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PubMed2001

Increased ErbB-2 tyrosine kinase activity, MAPK phosphorylation, and cell proliferation in the prostate cancer cell line LNCaP following treatment by select pesticides.

The oncogene erbB-2 codes for a receptor tyrosine kinase that functions as a key mitotic signal in a variety of cell types. Amplification or overexpression of erbB-2 occurs in many forms of cancer, such as of the breast, colon, and prostate, and is an indicator of poor prognosis in those diseases. In the human prostate cancer cell lines LNCaP and PC-3, erbB-2 kinase was activated by pesticides of different chemical classes: (1) the organochlorine insecticides beta-hexa-chlorocyclohexane (beta-HCH), o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), and heptachlor epoxide; (2) the pyrethroid insecticide trans-permethrin, and (3) the fungicide chlorothalonil. o,p'-DDT also causes phosphorylation of mitogen-activated protein kinase (MAPK) and cellular proliferation of the androgen-dependent LNCaP line. However, no proliferative effect was observed in the androgen-independent PC-3 line. The proliferative effect of o,p'-DDT in LNCaP could not be blocked by the androgen receptor antagonist p,p'-dichlorodiphenyldichloroethene (p,p'-DDE), indicating that this effect of o,p'-DDT does not occur through direct interaction with the androgen receptor. Together these data demonstrate a putative mechanism for the action of certain pesticides in hormonal carcinogenesis.

Adenocarcinoma↗
PubMed2004

Organophosphorus insecticides induce airway hyperreactivity by decreasing neuronal M2 muscarinic receptor function independent of acetylcholinesterase inhibition.

We previously demonstrated that the organophosphorus (OP) insecticide chlorpyrifos potentiates vagally induced bronchoconstriction independent of acetylcholinesterase (AChE) inhibition by decreasing the function of neuronal M2 muscarinic receptors that normally inhibit acetylcholine release from parasympathetic nerves supplying airway smooth muscle. However, it has been reported that different OPs may not affect muscarinic receptors equally. To determine if the effects of chlorpyrifos on airway hyperreactivity can be generalized to other OPs, we tested whether parathion and diazinon also inhibit neuronal M2 receptor function resulting in airway hyperreactivity. In control animals, the M2 agonist pilocarpine inhibits vagally induced bronchoconstriction in a dose-related manner. Treatment of guinea pigs with either parathion (1-10 mg/kg, sc) or diazinon (0.75-75 mg/kg, sc) shifted pilocarpine dose-response curves significantly to the right, indicating loss of neuronal M2 receptor function. These OP treatments also significantly potentiated vagally induced bronchoconstriction. Treatments that did not decrease M2 receptor function (parathion at 0.1 mg/kg, sc, or the non-OP insecticide permethrin at 150 mg/kg, sc) also did not cause airway hyperreactivity. None of the OP treatments altered bronchoconstriction induced by iv acetylcholine or methacholine in vagotomized guinea pigs, suggesting that OP-induced airway hyperreactivity is not due to altered function of muscarinic receptors on airway smooth muscle or to AChE inhibition. AChE assays of lung, blood, and brain confirmed that parathion and diazinon decreased M2 function at concentrations that did not inhibit AChE. These data suggest that multiple diethyl phosphorothionate OPs cause airway hyperreactivity via a common mechanism of M2 receptor dysfunction independent of AChE inhibition.

Acetylcholinesterase↗
PubMed2005

Relative potencies for acute effects of pyrethroids on motor function in rats.

The prevalence of pyrethroids in insecticide formulations has increased in the last decade. A common mode-of-action has been proposed for pyrethroids based on in vitro studies, which includes alterations in sodium channel dynamics in nervous system tissues, consequent disturbance of membrane polarization, and abnormal discharge in targeted neurons. The objective of this work was to characterize individual dose-response curves for in vivo motor function and calculate relative potencies for eleven commonly used pyrethroids. Acute oral dose-response functions were determined in adult male Long Evans rats for five Type I (bifenthrin, S-bioallethrin, permethrin, resmethrin, tefluthrin), five Type II (beta-cyfluthrin, lambda-cyhalothrin, cypermethrin, deltamethrin, esfenvalerate) and one mixed Type I/II (fenpropathrin) pyrethroids (n = 8-18 per dose; 6-11 dose levels per chemical, vehicle = corn oil, at 1 ml/kg). Motor function was measured using figure-8 mazes. Animals were tested for 1 h during the period of peak effects. All pyrethroids, regardless of structural class, produced dose-dependent decreases in motor activity. Relative potencies were calculated based on the computed ED30s. Deltamethrin, with an ED30 of 2.51 mg/kg, was chosen as the index chemical. Relative potency ratios ranged from 0.009 (resmethrin) to 2.092 (esfenvalerate). Additional work with environmentally-based mixtures is needed to test the hypothesis of dose-additivity of pyrethroids.

Administration, Oral↗
PubMed2006

Identification of new human pregnane X receptor ligands among pesticides using a stable reporter cell system.

Pregnane X receptor (PXR, NR1I2) is activated by various chemically unrelated compounds, including environmental pollutants and drugs. We proceeded here to in vitro screening of 28 pesticides with a new reporter system that detects human pregnane X receptor (hPXR) activators. The cell line was obtained by a two-step stable transfection of cervical cancer HeLa cells. The first transfected cell line, HG5LN, contained an integrated luciferase reporter gene under the control of a GAL4 yeast transcription factor-binding site. The second cell line HGPXR was derived from HG5LN and stably expressed hPXR ligand-binding domain fused to GAL4 DNA-binding domain (DBD). The HG5LN cells were used as a control to detect nonspecific activities. Pesticides from various chemical classes were demonstrated, for the first time, to be hPXR activators: (1) herbicides: pretilachlor, metolachlor, and alachlor chloracetanilides, oxadiazon oxiconazole, and isoproturon urea; (2) fungicides: bupirimate and fenarimol pyrimidines, propiconazole, fenbuconazole, prochloraz conazoles, and imazalil triazole; and (3) insecticides: toxaphene organochlorine, permethrin pyrethroid, fipronil pyrazole, and diflubenzuron urea. Pretilachlor, metolachlor, bupirimate, and oxadiazon had an affinity for hPXR equal to or greater than the positive control rifampicin. Some of the newly identified hPXR activators were also checked for their ability to induce cytochrome P450 3A4 expression in a primary culture of human hepatocytes. HGPXR, with HG5LN as a reference, was grafted onto nude mice to assess compound bioavailability through in vivo quantification of hPXR activation. Altogether, our data indicate that HGPXR cells are an efficient tool for identifying hPXR ligands and establishing pesticides as hPXR activators.

Animals↗
PubMed1994

Identification and management of pediculosis.

Currently, pediculosis affects 6-12 million persons in the United States each year, and this number continues to rise. Social stigma and persistent misconceptions complicate the implementation of appropriate management strategies. Diagnosis is made on the basis of finding nits (i.e., silvery-white eggs firmly attached to the hair shaft), concentrated on the crown, behind the ears, and at the nape of the neck. Transmission occurs by direct contact with an infested person or indirectly by contact with clothing, personal grooming articles, bedding, or upholstered furniture containing viable nits or lice. Although three chemical agents are currently available, permethrin 1.0% (Nix Creme Rinse) is the treatment of choice. Environmental treatment is also necessary for the eradication of the infestation. Health care personnel who come into contact with this population need to be well informed of the facts in order to disseminate accurate information for diagnosis and management.

Adolescent↗
PubMed2001

Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.

Scabies. which constitutes a significant proportion of the outpatient attendance in tropical dermatology clinics, has so far been treated with lindane, crotamiton, sulphur, permethrin, etc. Ivermectin, an orally administered drug, was tried in scabies patients and compared with 1% topical lindane lotion to evaluate its effects and toxicity profile. Two hundred scabies patients were randomly allocated to one of two groups. One group received oral invermectin in a single dose of 200 micrograms/kg body weight. The other received 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindance group showed a similar response. A side effects in the form of severe headache were noted in one patient in group A. Oral ivermectin is an easy drug to administer. It is given as a single oral dose, unlike lindane, which has to be applied topically. The compliance is accordingly increased. Moreover, ivermectin induces an early and effective improvement in signs and symptoms. Thus, it may be a better option for scabies than the traditional topical linlane lotion.

Administration, Oral↗
PubMed1987

The relative efficacy of repellents against mosquito vectors of disease.

Laboratory tests of insect repellents by various different methods showed that An.stephensi Liston was consistently more susceptible than An.gambiae Giles, An.albimanus Wiedemann or An.pulcherrimus Theobald. The six repellents tested were di-ethyl toluamide (deet), di-methyl phthalate (DMP), ethyl-hexanediol, permethrin, citronella and cedarwood oil. Testing systems in which the mosquitoes were presented with a choice gave consistently lower ED50 values than when there was no choice, i.e. the standards of tolerance are not absolute but depend on the options available. In field tests in an experimental hut a curtain with a high dose of di-ethyl toluamide (deet) reduced biting in the hut but had to be re-impregnated frequently. Deet-impregnated anklets gave about 84% protection against Culex quinquefasciatus Say for 80 days after one impregnation, in a trial in which the anklets were brought out of sealed storage and tested for 2 h nightly. Similar protection was found against An.funestus Giles but the protection against An.gambiae s.l., An. coustani Laveran and Mansonia spp. was not as good. There were highly significant differences between the four collectors' mosquito attractiveness but this varied highly significantly between the mosquito species.

Animals↗
PubMed1997

Repellency of synthetic and plant-derived preparations for Culicoides imicola.

The study was conducted to find a safer and longer lasting repellent for C.imicola than di-ethyl toluamide (DEET), to validate whether the current recommendations in Israel for application of repellents during an outbreak of disease caused by pathogens borne by Culicoides imicola are justified, and to test plant-derived preparations as potential replacements for the synthetic repellents. Seven repellents were compared by a method using treated netting across the entrance of a suction light trap. Those inferior to DEET were: oregano and Herbipet which showed a slight non-significant repellency for 2 h, Tri-Tec 14TM which showed significant (P < 0.05) repellency with respect to controls for 2 h and Stomoxin which showed significant (P < 0.05) repellency for 1 h. As the active ingredient of Stomoxin is permethrin, this indicates that recommendations to spray animals with this insecticide to prevent the spread of C.imicola-borne pathogens will not be useful. The repellents superior to DEET were: the plant-derived material Ag 1000 that repelled significantly (P < 0.05) with respect to controls for up to 4 h following a similar pattern to but somewhat more strongly than DEET, and pyrethroid-T which exerted significant (P < 0.05) repellency for 9 h. Pyrethroid-T proved to be the best repellent tested, and if sprayed nightly it might provide protection from C.imicola-borne pathogens.

Animals↗
PubMed2004

DEET mosquito repellent provides personal protection against malaria: a household randomized trial in an Afghan refugee camp in Pakistan.

Synthetic repellents based on di-ethyl 3-methyl benzamide (DEET) are a popular method of obtaining protection from mosquitoes and yet clear evidence for a protective effect against malaria has hitherto never been convincingly demonstrated. A household randomized trial was undertaken among a study population of 127 families (25%) in an Afghan refugee village in Pakistan to compare the efficacy of repellent soap (Mosbar containing 20% DEET and 0.5% permethrin) vs. a placebo lotion. Cases of falciparum and vivax malaria were detected by passive case detection at the camp's clinic. At the end of the 6 month trial 3.7% (23 of 618) of individuals in the Mosbar group had presented with one or more episodes of falciparum malaria compared with 8.9% (47 of 530) of the placebo group (odds ratio 0.44, 95% CI 0.25-0.76). 16.7% of the Mosbar group (103 of 618) presented with vivax malaria compared with 11.7% (62 of 530) of the placebo group, and thus no effect was shown against vivax malaria (odds ratio 1.29, 95% CI 0.86-1.94). A considerable proportion of individuals (22%) had presented with vivax malaria during the 7 months leading up to the trial and thus any intervention effect would be partially masked by relapsed infections. The distribution of mosquitoes among households was broadly similar between Mosbar and placebo groups. The repellent was popularly received and very few side-effects were reported. There is a case for giving repellents more prominence in public health as a preventive measure in regions where vectors bite in the early evening or in emergency situations such as epidemics or newly established refugee camps.

Adolescent↗
PubMed2005

Treatment of canine Old World visceral leishmaniasis: a systematic review.

Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of efficacy of interventions for treatment or prevention of canine visceral leishmaniasis, and to propose recommendations for or against their use. Forty-seven articles describing clinical trials published between 1980 and 2004 fulfilled selection criteria. The evaluation of clinical trials provided good evidence for recommending the use of meglumine antimoniate at a minimum dosage of 100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the articles also provided fair evidence for recommending the use of pentamidine (4 mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks. There was insufficient evidence for recommending the use of allopurinol alone, amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was proposed due to its side effects. Evaluation of articles on repellent measures against sand fly vectors of leishmaniasis provided good evidence for recommending deltamethrin collars and fair evidence for recommending spot-on permethrin.

Animals↗
PubMed1997

Successful use of ivermectin in the treatment of endemic scabies in a nursing home.

Ivermectin, an antiparasitic agent, was successfully used as a sole agent to combat endemic scabies in a closed 33-bed ward of a rural nursing home. Previous topical therapies, including multiple applications of permethrin, gamma-benzene hexachloride, benzyl benzoate and precipitated sulfur in white soft paraffin, had failed. Several patients exhibited hyperkeratotic crusted scabies with head and neck involvement and all residents except one recently arrived resident had evidence of active infestation. All residents were treated with 200 micrograms/kg of ivermectin and this dose was repeated 2 weeks later in all subjects. Four weeks after the first dose of ivermectin there was no evidence of active scabies and all rashes were totally resolved by 6 weeks. The action of ivermectin, its safety and its indications are discussed.

Administration, Oral↗
PubMed2006

Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals.

Cytochromes P450 (P450s) are major catalysts in the metabolism of xenobiotics and endogenous substrates such as estradiol (E2). It has previously been shown that E2 is predominantly metabolized in humans by CYP1A2 and CYP3A4 with 2-hydroxyestradiol (2-OHE2) the major metabolite. This study examines effects of deployment-related and other chemicals on E2 metabolism by human liver microsomes (HLM) and individual P450 isoforms. Kinetic studies using HLM, CYP3A4, and CYP1A2 showed similar affinities (Km) for E2 with respect to 2-OHE2 production. Vmax and CLint values for HLM are 0.32 nmol/min/mg protein and 7.5 microl/min/mg protein; those for CYP3A4 are 6.9 nmol/min/nmol P450 and 291 microl/min/nmol P450; and those for CYP1A2 are 17.4 nmol/min/nmol P450 and 633 microl/min/nmol P450. Phenotyped HLM use showed that individuals with high levels of CYP1A2 and CYP3A4 have the greatest potential to metabolize E2. Preincubation of HLM with a variety of chemicals, including those used in military deployments, resulted in varying levels of inhibition of E2 metabolism. The greatest inhibition was observed with organophosphorus compounds, including chlorpyrifos and fonofos, with up to 80% inhibition for 2-OHE2 production. Carbaryl, a carbamate pesticide, and naphthalene, a jet fuel component, inhibited ca. 40% of E2 metabolism. Preincubation of CYP1A2 with chlorpyrifos, fonofos, carbaryl, or naphthalene resulted in 96, 59, 84, and 87% inhibition of E2 metabolism, respectively. Preincubation of CYP3A4 with chlorpyrifos, fonofos, deltamethrin, or permethrin resulted in 94, 87, 58, and 37% inhibition of E2 metabolism. Chlorpyrifos inhibition of E2 metabolism is shown to be irreversible.

Carbaryl↗
PubMed2005

Treatment of scabies: newer perspectives.

Scabies is a common dermatological problem managed by general physicians, family physicians, and dermatologists. Scabies manifests itself in various forms in different individuals. The treatment of scabies has undergone developments with the evolution of new treatment strategies and antiectoparasitic drugs. The advent of drugs such as permethrin and ivermectin has revolutionised treatment. Management of scabies not only includes prescribing the drugs but also educating patients properly about the method of application of the drug. Treatment failures may result for various reasons and must be managed appropriately.

Administration, Cutaneous↗
PubMed2002

Ivermectin-responsive Demodex infestation during human immunodeficiency virus infection. A case report and literature review.

We report the case of a 56-year-old HIV-seropositive man who presented a facial Demodex infection developed 2 months after initiation of highly active antiretroviral therapy. The Demodex infection was confirmed by scrapings and histopathologic examination and by the dramatic response to antiparasitic treatment with oral ivermectin associated with 5% permethrin cream.

AIDS-Related Opportunistic Infections↗
PubMed2004

Bancroftian filariasis in 12 villages in Kwale district, Coast province, Kenya - variation in clinical and parasitological patterns.

As part of a larger study on the effects of permethrin-impregnated bednets on the transmission of Wuchereria bancrofti, subjects from 12 villages in the Coastal province of Kenya, south of Mombasa, were investigated. The aims were to update the epidemiological data and elucidate the spatial distribution of W. bancrofti infection. Samples of night blood from all the villagers aged i 1 year were checked for the parasite, and all the adult villagers (aged >/= 15 years) were clinically examined for elephantiasis and, if male, for hydrocele. Overall, 16.0% of the 6531 villagers checked for microfilariae (mff) were found microfilaraemic, although the prevalence of microfilaraemia in each village varied from 8.1%-27.4%. The geometric mean intensity of infection among the microfilaraemic was 322 mff/ml blood. At village level, intensity of the microfilaraemia was positively correlated with prevalence, indicating that transmission has a major influence on the prevalence of microfilaraemia. Clinical examination of 2481 adults revealed that 2.9% had elephantiasis of the leg and that 19.9% of the adult men (10.8%-30.1% of the men investigated in each village) had hydrocele. Although the overall prevalence of microfilaraemia in the study villages had not changed much since earlier studies in the 1970s, both prevalence and intensity varied distinctly between the study villages. Such geographical variation over relatively short distances appears to be a common but seldom demonstrated feature in the epidemiology of bancroftian filariasis, and the focal nature of the geographical distribution should be carefully considered by those mapping the disease.

Adolescent↗
PubMed2006

Status of insecticide susceptibility in Anopheles arabiensis from Mwea rice irrigation scheme, Central Kenya.

BACKGROUND: Control of the Anopheline mosquito vectors of malaria by use of insecticides has been shown to impact on both morbidity and mortality due to this disease. Evidence of insecticide resistance in different settings necessitates surveillance studies to allow prompt detection of resistance should it arise and thus enable its management. Possible resistance by Anopheles arabiensis mosquitoes from Mwea rice irrigation scheme in Central Kenya to insecticides in the four classes of insecticides approved by WHO for indoor residual spraying was investigated. METHODS: Susceptibility to DDT (an organochlorine), fenitrothion (an organophosphate), bendiocarb (a carbamate), lambdacyhalothrin and permethrin (both pyrethroids) was tested using standard WHO diagnostic bioassay kits. Bioassays were performed on non-blood fed mosquitoes one- to three-day old. Knockdown was recorded every 10 min and mortality 24 h post-exposure was noted. RESULTS: Mortality 24 h post-exposure was 100% for all insecticides except for lambdacyhalothrin, which averaged 99.46%. Knockdown rates at 10 min intervals were not significantly different between the Mwea population and the susceptible KISUMU strain of Anopheles gambiae sensu stricto control. The KDT50 and KDT95 values for the Mwea population were either lower than those for the control or higher by factors of no more than 2 for most comparisons and compared well with those of An. gambiae sensu lato categorized as susceptible in other studies. CONCLUSION: These results suggest that the Mwea population of An. arabiensis is susceptible to all the insecticides tested. This implies that vector control measures employing any of these insecticides would not be hampered by resistance.

Agriculture↗
PubMed2006

Effects of possible endocrine disrupting chemicals on bacterial component-induced activation of NF-kappaB.

Endocrine disrupting chemicals (EDCs) have a possibility to exacerbate infectious diseases because EDCs disturb the human immune system by interfering with endocrine balance. To assess the influence of EDCs on the innate immune function of macrophages, we investigated the effects of thirty-seven possible endocrine disruptors on lipopolysaccharide (LPS)- or bacterial lipopeptide (Pam3CSK4)-induced activation of nuclear factor kappa B (NF-kappaB). Alachlor, benomyl, bisphenol A, carbaryl, kelthane, kepone, octachlorostyrene, pentachlorophenol, nonyl phenol, p-octylphenol and ziram inhibited both LPS- and Pam3CSK4-induced activation of NF-kappaB. Simazine inhibited only LPS-induced activation. A strong inhibitory effect was observed with ziram and benomyl. On the other hand, diethylhexyl adipate and 4-nitrotoluene tended to enhance the activation induced by Pam3CSK4 and LPS, respectively. Aldicarb, amitrole, atrazine, benzophenone, butyl benzyl phthalate, 2,4-dichlorophenoxy acetic acid, dibutyl phthalate, 2,4-dichlorophenol, dicyclohexyl phthalate, diethylhexyl phthalate, diethyl phthalate, dihexyl phthalate, di-n-pentyl phthalate, dipropyl phthalate, malathion, methomyl, methoxychlor, metribuzin, nitrofen, permethrin, trifluralin, 2,4,5-trichlorophenoxyacetic acid and vinclozolin had no significant effects at 100 microM. These results indicate that some agrochemicals have the potential to inhibit macrophage function and suggest that endocrine disruptors may influence the development of bacterial infections.

Animals↗
PubMed2002

Residential pesticide use during pregnancy among a cohort of urban minority women.

Residential pesticide use is widespread in the United States. However, data are limited specific to use among minority populations. Nor are data available on the extent of pesticide exposure resulting from residential use during pregnancy. We have gathered questionnaire data on pesticide use in the home during pregnancy from 316 African-American and Dominican women residing in northern Manhattan and the South Bronx. Additionally, 72 women underwent personal air monitoring for 48 hr during their third trimester of pregnancy to determine exposure levels to 21 pesticides (19 insecticides and 2 fungicides). Of the women questioned, 266 of 314 (85%) reported that pest control measures were used in the home during pregnancy; 111 of 314 (35%) reported that their homes were sprayed by an exterminator, and of those, 45% said the spraying was done more than once per month. Most (>or= 90%) of the pesticide was used for cockroach control. Use of pest control measures increased significantly with the level of housing disrepair reported. Of the women monitored, all (100%) had detectable levels of three insecticides: the organophosphates diazinon (range, 2.0-6,010 ng/m3) and chlorpyrifos (range, 0.7-193 ng/m3) and the carbamate propoxur (range, 3.8-1,380 ng/m3), as well as the fungicide o-phenylphenol (range, 5.7-743 ng/m3). We also frequently detected the following four insecticides (47-83% of samples) but at lower concentrations: the pyrethroid trans-permethrin, piperonyl butoxide (an indicator of exposure to pyrethrins), and the organochlorines 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and chlordane. Thirty percent of the women had detectable levels of all eight pesticides. Exposures were generally higher among African Americans than among Dominicans. We detected other pesticides in <or= 10% of samples. Results show widespread prenatal pesticide use among minority women in this cohort. Diazinon exposures for some women may have exceeded health-based levels, and our findings support recent federal action to phase out residential use of this insecticide.

Adult↗