A PHARMACOGNOSTIC AND PHARMACOLOGICAL REVIEW ON ALSTONIA SCHOLARIS

Alstonia scholaris, commonly known as devil's tree, is an important medicinal plant in the various folk and traditional systems of medicine in Asia, Australia, and Africa. The plant is used in Ayurvedic, Unani, and Siddha types of alternative medicinal systems. The decoction, mostly prepared from the bark, is used to treat a variety of diseases, of which the most important is malaria. In Ayurveda, it is used as a bitter and as an astringent herb for treating skin disorders, malarial fever, urticaria, chronic dysentery, diarrhea, and in snake bite. A. scholaris is also observed to possess antioxidant, immunomodulatory effects, and free radical scavenging, anti-inflammatory, antimutagenic, anticancer, analgesic, hepatoprotective, wound healing, antidiarrheal, and antiplasmodial activities. The current review summarizes the numerous ethnobotanical and traditional uses as well as the phytochemical and pharmacological report on A. scholaris

A novel 1-bp deletion in PITX3 causing congenital posterior polar cataract

Purpose: Cataracts are the most common cause of blindness worldwide. Inherited cataract is a clinically and genetically heterogeneous disease. Here we report a novel mutation in the paired-like homeodomain 3 (PITX3) gene segregating in a four generation English family with an isolated autosomal dominant posterior polar cataract.Methods: A genome-wide linkage was performed by means of single nucleotide polymorphism (SNP) and microsatellite markers. Linkage analyses were performed with the GeneHunter and MLINK programs. Direct sequencing of PCR products was performed to detect mutation in the gene, using the BigDye version 3.1 and analyzed using Sequence analysis version 5.2.Results: Genome-wide linkage analysis with SNP markers, identified a disease-haplotype interval on chromosome 10q. Two point positive logarithm of odds (LOD) scores was obtained with markers D10S205 (Z=3.10 at theta=0.00), flanked by markers D10S1709 and D10S543, which harbors the homeobox gene PITX3. Sequence analysis of PITX3 revealed a 1-bp deletion that cosegregated with all the affected members of this family which resulted in a frameshift in codon 181 and likely to produce an aberrant protein consisting of 127 additional residues.Conclusions: The 542delC is a novel mutation in PITX3 causing an isolated posterior polar cataract

Queering Development? The Unsettling Geographies of South–South Cooperation

This paper deploys queer theory as a way of approaching South–South Cooperation (SSC). It examines the ways in which Southern development partners are not simply up-ending the long-standing spatialities, imaginaries and identities (re)produced through the mainstream international development regime, but queering terminologies and definitions, while presenting themselves in fluid ways, enrolling different identities and attributes in different places and to different audiences. At the same time, a queer lens reveals the (re)inscription of gendered, sexualised and racialised identities and hierarchies through the relationships, intimacies and practices of SSC. The paper proposes that queer theory can offer productive insights into the complex and compelling phenomenon of SSC, and the transgressive challenges to the postcolonial hierarchies and binaries of “traditional” international development

αA-crystallin R49Cneo mutation influences the architecture of lens fiber cell membranes and causes posterior and nuclear cataracts in mice

<p>Abstract</p> <p>Background</p> <p>αA-crystallin (CRYAA/HSPB4), a major component of all vertebrate eye lenses, is a small heat shock protein responsible for maintaining lens transparency. The R49C mutation in the αA-crystallin protein is linked with non-syndromic, hereditary human cataracts in a four-generation Caucasian family.</p> <p>Methods</p> <p>This study describes a mouse cataract model generated by insertion of a neomycin-resistant (neo^r) gene into an intron of the gene encoding mutant R49C αA-crystallin. Mice carrying the neo^rgene and wild-type <it>Cryaa </it>were also generated as controls. Heterozygous knock-in mice containing one wild type gene and one mutated gene for αA-crystallin (WT/R49C^neo) and homozygous knock-in mice containing two mutated genes (R49C^neo/R49C^neo) were compared.</p> <p>Results</p> <p>By 3 weeks, WT/R49C^neomice exhibited large vacuoles in the cortical region 100 μm from the lens surface, and by 3 months posterior and nuclear cataracts had developed. WT/R49C^neomice demonstrated severe posterior cataracts at 9 months of age, with considerable posterior nuclear migration evident in histological sections. R49C^neo/R49C^neomice demonstrated nearly complete lens opacities by 5 months of age. In contrast, R49C mice in which the neo^rgene was deleted by breeding with CreEIIa mice developed lens abnormalities at birth, suggesting that the neo^rgene may suppress expression of mutant R49C αA-crystallin protein.</p> <p>Conclusion</p> <p>It is apparent that modification of membrane and cell-cell interactions occurs in the presence of the αA-crystallin mutation and rapidly leads to lens cell pathology <it>in vivo</it>.</p

(Un)becoming women: Indian factory women's counternarratives of gender

This paper portrays the life stories of five factory workers in Delhi whose life trajectories run counter to normative femininity. As daughters and wives, they are neglected, abandoned or rejected by their families; they live alone, with their parents past the age that is their natal right, with siblings, or with families and men who are not related to them. I explore the circulation of their counternarratives and how their gender transgressions go public through ordinary forms of talk, such as gossip and rumor. I argue that their move out of the normative is not produced by, but produces, their gender politics; that their agency emerges cognitively from the telling of their stories in tandem with their interlocutors' credulity and uptake; and that the site of gender politics for working class Indian women lies in the informal subaltern publics that are formed by the circulation of their stories. Contrary to the notion of a stable unitary subject that precedes the political, these women's counternarratives demonstrate the subject‐in‐process as a political effect. Their alterity does not exist outside the heteronormative gender order but demarcates the boundaries of its historicity, hinting at both the internal contradictions of existing gender relations and their future possibilities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112196/1/j.1467-954X.2011.02026.x.pd

From Mexico to Beijing: "Women in Development" Twenty Five Years On

During the past twenty five years the Women in Development (WID)approach has become an increasingly important issue in the literature on Third World development. WID issues and related activities have now been incorporated into the aid practice of most development agencies. This paper critically analyses the diverse and conflicting ideologies that have emerged in the WID literature since the early seventies

KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients

The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2. We further used this inducer to probe the functional consequences of selective activation of NRF2 signaling in Huntington's disease (HD) mouse and human model systems. Surprisingly, we discovered a muted NRF2 activation response in human HD neural stem cells, which was restored by genetic correction of the disease-causing mutation. In contrast, selective activation of NRF2 signaling potently repressed the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes. Moreover, in primary monocytes from HD patients and healthy subjects, NRF2 induction repressed expression of the proinflammatory cytokines IL-1, IL-6, IL-8, and TNFα. Together, our results demonstrate a multifaceted protective potential of NRF2 signaling in key cell types relevant to HD pathology

Leukotriene biosynthesis inhibition ameliorates acute lung injury following hemorrhagic shock in rats

<p>Abstract</p> <p>Background</p> <p>Hemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity.</p> <p>Objectives</p> <p>The objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways.</p> <p>Materials and methods</p> <p>Eighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS) for 1 hr then resuscitated with Ringer's lactate (1 hr) (induced untreated group, HS); group III, HS + MK-886 (0.6 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period). At the end of experiment (2 hr after completion of resuscitation), blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The trachea was then isolated and bronchoalveolar lavage fluid (BALF) was carried out for measurement of leukotriene B₄(LTB₄), leukotriene C₄(LTC₄) and total protein. The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed in 10% formalin for histological examination.</p> <p>Results</p> <p>MK-886 treatment significantly reduced the total lung injury score compared with the HS group (<it>P </it>< 0.05). MK-886 also significantly decreased serum TNF-α & IL-6; lung MDA; BALF LTB₄, LTC₄& total protein compared with the HS group (<it>P </it>< 0.05). MK-886 treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>The results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation.</p