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1.
J Intellect Disabil Res ; 64(7): 489-496, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32490559

RESUMO

BACKGROUND: It is unknown how the novel Coronavirus SARS-CoV-2, the cause of the current acute respiratory illness COVID-19 pandemic that has infected millions of people, affects people with intellectual and developmental disability (IDD). The aim of this study is to describe how individuals with IDD have been affected in the first 100 days of the COVID-19 pandemic. METHODS: Shortly after the first COVID-19 case was reported in the USA, our organisation, which provides continuous support for over 11 000 individuals with IDD, assembled an outbreak committee composed of senior leaders from across the health care organisation. The committee led the development and deployment of a comprehensive COVID-19 prevention and suppression strategy, utilising current evidence-based practice, while surveilling the global and local situation daily. We implemented enhanced infection control procedures across 2400 homes, which were communicated to our employees using multi-faceted channels including an electronic resource library, mobile and web applications, paper postings in locations, live webinars and direct mail. Using custom-built software applications enabling us to track patient, client and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission, which included the use of personal protective equipment. A COVID-19 case was defined as a positive nucleic acid test for SARS-CoV-2 RNA. RESULTS: In the 100-day period between 20 January 2020 and 30 April 2020, we provided continuous support for 11 540 individuals with IDD. Sixty-four per cent of the individuals were in residential, community settings, and 36% were in intermediate care facilities. The average age of the cohort was 46 ± 12 years, and 60% were male. One hundred twenty-two individuals with IDD were placed in quarantine for exhibiting symptoms and signs of acute infection such as fever or cough. Sixty-six individuals tested positive for SARS-CoV-2, and their average age was 50. The positive individuals were located in 30 different homes (1.3% of total) across 14 states. Fifteen homes have had single cases, and 15 have had more than one case. Fifteen COVID-19-positive individuals were hospitalised. As of 30 April, seven of the individuals hospitalised have been discharged back to home and are recovering. Five remain hospitalised, with three improving and two remaining in intensive care and on mechanical ventilation. There have been three deaths. We found that among COVID-19-positive individuals with IDD, a higher number of chronic medical conditions and male sex were characteristics associated with a greater likelihood of hospitalisation. CONCLUSIONS: In the first 100 days of the COVID-19 outbreak in the USA, we observed that people with IDD living in congregate care settings can benefit from a coordinated approach to infection control, case identification and cohorting, as evidenced by the low relative case rate reported. Male individuals with higher numbers of chronic medical conditions were more likely to be hospitalised, while most younger, less chronically ill individuals recovered spontaneously at home.


Assuntos
Betacoronavirus , Doença Crônica/epidemiologia , Infecções por Coronavirus/epidemiologia , Cuidados Críticos/estatística & dados numéricos , Deficiências do Desenvolvimento/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Controle de Infecções/estatística & dados numéricos , Deficiência Intelectual/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , COVID-19 , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Instituições Residenciais/estatística & dados numéricos , SARS-CoV-2 , Fatores Sexuais , Estados Unidos/epidemiologia
2.
Reumatismo ; 69(4): 189-190, 2017 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-29320846

RESUMO

The case is described of a patient with chronic plantar pain, diagnosed as fasciitis, which was not improved by conventional treatment. Magnetic resonance imaging revealed flexor hallucis longus tenosynovitis, which improved after local glucocorticoid injection.


Assuntos
Erros de Diagnóstico , Imageamento por Ressonância Magnética/métodos , Tenossinovite/diagnóstico , Fasciíte Plantar/diagnóstico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Tenossinovite/tratamento farmacológico
3.
Am J Obstet Gynecol ; 212(5): 624.e1-17, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25582098

RESUMO

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.


Assuntos
Síndrome HELLP/epidemiologia , Hipertensão/epidemiologia , Pré-Eclâmpsia/epidemiologia , Adulto , Anticonvulsivantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Estudos de Coortes , Feminino , Síndrome HELLP/tratamento farmacológico , Humanos , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Período Pós-Parto , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Nascimento Prematuro/epidemiologia , Recidiva , Índice de Gravidade de Doença , Adulto Jovem
4.
Adv Exp Med Biol ; 846: 139-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25472537

RESUMO

The output of prolactin (PRL) is highly dynamic with dramatic changes in its secretion from the anterior pituitary gland depending on prevailing physiological status. In adult female mice, there are three distinct phases of output and each of these is related to the functions of PRL at specific stages of reproduction. Recent studies of the changes in the regulation of PRL during its period of maximum output, lactation, have shown alterations at both the level of the anterior pituitary and hypothalamus. The PRL-secreting cells of the anterior pituitary are organised into a homotypic network in virgin animals, facilitating coordinated bouts of activity between interconnected PRL cells. During lactation, coordinated activity increases due to the changes in structural connectivity, and this drives large elevations in PRL secretion. Surprisingly, these changes in connectivity are maintained after weaning, despite reversion of PRL output to that of virgin animals, and result in an augmented output of hormone during a second lactation. At the level of the hypothalamus, tuberoinfundibular dopamine (TIDA) neurons, the major inhibitors of PRL secretion, have unexpectedly been shown to remain responsive to PRL during lactation. However, there is an uncoupling between TIDA neuron firing and dopamine secretion, with a potential switch to enkephalin release. Such a process may reinforce hormone secretion through dual disinhibition and stimulation of PRL cell activity. Thus, integration of signalling along the hypothalamo-pituitary axis is responsible for increased secretory output of PRL cells during lactation, as well as allowing the system to anticipate future demands.


Assuntos
Lactotrofos/metabolismo , Prolactina/metabolismo , Adulto , Animais , Feminino , Crescimento e Desenvolvimento/fisiologia , Humanos , Lactação/fisiologia , Camundongos , Plasticidade Neuronal/fisiologia , Gravidez , Reprodução/fisiologia , Transdução de Sinais/genética
6.
J Prev Med Hyg ; 53(4): 181-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23469584

RESUMO

INTRODUCTION: In recent years an increase in the number of sexually transmitted infections (STIs) in men who have sex with men (MSM) has been reported in different industrialised countries. Because few epidemiological data on the STls/MSM population in Sicily are available, a survey was conducted to assess the prevalence of STls/enteric protozoa and risky sexual behaviours among MSM in western Sicily. METHODS: In 2010, 74 MSM with median age of 30 years old, were recruited via networks. All participants to the study were interviewed by anonymous self-administered questionnaire in order to collect social/demographic information, clinic data and STI-related risky sexual behaviours. After completing the questionnaire, blood samples were collected to determine HIV, HCV, HHV8 and Treponema pallidum antibodies; presence of Giardia duodenalis and Cryptosporidium parvum was also investigated in faecal samples by immunofluorescence assay. RESULTS: HIV, HHV8, T. pallidum and Giardia prevalence were 8.1%, 16.2%, 21.6% and 16.4% respectively; all patients were negative for HCV and Cryptosporidium infections. The median values of sexual anal intercourse and oral sex per week were 2 and 1, respectively. 7% of participants always had unprotected anal sex, 50.7% sometimes used condom during sexual anal intercourse and 42.3% always had protected anal sex. All MSM-HIV+ and 7 (43.7%) syphilis seropositives were unaware of their own infection. DISCUSSION: MSM in western Sicily are a high risk group for important STIs. It seems necessary that continuous interventions for preventing HIV/AIDS and other STls and for improving the level of knowledge of symptoms are needed.


Assuntos
Homossexualidade Masculina/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Adolescente , Adulto , Fezes/microbiologia , Fezes/parasitologia , Imunofluorescência , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Hepacivirus/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/parasitologia , Sicília/epidemiologia , Sífilis/epidemiologia , Sífilis/microbiologia , Treponema pallidum/isolamento & purificação , Adulto Jovem
7.
Br J Cancer ; 104(3): 433-6, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21245864

RESUMO

BACKGROUND: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. METHODS: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. RESULTS: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), whereas this was not observed in cKS cases (-2.2 mm, P=0.32) or KSHV-positives (0.5 mm, P=0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P=0.004) and KSHV-positives (P=0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P=0.60), but it was reduced in KSHV-positives (11.8 mm, P=0.02), particularly in the leg (P=0.004) and marginally in the forearm (P=0.07). CONCLUSION: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy.


Assuntos
Herpesvirus Humano 8/imunologia , Hipersensibilidade Tardia/imunologia , Sarcoma de Kaposi/imunologia , Idoso , Feminino , Antebraço , Humanos , Perna (Membro) , Masculino
8.
J Prev Med Hyg ; 52(4): 191-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22442924

RESUMO

INTRODUCTION: The aim of this paper is to improve the feasibility perception of policymakers, health care workers and target population about the cost-effectiveness of the implementation of colorectal screening as Public Health strategy. METHODS: Retrospective study by application of a three-step model designed for a local setting in Sicily (Palermo and its Province) in order to distribute Fecal Occult Blood Tests (FOBTs), offer colonoscopy and surgery, by district allocation of pharmacies, public digestive endoscopic centres and oncologic and general surgery units. Mean adherence to consolidated colorectal screening programs in Italy was applied in order to evaluate the feasibility of an operative model in our area. RESULTS: Applying the model to the target population (269,368 individuals of both sexes), it can be expected a mean percentage of 79% delivered invitation and a mean participation rate of 46.3% accounting for a total of 213,070 invited individuals and 98,651 participating in the first round of the program. Furthermore, considering the national mean of 6% positive FOBT, 82% of colonscopy adhesion and 7% CRC detection rate, it can be scheduled a burden for health care structures involved in the program accounting for 49,325 FOBTs, 2,338 colonscopies and 141 surgeries for each year. DISCUSSION: This work demonstrates the feasibility of a colorectal screening project in our area, showing a sustainable impact for local health care involved structures. Furthermore, this program may be spread as an applicative model to other areas, adapting the project to the needs of the local setting in which the colorectal screening will be organized.


Assuntos
Neoplasias Colorretais/diagnóstico , Programas de Rastreamento , Modelos Econômicos , Carcinoma/diagnóstico , Carcinoma/economia , Carcinoma/prevenção & controle , Colonoscopia , Neoplasias Colorretais/economia , Neoplasias Colorretais/prevenção & controle , Análise Custo-Benefício , Estudos de Viabilidade , Feminino , Humanos , Itália , Masculino , Programas de Rastreamento/economia , Sangue Oculto , Estudos Retrospectivos
9.
Insights Imaging ; 10(1): 98, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31549248

RESUMO

In the last years, there has been a significant increase in the number of cesarean deliveries and, with it, of the number of complications following the procedure. They can be divided into early and late ones. We will illustrate herein the most common complications following cesarean section to help radiologists to recognize them. To familiarize with these various pathologic conditions is crucial to alert referring clinicians for a prompt and appropriate maternal and fetal management. Special attention will be given to the cesarean scar defect (CSD), the most common but also the most unknown of such conditions. Although often asymptomatic, a severe CSD represents a predisposing factor for subsequent complications especially in future pregnancies.

10.
Midwifery ; 24(2): 183-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17320253

RESUMO

OBJECTIVE: to explore the perceptions among post-delivery mothers of skin-to-skin contact and newborn baby care. DESIGN: a qualitative design using focus-group discussions. Five focus groups were conducted with post-delivery mothers who had had normal deliveries. A latent content analysis was used to derive the themes from the focus-group discussions. SETTINGS AND PARTICIPANTS: 30 post-delivery mothers were purposely sampled from 249 mothers in the postnatal ward at St Francis Hospital, Nsambya, which is located in a periurban area in Kampala, Uganda. FINDINGS: two main themes emerged from the focus-group discussions: 'acceptability of health practices are influenced by knowledge and sensitisation' and 'pregnant women's choices are dependent on social, cultural and economic factors'. Mothers expressed varying opinions about the usefulness of skin-to-skin contact: some knew about its use to reduce the risk of hypothermia; others were ignorant, whereas some believed skin-to-skin contact was an intervention used to distract them from the pain in the post-delivery period. The vernix caseosa and the mixture of amniotic fluid with blood in the post-delivery period were perceived as dirty and infectious. The best informants for helping mothers understand the skin-to-skin intervention were the health-care providers. Social, cultural and economic factors, as well as the dominant role of the husband, were identified as important determinants for their choice and place of delivery. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the gap between the knowledge and practice of skin-to-skin contact in hospital needs to be bridged. Health-care providers need to be encouraged to continuously advocate for, educate and implement regular skin-to-skin contact.


Assuntos
Atitude Frente a Saúde/etnologia , Cuidado do Lactente/métodos , Relações Mãe-Filho/etnologia , Mães/psicologia , Assistência Perinatal/métodos , Adulto , Características Culturais , Feminino , Grupos Focais , Hospitais Urbanos , Humanos , Cuidado do Lactente/psicologia , Recém-Nascido , Relações Enfermeiro-Paciente , Apego ao Objeto , Pesquisa Qualitativa , Cônjuges/etnologia , Tato , Uganda , População Urbana
11.
Mol Cell Biol ; 9(3): 1271-6, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2524647

RESUMO

The albino-3 (al-3) gene of Neurospora crassa, which probably encodes the carotenoid biosynthetic enzyme geranylgeranyl pyrophosphate synthetase, was cloned. The N. crassa triple mutant al-3 qa-2 aro-9 was transformed to qa-2+ with mixtures of plasmids bearing N. crassa DNA inserts, and the transformants were screened for the al-3+ phenotype. One al-3+ qa-2+ transformant (AL3-1) was examined in detail and shown to contain intact vector sequences integrated into the N. crassa genome. The vector and some flanking sequences were recovered from AL3-1 after restriction, ligation, and selection of chloramphenicol-resistant transformants of Escherichia coli. The flanking sequences were subsequently used to detect the al-3-containing plasmid in the mixture of about 1,800 plasmids. Restriction fragment length polymorphism mapping was carried out to confirm the identity of the cloned fragment. The level of the al-3 mRNA was shown to be increased 15-fold in light-induced (compared with that in dark-grown) wild-type mycelia. The light-dependent increase in al-3 mRNA levels was not observed in presumed regulatory mutant (white collar) strains.


Assuntos
Carotenoides/genética , Genes Fúngicos , Neurospora crassa/genética , Neurospora/genética , Carotenoides/biossíntese , Clonagem Molecular , Dimetilaliltranstransferase/genética , Regulação da Expressão Gênica/efeitos da radiação , Vetores Genéticos , Luz , Mutação , Neurospora crassa/metabolismo , Neurospora crassa/efeitos da radiação , Pigmentação/genética , Plasmídeos , RNA Fúngico/genética , RNA Fúngico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mapeamento por Restrição
12.
Trop Biomed ; 34(4): 963-969, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592966

RESUMO

The aim of the present study was to determine the gastro-intestinal (GI) parasitic infections among small ruminants (i.e., goats, sheep, deer) in Malaysia through formalin-ether concentration technique. Overall, 70.9% or 302 out of 426 small ruminants (79.4% or 251/316 goats; 87.5% or 35/40 sheep; 22.9% or 16/70 deer) were infected with at least one species of GI parasites. Overall, ten types of GI parasites [Helminth: strongyle (57.7%), Moniezia spp. (5.4%), Paramphistomum spp. (4.5%), Strongyloides spp. (4.2%), Dicrocoelium spp. (2.3%), Trichuris spp. (2.3%); Protozoa: Eimeria spp. (23.7%), Entamoeba spp. (18.8%), Giardia spp. (1.9%), Cryptosporidium spp. (0.2%)] were detected in this study. Among the studied animals, goats harboured the highest diversity of GI parasites (ten types), followed by sheep (six types) and deer (two types). Polyparasitism was observed in goats (43.7% or 138 of 316) and sheep (15.0% or 6 of 40). Cumulatively, a total of 32 combinations of coinfections (Helminth+Helminth: 8 combinations; Helminth+Protozoa: 20 combinations; Protozoa+Protozoa: 4 combinations) between detected parasites with up to quintuple infections were reported. Among these parasites, "strongyle + Eimeria spp." and "Moniezia spp. + strongyle" were the commonest infections in goats (13.5% or 34 of 251) and sheep (5.7% or 2 of 6), respectively. This study is a comprehensive documentation on multiple GI parasitisms among small ruminant in Malaysia, and the findings are crucial for effective farm management, especially for the formulation of parasitic control and elimination strategies.

13.
Eur J Histochem ; 50(1): 69-78, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16584987

RESUMO

Changes in chicken embryo thymus after partial decerebration (including the hypophysis) and hypophyseal allograft were investigated. Chicken embryos were partially decerebrated at 36-40 hr of incubation and on day 12 received a hypophyseal allograft from 18-day-old donor embryos. The embryonic thymuses were collected on day 18 and examined with histological methods, tested for the anti-thymostimulin-like immune-reaction, and for histoenzymatic activities and compared with normal and sham-operated embryos at the same age. After partial decerebration, the thymic cortical and medullary compartments diminished markedly in size. Anti-thymostimulin, succinic dehydrogenase and ATPase enzymatic activities tested, yielded negative reactions. In partially decerebrated hypophyseal allografted embryos, the same thymic compartments improved and anti-thymostimulin-like immune-reaction and enzymatic activities partially recovered. These findings confirmed the key role of hypophysis in thymic ontogenic development and provided new information in metabolic enzymatic pathways and synthesis of a thymostimulin-like substance in the thymus.


Assuntos
Extratos do Timo/metabolismo , Timo/metabolismo , Animais , Embrião de Galinha , Enzimas/metabolismo , Hipofisectomia , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Hipófise/transplante , Timo/patologia , Timo/fisiopatologia , Transplante Homólogo
14.
J Ovarian Res ; 9(1): 28, 2016 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-27184254

RESUMO

BACKGROUND: Chemotherapy resistance presents a difficult challenge in treating epithelial ovarian cancer patients, particularly when tumors exhibit resistance to multiple chemotherapeutic agents. A few studies have shown that elevated serum levels of the ovarian cancer biomarker HE4 correlate with tumor chemoresistance, response to treatment, and survival. Here, we sought to confirm our previous results that HE4 contributes to collateral resistance to cisplatin and paclitaxel in vitro and uncover factors that may contribute to HE4-mediated chemoresistance. METHODS: MTS assays and western blots for cleaved PARP were used to assess resistance of HE4-overexpressing SKOV3 and OVCAR8 clones to cisplatin and paclitaxel. CRISPR/Cas technology was used to knockdown HE4 in HE4-overexpressing SKOV3 cells. A microarray was conducted to determine differential gene expression between SKOV3 null vector-transfected and HE4-overexpressing clones upon cisplatin exposure, and results were validated by quantitative RT-PCR. Regulation of mitogen activated protein kinases (MAPKs) and tubulins were assessed by western blot. RESULTS: HE4-overexpressing SKOV3 and OVCAR8 clones displayed increased resistance to cisplatin and paclitaxel. Knockdown of HE4 in HE4-overexpressing SKOV3 cells partially reversed chemoresistance. Microarray analysis revealed that HE4 overexpression resulted in suppression of cisplatin-mediated upregulation of EGR1, a MAPK-regulated gene involved in promoting apoptosis. Upregulation of p38, a MAPK activated in response to cisplatin, was suppressed in HE4-overexpressing clones. No differences in extracellular signal-regulated kinase (ERK) activation were noted in HE4-overexpressing clones treated with 25 µM cisplatin, but ERK activation was partially suppressed in HE4-overexpressing clones treated with 80 µM cisplatin. Furthermore, treatment of cells with recombinant HE4 dramatically affected ERK activation in SKOV3 and OVCAR8 wild type cells. Recombinant HE4 also upregulated α-tubulin and ß-tubulin levels in SKOV3 and OVCAR8 cells, and microtubule associated protein tau (MAPT) gene expression was increased in SKOV3 HE4-overexpressing clones. CONCLUSIONS: Overexpression of HE4 promotes collateral resistance to cisplatin and paclitaxel, and downregulation of HE4 partially reverses this chemoresistance. Multiple factors could be involved in HE4-mediated chemoresistance, including deregulation of MAPK signaling, as well as alterations in tubulin levels or stability.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/genética , Paclitaxel/farmacologia , Proteínas/genética , Apoptose/efeitos dos fármacos , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases , Neoplasias Ovarianas/metabolismo , Tubulina (Proteína)/metabolismo , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Proteínas tau/genética , Proteínas tau/metabolismo
15.
J Neuroendocrinol ; 28(2): 12352, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26686489

RESUMO

Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, ß-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.


Assuntos
Caderinas/metabolismo , Galectina 3/biossíntese , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , Proteínas de Ligação a RNA/biossíntese , Securina/biossíntese , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Proteínas Sanguíneas , Caderinas/biossíntese , Criança , Pré-Escolar , Feminino , Galectinas , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Hipófise/metabolismo , Neoplasias Hipofisárias/metabolismo , Prolactinoma/metabolismo , Adulto Jovem
16.
AIDS ; 19(18): 2149-56, 2005 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-16284465

RESUMO

OBJECTIVE: To assess the safety of dextrin sulphate (DS) gel compared to placebo gel in terms of local and systemic adverse events, and to determine the acceptability of dextrin sulphate gel. DESIGN: A 4-week randomized trial of DS intra-vaginal gel, partially blinded, with placebo and observation control arms. Participants were randomized to use DS gel twice daily, placebo gel twice daily, DS gel pre-sex, or into an observation only arm. METHODS: Sexually active women were recruited from post natal and HIV clinics at Nsambya Hospital, Kampala, Uganda. Screening, enrollment and follow-up visits took place every 1 or 2 weeks over an 8-week period and consisted of questionnaire interviews, colposcopy examinations, sexually transmitted infection screen and routine laboratory testing. RESULTS: Out of a total of 172 women screened, 109 were randomized to use DS gel twice daily (65 women), placebo gel twice daily (15 women), DS gel pre-sex (nine women) or into an observation only arm (20 women). Two individuals had abnormal colposcopy findings in the DS twice daily gel use arm. Vaginal bleeding was reported as frequently by participants in the active gel arm as by participants in the placebo and observation only arms. No clinically significant difference was observed between arms in terms of vaginal flora, Candida, haemoglobin, white cell count, platelets, thrombin time, activated partial thromboplastin time, creatinine and aspartate aminotransferase results after 4 weeks of gel use. DS gel appeared to be acceptable to over 95% of the users. CONCLUSIONS: Results show a satisfactory safety and acceptability profile of dextrin sulphate gel.


Assuntos
Anti-Infecciosos/efeitos adversos , Dextrinas/efeitos adversos , Infecções Sexualmente Transmissíveis/prevenção & controle , Cremes, Espumas e Géis Vaginais/efeitos adversos , Administração Intravaginal , Adulto , Anti-Infecciosos/administração & dosagem , Dextrinas/administração & dosagem , Feminino , Humanos , Satisfação do Paciente , Segurança , Comportamento Sexual , Uganda , Cremes, Espumas e Géis Vaginais/administração & dosagem
17.
J Neuroendocrinol ; 17(11): 753-60, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16219004

RESUMO

Transforming growth factor beta (TGFbeta) is one of the growth factors involved in the neuroendocrine control of the gonadotrophin-releasing hormone (GnRH) neurones. It is produced and released by the astrocytes surrounding GnRH neurones and directly controls their secretory activity. TGFbeta signalling is based on a complex of two receptors that transduces the signal through peculiar intracellular substrates, the Smad proteins, which, upon activation, move into the nucleus, and modify the transcription of TGFbeta responsive genes. The present study aimed to verify whether TGFbeta1 is able to regulate the Smad pathway in GT1-1 cells (i.e. an immortalised neuronal cell line releasing GnRH). We show that: (i) GT1-1 cells express Smad 2, 3, 4, and 7; (ii) TGFbeta1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15-30 min); (iii) TGFbeta1 induces the synthesis of the inhibitory Smad 7 at longer times (60-120-240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1-1 cells and a TGFbeta1 neutralising antibody counteracts this effect. The results indicate that Smads are targets of TGFbeta1 and that astrocytes are able to modulate Smads proteins in GT1-1 cells through the release of TGFbeta1. Taken together, the data provide new evidence that glial cells are important regulators of the GnRH neuronal activity.


Assuntos
Hormônio Liberador de Gonadotropina/fisiologia , Neurônios/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Animais , Western Blotting , Linhagem Celular , Meios de Cultivo Condicionados , Relação Dose-Resposta a Droga , Neuroglia/fisiologia , Neurônios/efeitos dos fármacos , Fosforilação , RNA/biossíntese , RNA/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1
18.
Ann Ig ; 17(3): 185-96, 2005.
Artigo em Italiano | MEDLINE | ID: mdl-16041921

RESUMO

The knowledge and preventive practices toward the risk of infection with HIV, HBV and HCV were evaluated in a sample of 254 dentists and odontostomatologies in Palermo, by answering to an anonymous questionnaire sent by mail. Overall, most of the participants showed a good knowledge of the transmission pattern of blood-borne viruses as well as good practice for personal hygiene (washing of hands, routine use of gloves, etc.). However 80.8% answered to recap needles after use and more than 40% have had at least one needle injury during the last year in their occupational setting. Moreover, nearly 24% of the interviewed declared to have not made vaccination against Hepatitis B virus infection. Statistical analysis showed a significant correlation between better knowledge, safer practice and different teaching training suggesting that odontostomatology degree might be more appropriate for a better training in preventive medicine for blood borne pathogens. Data also suggest the need of continuous worker education to reduce occupational blood exposures in dentistry.


Assuntos
Odontologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/prevenção & controle , Hepatite C/prevenção & controle , Doenças Profissionais/prevenção & controle , Padrões de Prática Odontológica , Adulto , Idoso , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Hepatite B/epidemiologia , Hepatite B/transmissão , Hepatite C/epidemiologia , Hepatite C/transmissão , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Exposição Ocupacional , Risco , Inquéritos e Questionários
20.
Glob Health Action ; 8: 24271, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25843496

RESUMO

BACKGROUND: In Uganda maternal and neonatal mortality remains high due to a number of factors, including poor quality of care at health facilities. OBJECTIVE: This paper describes the experience of building capacity for maternal and newborn care at a district hospital and lower-level health facilities in eastern Uganda within the existing system parameters and a robust community outreach programme. DESIGN: This health system strengthening study, part of the Uganda Newborn Study (UNEST), aimed to increase frontline health worker capacity through district-led training, support supervision, and mentoring at one district hospital and 19 lower-level facilities. A once-off supply of essential medicines and equipment was provided to address immediate critical gaps. Health workers were empowered to requisition subsequent supplies through use of district resources. Minimal infrastructure adjustments were provided. Quantitative data collection was done within routine process monitoring and qualitative data were collected during support supervision visits. We use the World Health Organization Health System Building Blocks to describe the process of district-led health facility strengthening. RESULTS: Seventy two per cent of eligible health workers were trained. The mean post-training knowledge score was 68% compared to 32% in the pre-training test, and 80% 1 year later. Health worker skills and competencies in care of high-risk babies improved following support supervision and mentoring. Health facility deliveries increased from 3,151 to 4,115 (a 30% increase) in 2 years. Of 547 preterm babies admitted to the newly introduced kangaroo mother care (KMC) unit, 85% were discharged alive to continue KMC at home. There was a non-significant declining trend for in-hospital neonatal deaths across the 2-year study period. While equipment levels remained high after initial improvement efforts, maintaining supply of even the most basic medications was a challenge, with less than 40% of health facilities reporting no stock-outs. CONCLUSION: Health system strengthening for care at birth and the newborn period is possible even in low-resource settings and can be associated with improved utilisation and outcomes. Through a participatory process with wide engagement, training, and improvements to support supervision and logistics, health workers were able to change behaviours and practices for maternal and newborn care. Local solutions are needed to ensure sustainability of medical commodities.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Atenção à Saúde/organização & administração , Pessoal de Saúde/educação , Maternidades/organização & administração , Cuidado do Lactente/organização & administração , Mortalidade Infantil , Serviços de Saúde Materno-Infantil/organização & administração , Adulto , Competência Clínica , Feminino , Humanos , Lactente , Recém-Nascido , População Rural , Uganda/epidemiologia
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