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1.
MMWR Morb Mortal Wkly Rep ; 73(22): 514-516, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38843099

RESUMO

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).


Assuntos
Infecções Meningocócicas , Neisseria meningitidis , Humanos , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Estados Unidos/epidemiologia , França/epidemiologia , Arábia Saudita/epidemiologia , Adulto Jovem , Adulto , Adolescente , Masculino , Feminino , Neisseria meningitidis/isolamento & purificação , Criança , Pré-Escolar , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Lactente , Idoso , Doença Relacionada a Viagens , Surtos de Doenças/prevenção & controle , Viagem
2.
Mol Pharm ; 19(9): 3163-3177, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35876358

RESUMO

Increasing antibiotic concentrations within bacterial cells while reducing them in mammalian ones would ultimately result in an enhancement of antibacterial actions, overcoming multidrug resistance, all while minimizing toxicity. Nanoparticles (NPs) have been used in numerous occasions to overcome antibiotic resistance, poor drug solubility, and stability. However, the concomitant increase in antibiotic concentration in mammalian cells and the resultant toxicity are usually overlooked. Without compromising bacterial cell fusion, large liposomes (Lip) have been reported to show reduced uptake in mammalian cells. Therefore, in this work, small NP fraught liposomes (NP-Lip) were formulated with the aim of increasing NP uptake and antibiotic delivery in bacterial cells but not in mammalian ones. Small polylactic-co-glycolic acid NPs were therefore loaded with erythromycin (Er), an antibiotic with low membrane permeability that is susceptible to drug efflux, and 3c, a 5-cyanothiazolyl urea derivative with low solubility and stability. In vitro experiments demonstrated that the incorporation of small NPs into large Lip resulted in a reduction in NP uptake by HEK293 cells while increasing it in Gram-negative bacteria (Escherichia coli DH5α, E. coli K12, and Pseudomonas aeruginosa), consequently resulting in an enhancement of antibiotic selectivity by fourfold toward E. coli (both strains) and eightfold toward P. aeruginosa. Ocular administration of NP-Lip in a P. aeruginosa keratitis mouse model demonstrated the ability of Er/3c-loaded NP-Lip to result in a complete recovery. More importantly, in comparison to NPs, the ocular administration of NP-Lip showed a reduction in TNF-alpha and IL-6 levels, implying reduced interaction with mammalian cells in vivo. This work therefore clearly demonstrated how tailoring the nano-bio interaction could result in selective drug delivery and a reduction in toxicity.


Assuntos
Antibacterianos , Nanopartículas , Animais , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Escherichia coli/metabolismo , Células HEK293 , Humanos , Lipossomos/metabolismo , Mamíferos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa
3.
J Gen Virol ; 102(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33709903

RESUMO

The p7 viroporin of the hepatitis C virus (HCV) forms an intracellular proton-conducting transmembrane channel in virus-infected cells, shunting the pH of intracellular compartments and thus helping virus assembly and release. This activity is essential for virus infectivity, making viroporins an attractive target for drug development. The protein sequence and drug sensitivity of p7 vary between the seven major genotypes of the hepatitis C virus, but the essential channel activity is preserved. Here, we investigated the effect of several inhibitors on recombinant HCV p7 channels corresponding to genotypes 1a-b, 2a-b, 3a and 4a using patch-clamp electrophysiology and cell-based assays. We established a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based cell viability assay for recombinant p7 expressed in HEK293 cells to assess channel activity and its sensitivity to inhibitors. The results from the cell viability assay were consistent with control measurements using established assays of haemadsorption and intracellular pH, and agreed with data from patch-clamp electrophysiology. Hexamethylene amiloride (HMA) was the most potent inhibitor of p7 activity, but possessed cytotoxic activity at higher concentrations. Rimantadine was active against p7 of all genotypes, while amantadine activity was genotype-dependent. The alkyl-chain iminosugars NB-DNJ, NN-DNJ and NN-DGJ were tested and their activity was found to be genotype-specific. In the current study, we introduce cell viability assays as a rapid and cost-efficient technique to assess viroporin activity and identify channel inhibitors as potential novel antiviral drugs.


Assuntos
Hepacivirus/genética , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética , Montagem de Vírus , Liberação de Vírus , Amantadina/farmacologia , Sequência de Aminoácidos , Antivirais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Hepacivirus/efeitos dos fármacos , Humanos , Técnicas de Patch-Clamp , Rimantadina/farmacologia
4.
Int J Health Geogr ; 20(1): 27, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098981

RESUMO

BACKGROUND: Social instability and logistical factors like the displacement of vulnerable populations, the difficulty of accessing these populations, and the lack of geographic information for hard-to-reach areas continue to serve as barriers to global essential immunizations (EI). Microplanning, a population-based, healthcare intervention planning method has begun to leverage geographic information system (GIS) technology and geospatial methods to improve the remote identification and mapping of vulnerable populations to ensure inclusion in outreach and immunization services, when feasible. We compare two methods of accomplishing a remote inventory of building locations to assess their accuracy and similarity to currently employed microplan line-lists in the study area. METHODS: The outputs of a crowd-sourced digitization effort, or mapathon, were compared to those of a machine-learning algorithm for digitization, referred to as automatic feature extraction (AFE). The following accuracy assessments were employed to determine the performance of each feature generation method: (1) an agreement analysis of the two methods assessed the occurrence of matches across the two outputs, where agreements were labeled as "befriended" and disagreements as "lonely"; (2) true and false positive percentages of each method were calculated in comparison to satellite imagery; (3) counts of features generated from both the mapathon and AFE were statistically compared to the number of features listed in the microplan line-list for the study area; and (4) population estimates for both feature generation method were determined for every structure identified assuming a total of three households per compound, with each household averaging two adults and 5 children. RESULTS: The mapathon and AFE outputs detected 92,713 and 53,150 features, respectively. A higher proportion (30%) of AFE features were befriended compared with befriended mapathon points (28%). The AFE had a higher true positive rate (90.5%) of identifying structures than the mapathon (84.5%). The difference in the average number of features identified per area between the microplan and mapathon points was larger (t = 3.56) than the microplan and AFE (t = - 2.09) (alpha = 0.05). CONCLUSIONS: Our findings indicate AFE outputs had higher agreement (i.e., befriended), slightly higher likelihood of correctly identifying a structure, and were more similar to the local microplan line-lists than the mapathon outputs. These findings suggest AFE may be more accurate for identifying structures in high-resolution satellite imagery than mapathons. However, they both had their advantages and the ideal method would utilize both methods in tandem.


Assuntos
Imunização , Vacinação , Adulto , Criança , Características da Família , Sistemas de Informação Geográfica , Humanos , Imagens de Satélites
5.
MMWR Morb Mortal Wkly Rep ; 69(28): 913-917, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32673297

RESUMO

Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses.


Assuntos
Saúde Global/estatística & dados numéricos , Síndromes de Imunodeficiência/complicações , Poliomielite/epidemiologia , Vacina Antipólio Oral/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Poliomielite/prevenção & controle , Poliovirus/genética , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem , Sorogrupo
6.
Can J Physiol Pharmacol ; 97(11): 1053-1063, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31116952

RESUMO

Angiogenesis is regulated in a tissue-specific manner in all patients, especially those with diabetes. In this study, we describe a novel molecular pathway of angiogenesis regulation in diabetic rats with myocardial infarction (MI) and examine the cardioprotective effects of different doses of sitagliptin. Male rats were divided into 5 groups: normal vehicle group, diabetic group, diabetic + MI, diabetic + MI + 5 mg/kg sitagliptin, and diabetic + MI + 10 mg/kg sitagliptin. Isoproterenol in diabetic rats resulted in significant (p < 0.05) disturbance to the electrocardiogram, cardiac histopathological manifestations, and an increase in inflammatory markers compared with the vehicle and diabetic groups. Treatment with sitagliptin improved the electrocardiogram and histopathological sections, upregulated vascular endothelial growth factor (VEGF) and transmembrane phosphoglycoprotein protein (CD34) in cardiac tissues, and increased serum insulin-like growth factor 1 (IGF-1) and decreased cardiac tissue homogenate for interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2). A relationship was found between serum IGF-1 and cardiac VEGF and CD34 accompanied by an improvement in cardiac function of diabetic rats with MI. Therefore, the observed effects of sitagliptin occurred at least partly through an improvement in angiogenesis and the mitigation of inflammation. Consequently, these data suggest that sitagliptin may contribute, in a dose-dependent manner, to protection against acute MI in diabetic individuals.


Assuntos
Diabetes Mellitus Experimental/complicações , Fator de Crescimento Insulin-Like I/metabolismo , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Fosfato de Sitagliptina/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Doença Aguda , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Eletrocardiografia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Interleucina-6/metabolismo , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos
7.
Risk Anal ; 38(8): 1701-1717, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29314143

RESUMO

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.


Assuntos
Poliomielite/prevenção & controle , Poliomielite/transmissão , Afeganistão , Erradicação de Doenças , Humanos , Modelos Biológicos , Paquistão , Poliomielite/imunologia , Poliovirus/classificação , Poliovirus/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Gestão de Riscos , Sorotipagem , Vacinação/métodos
8.
MMWR Morb Mortal Wkly Rep ; 66(8): 227-231, 2017 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-28253229

RESUMO

As the world advances toward the eradication of polio, outbreaks of wild poliovirus (WPV) in polio-free regions pose a substantial risk to the timeline for global eradication. Countries and regions experiencing active conflict, chronic insecurity, and large-scale displacement of persons are particularly vulnerable to outbreaks because of the disruption of health care and immunization services (1). A polio outbreak occurred in the Middle East, beginning in Syria in 2013 with subsequent spread to Iraq (2). The outbreak occurred 2 years after the onset of the Syrian civil war, resulted in 38 cases, and was the first time WPV was detected in Syria in approximately a decade (3,4). The national governments of eight countries designated the outbreak a public health emergency and collaborated with partners in the Global Polio Eradication Initiative (GPEI) to develop a multiphase outbreak response plan focused on improving the quality of acute flaccid paralysis (AFP) surveillance* and administering polio vaccines to >27 million children during multiple rounds of supplementary immunization activities (SIAs).† Successful implementation of the response plan led to containment and interruption of the outbreak within 6 months of its identification. The concerted approach adopted in response to this outbreak could serve as a model for responding to polio outbreaks in settings of conflict and political instability.


Assuntos
Surtos de Doenças/prevenção & controle , Poliomielite/prevenção & controle , Guerra , Humanos , Programas de Imunização , Oriente Médio/epidemiologia , Poliomielite/epidemiologia , Poliovirus/isolamento & purificação , Vacinas contra Poliovirus/administração & dosagem
9.
MMWR Morb Mortal Wkly Rep ; 66(47): 1295-1299, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29190264

RESUMO

Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.


Assuntos
Surtos de Doenças/prevenção & controle , Programas de Imunização/organização & administração , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Humanos , Lactente , Paquistão/epidemiologia , Poliomielite/epidemiologia , Poliovirus/isolamento & purificação , Avaliação de Programas e Projetos de Saúde , Esgotos/virologia
10.
Biophys J ; 110(11): 2419-2429, 2016 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-27276260

RESUMO

Hepatitis C is a major worldwide disease and health hazard, affecting ∼3% of the world population. The p7 protein of hepatitis C virus (HCV) is an intracellular ion channel and pH regulator that is involved in the viral replication cycle. It is targeted by various classical ion channel blockers. Here, we generated p7 constructs corresponding to HCV genotypes 1a, 2a, 3a, and 4a for recombinant expression in HEK293 cells, and studied p7 channels using patch-clamp recording techniques. The pH50 values for recombinant p7 channels were between 6.0 and 6.5, as expected for proton-activated channels, and current-voltage dependence did not show any differences between genotypes. Inhibition of p7-mediated currents by amantadine, however, exhibited significant, genotype-specific variation. The IC50 values of p7-1a and p7-4a were 0.7 ± 0.1 nM and 3.2 ± 1.2 nM, whereas p7-2a and p7-3a had 50- to 1000-fold lower sensitivity, with IC50 values of 2402 ± 334 nM and 344 ± 64 nM, respectively. The IC50 values for rimantadine were low across all genotypes, ranging from 0.7 ± 0.1 nM, 1.6 ± 0.6 nM, and 3.0 ± 0.8 nM for p7-1a, p7-3a, and p7-4a, respectively, to 24 ± 4 nM for p7-2a. Results from patch-clamp recordings agreed well with cellular assays of p7 activity, namely, measurements of intracellular pH and hemadsorption assays, which confirmed the much reduced amantadine sensitivity of genotypes 2a and 3a. Thus, our results establish patch-clamp studies of recombinant viroporins as a valid analytical tool that can provide quantitative information about viroporin channel properties, complementing established techniques.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Técnicas de Patch-Clamp , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética , Amantadina/farmacologia , Western Blotting , Genótipo , Células HEK293 , Hemadsorção/efeitos dos fármacos , Hemadsorção/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rimantadina/farmacologia , Transfecção
11.
MMWR Morb Mortal Wkly Rep ; 65(46): 1295-1299, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27880752

RESUMO

Pakistan, Afghanistan, and Nigeria remain the only countries where endemic wild poliovirus type 1 (WPV1) transmission continues. This report describes the activities, challenges, and progress toward polio eradication in Pakistan during January 2015-September 2016 and updates previous reports (1,2). In 2015, a total of 54 WPV1 cases were reported in Pakistan, an 82% decrease from 2014. In 2016, 15 WPV1 cases had been reported as of November 1, representing a 61% decrease compared with the 38 cases reported during the same period in 2015 (Figure 1). Among the 15 WPV1 cases reported in 2016, children aged <36 months accounted for 13 cases; four of those children had received only a single dose of oral poliovirus vaccine (OPV). Seven of the 15 WPV1 cases occurred in the province of Khyber Pakhtunkhwa (KP), five in Sindh, two in the Federally Administered Tribal Areas (FATA), and one in Balochistan (3). During January-September 2016, WPV1 was detected in 9% (36 of 384) of environmental samples collected, compared with 19% (69 of 354) of samples collected during the same period in 2015. Rigorous implementation of the 2015-2016 National Emergency Action Plan (NEAP) (4), coordinated by the National Emergency Operations Center (EOC), has resulted in a substantial decrease in overall WPV1 circulation compared with the previous year. However, detection of WPV1 cases in high-risk areas and the detection of WPV1 in environmental samples from geographic areas where no polio cases are identified highlight the need to continue to improve the quality of supplemental immunization activities (SIAs),* immunization campaigns focused on vaccinating children with OPV outside of routine immunization services, and surveillance for acute flaccid paralysis (AFP). Continuation and refinement of successful program strategies, as outlined in the new 2016-2017 NEAP (5), with particular focus on identifying children missed by vaccination, community-based vaccination, and rapid response to virus identification are needed to stop WPV transmission.


Assuntos
Erradicação de Doenças , Poliomielite/prevenção & controle , Vigilância da População , Pré-Escolar , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Paquistão/epidemiologia , Poliomielite/epidemiologia , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem , Vacinas contra Poliovirus/administração & dosagem
12.
Birth Defects Res A Clin Mol Teratol ; 106(3): 155-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26690723

RESUMO

BACKGROUND: State-specific information about hospitalizations of children with birth defects can improve understanding of changes in occurrence, treatment practices, and health care financing policies. This study analyzed aggregated data on hospital charges and length of stay for a large, diverse population. METHODS: We extracted hospitalization data for children diagnosed with birth defects from the Texas Hospital Inpatient Discharge Public Use Data File (2001-2010). Analyses compared total charges and length of stay for children with and without a diagnosis code of any birth defect among 45 standard categories. We also examined trends for total charges by expected payer type. RESULTS: In Texas, 431,296 hospital stays were reported for children with birth defects, with total charges of $24.8 billion. Mean hospital stay for children with birth defects was more than twice that of those without, whereas mean of hospital total charges was approximately six times greater. Pyloric stenosis accounted for the largest number of hospitalizations, followed by certain cardiac defects. Pediatric hospitalizations for birth defects increased 273.7%, compared with a 214.7% increase overall. The percentage of charges with Medicaid as expected payer (2004-2010) ranged from 56.5 to 62.0%. CONCLUSION: Charges associated with these conditions are far greater than those associated with pediatric hospitalizations for other causes, whether in the newborn period or beyond. However, these charges vary depending on specific diagnoses, expected payer source, and year of treatment.


Assuntos
Anormalidades Congênitas/economia , Preços Hospitalares/estatística & dados numéricos , Hospitalização/economia , Tempo de Internação/economia , Adolescente , Criança , Pré-Escolar , Anormalidades Congênitas/terapia , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Medicaid/estatística & dados numéricos , Texas , Estados Unidos
13.
Can J Physiol Pharmacol ; 94(5): 463-76, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27119311

RESUMO

Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Tiazolidinedionas/uso terapêutico , Agonistas Adrenérgicos beta/intoxicação , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Cardiomiopatias Diabéticas/induzido quimicamente , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/sangue , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Isoproterenol/intoxicação , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/complicações , Tamanho do Órgão/efeitos dos fármacos , Sobrepeso/complicações , Sobrepeso/etiologia , Sobrepeso/prevenção & controle , Pioglitazona , Distribuição Aleatória , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/efeitos adversos
14.
MMWR Morb Mortal Wkly Rep ; 64(45): 1271-5, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26584026

RESUMO

Since Nigeria reported its last case of wild poliovirus type 1 (WPV1) in July 2014, Pakistan and Afghanistan remain the only two countries where WPV transmission has never been interrupted. This report describes actions taken and progress achieved toward polio eradication in Pakistan during January 2014-September 2015 and updates previous reports. A total of 38 WPV1 cases were reported in Pakistan during January-September 2015, compared with 243 during the same period in 2014 (an 84% decline). Among WPV1 cases reported in 2015, 32 (84%) occurred in children aged <36 months, nine (32%) of whom had never received oral poliovirus vaccine (OPV). Twenty-six (68%) of the 38 reported cases occurred in the Federally Administered Tribal Areas (FATA) and Khyber Pakhtunkhwa (KPK) Province. During January-September 2015, WPV1 was detected in 20% (64 of 325) of environmental samples collected, compared with 34% (98 of 294) of samples collected during the same period in 2014. The quality and scope of polio eradication activities improved considerably following the establishment of a national Emergency Operations Center, which coordinated polio eradication partners' activities. All activities are following a National Polio Eradication Emergency Action Plan that includes a rigorous action plan for the polio low transmission season (January-April). The presence of WPV1 in environmental samples in areas where no polio cases are detected highlights the need to improve surveillance for acute flaccid paralysis (AFP). Focused efforts to close remaining immunity gaps by locating, tracking, and vaccinating continually missed children and improving coverage with OPV through the routine vaccination program are needed to stop WPV transmission in Pakistan.


Assuntos
Erradicação de Doenças , Poliomielite/prevenção & controle , Vigilância da População , Pré-Escolar , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Paquistão/epidemiologia , Poliomielite/epidemiologia , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem , Fatores de Tempo , Vacinação/estatística & dados numéricos
15.
Ann Clin Microbiol Antimicrob ; 14: 21, 2015 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-25885806

RESUMO

BACKGROUND: Candida albicans is a common cause of a variety of superficial and invasive disseminated infections the majority of which are associated with biofilm growth on implanted devices. The aim of the study is to evaluate the activity of amphotericin B and voriconazole against the biofilm and the biofilm-dispersed cells of Candida albicans using a newly developed in vitro pharmacokinetic model which simulates the clinical situation when the antifungal agents are administered intermittently. METHODS: RPMI medium containing 1-5 X 10(6) CFU/ml of C. albicans was continuously delivered to the device at 30 ml/h for 2 hours. The planktonic cells were removed and biofilms on the catheter were kept under continuous flow of RPMI medium at 10 ml/h. Five doses of amphotericin B or voriconazole were delivered to 2, 5 and 10 day-old biofilms at initial concentrations (2 and 3 µg/ml respectively) that were exponentially diluted. Dispersed cells in effluents from the device were counted and the adherent cells on the catheter were evaluated after 48 h of the last dose. RESULTS: The minimum inhibitory concentration of voriconazole and amphotericin B against the tested isolate was 0.0325 and 0.25 µg/ml respectively. Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm. The log10 reduction in the dispersed cells was 2.54-3.54, 2.30-3.55, and 1.94-2.50 following addition of 5 doses of amphotericin B to 2-, 5- and 10-day old biofilms respectively. The number of the viable cells within the biofilm was reduced by 18 (±7.63), 5 and 4% following addition of the 5 doses of amphotericin B to the biofilms respectively. Voriconazole showed no significant effect on the viability of C. albicans within the biofilm. CONCLUSION: Both antifungal agents failed to eradicate C. albicans biofilm or stop cell dispersion from them and the resistance progressed with maturation of the biofilm. These findings go along with the need for removal of devices in spite of antifungal therapy in patients with device-related infection. This is the first study which investigates the effects of antifungal agents on the biofilm and biofilm-dispersion of C. albicans in an in vitro pharmacokinetic biofilm model.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase/microbiologia , Voriconazol/farmacologia , Anfotericina B/farmacocinética , Antifúngicos/farmacocinética , Candida albicans/crescimento & desenvolvimento , Candidíase/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Voriconazol/farmacocinética
16.
J Infect Dis ; 209(12): 1870-2, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24474813

RESUMO

We conducted an epidemiologic investigation among survivors of an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Jordan. A second-trimester stillbirth occurred during the course of an acute respiratory illness that was attributed to MERS-CoV on the basis of exposure history and positive results of MERS-CoV serologic testing. This is the first occurrence of stillbirth during an infection with MERS-CoV and may have bearing upon the surveillance and management of pregnant women in settings of unexplained respiratory illness potentially due to MERS-CoV. Future prospective investigations of MERS-CoV should ascertain pregnancy status and obtain further pregnancy-related data, including biological specimens for confirmatory testing.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavirus/isolamento & purificação , Infecções Respiratórias/epidemiologia , Natimorto/epidemiologia , Adolescente , Adulto , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Jordânia , Gravidez , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Estudos Retrospectivos , Adulto Jovem
17.
Clin Infect Dis ; 59(9): 1225-33, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24829216

RESUMO

BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti-MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti-MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. CONCLUSIONS: Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Adulto , Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/imunologia , Infecção Hospitalar/prevenção & controle , Feminino , Pessoal de Saúde , Humanos , Jordânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
18.
MMWR Morb Mortal Wkly Rep ; 63(43): 973-7, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25356605

RESUMO

In 2012, the World Health Assembly declared the completion of polio eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. Afghanistan and Pakistan are two of the three remaining countries (the other is Nigeria) where circulation of indigenous wild poliovirus (WPV) has never been interrupted. This report updates previous reports and describes polio eradication activities and progress in Afghanistan and Pakistan during January 2013-August 2014. In Afghanistan, 14 WPV cases were reported in 2013, compared with 37 cases in 2012; nine cases were reported during January-August 2014, compared with six cases during the same period in 2013. In Pakistan, 93 WPV cases were reported in 2013, compared with 58 cases in 2012; 170 cases were reported during January-August 2014, compared with 33 cases during the same period in 2013. All WPV cases reported during January 2013-August 2014 were WPV type 1 (WPV1). Vaccination campaigns have been banned since June 2012 in specific areas in Pakistan, where an estimated 300,000 children aged <5 years reside and where 69% of WPV cases have occurred in 2014. To accomplish the objectives of the Polio Eradication and Endgame Strategic Plan for 2013-2018 both countries should continue to negotiate access of vaccinators to insecure and temporarily inaccessible areas, improve immunization program performance to reach more children in accessible areas, and ensure that political and health leaders at all levels are fully committed to the program, including being committed to providing financial resources needed to fully implement all the recommendations of external technical advisory groups. Both countries should also continue to strengthen cross-border collaboration to improve surveillance and case detection, coordinate outbreak response, and maximize vaccination coverage of children moving between the two countries.


Assuntos
Erradicação de Doenças , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vigilância da População , Adolescente , Afeganistão/epidemiologia , Criança , Pré-Escolar , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Paquistão/epidemiologia , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem
19.
Clin Infect Dis ; 56(1): 20-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22997210

RESUMO

BACKGROUND: Listeria monocytogenes causes often-fatal infections affecting mainly immunocompromised persons. Sources of hospital-acquired listeriosis outbreaks can be difficult to identify. We investigated a listeriosis outbreak spanning 7 months and involving 5 hospitals. METHODS: Outbreak-related cases were identified by pulsed-field gel electrophoresis (PFGE) and confirmed by multiple-locus variable-number tandem-repeat analysis (MLVA). We conducted patient interviews, medical records reviews, and hospital food source evaluations. Food and environmental specimens were collected at a hospital (hospital A) where 6 patients had been admitted before listeriosis onset; these specimens were tested by culture, polymerase chain reaction (PCR), and PFGE. We collected and tested food and environmental samples at the implicated processing facility. RESULTS: Ten outbreak-related patients were immunocompromised by ≥1 underlying conditions or treatments; 5 died. All patients had been admitted to or visited an acute-care hospital during their possible incubation periods. The outbreak strain of L. monocytogenes was isolated from chicken salad and its diced celery ingredient at hospital A, and in 19 of >200 swabs of multiple surfaces and in 8 of 11 diced celery products at the processing plant. PCR testing detected Listeria in only 3 of 10 environmental and food samples from which it was isolated by culturing. The facility was closed, products were recalled, and the outbreak ended. CONCLUSIONS: Contaminated diced celery caused a baffling, lengthy outbreak of hospital-acquired listeriosis. PCR testing often failed to detect the pathogen, suggesting its reliability should be further evaluated. Listeriosis risk should be considered in fresh produce selections for immunocompromised patients.


Assuntos
Apium/microbiologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Listeria monocytogenes/isolamento & purificação , Listeriose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/microbiologia , Eletroforese em Gel de Campo Pulsado , Feminino , Serviço Hospitalar de Nutrição , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Período de Incubação de Doenças Infecciosas , Listeriose/microbiologia , Masculino , Pessoa de Meia-Idade , Texas/epidemiologia
20.
Alcohol Clin Exp Res ; 37(4): 616-23, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23126641

RESUMO

BACKGROUND: Stressful early life experience may have adverse consequences in adulthood and may contribute to behavioral characteristics that increase vulnerability to alcoholism. We examined early life adverse experience in relation to cognitive deficits and impulsive behaviors with a reference to risk factors for alcoholism. METHODS: We tested 386 healthy young adults (18 to 30 years of age; 224 women; 171 family history positive for alcoholism) using a composite measure of adverse life experience (low socioeconomic status plus personally experienced adverse events including physical and sexual abuse and separation from parents) as a predictor of performance on the Shipley Institute of Living scale, the Stroop color-word task, and a delay discounting task assessing preference for smaller immediate rewards in favor of larger delayed rewards. Body mass index (BMI) was examined as an early indicator of altered health behavior. RESULTS: Greater levels of adversity predicted higher Stroop interference scores (F = 3.07, p = 0.048), faster discounting of delayed rewards (F = 3.79, p = 0.024), lower Shipley mental age scores (F = 4.01, p = 0.019), and higher BMIs in those with a family history of alcoholism (F = 3.40, p = 0.035). These effects were not explained by age, sex, race, education, or depression. CONCLUSIONS: The results indicate a long-term impact of stressful life experience on cognitive function, impulsive behaviors, and early health indicators that may contribute to risk in persons with a family history of alcoholism.


Assuntos
Alcoolismo/epidemiologia , Maus-Tratos Infantis , Transtornos Cognitivos/epidemiologia , Saúde da Família , Comportamento Impulsivo/epidemiologia , Acontecimentos que Mudam a Vida , Adolescente , Adulto , Fatores Etários , Alcoolismo/diagnóstico , Alcoolismo/psicologia , Maus-Tratos Infantis/diagnóstico , Maus-Tratos Infantis/tendências , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Saúde da Família/tendências , Feminino , Humanos , Comportamento Impulsivo/diagnóstico , Comportamento Impulsivo/psicologia , Masculino , Oklahoma/epidemiologia , Teste de Stroop , Adulto Jovem
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