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1.
Epidemiol Infect ; 143(12): 2520-31, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25592266

RESUMEN

Helicobacter pylori imparts a considerable burden to public health. Infections are mainly acquired in childhood and can lead to chronic diseases, including gastric ulcers and cancer. The bacterium subsists in water, but the environment's role in transmission remains poorly understood. The nationally representative National Health and Nutrition Examination Survey (NHANES) was examined for environmental risk factors associated with H. pylori seroprevalence. Data from 1999-2000 were examined and weighted to represent the US population. Multivariable logistic regression estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations with seropositivity. Self-reported general health condition was inversely associated with seropositivity. Of participants aged <20 years, seropositivity was significantly associated with having a well as the source of home tap water (aOR 1·7, 95% CI 1·1-2·6) and living in a more crowded home (aOR 2·3, 95% CI 1·5-3·7). Of adults aged ⩾20 years, seropositivity was not associated with well water or crowded living conditions, but adults in soil-related occupations had significantly higher odds of seropositivity compared to those in non-soil-related occupations (aOR 1·9, 95% CI 1·2-2·9). Exposures to both well water and occupationally related soil increased the effect size of adults' odds of seropositivity compared to non-exposed adults (aOR 2·7, 95% CI 1·3-5·6). Environmental exposures (well-water usage and occupational contact with soil) play a role in H. pylori transmission. A disproportionate burden of infection is associated with poor health and crowded living conditions, but risks vary by age and race/ethnicity. These findings could help inform interventions to reduce the burden of infections in the United States.


Asunto(s)
Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Estudios Transversales , Femenino , Estado de Salud , Infecciones por Helicobacter/etnología , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Ocupaciones/estadística & datos numéricos , Estudios Seroepidemiológicos , Factores Socioeconómicos , Microbiología del Suelo , Estados Unidos/epidemiología , Pozos de Agua/microbiología , Adulto Joven
2.
Plant Dis ; 97(2): 231-244, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30722318

RESUMEN

Eighteen different fungal species were isolated from symptomatic wood of olive trees (Olea europaea) affected by twig and branch dieback in California and identified by means of morphological characters and multigene sequence analyses of the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2), a partial sequence of the ß-tubulin gene, and part of the translation elongation factor 1-α gene (EF1-α). These species included Diaporthe viticola, Diatrype oregonensis, Diatrype stigma, Diplodia mutila, Dothiorella iberica, Lasiodiplodia theobromae, Phaeomoniella chlamydospora, Phomopsis sp. group 1, Phomopsis sp. group 2, and Schizophyllum commune, which are for the first time reported to occur in olive trees; Eutypa lata, Neofusicoccum luteum, Neofusicoccum vitifusiforme, and Phaeoacremonium aleophilum, which are for the first time reported to occur in olive trees in the United States; and Botryosphaeria dothidea, Diplodia seriata, Neofusicoccum mediterraneum, and Trametes versicolor, which have been previously reported in olive trees in California. Pathogenicity studies conducted in olive cultivars Manzanillo and Sevillano showed N. mediterraneum and Diplodia mutila to be the most virulent species and Diatrype stigma and D. oregonensis the least virulent when inoculated in olive branches. Intermediate virulence was shown for the rest of the taxa. This study demystifies the cause of olive twig and branch dieback and elucidates most of the fungal pathogens responsible for this disease in California.

3.
Infection ; 37(2): 123-32, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19277465

RESUMEN

BACKGROUND: The oxazolidinone antibiotic linezolid has demonstrated efficacy in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In a retrospective analysis of two prospective randomized clinical trials in patients with nosocomial pneumonia (NP), initial therapy with linezolid produced significantly better clinical cure and survival rates than vancomycin in the subset of patients with documented MRSA infection. This study was designed to evaluate the economic impact of these clinical outcomes from the perspective of the German health care system to determine the use of these regimens in the light of limited resources and rising costs. METHODS: A decision-analytic model using clinical trial data was developed to examine the costs and outcomes of treatment with linezolid or vancomycin in hospitalized patients with NP caused by suspected MRSA. The model followed an average patient from initiation of empiric treatment until treatment success, death, or second-line treatment failure. Local treatment patterns and resource use were obtained from a Delphi panel. Costs were taken from published sources. Outcomes included total cost per patient, cost per additional cure, cost per death avoided, and cost per life-year gained. RESULTS: The model calculated that linezolid was associated with an 8.7% higher cure rate compared with vancomycin (73.6% vs 64.9%, respectively). Average total costs per episode for linezolid- and vancomycin-treated patients were 12,829 and 12,409, respectively. Death rates were 13.2% lower with linezolid than with vancomycin (20.7% vs 33.9%), resulting in an average of 2.3 life-years gained per linezolid-treated patient in a 65-year-old cohort (14.0 life-years vs 11.7 life-years). With linezolid, incremental costs per death avoided and per patient cured were 3,171 and 4,813, respectively. The base case estimated a similar mean length of stay for both drugs (11.2 vs 10.8 days). One-way sensitivity analyses did not change the overall results. CONCLUSION: The model estimated a higher clinical cure (+8.7%) and survival (+13.2%) for linezolid compared with vancomycin at an incremental cost of 420 per treatment episode. The cost-benefit profile suggests that linezolid could be considered a cost-effective alternative to vancomycin in the treatment of patients with NP caused by suspected MRSA in Germany.


Asunto(s)
Acetamidas/economía , Antibacterianos/economía , Infección Hospitalaria/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina , Oxazolidinonas/economía , Neumonía Estafilocócica/tratamiento farmacológico , Vancomicina/economía , Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Análisis Costo-Beneficio , Infección Hospitalaria/economía , Infección Hospitalaria/epidemiología , Técnicas de Apoyo para la Decisión , Costos de los Medicamentos , Femenino , Alemania , Humanos , Linezolid , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Modelos Económicos , Oxazolidinonas/uso terapéutico , Neumonía Estafilocócica/economía , Neumonía Estafilocócica/epidemiología , Estudios Retrospectivos , Vancomicina/uso terapéutico
4.
Anaesthesia ; 64(1): 27-31, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18671685

RESUMEN

In a quality improvement audit on epidural analgesia in 300 patients after major abdominal surgery, we identified postoperative lower leg weakness and premature catheter dislodgement as the most frequent causes of premature discontinuation of postoperative epidural infusion. Lower limb motor weakness occurred in more than half of the patients with lumbar epidural analgesia. In a second period monitoring 177 patients, lumbar catheter insertion was abandoned in favour of exclusive thoracic placement for epidural catheters. Additionally, to prevent outward movement, the catheters were inserted deeper into the epidural space (mean (SD) 5.2 (1.5) cm in Period Two vs 4.6 (1.3) cm in Period One). Lower leg motor weakness declined from 14.7% to 5.1% (odds ratio 0.35; 95% confidence interval 0.16-0.74) between the two periods. Similarly, the frequency of premature catheter dislodgement was reduced from 14.5% to 5.7% (odds ratio 0.35; 95% confidence interval 0.17-0.72). With a stepwise logistic regression model we demonstrated that the odds of premature catheter dislodgement was reduced by 43% for each centimetre of additional catheter advancement in Period Two. We conclude that careful audit of specific complications can usefully guide changes in practice that improve success of epidural analgesia regimens.


Asunto(s)
Abdomen/cirugía , Analgesia Epidural/normas , Dolor Postoperatorio/prevención & control , Parálisis/etiología , Adulto , Anciano , Analgesia Epidural/efectos adversos , Analgesia Epidural/instrumentación , Analgesia Epidural/métodos , Femenino , Alemania , Humanos , Pierna , Vértebras Lumbares , Masculino , Auditoría Médica , Persona de Mediana Edad , Parálisis/prevención & control , Vértebras Torácicas , Factores de Tiempo , Insuficiencia del Tratamiento
6.
Clin Microbiol Infect ; 24(5): 505-513, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-28870727

RESUMEN

OBJECTIVES: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients. METHODS: In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. RESULTS: Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality. CONCLUSIONS: In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD.


Asunto(s)
Descontaminación , Desinfección , Tracto Gastrointestinal/microbiología , Unidades de Cuidados Intensivos , Orofaringe/microbiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Infección Hospitalaria/prevención & control , Descontaminación/métodos , Desinfección/métodos , Farmacorresistencia Microbiana , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos/normas , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Mol Cell Biol ; 21(6): 2133-43, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11238947

RESUMEN

Intracellular trafficking of retroviral RNAs is a potential mechanism to target viral gene expression to specific regions of infected cells. Here we show that the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized extensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2 dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the same RNA trafficking granules and are cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in targeting HIV gene expression is discussed.


Asunto(s)
VIH-1/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B , Oligodendroglía/virología , ARN Viral/análisis , ARN Viral/metabolismo , Elementos de Respuesta/genética , Animales , Secuencia de Bases , Transporte Biológico , Células Cultivadas , Productos del Gen gag/genética , Productos del Gen vpr/genética , VIH-1/patogenicidad , Ribonucleoproteínas Nucleares Heterogéneas , Ratones , Biología Molecular/métodos , Datos de Secuencia Molecular , Oligodendroglía/citología , Fragmentos de Péptidos/genética , Ribonucleoproteínas/genética , Productos del Gen vpr del Virus de la Inmunodeficiencia Humana
8.
Cancer Res ; 49(8): 1983-8, 1989 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-2702639

RESUMEN

CC-1065 is a potent antitumor antibiotic which is cytotoxic to P388 and L1210 leukemia cells in vitro and in vivo. CC-1065 covalently binds to calf thymus DNA preferentially to adenine-thymine regions at N3 of adenine. Here, we compare CC-1065 interaction with P388-derived chromatin, DNA, and histones as measured by electronic absorption and circular dichroism. Two CC-1065 analogues (U-71,184 and its enantiomer, U-71,185) which show different biological activities from CC-1065 were also studied. The shape and temporal behavior of the induced circular dichroism curves generated by CC-1065 or its analogues bound to chromatin were similar to CC-1065 plus DNA. This suggested that CC-1065 and its analogues bind to the minor groove of chromatin DNA in a manner similar to calf thymus DNA. However, the binding of CC-1065 and its analogues to DNA induced a more intense circular dichroism band than binding to chromatin. The order of interaction for both chromatin and DNA was CC-1065 greater than U-71,184 greater than U-71,185. In contrast to the essentially irreversible binding to DNA after 24-h incubation, binding to chromatin was primarily a reversible interaction, the degree of reversibility being U-71,185 greater than U-71,184 = CC-1065. CC-1065 binds weakly and nonspecifically to histones.


Asunto(s)
Antibióticos Antineoplásicos/metabolismo , Cromatina/metabolismo , ADN/metabolismo , Indoles , Leucomicinas/metabolismo , Animales , Dicroismo Circular , Duocarmicinas , Histonas/metabolismo , Leucomicinas/farmacología , Ratones , Cloruro de Sodio/farmacología
9.
Cancer Res ; 41(6): 2235-40, 1981 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7237423

RESUMEN

Nogalamycin, an anthracycline antibiotic, interacts with DNA. This interaction is measured by a competitive fluorescence polarization assay in which nogalamycin displaces acridine orange. The amount of acridine orange displaced is dependent upon the concentration and DNA-binding capability of the drug. The relative DNA-binding capacities of several nogalamycin analogs are also determined by this method. A comparison of these results with circular dichroism and thermal denaturation yields a positive correlation. The base-pair specificities of these compounds are also evaluated by competitive fluorescence polarization using DNA's of differing base composition. These results indicate that compounds containing the nogalose moiety generally prefer adenine and thymine. On the other hand, some of the 7-O-alkyl analogs appear to interact similarly with DNA's of differing base composition, and others show a preference for DNA's with high guanine and cytosine content. Specificities obtained with this method are compared with DNA thermal denaturation and polymerase inhibition studies. The potential value of this relatively new competitive method for the study of DNA-reactive antitumor compounds is discussed.


Asunto(s)
Naranja de Acridina/metabolismo , ADN/metabolismo , Daunorrubicina/análogos & derivados , Nogalamicina/metabolismo , Animales , Composición de Base , Unión Competitiva , Bovinos , Dicroismo Circular , ADN Polimerasa Dirigida por ADN/metabolismo , Polarización de Fluorescencia , Métodos , Nogalamicina/análogos & derivados , Desnaturalización de Ácido Nucleico , Moldes Genéticos
10.
Cancer Res ; 42(7): 2821-8, 1982 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7083173

RESUMEN

CC-1065 (NSC 298223), a potent new antitumor antibiotic produced by Streptomyces zelensis, interacts strongly with double-stranded DNA and appears to exert its cytotoxic effects through disruption of DNA synthesis. We undertook this study to elucidate the sites and mechanisms of CC-1065 interaction with DNA. The binding of CC-1065 to synthetic and native DNA was examined by differential circular dichroism or by Sephadex chromatography with photometric detection. The binding of CC-1065 with calf thymus DNA was rapid, being complete within 2 hr, and saturated at 1 drug per 7 to 11 base pairs. The interaction of CC-1065 with synthetic DNA polymers indicated a specificity for adenine- and thymine-rich sites. Agarose gel electrophoresis of CC-1065-treated supercoiled DNA showed that CC-1065 did not intercalate. Site exclusion studies using substitutions in the DNA grooves showed CC-1065 to bind primarily in the minor groove. CC-1065 did not cause DNA breaks; it inhibited susceptibility of DNA to nuclease S1 digestion. It raised the thermal melting temperature of DNA, and it inhibited the ethidium-induced unwinding of DNA. Thus, in contrast to many antitumor agents, CC-1065 stabilized the DNA helix. DNA helix overstabilization may be relevant to the mechanism of action of CC-1065.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , ADN , Indoles , Leucomicinas/farmacología , Animales , Antramicina/metabolismo , Bovinos , Dicroismo Circular , ADN/metabolismo , Desoxirribonucleasas/farmacología , Duocarmicinas , Electroforesis en Gel de Agar , Calor , Leucomicinas/metabolismo , Timo/metabolismo
11.
Cancer Res ; 42(3): 999-1004, 1982 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-6174220

RESUMEN

CC-1065, a novel antibiotic produced by Streptomyces zelensis, was active against several experimental tumors in vivo and a broad spectrum of human tumor cells in vitro. This report describes its biological and biochemical effects of L1210 leukemia cells. CC-1065 is one of the most cytotoxic agents known. The concentrations required for a 50 and 90% inhibition of cell growth are 0.02 and 0.05 ng/ml, respectively. It is about 400 times more cytotoxic than was Adriamycin. The action of CC-1065 is rapid and is dose and time dependent. CC-1065 inhibits DNA synthesis much more than it inhibits RNA and protein synthesis. The concentrations required for a 50% inhibition of DNA synthesis and RNA synthesis are 4 to 6 and 45 to 60 ng/ml, respectively. Although the drug inhibition of DNA synthesis cannot completely account for its cytotoxic effects on L1210 cells, these results, along with those generated by other investigators, suggest that the inhibition of DNA synthesis represents a major mode of action of CC-1065. CC-1065 inhibited both thymidine kinase and DNA polymerase alpha activities, but the effect on highly purified DNA polymerase alpha was more pronounced. At 1 microgram/ml, CC-1065 inhibited more than 70% of the enzyme activity. In order to elucidate the mechanism of inhibition of DNA polymerase alpha, the interaction between CC-1065 and DNA was investigated. The studies with thermal melting of DNA and difference circular dichroism measurement indicate that CC-1065 is one of the strongest DNA-binding agents. It induced an increase in thermal melting temperature of calf thymus DNA by at least 31 degrees. The circular dichroism studies also reveal that CC-1065 binds only to double-stranded DNA but not to heat-denatured DNA or yeast RNA. These observations were supported by those obtained with two other experimental approaches. CC-1065 also appeared to interact with proteins, but the interaction was weak and reversible.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , ADN/biosíntesis , Indoles , Leucomicinas/farmacología , Leucemia L1210/metabolismo , Animales , Bovinos , División Celular/efectos de los fármacos , Línea Celular , Dicroismo Circular , ADN Polimerasa II/metabolismo , Relación Dosis-Respuesta a Droga , Duocarmicinas , Leucomicinas/metabolismo , Leucemia L1210/enzimología , Ratones , ARN/biosíntesis , Moldes Genéticos , Timidina Quinasa/metabolismo , Factores de Tiempo
12.
Cancer Res ; 52(18): 4904-13, 1992 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-1516047

RESUMEN

The cyclopropylpyrroloindole analogues are DNA minor-groove binders containing a cyclopropyl group, which mediates N3-adenine covalent adduct formation in a sequence-selective fashion. Carzelesin (U-80244) is a cyclopropylpyrroloindole prodrug containing a relatively nonreactive chloromethyl precursor to the cyclopropyl function. Activation of carzelesin requires two steps, (a) hydrolysis of a phenylurethane substituent to form U-76073, followed by (b) ring closure to form the cyclopropyl-containing DNA-reactive U-76074. The formation of the DNA-reactive U-76074, via U-76073, from carzelesin was shown to proceed very slowly in phosphate-buffered saline (t1/2 greater than 24 h) but to occur rapidly in plasma from mouse, rat, dog, and human (initial t1/2 values ranging from 18 min for mouse to 52 min for rat) and in cell culture medium (t1/2 approximately 40 min). Although carzelesin was less potent in terms of in vitro cytotoxicity and in vivo optimal dosage and showed low affinity for binding to DNA, it was therapeutically more efficacious against mouse L1210 leukemia than was U-76074 or adozelesin (U-73975), another cyclopropylpyrroloindole analogue which is currently in phase I clinical trials. Carzelesin also proved to be more efficacious than U-76074 or adozelesin against mouse pancreatic ductal 02 adenocarcinoma, a system reported to be resistant to every agent tested. Carzelesin was highly effective against this tumor and produced 97% tumor growth inhibition. In addition, i.v. administered carzelesin showed significant activity (National Cancer Institute criteria) against i.v. or s.c. implanted Lewis lung carcinoma, i.p. or s.c. implanted B16 melanoma, s.c. implanted colon 38 carcinoma, and five s.c. implanted human tumor xenografts, including clear cell Caki-1 carcinoma, colon CX-1 adenocarcinoma, lung LX-1 tumor, ovarian 2780 carcinoma, and prostatic DU-145 carcinoma. Carzelesin treatment produced 100% complete remissions (no palpable tumor mass at the termination of the experiment) in mice bearing early-stage human ovarian 2780. Pharmacologically, carzelesin proved to be relatively schedule and route independent and was highly active against i.p. implanted L1210 leukemia, regardless of whether the analogue was given i.v., i.p., s.c., or p.o. These results, collectively, suggest that carzelesin is absorbed and distributed well. Both carzelesin and adozelesin caused marked tumor shrinkage in mice bearing human lung LX-1 or advanced-stage human ovarian 2780 carcinoma; however, tumor regrowth occurred shortly after the treatment with adozelesin was stopped. Little or no apparent tumor regrowth occurred after treatment with carzelesin.(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Antineoplásicos , Benzofuranos , Indoles/toxicidad , Profármacos/toxicidad , Adenocarcinoma/tratamiento farmacológico , Animales , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Medios de Cultivo , Duocarmicinas , Indoles/farmacocinética , Leucemia L1210/tratamiento farmacológico , Tasa de Depuración Metabólica , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Pancreáticas/tratamiento farmacológico , Plasma/metabolismo , Profármacos/farmacocinética , Trasplante Heterólogo
13.
Zoonoses Public Health ; 63(4): 311-9, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26514953

RESUMEN

To understand the etiological burden of disease associated with acute health symptoms [e.g. gastrointestinal (GI), respiratory, dermatological], it is important to understand how common exposures influence these symptoms. Exposures to familiar and unfamiliar animals can result in a variety of health symptoms related to infection, irritation and allergy; however, few studies have examined this association in a large-scale cohort setting. Cross-sectional data collected from 50 507 participants in the United States enrolled from 2003 to 2009 were used to examine associations between animal contact and acute health symptoms during a 10-12 day period. Fixed-effects multivariable logistic regression estimated adjusted odds ratios (AORs) and 95% confident intervals (CI) for associations between animal exposures and outcomes of GI illness, respiratory illness and skin/eye symptoms. Two-thirds of the study population (63.2%) reported direct contact with animals, of which 7.7% had contact with at least one unfamiliar animal. Participants exposed to unfamiliar animals had significantly higher odds of self-reporting all three acute health symptoms, when compared to non-animal-exposed participants (GI: AOR = 1.4, CI = 1.2-1.7; respiratory: AOR = 1.5, CI = 1.2-1.8; and skin/eye: AOR = 1.9, CI = 1.6-2.3), as well as when compared to participants who only had contact with familiar animals. Specific contact with dogs, cats or pet birds was also significantly associated with at least one acute health symptom; AORs ranged from 1.1 to 1.5, when compared to participants not exposed to each animal. These results indicate that contact with animals, especially unfamiliar animals, was significantly associated with GI, respiratory and skin/eye symptoms. Such associations could be attributable to zoonotic infections and allergic reactions. Etiological models for acute health symptoms should consider contact with companion animals, particularly exposure to unfamiliar animals. Prevention of pet-associated zoonotic diseases includes commonsense measures such as hand-washing, but are often overlooked by pet owners and non-pet owners alike.


Asunto(s)
Hipersensibilidad , Mascotas , Adolescente , Adulto , Animales , Niño , Preescolar , Femenino , Enfermedades Gastrointestinales/etiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedades Respiratorias/etiología , Enfermedades de la Piel/etiología , Adulto Joven
14.
Pharmacol Ther ; 51(2): 239-55, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1838416

RESUMEN

This review assimilates up-to-date information on the biochemical pharmacology of nogalamycin and selected derivatives that have shown good biological activities and/or received a relatively detailed investigation. The structure and chemical preparation of these derivatives from nogalamycin is described and the nomenclature which has been rather perplexing in the literature is clarified. The interaction of this class of compounds, particularly nogalamycin, with DNA is extensively reviewed. The biochemical mechanism of action of nogalamycin and its structurally closely-related derivatives is described. Among nogalamycin derivatives, menogaril showed distinct biochemical effects as well as superior cytotoxicity and antitumor activity and also proved to be effective against breast cancer clinically.


Asunto(s)
ADN/efectos de los fármacos , Nogalamicina/farmacología , Antineoplásicos/uso terapéutico , Humanos , Menogaril , Nogalamicina/análogos & derivados , Nogalamicina/uso terapéutico , Nogalamicina/toxicidad
15.
J Med Chem ; 33(8): 2080-6, 1990 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2197411

RESUMEN

The independent subsite model is widely used for the design of peptide inhibitors of enzymes with extended active sites. This model assumes that the subsites are independent of each other and that the free energies of binding contributed by the several subsites are additive. We questioned the strict application of this model for structure-activity studies, since one can, a priori, conceive of likely deviations from this model. Accordingly, we tested the independent subsite model by measuring the thermodynamic binding parameters of a series of peptide inhibitors of human renin. This enzyme-inhibitor system was chosen as a model by virtue of the high degree of specificity of renin for its natural substrate, angiotensinogen, and the availability of a large number of structurally similar peptide inhibitors. Although we found the general mode of binding of these renin inhibitors to be primarily hydrophobic, serious deviations from additivity and independent subsite model constraints were observed. We conclude that an important determinant of binding is most probably the conformation assumed by the peptide inhibitor in solution. Thus, we suggest that caution be exercised in using affinity constants to assess the interactions of peptide inhibitors with human renin and possibly with other enzymes having extended binding sites. Furthermore, the thermodynamic parameters of a class of compounds provide more information as to the mode of binding of ligands to their respective receptors than do dissociation constants.


Asunto(s)
Péptidos/metabolismo , Renina/antagonistas & inhibidores , Secuencia de Aminoácidos , Sitios de Unión , Unión Competitiva , Dicroismo Circular , Humanos , Datos de Secuencia Molecular , Estructura Molecular , Péptidos/farmacología , Proteínas Recombinantes , Renina/metabolismo , Relación Estructura-Actividad , Termodinámica
16.
J Med Chem ; 31(3): 590-603, 1988 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3346875

RESUMEN

The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency. Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA.


Asunto(s)
Antibióticos Antineoplásicos/metabolismo , ADN/metabolismo , Indoles , Leucomicinas/metabolismo , Animales , Antibióticos Antineoplásicos/síntesis química , Fenómenos Químicos , Química Física , Dicroismo Circular , Duocarmicinas , Femenino , Leucomicinas/síntesis química , Leucomicinas/farmacología , Leucemia L1210/tratamiento farmacológico , Leucemia P388/tratamiento farmacológico , Ratones , Ratones Endogámicos DBA , Solubilidad
17.
J Med Chem ; 35(21): 3928-33, 1992 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-1433201

RESUMEN

To test the hypothesis that replacing Ala19 in growth hormone-releasing factor (GRF) with more hydrophobic residues will increase growth hormone releasing activity, four GRF analogs were prepared and tested. The molecules were made by substituting Val, Ile, or Leu at position 19 of [Thr2,Ala15,Leu27]bGRF(1-29)NH2. The compounds were evaluated for growth hormone (GH) releasing activity in vitro (rat anterior pituitary cells) and in vivo (steers). Additionally, their half-life in vitro was determined in bovine plasma, and their secondary structure was examined by circular dichroism. In pituitary cells, peptides with substitutions at position 19 had the following potencies: Ala (native), 0.37; Val, 1.16; Ile, 0.37; Leu, 0.043. When assayed in steers as a single iv bolus, over a 2-h period, the compounds gave the following integrated GH response: Ala, 2.75; Val, 2.67; Ile, 2.57; Leu, 1.55. Only the Leu analog was statistically different from the other three (p = 0.05). In bovine plasma, the half-lives (hours) were as follows: Ala, 4.9; Val, 6.6; Ile, 12.3; Leu, 14.7. In phosphate buffer the compounds were calculated to have the following percent helical content: Ala, 26; Val, 21; Ile, 27; Leu, 32. For these analogs, helicity in aqueous buffer is inversely related to their in vitro activity. Using a linear multiple regression model, the plasma half-life of the analogs positively correlated (r2 = 0.999) with both the hydrophobicity of the residue at position 19 and the helicity of the analog. Although the Val analog had both increased inherent activity and increased plasma stability in vitro compared to the Ala analog, in this study we were unable to demonstrate an increase in activity in vivo. The in vivo GH releasing activity of the analogs was not simply related to a combination of their intrinsic GH releasing activity and their in vitro plasma half-life. This suggests that in vivo additional factors are moderating the expression of activity.


Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Secuencia de Aminoácidos , Animales , Bovinos , Células Cultivadas , Dicroismo Circular , Hormona Liberadora de Hormona del Crecimiento/sangre , Hormona Liberadora de Hormona del Crecimiento/química , Hormona Liberadora de Hormona del Crecimiento/farmacología , Semivida , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Ratas , Espectrofotometría Ultravioleta
18.
Cancer Lett ; 23(3): 279-88, 1984 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-6744252

RESUMEN

With the brush border membrane vesicles prepared from the rat kidney cortex, didemnin B and its parent compound, didemnin A function neither as a K+-specific ionophore nor as an ionophore for Na+ ions while other depsipeptide antibiotics such as valinomycin and gramicidin promote transmembrane movement of K+ and Na+ ions, respectively. Didemnin B inhibits protein synthesis and DNA synthesis much more than RNA synthesis and is in general more potent than didemnin A. Time course studies reveal that the action of didemnin B is rapid and cannot be reversed after 2 h in contact with the cells. The inhibition of protein synthesis is almost superimposable to that of L1210 cells growth. DNA synthesis is also markedly inhibited. These results collectively suggest that didemnin B acts differently, at least in part, from other depsipeptide antibiotics and its biological effect is primarily mediated through its inhibition of protein synthesis and to a lesser extent its inhibition of DNA synthesis.


Asunto(s)
Antibióticos Antineoplásicos , Depsipéptidos , Animales , Transporte Biológico Activo/efectos de los fármacos , ADN de Neoplasias/biosíntesis , Técnicas In Vitro , Ionóforos , Corteza Renal/efectos de los fármacos , Corteza Renal/metabolismo , Leucemia L1210/tratamiento farmacológico , Leucemia L1210/metabolismo , Masculino , Ratones , Microvellosidades/efectos de los fármacos , Microvellosidades/metabolismo , Proteínas de Neoplasias/biosíntesis , Péptidos Cíclicos/farmacología , Potasio/metabolismo , ARN Neoplásico/biosíntesis , Ratas , Sodio/metabolismo
19.
Invest Radiol ; 14(1): 97-102, 1979.
Artículo en Inglés | MEDLINE | ID: mdl-383644

RESUMEN

Although xeroradiography has had many medical applications, its utilization and the advantages it offers in the study of cadaveric sections has not previously been fully explored. It was our purpose to determine possible advantages or disadvantages this modality might have for this purpose. The edge enhancement which xeroradiography allows is a distinct advantage since the various anatomic structures become more clearly defined. On the other hand, the hollow viscera and the lumina of blood vessels are not enhanced, but rather blend with the walls of these "hollow" structures. Also, there is some loss of detail in the depiction of some of the glandular structures, such as the seminal vesicles. An artist's assistance to define these by comparison with the gross specimen gives us an optimum result. An x-ray enhanced image is thereby attained which exceeds the usual line drawing or artist's depiction of the cross-sectional specimen, and both can be similarly labeled for study.


Asunto(s)
Cadáver , Xerorradiografía/métodos , Abdomen/anatomía & histología , Femenino , Técnicas Histológicas , Humanos , Masculino , Pelvis/anatomía & histología , Pelvis/diagnóstico por imagen , Radiografía Abdominal , Tomografía por Rayos X
20.
Ann N Y Acad Sci ; 247: 391-400, 1975 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-1054241

RESUMEN

Egg production was reduced when young laying hens were kept in contact with metal cages while being continuously exposed to the following cw fields: a vhf field at a frequency of 260 MHz, with an incident power that decreased from 100 to 4mW during the experiment; a uhf field at a frequency of 915 MHz, with an incident power of 800 mW during the first 2.5 weeks, zero during the following week, and 200 mW for the remainder of the experiment; a uhf field at 2.435 GHz, with an incident power of 800 mW; an elf electric field at a frequency of 60 Hz, with a calculated value of field strength of 1600 V/m; an elf magnetic field at 60 Hz, with a value of magnetic flux density of 1.4G. With the exception of the hens exposed to the uhf field at 915 MHz, all other treated groups laid significantly less eggs than the controls (p smaller than or equal to 0.01). This reduction (similar 15% less than the controls) began with the first 4-week production period. The egg production curves for the hens exposed to the vhf field at 260 MHz and to the uhf field at 2.435 GHz were approximately the same beginning with the sixth week of production, and they maintained comparable production levels for the remainder of the experiment. An 8% total drop in production also was experienced in the group of birds exposed to the 915-MHz field, which pulsed because of equipment failure. Egg production rate curves for the birds in the elf electric and magnetic fields were substantially different from those exhibited by birds in the other electromagnetic fields. The birds in the E-field regained a production level comparable to the controls after 11 weeks production, whereas those in the B-field dropped to 31% production, which was approximately 40% poorer than the controls by the twelfth week of production. Fertility of cocks and hens was not affected by continuous low-power vhf and uhf near-zone electromagnetic exposure or elf electric or magnetic field treatment. Fertility was exceptionally good, except for the controls and the hens exposed to the elf electric field. The hatchs of fertile and of total eggs were not significantly influenced by exposure to any of the five fields. A considerably lower incidence of male chicks was noted in the elf magnetic field treatment (32.3%). The sex ratio in the other groups appeared to be relatively normal. No macroscopic abnormalities attributable to treatments were noted in the chicks hatched or in the dead embryos.


Asunto(s)
Fertilidad , Magnetismo , Microondas , Ondas de Radio , Animales , Pollos , Femenino , Masculino
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