RESUMO
Headache is a common finding in the postpartum period, caused by a spectrum of different conditions. Most headaches in the postpartum period are self-limiting and benign in etiology, but there are some potentially serious causes to be considered. We disclose two cases of postpartum headache, initially considered as post-dural puncture headache (PDPH), that evolved into a harmful condition and showed that an expanded differential diagnosis for headache in the postpartum is mandatory, requiring a high level of attention from health professionals. In fact, a careful examination of the medical history, physical examination, and the recognition for the need for early neuroradiological imaging should increase diagnostic accuracy.
Assuntos
Cefaleia Pós-Punção Dural , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Humanos , Cefaleia Pós-Punção Dural/diagnóstico , Cefaleia Pós-Punção Dural/etiologia , Período Pós-PartoRESUMO
The promotion and progression of carcinogenesis are susceptible to nutritional interventions aimed at counteracting cancer development. Lipid metabolism is essential in the onset and progression of tumors and for cancer cell survival. In this study, we tested the effects of diets enriched with natural compounds, such as olive oil and salmon oil, in mice that spontaneously develop intestinal polyps (Apc(Min/+) mice). For this purpose, we evaluated polyp number and volume, intestinal mucosa proliferation/apoptosis, estrogen receptors (ERs) expression, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase gene expression and enzymatic activity. Compared with the standard diet, the salmon oil-enriched diet, containing a high percentage of omega-3 polyunsaturated fatty acids, and, to a lesser extent, olive oil-enriched diet reduced polyp number and volume through a reduction of proliferation and a marked proapoptotic effect. These biological effects were mediated by an inhibition of fatty acid synthase and HMGCoA reductase gene expression and activity and an increase of ERß/ERα ratio. Our findings suggest that a proper dietary lifestyle could contribute to primary cancer prevention.
Assuntos
Proteína da Polipose Adenomatosa do Colo/fisiologia , Apoptose , Neoplasias do Colo/prevenção & controle , Ácidos Graxos Ômega-3/uso terapêutico , Pólipos Intestinais/prevenção & controle , Óleos de Plantas/administração & dosagem , Animais , Western Blotting , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Mucosa Intestinal/metabolismo , Pólipos Intestinais/metabolismo , Pólipos Intestinais/patologia , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microssomos/enzimologia , Azeite de Oliva , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor fas/genética , Receptor fas/metabolismoRESUMO
Anisakis simplex is a parasite that, if present in uncooked and contaminated saltwater fish, can invade the human gut. Two different clinical situations are recognized: the first, known as a gastrointestinal disease, varying from an asymptomatic episode to vomiting and diarrhea, and the second, classified as an adverse reaction to food, characterized by a wide spectrum of allergic reactions like rhinitis, conjunctivitis, or even anaphylaxis causing hypotension and/or shock. The intestinal epithelium, the major defense system against external molecules, represents an open gate for toxins and allergens if its protective function is compromised. Previous data have demonstrated a strict relationship between an altered intestinal permeability (I.P.) and worsening of the clinical manifestations in patients with adverse reactions to the food. In this article we evaluated the sensitization to A. simplex among patients who referred clinical symptoms of allergy. All subjects underwent commonly used alimentary skin prick test for food allergens, to which Ani s1, an A. simplex allergen, was added. In addition, in A. simplex-sensitized subjects, I.P. was determined upon their enrolment to the study (time 0) and after 6 months of consuming a raw fish-free diet (time 6). Five hundred and forty subjects were screened, and 170 had a positive skin prick test, 87 (51.2%) of whom were positive to Ani s1. Increased I.P. was evidenced in A. simplex-sensitized subjects with worse clinical symptoms, which receded after 6 months' elimination of raw seafood. With our data we demonstrated that the alimentary habit to eat raw fish represents a high risk for the integrity of the intestinal mucosa, and we suggest that this pathological situation may constitute an ideal, under-estimated, open gate for molecules that predispose to other, more important pathologies.
Assuntos
Anisaquíase/fisiopatologia , Anisakis/imunologia , Hipersensibilidade Alimentar/fisiopatologia , Doenças Transmitidas por Alimentos/fisiopatologia , Intestinos/imunologia , Intestinos/fisiopatologia , Adolescente , Adulto , Idoso , Alérgenos/imunologia , Animais , Anisaquíase/sangue , Anisaquíase/diagnóstico , Anisaquíase/dietoterapia , Culinária , Diagnóstico Diferencial , Dieta , Feminino , Peixes/parasitologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/imunologia , Parasitologia de Alimentos , Doenças Transmitidas por Alimentos/sangue , Doenças Transmitidas por Alimentos/diagnóstico , Doenças Transmitidas por Alimentos/dietoterapia , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Permeabilidade , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/parasitologia , Índice de Gravidade de Doença , Testes Cutâneos , Adulto JovemRESUMO
Mitochondrial DNA (mt-DNA) disorders and abnormal regulation of nuclear-derived proteins devoted to the cross-talk between the two cellular genomes have recently interested researchers in the field of neuromuscular diseases. We have identified, isolated and sequenced a new gene, augmenter of liver regeneration (ALR) that stimulates in vivo hepatocyte proliferation and up-regulates mt-DNA expression and ATP production. ALR protein (Alrp) is mainly located, in rat, in the mitochondrial inter-membrane space and its mRNA is particularly abundant in brain, muscle, testis and liver, tissues whose activity is mostly dependent on mitochondrial metabolism. Studies on rat Alrp sequence revealed the presence of homologous amino-acid sections into proteins derived from mouse, human, Drosophyla, plants and even DNA viruses. In this article, we evaluated ALR expression in normal human muscular tissues, both as protein and as mRNA. The data, obtained by molecular biology, immunohistochemistry and electron microscopy, demonstrated that: (i) Alrp and ALR mRNA are present in human muscular tissue; (ii) Alrp is particularly expressed in muscular fibres rich in mitochondria; (iii) Alrp is localized in the mitochondrial inter-membrane space or associated to mitochondrial cristae; and (iv) in subjects younger then 35 years of age, ALR mRNA expression is different between male and female subjects. In conclusion, the present data set Alrp, as a factor associated with mitochondria also in human tissue, call for future studies aimed at establishing Alrp as an important factor involved in the molecular events that trigger neuromuscular diseases.
Assuntos
Redutases do Citocromo/análise , Regeneração Hepática/fisiologia , Músculo Esquelético/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Redutases do Citocromo/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/química , Membranas Mitocondriais/química , Proteínas Mitocondriais/análise , Oxirredutases atuantes sobre Doadores de Grupo Enxofre , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adulto JovemRESUMO
BACKGROUND AND AIMS: Augmenter of Liver Regeneration is a protein encoded by the Growth Factor Erv1-Like gene. Its biological properties are crucial for cell survival since knock-out mice for Growth Factor Erv1-Like gene do not survive. In this study, we injected hepatotropic adenoviral particles harboring oligonucleotide sequences against Growth Factor Erv1-Like gene into 70% partially hepatectomized rats and studied the effect of gene silencing on the progression liver regeneration. METHODS: Partially hepatectomized rats were divided into three groups of animals and, before surgery, received either phosphate buffer saline, or adenoviral particles alone or adenoviral particles harboring the oligonucleotide silencing sequence. In each group, rats were sacrificed at 12, 24 and 48 h after surgery. Liver tissues were collected to analyze the expression of Augmenter of Liver Regeneration, Bax, Bcl-2 and activated Caspase-9 and -3, as well as hepatocyte proliferation and apoptosis, polyamines levels and histological and ultrastructural features. RESULTS: Growth Factor Erv1-Like gene silencing reduced the compensatory hepatocellular proliferation triggered by surgery through (i) the reduction of polyamines synthesis, hepatocyte proliferation and anti-apoptotic gene expression and (ii) the increase of pro-apoptotic gene expression and caspase activation. CONCLUSIONS: For the first time, using a technique of gene silencing in vivo, our results demonstrate that Growth Factor Erv1-Like gene knock-down, i.e., the lack of Augmenter of Liver Regeneration, modifies the expression of genes involved in cell apoptosis and inhibits early phase of DNA synthesis. As a consequence, a promotion of cell death and a reduction of cell proliferation occurs.
Assuntos
Apoptose/genética , Hepatopatias/genética , Regeneração Hepática/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/biossíntese , Proteínas/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Inativação Gênica , Hepatectomia , Humanos , Hepatopatias/terapia , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , RatosRESUMO
Mitochondria-related myopathies (MM) are a group of different diseases defined by a varying degree of dysfunctions of the mitochondrial respiratory chain which leads to reactive oxygen species (ROS) generation followed by oxidative stress and cellular damage. In mitochondrial myopathy muscle tissue an overexpression of antioxidant enzymes has been documented probably as an attempt to counteract the free radical generation. We previously documented, in human non-pathological muscle fibres, the expression of the augmenter of liver regeneration (ALR), a sulfhydryl oxidase enzyme, whose presence is related to the mitochondria; indeed it has been demonstrated that ALR mainly localizes in the mitochondrial inter-membrane space. Furthermore we reported, in different experimental models, in vivo and in vitro, the anti-apoptotic and anti-oxidative capacities of ALR, achieved by up-regulating Bcl-2 anti-apoptotic family factors and the anti-apoptotic/anti-oxidative secretory isoform of clusterin (sClu). With the present study we aimed to determine ALR, Bcl-2 protein, clusterin and ROS expression in muscle tissue biopsies from MM-affected patients. Non-pathological muscle tissue was used as control. Enzymatic, histochemical, immunohistochemical and immune electron microscopy techniques were performed. The data obtained revealed in MM-derived muscle tissue, compared to non-pathological tissue, the over-expression of ROS, ALR and Bcl-2 and the induction of the nuclear, pro-apoptotic, isoform of clusterin (nCLU).
Assuntos
Redutases do Citocromo/metabolismo , Miopatias Mitocondriais/metabolismo , Miopatias Mitocondriais/patologia , Músculos/patologia , Estresse Oxidativo , Substâncias Protetoras/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Clusterina/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Imunofluorescência , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Modelos Biológicos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Músculos/metabolismo , Músculos/ultraestrutura , Oxirredutases atuantes sobre Doadores de Grupo Enxofre , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
Augmenter of Liver Regeneration (Alrp) enhances, through unknown mechanism/s, hepatocyte proliferation only when administered to partially hepatectomized (PH) rats. Liver resection, besides stimulating hepatocyte proliferation, induces reactive oxygen species (ROS), triggering apoptosis. To clarify the role of Alrp in the process of liver regeneration, hepatocyte proliferation, apoptosis, ROS-induced parameters and morphological findings of regenerating liver were studied from PH rats Alrp-treated for 72 h after the surgery. The same parameters, evaluated on regenerating liver from albumin-treated PH rats, were used as control. The results demonstrated that Alrp administration induces the anti-apoptotic gene expression, inhibits hepatocyte apoptosis and reduces ROS-induced cell damage. These and similar data from in vitro studies and the presence of 'Alrp homologous proteins' in viruses as well as in mammals (i) allow to hypothesize that Alrp activity/ies may not be exclusive for regenerating liver and (ii) suggest the use of Alrp in the treatment of oxidative stress-related diseases.
Assuntos
Apoptose/fisiologia , Clusterina/metabolismo , Hepatócitos/metabolismo , Regeneração Hepática/fisiologia , Fígado/citologia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Animais , Clusterina/efeitos dos fármacos , Hepatectomia , Hepatócitos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Masculino , Estresse Oxidativo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/administração & dosagem , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/sangue , Ratos , Ratos Endogâmicos F344 , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
Our previous research and a comprehensive meta-analysis of data from the literature on epitope mapping has revealed that the B cell epitope repertoire is allocated to rare peptide motifs, i.e., antigenic peptide sequences endowed with a low level of similarity to the host proteome. From a clinical point of view, low-similarity peptides able to evoke an immune response appear to be of special interest for the rational design of vaccines for poorly treatable diseases such as hepatitis-C virus (HCV) infection. Indeed, low similarity peptides would guarantee the highest specificity and lowest cross-reactivity, i.e., effectiveness without adverse side-effects. In this study, aimed at gaining further information for the development of effective anti-HCV peptide-based vaccines, the HCV epitopes recognized by human antibodies and currently catalogued in the Immune Epitope Data Base (IEDB) were examined for pentamer sequence similarities to the human proteome. We report that the analyzed HCV determinants are characterized by the presence of fragment absent from (or scarcely represented in) human proteins. These data confirm the low-similarity hypothesis, according to which a low-similarity to the host proteome defines the nonself character of microbial antigens and modulates peptide immunogenicity. Moreover, this study indicates a concrete and safe immunotherapeutic approach which might be used in a universal anti-HCV vaccine.
RESUMO
BACKGROUND: Hydrogen peroxide, as other reactive oxygen species (ROS) produced during redox processes, induces lipid membrane peroxidation and protein degeneration causing cell apoptosis. ROS are recently considered as messengers in cell signalling processes, which, through reversible protein disulphide bridges formation, activate regulatory factors of cell proliferation and apoptosis. Disulphide bridges formation is catalysed by sulphydryl oxidase enzymes. AIM: The neuroprotective effect of ALR protein (Alrp), a sulphydryl oxidase enzyme, on H(2)O(2)-induced apoptosis in SH-SY5Y cells has been evaluated. METHODS: Cell viability, flow cytometric evaluation of apoptotic cells, fluorescent changes of nuclear morphology, immunocytochemistry Alrp detection, Western blot evaluation of mitochondrial cyt c release and mitochondrial swelling were determined. RESULTS: Alrp prevents the H(2)O(2)-induced cell viability loss, apoptotic cell death and mitochondrial swelling in SH-SY5Y cells in culture. CONCLUSIONS: The data demonstrate that Alrp improves SH-SY5Y cells survival in H(2)O(2)-induced apoptosis. It is speculated that this effect could be related to the Alrp enzymatic activity.