RESUMO
STUDY DESIGN: This work is an experimental and prospective study in adult, female, Long-Evans rats. OBJECTIVES: The aim of this study was to probe the effect of metabolic inhibition after an acute traumatic spinal cord injury (TSCI) using a standardized contusion model (NYU impactor) to know whether the metabolic inhibition is a 'secondary mechanism of injury' or a mechanism of protection. SETTING: All experimental procedures were carried out in the Mexico City. METHODS: Animals were divided into five groups: one sham and four with TSCI, including no treatment, rotenone (inhibitor of mitochondrial complex I), sodium azide (inhibitor of mitochondrial complex IV) and pyrophosphate of thiamine or non-degradable cocarboxylase as a metabolic reactivator. RESULTS: After TSCI, the metabolic inhibition with sodium azide treatment diminished the lipid peroxidation process (malondialdehyde levels by spectrophotometric procedures) and the damage to the spinal cord tissue (morphometric analysis), and increased the activity of creatine kinase and lactate dehydrogenase enzymes (P<0.05) (measured by spectrophotometric procedures 24 h after TSCI as well as after the functional recovery of the hind limb (evaluated weekly for 2 months by the BBB (Basso, Beattie and Bresnahan) scale)) when compared with the TSCI group without treatment. CONCLUSION: The results show that the partial and transitory inhibition of the aerobic metabolism after an acute TSCI could be a self-protection mechanism instead of being a 'secondary mechanism of injury'.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Animais , Creatina Quinase/efeitos dos fármacos , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Complexo de Proteínas da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/fisiologia , Inibidores Enzimáticos/farmacologia , Feminino , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Estudos Prospectivos , Ratos , Ratos Long-Evans , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Rotenona/farmacologia , Azida Sódica/farmacologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Tiamina Pirofosfato/farmacologia , Resultado do Tratamento , Desacopladores/farmacologia , Complexo Vitamínico B/farmacologiaRESUMO
Human growth and its resulting patterns display a great inter- and intra-population heterogeneity that reflects the quality of life, health and nutritional condition of populations. The aim of this work was to expand the knowledge about the growth of Jujenean children by statistical procedures that graphically express the relation of anthropometric variables to age and allow their comparison with specific references. Anthropometric data came from 9092 children (0-5 years) from various localities of Jujuy province (northwest Argentina) located at 1200 m above sea level (ma.s.l.). The centiles of weight for age (W/A) and height for age (H/A) were obtained by the LMS method using maximum penalized likelihood. A statistical and graphic comparison was made with the corresponding Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) centile references. In general, estimated centiles were lower than those in both references. Discrepancies for H/A in comparison with the CDC reference ranged between 1.09+/-0.59% and 1.66+/-0.34%, and for W/A between 1.82+/-1.56% and 3.36+/-1.4%. In comparison with the WHO reference, discrepancies ranged from 1.38+/-0.65% to 1.87+/-0.41% for H/A, and from 1.12+/-1.28% to 2.74+/-1.49% for W/A. Centile discrepancies were attributed to the characteristics of early childhood feeding and the interaction of a set of biological and mesological factors that the Jujenean population is exposed to. Growth and nutritional conditions of this population should be evaluated with the WHO reference, for it reflects the recent growth pattern of biologically and culturally healthy children raised in favourable conditions, a pattern that also reflects that of Jujenean children.
Assuntos
Antropometria/métodos , Estatura , Peso Corporal , Desenvolvimento Infantil , Argentina , Centers for Disease Control and Prevention, U.S. , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estados Unidos , Organização Mundial da SaúdeRESUMO
Microdistributions of the prospective BNCT-compound CuTCPH, a carborane-containing tetraphenylporphyrin with one Cu atom in its molecular structure, have been obtained in tissue sections of different organs of tumor-bearing and normal Syrian hamsters injected with the boron compound by employing a heavy ion microbeam. High resolution X-ray spectroscopy following micro-PIXE (Particle Induced X-ray Emission with micrometer-sized beams) with a focused (16)O ion beam was used. Focusing was performed with a heavy-ion scanning high-precision magnetic quadrupole triplet microprobe. Squamous Cell Carcinomas were induced on the right Cheek Pouch of Syrian Hamsters (HCP), sampled, cryo-sectioned and freeze-dried. Two-dimensional maps of elemental concentration were obtained by scanning the beam over the samples. Very non-uniform Cu concentrations were found in all sections.
Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Metaloporfirinas/farmacocinética , Metaloporfirinas/uso terapêutico , Animais , Terapia por Captura de Nêutron de Boro/instrumentação , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Bochecha , Cricetinae , Mesocricetus , Neoplasias Bucais/metabolismo , Neoplasias Bucais/radioterapia , Espectrometria por Raios X , Distribuição TecidualRESUMO
Of 26 cases of coccidioidomycosis reported here, 15 showed hyphae, atypical parasitic structures of Coccidioides spp. in fresh cytologic and/or histologic specimen preparations. The finding of this morphology could have implications which should be considered, especially when the disease affects areas of nonendemicity.
Assuntos
Coccidioides/isolamento & purificação , Coccidioidomicose/diagnóstico , Coccidioides/citologia , Coccidioides/fisiologia , Coccidioidomicose/fisiopatologia , Feminino , Humanos , Masculino , MéxicoRESUMO
A prospective study was undertaken to assess the radiotoxicity of accelerated particles in pulmonary alveolar macrophages (AM). We evaluated the effects of a single dose (10-75 Gy) of an external low-energy (20 MeV) proton beam on cultured AM oxidative metabolism and phagocytic function. Macrophages are the first line of defense against invading pathogens and are known to generate superoxide anion (O2), nitric oxide (NO), and mediators of antimicrobial and antitumoral defense mechanisms. We obtained AM by bronchoalveolar lavage from young (1-2 month old) and aged (9-12 month old) male Wistar rats. Cell viability, phagocytosis, O2 and NO production in control and proton-irradiated cultured AM were evaluated The effect of proton irradiation on cell viability was dose-dependent The higher doses induced a dramatic decrease in viability in the aged population. Phagocytosis increased 1.3-1.4 fold inboth populations irrespective of the dose delivered. Generation of O2 was always higher in the aged population for all the doses assayed and showed no significant variation from the control values. In the young population a clear increase was observed with doses of 25 and 50 Gy. NO production in AM from young animals rose in a dose-dependent manner. Conversely, proton irradiation did not affect NO production in macrophages from aged animals. The results of this study demonstrate that AM isolated from young and aged rats are functionally different and show a distinct behavior when exposed to proton irradiation. These findings suggest that age may condition response and must be taken into account when accelerated particle-radiotherapy protocols are considered as a valid therapeutic option for the treatment of cancer. To the best of our knowledge, this is the first report comparing sham-irradiated and proton-irradiated young and aged AM.
Assuntos
Envelhecimento/fisiologia , Macrófagos Alveolares/efeitos da radiação , Prótons , Animais , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Óxido Nítrico/metabolismo , Fagocitose/efeitos da radiação , Ratos , Ratos Wistar , Superóxidos/metabolismoRESUMO
Long-term exposure of aquatic organisms to metals, even those considered micronutrients, may affect their metabolism and produce sublethal effects. We evaluated the effects of long-term exposure of adult amphibian (Bufo arenarum) females to 4 microg/L of Zn(2+) (ZnSO(4) x H(2)O) in Ringer solution on the concentration of Zn and Fe, the activity of the key enzyme of the pentose phosphate pathway glucose 6-phosphate dehydrogenase, and glutathione content, both in the liver and ovary of these animals. We also performed early embryonic development studies by in vitro insemination from control and treated females. Zn exposure rendered lower Zn concentrations in the ovaries than did exposure of animals to Ringer solution without metal addition (97 +/- 50 versus 149 +/- 46 Zn microg/wet tissue g). Zn and Fe concentration correlation was positive and linear in the ovary, but was negative and nonlinear in the liver of the studied females. The activity of the enzyme glucose 6-phosphate dehydrogenase decreased (0.0599 +/- 0.0109 versus 0.0776 +/- 0.0263 micromol of NADPH/min x mg of proteins) and the endogenous glutathione content increased (0.027 +/- 0.005 versus 0.018 +/- 0.007 mg/10 mg of proteins) in the ovary but remained unaltered in the liver as a consequence of Zn treatment. Our results suggest the existence of different mechanisms of regulation of Zn and Fe concentrations in the ovary and in the liver of adult B. arenarum females. Binding of Zn to low-molecular-weight proteins, as metallothioneins, may occur in the liver, thus protecting this organ from toxic effects. In the ovary high-molecular-weight proteins, like glucose-6-phosphate dehydrogenase, should be able to bind Zn, leading to oxidative stress responsible for the observed increase in endogenous glutathione content. Inhibition of the pentose phosphate pathway in the ovary by Zn can be responsible for the reproductive failure that we detected through embryos survival studies during early life stages: 81.3 +/- 6.3% of embryos from control females survived versus 63.1 +/- 13.8% of embryos from Zn-treated females at the branchial circulation stage of development.
Assuntos
Bufo arenarum/fisiologia , Embrião não Mamífero/efeitos dos fármacos , Ovário/fisiologia , Poluentes Químicos da Água/efeitos adversos , Zinco/efeitos adversos , Animais , Bufo arenarum/embriologia , Desenvolvimento Embrionário , Feminino , Glucose-6-Fosfatase/efeitos dos fármacos , Glucose-6-Fosfatase/metabolismo , Fígado/efeitos dos fármacos , Fígado/fisiologia , Ovário/química , Ovário/efeitos dos fármacos , Estresse Oxidativo , Análise de Sobrevida , Distribuição Tecidual , Poluentes Químicos da Água/farmacocinética , Zinco/farmacocinéticaRESUMO
The occurrence and characteristics of remissions in patients with systematic lupus erythematosus (SLE) have not been determined. We therefore studied this in a cohort of 667 patients and found that 156 patients had achieved at least 1 period of 1 year or more of treatment-free clinical remission. This represents an incidence density of 0.028 new cases/person/year. Remission occurred within the first 2 years of disease in 62 patients. The mean duration of first remission was 4.6 years (range, 1-21 yr), and 81 patients were still in the initial remission up until cutoff time. Half of the remaining 75 patients who flared after achieving remission have not entered again in remission. Twenty-six of the 38 patients who did remained in remission, and the remaining 12 had subsequent flares and remissions. Treatment-free remission accounted for a mean of 5.8 years, corresponding to half the time of follow-up. Remission was not limited to patients with mild disease: at least 41 patients achieved remission despite renal involvement, 19 had had neuropsychiatric lupus, 15 had had thrombocytopenia, and 8 had had hemolytic anemia. We also found that the longer the time lapse between the initial manifestation and the diagnosis of SLE, the less likely it was for a patient to enter into remission. There was a continuous increase in likelihood of achieving a first remission from the beginning of disease up to 30 years of disease duration, when it reached 70%. Patients who achieved remission had increased survival, independently of the effect of other disease manifestations that cause increased mortality. We conclude that a significant proportion of patients with SLE, including those with severe organ involvement, may become symptom-free and in need of no more medication, perhaps indefinitely. Our findings support the notion that, in general, SLE is a more benign disease than previously considered.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Cloroquina/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/mortalidade , Modelos de Riscos Proporcionais , Indução de Remissão , Esteroides , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To determine prognostic factors for mortality in a cohort of 667 patients with systemic lupus erythematosus (SLE) including those variables associated with the presence of antiphospholipid antibodies (aPL) as well as antiphospholipid syndrome (APS) itself. METHODS: Analysis of the cohort under a nested case control design by means of Cox proportional hazards regression with and without stepwise method. RESULTS: During the 2039 person-years of followup, there were 49 deaths (cases). Thrombocytopenia, arterial occlusions, and hemolytic anemia were the aPL related manifestations that were associated with decreased survival in univariate analyses. The first 2 were also selected among risk factors for mortality in stepwise Cox multivariate analysis. The syndrome itself was also associated with increased mortality rates, independently of other variables. CONCLUSION: APS is among the variables that confer decreased survival on patients with SLE. This decreased survival is due to some (e.g., thrombocytopenia or arterial occlusions), but not all, of the manifestations of APS.
Assuntos
Síndrome Antifosfolipídica/complicações , Lúpus Eritematoso Sistêmico/complicações , Anemia Hemolítica/complicações , Arteriopatias Oclusivas/complicações , Estudos de Coortes , Humanos , Lúpus Eritematoso Sistêmico/mortalidade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida , Trombocitopenia/complicaçõesRESUMO
PURPOSE: Having observed a decrease in antiphospholipid antibodies (aPL) upon the development of nephrotic syndrome, as well as a negative association between nephrotic syndrome and secondary antiphospholipid syndrome, in patients with systemic lupus erythematosus (SLE), we sought to determine if this could be due to urinary loss of aPL and/or other factors. SUBJECTS AND METHODS: IgG and IgM aPL as well as other autoantibodies were studied by enzyme-linked immunosorbent assay with cardiolipin as antigen in serum and urine from six patients with SLE who had elevated serum aPL levels and developed nephrotic syndrome (cases). For controls, we studied: (1) three SLE patients with nephrotic syndrome but low aPL levels; (2) three patients with non-SLE nephrotic syndrome; (3) three SLE patients with high-titer aPL but no proteinuria; and (4) 10 healthy volunteers. RESULTS: We found urinary IgG, but no IgM, aPL in all cases and in one control from Group 2. Serum IgG aPL had gradually decreased after the development of nephrotic syndrome and had become normal. IgM aPL had also decreased in the four patients who had elevated levels, having reached normal levels at the time of the study in two. There was an apparent correlation between serum and urine IgG aPL levels but not between urinary IgG aPL and total proteinuria. By Farr's method, we found no urinary anti-DNA despite high serum titers in three cases. The two cases and one of the controls in Group 1 who had serum antibodies to extractable antigens also had these antibodies in the urine. CONCLUSION: Urinary loss of IgG aPL during nephrotic syndrome does not completely explain the reduction in serum aPL, since IgM also decreases. There could also be decreased synthesis and/or increased catabolism of immunoglobulins.
Assuntos
Autoanticorpos/análise , Imunoglobulina G/urina , Lúpus Eritematoso Sistêmico/imunologia , Síndrome Nefrótica/imunologia , Fosfolipídeos/imunologia , Adulto , Sangue , Feminino , Seguimentos , Humanos , Imunoglobulina G/análise , Isotipos de Imunoglobulinas/análise , Isotipos de Imunoglobulinas/urina , Imunoglobulina M/análise , Imunoglobulina M/urina , Lúpus Eritematoso Sistêmico/urina , Síndrome Nefrótica/patologia , Síndrome Nefrótica/urina , Proteinúria/imunologia , Proteinúria/urinaRESUMO
Ten percent of 667 consecutive systemic lupus erythematosus (SLE) patients were considered to have definite antiphospholipid syndrome (aPLS) because they had two or more antiphospholipid (aPL)-related clinical manifestations and aPL titers more than 5 SD above the mean of normal controls. Another 14% had either one aPL-related manifestation but high titers of the antibody or two manifestations and low aPL titers (probable aPLS). One fourth of the patients had no manifestations but high titers, one manifestation and low titers, or two or more manifestations and negative aPL titers ("doubtful" aPLS); the other half were considered negative for aPLS. In patients with high-titer aPL, the number of aPL-related manifestations was influenced by disease duration and number of pregnancies, indicating potential mobility of category with time or with risk of recurrent pregnancy loss. Patients with two or more manifestations but variable aPL levels differed in immunosuppressive treatment and in the number of times they had been tested, indicating potential mobility of category with lower treatment and/or further aPL testing. Patients with definite aPLS had increased risk of cutaneous vasculitis, peripheral neuropathy, seizures, psychosis, transient ischemic attacks, and leukopenia. In 11 of 52 SLE patients with definite aPLS the initial manifestation was related to aPL, and in 16 it concurred with an unrelated one. Only two patients fulfilled criteria for aPLS before having other evidence of SLE. The authors conclude that aPLS occurring within SLE is part of the disease rather than an associated condition and propose the use of definite and probable classification categories. These criteria, with appropriate follow-up and clinical and serological exclusion clauses for potential primary conditions, could also be applied to primary aPLS.