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1.
Int J Obes (Lond) ; 46(3): 661-668, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34974543

RESUMO

BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.


Assuntos
COVID-19 , Obesidade , Adulto , Idoso , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Comorbidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
2.
Phys Rev Lett ; 128(25): 252002, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35802440

RESUMO

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

3.
Environ Sci Technol ; 56(2): 1053-1068, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34942073

RESUMO

People spend increasing amounts of time at home, yet the indoor home environment remains understudied in terms of potential exposure to toxic trace metals. We evaluated trace metal (and metalloid) concentrations (As, Cu, Cr, Mn, Ni, Pb, and Zn) and health risks in indoor dust from homes from 35 countries, along with a suite of potentially contributory residential characteristics. The objective was to determine trace metal source inputs and home environment conditions associated with increasing exposure risk across a range of international communities. For all countries, enrichments compared to global crustal values were Zn > Pb > Cu > As > Cr > Ni; with the greatest health risk from Cr, followed by As > Pb > Mn > Cu > Ni > Zn. Three main indoor dust sources were identified, with a Pb-Zn-As factor related to legacy Pb sources, a Zn-Cu factor reflecting building materials, and a Mn factor indicative of natural soil sources. Increasing home age was associated with greater Pb and As concentrations (5.0 and 0.48 mg/kg per year of home age, respectively), as were peeling paint and garden access. Therefore, these factors form important considerations for the development of evidence-based management strategies to reduce potential risks posed by indoor house dust. Recent findings indicate neurocognitive effects from low concentrations of metal exposures; hence, an understanding of the home exposome is vital.


Assuntos
Metaloides , Metais Pesados , Oligoelementos , China , Poeira/análise , Monitoramento Ambiental , Humanos , Metaloides/análise , Medição de Risco , Oligoelementos/análise
4.
Phys Rev Lett ; 127(15): 152301, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34678020

RESUMO

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4 GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

5.
J Mol Model ; 29(8): 232, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37407749

RESUMO

CONTEXT: Some structural properties can be involved in the antioxidant capacity of several polyphenol derivatives, among them their simplified structures. This study examines the contribution of simplified structure for the antioxidant capacity of some natural and synthetic antioxidants. The resonance structures were related to the π-type electron system of carbon-carbon double bonds between both phenyl rings. Trans-resveratrol, phenyl-benzofuran, phenyl-indenone, and benzylidene-benzofuranone are the best basic antioxidant templates among the simplified derivatives studied here. Additionally, the stilbene moiety was found on the molecules with the best antioxidant capacity. Furthermore, our investigation suggests that these compounds can be used as antioxidant scaffold for designing and developing of new promising derivatives. METHODS: To investigate the structure-antioxidant capacity for sixteen simplified natural and proposed derivatives we have employed density functional theory and used Gaussian 09. Our DFT calculations were performed using the B3LYP functional and the 6-31+G(d,p) basis set. All electron transfer mechanisms were investigated by using values of HOMO, ionization potential, energy affinity, stabilization energies, and spin density distributions.

6.
Eur Respir J ; 37(5): 1144-50, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20817710

RESUMO

The aim of the present study was to estimate slow-wave activity (SWA), a marker of sleep homeostasis, in children with obstructive sleep apnoea (OSA) before and after adenotonsillectomy (AT) compared with untreated OSA children (comparison group). 14 children with OSA (mean ± sd age 6.4 ± 2.5 yrs; apnoea-hypopnoea index (AHI) 10.0 ± 10.3 events·h⁻¹) who underwent AT were consecutively recruited to the study. The comparison group comprised six retrospectively recruited children (age 5.4 ± 2.2 yrs; AHI 9.4 ± 7.6 events·h⁻¹) with OSA that did not undergo treatment. Electroencephalogram (derivation C3/A2) was analysed using spectral and waveform analysis to determine SWA energy and slow-wave slope. The same procedure was repeated 5.4 and 19 months later for the AT and comparison groups, respectively. AT improved respiration without a change in duration of sleep stages. Following AT, >50% elevation of SWA during the first two sleep cycles (p<0.01) and a more physiological decay of SWA across the night (p<0.0001) were noted. The slow-wave slope increased by >30% following AT (p<0.03). No significant changes were found in SWA in the comparison group. Sleep homeostasis is considerably impaired in pre-pubescent children with OSA. AT restores more physiological sleep homeostasis in children with OSA. SWA analysis may provide a useful addition to standard sleep-stage analyses in children with OSA.


Assuntos
Adenoidectomia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Sono , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Homeostase/fisiologia , Humanos , Masculino , Respiração , Estudos Retrospectivos , Resultado do Tratamento
7.
J Vet Pharmacol Ther ; 34(4): 322-31, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20950346

RESUMO

Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.


Assuntos
Doenças do Cão/tratamento farmacológico , Insuficiência Cardíaca/veterinária , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Cardiotônicos/uso terapêutico , Diuréticos/uso terapêutico , Doenças do Cão/mortalidade , Cães , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação/veterinária , Quimioterapia Combinada/veterinária , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Masculino , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Espironolactona/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento
8.
Isr Med Assoc J ; 13(9): 542-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21991714

RESUMO

BACKGROUND: Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation. OBJECTIVES: To review the management and outcome of benign liver masses in children. METHODS: We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997-2009. RESULTS: Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (17%). Diagnosis was made based on characteristic radiographic findings in 31 (58%), but histopathological examination was required for the remaining 22 (42%). Of the 53 children, 27 (51%) were under observation while 17 (32%) had masses resected. Medications targeting masses were used in 9 (17%) and liver transplantation was performed in 4 (8%). The only death (2%) occurred in a child with multifocal IHH unresponsive to medical management and prior to liver transplant availability. CONCLUSIONS: IHH and focal nodular hyperplasia were the most common lesions. The majority of benign lesions were found incidentally and diagnosed radiologically. Expectant management was sufficient in most children after diagnosis, although surgical intervention including liver transplant was occasionally necessary.


Assuntos
Neoplasias Hepáticas/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hiperplasia Nodular Focal do Fígado/diagnóstico , Hiperplasia Nodular Focal do Fígado/tratamento farmacológico , Hiperplasia Nodular Focal do Fígado/cirurgia , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/cirurgia , Hemangioma/diagnóstico , Hemangioma/tratamento farmacológico , Hemangioma/cirurgia , Humanos , Achados Incidentais , Lactente , Recém-Nascido , Fígado/patologia , Fígado/cirurgia , Hepatopatias/diagnóstico , Hepatopatias/tratamento farmacológico , Hepatopatias/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Sci Total Environ ; 733: 137931, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438193

RESUMO

Trace metal contaminants in indoor dust pose a significant potential exposure risk to people because of the time spent indoors and the readily ingested and inhaled fine-grained composition of indoor dusts. However, there is limited trace metal data available on the specific interaction of dust particle size fraction and their respective bioaccessibility/bioavailability and its consequent effect on health risk assessment. This study addresses this knowledge gap by examining bioaccessible and bioavailable trace element concentrations (As, Cr, Cu, Mn, Ni, Pb, Zn) in 152 discrete size fractions from 38 indoor vacuum samples from a larger dataset (n = 376) of indoor dust from Sydney, Australia. Arsenic, Cu, Ni, Pb and Zn were most concentrated in the 90-150 µm fraction with Cr and Mn being more concentrated in < 45 µm fraction. Dust particle size fractions < 45 µm, 45-90 µm, 90-150 µm and 150-250 µm were analysed for their individual gastric phase (G-alone) in vitro trace element bioaccessibilities. Lead exposure risk was estimated using the United States Environmental Protection Agency's Integrated Exposure Uptake Biokinetic (IEUBK) children's model. Mean Pb bioaccessibility was 59.6%, 42%, 62% and 62.2% for < 45 µm, 45-90 µm, 90-150 µm, and 150-250 µm, respectively. Mean Pb absolute bioavailability (ABA) was lower at 26.2%, 18.4%, 27.2% and 27.3% for size fractions < 45 µm, 45-90 µm, 90-150 µm, and 150-250 µm, respectively. The predicted blood Pb (PbB) levels for a hypothetical child aged 1 to 3 years for each of the dust particle size fractions was > 5 µg/dL. Lead concentrations measured in the selected dust samples show a potential for adverse health impacts on young children with the greatest risk being from indoor dust sized 90-150 µm.


Assuntos
Metais Pesados/análise , Oligoelementos , Austrália , Criança , Pré-Escolar , Poeira/análise , Exposição Ambiental/análise , Monitoramento Ambiental , Humanos , Lactente , Tamanho da Partícula , Medição de Risco
10.
Environ Int ; 133(Pt A): 105125, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31634663

RESUMO

This study examines residential indoor dust from 224 homes in Sydney, Australia for trace element concentrations measured using portable X-ray Fluorescence (pXRF) and their potential risk of harm. Samples were collected as part of a citizen science program involving public participation via collection and submission of vacuum dust samples for analysis of their As, Cr, Cu, Mn, Ni, Pb and Zn concentrations. The upper 95% confidence level of the mean values for 224 samples (sieved to <250 µm) were 20.2 mg/kg As, 99.8 mg/kg Cr, 298 mg/kg Cu, 247 mg/kg Mn, 56.7 mg/kg Ni, 364 mg/kg Pb and 2437 mg/kg Zn. The spatial patterns and variations of the metals indicate high homogeneity across Sydney, but with noticeably higher Pb values in the older areas of the city. Potential hazard levels were assessed using United States Environmental Protection Agency's (US EPA) carcinogenic, non-carcinogenic and Integrated Exposure Uptake Biokinetic (IEUBK) model human health risk assessment tools for children and adults. US EPA hazard indexes (HI) for Cr and Pb were higher than the safe level of 1.0 for children. HI > 1 suggests potential non-carcinogenic health effects. Carcinogenic risks were estimated for As, Cr and Pb whose carcinogenic slope factors (CSF) were available. Only the risk factor for Cr exceeded the US EPA's carcinogenic threshold (1 × 10-4) for children. Children aged 1-2 years had the highest predicted mean child blood lead (PbB) of 4.6 µg/dL, with 19.2% potentially having PbB exceeding 5 µg/dL and 5.80% exceeding 10 µg/dL. The Cr and Pb levels measured in indoor dust therefore pose potentially significant adverse health risks to children.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Poeira , Oligoelementos/efeitos adversos , Adulto , Austrália , Carcinógenos/análise , Criança , Pré-Escolar , Poeira/análise , Exposição Ambiental/análise , Monitoramento Ambiental , Humanos , Lactente , Medição de Risco , Oligoelementos/análise
11.
Cancer Res ; 38(11 Pt 2): 4314-7, 1978 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-698973

RESUMO

The hormone dependence of human breast tumors has been investigated in two ways: (a) estradiol and progesterone receptor determination in tumor tissue; and (b) measurement of the growth-stimulating effect of hormones on cells in short-term culture. Preliminary results from 15 tumors suggest that such a model may be used for human breast tumors. The behavior of the cultures under hormonal stimulation depended on their receptor content. In this series of patients, the tumors containing both estradiol and progesterone receptors were stimulated by addition of insulin and estradiol while the tumors containing either estradiol receptor alone or no steroid receptor were not modified by hormonal addition.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Hormônios/farmacologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Receptores de Estrogênio , Receptores de Progesterona , Neoplasias da Mama/metabolismo , DNA de Neoplasias/biossíntese , Estradiol/farmacologia , Feminino , Humanos , Hidrocortisona/farmacologia , Técnicas In Vitro , Insulina/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Hormônio-Dependentes/metabolismo , Lactogênio Placentário/farmacologia
12.
Oncogene ; 4(11): 1359-62, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2682462

RESUMO

Transient transfection of ras expression vectors into human fibroblasts and astrocytes has been used to test the hypothesis that p21 ras, a known membrane signal transductor, may participate in pathways linking cellular activation and human immunodeficiency virus (HIV) reactivation. Expression vectors carrying the chloramphenicol acetyl transferase coding sequence under the control of various fragments of the long terminal repeat (LTR) of HIV were co-transfected with expression vectors of the mutated (val 12) c-Ha-ras gene or of its normal counterpart. Both forms of the ras gene induced transactivation of the HIV-LTR via the two direct repeat sequences which constitute the HIV enhancer. This repeat sequence was shown to be sufficient for ras-induced LTR transactivation. Other LTR sequences tested were not found to be responsive to co-transfected ras expression vectors. Deletion of the TAR sequence impaired the response to tat, but not to ras co-transfection. The mutated ras gene was more efficient than the proto-oncogene in activating the HIV enhancer. Transfection of ras was shown to enhance transcription of a complete provirus DNA clone of HIV-1. Such findings may shed new light on the mechanisms through which cell membrane activation signals result in HIV reactivation.


Assuntos
Astrócitos/metabolismo , Elementos Facilitadores Genéticos , Genes ras , HIV/genética , Transcrição Gênica , Transfecção , Astrocitoma , Sequência de Bases , Linhagem Celular , Células Cultivadas , Fibroblastos , Vetores Genéticos , Humanos , Dados de Sequência Molecular , Mutação , Sondas de Oligonucleotídeos/síntese química , Proto-Oncogene Mas , Transdução de Sinais , Ativação Transcricional
13.
J Small Anim Pract ; 46(3): 121-30, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15789807

RESUMO

OBJECTIVES: To evaluate the clinical efficacy and safety of pimobendan by comparing it with ramipril over a six-month period in dogs with mild to moderate heart failure (HF) caused by myxomatous mitral valve disease (MMVD). METHODS: This was a prospective randomised, single-blind, parallel-group trial. Client-owned dogs (n = 43) with mild to moderate HF caused by MMVD were randomly assigned to one of two groups, which received either pimobendan (P dogs) or ramipril (R dogs) for six months. The outcome measures studied were: adverse HF outcome, defined as failure to complete the trial as a direct consequence of HF; maximum furosemide dose (mg/kg/day) administered during the study period; and any requirement for additional visits to the clinic as a direct consequence of HF. RESULTS: Treatment with pimobendan was well tolerated compared with treatment with ramipril. P dogs were 25 per cent as likely as R dogs to have an adverse HF outcome (odds ratio 4.09, 95 per cent confidence interval 1.03 to 16.3, P = 0.046). CLINICAL SIGNIFICANCE: R dogs had a higher overall score and thus may have had more advanced disease than P dogs at baseline (P = 0.04). These results should be interpreted cautiously but such a high odds ratio warrants further investigation.


Assuntos
Cardiotônicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Insuficiência Cardíaca/veterinária , Insuficiência da Valva Mitral/veterinária , Piridazinas/uso terapêutico , Animais , Cardiotônicos/efeitos adversos , Cães , Eletrocardiografia/veterinária , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Valva Mitral/patologia , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/tratamento farmacológico , Razão de Chances , Estudos Prospectivos , Piridazinas/efeitos adversos , Ramipril/uso terapêutico , Segurança , Método Simples-Cego , Resultado do Tratamento
14.
Mol Immunol ; 33(11-12): 999-1006, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8960124

RESUMO

Recently, we characterized a polymorphism within IL-1 alpha intron 6 as a variable number of a 46 bp tandem repeat (ranging from 5 to 18 repeats). We now analyse whether this polymorphism could play a role in IL-1 alpha gene regulation. We have found that reporter gene expression driven by the IL-1 alpha promoter or a heterologous promoter was decreased by increasing numbers of the repeat sequence corresponding to the most frequent alleles seen in the human population. Furthermore, we showed that the transcription factor Sp1 can bind to the 46 bp sequence. Finally, we were unable to show a statistically-significant relation between in vitro IL-1 alpha production and the number of repeats although there was a clear trend towards an inverse relation. Taken together, these results are consistent with a negative regulatory role for IL-1 alpha intron 6 repeat sequence on IL-1 alpha basal gene transcription.


Assuntos
Regulação da Expressão Gênica/imunologia , Interleucina-1/biossíntese , Interleucina-1/genética , Íntrons/imunologia , Polimorfismo Genético/imunologia , Sequências Repetitivas de Ácido Nucleico/imunologia , Adulto , Células Cultivadas , Humanos , Leucócitos Mononucleares , Transcrição Gênica/imunologia
15.
J Small Anim Pract ; 56(9): 537-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26331869

RESUMO

OBJECTIVES: There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS: Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS: Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION: The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.


Assuntos
Síndrome Cardiorrenal/veterinária , Doenças do Gato/diagnóstico , Doenças do Gato/terapia , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Animais , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/epidemiologia , Síndrome Cardiorrenal/terapia , Doenças do Gato/epidemiologia , Gatos , Consenso , Técnica Delphi , Doenças do Cão/epidemiologia , Cães , Guias de Prática Clínica como Assunto , Medicina Veterinária
16.
Gene ; 51(2-3): 197-204, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3036651

RESUMO

We have constructed a prototype of a general expression vector for mammalian cells, which carriers a strong promoter active in a variety of tissues and animal species for expression of the gene of interest and a truncated gene for amplification in selective medium. Expression of the S gene of HBV encoding the surface antigen was used to evaluate various versions of this vector. The human metallothionein IIA promoter was found to be particularly efficient for expression of this gene, both in mouse L and monkey Vero cells. Including a promoterless tk gene in the vector led to gene amplification in Ltk- cells by selection of TK+ variants in selective medium containing hypoxanthine, aminopterine and thymidine (HAT medium). Concomitant increases of the S gene expression levels were initially 50-100 fold. Although many clones were unstable, even in selective medium, some maintained the high expression levels for over one year.


Assuntos
Amplificação de Genes , Vetores Genéticos , Regiões Promotoras Genéticas , Animais , Linhagem Celular , Regulação da Expressão Gênica , Vírus da Hepatite B/genética , Metalotioneína/genética , Camundongos , Vírus 40 dos Símios/genética , Timidina Quinase/genética , Transformação Genética
17.
Gene ; 81(2): 369-72, 1989 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-2806920

RESUMO

We have constructed two new multi-purpose cloning vectors, pNI1 and pNI2, that carry the Escherichia coli gene Ecogpt encoding the enzyme xanthine-guanine phosphoribosyl transferase as a dominant selective marker. The Ecogpt gene is under the control of either the long-terminal-repeat promoter of mouse mammary tumor virus, pNI1, or the simian virus 40 early promoter, pNI2. Another feature of the vectors is a polylinker preceded by the human metallothionein IIA promoter. We have used pNI2 for the synthesis of the hepatitis B surface antigen (HBsAg) at a high level in monkey Vero cells. We show that gene amplification and a concomitant stable increase of HBsAg synthesis can be achieved in these cells using modified selective medium containing hypoxanthine, aminopterin and thymidine, i.e., increasing the aminopterin and decreasing the hypoxanthine concentrations.


Assuntos
Vetores Genéticos/genética , Proteínas Recombinantes/biossíntese , Células Vero/metabolismo , Animais , Amplificação de Genes , Antígenos de Superfície da Hepatite B/biossíntese , Plasmídeos/genética
18.
FEBS Lett ; 462(3): 295-301, 1999 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-10622714

RESUMO

Hypericin (HY) is a powerful photo-inducer of apoptosis in Jurkat cells as measured by caspase-3 activation, cell shrinkage, phosphatidylserine (PS) exposure and the appearance of hypoploid DNA. These processes are preceded by rapid Bcl-2-independent mitochondrial transmembrane depolarization and a drop in cytoplasmic pH. Pre-incubation of cells with inhibitors of the mitochondrial permeability transition pore, such as cyclosporin A or bongkrekic acid, does not protect cells from mitochondrial membrane potential (deltapsim) decrease. However, monitoring of mitochondrial entrapped calcein by confocal fluorescence imaging gives clear evidence of HY photo-induced mitochondrial permeability. This should be considered as the result of a non-specific alteration of mitochondrial membrane integrity brought about by lipid peroxidation. Nevertheless, synthesis of the anti-apoptotic protein Bcl-2 appears to delay the subsequent time course of PS exposure and to reduce caspase-3 activation and the fraction of cells which become hypoploid. We interpret this partially protective effect as the consequence of a direct interaction of Bcl-2 with cytosolic cytochrome c previously released from mitochondria upon deltapsim decrease and/or of Bcl-2 inhibition of the deleterious retro-effect of caspase-3 on the mitochondrial permeability transition pore and/or the mitochondrial membrane components.


Assuntos
Apoptose/efeitos da radiação , Mitocôndrias/metabolismo , Perileno/análogos & derivados , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Células 3T3 , Animais , Antracenos , Ácido Bongcréquico/farmacologia , Caspase 3 , Caspases/metabolismo , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos da radiação , Ciclosporina/farmacologia , Relação Dose-Resposta à Radiação , Ativação Enzimática/efeitos da radiação , Fibroblastos/citologia , Fibroblastos/enzimologia , Citometria de Fluxo , Fluoresceínas/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos da radiação , Membranas Intracelulares/metabolismo , Membranas Intracelulares/efeitos da radiação , Potenciais da Membrana/efeitos da radiação , Camundongos , Microscopia Confocal , Mitocôndrias/efeitos da radiação , Perileno/metabolismo , Fosfatidilserinas/metabolismo , Transtornos de Fotossensibilidade , Fatores de Tempo
19.
AIDS Res Hum Retroviruses ; 10(4): 405-11, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7915123

RESUMO

Antioxidant molecules have been suggested to be of therapeutic value in the treatment of HIV-infected patients. To evaluate this possibility, we examined in vitro the effects of two types of antioxidant molecules in terms of inhibition of HIV replication in monocytes, one of the main reservoirs of HIV, and also in terms of modulation of the immune competence as measured by PBMC proliferation. We tested the effects of BHA, a phenolic, lipid-soluble, chain-breaking antioxidant, and NAC, a known glutathione precursor with some direct free-radical scavenging properties as well, on the regulation of HIV-1 expression in latently infected U1 cells and in productively and chronically infected U937 cells. Both antioxidants inhibited TNF- or PMA-induced NF-kappa B activity in U1 cells, as well as the sustained NF-kappa B activity permanently induced by the virus itself in chronically HIV-infected U937 cells. This resulted in only a partial inhibition of TNF- or PMA-induced HIV replication in U1 cells, and no detectable effect on HIV replication in chronically infected U937 cells. This may be the first limitation to potential antiviral effects of antioxidant therapies. Another limitation is that antioxidant concentrations high enough to block NK-kappa B activation were shown to have a suppressive effect on immune functions in vitro, because NAC and BHA blocked IL-2-induced PBMC proliferation. These data warrant prudence in the design of antioxidant-based therapies aimed at suppressing HIV replication.


Assuntos
Antioxidantes/farmacologia , HIV-1/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Acetilcisteína/farmacologia , Antioxidantes/administração & dosagem , Sequência de Bases , Hidroxianisol Butilado/farmacologia , Linfócitos T CD4-Positivos/microbiologia , Linhagem Celular , DNA Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , HIV-1/fisiologia , Humanos , Interleucina-2/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Dados de Sequência Molecular , Monócitos/microbiologia , NF-kappa B/metabolismo
20.
J Clin Virol ; 20(3): 99-109, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11166656

RESUMO

BACKGROUND: in response to a variety of stimuli, phagocytes release large quantities of reactive oxygen species (ROS), which are essential for bacterial killing. However, excessive ROS production not appropriately compensated by antioxidant molecules can lead to oxidative stress, which may also play an important role in pathogenesis of HIV infection. In fact, ROS participate in chronic inflammation, HIV replication and the apoptosis of cells of the immune system. OBJECTIVE AND STUDY DESIGN: we used flow cytometry to study, in whole blood, the activation and redox status of polymorphonuclear neutrophils (PMN) and monocytes at different stages of the disease. RESULTS: we showed that neutrophils and monocytes from HIV-infected patients spontaneously produced increased amounts of H2O2. This increased H2O2 production was associated with alterations of adhesion molecules expression at the cell surface, which also reflected basal activation of phagocytes from the HIV-infected patients. In monocytes, basal H2O2 production correlated with viral load. This increased ROS production was associated with changes in the expression of the antiapoptotic/antioxidant compounds Bcl-2 and thioredoxin along the course of the disease. This modulation could result from a dual regulation by oxidative stress and could explain at least in part why monocyte numbers remain relatively stable throughout the disease. Monocytes expressed a normal maximal capacity to produce ROS in optimal conditions of stimulation. In contrast, after ex vivo priming with TNFalpha or IL-8, neutrophils showed a decreased H2O2 production in response to bacterial N-formyl peptides. This latter impairment correlated with the decrease in CD4+ lymphocyte numbers and with IL-8 and IL-6 plasma levels. CONCLUSIONS: the increased basal ROS production by phagocytes could participate to the oxidative injury which has been implicated in the pathophysiology of HIV infection. In addition, the decreased priming of H2O2 production by neutrophils could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.


Assuntos
Soropositividade para HIV/imunologia , HIV-1 , Monócitos/metabolismo , Neutrófilos/metabolismo , Estresse Oxidativo , Actinas/sangue , Adulto , Citocinas/sangue , Citometria de Fluxo , Soropositividade para HIV/sangue , Humanos , Peróxido de Hidrogênio/sangue , Selectina L/sangue , Receptores de Lipopolissacarídeos/sangue , Antígeno de Macrófago 1/sangue , Ativação de Neutrófilo , Oxirredução , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/sangue
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