RESUMO
AIM: Evaluate the development of multiple complications, their interactions, and common mechanisms in the same individual with T2D. MATERIAL AND METHODS: 4-week-old male C57BL/6J mice were divided into: control (n = 6) and T2D (n = 6). T2D was induced through a high-carbohydrate-diet and low doses of streptozotocin. T2D was validated by metabolic parameters. Diabetic neuropathy was evaluated by mechanical and thermal sensitivity tests. We performed a histopathological analysis of the heart, kidney, liver, and parotid salivary glands and changes in bone microarchitecture by µCT. We calculated the relative risk (RR), odd ratios (OR) and Pearson correlation coefficients between the different complications and metabolic features. RESULTS: T2D mice have cardiomyopathy, neuropathy, nephropathy, liver steatosis and fibrosis, structural damage in parotid salivary glands, and bone porosity. RR analysis shows that all complications are interrelated by hyperglycaemia, insulin resistance, obesity, and systemic inflammation. CONCLUSIONS: T2D mice develop multiple complications simultaneously, which are related to each other, and this is associated with metabolic alterations. Our findings open up new approaches for the study and new therapeutic approaches of the pathophysiology of T2D and its complications.
Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Complicações do Diabetes/complicações , Modelos Animais de DoençasRESUMO
Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.
Assuntos
Antineoplásicos/normas , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE AND DESIGN: Sodium caseinate (CasNa) induces differentiation and M-CSF production in mouse band granulocytes in vitro; however, it is not yet known if this molecule can also induce the proliferation and activation of the granulocyte lineage in vivo. In this work we evaluated the induction in vivo of granulopoiesis and the activation of granulocytes in mice treated with CasNa. MATERIAL OR SUBJECTS: BALB/c male mice 8-12 weeks old were used. TREATMENT: The animals were inoculated intraperitoneally with 1 ml of CasNa (10% in PBS p/v) four times (every 48 h). METHODS: Granulocyte proliferation was evaluated by flow cytometry; activation was evaluated by phagocytic indices. The cytokine was measured using an ELISA assay. RESULTS: We show that CasNa increased bone marrow granulopoiesis percentage (38.35 ± 10.88 vs. 64.94 ± 34.14 BrdU+/Gr-1+ cells) and the granulocytes generated presented increased phagocytic indices (0.3 ± 0.1 vs. 0.6 ± 0.11, p < 0.05). We also show that G-CSF (974 ± 411 vs. 3189 ± 350 pg/ml, p < 0.05) and GM-CSF increased in serum, but only G-CSF in bone marrow plasma. CONCLUSIONS: CasNa induces granulopoiesis with functional granulocytes, suggesting that this molecule could be an innate immune system activator.
Assuntos
Caseínas/farmacologia , Granulócitos/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Mielopoese/efeitos dos fármacos , Animais , Candida albicans , Proliferação de Células/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Granulócitos/citologia , Granulócitos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacosRESUMO
Prokaryotes have developed multiple strategies to survive phage attack and invasive DNA. Recently, a novel genetic program denominated the CRISPR/Cas system was demonstrated to have a role in these biological processes providing genetic immunity. This defense mechanism is widespread in the Archaea and Bacteria, suggesting an ancient origin. In the last few years, progress has been made regarding the functionality of the CRISPR/Cas system; however, many basic aspects of the system remain unknown. For instance, there are few studies about the conditions and regulators involved in its transcriptional control. In this work, we analyzed the transcriptional organization of the CRISPR/Cas system as well as the positive and negative regulators involved in its genetic expression in Salmonella enterica serovar Typhi. The results obtained show that in S. Typhi the CRISPR/Cas system is a LeuO-dependent operon silenced by the global regulator LRP, in addition to the previously known nucleoid-associated protein H-NS; both LRP and H-NS bind upstream and downstream of the transcriptional start site of casA. In this study, relevant nucleotides of the casA regulatory region that mediate its LeuO transcriptional activation were identified. Interestingly, specific growth conditions (N-minimal medium) were found for the LeuO-independent expression of the CRISPR/Cas system in S. Typhi. Thus, our work provides evidence that there are multiple modulators involved in the genetic expression of this immune system in S. Typhi IMSS-1.
Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteína Reguladora de Resposta a Leucina/metabolismo , Óperon , Salmonella typhi/genética , Fatores de Transcrição/metabolismo , Análise Mutacional de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica , Análise de Sequência de DNA , Deleção de SequênciaRESUMO
It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.
Assuntos
Arsênio/efeitos adversos , Indígenas Sul-Americanos , Estado Nutricional , Dermatopatias/induzido quimicamente , Abastecimento de Água , Adolescente , Adulto , Criança , Chile , Dieta , Exposição Ambiental , Feminino , Humanos , Incidência , Masculino , Dermatopatias/epidemiologiaRESUMO
Pseudomonas aeruginosa produces rhamnolipids which are tenso-active compounds with potential industrial and environmental applications. There are two main types of rhamnolipids produced in liquid cultures, rhamnosyl-beta-hydroxydecanoyl-beta-hydroxydecanoate (mono-rhamnolipid) and rhamnosyl-rhamnosyl-beta-hydroxydecanoyl-beta-hydroxyd ecanoate (di-rhamnolipid). In this work we report the selective isolation of a rhamnolipid deficient mutant (IBT8), which does not accumulate mono-rhamnolipid while still producing di-rhamnolipid. IBT8 was selected after random mutagenesis with Tn501; yet, its mono-rhamnolipid deficiency was found associated neither with its Tn501 insertion nor with a possible alteration in the rhlABRI genes for rhamnosyl-transferase 1 synthesis. Different possibilities to explain IBT8 phenotype are discussed.
Assuntos
Decanoatos/metabolismo , Glicolipídeos/biossíntese , Pseudomonas aeruginosa/metabolismo , Ramnose/análogos & derivados , Proteínas de Bactérias/genética , Genes Bacterianos , Hexosiltransferases/genética , Mutagênese Insercional , Mutação , Pseudomonas aeruginosa/genética , Ramnose/metabolismoRESUMO
The present study was carried out with the objective to learn about the effect of the nixtamalization process of corn on the content of phytic acid and availability of iron in the lime-cooked corn. For the study, lots of corn with 0, 0.4, 0.8 and 1.20% of lime on the basis of corn weight, in water in the ratio of 3 to 1, and cooking times at each level of lime of 55, 65 and 75 minutes, were processed. Half of the treatments were not soaked after cooking, while the other half were soaked in the cooking solution for a 12-hour period. Statistical analysis of the data and correlations calculated showed that the phytic acid content decreased significantly during the nixtamalization process, affected by the cooking time and the level of lime used, reaching levels of reduction of around 35%. Both the ionizable iron and calcium level increased up to 52-77% and 400-478% respectively. The amount of calcium present in the cooked corn as the result of the lime cooking process, is significantly higher in comparison with the phytic acid content, which may be easily saturated and thus, unavailable to bind iron. An inverse relationship was found between phytic acid and bioavailable iron and its absorption percentage. On the other hand, soaking time did not significantly affected the phytic acid and available iron, although it contributed to a slightly higher Ca accumulation. The amount of ionizable iron was higher at higher levels of lime, which suggested that the nixtamalization process would favor the biological utilization of iron in lime-cooked corn and provide calcium to the diet.
Assuntos
Cálcio/análise , Grão Comestível/química , Manipulação de Alimentos , Ferro/análise , Ácido Fítico/análise , Análise de Variância , Fatores de TempoRESUMO
A specific antiserum to Candida albicans serotype A was prepared absorbing a total antiserum with Candida albicans serotype B cells. This specific antiserum was used for serotyping C. albicans strains obtained from patients in different hospitals of Havana City, Cuba. Two hundred strains (95.2%) were serotype A, the remaining 10 (4.8%) were serotype B. Results were also correlated with strains isolated from the specimen origin, sex and race of the patient. The usefulness of this specific antiserum to determine C. albicans serotypes and its therapeutic value are pointed out.
Assuntos
Candida albicans/classificação , Candida albicans/isolamento & purificação , Cuba , Feminino , Humanos , Masculino , Sorotipagem/métodosRESUMO
Con el antecedente del hallazgo en el estado de Oaxaca de casos agudos de enfermedad de Chagas detectados por la Comisión Nacional para la Erradicación del Paludismo y con objeto de poner de manifiesto la importancia de esta parasitosis en dicho estado, se llevó a cabo el presente estudio por medio de un muestreo de la población humana en cuatro municipios, con un total de 1.210 sueros procesados mediante la técnica de hemaglutinación indirecta. Los resultados dieron 158 negativos y 1.052 reactores con anticuerpos de los que 111 se consideraron positivos. Llama la atención la seropositividad detectada en el grupo de los escolares
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Doença de Chagas/epidemiologia , México , Testes de HemaglutinaçãoAssuntos
Doença de Chagas/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Testes de Hemaglutinação/métodos , Humanos , Lactente , Masculino , MéxicoAssuntos
Cisticercose/transmissão , Contaminação de Alimentos , Animais , Cisticercose/veterinária , Cysticercus/crescimento & desenvolvimento , Cysticercus/isolamento & purificação , Manipulação de Alimentos , Humanos , Legislação sobre Alimentos , Carne/efeitos adversos , México , Suínos/parasitologia , Doenças dos Suínos/transmissãoRESUMO
Con base en la hipotesis de que existe otro mecanismo de infeccion en la cisticercosis que actua juntamente con el fecalismo en la transmision de esta importante enfermedad, y que consiste en la ingestion de formas embrionarias precisticercosas en la carne de cerdo cisticercosa insuficientemente cocida, se presentan los resultados iniciales de esta investigacion, consistentes en el hallazgo de formas intermedias entre embrion hexacanto y cisticerco en preparados de carne macerada de cerdo con solucion salina y cortes de musculo; estas formas sirvieron para inocular cerdos sanos comprobados con serologia para cisticercosis, los cuales volvieron a desarrollar las formas, aunque no evolucionarion hasta la de cisticercos. Posteriormente uno de los cerdos se inmunodeprimio con corticoesteroides y desarrollo un cisticerco completamente formado en globo ocular, y otros en distintos grados de evolucion en el musculo esqueletico;los resultados mencionados se completan con fotografias de microscopia optica y electronica
Assuntos
Cisticercose , CysticercusRESUMO
Se realizo un estudio de la frecuencia de las parasitosis intestinales en colonias comprendidas en dos delegaciones del area sur del Distrito Federal por medio de examenes coproparasitoscopicos cualitativos con el metodo de Faust. Se obtuvieron frecuencia de protozoosis y helmintiasis inse senalan en cuadros. Se hacen comentarios de los resultados obtenidos en esta encuesta epidemiologica.encuesta epidemiologica