounting for only 0.76% of solid malignant tumors among Indian children. A case of BL of the mandible in a 9-year-old girl of Indian origin is reported.

Facial plexiform neurofibroma in a child with neurofibromatosis type I: a case report.

Plexiform neurofibroma is a non-circumscribed, thick and irregular benign tumor of the peripheral nerve sheath. It is a virtually pathognomonic and often disabling feature of neurofibromatosis type I. The diffuse and soft nature of plexiform neurofibroma is often compared to 'a bag of worms' and is difficult to distinguish from a vascular malformation or a lymphangioma, thus necessitating thorough clinical and histopathological examination and imaging of the lesion. We present a case of plexiform neurofibroma in a 12-year-old male child.

Gorlin syndrome: A case report.

Gorlin syndrome is an autosomal dominant inherited condition that exhibits high penetrance and variable expressivity. It is characterized mainly by Basal cell carcinomas, Odontogenic keratocysts and skeletal anomalies. However, medical literature documents both common and lesser known manifestations of the disorder involving the skin, central nervous system, skeletal system etc. Diagnosis of the syndrome in childhood is basically through oral abnormalities. A case of Gorlin syndrome has been reported here, with review of literature.

Juvenile aggressive cemento-ossifying fibroma. A case report.

Juvenile Aggressive Cemento-Ossifying Fibroma is a benign, fibro osseous neoplasm commonly affected maxilla but also other bones including mandible, arising in children. It is considered to be a locally aggressive and quickly expansile lesion. Because of its aggressive nature and high recurrence rate, an early detection and a complete surgical excision is essential. A case of Juvenile Aggressive Cemento-Ossifying Fibroma in a 9 year old male child who visited the Department of Oral Medicine and Radiology, J.S.S. Dental college and Hospital, Mysore is being reported and discussed.

Juvenile aggressive cemento-ossifying fibroma. A case report.

Juvenile Aggressive Cemento-Ossifying Fibroma is a benign, fibro osseous neoplasm commonly affecting maxilla but also other bones including mandible, arising in children. It is considered to be a locally aggressive and quickly expansile lesion. Because of its aggressive nature and high recurrence rate, an early detection and a complete surgical excision is essential. A case of Juvenile Aggressive Cemento-Ossifying Fibroma in a 9 year old male child who visited the Department of Oral Medicine and Radiology, J.S.S. Dental College and Hospital, Mysore is being reported and discussed.

Mechanics of tarsal disintegration and plantar ulcers in leprosy by stress analysis in three dimensional foot models.

This paper describes three dimensional two arch models of feet of a normal subject and two leprosy subjects, one in the early stage and the other in the advanced stage of tarsal disintegration, used for analysis of skeletal and plantar soft tissue stresses by finite element technique using NISA software package. The model considered the foot geometry (obtained from X-rays), foot bone, cartilages, ligaments, important muscle forces and sole soft tissue. The stress analysis is carried out for the foot models simulating quasi-static walking phases of heel-strike, mid-stance and push-off. The analysis of the normal foot model shows that highest stresses occur at push-off over the dorsal central part of lateral and medial metatarsals and dorsal junction of calcaneus and cuboid and neck of talus. The skeletal stresses, in early state leprosy with muscle paralysis and in the advanced stage of tarsal distintegration (TD), are higher than those for the normal foot model, by 24% to 65% and 30% to 400%, respectively. The vertical stresses in the soft tissue at the foot-ground interface match well with experimentally measured foot pressures and for the normal and leprosy subjects they are the highest in the push-off phase. In the leprosy subject with advanced TD, the highest soft tissue stresses and shear stresses (about three times the normal value) occur in push-off phase in the scar tissue region. The difference in shear stresses between the sole and the adjacent soft tissue layer in the scar tissue for the same subject is about three times the normal value. It is concluded that the high bone stresses in leprosy may be responsible for tarsal distintegration when the bone mechanical strength decreases due to osteoporosis and the combined effect of high value of footsole vertical stresses, shear stresses and the relative shear stresses between two adjacent soft tissue layers may be responsible for plantar ulcers in the neuropathic leprosy feet.

Absence of wild poliovirus circulation among healthy children in a rural area with high oral poliovirus vaccination coverage.

Poliovirus circulation in a rural community was studied by a stool sample survey. No acute paralytic poliomyelitis case had been reported from the study area during the previous 5 months. Immunization coverage in age groups 7 to 12 months and 12 to 60 months was 95.8 and 94 per cent, respectively. Of the 257 children from whom stool samples were collected (about 6% of the child population), 161 (62.6%) were positive for virus isolation. Poliovirus was isolated from 60 (23.3%) children. All three poliovirus types were detected (41 type 1, 16 type 2 and 3 type 3). Intratypic differentiation tests classified these isolates as vaccine-like. Among the children excreting poliovirus, the proportion of those who did not receive polio vaccine within 30 days prior to the sample collection was 46.3, and 68.7 per cent for poliovirus type 1 and 2, respectively. It was concluded that these poliovirus excreting children were infected by the vaccine strains circulating in the environment. The survey showed that wild poliovirus was not detectable within five months after the last case of acute poliomyelitis. Displacement of the wild virus from the environment and circulation of vaccine virus was achieved by high vaccination coverage in this area.

Foot pressure measurement in leprosy and footwear design.

Leprosy patients deprived of sensory feedback allow excessive pressures to be applied to feet, thereby cause foot ulcers. Quantitative knowledge of the pressure distribution under leprotic feet is helpful to prevent further damage to foot by designing suitable footwear. This paper describes barographic technique for measurement of pressures under the leprotic feet and the design of special footwear for prevention of foot ulcers.