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1.
Science ; 381(6664): 1345-1350, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37733841

RESUMO

An estimated 23 million people live on floodplains affected by potentially dangerous concentrations of toxic waste derived from past and present metal mining activity. We analyzed the global dimensions of this hazard, particularly in regard to lead, zinc, copper, and arsenic, using a georeferenced global database detailing all known metal mining sites and intact and failed tailings storage facilities. We then used process-based and empirically tested modeling to produce a global assessment of metal mining contamination in river systems and the numbers of human populations and livestock exposed. Worldwide, metal mines affect 479,200 kilometers of river channels and 164,000 square kilometers of floodplains. The number of people exposed to contamination sourced from long-term discharge of mining waste into rivers is almost 50 times greater than the number directly affected by tailings dam failures.

2.
Symbiosis ; : 1-14, 2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37360551

RESUMO

Despite the current decline of scleractinian coral populations, octocorals are thriving on reefs in the Caribbean Sea and western North Atlantic Ocean. These cnidarians are holobiont entities, interacting with a diverse array of microorganisms. Few studies have investigated the spatial and temporal stability of the bacterial communities associated with octocoral species and information regarding the co-occurrence and potential interactions between specific members of these bacterial communities remain sparse. To address this knowledge gap, this study investigated the stability of the bacterial assemblages associated with two common Caribbean octocoral species, Eunicea flexuosa and Antillogorgia americana, across time and geographical locations and performed network analyses to investigate potential bacterial interactions. Results demonstrated that general inferences regarding the spatial and temporal stability of octocoral-associated bacterial communities should not be made, as host-specific characteristics may influence these factors. In addition, network analyses revealed differences in the complexity of the interactions between bacteria among the octocoral species analyzed, while highlighting the presence of genera known to produce bioactive secondary metabolites in both octocorals that may play fundamental roles in structuring the octocoral-associated bacteriome. Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-023-00923-x.

3.
Ecol Appl ; 31(4): e02262, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33222325

RESUMO

Coral bleaching is the single largest global threat to coral reefs worldwide. Integrating the diverse body of work on coral bleaching is critical to understanding and combating this global problem. Yet investigating the drivers, patterns, and processes of coral bleaching poses a major challenge. A recent review of published experiments revealed a wide range of experimental variables used across studies. Such a wide range of approaches enhances discovery, but without full transparency in the experimental and analytical methods used, can also make comparisons among studies challenging. To increase comparability but not stifle innovation, we propose a common framework for coral bleaching experiments that includes consideration of coral provenance, experimental conditions, and husbandry. For example, reporting the number of genets used, collection site conditions, the experimental temperature offset(s) from the maximum monthly mean (MMM) of the collection site, experimental light conditions, flow, and the feeding regime will greatly facilitate comparability across studies. Similarly, quantifying common response variables of endosymbiont (Symbiodiniaceae) and holobiont phenotypes (i.e., color, chlorophyll, endosymbiont cell density, mortality, and skeletal growth) could further facilitate cross-study comparisons. While no single bleaching experiment can provide the data necessary to determine global coral responses of all corals to current and future ocean warming, linking studies through a common framework as outlined here, would help increase comparability among experiments, facilitate synthetic insights into the causes and underlying mechanisms of coral bleaching, and reveal unique bleaching responses among genets, species, and regions. Such a collaborative framework that fosters transparency in methods used would strengthen comparisons among studies that can help inform coral reef management and facilitate conservation strategies to mitigate coral bleaching worldwide.


Assuntos
Antozoários , Dinoflagellida , Animais , Recifes de Corais , Temperatura
4.
Sci Rep ; 10(1): 2562, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054937

RESUMO

Seafloor methane seepage is a significant source of carbon in the marine environment. The processes and temporal patterns of seafloor methane seepage over multi-million-year time scales are still poorly understood. The microbial oxidation of methane can store carbon in sediments through precipitation of carbonate minerals, thus providing a record of past methane emission. In this study, we compiled data on methane-derived carbonates to build a proxy time series of methane emission over the last 150 My and statistically compared it with the main hypothesised geological controllers of methane emission. We quantitatively demonstrate that variations in sea level and organic carbon burial are the dominant controls on methane leakage since the Early Cretaceous. Sea level controls methane seepage variations by imposing smooth trends on timescales in the order of tens of My. Organic carbon burial is affected by the same cyclicities, and instantaneously controls methane release because of the geologically rapid generation of biogenic methane. Both the identified fundamental (26-27 My) and higher (12 My) cyclicities relate to global phenomena. Temporal correlation analysis supports the evidence that modern expansion of hypoxic areas and its effect on organic carbon burial may lead to higher seawater methane concentrations over the coming centuries.

5.
Health Educ Res ; 34(1): 38-49, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30358853

RESUMO

Exposure to cigarette advertising can increase the likelihood of youth smoking initiation and may encourage people who already smoke to continue. Requiring prominent, graphic warning labels could reduce these effects. We test whether graphic versus text-only warning labels in cigarette advertisements influence cognitive and emotional factors associated with youth susceptibility to smoking and adult intentions to quit. We conducted two randomized, between-subjects experiments with middle-school youth (n = 474) and adult smokers (n = 451). Both studies employed a two (graphic or text-only warnings) by two (advertisements with social cues or brand imagery) factorial design with a fifth, offset control group (social cue advertisements with the current US Surgeon General's Warning). Graphic warnings outperformed text-only warnings in reducing visual attention to the advertisement, generating visual attention to the warning and arousing more negative affect. Graphic warnings also reduced the appeal of cigarette brands among youth relative to social cue advertisements with the Surgeon General's warnings. None of the warnings (graphic or textual) influenced health risk beliefs. Graphic warning labels on cigarette advertisements appear to have effects similar to those observed on cigarette packs in previous work, with an added benefit of reducing cigarette brand appeal among youth.


Assuntos
Publicidade/métodos , Rotulagem de Produtos/métodos , Abandono do Hábito de Fumar/psicologia , Produtos do Tabaco/economia , Adolescente , Adulto , Feminino , Humanos , Intenção , Masculino , Pobreza , Fumantes/psicologia , Fumar/psicologia
6.
Heredity (Edinb) ; 118(3): 284-292, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27731327

RESUMO

Theory predicts unified sex ratios for most organisms, yet biases may be engendered by selfish genetic elements such as endosymbionts that kill or feminize individuals with male genotypes. Although rare, feminization is established for Wolbachia-infected Eurema butterflies. This paradigm is presently confined to islands in the southern Japanese archipelago, where feminized phenotypes produce viable all-daughter broods. Here, we characterize sex bias for E. hecabe in continental Australia. Starting with 186 wild-caught females, we reared >6000 F1-F3 progeny in pedigree designs that incorporated selective antibiotic treatments. F1 generations expressed a consistent bias across 2 years and populations that was driven by an ~5% incidence of broods comprising ⩾80% daughters. Females from biased lineages continued to overproduce daughters over two generations of outcrossing to wild males. Treatment with antibiotics of differential strength influenced sex ratio only in biased lineages by inducing an equivalent incomplete degree of son overproduction. Brood sex ratios were nevertheless highly variable within lineages and across generations. Intriguingly, the cytogenetic signature of female karyotype was uniformly absent, even among phenotypic females in unbiased lineages. Molecular evidence supported the existence of a single Wolbachia strain at high prevalence, yet this was not clearly linked to brood sex bias. In sum, we establish an inherited, experimentally reversible tendency for incomplete offspring bias. Key features of our findings clearly depart from the Japanese feminization paradigm and highlight the potential for more subtle degrees of sex distortion in arthropods.


Assuntos
Borboletas/genética , Razão de Masculinidade , Animais , Austrália , Borboletas/microbiologia , Feminino , Masculino , Linhagem , Wolbachia
7.
Acta Psychiatr Scand ; 133(2): 144-153, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26114830

RESUMO

OBJECTIVE: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. METHOD: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. RESULTS: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. CONCLUSION: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment.

8.
Toxicol Appl Pharmacol ; 289(1): 117-23, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26386191

RESUMO

HMG-CoA reductase inhibitors (e.g., statins) are an important clinical option to lower cholesterol and treat co-morbidities. Atorvastatin is the most prescribed statin and has obtained generic status. We recently had a clinical development program evaluating a combination of atorvastatin with a GPR119 agonist as a treatment for dyslipidemia, where toxicological evaluations in dogs were completed. There were several challenges related to selecting doses for atorvastatin, including understanding the dose-exposure relationship from different drug forms used by the innovator in their general toxicology studies, bioanalytical assays that did not separate and quantify parent from metabolites, and high variability in the systemic exposures following oral dosing. The studies in this report characterized the toxicokinetics and toxicity of atorvastatin in the dog for up to 13-weeks. Overall, there were no notable differences in the toxicokinetics of atorvastatin or the two active hydroxylated metabolites between the sexes at Week 13. However, systemic exposures were markedly lower at Week 13 compared to that observed at Week 4, suggesting induction of metabolism or reduced absorption from the gastrointestinal tract following oral dosing. Changes in laboratory chemistries included increased liver enzyme levels and lower cholesterol levels. Histopathologic evaluation revealed multifocal minimal to slight hemorrhages in the submucosa of the gallbladder; all findings were reversible. The information from these studies along with the existing clinical experience with atorvastatin can be used to design robust toxicology studies in dogs and reduce animal use.


Assuntos
Atorvastatina/farmacocinética , Atorvastatina/toxicidade , Animais , Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/toxicidade , Cães , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Masculino , Testes de Toxicidade
9.
Oncogenesis ; 3: e113, 2014 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-25111862

RESUMO

MicroRNAs (miRNAs) are deregulated in cancer and have been shown to exhibit both oncogenic and tumor suppressive functions. Although the functional effects of several miRNAs have been elucidated, those of many remain to be discovered. In silico analysis identified microRNA-206 (miR-206) binding sites in the 3'-untranslated regions (3'-UTR) of both the mouse and human CCND1 gene. Cyclin D1 is a recognized oncogene involved in direct phosphorylation of the retinoblastoma (Rb) protein and promoting cell cycle transition from G1 to S. miR-206 specifically binds to the CCND1 3'-UTR and mediates reduction of both cyclin D1 protein and mRNA. Expression of miR-206 induced a G1 arrest and a decrease in cell proliferation in breast cancer cells. Ectopic expression of miRNA-resistant cyclin D1 was able to reverse the miR-206-induced decrease in cell proliferation. Therefore, we identified miR-206 as an activator of cell cycle arrest resulting in a decrease in cell proliferation that is dependent on the inhibition of cyclin D1. Interestingly, prostatic cancer (PCa) cells express low levels of miR-206 resulting in deregulated cyclin D1 expression compared with non-transformed primary prostatic epithelial cells (PrEC). Finally, we demonstrate that cyclin D1 is regulated by miR-206 in PrEC but not in PCa cells and this is due to the absence of a CCND1 3'-UTR in these cells. This suggests that miR-206-based anti-cyclin D1 targeted therapy would be beneficial in cancers where cyclin D1 is overexpressed and contains a 3'-UTR.

10.
Acta Psychiatr Scand ; 129(1): 24-34, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23465084

RESUMO

OBJECTIVE: This study examined general medical illnesses and their association with clinical features of bipolar disorder. METHOD: Data were cross-sectional and derived from the Lithium Treatment - Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n = 264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score ≥4 and <4 respectively. RESULTS: The baseline prevalence of significant medical comorbidity was 53% (n = 139). Patients with high medical burden were more likely to present in a major depressive episode (P = .04), meet criteria for obsessive-compulsive disorder (P = .02), and experience a greater number of lifetime mood episodes (P = 0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P = .002). Sixty-nine per cent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI ≥35; 31%, n = 14). CONCLUSION: The burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns.


Assuntos
Asma/epidemiologia , Transtorno Bipolar/epidemiologia , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Sobrepeso/epidemiologia , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Asiático/estatística & dados numéricos , Transtorno Bipolar/tratamento farmacológico , Índice de Massa Corporal , Comorbidade , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Obesidade/etnologia , Sobrepeso/etnologia , Psicotrópicos/uso terapêutico , População Branca/estatística & dados numéricos , Adulto Jovem
11.
Gene Ther ; 20(9): 939-48, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23552473

RESUMO

DNA vaccines are attractive candidates for tumor immunotherapy. However, the potential of DNA vaccines in treating established malignant lesions has yet to be demonstrated. Here we demonstrate that transient alteration of either intratumoral or intradermal (ID) chemotactic gradients provide a favorable milieu for DNA vaccine-mediated activation of tumor-specific immune response in both prophylactic and therapeutic settings. Specifically, we show that priming of established B16 ID melanoma lesions via forced intratumoral expression of CCL21 boosted DNA vaccination-dependent systemic cytotoxic immune response leading to the regression of tumor nodules. In this setting, application of CCL20 was not effective likely due to the engagement of the regulatory T cells. However, priming of the skin at DNA vaccine administration sites outside the tumor bed with both CCL20 and CCL21 chemokines along with structural modifications of the DNA vaccine significantly improved vaccine efficacy. This optimized ID vaccination regimen led to the inhibition of distant established melanomas and prolonged tumor-free survival of mice observed in 60% of vaccinated animals with complete tumor remission in 30%. These effects were mediated by extranodal priming and activation of T cells at vaccine administration sites and progressive accumulation of systemic antigen-specific cytotoxic T cells (CTLs) on successive vaccinations. These results underscore the potential of chemokine-enhanced DNA vaccination to mount therapeutic immune response against established tumors.


Assuntos
Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Quimiocina CCL20/imunologia , Quimiocina CCL21/imunologia , Melanoma Experimental/terapia , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Animais , Vacinas Anticâncer/administração & dosagem , Linhagem Celular Tumoral , Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL21/genética , Quimiocina CCL21/metabolismo , Terapia Genética , Imunoterapia , Ativação Linfocitária , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Melanoma Experimental/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Pele/imunologia , Pele/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas de DNA/metabolismo
12.
Psychopharmacol Bull ; 43(2): 5-27, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21052040

RESUMO

OBJECTIVE: To evaluate the value of early improvement to predict treatment outcome in patients with bipolar depression. METHODS: Data were pooled from two aripiprazole, 8-week, randomized, double-blind, placebo-controlled trials in patients with bipolar depression without psychotic features to determine whether early improvement (≥20% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score at Week 2 or 3) predicts later response (≥50% MADRS Total score reduction at Week 8) or remission (MADRS Total ≤10 at Week 8). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated (LOCF). Univariate and multivariate logistic regression models were used to evaluate early improvement and baseline demographic/clinical characteristics as predictors of response/remission. RESULTS: In total, 311 patients were randomized to placebo and 306 to aripiprazole. Predictive values of early improvement (≥20% MADRS Total score reduction) for remission with aripiprazole at Week 2/3, respectively, were: sensitivity 83%/94%; specificity 41%/33%; PPV 44%/45%; NPV 81%/91%. The corresponding values with placebo were as follows: sensitivity 70%/84%; specificity 60%/51%; PPV 50%/51%; NPV 77%/84%. Univariate linear regression showed that early improvement (≥15%, ≥20%, ≥25%, ≥30% at Week 3) was a significant potential predictor of remission. CONCLUSION: Absence of early improvement after 3 weeks of treatment reliably predicted non-response/non-remission at study endpoint with high sensitivity and NPV. In patients with <20% improvement after 21 days of aripiprazole monotherapy, treatment should be modified, as continued use is unlikely to result in response/remission. Clinical decision-making to optimize treatment course in bipolar I depression may be appropriate after as little as 2 weeks and certainly within the first 3 weeks of treatment.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Adulto , Aripiprazol , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do Tratamento
13.
Opt Lett ; 35(10): 1632-4, 2010 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-20479832

RESUMO

We have demonstrated repetitive operation of a table-top lambda=13.9 nm Ni-like Ag soft-x-ray laser that generates laser pulses with 10 microJ energy. The soft-x-ray laser is enabled by a Ti:sapphire laser pumped by high-repetition-rate frequency-doubled high-energy Nd:glass slab amplifiers. Soft-x-ray laser operation at 2.5 Hz repetition rate resulted in 20 microwatt average power.

14.
Int J Clin Pract ; 64(3): 336-44, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20456174

RESUMO

OBJECTIVE: To study mood stabiliser treatment in patients with bipolar disorder with or without anxiety disorders (ADs) and/or substance use disorders (SUDs). METHODS: Extensive clinical interview and Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV diagnoses of rapid cycling bipolar I (RCBDI) or II (RCBDII), SUDs and ADs. Previous treatment statuses with a mood stabiliser after the first onset of mania/hypomania (unmedicated, mismedicated and correctly medicated) were retrospectively determined in patients enrolled into four similar clinical trials. T-test and chi-square/Fisher's exact were used wherever appropriate. RESULTS: Of 566 patients (RCBDI n = 320, RCBDII n = 246), 46% had any lifetime AD, 67% had any lifetime SUD and 40% had any recent SUD. Overall, 12% of patients were unmedicated, 37% were mismedicated at the onset of first mania/hypomania and 51% were correctly medicated. Presence of lifetime ADs and recent SUDs was associated with fewer mood stabiliser treatments. Patients with RCBDI were more likely correctly medicated than those with RCBDII (OR = 3.64) regardless of the presence (OR = 2.6) or absence (OR = 4.2) of ADs, or the presence (OR = 2.8) or absence (OR = 3.13) of recent SUDs. Presence of lifetime ADs and recent SUDs increased the risk for mismedicated in RCBDI with odds ratios of 1.8 and 1.9, respectively, but not in RCBDII. CONCLUSION: In this multi-morbid cohort of patients with RCBD, 51% of patients (64% of RCBDI and 33% with RCDBII) were correctly medicated with a mood stabiliser after the onset of first mania/hypomania. The presence of ADs and SUDs was associated with an increased risk of mismedicated in patients with RCBDI, but not with RCBDII.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Adulto , Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Estudos Transversais , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Vet Parasitol ; 169(1-2): 157-64, 2010 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-20079571

RESUMO

A farmlet study was conducted over 4 years in which three treatments were applied to six groups of Holstein dairy calves. Calves in each group were infested with equal numbers of N-strain (susceptible) and Ultimo strain (amitraz and synthetic pyrethroid resistant) tick larvae to establish self-sustaining populations with an initial, measurable level of resistance to amitraz. Standard counts of all ticks between 4.5 and 8.0mm diameter on one side of each animal were made each week and treatment was applied when tick numbers exceeded a threshold of 25 engorged adults per side. The three treatments were: 1, spinosad spray whenever tick numbers exceeded the threshold; 2, amitraz spray whenever tick numbers exceeded the threshold; 3, spinosad whenever tick numbers exceeded the threshold for the first 2 months, then amitraz for 2 months, with alternation every subsequent 2 months. Engorged adult female ticks were collected from each treatment group on 10 or 11 occasions during the study and tested using the larval packet test bioassay (LPT) for acaricide resistance. Spinosad 250ppm provided effective control of amitraz-resistant tick populations in the field, using a similar number of treatments as in the amitraz and rotation groups. The initial infestations of all of the groups resulted in the establishment of populations with in vitro evidence of resistance to amitraz using the LPT. Treatment with spinosad or with a rotation between spinosad and amitraz every 2 months resulted in reduced levels of resistance to amitraz according to the LPT. The animals treated with amitraz alone showed increasing resistance to amitraz according to the LPT each summer and autumn with a return to full or almost full susceptibility to amitraz in early spring in all years. This pattern suggests a relative lack of fitness of amitraz-resistant ticks that might be exploited by using an acaricide rotation strategy.


Assuntos
Doenças dos Bovinos/tratamento farmacológico , Ectoparasitoses/veterinária , Inseticidas/administração & dosagem , Macrolídeos/administração & dosagem , Rhipicephalus , Toluidinas/administração & dosagem , Animais , Bovinos , Combinação de Medicamentos , Ectoparasitoses/tratamento farmacológico , Feminino , Resistência a Inseticidas , Distribuição Aleatória , Análise de Sobrevida , Fatores de Tempo
16.
Biochim Biophys Acta ; 1770(9): 1369-73, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17616257

RESUMO

We have studied the effect of PTK787 (Vatalanib), an inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, on adipose tissue development. Oral administration of PTK787 for 4 weeks (2 mg/g high fat diet, HFD) to C57Bl/6 mice resulted in a significant reduction in total body weight and of subcutaneous (SC) and gonadal (GON) adipose tissue mass, as compared to control animals fed HFD only (all p<0.0005). In the GON adipose tissue adipocytes were hypertrophic after PTK787 treatment. Blood vessel size and density were not significantly affected by PTK787 treatment. Expression of Flk-1 (VEGFR-2) mRNA was significantly reduced in SC and GON adipose tissues of PTK787 treated mice. De novo fat pad formation following injection of preadipocytes in NUDE mice was significantly (p<0.005) impaired by PTK787 administration (2 mg/g HFD for 4 weeks), without associated effect on blood vessel size or density. Thus, in nutritionally induced murine obesity models, oral administration of the VEGFR tyrosine kinases inhibitor PTK787 resulted in reduced adipose tissue development.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/crescimento & desenvolvimento , Obesidade/fisiopatologia , Ftalazinas/farmacologia , Piridinas/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Gorduras na Dieta/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus
17.
Vet Parasitol ; 136(1): 29-43, 2006 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-16377090

RESUMO

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of the efficacy of acaricides (excluding vaccines and other bio-control agents) against single and multi-host ticks (Ixodidae) on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. The use of pen facilities is advocated for dose determination and confirmation studies for defining therapeutic and persistent efficacy. A minimum of two studies per tick species for which claims are sought is recommended for each dose determination and dose confirmation investigation. If dose confirmation studies demonstrate greater than 95% efficacy the sponsor may proceed to field studies, where a minimum of two studies per geographical location is preferred to confirm the therapeutic and persistent efficacy under field conditions. If dose confirmation studies demonstrate less than 95% efficacy then longer-term field studies can be conducted over two tick seasons with a minimum of two studies per geographical location. These studies can incorporate other control methods such as tick vaccines, to demonstrate stable long-term tick management. Specific advice is also given on conducting studies with paralysis ticks. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new acaricides, and to facilitate the worldwide adoption of standard procedures.


Assuntos
Inseticidas/normas , Ixodidae , Projetos de Pesquisa/normas , Ruminantes/parasitologia , Infestações por Carrapato/veterinária , Animais , Bovinos , Ixodidae/efeitos dos fármacos , Controle de Ácaros e Carrapatos/normas , Infestações por Carrapato/prevenção & controle , Resultado do Tratamento
18.
Int J Parasitol ; 35(9): 1013-22, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15964574

RESUMO

A collection of Bacillus thuringiensis (Bt) strains (Bts) were screened for activity against the free-living larval stages of nematode parasites of livestock. Two strains were identified with significant activity in inhibiting larval development of Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta. These strains were also toxic to the adult parasitic stages of these nematode species in vitro. Adult H. contortus and O. circumcincta showed complete cessation of movement within 2 and 4 days, respectively. Trichostrongylus colubriformis adults were less affected, however, movement was still significantly reduced compared with controls. The in vitro activity against the larval stages was of a magnitude similar to or greater than that seen with the anthelmintic drugs thiabendazole and levamisole. N-terminal amino acid sequencing indicated that the two Bts contained either Cry5A and Cry5B proteins, or a Cry13 protein, and the presence of the corresponding cry5A, cry5B and cry13 genes was confirmed by PCR and sequencing. Bacillus thuringiensis spore-crystal suspensions exposed to acidic pH conditions (pH

Assuntos
Bacillus thuringiensis/patogenicidade , Nematoides/microbiologia , Animais , Anti-Helmínticos/farmacologia , Bacillus thuringiensis/química , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/análise , Proteínas de Bactérias/genética , Toxinas Bacterianas/análise , Toxinas Bacterianas/genética , Bioensaio/métodos , DNA Bacteriano/genética , Relação Dose-Resposta a Droga , Endotoxinas/análise , Endotoxinas/genética , Fezes/parasitologia , Haemonchus/efeitos dos fármacos , Haemonchus/microbiologia , Haemonchus/fisiologia , Proteínas Hemolisinas , Concentração de Íons de Hidrogênio , Larva/microbiologia , Larva/fisiologia , Movimento , Nematoides/efeitos dos fármacos , Nematoides/fisiologia , Infecções por Nematoides/parasitologia , Infecções por Nematoides/veterinária , Ostertagia/efeitos dos fármacos , Ostertagia/microbiologia , Ostertagia/fisiologia , Controle Biológico de Vetores/métodos , Ovinos/parasitologia , Doenças dos Ovinos/parasitologia , Trichostrongylus/efeitos dos fármacos , Trichostrongylus/microbiologia , Trichostrongylus/fisiologia
19.
Int J Parasitol ; 35(2): 131-5, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15710433

RESUMO

The endosymbiont Wolbachia has been detected in a range of filarial nematodes and parasitic mites and is known to affect host reproductive compatibility and potentially evolutionary processes. PCR of Wolbachia surface protein (wsp), ftsZ and 16SrRNA genes from individual Sarcoptes scabiei mites obtained from a series of individual hosts, and database searches of an S. scabiei var. hominis EST library failed to detect Wolbachia genes. Therefore, Wolbachia appears not to be involved in the genetic subdivision observed between varieties of host-associated S. scabiei or, involved in the inflammatory disease pathogenesis of scabies unlike its activity in filarial infection.


Assuntos
Sarcoptes scabiei/genética , Escabiose/genética , Wolbachia/genética , Animais , Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , DNA Bacteriano/genética , Bases de Dados de Ácidos Nucleicos , Humanos , Reação em Cadeia da Polimerase/métodos , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Infecções por Rickettsiaceae/genética , Infecções por Rickettsiaceae/veterinária , Sarcoptes scabiei/parasitologia , Escabiose/parasitologia
20.
Postgrad Med J ; 80(945): 382-7, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15254301

RESUMO

Human scabies, caused by skin infestation with the arthropod mite, Sarcoptes scabiei, typically results in a papular, intensely pruritic eruption involving the interdigital spaces, and flexure creases. Recent research has led to a reassessment of the morbidity attributable to this parasite in endemic communities, particularly resulting from secondary skin sepsis and postinfective complications including glomerulonephritis. This has led to studies of the benefits of community based control programmes, and to concerns regarding the emergence of drug resistance when such strategies are employed. The renewed research interest into the biology of this infection has resulted in the application of molecular tools. This has established that canine and human scabies populations are genetically distinct, a finding with major implications for the formulation of public health control policies. Further research is needed to increase understanding of drug resistance, and to identify new drug targets and potential vaccine candidates.


Assuntos
Escabiose , Doenças dos Animais/diagnóstico , Doenças dos Animais/terapia , Animais , Aglomeração , Surtos de Doenças , Humanos , Higiene , Pobreza , Recidiva , Escabiose/diagnóstico , Escabiose/parasitologia , Escabiose/terapia , Escabiose/veterinária
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