RESUMO
Cis and trans proline conformers are often associated with dramatic changes in the biological function of peptides. A slow equilibrium between cis and trans Ile-Pro amide bond conformers occurs in constrained derivatives of the native marine cyclic heptapeptide stylostatin 1 (cyclo-(NSLAIPF)), a potential anticancer agent. In this work, four cyclopeptides, cyclo-(NSTAIPF), cyclo-(KSTAIPF), cyclo-(RSTAIPF) and cyclo-(DSTAIPF), which are structurally related to stylostatin 1, are experimentally and computationally examined in order to assess the effect of residue mutations on the cis-trans conformational ratio and the apparent capacity to form dimeric aggregates. Primarily, cyclo-(KSTAIPF) and cyclo-(RSTAIPF) showed specific trends in circular dichroism, MALDI-TOF and HPLC purification experiments, which suggests the occurrence of peptide dimerization. Meanwhile, the NMR spectrum of cyclo-(KSTAIPF) indicates that this cyclopeptide exists in the two slow-exchange families of conformations mentioned above. Molecular dynamics simulations combined with quantum mechanical calculations have shed light on the factors governing the cis/trans conformational ratio. In particular, we have found that residue mutations affect the internal hydrogen bond pattern which ultimately tunes the cis/trans conformational ratio and that only trans conformers are capable of aggregating due to the shape complementarity of the two subunits.
Assuntos
Peptídeos Cíclicos/química , Prolina/química , Dimerização , Isomerismo , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
BACKGROUND: Pre-emptive isolation refers to the application of contact precaution measures in patients with strongly suspected colonization by multiresistant bacteria. OBJECTIVE: To assess the impact of an intervention program involving the implementation of a consensus-based protocol of pre-emptive isolation (CPPI) on admission to a polyvalent ICU of a general hospital. METHODS: A comparative analysis of 2 patient cohorts was made: a historical cohort including patients in which pre-emptive isolation was established according to physician criterion prior to starting CPPI (from January 2010 to February 2011), and a prospective cohort including patients in which CPPI was implemented (from March to November 2011). CPPI included the identification and diffusion of pre-emptive isolation criteria, the definition of sampling methodology, the evaluation of results, and the development of criteria for discontinuation of pre-emptive isolation. Pre-emptive isolation was indicated by the medical staff, and follow-up was conducted by the nursing staff. Pre-emptive isolation was defined as "adequate" when at least one multiresistant bacteria was identified in any of the samples. Comparison of data between the 2 periods was made with the chi-square test for categorical variables and the Student t-test for quantitative variables. Statistical significance was set at P<.05. RESULTS: Among the 1,740 patients admitted to the ICU (1,055 during the first period and 685 during the second period), pre-emptive isolation was indicated in 199 (11.4%); 111 (10.5%) of these subjects corresponded to the historical cohort (control group) and 88 (12.8%) to the posterior phase after the implementation of CPPI (intervention group). No differences were found in age, APACHE II score or patient characteristics between the 2 periods. The implementation of CPPI was related to decreases in non-indicated pre-emptive isolations (29.7 vs. 6.8%, P<.001), time of requesting surveillance cultures (1.56 vs. 0.37 days, P<.001), and days of duration of treatment (4.77 vs. 3.58 days, P<.001). In 44 patients (22.1%) in which pre-emptive isolation was indicated, more than one multiresistant bacteria was identified, with an "adequate pre-emptive isolation rate" of 19.8% in the first period and 25.0% in the second period (P<.382). CONCLUSIONS: The implementation of CPPI resulted in a significant decrease in pre-emptive isolations which were not indicated correctly, a decrease in the time elapsed between isolation and collection of samples, and a decrease in the duration of isolation measures in cases in which isolation was unnecessary, without increasing the rate of "adequate pre-emptive isolation".
Assuntos
Infecções Bacterianas/prevenção & controle , Infecção Hospitalar/prevenção & controle , Unidades de Terapia Intensiva/organização & administração , Isolamento de Pacientes/organização & administração , Idoso , Infecções Bacterianas/epidemiologia , Protocolos Clínicos , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Grupos Diagnósticos Relacionados , Farmacorresistência Bacteriana Múltipla , Feminino , Estudo Historicamente Controlado , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Isolamento de Pacientes/métodos , Isolamento de Pacientes/estatística & dados numéricos , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.77 (SD: 16.35) (range, 0-100). The MD prioritizes consumption of vegetable and fruit over meat and dairy products, and OCs are generally lipophilic molecules that accumulate in foods of animal origin. Consumption of meat, fish, and dairy products was associated with dichlorodiphenyldichloroethylene (DDE) in umbilical cord serum, and dairy product intake with lindane. Vegetable consumption was also associated with lindane and fruit intake with endosulfan I. We found no significant association between MD adherence and the presence of OC residues in serum. However, closer adherence to the MD may offer greater protection against OC exposure because of its reduced content in meat and dairy products.
Assuntos
Dieta Mediterrânea , Poluentes Ambientais/sangue , Sangue Fetal/química , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adulto , Monitoramento Ambiental , Feminino , Humanos , Masculino , Exposição Materna , Troca Materno-Fetal , Pessoa de Meia-Idade , Gravidez , Espanha , Adulto JovemRESUMO
OBJECTIVE: Different studies show the scarce attention granted to the nutritional state in historical and clinical practice, what determines the ignorance of the patient's nutritional status to their entrance in the hospital and, therefore, the impossibility to prevent the hospital malnutrition. The objective of our study has been to determine the prevalence of patients' malnutrition entered in a Hospital of Orthopedic surgery and Rehabilitation. METHODS: Observational and analytical study in 250 randomized patients (60% men and 40% women), who were nutritionally evaluated when entering, the hospital, by means of anthropometry (Weigh, height, BMI, skin-fold, corporal circumferences) and biochemical tests (Albumin, Prealbumin and Transferrin). RESULTS: According to the BMI the prevalence of malnutrition was of 8%, the average of caloric malnutrition was of 2.8% (according to anthropometry) and the prevalence of many-sided malnutrition rises to 54.8% (according to biochemical markers). CONCLUSIONS: The high prevalence of fundamental malnutrition (54.8%) demonstrated in this study, it shows the importance of determining the nutritional status when entering the hospital, particularly surgical type' patiens as is the case of most of those who enter the Orthopedic surgery hospitals.
Assuntos
Hospitalização , Desnutrição/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos , Prevalência , Centros de ReabilitaçãoAssuntos
Aneurisma/terapia , Duodeno/irrigação sanguínea , Embolização Terapêutica/métodos , Complicações Pós-Operatórias/terapia , Estômago/irrigação sanguínea , Adulto , Aneurisma/etiologia , Artérias , Úlcera Duodenal/complicações , Úlcera Duodenal/cirurgia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Hemoperitônio/etiologia , Hemoperitônio/terapia , Humanos , Complicações Pós-Operatórias/etiologia , ReoperaçãoRESUMO
Serum and urine selenium levels were determined in patients with cardiovascular diseases by hydride generation atomic absorption spectrometry. Mean serum Se concentrations measured in patients with acute myocardial infarction (AMI; n = 32) or with ischemic cardiomyopathy (n = 50) were significantly lower than those determined in control groups. In AMI patients, serum triglyceride levels showed a positive significant correlation with the serum Se concentration (r = 0.59, p < 0.05). This result reinforces the important role of Se as an antioxidant agent in this disease. Mean urine Se concentrations of AMI patients (n = 33) were also significantly lower to those determined in the control group (p < 0. 05). This reaction of the organism contributes to regulate the Se homeostasis to keep the body Se status as high as possible.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/urina , Estado Nutricional , Selênio/sangue , Selênio/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/urina , Isquemia Miocárdica/sangue , Isquemia Miocárdica/urina , Inquéritos Nutricionais , Fatores Sexuais , Triglicerídeos/sangueRESUMO
Serum and urine selenium levels were determined in patients with diabetes by hydride generation atomic absorption spectrometry. Mean serum selenium concentrations measured in patients with diabetes mellitus (64.9 +/- 22.8 micrograms/l) were significantly lower than those determined in the control group (74.9 +/- 27.3 micrograms/l) (P < 0.05). Mean serum selenium concentrations were not significantly different between the two groups of diabetic patients considered (P > 0.05). Mean urine selenium concentration in diabetic patients (18.8 +/- 10.7 micrograms/l) were not significantly different from those measured in the control group (20.2 +/- 10.1 micrograms/l) (P < 0.05). No significant differences in serum and urine selenium levels were found if related to sex of patients (P > 0.05). Application of linear regression analysis to serum and urine selenium levels and patients' age showed a non-statistically significant correlation (P > 0.05). Given the marked overlap between the two ranges of the populations, the predictive values of serum selenium in diabetic patients are low.
Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/urina , Selênio/sangue , Selênio/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine the experience of the National Health Ministry physicians in the management of HIV-infected patients and in the use of antiretrovirals. MATERIAL AND METHOD: A descriptive, observational and transversal study was performed, with support from the National AIDS Council from March to May 1998. Self-applicable questionnaires were filled by National Health Ministry physicians with experience in HIV patient clinical care, at the beginning of 5 different meetings on HIV/AIDS in several cities of the country. Statistical analysis included the chi-square test. RESULTS: One hundred and eighty-one questionnaires were applied. The median of HIV patients attended by physicians was 4 (interval 1-97); 36.5% of the physicians had used antiretrovirals (35.4% prescribed nucleoside analogs and 9.9% protease inhibitors). The most frequently used drugs were AZT and/or ddl (40.3%); 17.7% had administered CD4+ lymphocyte count and 8.8% viral load. CONCLUSIONS: The proportion of National Health Ministry physicians with experience in VIH patient care was low, as was the use of antiretrovirals. Efforts should be focus on improving care of HIV patients through physician training.
Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1 , Médicos , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Competência Clínica/estatística & dados numéricos , Quimioterapia Combinada , Feminino , Órgãos Governamentais , Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/tratamento farmacológico , HIV-1/imunologia , Humanos , Masculino , México , Médicos/estatística & dados numéricos , Saúde Pública , Inquéritos e Questionários , Carga ViralRESUMO
OBJECTIVE: To evaluate if the combination of AZT/ddl offered any advantages in surrogate markers among HIV infected asymptomatic patients previously treated with AZT for at least six months. METHODS: We used a prospective cohort of 269 asymptomatic HIV patients with CD4+ cell counts between 200 and 500 cells/microL. They were given didanosine (ddl 400 mg/d) in addition to AZT (500 mg/d) and had received AZT monotherapy for an average of 20 months. End points were progression to AIDS, death, or toxicity. RESULTS: Median CD4+ cell count at the start of the combination therapy was 339 cells/microL which increased at three months to 451 and subsequently declined at 6, 12 and 18 months of followup (medians of 392, 360, 307 cells/microL respectively). Five patients progressed to AIDS, six developed toxicity (myelosuppression, hepatitis or pancreatitis) and 26 had minor side effects that required only dose reduction. CONCLUSIONS: The addition of ddl to patients with prolonged ZDV monotherapy can be useful. CD4+ T cell counts showed a significant increase at 3 months with a gradual subsequent decline to below baseline at 18 months. Adverse effect of the drugs, although frequent, did not stop therapy in most patients.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Zidovudina/uso terapêutico , Adolescente , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
A cross-sectional study of serum selenium levels in patients (n = 59) with different types of cancer from southeastern Spain was carried out using hydride generation atomic absorption spectrometry. The subjects were divided into four groups according to the cancer location (respiratory, digestive, haematological and gynaecological groups). Serum selenium levels in all patients (54.41 +/- 24.80 mg/l) were significantly lower (P < 0.001) than those determined in control groups [healthy subjects from the same area (n = 130) and institutionalized elderly people (n = 93)]. Mean serum selenium concentrations were not significantly different among the four groups considered (P > 0.05). Linear regression analyses performed on serum selenium levels and biochemical markers (total cholesterol, triglycerides, transaminases, uric acid and urea) did not establish any statistically significant correlation (P > 0.05). No significant relationships between serum selenium concentrations and sex or age of patients was observed (P > 0.05). Given the marked overlap between the two ranges of the populations (the means are within approx. 1/2 S.D.) the predictive values of serum selenium are low. Thus, there is indeed a statistical significance between the means, but selenium cannot be used to determine whether or not a patient has cancer disease.