ANTI-ULCER STUDY OF STANDARDIZED ETHANOL ROOT EXTRACT OF AGANOSMA DICHOTOMA AND ISOLATED URSOLIC ACID

Objective: Aganosma dichotoma K. Schum (Apocynaceae) has been traditionally used as an Ayurvedic ulcer treatment and the study scientifically validates the antiulcer effect of A. dichotoma ethanol root extract (EAD).Methods: The studies included the isolation, quantification of ursolic acid through HPTLC. Acute and sub-acute toxicity study of EAD for 28 d and antiulcer effect of ursolic acid (50 mg/kg, p. o.), EAD (100, 200 and 400 mg/kg, p. o.) were also evaluated on both the physical (pyloric ligation, PL; cold restrain stress, CRS;) and chemical (absolute ethanol, aspirin, ASP;) induced ulcer in Charles Foster albino rats for 7 d. The various gastric-ulcer parameters, viz. gastric pH, volume, acid-pepsin output, DNA content, H+K+-ATPase activity, mucus content, microvascular permeability, antioxidant enzyme, and gastric histopathological study were performed.Results: The isolated ursolic acid was characterized by NMR and mass spectrometer and quantified through HPTLC in EAD (4.26% w/w). Acute oral toxicity study indicated that LD50 of extract was ≥ 5 g/kg. EAD at the dose of 200 and 400 mg/kg, p. o. reduced the ulcer score in both physical and chemical-induced ulcer models. In PL model EAD (400 mg/kg, p. o.) and ursolic acid (50 mg/kg, p. o.) showed antisecretory property by inhibiting aggressive factors [increase in gastric pH (35.02%, 26.73%), whereas decreased gastric volume (43.55%, 34.35%) and acid-pepsin output (75.23%, 68.81%), respectively]. EAD at 400 mg/kg p. o. showed significant effect on proton pump inhibition while ursolic acid didn't showed any effect.Conclusion: The effects of EAD were accredited mainly to the offensive mechanism and justify its traditional usage in the treatment of gastric ulcers

Visual inspection with acetic acid for cervical cancer screening in a tertiary health care centre

Background: Cervical cancer is one of the most prevalent malignant neoplasms among women in developing countries. Invasive cervical cancer is preceded by a long premalignant phase known as cervical intraepithelial neoplasia (CIN). The goal of cervical cancer screening is the detection and treatment of precancereous lesions before cancer develops. The objective of the study was to assess visual inspection with acetic acid (VIA) as a screening tool for use in a well-equipped health center , to evaluate VIA as an alternative or adjunct to the Papanicolaou (Pap) smear, and to determine if VIA can play a role in settings other than low resource ones.Methods: This was a prospective study of 1520 asymptomatic women, carried out in 2014-2015. The study was performed at a tertiary care center equipped with the latest-generation technology and highly trained oncologists. The women underwent a complete clinical evaluation, including a Pap smear and VIA. Participants with any positive test were referred for colposcopy and biopsy.Results: More women tested positive by VIA than on the Pap smear (6.9% vs. 4.2%; P =0.0001). There were 27 women with histologic cervical intraepithelial neoplasia grade 1 (CIN1); of these, 12 were detected by Pap and 15 by VIA (P = 0.4). A diagnosis of CIN 2 or 3 (CIN2–3) was confirmed in a total of 11 cases; Pap detected 4 of the cases and VIA 9 of the cases (P = 0.06). The positive predictive value for detection of CIN 2+ was 8.5% for VIA and 6.2% for Pap (P = 0.5). Most importantly, while only 2.8% of patients with a positive VIA were lost to follow-up before colposcopy that was true for 26.5% of the women with a positive Pap smear (P < 0.0001).Conclusions: VIA is useful for detection of precursor lesions of cervical cancer not only in low-resource settings but also in well-equipped health centers and cancer centers. In these non low-resource settings, VIA has a positive predictive value comparable to the conventional Pap smear, but it is more likely to achieve earlier diagnosis, follow-up, and treatment than cytology based screening

Sleeping habits among school children and their effects on sleep pattern

Introduction: Sleep problems can occur at any age. Inadequate sleep affects the physiological as well as psychological well-being of an individual. Thus, the objective of the present study is, to determine the pre sleep habits, duration and pattern of sleep among school children and to determine association between their sleep schedules and sleep habits.Method: The study comprised of 1050 children attending the government school. Based on inclusion and exclusion criteria children were divided into three age groups: 4-5 years, 6-10 years and 11-15 years of age. A questionnaire about demographical data, sleep problems and habits, was duly filled by the parents. The parents of children were questioned for bed time, wakeup time, sleep time and sleep duration during both weekdays and weekends.Results: Total sleep time during weekdays was 8.9± 1.2 hours and 10.7 ± 1.1 hours during weekends. The wakeup time was significantly delayed during weekends in all age groups (p<0.05). Moreover, total sleep time increased significantly during weekends in all age groups (p<0.05). Children using media after 8 pm and sleeping alone are also in significant sleep debt.Conclusion: Screen activities such as TV, internet and cellular phones in a child’s bedroom had a negative effect on children’s sleep/wake patterns, duration of sleep. Children in higher grades are sleep debt compared to younger ones. Practices such as co sleeping and sharing bed with parents significantly improve the duration and quality of sleep

MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation

MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-γ agonist that lowers glucose in the absence of some of the side effects, such as weight gain and edema, that are observed with the TZDs. Interestingly MBX-102 also displays pronounced triglyceride lowering in preclinical rodent models and in humans. Although in vitro reporter gene studies indicated that MBX-102 acid is a highly selective PPAR-γ agonist that lacks PPAR-α activity, we sought to determine if PPAR-α activation in vivo could possibly contribute to the triglyceride lowering abilities of MBX-102. In vivo studies using ZDF and ZF rats demonstrated that MBX-102 lowered plasma triglycerides. However in ZF rats, MBX-102 had no effect on liver weight or on hepatic expression levels of PPAR-α target genes. Further in vitro studies in primary human hepatocytes supported these findings. Finally, the ability of MBX-102 to lower triglycerides was maintained in PPAR-α knockout mice, unambiguously establishing that the triglyceride lowering effect of MBX-102 is PPAR-α independent. The in vivo lipid lowering abilities of MBX-102 are therefore mediated by an alternate mechanism which is yet to be determined

Pacti: Scaling Assume-Guarantee Reasoning for System Analysis and Design

Contract-based design is a method to facilitate modular system design. While there has been substantial progress on the theory of contracts, there has been less progress on scalable algorithms for the algebraic operations in this theory. In this paper, we present: 1) principles to implement a contract-based design tool at scale and 2) Pacti, a tool that can efficiently compute these operations. We then illustrate the use of Pacti in a variety of case studies

A Salmochelin S4-inspired Ciprofloxacin Trojan Horse Conjugate

A novel ciprofloxacin-siderophore Trojan Horse antimicrobial was prepared by incorporating key design features of salmochelin S4, a stealth siderophore that evades mammalian siderocalin capture via its glycosylated catechol units. As-sessment of the antimicrobial activity of the conjugate revealed that attachment of the salmochelin mimic resulted in decreased potency, compared to ciprofloxacin, against two Escherichia coli strains, K12 and Nissle 1917, in both iron-replete and deplete conditions. This observation could be attributed to a combination of reduced DNA gyrase inhibi-tion, as confirmed by in vitro DNA gyrase assays, and reduced bacterial uptake. Uptake was monitored using radio-labelling with iron-mimetic 67Ga3+, which revealed limited cellular uptake in E. coli K12. In contrast, previously reported staphyloferrin-based conjugates displayed measurable uptake in analogous 67Ga3+, labelling studies. These results suggest that in designing Trojan Horse antimicrobials, the choice of siderophore and the nature and length of the link-er remains a significant challenge

Harmful and beneficial aspects of Parthenium hysterophorus: an update

Parthenium hysterophorus is a noxious weed in America, Asia, Africa and Australia. This weed is considered to be a cause of allergic respiratory problems, contact dermatitis, mutagenicity in human and livestock. Crop production is drastically reduced owing to its allelopathy. Also aggressive dominance of this weed threatens biodiversity. Eradication of P. hysterophorus by burning, chemical herbicides, eucalyptus oil and biological control by leaf-feeding beetle, stem-galling moth, stem-boring weevil and fungi have been carried out with variable degrees of success. Recently many innovative uses of this hitherto notorious plant have been discovered. Parthenium hysterophorus confers many health benefits, viz remedy for skin inflammation, rheumatic pain, diarrhoea, urinary tract infections, dysentery, malaria and neuralgia. Its prospect as nano-medicine is being carried out with some preliminary success so far. Removal of heavy metals and dye from the environment, eradication of aquatic weeds, use as substrate for commercial enzyme production, additives in cattle manure for biogas production, as biopesticide, as green manure and compost are to name a few of some other potentials. The active compounds responsible for hazardous properties have been summarized. The aim of this review article is to explore the problem P. hysterophorus poses as a weed, the effective control measures that can be implemented as well as to unravel the latent beneficial prospects of this weed

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Tracking Uptake and Metabolism of Xenometallomycins Using a Multi-Isotope Tagging Strategy.

Synthetic and naturally occurring siderophores and their conjugates provide access to the bacterial cytoplasm via active membrane transport. Previously, we displaced iron with the radioactive isotope 67Ga to quantify and track in vitro and in vivo uptake and distribution of siderophore Trojan Horse antibiotic conjugates. Here, we introduce a multi-isotope tagging strategy to individually elucidate the fate of metal cargo and the ligand construct with radioisotopes 67Ga and 124I. We synthesized gallium(III) model complexes of a ciprofloxacin-functionalized linear desferrichrome (Ga-D6) and deferoxamine (Ga-D7) incorporating an iodo-tyrosine linker to enable radiolabeling using the metal-binding (67Ga) and the cargo-conjugation site (124I). Radiochemical experiments with Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa wt strains show that 67Ga-D6/D7 and Ga-D6-124I/D7-124I have comparable uptake, indicating intact complex import and siderophore-mediated uptake. In naive mice, 67Ga-D6/D7 and Ga-D6-124I/D7-124I demonstrate predominantly renal clearance; urine metabolite analysis indicates in vivo dissociation of Ga(III) is a likely mechanism of degradation for 67Ga-D6/D7 when compared to ligand radiolabeled compounds, Ga-D6-124I/D7-124I, which remain &gt;60% intact in urine. Cumulatively, this work demonstrates that a multi-isotope tagging strategy effectively elucidates the in vitro uptake, pharmacokinetics, and in vivo stability of xenometallomycins with modular chemical structures

A Comparative Evaluation of Sucrose, Sorbitol and Sugar Free Chewing Gum on Plaque pH in Children after Sucrose Challenge

Introduction: Dental caries is a multifactorial disease. Ingestion of various dietary sugars plays dominant role in the caries etiology. Clinical evidence shows that the use of sugar -free chewing gum does not lead to caries, presumably because the sugar substitutes used do not lead to the production of metabolic acids in plaque at a rate sufficient to cause a fall in pH and to attack the teeth. The present study aimed to evaluate and compare the effect of sucrose and sorbitol chewing gums and sugar free chewing gum on acidogenicity of plaque after sucrose challenge. Methodology: 78 volunteers (48 boys and 30 girls) aged 6-14 years were randomly divided into 3 groups comprising 26 children in each group. In the present controlled trial, three types of chewing gums: sucrose based, sorbitol based and natural gum were used. One type of chewing gum was used in each group. Plaque pH was recorded before and after sucrose challenge at different time intervals. Same experiments were repeated along with other chewing gums. Results: The sucrose challenge decrease the plaque pH, however all the types of chewing gums used in the present study prevented the decrease in plaque pH caused by sucrose challenge. The effects were statistically significant (p<0.01). The prevention of the fall in plaque pH was observed to be less by sucrose gum as compared to the effect caused by sweetener gum and natural gum. Conclusion: It is concluded that the use of sugar free chewing gums prevents the fall in plaque pH caused by sucrose challenge. The patient should be instructed to use a sugar free gum within 5 minutes of eating and to continue chewing for at least 20 minutes