A randomised comparative study on sublingual versus vaginal administration of misoprostol for termination of pregnancy between 13 to 20 weeks

BACKGROUND: Misoprostol is the drug of choice for medical abortion worldwide but consensus is yet to be reached regarding its preferred route of administration. AIMS: To compare the outcome of sublingual with vaginal administrations of misoprostol for induction of second trimester abortion. METHODS: A randomised comparative trial where 300 women at 13-20 weeks gestation, requiring medical abortion, were randomly assigned to sublingual or vaginal route for misoprostol administration with a dose schedule of 400 microg three-hourly, up to a maximum five doses over 24 h. The same doses were repeated for another 24 h in non-responders. Primary outcome measure was complete abortion rate at 24 and 48 h, and the secondary outcome measures were induction-abortion interval, failure rate, side-effects and patients' preference to the route. RESULTS: No statistically significant differences in the complete abortion rates were observed at 24 h (64.03% vs 61.59%, P = 0.767) and at 48 h (79.14% vs 82.01%, P = 0.651) when sublingual and vaginal groups were compared. Mean induction-abortion intervals in sublingual and vaginal groups were 14.1 and 14.5 h, respectively (P = 0.066). Other outcome measures were also more or less similar in both groups. Differences in the incidence of side-effects were also statistically insignificant when both groups were compared. Sublingual administration of the drug was preferred by most of the women as compared to vaginal administration (P < 0.0001). CONCLUSION: Both sublingual and vaginal administrations of misoprostol are equally effective in inducing medical abortion during second trimester but sublingual route was preferred by the patients.     

Activation of apoptosis by 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde, a novel compound from Aegle marmelos

We have identified a natural compound that activates apoptosis of epithelial cancer cells through activation of tumor necrosis factor-alpha (TNF-alpha), TNF receptor (TNFR)-associated death domain (TRADD), and caspases. The molecule 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC, marmelin) was isolated and characterized from ethyl acetate fraction of extracts of Aegle marmelos. HDNC treatment inhibited the growth of HCT-116 colon cancer tumor xenografts in vivo. Immunostaining for CD31 showed that there was a significant reduction in microvessels in the HDNC-treated animals, coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA. Using hexoseaminidase assay, we determined that HDNC inhibits proliferation of HCT-116 colon and HEp-2 alveolar epithelial carcinoma cells. Furthermore, the cancer cells showed increased levels of activated caspase-3 and induced G(1) cell cycle arrest, which was suppressed by caspase-3 inhibitors. HDNC induced TNF-alpha, TNFR1, and TRADD mRNA and protein expression. Moreover, caspase-8 and Bid activation, and cytochrome c release, were observed, suggesting the existence of a cross-talk between death receptor and the mitochondrial pathways. HDNC inhibited AKT and extracellular signal-regulated kinase phosphorylation both in cells in culture and in tumor xenografts. In addition, electrophoretic mobility shift assay and luciferase reporter assays showed that HDNC significantly suppressed TNF-alpha-mediated activation and translocation of nuclear factor-kappaB (NF-kappaB). This was further confirmed by Western blot analysis of nuclear extracts wherein levels of RelA, the p65 component of NF-kappaB, were significantly less in cells treated with HDNC. Together, the data suggest that the novel compound HDNC (marmelin) is a potent anticancer agent that induces apoptosis during G(1) phase of the cell cycle and could be a potential chemotherapeutic candidate.     

Exposure to chewing tobacco promotes primary oral squamous cell carcinoma and regional lymph node metastasis by alterations of SDF1α/CXCR4 axis

A high incidence of oral squamous cell carcinoma (OSCC) is observed in South‐East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in OSCC. This study aimed to understand the alterations in metastasis biomarkers, such as stromal cell–derived factor‐1α (SDF‐1 or SDF1α) and its receptor C‐X‐C chemokine receptor type 4 (CXCR4), in OSCC patient samples that were stratified based on the history of addiction to chewing tobacco. Targeted immunohistochemical staining and Western blotting were performed on primary tumour and metastatic lymph node (LN) tissues in parallel. Overexpression of hepatocyte growth factor (HGF), activated form of its cognate receptor tyrosine kinase, c‐Met (p‐Met), GRB2‐associated‐binding protein 1 (Gab1), phospho‐protein kinase B (pAkt), nuclear factor kappa B (NF‐κB) and cyclooxygenase‐2 (COX‐2) were observed in primary tumour and metastatic lymph nodes in both chewer and non‐chewer cohorts. Variance analysis showed significant positive correlation between them (P < .0001) indicating upregulation of these biomarkers upon ligand‐induced activation of c‐Met in both tobacco chewers and non‐chewers. Significantly higher expressions of SDF1α and CXCR4 were observed in both primary tumours and metastatic lymph nodes of tobacco chewers (P < .0001) and coincided with overexpressed HGF. In contrast, no significant correlation was observed between expression of HGF and that of SDF1α and CXCR4 in non‐chewers. Together, our findings provide important insights into the association of HGF/c‐Met and the SDF1α/CXCR4 axis in lymph node metastasis and to an aetiological link with the habit of chewing tobacco.     

Real-time PCR-based mismatch amplification mutation assay for specific detection of CS6-expressing allelic variants of enterotoxigenic Escherichia coli and its application in assessing diarrheal cases and asymptomatic controls

Enterotoxigenic Escherichia coli (ETEC) expressing the colonization factor CS6 is widespread in many developing countries, including India. The different allelic variants of CS6, caused by point mutations in its structural genes, cssA and cssB, are designated AIBI, AIIBII, AIIIBI, AIBII, and AIIIBII. A simple, reliable, and specific mismatch amplification mutation assay based on real-time quantitative PCR (MAMA-qPCR) was developed for the first time for the detection of CS6-expressing ETEC, along with the identification of allelic variations. The assay was based on mismatched nucleotide incorporation at the penultimate base at the 3' ends of the reverse primers specific for cssA and cssB and was validated using 38 CS6-expressing ETEC isolates. This strategy was effective in detecting all the alleles containing single-nucleotide polymorphisms. Using MAMA-qPCR, we also tested CS6 allelic variants in 145 ETEC isolates from children with acute diarrhea and asymptomatic infections, with the latter serving as controls. We observed that the AIBI and AIIIBI allelic variants were mostly associated with cases rather than controls, whereas the AIIBII variants were detected mostly in controls. In addition, the AIBI and AIIIBI alleles were frequently associated with ETEC harboring the heat-stable toxin gene (est) alone or with the heat-labile toxin gene (elt), whereas the AIIBII allele was predominant in ETEC isolates harboring the elt gene. This study may help in understanding the association of allelic variants in CS6-expressing ETEC with the clinical features of diarrhea, as well as in ETEC vaccine studies.     

A randomized comparative study on vaginal administration of acetic acid-moistened versus dry misoprostol for mid-trimester pregnancy termination

Purpose  

Absorption and effectiveness of vaginally administered misoprostol tablets may vary according to the medium in which it is placed. This study was directed to compare the outcomes of vaginal administrations of acetic acid-moistened misoprostol tablets with those of dry tablets for induction of second-trimester abortion.     

Urinary uric acid in preterm neonates

Objective  

Study of uric acid level in spot urine of normal preterm AGA (appropriate for gestational age) babies in day one of their life.     

DISFIGURING MOLLUSCUM CONTAGIOSUM IN A HIV-POSITIVE PATIENT RESPONDING TO ANTIRETROVIRAL THERAPY

Molluscum contagiosum (MC) is caused by a double stranded DNA virus belonging to the pox virus family. MC lesions are usually pearly, dome shaped, small, discrete lesions with central umbilication. In HIV-positive patients atypical varieties are found. They may be large or nonumbilicated. Individual papules may join to form the agminate variety. This form is rare. Lesions of MC in healthy immunocompetent patients may occur at any part of the body including face, trunk, and limbs. Sexually active adults have lesions usually on the genitalia, pubis, and inner thigh, rarely on the face and scalp. We present a case of agminate MC occurring in a patient with acquired immunodeficiency disease responding to highly active antiretroviral therapy.     

Genes induced by a high-oxygen environment in Entamoeba histolytica

Entamoeba histolytica, although a microaerophilic protozoan parasite, encounters a high-oxygen environment, during invasive amoebiasis. The parasite requires specific regulation of certain proteins to maintain its physiological functions to survive in the more oxygenated condition. Our endeavor was to know how does amoeba adapt itself in a high-oxygen environment. Reactive oxygen species (ROS) was found to accumulate in an increasing concentration within the stressed trophozoites in a time-dependent manner. Increased cytopathic activity was detected at 2h in high-oxygen-exposed E. histolytica lysate compared to lysate of normal E. histolytica trophozoites by Ussing chamber assay. The differential display and semi-quantitative polymerase chain reaction showed overexpression in the mRNA levels of thiol-dependent peroxidase (Eh29), superoxide dismutase (SOD), EhCP5, G protein, HSP70, and peptidylprolyl isomerase at different time periods of oxidative stressed trophozoites compared to normally cultured E. histolytica. Analyses of the up-regulated genes that are associated with stress response, viz., signal transduction, tissue destruction, and oxidative stress management, including enhanced expression of a 29-kDa Eh29, suggest that this organism has several protective mechanisms to deal with oxidative stress during invasion.     

Enterotoxigenic Escherichia coli CS6 gene products and their roles in CS6 structural protein assembly and cellular adherence

Enterotoxigenic Escherichia coli (ETEC) produces a variety of colonization factors necessary for attachment to the host cell, among which CS6 is one of the most prevalent in ETEC isolates from developing countries. The CS6 operon is composed of 4 genes, cssA, cssB, cssC, and cssD. The molecular mechanism of CS6 assembly and cell surface presentation, and the contribution of each protein to the attachment of the bacterium to intestinal cells remain unclear. In the present study, a series of css gene-deletion mutants of the CS6 operon were constructed in the ETEC genetic background, and their effect on adhesion to host cells and CS6 assembly was studied. Each subunit deletion resulted in a reduction in the adhesion to intestinal cells to the same level of laboratory E. coli strains, and this effect was restored by complementary plasmids, suggesting that the 4 proteins are necessary for CS6 expression. Bacterial cell fractionation and western blotting of the mutant strains suggested that the formation of a CssA-CssB-CssC complex is necessary for recognition by CssD and transport of CssA-CssB to the outer membrane as a colonization factor.