Microtubules: dynamics,drug interaction and drug resistance in Leishmania

Microtubules are cytoskeletal polymers essential for the survival of all eukaryotes. These proteins are the proposed cellular targets of many anticancerous, antifungal and antihelminthic drugs. Sufficient differences exist between the microtubules of kinetoplastid parasites like Leishmania and humans to explore the selective targeting of these proteins for therapeutic purposes. This review describes the basic structure of microtubules and its dynamics in general, with specific insights into leishmanial microtubules, the salient features of microtubule-drug interactions including the specificity of certain drugs for parasitic microtubules. Chemotherapy against leishmanial parasites is failing because of the emergence of drug resistant strains. The possible mechanisms of resistance to antimicrotubule agents along with insights into the role of microtubules in mediating drug resistance in Leishmania are discussed.     

Facts about artefacts in diagnostic pathology

Literal meaning of artefact given by 'Oxford Advanced Learner Dictionary' is 'a thing made by people'. In medical science 'the fact' is not true; but we observe routinely is called artefact. We face various types of artefacts in daily reporting of pathology specimen. Many times artefacts hinder the actual diagnosis. The artefacts i. e. fixation artefact, processing artefact, staining artefact, mounting artefact, air bubbles etc. can cause difficulty in diagnosis and a pathologist should be trained to identify those artefacts.     

Asphalt exposure enhances neuropeptide levels in sensory neurons projecting to the rat nasal epithelium

Asphalt fumes have been reported to produce nasal irritation in road workers. Since inhaled irritants can increase substance P (SP) production in airway neurons, the effects of asphalt fumes on SP production in trigeminal ganglia (TG) sensory neurons innervating the nasal mucosa were investigated. The effects of asphalt fumes on nasal mucosal innervation were examined by measuring SP and calcitonin-gene-related peptide (CGRP) levels in rat TG neurons projecting to the nasal epithelium. Female Sprague-Dawley rats were exposed to asphalt fumes at 16.0 +/- 8.1mg /m3 for 5 consecutive days, 3.5 h/d. Inflammatory cells were measured in nasal cavity lavage fluid. SP and CGRP immunoreactivity (IR) was measured in the cell bodies of trigeminal ganglion sensory neurons projecting to the nasal cavity. A significant increase in neutrophils and macrophages was observed after asphalt fume exposure indicating an inflammatory response in the nasal cavity. The percentage of SP-IR neurons increased significantly in the asphalt-exposed rats, and the proportion of CGRP-IR neurons was also elevated following asphalt exposure. These results indicate that exposure to asphalt fumes produces inflammation and increases the levels of SP and CGRP in TG neurons projecting to the nasal epithelium. The findings are consistent with asphalt-induced activation of sensory C-fibers in the nasal cavity. Enhanced sensory neuropeptide release from nerve terminals in the nasal cavity may produce neurogenic inflammation associated with nasal irritation following exposure to asphalt fumes.     

Transdermal iontophoresis of insulin. Part 1: A study on the issues associated with the use of platinum electrodes on rat skin

We have studied the issues associated with the use of platinum electrodes for transdermal iontophoretic delivery of peptides, using insulin as a model peptide. Insulin permeation was studied using full-thickness rat skin by varying the donor solution pH as a function of electrode polarity. The stability of insulin under the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel electrophoresis and HPLC. Large pH shifts were observed during anodal iontophoresis (AI), when the donor solution pH was above the isoelectric point of insulin and in cathodal iontophoresis (CI), when the donor solution pH was below the isoelectric point of insulin. The direction and magnitude of electroosmotic flow was influenced by pH of the donor solution and the electrode polarity. On the other hand, the buffer used to maintain the pH governed the contribution of electrorepulsion to the overall transport of insulin. Electrochemical degradation of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively less and electrochemically more stable during iontophoresis as compared with other pH. In summary, the pH shift caused by platinum electrodes had a significant influence on the permeation and stability of insulin.     

Outbreaks of Escherichia coli O157 infections at multiple county agricultural fairs: a hazard of mixing cattle, concession stands and children

Escherichia coli O157 infections cause an estimated 60 deaths and 73 000 illnesses annually in the United States. A marked summer peak in incidence is largely unexplained. We investigated an outbreak of E. coli O157 infections at an agricultural fair in Ohio and implicated consumption of beverages made with fairground water and sold by a geographically localized group of vendors who were all on the same branch of the fairground water distribution system. To examine county fair attendance as a risk factor for infection, we conducted two further epidemiological studies. In the first, we enhanced surveillance for E. coli O157 infections in 15 Northeast Ohio counties during the 2000 agricultural fair season and showed increased risk of E. coli O157 infection among fair attendees. In the second study, we examined Ohio Public Health Laboratory Information Service (PHLIS) data for 1999 using a time-varying covariate proportional hazards model and demonstrated an association between agricultural fairs and E. coli O157 infections, by county. Agricultural fair attendance is a risk factor for E. coli O157 infection in the United States and may contribute to the summer peak in incidence. Measures are needed to reduce transmission of enteric pathogens at agricultural fairs.     

<Emphasis Type="Italic">Scutellaria baicalensis</Emphasis> extract decreases cisplatin-induced pica in rats

Purpose Nausea/vomiting are significant side effects associated with the use of chemotherapy in cancer patients. Treatment of nausea/vomiting caused by cisplatin, a potent chemotherapeutic agent and one of the most emetogenic stimuli, requires a combination of different antiemetic drugs. In this study, we investigated the effects of Scutellaria baicalensis, an antioxidant herbal medicine, on cisplatin-induced nausea using a rat model.Methods Rats react to emetic/nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by pica or increased consumption of kaolin (a type of clay). We measured pica in rats to quantify cisplatin-induced nausea, and to evaluate the antinausea effect of pretreatment with S. baicalensis extract (SbE) given intraperitoneally.Results Cisplatin at 3 mg/kg induced significant pica accompanied by reduced food intake, suggesting the presence of nausea. Hence, this cisplatin dose was selected for testing the antinausea activity of SbE. Cisplatin-induced pica decreased significantly when animals were pretreated with SbE at doses of 1 mg/kg and 3 mg/kg (P<0.01). At a higher SbE dose (10 mg/kg), kaolin consumption increased, rather than further decreased, and was significantly different from that in the groups treated with low SbE doses.Conclusions SbE pretreatment decreased cisplatin-induced kaolin intake in the rat model of simulated nausea, suggesting that SbE and its active constituent(s) may play a therapeutic role in chemotherapy-induced emesis. Absence of therapeutic effect at the highest tested SbE dose could have been a result of prooxidant activity often associated with excess antioxidant concentration.This work was supported in part by NIH grants R01 CA79042, P30 CA14599, and R21 AT00381.     

Developing public health indicators in complex emergency response

During the past decade, indicators for the assessment, monitoring, and evaluation of services provided by humanitarian organizations to populations affected by complex emergencies (CEs) were developed to improve the effectiveness and accountability of humanitarian response. The quality of data used to develop individual indicators and their relationship to positive health outcomes varies greatly. This article states the essential characteristics necessary for the development and implementation of effective indicators in CE response and proposes the establishment of an evidence-based grading system. The importance of trend analysis and the modification or addition of various indicators and their thresholds, according to phase and location of CEs, are stressed. Limitations in the development, implementation, and interpretation of these indicators, including those outside of the organizations' control are discussed. More evidence-based research is needed as to the type and thresholds of indicators that lead to improved health outcomes in populations affected by CEs. The use of indicators by non-governmental organizations, and how they affect their program's decision-making in different phases and settings within CEs need further study. Finally, the establishment of a regulating body with the authority to enforce the attainment of standards by use of these indicators is necessary to avoid inappropriate humanitarian assistance causing loss of life in the future.     

Nosocomial ocular infection--a prospective study

Nosocomial infection of the eye is an uncommon complication, acquired during the course of hospital management. It may prolong the disease process or even destroy the eye. The overall incidence varies considerably by hospital services. To ascertain the various types of ocular infections and its responsible pathogens, a laboratory-based, nosocomial ocular infection control study was performed in a large referral hospital during a period of January 1997 to June 1999. The study revealed 29 cases (0.08%) of culture proven ocular infections, out of 35,758 total admission during the period of one calendar year. Fifty-one eyes of 29 cases (22 bilateral) had nosocomial infection. Staphylococcus aureus (9), Staphylococcus epidermidis (8) and Pseudomonas aeruginosa (5), were the most frequent bacteria. Laboratory investigations helped in initiation and modification of specific antimicrobial therapy and also prognosis. Proper surveillance with the help of laboratory investigations has effective role in the management of nosocomial ocular infection.