RESUMO
Non-proteincoding transcripts bearing 200 base pairs known as long non-coding RNAs (lncRNAs) play a role in a variety of molecular mechanisms, including cell differentiation, apoptosis and metastasis. Previous studies have suggested that frequently dysregulated lncRNAs play a crucial role in various aspects of cancer metastasis. Metastasis is the main leading cause of death in cancer. The role of lncRNAs in different stages of metastasis is the subject of this review. Based on in vitro and in vivo investigations on metastasis, we categorized lncRNAs into distinct stages of metastasis including angiogenesis, invasion, intravasation, survival in circulation, and extravasation. The involvement of lncRNAs in angiogenesis and invasion has been extensively studied. Here, we comprehensively discuss the role and functions of these lncRNAs with a particular focus on the molecular mechanisms.
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Neoplasias , RNA Longo não Codificante , Apoptose , Humanos , Neoplasias/genética , Neovascularização Patológica , RNA Longo não Codificante/genéticaRESUMO
Background: The evidence regarding the prognostic impact of a positive circumferential resection margin (CRM) in oesophageal cancer is conflicting, and there is global variability in the definition of a positive CRM. The aim of this study was to determine the impact of a positive CRM on survival in patients undergoing oesophagectomy for oesophageal cancer. Methods: A systematic review and meta-analysis was performed. PubMed and Embase databases were searched for articles to May 2018 examining the effect of a positive CRM on survival. Cohort studies written in English were included. Meta-analyses of univariable and multivariable hazard ratios (HRs) were performed using both Royal College of Pathologists (RCP) and College of American Pathologists (CAP) criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale. Egger regression, and Duval and Tweedie trim-and-fill statistics were used to assess publication bias. Results: Of 133 studies screened, 29 incorporating 6142 patients were finally included for analysis. Pooled univariable HRs for overall survival in patients with a positive CRM were 1·68 (95 per cent c.i. 1·48 to 1·91; P < 0·001) and 2·18 (1·84 to 2·60; P < 0·001) using RCP and CAP criteria respectively. Subgroup analyses demonstrated similar results for patients by T category, neoadjuvant therapy and tumour type. Pooled HRs from multivariable analyses suggested that a positive CRM was independently predictive of a worse overall survival (RCP: 1·41, 1·21 to 1·64, P < 0·001; CAP: 2·37, 1·60 to 3·51, P < 0·001). Conclusion: A positive CRM is associated with a worse prognosis regardless of classification system, T category, tumour type or neoadjuvant therapy.
Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/mortalidade , Idoso , Regras de Decisão Clínica , Neoplasias Esofágicas/mortalidade , Esofagectomia/métodos , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
Phosphopantetheine adenylyltransferase (PPAT, EC. 2.7.7.3) catalyzes an essential step in the reaction that transfers an adenylyl group from adenosine tri phosphate (ATP) to 4'-phosphopantetheine (pPant) yielding 3'- dephospho-coenzyme A (dPCoA) and pyrophosphate (PP) in the coenzyme A (CoA) biosynthesis pathway. The enzyme PPAT from Acinetobacter baumannii (AbPPAT) was cloned, expressed and purified. The binding studies of AbPPAT were carried out with two compounds, trisodium citrate (TSC) and l-ascorbic acid (LAA, vitamin-C) using fluorescence spectroscopic (FS) and surface Plasmon resonance (SPR) methods. Both methods provided similar values of dissociation constants for TSC and LAA which were of the order of 10-8â¯M and 10-5â¯M respectively. The computer aided docking studies indicated fewer interactions of LAA with AbPPAT as compared to those of TSC. The freshly purified samples of AbPPAT were crystallized. The crystals of AbPPAT were soaked in the solutions containing TSC and LAA. However, the crystals of the complex of AbPPAT with LAA did not diffract well and hence the structure of the complex of AbPPAT with LAA could not be determined. On the other hand, the crystals of the complex of AbPPAT with TSC diffracted well and the structure was determined at 1.76â¯Å resolution. It showed that TSC bound to AbPPAT at the ATP binding site and formed several intermolecular contacts including 12 hydrogen bonds. The results of binding studies for both TSC and LAA and the structure of the complex of AbPPAT with TSC clearly indicated a potential role of TSC and LAA as antibacterial agents.
Assuntos
Acinetobacter baumannii/enzimologia , Nucleotidiltransferases/química , Nucleotidiltransferases/metabolismo , Acinetobacter baumannii/química , Acinetobacter baumannii/genética , Ácido Ascórbico/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Clonagem Molecular , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Nucleotidiltransferases/genética , Ligação Proteica , Citrato de Sódio/metabolismo , Espectrometria de Fluorescência , Ressonância de Plasmônio de SuperfícieRESUMO
Bovine tropical theileriosis caused by Theileria annulata is an overwhelming haemoprotozoan tick-borne disease in taurine and cross-bred cattle in Punjab, India. However, there seems to be no report from India of cutaneous nodules associated with the disease. This report describes a five-year-old cross-bred cow presented to a university clinic with a history of fever, inappetence and malaise for the past six to seven days. Clinical examination revealed normal vital parameters, pale mucous membranes, mild enlargement of the prescapular lymph nodes and multiple subcutaneous nodular masses (2-4 cm) on the neck and abdomen. Haematology revealed mild anaemia and leucopenia with 48% neutrophils, 48% lymphocytes and 4% eosinophils. Romanowsky-stained smears of fineneedle aspiration biopsy samples from swollen lymph nodes and subcutaneous masses showed an increased number of lymphoid cells, suggesting cutaneous lymphomatosis. However, a critical examination of the smears from subcutaneous nodules showed a large number of Koch's blue bodies in macrophages and lymphoblasts, and several piroplasms were also noticed within the red blood cells in lymph node smears. A peripheral blood smear revealed mild to moderate parasitaemia. Extracted DNA from the parasitologically positive blood sample was subjected to nested polymerase chain reaction (nPCR) using T. annulata speciesspecific primers encoding the 30-kiloDalton major sporozoite surface antigen. The desired 572-base pair amplified product of the nPCR was comparable to the positive control. This seems to be a rare case of T. annulata in an adult cross-bred cow, showing cutaneous nodular involvement.
La theilériose bovine tropicale est une maladie causée par le protozoaire Theileria annulata et transmise par les tiques, affectant massivement les populations de bovins et de bovidés métis au Pendjab (Inde). Il semble toutefois que la présence de nodules cutanés associés à la maladie n'y ait jamais été rapportée jusqu'à présent. Les auteurs décrivent le cas soumis à une clinique vétérinaire universitaire d'une vache métisse âgée de cinq ans qui présentait depuis six à sept jours un tableau fébrile accompagné d'une perte d'appétit et d'un affaiblissement général. À l'examen clinique, les paramètres vitaux étaient normaux mais une pâleur des membranes muqueuses a été observée, ainsi qu'un gonflement modéré des ganglions lymphatiques préscapulaires et de nombreuses masses nodulaires sous-cutanées (de 2 à 4 cm d'épaisseur) au niveau du cou et de l'abdomen. L'hématologie a mis en évidence une anémie modérée et une leucopénie, les leucocytes se répartissant en 48 % de neutrophiles, 48 % de lymphocytes et 4 % d'éosinophiles. Les frottis à coloration de Romanowsky d'une biopsie par aspiration à l'aiguille fine des ganglions lymphatiques enflés et des masses sous-cutanées ont fait apparaître une augmentation du nombre de cellules lymphatiques évocatrice d'une lymphomatose cutanée. Néanmoins, un examen critique des prélèvements de nodules sous-cutanés a permis de constater la présence d'un grand nombre de corps bleus de Koch dans les macrophages et les lymphoblastes ; en outre, de nombreux piroplasmes ont été trouvés dans les globules rouges des frottis de ganglions lymphatiques. Un frottis de sang périphérique a permis de quantifier la parasitémie comme étant de niveau faible à modéré. L'ADN extrait de l'échantillon de sang à parasitologie positive a été soumis à une amplification en chaîne par polymérase nichée (nPCR) utilisant des amorces spécifiques de T. annulata codant pour l'antigène majeur de surface (30 kDa) du sporozoïte. Le produit amplifié par nPCR de la séquence souhaitée de 572 paires de bases était similaire à celui de l'échantillon de contrôle positif. Il s'agit probablement d'un cas rare d'infection à T. annulata chez une vache adulte métisse présentant des manifestations nodulaires cutanées.
La teileriosis tropical bovina causada por Theileria annulata es una devastadora enfermedad hemoprotozoaria transmitida por garrapatas que afecta al ganado taurino e híbrido del Punjab (India). Ahora bien, en la India no parece haber ningún caso descrito de esta enfermedad que se acompañe de la presencia de nódulos cutáneos. Los autores describen el caso de una vaca de cinco años híbrida que fue presentado a una clínica universitaria con un cuadro de fiebre, pérdida de apetito y decaimiento en los seis a siete días anteriores. El examen clínico puso de manifiesto parámetros vitales normales, mucosas pálidas, leve hipertrofia de los ganglios linfáticos prescapulares y múltiples bultos subcutáneos de tipo nodular (2 a 4 cm) en cuello y abdomen. El análisis hematológico reveló una leve anemia y leucocitopenia, con un 48% de neutrófilos, un 48% de linfocitos y un 4% de eosinófilos. Tras proceder a una biopsia de ganglios inflamados y bultos subcutáneos por aspiración con aguja fina, el examen de frotis de estas muestras con tinción de Romanowsky reveló un número excesivo de células linfáticas, lo que parece apuntar a una linfomatosis cutánea. No obstante, al examinar más a fondo los frotis de nódulos subcutáneos se observó que macrófagos y linfoblastos albergaban un gran número de cuerpos azules de Koch. También se observaron varios piroplasmas dentro de los eritrocitos presentes en los frotis de ganglios linfáticos. Un frotis de sangre periférica reveló una parasitemia entre leve y moderada. El ADN extraído de esta muestra de sangre positiva fue sometido a una técnica de reacción en cadena de la polimerasa (PCR) anidada en la que se emplearon cebadores específicos de la especie T. annulata que codifican el antígeno de superficie principal de 30 kDa del esporozoíto. La deseada secuencia de 572 pares de bases amplificada por PCR resultó comparable con la correspondiente secuencia de la muestra positiva de control. Parece tratarse pues de un caso raro de infestación por T. annulata de una vaca adulta híbrida que se acompaña de nódulos cutáneos.
Assuntos
Doenças dos Bovinos/diagnóstico , Theileriose/diagnóstico , Animais , Bovinos , Feminino , Índia , Theileria annulataRESUMO
It is shown that water-in-oil microemulsions (m/e or µE) can produce BaCeO3 (BCO) and LaCoO3 (LCO) precursors. The nanoparticles (NPs) adsorb on AlOOH sols, in much the same way as Turkevich previously immobilised platinum group metal sols. BCO is active in CO and propane oxidation and NO removal under stoichiometric exhaust conditions, but LCO is a better oxidation catalyst. Activity was also seen when Ba,Ce and La,Co are inserted into/segregate at the surface of AlOOH/Al2O3. However, there is only formation of low levels of BCO, CAIO3 (CAO), LCO and LaAIO3 (LAO) perovskites, along with aluminates and separate oxides. The complexing of cations by AlOOH surface-held oxalate ions, albeit with different efficiencies, has also been explored. All three routes yield active catalysts with micro-domains of crystallinity; microemulsions produce the best defined perovskite NPs, but even those from surface segregation have higher turnover numbers than traditional Pt catalysts. Perovskite NPs may open up green chemistry for air pollution control that is consistent with a circular economy.
RESUMO
INTRODUCTION: Structure-based drug discovery offers a rational approach for the design and development of novel anti-mitotic agents which target specific proteins involved in mitosis. This strategy has paved the way for development of a new generation of chemotypes which selectively interfere with the target proteins. The interference of these anti-mitotic targets implicated in diverse stages of mitotic cell cycle progression culminates in cancer cell apoptosis. AREAS COVERED: This review covers the various mitotic inhibitors developed against validated mitotic checkpoint protein targets using structure-based design and optimization strategies. The protein-ligand interactions and the insights gained from these studies, culminating in the development of more potent and selective inhibitors, have been presented. EXPERT OPINION: The advent of structure-based drug design coupled with advances in X-ray crystallography has revolutionized the discovery of candidate lead molecules. The structural insights gleaned from the co-complex protein-drug interactions have provided a new dimension in the design of anti-mitotic molecules to develop drugs with a higher selectivity and specificity profile. Targeting non-catalytic domains has provided an alternate approach to address cross-reactivity and broad selectivity among kinase inhibitors. The elucidation of structures of emerging mitotic drug targets has opened avenues for the design of inhibitors that target cancer.
Assuntos
Antimitóticos/farmacologia , Desenho de Fármacos , Mitose/efeitos dos fármacos , Antimitóticos/química , Apoptose/efeitos dos fármacos , Cristalografia por Raios X , Descoberta de Drogas/métodos , Humanos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
The present study has been designed to investigate the potential of rifampicin [Pregnane X receptors (PXR) agonist] in experimental dementia. Aluminum chloride (AlCl3) [100mg/kg, p.o. for 42days] was administered to Wistar rats (n=6) to induce dementia. Morris water maze (MWM) test was used to assess learning and memory and rota rod test was used to assess locomotor activity of the animals. A battery of biochemical tests and histopathological evaluation using hematoxylin and eosin (H&E) and Congo Red stains were performed at the end of the study. AlCl3-treated rats demonstrated impaired cognition and locomotor activity on MWM apparatus and rota rod test, respectively. These animals exhibited a significant rise in acetylcholinesterase (AChE) activity (138±3.6), thiobarbituric acid reactive species (TBARS) level (15±1.6), nitrite (56±2.4) level and myeloperoxidase (MPO) activity (4.1±0.9) along with decline in reduced glutathione (GSH) level (22±1.3) in comparison to the control group (p<0.05). Further the H&E and Congo Red-stained cerebral cortex sections of AlCl3-treated rats indicated severe neutrophilic infiltration and amyloid deposition. Rifampicin-treated AlCl3-rats exhibited significant attenuation in memory deficits, biochemical parameters like AChE activity (33±1.4), TBARS level (4.1±1.0), nitrite level (64±2.6), MPO activity (3.6±1.0) and GSH level (53±2.4) along with improved histopathological alterations and locomotor activity when compared with AlCl3-treated rats (p<0.05). Combined administration of ketoconazole (a PXR antagonist) and rifampicin to AlCl3-treated animals reversed the rifampicin-induced protective effects. Therefore the results obtained from the study indicate a defensive role of rifampicin in memory dysfunction which may probably be due to its anti-cholinesterase, anti-oxidative, anti-inflammatory and amyloid lowering effects. Moreover the study speculates the potential of PXR in the pathophysiology of dementia which is subject to further evaluation.
Assuntos
Demência/tratamento farmacológico , Demência/fisiopatologia , Nootrópicos/farmacologia , Receptores de Esteroides/metabolismo , Rifampina/farmacologia , Acetilcolinesterase/metabolismo , Cloreto de Alumínio , Compostos de Alumínio , Amiloide/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Cloretos , Cognição/efeitos dos fármacos , Cognição/fisiologia , Demência/patologia , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Cetoconazol/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Neutrófilos/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Receptor de Pregnano X , Ratos Wistar , Receptores de Esteroides/antagonistas & inibidores , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
UNLABELLED: Multiple myeloma is a plasma cell neoplasm with a spectrum spanning from localized to disseminated forms, plasma cell infiltration of various organs, plasma cell leukemia and abnormal immunoglobulin chain deposition in the tissues. In the bone marrow, myeloma cells are seen, and vary from mature forms to immature pleomorphic, anaplastic cells. M component is found in the serum or urine in 99% of the patients. MATERIALS AND METHODS: This study included all cases of MM diagnosed at Dayanand Medical College and Hospital, Ludhiana, India from March 2003 to August 2004. Clinical findings were recorded and relevant investigations done. RESULTS: Multiple myeloma comprised 11.1% of all hematological malignancies. The mean age was 58.8 years. Bony pain was the most common presenting complaint. Other findings were anemia, raised serum creatinine levels, high serum lactate dehydrogenase and C-reactive protein levels. Plasmablastic morphology was seen in 60% patients with diffuse marrow involvement being the most common pattern. CONCLUSION: The percentage incidence of Multiple Myeloma, out of all hematological malignancies reported in our study is comparable with other studies as regards to the median age of incidence, male to female ratio, clinical presentation and percentage of M band positivity. However, a higher percentage of our patients had hypercalcemia, higher Serum Lactate Dehydrogenase levels and C -Reactive protein positivity and more lytic lesions. This corresponds with a higher tumor cell burden and a more frequent diffuse pattern of bone marrow involvement in our study group. This could be due to the smaller size of our study group, or due to late referral of patients to our tertiary care hospital.
RESUMO
Collagenase-3 (matrix metalloproteinase-13) is a metalloproteinase (MMP) that is associated with bone lesions and exhibits variable expression patterns in odontogenic cysts; it may play a role in regulating focal proliferation and maturation of jaw cyst epithelium. We studied the localization, staining intensity and distribution of collagenase-3 in 13 periapical granulomas with epithelium, 16 periapical granulomas without epithelium and 10 radicular cysts using archived formalin fixed, paraffin embedded tissues. A monoclonal antibody against human collagenase-3 was used to evaluate its expression. Immunohistochemical staining intensities of collagenase-3 in all periapical lesions were (-), 4 (10%); (+), 1 (3%); (++), 22 (56%) and (+++), 12 (31%); differences were not statistically significant. Immunohistochemical distribution of collagenase-3 in epithelial cells was (-), 17 (44%); (+), 17 (44%); (++), 5 (13%); in fibroblasts it was (-), 8 (20%); (+), 23 (59%); (++), 8 (21%); in plasma cells it was (-), 7 (18%); (+), 22 (56%); (++), 10 (26%); in macrophages it was (-), 7 (18%); (+), and 15 (38%); and (++), 17 (44%). Statistically significant differences were found in epithelial cells (p = 0.00) and fibroblasts (p = 0.02), whereas differences were not statistically significant for plasma cells and macrophages. Collagenase-3 may play a role in the conversion of a periapical granuloma with epithelium to radicular cyst. MMP's influence not only epithelial rest cell migration, but also invasion of various stromal cells into granulomatous tissue.
Assuntos
Epitélio/enzimologia , Metaloproteinase 13 da Matriz/metabolismo , Granuloma Periapical/enzimologia , Cisto Radicular/enzimologia , Movimento Celular/fisiologia , Epitélio/patologia , Humanos , Imuno-Histoquímica/métodos , Macrófagos/metabolismo , Granuloma Periapical/patologia , Cisto Radicular/patologiaRESUMO
AIMS: To assess accuracy of multidetector computed tomography (MDCT) and individual radiological signs in the diagnosis of anastomotic leaks. MATERIALS AND METHODS: Patients undergoing anterior resection with a stapled anastomosis over a 2 year period were identified. Electronic and clinical records of these patients were reviewed. Unenhanced and/or enhanced MDCT was performed with intravenous and/or per-rectal contrast medium and read by a radiologist blinded to the patients' clinical details to determine the sensitivity and specificity of specific findings at MDCT for identifying leaks. RESULTS: Seventeen percent (30/170) of the anterior resections were suspected to have an anastomotic leak. Ninety-three percent (28/30) of patients underwent MDCT. Seven point six percent (11+2/170) had a confirmed leak. Two patients underwent surgery without MDCT. A leak was confirmed by MDCT in 91% (10/11) of patients. The sensitivity, specificity, and positive and negative predictive values of MDCT in diagnosing a leak was 0.91, 1, 1, and 0.95, respectively. The sensitivity of peri-anastomotic air, peri-anastomotic collection, extravasation of rectal contrast medium, and staple line integrity was 0.81, 0.63, 0.54, and 0.72, respectively. Use of rectal contrast medium (8/11 cases) increased the subjective ease of diagnosis and was the only sign in one patient. CONCLUSIONS: Presence of peri-anastomotic air is a reliable marker of anastomotic leaks at MDCT. Leakage of rectal contrast medium is highly accurate and increases confidence of diagnosis. The appearance of the staple line itself is not accurate in assessing anastomotic integrity.
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Fístula Anastomótica/diagnóstico por imagem , Doenças do Colo/cirurgia , Tomografia Computadorizada por Raios X/métodos , Anastomose Cirúrgica , Meios de Contraste , Diatrizoato de Meglumina , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Grampeamento CirúrgicoAssuntos
Antimetabólitos Antineoplásicos/farmacocinética , Desoxicitidina/análogos & derivados , Adulto , Idoso , Antimetabólitos Antineoplásicos/sangue , Antimetabólitos Antineoplásicos/uso terapêutico , Estudos Cross-Over , Desoxicitidina/sangue , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapêutico , Feminino , Coração/efeitos dos fármacos , Coração/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Equivalência Terapêutica , Resultado do TratamentoRESUMO
Surveillance endoscopy with biopsy is the standard method to monitor intestinal transplant recipients but it is invasive, costly and prone to sampling error. Early noninvasive biomarkers of intestinal rejection are needed. In this pilot study we applied metabolomics to characterize the metabolomic profile of intestinal allograft rejection. Fifty-six samples of ileostomy fluid or stool from 11 rejection and 45 nonrejection episodes were analyzed by ultraperformance liquid chromatography in conjunction with Quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). The data were acquired in duplicate for each sample in positive ionization mode and preprocessed using XCMS (Scripps) followed by multivariate data analysis. We detected a total of 2541 metabolites in the positive ionization mode (mass 50-850 Daltons). A significant interclass separation was found between rejection and nonrejection. The proinflammatory mediator leukotriene E4 was the metabolite with the highest fold change in the rejection group compared to nonrejection. Water-soluble vitamins B2, B5, B6, and taurocholate were also detected with high fold change in rejection. The metabolomic profile of rejection was more heterogeneous than nonrejection. Although larger studies are needed, metabolomics appears to be a promising tool to characterize the pathophysiologic mechanisms involved in intestinal allograft rejection and potentially to identify noninvasive biomarkers.
Assuntos
Rejeição de Enxerto/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/transplante , Metabolômica , Transplante de Órgãos , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Criança , Pré-Escolar , Cromatografia Líquida , Feminino , Humanos , Ileostomia , Lactente , Intestino Delgado/cirurgia , Leucotrieno E4/metabolismo , Masculino , Espectrometria de Massas , Metabolômica/métodos , Pessoa de Meia-Idade , Projetos Piloto , Riboflavina/metabolismo , Ácido Taurocólico/metabolismo , Transplante Homólogo , Adulto JovemRESUMO
Heat shock proteins (HSP) are a group of physiologically-essential, highly-conserved proteins that are induced by heat shock, as well as by other environmental and pathophysiological stressors. The twentyseven kDa heat shock protein (Hsp27; HspB1) is highly expressed in tumor tissues of patients diagnosed with cancer and expression levels correlate with poor prognosis. HspB1 plays a dual role in cancer and promotes both cancer development by suppressing host anti-cancer response, such as apoptosis and senescence, and facilitates the enhanced expression of metastastic genes. HspB1-mediated protection from tumor cell apoptosis induced by chemotherapeutic drugs occurs through several mechanisms, including decreased production of reactive oxygen species, restoration of protein homeostasis and promotion of cell survival by protein folding, stabilization of actin-cytoskeleton, delayed release of cytochrome c from mitochondria and inhibition of activation of caspase-3. High levels of HSP expression affect tumor susceptibility to adjuvant cancer treatments, including chemotherapy, hyperthermia, and radiation. This review highlights the most recent findings and role of HspB1 in metastasis.
Assuntos
Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico/metabolismo , Metástase Neoplásica/patologia , Proteínas de Neoplasias/metabolismo , Envelhecimento/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Sobrevivência Celular , Humanos , Camundongos , Chaperonas Moleculares , Dobramento de Proteína , Espécies Reativas de Oxigênio/metabolismoRESUMO
A 10-year-old girl, who was referred with refractory epilepsy, had 1.5 years of episodic abnormal behavior. On examination, she also had hypertension and peripheral neuropathy. Hypoglycemia with correspondingly high insulin levels was documented during a confusional episode. MRI of the abdomen revealed an islet cell tumor in the body of the pancreas. One year after tumor excision, both the neuropathy and hypertension showed remarkable improvement. A final diagnosis of insulinoma with hypoglycemic axonal neuropathy and hypertension (reversed with tumor excision) was made. Insulinoma is the commonest cause of hyperinsulinemic hypoglycemia in adults, but is rare in childhood. To our knowledge, distal symmetrical motor-sensory axonal neuropathy has been described in only 40 patients, and hypertension has not been reported with insulinoma.
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Hipertensão/complicações , Doenças do Sistema Nervoso Periférico/complicações , Criança , Epilepsia/etiologia , Feminino , Humanos , Hipertensão/etiologia , Insulinoma/complicações , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/complicações , Doenças do Sistema Nervoso Periférico/etiologiaRESUMO
UNLABELLED: The final analysis of this 2-year, randomized, crossover study showed that postmenopausal women with osteoporosis were more adherent, compliant, and persistent with subcutaneous denosumab injections every 6 months than with once-weekly alendronate tablets. After receiving both treatments, women reported greater satisfaction with injectable denosumab and preferred it over oral alendronate. INTRODUCTION: Osteoporosis patients who are non-compliant or non-persistent with therapy may have suboptimal clinical outcomes. This 2-year, randomized, open-label, crossover study compared treatment adherence between subcutaneous denosumab, 60 mg every 6 months, and oral alendronate, 70 mg once weekly. METHODS: Postmenopausal women at 25 centers in the USA and Canada with bone mineral density T-scores -4.0 to -2.0 and no prior bisphosphonate use received alendronate then denosumab, or denosumab then alendronate, over successive 12-month periods. Adherence required both compliance (denosumab injections 6 months apart or ≥ 80% of alendronate tablets) and persistence (both denosumab injections or ≥ 2 alendronate doses in the last month and completion of the treatment period). RESULTS: Of the 250 women enrolled (124 alendronate, 126 denosumab), 221 entered the second year (106 denosumab, 115 alendronate). Denosumab was associated with less non-adherence than alendronate (first year, 11.9% vs 23.4%; second year, 7.5% vs 36.5%). Risk ratios for non-adherence, non-compliance, and non-persistence favored denosumab in both years (p < 0.05). Of 198 subjects expressing treatment preference, 183 (92.4%) preferred the injections over the oral therapy. BMD improved further when subjects received denosumab after alendronate and remained stable when they received alendronate after denosumab. CONCLUSION: Based on the final results of this crossover study after women had received each treatment for up to 1 year, postmenopausal women with osteoporosis were more adherent, compliant, and persistent with subcutaneous denosumab injections every 6 months than with once-weekly alendronate tablets and reported increased treatment preference and satisfaction with injectable denosumab over oral alendronate.
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Alendronato/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Preferência do Paciente , Administração Oral , Idoso , Alendronato/administração & dosagem , Alendronato/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Estudos Cross-Over , Denosumab , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Adesão à Medicação , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia , Ligante RANK/antagonistas & inibidores , Resultado do TratamentoRESUMO
Adenoviruses (AdV) are increasingly recognized as important viral pathogens in immunocompromised hosts. The clinical spectrum ranges from asymptomatic viremia to allograft dysfunction, and death. Most of the medical literature is on AdV infection in children and bone marrow transplant recipients. We report a case of AdV in an adult recipient in the first month after simultaneous kidney-pancreas transplant with thymoglobulin induction. This is a rare report of adenovirus infection after multiorgan transplant, and is unique in that it exhibited tissue invasive disease without any localizing signs or allograft dysfunction, while other cases in medical literature had invasive disease of the allograft with allograft dysfunction, failure, or death. In addition, this is the first report of a radiologic presentation of AdV nephritis.
Assuntos
Adenoviridae/patogenicidade , Infecções por Adenovirus Humanos/etiologia , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Complicações Pós-Operatórias , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Cardiovascular diseases are one of the leading causes of death in India. There is high prevalence of cardiovascular risk factors in urban Tamil Nadu. There are limited data on the prevalence of behavioral risk factors and overweight in rural Tamil Nadu. AIM: We estimated prevalence of behavioral risk factors, overweight and central obesity in a rural population in Tamil Nadu, India. SETTING AND DESIGN: We conducted a cross-sectional survey in 11 villages in Kancheepuram/Thiruvallur districts, Tamil Nadu. MATERIALS AND METHODS: Study population included 10,500 subjects aged 25-64 years. We collected data on behavioral risk factors and anthropometric measurements. Body mass index (BMI) was categorized using the classification recommended for Asians. Central obesity was defined as waist circumference ≥90 cm for men and ≥80 cm for women. We computed proportions for all risk factors and used trend chi-square to examine trend. RESULTS: Among the 10,500 subjects, 4927 (47%) were males. Among males, 1852 (37.6%) were current smokers and 3073 (62.4%) were current alcohol users. Among females, 840 (15.1%) were smokeless tobacco users. BMI was ≥23.0 kg/m 2 for 1618 (32.8%) males and 2126 (38.2%) females. 867 (17.6%) males and 1323 (23.7%) females were centrally obese. Most commonly used edible oil was palm oil followed by sunflower oil and groundnut oil. CONCLUSION: We observed high prevalence of tobacco use, alcohol use and central obesity in the rural population in Tamil Nadu. There is need for health promotion programs to encourage adoption of healthy lifestyle and policy interventions to create enabling environment.
Assuntos
Alcoolismo/epidemiologia , Sobrepeso/epidemiologia , Tabagismo/epidemiologia , Adulto , Distribuição por Idade , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural/estatística & dados numéricos , Distribuição por Sexo , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
Skin adnexal tumors arising in dermoid cysts of the ovary are exceedingly rare. We report a trichoadenoma arising in a dermoid cyst in a 42-year-old female. The histopathology of trichoadenoma has also been described briefly. Mature teratomas, which are almost all cystic (dermoid cysts), account for approximately 25% of all ovarian tumors, and 30% of benign ovarian tumors. They usually develop in children or women of the reproductive age group. Histologically, they are composed of variable proportions of tissue originating from the ectoderm, mesoderm, and endoderm. Cystic cavities are lined by mature epidermis. Although skin appendages and neural tissue are extremely common, there are only few case reports of skin adnexal tumors arising in a mature teratoma. We report a case of ovarian teratoma with a trichoadenoma. To the best of the authors' knowledge, this is the first report describing this rare benign skin adnexal tumor, in a mature cystic teratoma of the ovary.
Assuntos
Adenoma/patologia , Cisto Dermoide/patologia , Neoplasias Ovarianas/patologia , Neoplasias Cutâneas/patologia , Teratoma/patologia , Adulto , Feminino , HumanosRESUMO
Johne's disease is chronic granulomatous infectious enteritis of animals caused by Mycobacterium avium subspecies paratuberculosis. A total of 153 animals from 19 dairy farms, 2 gaushalas (unproductive-animal rehabilitation centers), 2 goat and 2 sheep farms from different districts of the Punjab region were selected on the basis of clinical signs of disease. All samples from cattle (n=86), buffalo (n=34), goat (n=25) and sheep (n=26) were subjected to Ziehl-Neelsen staining and DNA extraction by a freeze and thaw method. Ziehl-Neelsen staining detected 71% samples positive for acid-fast bacilli whereas IS900 PCR detected 55% positive for Map DNA. IS1311 PCR-REA analysis of IS900 positive samples revealed 'Bison' type as the most prevalent (82%) genotype of Map, infecting all domestic ruminants. 'Cattle' type was present in a minority of cases (15%) from cattle, buffaloes and goats. This is the first report of 'Cattle' type Map from buffalo and goat species in India.