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1.
Epidemiol Mikrobiol Imunol ; 71(1): 21-31, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35477267

RESUMEN

AIM: Homelessness is a social, societal, economic, and health problem. The aim of the study was to describe the characteristics of hospitalized homeless persons in the Czech Republic in relation to their health status and to propose targeted measures for improvement. MATERIAL AND METHODS: The study used anonymous data from the National Registry of Hospitalized Patients from 2006-2015, including the primary diagnosis at hospital admission and up to five additional diagnoses according to the 10th revision of the International Classification of Diseases (ICD-10). The basic statistical unit is the completed case of hospitalization of a homeless person in an inpatient health care facility such as hospital or nursing home. RESULTS: Over the 10-year study period (2006-2015), 3387 homeless persons, 77.5% of them male, were admitted to inpatient health care facilities in the Czech Republic. The length of hospital stay tended to decrease over the years, with a median of six days. The majority of hospitalized homeless persons were aged between 40 and 69 years. Their distribution by type of health care facility: 2,710 (80.0%) were admitted to hospitals, 468 (13.8%) to psychiatric hospitals, 180 (5.3%) to long-term care facilities, and 29 (0.9%) to tuberculosis and respiratory disease hospitals. According to the mode of termination of hospitalization, 2189 (64.6%) homeless persons were discharged to their original environment, 280 (8.3%) were transferred to an after-care facility, 277 (8.2%) were transferred to an acute care facility, 222 (6.6%) left against medical advice, 180 (5.3%) were transferred to another ward, and 80 (2.4%) were transferred to a social care facility. A total of 159 (4.7%) in-hospital deaths occurred. The underlying causes of hospitalization according to ICD-10 were mostly those under Chapter V - Mental and behavioural disorders (19.9%) and Chapter XIX - Injury, poisoning and certain other consequences of external causes (18.1%). Among the 175 cases with a primary diagnosis from Chapter I - Certain infectious and parasitic diseases, the most common conditions were scabies, pediculosis, mycosis, bacterial infections, and tuberculosis. CONCLUSION: Data on hospital admissions is one of the important tools for monitoring the health of homeless people. They illustrate the seriousness of the situation of homeless people and point to the need to obtain more information on this issue in order to improve the availability of specific health care and social care for sick homeless people. Prevention programs, residential services, and specific outreach health and social activities can contribute to reducing the negative impacts.


Asunto(s)
Personas con Mala Vivienda , Tuberculosis , Adulto , Anciano , República Checa/epidemiología , Atención a la Salud , Personas con Mala Vivienda/psicología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad
2.
Epidemiol Mikrobiol Imunol ; 71(3): 139-147, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36257793

RESUMEN

BACKGROUND: We estimated what risk factors affect hospitalisation for confirmed pertussis cases among infants (child up to 1 year) in the Czech Republic based on data from the questionnaire-based enhanced surveillance system (ESS) in years 2015, 2017 and 2019. METHODS: Retrospective cohort study was conducted in which we assessed demographic, clinical data, vaccination status and risk/protective factors. Vaccination status was extracted from the electronic nationwide notification system (NNS). We performed descriptive, univariable and multivariable analysis using risk ratio (RR) and logistic regression with odds ratio (OR). RESULTS: A total of 104 confirmed cases (27, 13, 64) were reported in the ESS during 2015, 2017 and 2019. Most cases were in age group 1 month (24), more males (57). Fifteen cases were vaccinated and 89 unvaccinated. Of 88 hospitalised cases, 31 cases reported stay in Intensive Care Unit (ICU). The median length of hospitalisation was 8 days. Although the variable vaccinated in infants was statistically significant in a univariable analysis for outcome hospitalisation, RR 0.76 (95% CI 0.53-1.10), it was not in multivariable. Hospitalisation was strongly associated with the younger age group of 0-3 months adjusted by a smoking family member in a household (OR = 9.72; 95% CI: 2.97-31.81). Stay in ICU was strongly correlated with the younger age group of 0-3 months (OR = 5.07; 95% CI: 1.44-17.87) and with a contact with confirmed or probable pertussis (OR = 7.05; 95% CI: 1.36-36.52). CONCLUSIONS: Our study demonstrated younger age and contact with other pertussis case as risk factors for hospitalisation of infants with pertussis. It is necessary to consider adolescent and adult boosters, including vaccination during pregnancy. We suggest integrating the variables from the enhanced surveillance system into the nationwide notification system, in order to simplify the data reporting and evaluation. Further studies are needed to evaluate the ESS and to monitor the vaccination of pregnant women against pertussis.


Asunto(s)
Vacunación , Tos Ferina , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , República Checa/epidemiología , Hospitalización , Vacuna contra la Tos Ferina , Estudios Retrospectivos , Factores de Riesgo , Tos Ferina/epidemiología , Tos Ferina/prevención & control
3.
Epidemiol Mikrobiol Imunol ; 70(2): 91-97, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34412484

RESUMEN

OBJECTIVES: On 17th Dec 2019 gastroenteritis outbreak occurred in two Pragues neighbouring institutions. Investigation aimed to describe outbreak, identify etiological agent, vehicle and propose control measures. METHODS: Routine outbreak investigation and retrospective cohort study was done. Data collected via online questionnaire were analysed using descriptive, univariate and stratified analysis. RESULTS: Of 960 employees, 276 responded (29%). We identified 39 (14%) cases, one tested norovirus positive. Canteen staff didnt report illness. No food item or environmental sample was tested. Sichuan pork served for lunch on 17th Dec was the most likely vehicle of outbreak (odds ratio (OR) 5.02, 95% confidence interval (CI) 1.98-12.64). Eating Sichuan pork and Chinese soup showed OR 31.5, 95% CI 5.0-320.7. Twenty-two (56%) cases can be explained by consumption of these food items. CONCLUSIONS: Epidemiological analytical method provided evidence of likely vehicle. We did not find the source. Control measures were early ensured and outbreak ceased. We emphasise full outbreak investigation using analytical epidemiology, environmental screening and microbiological testing of cases and possibly all kitchen staff.


Asunto(s)
Enfermedades Transmitidas por los Alimentos , Gastroenteritis , Brotes de Enfermedades , Contaminación de Alimentos/análisis , Enfermedades Transmitidas por los Alimentos/epidemiología , Gastroenteritis/epidemiología , Humanos , Estudios Retrospectivos , Encuestas y Cuestionarios
4.
Epidemiol Mikrobiol Imunol ; 70(1): 62-67, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33853339

RESUMEN

Reports of SARS-CoV-2 reinfections are on the rise. This study focused on reinfections in patients with confirmed COVID-19 in the Czech Republic. Between 1 March 2020 and 9 November 2020, 362 084 cases with the onset of symptoms before 31 October 2020 were reported. Overall, 28 cases of symptomatic SARS-CoV-2 reinfections were identified, 11 in males and 17 in females, age range 25-80 years, median age 46 years. The interval between the first and second episodes of the disease ranged from 101 to 231 days, and the median interval was 201.5 days. During both symptomatic episodes, all patients have been tested by RT-PCR. Altogether 26 patients (92.9%) have been tested negative after recovery from the first episode of COVID-19. Symptomatic reinfections occurred in nearly 0.2% of all patients at risk. Most patients with reinfection had mild symptoms in both episodes, and only three episodes were moderate to severe. Thus, reinfections may have been underdiagnosed. In summary, COVID-19 reinfections are possible and not exceptional.


Asunto(s)
COVID-19 , Adulto , Anciano , Anciano de 80 o más Años , República Checa/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reinfección , SARS-CoV-2
5.
Epidemiol Mikrobiol Imunol ; 67(4): 155-160, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30630318

RESUMEN

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a prion disease. It is a rare, rapidly progressing fatal disorder of the central nervous system, which occurs in four forms: sporadic (sCJD), genetic/familial (gCJD), iatrogenic (iCJD), and variant (vCJD). METHODS: CJD research in the Czech Republic (CR) is conducted by the National Reference Laboratory for Human Transmissible Spongiform Encephalopathies and Creutzfeldt-Jakob Disease, Department of Pathology and Molecular Medicine, established in 2001 at the Department of Pathology, Thomayer Hospital, Prague. In 2003, this NRL was included in the European network of laboratories monitoring prion diseases. The purpose of the article is to analyse data reported to the EPIDAT system. RESULTS: From June 2000 to June 2017, 207 deaths in persons diagnosed with CJN and four suspected deaths due to gCJD were reported to the EPIDAT system (national program of reporting, recording, and analysis of data on transmissible diseases in the CR). CONCLUSION: Reporting CJD cases to the EPIDAT is helpful in meeting the important goals, i.e. monitoring the incidence and trends of the disease. The incidence of gCJD in particular requires improved diagnosis based on a detailed personal and family history, and thorough epidemiological investigation is crucial to detect possible iatrogenic diseases.


Asunto(s)
Síndrome de Creutzfeldt-Jakob , Enfermedades por Prión , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiología , Síndrome de Creutzfeldt-Jakob/mortalidad , República Checa/epidemiología , Humanos , Incidencia , Enfermedades por Prión/diagnóstico , Enfermedades por Prión/epidemiología , Enfermedades por Prión/mortalidad
6.
Epidemiol Mikrobiol Imunol ; 65(2): 92-101, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27467326

RESUMEN

The 2014/2015 influenza epidemic season was characterized by the predominance of the H3N2 subtype. The presented study investigated the genetic and antigenic heterogeneity of the H3N2 strains collected in the Czech Republic from November 2014 to March 2015. Phylogenetic analysis of the representative H3 hemagglutinin sequences was performed and the glycosylation status and crucial antigenic mutations were compared relative to the 2014 and 2015 vaccine strains (A/Texas/50/2012 and A/Switzerland/9715293/2013) and visualized in the H3 crystal structure. The molecular data were further supplemented by hemagglutination-inhibition test (HIT) results on fifteen H3N2 2014/2015 strains by using the A/Texas/50/2012 (H3N2) and A/Switzerland/9715293/13 (H3N2) antisera. Our data on the Czech H3N2 viruses from the 2014/2015 epidemic season could supplement the reports of official authorities with data from a particular geographi-cal area.


Asunto(s)
Antígenos Virales , Epidemias , Glicoproteínas Hemaglutininas del Virus de la Influenza , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana , Antígenos Virales/genética , Antígenos Virales/inmunología , República Checa/epidemiología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/epidemiología , Gripe Humana/virología , Mutación
7.
Epidemiol Mikrobiol Imunol ; 63(3): 245-8, 2014 Sep.
Artículo en Checo | MEDLINE | ID: mdl-25412491

RESUMEN

Influenza is one of the most common causes of human morbidity and mortality. Analysis of severe cases of influenza during the influenza season 2012/2013 found that 84 % of patients had at least one risk factor and the cohort of patients had lower influenza vaccine coverage in comparison with the general population. Influenza vaccine reduces the risk for cardiovascular disease and, therefore, should be recommended particularly to patients with chronic conditions who suffer more often from severe influenza. The education of physicians specialists is also desirable.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/complicaciones , Gripe Humana/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Niño , Preescolar , República Checa , Femenino , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estaciones del Año , Vacunación , Adulto Joven
8.
Epidemiol Mikrobiol Imunol ; 63(2): 83-7, 2014 Jun.
Artículo en Checo | MEDLINE | ID: mdl-25025668

RESUMEN

AIM: To perform phylogenetic and molecular analysis of A/H1N1pdm influenza viruses isolated in the epidemic season 2012/2013 from hospitalised patients with symptoms of influenza-like illness (ILI). MATERIAL AND METHODS: The study set included 34 strains of the A/H1N1pdm influenza virus isolated in the Czech Republic in the epidemic season 2012/2013. The strains were analysed by partial or whole-genome sequencing. The genome segments were compared at the nucleotide and amino acid levels, absolute and percentage sequence identity were determined, and phylogenetic relations were identified. The last steps were the comparison of the H1 molecule with that of the most recent vaccine strain and identification of the genotypic structure and molecular markers linked to the pathogenicity and antiviral resistance. RESULTS: Phylogenetic analysis of the H1 molecule suggested that all 34 A/H1N1pdm isolates from the 2012/2013 season in the Czech Republic should be assigned to H1 group 6 divided into sublineages 6A and 6B. The comparison of the known antigenic regions of the H1 molecule with those in the most recent vaccine strain revealed two stable changes in antigenic regions Sb and Ca1. Furthermore, sporadic mutations were identified in antigenic regions Ca2, Cb, and Sb. Genotyping revealed co-circulation of two related but clearly distiguishable genotypes of A/H1N1pdm. All isolates showed sensitivity to oseltamivir. One strain consisted of two N1 sub-populations, one oseltamivir sensitive and the other oseltamivir resistant, in nearly equimolar proportions. CONCLUSION: All A/H1N1pdm isolates from the epidemic season 2012/2013 in the Czech Republic formed a phenotypically uniform group. At the nucleotide level, the divergence was relatively more pronounced and H1 sublineages and discrete genotypes were possible to identify. H1 molecules were highly identical to those of the vaccine strain A/California/7/2009 (H1N1) which showed that the current vaccine was protective enough. All strains were sensitive to oseltamivir; however, the selection of oseltamivir resistant N1 subpopulations was observed.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Filogenia , República Checa/epidemiología , Farmacorresistencia Viral , Epidemias , Femenino , Hospitalización , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/virología , Masculino , Oseltamivir/farmacología , Factores de Tiempo
9.
Epidemiol Mikrobiol Imunol ; 63(1): 4-9, 2014 Feb.
Artículo en Checo | MEDLINE | ID: mdl-24730988

RESUMEN

AIM OF THE STUDY: To characterize the clinical and epidemiological features of patients hospitalized with moderate to severe influenza infection at the infec-tious diseases department of a tertiary care hospital in the epidemic season 2012-2013. MATERIAL AND METHODS: A prospective observational study of patients hospitalized with influenza infection in the season 2012-2013 was carried out at the Infectious Diseases Department, Na Bulovce Hospital in Prague. Influenza infection was diagnosed by real-time quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swab or tracheal aspirate specimens. Demographic, clinical, and laboratory data were recorded along with the disease course and outcome. RESULTS: One hundred and ninety-nine patients, 85 females and 114 males (age median 47, range 1-87 years), were hospitalized with confirmed influenza in the epidemic season 2012-2013. Only seven of them got the influenza vaccine. Altogether 136 patients were diagnosed with influenza type A (91 with H1N1pdm, 33 with H3N2, and 12 with an unknown subtype), 66 patients with type B, and three patients with both types A and B. One hundred and eight patients (54%) had an underlying chronic disease, most often cardiovascular or pulmonary. The main symptoms of influenza were fever, cough, headache, myalgia, and arthralgia. Pneumonia was the most common complication: twenty-one patients suffered from primary viral pneumonia and 35 from bacterial pneumonia. Twenty-three patients (12%) needed intensive care. Six patients died and the leading cause of death was heart failure. CONCLUSION: During the epidemic influenza season 2012-2013, more patients were hospitalized than in the pandemic season 2009-2010. Also the proportions of complicated cases and case fatality ratios were fully comparable in both seasons. The fact that most patients were not vaccinated clearly supports the recommendation to vaccinate every year both the individuals at high risk of complications due to comorbidities and the healthy population.


Asunto(s)
Gripe Humana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , República Checa/epidemiología , Femenino , Hospitalización , Humanos , Lactante , Gripe Humana/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo
10.
Euro Surveill ; 18(6)2013 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-23410257

RESUMEN

A sudden increase in severe influenza has been registered in the Czech Republic since the end of 2012, with 264 cases requiring intensive care, including 51 deaths. Most patients had at least one risk factor. Severe influenza in patients with obesity, smoking and/or haematological disorders including haematological cancers was more frequent than in the pre-pandemic period. The seasonal influenza vaccination status of the cases indicates indirect efficiency of the current vaccine in preventing severe influenza.


Asunto(s)
Epidemias , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Adolescente , Adulto , Anciano , Niño , Preescolar , República Checa/epidemiología , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Recién Nacido , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/virología , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Vigilancia de la Población , ARN Viral/genética , Factores de Riesgo , Estaciones del Año , Análisis de Secuencia de ADN , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto Joven
11.
Acta Virol ; 57(3): 347-51, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24020760

RESUMEN

A nation-wide vaccination against mumps that had been launched in the Czech Republic in 1987 eliminated great outbreaks (up to 100,000 cases per year) of this disease in 1955-1988, but did not prevent small outbreaks (a few thousand cases per year) in 1995-1996, 2005-2007, and 2010-2012. The extent of these small outbreaks shows an increasing trend. The article describes mumps outbreaks in the Czech Republic in 2011 and 2012 with the aim to bring additional data contributing to the clarification of repeated outbreak triggers. In the years 2011 and 2012 there have been reported 2885 and 3902 mumps cases, respectively, in the Czech Republic. Similarly to other countries, a shift in the age-specific incidence of the disease towards higher age has been found, with the highest occurrence seen in the age group of 15-19 years. Men were slightly more affected than women. Clinical complications and vaccination status of patients were also observed.


Asunto(s)
Paperas/epidemiología , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , República Checa/epidemiología , Femenino , Humanos , Incidencia , Lactante , Masculino , Paperas/prevención & control , Paperas/virología , Vacuna contra la Parotiditis/administración & dosificación , Adulto Joven
12.
Cas Lek Cesk ; 148(5): 191-3, 2009.
Artículo en Checo | MEDLINE | ID: mdl-19642311

RESUMEN

Intradermal vaccination against influenza represents a new method of protection against the heavy incidence disease. For its very good immunity response, intradermal injections are frequently used for many types of vaccines. Results of clinical studies are presented and the system of intradermal microinjections for vaccine administration is introduced. Sensitive vaccination can increase the prevalence of vaccinated persons and thus decrease morbidity and mortality of influenza.


Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vacunación/métodos , Humanos , Inyecciones Intradérmicas , Microinyecciones
13.
Euro Surveill ; 13(40)2008 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-18831951

RESUMEN

The public health protection authorities in the Czech Republic report a rise in cases of viral hepatitis A (HAV) since the end of May 2008. In total, as many as 602 HAV cases have been reported in 2008 until the end of calendar week 39 (28 September).


Asunto(s)
Hepatitis A/epidemiología , Adolescente , Adulto , República Checa/epidemiología , Femenino , Virus de la Hepatitis A/aislamiento & purificación , Humanos , Incidencia , Masculino , Persona de Mediana Edad
15.
Euro Surveill ; 10(3): 30-3, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15827371

RESUMEN

Respiratory virus activity is detected in Europe each winter, yet the precise timing and size of this activity is highly unpredictable. The impact of influenza infection and/or acute respiratory infection in European countries is continuously monitored through a variety of surveillance systems. All of these sources of information are used to assess the nature and extent of activity of influenza and other respiratory viruses, and to offer guidance on the prevention and control of morbidity and mortality due to influenza at a local, national and international level. The early warning system for a forthcoming influenza epidemic is mainly based on the use of a set of thresholds. In the Czech Republic, the acute respiratory infection (ARI) reporting system, with automated data processing, uses a statistical model for the early detection of unusual increased rates of the monitored indicators. The collected data consists of the number of ARI, the number of complications due to ARI and the population registered with the reporting general practitioners and paediatricians, all collected separately in five age groups. To improve the reporting system in the Czech Republic, clinical data on the weekly incidence of influenza-like illness (ILI) within the same population and the same age groups was started in January 2004. These data fit the European Commission's recently adopted ILI case definition and allows a better comparison of data with other countries in Europe, in particular those participating in EISS (European Influenza Surveillance Scheme).


Asunto(s)
Notificación de Enfermedades/métodos , Gripe Humana/epidemiología , Difusión de la Información/métodos , Vigilancia de la Población/métodos , Síndrome de Dificultad Respiratoria/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Comorbilidad , República Checa/epidemiología , Europa (Continente) , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Relaciones Interinstitucionales , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores de Riesgo
16.
Radiat Prot Dosimetry ; 115(1-4): 92-4, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16381689

RESUMEN

The fast-neutron and photon space-energy distributions have been measured in an axially (1.25 m active height) and azimuthally (60 degree symmetry sector) shortened model of the WWER-1000 reactor assembled in the LR-0 experimental reactor. The space-energy distributions have been calculated with the stochastic code MCNP and the deterministic three-dimensional code TORT. Selected results are presented and discussed in the paper. This work has been done in the frame of the EU 5th FW project REDOS REDOS, Reactor Dosimetry: Accurate determination and benchmarking of radiation field parameters, relevant for reactor pressure vessel monitoring. EURATOM Programme, Call 2000/C 294/04). All geometry and material composition data of the model as well as the available experimental data were carefully checked and revised.


Asunto(s)
Modelos Estadísticos , Reactores Nucleares , Monitoreo de Radiación/métodos , Protección Radiológica/instrumentación , Protección Radiológica/métodos , Medición de Riesgo/métodos , Algoritmos , Simulación por Computador , República Checa , Falla de Equipo , Análisis de Falla de Equipo/métodos , Arquitectura y Construcción de Instituciones de Salud/métodos , Método de Montecarlo , Neutrones , Fotones , Dosis de Radiación , Programas Informáticos
17.
Am J Med ; 80(5B): 12-9, 1986 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-2872801

RESUMEN

Terazosin is a quinazoline antihypertensive agent that is chemically similar to prazosin. The saturated furan ring of terazosin distinguishes these two compounds. Terazosin (0.1 to 3.0 mg/kg) lowered blood pressure without increasing heart rate when given orally to spontaneously hypertensive rats. No tolerance was observed during five days of repeated oral administration. Although equally efficacious in spontaneously hypertensive rats as its congener prazosin, terazosin exhibited a more gradual onset of action than prazosin, a more uniform and linear dose-response curve, and a less variable duration of action. When administered intravenously to dogs, terazosin lowered blood pressure primarily by decreasing peripheral vascular resistance. Pretreatment with phenoxybenzamine but not with atropine or propranolol resulted in a greatly reduced hypotensive response to terazosin, demonstrating that this effect of terazosin is mediated by a sympatholytic mechanism of the alpha type. The nature of the alpha-blocking properties of terazosin was evaluated in vitro using both radioligand binding studies and functional tests in rabbit aorta and pulmonary artery. These studies demonstrated that terazosin is highly selective for alpha1 receptors. The affinity for alpha1 receptors was approximately one-third that of prazosin. Like prazosin, terazosin displayed minimal interaction with alpha2 receptors. Median lethal dose values in rats ranged from 0.255 to 0.270 g/kg for intravenous administration and from 5.5 to 6.0 g/kg, for oral administration. Oral administration of high doses of the compound to rats did not produce any gastrointestinal irritation and/or apparent abnormal behavioral effects. Comparison of the oral activity of terazosin in spontaneously hypertensive rats with the oral toxicity values in normal rats revealed a high efficacy/safety ratio. Terazosin given intravenously to rats and mice was 2.6 to 5.0 times less toxic than prazosin. The absorption of terazosin appeared to be slower than that of prazosin in rats. However, from eight to 16 hours after dosing, terazosin concentrations in plasma exceeded those of prazosin, suggesting the possibility of once-daily dosing with terazosin. In addition, terazosin exhibited statistically significant cholesterol lowering effects in gerbils.


Asunto(s)
Antagonistas Adrenérgicos alfa , Piperazinas/farmacología , Administración Oral , Antagonistas Adrenérgicos alfa/sangre , Antagonistas Adrenérgicos alfa/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Fenómenos Químicos , Química , Perros , Relación Dosis-Respuesta a Droga , Femenino , Gerbillinae , Hemodinámica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Lipoproteínas/sangre , Masculino , Piperazinas/sangre , Piperazinas/toxicidad , Prazosina/farmacología , Conejos , Ratas , Ratas Endogámicas
18.
J Med Chem ; 26(2): 214-7, 1983 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6827538

RESUMEN

A number of azacannabinoids containing hydroxyacyl and aminoacetyl substituents on the nitrogen atom were synthesized. The hydroxyacetyl and gamma-hydroxybutyryl derivatives were potent antihypertensive agents (minimum effective dose, 3-5 mg/kg, orally) of the same order of activity as the highly CNS-active N-propargyl derivatives Ia and Ib. Furthermore, 4a showed weak stimulant properties at hypotensive dose levels, in contrast to the strongly CNS-depressant action characteristic of the N-propargyl analogues.


Asunto(s)
Antihipertensivos , Cannabinoides/síntesis química , Animales , Presión Sanguínea/efectos de los fármacos , Cannabinoides/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/fisiopatología , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Ratas , Relación Estructura-Actividad
19.
J Med Chem ; 18(4): 434-7, 1975 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1079053

RESUMEN

Starting from 3,4-dimethoxyphenacyl bromide, 2-amino-4-(3,4-dihydroxyphenyl)butyric acid (homodopa) was synthesized in six steps. 5-Hydroxyhomodopa was similarly prepared. alpha-Methylhomodopa was synthesized in four steps from zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone]. alpha-Methylhomodopa showed no antihypertensive activity in the genetic hypertensive rat. Homodopa did not potentiate the behavioral effect of Dopa or inhibit Dopa decarboxylase. Homodopamine, unlike dopamine, did not increase renal blood flow in the dog.


Asunto(s)
Dihidroxifenilalanina/análogos & derivados , Dopamina/análogos & derivados , Metildopa/análogos & derivados , 5-Hidroxitriptófano/farmacología , Animales , Inhibidores de Descarboxilasas de Aminoácidos Aromáticos , Presión Sanguínea/efectos de los fármacos , Encéfalo/enzimología , Química Encefálica/efectos de los fármacos , Dihidroxifenilalanina/síntesis química , Dihidroxifenilalanina/farmacología , Perros , Dopamina/síntesis química , Dopamina/farmacología , Dopamina beta-Hidroxilasa/antagonistas & inhibidores , Sinergismo Farmacológico , Riñón/irrigación sanguínea , Masculino , Metildopa/síntesis química , Metildopa/farmacología , Ratones , Miocardio/enzimología , Ratas , Flujo Sanguíneo Regional/efectos de los fármacos , Relación Estructura-Actividad
20.
J Med Chem ; 29(8): 1413-7, 1986 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3016266

RESUMEN

A series of modifications to positions 1, 2, and 4 of the tetralin ring of 5,6-dihydroxy-1-(2-imidazolinyl)tetralin (1, A-54741) succeeded in improving the separation of the potent alpha 1 and alpha 2 adrenergic agonism observed for the parent compound 1. In particular 5,6-dihydroxy-4,4-dimethyl-1-(2-imidazolinyl)tetralin (7) was found to be a specific alpha 1 adrenergic agonist, and 7,8-dihydroxy-4-(2-imidazolinyl)chroman (2) was found to have improved alpha 2 adrenergic agonistic selectivity relative to the parent compound 1.


Asunto(s)
Simpatomiméticos/síntesis química , Animales , Aorta/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Femenino , Conformación Molecular , Norepinefrina/metabolismo , Fenoxibenzamina/farmacología , Prazosina/metabolismo , Conejos , Receptores Adrenérgicos alfa/metabolismo , Relación Estructura-Actividad , Simpatomiméticos/farmacología
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