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1.
J Am Coll Health ; : 1-9, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37437203

RESUMO

Objective: To use social network analysis to examine exercise participation relative to health and wellness support provision within students' networks. Participants: 513 undergraduates from a large private university completed online surveys. Methods: Multilevel modeling assessed exercise engagement at the individual and dyadic level and support provision from network members. Results: More support was perceived by first and second-year students and individuals who reported more exercise engagement. Significant others, roommates, siblings, female network members, and those who exercised often provided greater support. Greater support was reported when both the participant and their social tie were involved in the campus group-exercise program. Conclusion: This study suggests individual and dyadic-level exercise was related to undergraduates feeling more supported. Findings support campus group exercise programs as opportunities to create reciprocal supportive ties for college students. Future research could further explore ways exercise and social support, particularly in group settings, affect health and well-being.

2.
Res Sq ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33619476

RESUMO

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg - 1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

3.
J Am Coll Health ; 69(4): 361-369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31662049

RESUMO

OBJECTIVE: This study aimed to evaluate the relationship between group exercise membership, social network characteristics, and general state anxiety in a sample of college students. Participants: 490 undergraduates from a private university in the southern US participated in the study. Methods: An egocentric network analysis was conducted to test whether demographic variables, leisure-time physical activity, group exercise membership, flourishing scores, and network variables were related to anxiety. Results: Regression analyses (R2 = .174, F = 7.650, p < .0001) suggest group exercise membership (ß = -.105, p = .034) and flourishing scores (ß = -.342, p < .0001) were related to lower anxiety scores, while being a racial/ethnic minority (ß = .094, p = .036), and having personal networks composed of more people who exercise often (ß = .100, p = .025), were related to higher anxiety scores in this sample. Conclusions: Findings suggest a connection between group exercise membership, activity habits of peers, and anxiety. Encouraging group exercise participation could be an effective way of combating anxiety for college students.


Assuntos
Etnicidade , Estudantes , Ansiedade , Humanos , Grupos Minoritários , Rede Social , Universidades
4.
BJOG ; 128(7): 1145-1150, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33184969

RESUMO

OBJECTIVE: To estimate the association between threatened preterm labour (TPTL) and perinatal outcomes of infants born at term. DESIGN: A population-based cohort study of perinatal outcomes following TPTL <37 weeks of gestation with delivery at term. SETTING: Nova Scotia, Canada. POPULATION: All non-anomalous, singleton pregnancies ≥37 weeks of gestation without antepartum haemorrhage from 1988 to 2019. METHODS: Using data from the Nova Scotia Atlee Perinatal Database, TPTL was defined as pregnancies with a hospital admission between 20 and 37 weeks of gestation, with a diagnosis code denoting TPTL with administration of antenatal corticosteroids, or with administration of any tocolysis. Poisson regression models were used to estimate the risk ratios (RR) with 95% CI of maternal and perinatal outcomes in women who had an episode of TPTL relative to those who did not. MAIN OUTCOME MEASURES: Birthweight for gestational age below the tenth centile and a composite of perinatal mortality or severe perinatal morbidity. RESULTS: Of 256 599 term deliveries meeting the inclusion criteria, 2278 (0.9%) involved TPTL. The risks of the primary outcomes were higher among those with TPTL relative to those without: birthweight for gestational age below the tenth centile (RR 1.24, 95% CI 1.11-1.39) and the composite of perinatal mortality/severe perinatal morbidity (RR 1.33, 95% CI 1.15-1.54). CONCLUSIONS: Although the prevalence of TPTL in term deliveries is low, affected pregnancies are at increased risk for adverse perinatal outcomes. Increased fetal surveillance should be considered in the management of pregnancies affected by TPTL.


Assuntos
Trabalho de Parto Prematuro/epidemiologia , Estudos de Coortes , Feminino , Idade Gestacional , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Nova Escócia/epidemiologia , Mortalidade Perinatal , Gravidez , Complicações na Gravidez/epidemiologia , Transtornos Puerperais/epidemiologia , Tocolíticos/uso terapêutico
5.
Neuroimage Clin ; 11: 20-29, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26909322

RESUMO

Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with 'moderate to severe' VM impairments were compared to 23 patients with 'low to mild' VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with 'moderate to severe' VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with 'low to mild' VM impairments, patients with 'moderate to severe' VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with 'low to mild' VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.


Assuntos
Lobo Frontal/patologia , Transtornos da Memória/fisiopatologia , Memória/fisiologia , Esquizofrenia/fisiopatologia , Fala , Adulto , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Memória/diagnóstico , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Adulto Jovem
6.
Neuropsychologia ; 70: 227-34, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25708174

RESUMO

Sight is undoubtedly important for the perception and the assessment of the palatability of tastants. Although many studies have addressed the consequences of visual impairment on food selection, feeding behavior, eating habits and taste perception, nothing is known about the neural correlates of gustation in blindness. In the current study we examined brain responses during gustation using functional magnetic resonance imaging (fMRI). We scanned nine congenitally blind and 14 age- and sex-matched blindfolded sighted control subjects, matched in age, gender and body mass index (BMI), while they made judgments of either the intensity or the (un)pleasantness of different tastes (sweet, bitter) or artificial saliva that were delivered intra-orally. The fMRI data indicated that during gustation, congenitally blind individuals activate less strongly the primary taste cortex (right posterior insula and overlying Rolandic operculum) and the hypothalamus. In sharp contrast with results of multiple other sensory processing studies in congenitally blind subjects, including touch, audition and smell, the occipital cortex was not recruited during taste processing, suggesting the absence of taste-related compensatory crossmodal responses in the occipital cortex. These results underscore our earlier behavioral demonstration that congenitally blind subjects have a lower gustatory sensitivity compared to normal sighted individuals. We hypothesize that due to an underexposure to a variety of tastants, training-induced crossmodal sensory plasticity to gustatory stimulation does not occur in blind subjects.


Assuntos
Cegueira/complicações , Cegueira/patologia , Mapeamento Encefálico , Encéfalo/fisiopatologia , Transtornos da Percepção/etiologia , Percepção Gustatória/fisiologia , Adulto , Encéfalo/irrigação sanguínea , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Psicofísica , Estatística como Assunto , Estatísticas não Paramétricas , Paladar
7.
J Oncol Pharm Pract ; 18(1): 76-83, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21490115

RESUMO

PURPOSE: Bone metastases are the most common cause of cancer pain, with palliative radiotherapy (RT) the mainstay of treatment. However, relief from RT may be delayed, incomplete, or short-lived and therefore optimized pharmacologic therapy is essential. Our objective was to describe the contribution of the clinical pharmacist (CP) to an outpatient palliative RT clinic. METHODS: The Edmonton Symptom Assessment System, an 11-point scale for measuring nine symptoms, and other validated screening tools were administered, and a medication history performed by the CP. Baseline CP assessment also included opioid toxicity, need for supportive medications, and drug interactions. Anonymized clinical information was collected prospectively and descriptive statistics were compiled including themes of counselling performed by the CP. RESULTS: The CP reviewed 114 patients over 140 clinic visits (01/2007-12/2008). Median age was 68.3 years, 68.4% were male and 36.8% had prostate cancer. All symptoms improved or stabilized in ≥ 80% by 4 weeks. Median pain score was 6/10 (SD 2.6) at baseline, and 2.1/10 (SD 2.4) by week 4. Average morphine equivalent daily dose was 76.8 mg at baseline and 44.5 mg at week 4. CP assessment included screening for opioid toxicity (87.9%), recommending a change in analgesic (28.9%), and liaison with the community pharmacy (17.1%). Medication counselling took place in 84.3% of visits, on bowel routine (85.6% of the time), opioids (82.2%), and hydration (40.7%). CONCLUSIONS: The CP plays a key role in holistic patient assessment and optimization of pharmacologic therapy, contributing to improved symptom control of patients receiving palliative RT.


Assuntos
Neoplasias Ósseas/radioterapia , Dor/radioterapia , Cuidados Paliativos/métodos , Farmacêuticos/organização & administração , Idoso , Assistência Ambulatorial/organização & administração , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Neoplasias Ósseas/secundário , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Saúde Holística , Humanos , Masculino , Neoplasias/patologia , Dor/tratamento farmacológico , Dor/etiologia , Medição da Dor , Educação de Pacientes como Assunto , Serviço de Farmácia Hospitalar/organização & administração , Papel Profissional , Estudos Prospectivos , Resultado do Tratamento
8.
Support Care Cancer ; 17(2): 163-70, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18566840

RESUMO

GOALS OF WORK: Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). MATERIALS AND METHODS: Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. MAIN RESULTS: Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10-100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. CONCLUSIONS: Early needs assessment was advantageous in determining the optimal team and methods of assessment for our 'one-stop' BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Institutos de Câncer , Cuidados Paliativos/métodos , Radioterapia , Acessibilidade aos Serviços de Saúde , Humanos , Avaliação de Resultados em Cuidados de Saúde , Dor/radioterapia , Qualidade de Vida , Radioterapia (Especialidade)/organização & administração , Fatores de Tempo
9.
J Autism Dev Disord ; 36(2): 239-47, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16453069

RESUMO

The possible use of a calendar algorithm was assessed in DBC, an autistic "savant" of normal measured intelligence. Testing of all the dates in a year revealed a random distribution of errors. Re-testing DBC on the same dates one year later shows that his errors were not stable across time. Finally, DBC was able to answer "reversed" questions that cannot be solved by a classical algorithm. These findings favor a non-algorithmic retrieval of calendar information. It is proposed that multidirectional, non-hierarchical retrieval of information, and solving problems in a non-algorithmic way, are involved in savant performances. The possible role of a functional rededication of low-level perceptual systems to the processing of symbolic information in savants is discussed.


Assuntos
Algoritmos , Aptidão , Transtorno Autístico , Percepção do Tempo , Adolescente , Humanos , Masculino , Tempo de Reação
10.
Br J Nutr ; 86(5): 557-68, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11737954

RESUMO

It has been suggested that the current dietary recommendations (low-fat-high-carbohydrate diet) may promote the intake of sugar and highly refined starches which could have adverse effects on the metabolic risk profile. We have investigated the short-term (6-d) nutritional and metabolic effects of an ad libitum low-glycaemic index-low-fat-high-protein diet (prepared according to the Montignac method) compared with the American Heart Association (AHA) phase I diet consumed ad libitum as well as with a pair-fed session consisting of the same daily energy intake as the former but with the same macronutrient composition as the AHA phase I diet. Twelve overweight men (BMI 33.0 (sd 3.5) kg/m2) without other diseases were involved in three experimental conditions with a minimal washout period of 2 weeks separating each intervention. By protocol design, the first two conditions were administered randomly whereas the pair-fed session had to be administered last. During the ad libitum version of the AHA diet, subjects consumed 11695.0 (sd 1163.0) kJ/d and this diet induced a 28 % increase in plasma triacylglycerol levels (1.77 (sd 0.79) v. 2.27 (sd 0.92) mmol/l, P<0.05) and a 10 % reduction in plasma HDL-cholesterol concentrations (0.92 (sd 0.16) v. 0.83 (sd 0.09) mmol/l, P<0.01) which contributed to a significant increase in cholesterol:HDL-cholesterol ratio (P<0.05), this lipid index being commonly used to assess the risk of coronary heart disease. In contrast, the low-glycaemic index-low-fat-high-protein diet consumed ad libitum resulted in a spontaneous 25 % decrease (P<0.001) in total energy intake which averaged 8815.0 (sd 738.0) kJ/d. As opposed to the AHA diet, the low-glycaemic index-low-fat-high-protein diet produced a substantial decrease (-35 %) in plasma triacylglycerol levels (2.00 (sd 0.83) v. 1.31 (sd 0.38) mmol/l, P<0.0005), a significant increase (+1.6 %) in LDL peak particle diameter (251 (sd 5) v. 255 (sd 5) A, P<0.02) and marked decreases in plasma insulin levels measured either in the fasting state, over daytime and following a 75 g oral glucose load. During the pair-fed session, in which subjects were exposed to a diet with the same macronutrient composition as the AHA diet but restricted to the same energy intake as during the low-glycaemic index-low-fat-high-protein diet, there was a trend for a decrease in plasma HDL-cholesterol levels which contributed to the significant increase in cholesterol:HDL-cholesterol ratio noted with this condition. Furthermore, a marked increase in hunger (P<0.0002) and a significant decrease in satiety (P<0.007) were also noted with this energy-restricted diet. Finally, favourable changes in the metabolic risk profile noted with the ad libitum consumption of the low-glycaemic index-low-fat-high-protein diet (decreases in triacyglycerols, lack of increase in cholesterol:HDL-cholesterol ratio, increase in LDL particle size) were significantly different from the response of these variables to the AHA phase I diet. Thus, a low-glycaemic index-low-fat-high-protein content diet may have unique beneficial effects compared with the conventional AHA diet for the treatment of the atherogenic metabolic risk profile of abdominally obese patients. However, the present study was a short-term intervention and additional trials are clearly needed to document the long-term efficacy of this dietary approach with regard to compliance and effects on the metabolic risk profile.


Assuntos
Arteriosclerose/dietoterapia , Dieta com Restrição de Gorduras , Carboidratos da Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Obesidade/dietoterapia , Análise de Variância , Arteriosclerose/sangue , Arteriosclerose/etiologia , HDL-Colesterol/sangue , Ingestão de Energia , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Distribuição Normal , Obesidade/sangue , Obesidade/complicações , Fatores de Risco , Triglicerídeos/sangue
11.
IEEE Trans Med Imaging ; 20(11): 1193-200, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11700746

RESUMO

We report about the design and test of an image processing algorithm for the localization of the optic disk (OD) in low-resolution (about 20 micro/pixel) color fundus images. The design relies on the combination of two procedures: 1) a Hausdorff-based template matching technique on edge map, guided by 2) a pyramidal decomposition for large scale object tracking. The two approaches are tested against a database of 40 images of various visual quality and retinal pigmentation, as well as of normal and small pupils. An average error of 7% on OD center positioning is reached with no false detection. In addition, a confidence level is associated to the final detection that indicates the "level of difficulty" the detector has to identify the OD position and shape.


Assuntos
Disco Óptico/anatomia & histologia , Disco Óptico/irrigação sanguínea , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador , Doenças do Nervo Óptico/diagnóstico , Valores de Referência , Reprodutibilidade dos Testes
12.
Int Immunopharmacol ; 1(3): 539-50, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11367537

RESUMO

beta-Glucans are polysaccharides that act as nonspecific immune system stimulants. However, many beta-Glucans are sparingly soluble in water. This work describes an oxidative procedure, which solubilizes the beta-Glucan from Saccharomyces cerevisiae and maintains its immunostimulatory properties. Furthermore, the carboxylates at the site of oxidation allow for the conjugation of small molecule immunostimulants. Both the parent oxidized beta-glucan and its conjugates with O-beta-alanyl-5-[6-(N,N'-dimethylamino)purin-9-yl]pentanol stimulate cytotoxic T-lymphocytes (CTLs), B cells and macrophages. In addition, they both stimulate natural killer (NK) cells, a property which the small molecule purine does not possess.


Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Glucanos/química , Glucanos/farmacologia , Adjuvantes Imunológicos/isolamento & purificação , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Sequência de Carboidratos , Feminino , Glucanos/isolamento & purificação , Humanos , Técnicas In Vitro , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Oxirredução , Saccharomyces cerevisiae/química , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
14.
Am J Phys Med Rehabil ; 79(6): 526-35, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11083303

RESUMO

OBJECTIVE: To determine the prevalence of secondary impairments among individuals with long-standing spinal cord injury in Quebec and the potential relationships between these impairments and several variables. DESIGN: A review of 2,200 medical files was conducted to determine the target population; 976 patients were selected randomly and mailed questionnaires. The results were based on 482 individuals with spinal cord injury who returned the completed questionnaire. The questionnaire included 14 subsections, such as sociodemographic, medical, psychosocial, and environmental information. The medical section, including the type and level of lesion and the presence of secondary impairments, was analyzed. RESULTS: Urinary tract infection, spasticity, and hypotension were the most frequently reported secondary impairments, regardless of the severity of injury. Relationships between the prevalence of secondary impairments and the duration of injury, as well as perceived health status, were observed. CONCLUSIONS: This is the first study to describe secondary impairments after long-standing spinal cord injury in Quebec. Patients with spinal cord injury still present a high prevalence of secondary impairments many years after their rehabilitation, despite preventive education or medical follow-up visits. Further studies are required to determine the specific impact that these impairments have on the patients' social role and their quality-of-life.


Assuntos
Nível de Saúde , Traumatismos da Medula Espinal/complicações , Adulto , Idoso , Disreflexia Autonômica/epidemiologia , Disreflexia Autonômica/etiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipotensão/epidemiologia , Hipotensão/etiologia , Renda , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/epidemiologia , Espasticidade Muscular/etiologia , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Prevalência , Quebeque/epidemiologia , Dor de Ombro/epidemiologia , Dor de Ombro/etiologia , Traumatismos da Medula Espinal/economia , Traumatismos da Medula Espinal/epidemiologia , Fatores de Tempo , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia
15.
Int J Immunopharmacol ; 22(9): 659-71, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10884587

RESUMO

N,N-dimethylaminopurine pentoxycarbonyl D-arginine (BCH-1393) is a novel low molecular weight synthetic immunomodulator that has been shown to significantly stimulate cytotoxic T-lymphocyte responses both in vitro and in vivo (Zacharie B, Gagnon L, Attardo G, Connolly TP, St-Denis Y, Penney CL. Synthesis and activity of 6-substituted purine linker amine immunostimulants. J. Med. Chem. 1997;40:2883-94). Prompted by this evidence, we extended evaluation of BCH-1393 for anticancer activity in syngeneic mouse experimental tumor models. Consistent with previous findings, in vitro assessment of BCH-1393 activity demonstrated a significant increase in the CTL responses in the range of 10(-9)-10(-5) M. Treatment of mice with four consecutive daily intraperitoneal injections at 25 and 50 mg/kg resulted in a significant increase of the relative percentage of blood CD4+, CD8+, NK and monocyte subsets without any evidence of toxicity. In vivo anti-tumor activity of BCH-1393 was evaluated, either alone or in combination with subtherapeutic doses of cyclophosphamide (Cy), against weakly immunogenic mouse breast carcinoma DA-3 and strongly immunogenic colon adenocarcinoma MC38. Daily intraperitoneal injection of BCH-1393 at 50 mg/kg alone was well tolerated but produced a relatively weak anti-tumor effect in both tumor models. However, a significant inhibition of tumor outgrowth and suppression of established tumor growth was observed when BCH-1393 was administered in combination with subtherapeutic doses of Cy. Combination treatment of 50 mg/kg BCH-1393 with 100 mg/kg Cy (given as single intravenous bolus injection) starting 2 days prior to DA-3 tumor cell inoculation prevented tumor outgrowth in 70-80% of treated mice. In the remaining 20-30% of mice that had developed tumors, a nearly complete (90%) tumor growth inhibition was observed at days 22-24 post tumor implant. In the MC38 tumor model, combination treatment of established tumors with BCH-1393 and Cy (CTX) at 50 mg/kg resulted in a significant delay in tumor growth compared to CTX treatment alone. The observed concomitant anti-tumor activity of BCH-1393 with cyclophosphamide warrants further investigation of this immunomodulator as an adjunctive treatment of cancer.


Assuntos
Arginina/análogos & derivados , Arginina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Purinas/uso terapêutico , Linfócitos T Citotóxicos/imunologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arginina/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Neoplasias do Colo/imunologia , Ciclofosfamida/farmacologia , Testes Imunológicos de Citotoxicidade , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Imunofenotipagem , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Mamárias Experimentais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Monócitos/efeitos dos fármacos , Purinas/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Fatores de Tempo , Células Tumorais Cultivadas
16.
Brain Cogn ; 43(1-3): 206-10, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10857695

RESUMO

Right-handed university subjects were presented with monaural melodies that either conformed to the rules of the Western tonal system (tonal melodies) or that systematically deviated from it (atonal melodies) while containing similar contours and pitch skips. Subjects were tested under two different task instructions. One group was requested to judge whether each melody sounded correct or not (the nonaffective task); the other group had to judge whether each melody sounded pleasant or not (the affective task). The nonaffective task was found to elicit essentially no ear difference. In contrast, the affective instruction induced opposite and reliable laterality effects, depending on the valence of the response. The pleasant responses were indicative of a left hemisphere predominance and the unpleasant responses of a right hemisphere predominance. The results are consistent with the claim that the left hemisphere is biased toward positive emotions and the right to negative emotions. Moreover, the results suggest that affective appreciation of melodies is dissociable from their nonaffective judgment.


Assuntos
Afeto , Lateralidade Funcional/fisiologia , Música , Percepção da Fala/fisiologia , Adulto , Feminino , Humanos , Masculino , Distribuição Aleatória
17.
Vaccine ; 18(18): 1886-92, 2000 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-10699337

RESUMO

The tetrapeptide I (D-lysine-L-asparaginyl-L-prolyl-L-tyrosine or D-LysAsnProTyr), and analogue sequences, were synthesized and evaluated for the ability to stimulate immune cell subsets. These sequences were selected based on their perceived ability to readily adopt a beta-turn structure. In vitro immunological assays revealed a robust stimulation of mitogen activated B-cell proliferation and a modest to significant stimulation of cytotoxic T lymphocytes (CTLs). Further, this in vitro stimulation of B-cells was accompanied by an in vivo expansion of B-cells in C57BL/6 mice, as demonstrated by immunophenotyping experiments. Interestingly, a conformational analysis of the low energy conformers of I and the endogenous B-cell stimulant bursin (LysHisGlyNH2) shows that these molecules can be superimposed. However, I displayed significantly enhanced physiological stability. For a number of reasons, I may be a particularly useful vaccine adjuvant.


Assuntos
Subpopulações de Linfócitos B/imunologia , Ativação Linfocitária/imunologia , Mimetismo Molecular , Oligopeptídeos/química , Oligopeptídeos/imunologia , Animais , Asparagina/imunologia , Células Cultivadas , Feminino , Meia-Vida , Lisina/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Oligopeptídeos/farmacologia , Prolina/imunologia , Baço , Tirosina/imunologia
18.
Antimicrob Agents Chemother ; 44(3): 583-9, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10681322

RESUMO

It has been shown in enterobacteria that mutations in ampD provoke hyperproduction of chromosomal beta-lactamase, which confers to these organisms high levels of resistance to beta-lactam antibiotics. In this study, we investigated whether this genetic locus was implicated in the altered AmpC beta-lactamase expression of selected clinical isolates and laboratory mutants of Pseudomonas aeruginosa. The sequences of the ampD genes and promoter regions from these strains were determined and compared to that of wild-type ampD from P. aeruginosa PAO1. Although we identified numerous nucleotide substitutions, they resulted in few amino acid changes. The phenotypes produced by these mutations were ascertained by complementation analysis. The data revealed that the ampD genes of the P. aeruginosa mutants transcomplemented Escherichia coli ampD mutants to the same levels of beta-lactam resistance and beta-lactamase expression as wild-type ampD. Furthermore, complementation of the P. aeruginosa mutants with wild-type ampD did not restore the inducibility of beta-lactamase to wild-type levels. This shows that the amino acid substitutions identified in AmpD do not cause the altered phenotype of AmpC beta-lactamase expression in the P. aeruginosa mutants. The effects of AmpD inactivation in P. aeruginosa PAO1 were further investigated by gene replacement. This resulted in moderate-basal-level and hyperinducible expression of beta-lactamase accompanied by high levels of beta-lactam resistance. This differs from the stably derepressed phenotype reported in AmpD-defective enterobacteria and suggests that further change at another unknown genetic locus may be causing total derepressed AmpC production. This genetic locus could also be altered in the P. aeruginosa mutants studied in this work.


Assuntos
Proteínas de Bactérias/genética , N-Acetil-Muramil-L-Alanina Amidase/genética , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/genética , beta-Lactamases/metabolismo , Ampicilina/farmacologia , Proteínas de Bactérias/metabolismo , Sequência de Bases , Cefotaxima/farmacologia , Cefalosporinas/farmacologia , Indução Enzimática , Teste de Complementação Genética , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Penicilinas/farmacologia , Fenótipo , Plasmídeos/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Análise de Sequência de DNA , Resistência beta-Lactâmica/genética , beta-Lactamases/genética
19.
Genomics ; 59(3): 291-9, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10444330

RESUMO

Mutations in the mouse dreher (dr) gene cause skeletal defects, hyperactivity, abnormal gait, deafness, white belly spotting, and hypoplasia of Müllerian duct derivatives. To map dr to high resolution, we utilized two crosses. Initially, we analyzed an intersubspecific intercross to construct a detailed genetic map of simple sequence length polymorphism markers within a 6.3-cM region surrounding the dr locus. Subsequently, we analyzed a second intersubspecific intercross segregating for the dr(6J) allele, which positioned dr within a 0.13-cM region between Rxrg and D1Mit370. A physical contig of BAC clones spanning the dr critical region was constructed, and eight potential dr candidate genes were excluded by genetic or physical mapping. Together these results lay the foundation for positional cloning of the dr gene.


Assuntos
Anormalidades Múltiplas/genética , Mapeamento Cromossômico , Animais , Sequência de Bases , Cruzamentos Genéticos , Feminino , Marcadores Genéticos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Dados de Sequência Molecular , Mapeamento Físico do Cromossomo
20.
J Med Chem ; 42(11): 2046-52, 1999 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-10354413

RESUMO

Imreg (Tyr1-Gly2-Gly3) is a well-known immunostimulant. However, it possesses a short half-life. Stabilized analogues of Imreg were prepared by a regioselective insertion in which peptide bonds at position 1,2 or 2,3 were replaced by thioamide linkages. This was achieved by using new thioacylating agents based on thioacyl-fluoro-N-benzimidazolone. The synthesis and properties of these reagents are described herein. This peptide modification enhanced significantly the half-life of the thioanalogues relative to Imreg in blood. The thioanalogues and Imreg were tested in vitro in T and B cell proliferation assays and for their ability to stimulate cytotoxic T-lymphocytes (CTLs). Only thiotyrosyl glycyl glycine 11 displayed some activity as evidenced by a weak stimulation of CTLs. On the basis of this activity and the increased stability, an in vivo immunological evaluation was undertaken. Immunophenotyping of 11 revealed a significant increase in activated CTL and NK cell populations in the spleen. This expansion was also accompanied by a significant stimulation of NK cells and the B cell proliferative response. Thioanalogues of Imreg were generally nontoxic, as exemplified by 11. The latter is a promising immunostimulant which may be targeted for cancer and viral infections, where CTLs and NK cells play an important role, or as a vaccine adjuvant where stimulation of antibody-producing B cells is important.


Assuntos
Adjuvantes Imunológicos/síntese química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Estabilidade de Medicamentos , Endopeptidases/química , Feminino , Imunofenotipagem , Rim/enzimologia , Rim/ultraestrutura , Células Matadoras Naturais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microvilosidades/enzimologia , Oligopeptídeos/farmacologia , Ratos , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia
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