An integrated surveillance network for antimicrobial resistance,India

ObjectiveTo assess the preparedness of veterinary laboratories in India to participate in an integrated antimicrobial resistance surveillance network and to address gaps in provision identified.MethodsThe Indian Council of Medical Research and the Indian Council of Agricultural Research collaborated: (i) to select eight nationally representative veterinary microbiology laboratories whose capacity for participating in an integrated antimicrobial resistance surveillance network would be assessed using a standardized tool; (ii) to identify gaps in provision from the assessment findings; and (iii) to develop a plan, and take the necessary steps to address these gaps in consultation with participating organizations.FindingsThe main gaps in provision identified were: (i) a lack of dedicated funding for antimicrobial resistance surveillance; (ii) the absence of standard guidelines for antimicrobial susceptibility testing; (iii) a shortage of reference strains for testing and quality assurance; and (iv) the absence of mechanisms for sharing data. We addressed these gaps by creating a veterinary standard operating procedure for antimicrobial susceptibility testing, by carrying out a validation exercise to identify problems with implementing the procedure and by conducting capacity-building workshops for veterinary laboratories.ConclusionAntimicrobial resistance surveillance networks depend on the availability of accurate, quality-controlled testing. The challenges identified in creating an integrated surveillance network for India can be overcome by developing a comprehensive plan for improving laboratory capacity in human, veterinary and environmental sectors that is supported by the necessary funds. The study’s findings may provide guidance for other low- and middle-income countries planning to develop a similar network.     

Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: An animal trial

Purpose:

The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB).

Design:

Experimental, comparative, animal study.

Materials and Methods:

Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test.

Results:

The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P < 0.05).

Conclusion:

A higher trans-scleral permeability gradient is obtained with the novel nanoparticles than with the commercial drug, leading to sustained higher levels of carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in the treatment for advanced clinical RB, specifically those with vitreous seeds.     

The activation of phospholipase D by endothelin-1, angiotensin II, and platelet-derived growth factor in vascular smooth muscle A10 cells is mediated by small G proteins of the ADP-ribosylation factor family

We show here that A10 cells express the phospholipase D (PLD) isoforms PLD1b and PLD2. The activation of PLD in these cells by angiotensin II (AngII), endothelin-1 (ET-1), and platelet-derived growth factor (PDGF) was found to be sensitive to inhibitors of the activation of ADP-ribosylation factor (ARF) but not to blockers of Rho protein function. PDGF, AngII, and ET-1 induced the binding of ARF proteins to cell membranes in a permeabilized cell assay. Cells permeabilized and depleted of ARF were no longer sensitive to stimulation with AngII, ET-1, or PDGF, but the addition of recombinant myristoylated human ARF1 restored agonist-dependent PLD activity. Expression of dominant negative ARF mutants blocked receptor-dependent activation of PLD. PLD activity was also potently stimulated by treatment with phorbol esters, but this activity was only partially inhibited by brefeldin A or by the overexpression of ARF dominant negative mutants. Transient expression of catalytically inactive mutants of PLD2, but not PLD1, inhibited significantly PDGF- and AngII-dependent PLD activity. We conclude: 1) the activation of PLD by cell surface receptors occurs primarily by an ARF-dependent mechanism in A10 cells, whereas the activation of PLD by protein kinase C-dependent pathways is only partially dependent on the regulation of ARF proteins; and 2) cell surface receptors, such as AngII and PDGF, signal primarily via PLD2 in A10 cells.     

Temporal and Spatial Epidemiological Analysis of Peste Des Petits Ruminants Outbreaks from the Past 25 Years in Sheep and Goats and Its Control in India

This study was aimed to understand the temporal and spatial epidemiology of peste des petits ruminants (PPR) in India using national surveillance data available in the National Animal Diseases Referral Expert System (NADRES) along with its control plan undertaken. On analysis of the outbreaks/cases reports in sheep and goats in NADRES database from 1995 to 2019, it was observed that PPR features among the top ten diseases and stands first among viral diseases, and among reported deaths, PPR accounts for 36% of mortality in sheep and goats. PPR outbreaks occur round the year in all the seasons but are encountered most frequently during the lean period especially, in the winter season (January to February) in different regions/zones. The reported outbreaks have been progressively declined in most of the states in India due to the implementation of a mass vaccination strategic program since 2011. On state-wise analysis, the PPR risk-areas showed wide variations with different levels of endemicity. Andhra Pradesh, West Bengal, and Karnataka were the top three outbreaks reported states during 1995–2010, whereas Jharkhand and West Bengal states reported more outbreaks during 2011–2015 and 2016–2019 periods. The temporal and spatial distribution of PPR in India provides valuable information on the hotspot areas/zones to take appropriate policy decisions towards its prevention and control in different regions/zones of India. The study also identifies when and where intensive surveillance and vaccination along with biosecurity measures need to be implemented for the control and eradication of the disease from India in consonance with the PPR Global Control and Eradication Strategy.     

Stevens-Johnson syndrome following use of metronidazole in a dental patient

Metronidazole alone rarely causes Stevens-Johnson syndrome (SJS). We present a case of an elderly male patient who, following metronidazole use, developed neurological symptoms followed by pain and blisters on both soles, erythema of face and neck, scrotal itching and erosion, and hemorrhagic encrustation around the lips and oral mucous membrane. Initial neurological symptoms followed by mucocutaneous manifestation of SJS following metronidazole use is probably a new presentation of this case.KEY WORDS: Metronidazole, neurological manifestation, Stevens-Johnson syndrome     

Exhaled Nitric Oxide in Asthma: Variability, Relation to Asthma Severity, and Peripheral Blood Lymphocyte Cytokine Expression

Exhaled nitric oxide has been used as a means of indirectly measuring the underlying inflammation in asthma. The objectives of the study were to measure exhaled nitric oxide levels in asthma patients and healthy volunteers, to study peripheral blood lymphocyte cytokine expression, and to study the relationship between exhaled nitric oxide and intracellular cytokine expression. Exhaled nitric oxide was elevated in patients with moderate to severe asthma and with treatment decreased in the first week reaching to a near normal level by 4 weeks. Elevated exhaled nitric oxide was associated with decreased IL-4 and IL-13 cytokine expression by CD8 lymphocytes.