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SORCS2 is one of five proteins that constitute the Vps10p-domain receptor family. Members of this family play important roles in cellular processes linked to neuronal survival, differentiation and function. Genetic and functional studies implicate SORCS2 in cognitive function, as well as in neurodegenerative and psychiatric disorders. DNA damage and DNA repair deficits are linked to ageing and neurodegeneration, and transient neuronal DNA double-strand breaks (DSBs) also occur as a result of neuronal activity. Here, we report a novel role for SORCS2 in DSB formation. We show that SorCS2 loss is associated with elevated DSB levels in the mouse dentate gyrus and that knocking out SORCS2 in a human neuronal cell line increased Topoisomerase IIß-dependent DSB formation and reduced neuronal viability. Neuronal stimulation had no impact on levels of DNA breaks in vitro, suggesting that the observed differences may not be the result of aberrant neuronal activity in these cells. Our findings are consistent with studies linking the VPS10 receptors and DNA damage to neurodegenerative conditions.
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Roturas del ADN de Doble Cadena , Reparación del ADN , Humanos , Animales , Ratones , Neuronas/metabolismo , Daño del ADN , Línea Celular , Receptores de Superficie Celular/genética , Proteínas del Tejido Nervioso/metabolismoRESUMEN
OBJECTIVES: We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement. METHODS: Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine. RESULTS: U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A-C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A-D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome. CONCLUSION: While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.
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Antígenos CD/orina , Moléculas de Adhesión Celular Neuronal/orina , Proteínas Fetales/orina , Lupus Eritematoso Sistémico/orina , Nefritis Lúpica/etiología , Molécula 1 de Adhesión Celular Vascular/orina , Adulto , Biomarcadores/orina , Estudios de Casos y Controles , Creatinina/orina , Femenino , Humanos , Riñón/metabolismo , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Incisional hernias, that significantly affect the quality of life of patients, are common complications especially after major surgery, such as liver transplantation. The purpose of this meta-analysis is to outline the available evidence on the complications occurring after mesh implantation as a treatment of ventral incisional hernias (VIH) in liver transplant patients. METHODS: MEDLINE, SCOPUS, Clinicaltrials.gov, CENTRAL and Google Scholar databases were searched for articles that reported the complications after mesh repair in patients that had undergone liver transplantation. RESULTS: Eighteen studies, that involved 640 liver transplant patients who developed incisional hernia, were included. 546 of them underwent surgical repair with mesh implantation. 144 (26%) patients developed postoperative complications, and the most common was surgical site infection (17%). The pooled complication rate of open mesh repair of incisional hernia after liver transplantation was 23% (95% CI = 11%-37%), whereas the pooled complication rate of laparoscopic mesh repair was 20% (95% CI = 12%-29%). CONCLUSION: Laparoscopic VIH repair with the implantation of mesh showed promising results, since the percentage of patients with postoperative complications was lower compared to the available data of those who underwent open VIH repair with mesh.
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Hernia Incisional , Laparoscopía , Trasplante de Hígado , Humanos , Hernia Incisional/etiología , Hernia Incisional/cirugía , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Calidad de Vida , Recurrencia , Mallas QuirúrgicasRESUMEN
Erwinia carotovora, a widespread plant pathogen that causes soft rot disease in many plants, is considered a major threat in agriculture. Bacterial glutathione transferases (GSTs) play important roles in a variety of metabolic pathways and processes, such as the biodegradation of xenobiotics, protection against abiotic stress, and resistance against antimicrobial drugs. The GST family of canonical soluble enzymes from Erwinia carotovora subsp. atroseptica strain SCRI1043 (EcaGSTs) was investigated. Genome analysis showed the presence of six putative canonical cytoplasmic EcaGSTs, which were revealed by phylogenetic analysis to belong to the well-characterized GST classes beta, nu, phi, and zeta. The analysis also revealed the presence of two isoenzymes that were phylogenetically close to the omega class of GSTs, but formed a distinct class. The EcaGSTs were cloned and expressed in Escherichia coli, and their catalytic activity toward different electrophilic substrates was elucidated. The EcaGSTs catalyzed different types of reactions, although all enzymes were particularly active in reactions involving electrophile substitution. Gene and protein expression profiling conducted under normal culture conditions as well as in the presence of the herbicide alachlor and the xenobiotic 1-chloro-2,4-dinitrobenzene (CDNB) showed that the isoenzyme EcaGST1, belonging to the omega-like class, was specifically induced at both the protein and mRNA levels. EcaGST1 presumably participates in counteracting the xenobiotic toxicity and/or abiotic stress conditions, and may therefore represent a novel molecular target in the development of new chemical treatments to control soft rot diseases.
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Proteínas Bacterianas/química , Erwinia/enzimología , Glutatión Transferasa/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Erwinia/genética , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Filogenia , Conformación ProteicaRESUMEN
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an ultra-rare inborn error of mitochondrial fatty acid oxidation (FAO) and amino acid metabolism. Individual phenotypes and treatment response can vary markedly. We aimed to identify markers that predict MADD phenotypes. We performed a retrospective nationwide cohort study; then developed an MADD-disease severity scoring system (MADD-DS3) based on signs and symptoms with weighed expert opinions; and finally correlated phenotypes and MADD-DS3 scores to FAO flux (oleate and myristate oxidation rates) and acylcarnitine profiles after palmitate loading in fibroblasts. Eighteen patients, diagnosed between 1989 and 2014, were identified. The MADD-DS3 entails enumeration of eight domain scores, which are calculated by averaging the relevant symptom scores. Lifetime MADD-DS3 scores of patients in our cohort ranged from 0 to 29. FAO flux and [U-13 C]C2-, C5-, and [U-13 C]C16-acylcarnitines were identified as key variables that discriminated neonatal from later onset patients (all P < .05) and strongly correlated to MADD-DS3 scores (oleate: r = -.86; myristate: r = -.91; [U-13 C]C2-acylcarnitine: r = -.96; C5-acylcarnitine: r = .97; [U-13 C]C16-acylcarnitine: r = .98, all P < .01). Functional studies in fibroblasts were found to differentiate between neonatal and later onset MADD-patients and were correlated to MADD-DS3 scores. Our data may improve early prediction of disease severity in order to start (preventive) and follow-up treatment appropriately. This is especially relevant in view of the inclusion of MADD in population newborn screening programs.
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Carnitina/análogos & derivados , Ácidos Grasos/sangre , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/fisiopatología , Índice de Severidad de la Enfermedad , Carnitina/sangre , Femenino , Humanos , Recién Nacido , Masculino , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/sangre , Estudios RetrospectivosRESUMEN
Schizophrenia is a debilitating, often chronic, psychotic disorder with early onset and a lifetime prevalence of 7.2/1,000. The longer the period without treatment, the worse the outcome. In the UK, the mean duration of untreated psychosis is one to two years. The new NICE guidelines for schizophrenia recommend that all patients who are distressed and have a decline in social functioning accompanied by psychotic symptoms or behaviour suggesting psychosis should be comprehensively assessed by a specialist mental health service. Antipsychotic medication remains the cornerstone of treatment in schizophrenia for the acute and the stabilisation-maintenance phase. The NICE guidelines recommend the use of psychological, social, occupational and educational interventions early in treatment. Mortality rates in schizophrenia are high and the majority of premature deaths are accounted for by physical illnesses. These include cardiovascular disease, diabetes mellitus, COPD, certain cancers and infectious diseases e.g. HIV, hepatitis C, and tuberculosis. Primary care has a significant role to play in monitoring mental state and physical health. Monitoring mental state is crucial. When relapse is threatened because of poor response to treatment, non-adherence to medication, intolerable side effects from medication, comorbid substance misuse, or if risk to self or others is suspected, GPs should refer the patient to the mental health team. GPs should provide a comprehensive health check yearly or more often if there is an indication.
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Atención Primaria de Salud , Esquizofrenia/diagnóstico , Esquizofrenia/terapia , Antipsicóticos/uso terapéutico , HumanosRESUMEN
This paper presents a novel framework for implementing the k-NN algorithm, designed to enhance its accuracy in contexts with sparse data. The framework addresses limitations in the algorithm's training process by optimizing data structures. It employs composite datasets generated from the initial data using a data-driven fuzzy Analytic Hierarchy Process weighting scheme. This approach is designed to enhance the informational content in the initial datasets, thus reducing the entropy and implementation uncertainty. The framework was evaluated using 75 publicly available datasets and 3 generated datasets, demonstrating significant accuracy improvements across various k-parameter values. The findings were rigorously generalized using non-parametric hypothesis tests; while the resulting sensitivity was assessed by applying different distance metrics. By enhancing informational content, the composite data structures contribute to both accuracy improvements and scalability, particularly in data-sparse contexts. This relationship underscores the critical role of entropy in enhancing the performance of explainable machine learning algorithms, providing a valuable and interpretable tool for transforming data structures in sparse data environments.
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OBJECTIVE: Quantitatively measure the degree of patient satisfaction and perceived acquired knowledge through the development of a patient information booklet for rectal cancer survivors with a stoma, according to a novel three-step approach. METHODS: The study included a systematic literature review to identify relevant information for the booklet, which was validated by experts based on relevance, clarity and essentiality. It underwent testing on quality, readability, and layout and design and was quantitatively evaluated by rectal cancer survivors with a stoma. RESULTS: In total, 145 articles were used for the development of the booklet. It scored 91% for relevance according to 17 experts, 70% for readability, 75.63% for quality and 23 out of 32 for design. The mean score of patient satisfaction was 8.03 out of 10. All 20 patients found the booklet 'useful' and 95% felt better informed. CONCLUSIONS: The booklet scored high for patient satisfaction and increased perceived acquired information. It ensured satisfactory levels of quality, readability, and layout and design. PRACTICE IMPLICATIONS: This study offers a novel three-step approach for development of informational tools for cancer survivors, assuring that a variety of newly created written patient materials would be of increased quality and relevance to any target population.
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Supervivientes de Cáncer , Neoplasias del Recto , Comprensión , Humanos , Folletos , Neoplasias del Recto/cirugía , SobrevivientesRESUMEN
Background: Reprogrammed glucose metabolism is a hallmark of cancer making it an attractive therapeutic target, especially in cancers with high glucose uptake such as non-small cell lung cancer (NSCLC). Tools to select patients with high glucose uptake in the majority of tumor lesions are essential in the development of anti-cancer drugs targeting glucose metabolism. Type 2 diabetes mellitus (T2DM) patients may have tumors highly dependent on glucose uptake. Surprisingly, this has not been systematically studied. Therefore, we aimed to determine which patient and tumor characteristics, including concurrent T2DM, are related to high glucose uptake in the majority of tumor lesions in NSCLC patients as measured by 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) scans. Methods: Routine primary diagnostic 18F-FDG PET/CT scans of consecutive NSCLC patients were included. Mean standardized uptake value (SUVmean) of 18F-FDG was determined for all evaluable tumor lesions and corrected for serum glucose levels according to the European Association of Nuclear Medicine Research Ltd guidelines. Patient characteristics potentially determining degree of tumor lesion glucose uptake in the majority of tumor lesions per patient were investigated. Results: The cohort consisted of 102 patients, 28 with T2DM and 74 without T2DM. The median SUVmean per patient ranged from 0.8 to 35.2 (median 4.2). T2DM patients had higher median glucose uptake in individual tumor lesions and per patient compared to non-diabetic NSCLC patients (SUVmean 4.3 vs 2.8, P < 0.001 and SUVmean 5.4 vs 3.7, P = 0.009, respectively). However, in multivariable analysis, high tumor lesion glucose uptake was only independently determined by number of tumor lesions ≥1 mL per patient (odds ratio 0.8, 95% confidence interval 0.7-0.9). Conclusions: 18F-FDG PET/CT scans can identify sub-groups of NSCLC patients with high glucose uptake in the majority of their tumor lesions. T2DM patients had higher tumor lesion glucose uptake than non-diabetic patients. However, this was not independent of other factors such as the histological subtype and number of tumor lesions per patient.
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In common commercially available electrochromic glass panes, the active materials such as WO3 and NiOx films are typically deposited by either physical vapor or sputtering under vacuum. In the present studies, we report on the inkjet printing method to deposit both electrochromic and ion storage electrode layers under ambient conditions. An ion storage layer based on cerium modified TiO2 and electrochromic nanocrystalline WO3 were both prepared under the wet method and deposited as inks on conductive substrates. Both compounds possess porous morphology facilitating high ion diffusion during electrochemical processes. In particular, the ion storage layer was evaluated in terms of porosity, charge capacity and ion diffusion coefficient. A scaled up 90 cm2 electrochromic device with quasi-solid-state electrolyte was made with the aforementioned materials and evaluated in terms of optical modulation in the visible region, cyclic voltammetry and color efficiency. High contrast between 13.2% and 71.6% for tinted and bleached states measured at 550 nm was monitored under low bias at +2.5 volt and -0.3 volts respectively. Moreover, the calculated energy density equal to 1.95 × 10-3 mWh cm-2 and the high areal capacitance of 156.19 mF cm-2 of the device could combine the electrochromic behavior of the cell with energy storage capability so as to be a promising candidate for future applications into smart buildings.
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AIM: To identify and analyze the clinical presentation, management and outcome of patients with acute mechanical bowel obstruction along with the etiology of obstruction and the incidence and causes of bowel ischemia, necrosis, and perforation. METHODS: This is a prospective observational study of all adult patients admitted with acute mechanical bowel obstruction between 2001 and 2002. RESULTS: Of the 150 consecutive patients included in the study, 114 (76%) presented with small bowel and 36 (24%) with large bowel obstruction. Absence of passage of flatus (90%) and/or feces (80.6%) and abdominal distension (65.3%) were the most common symptoms and physical finding, respectively. Adhesions (64.8%), incarcerated hernias (14.8%), and large bowel cancer (13.4%) were the most frequent causes of obstruction. Eighty-eight patients (58.7%) were treated conservatively and 62 (41.3%) were operated (29 on the first day). Bowel ischemia was found in 21 cases (14%), necrosis in 14 (9.3%), and perforation in 8 (5.3%). Hernias, large bowel cancer, and adhesions were the most frequent causes of bowel ischemia (57.2%, 19.1%, 14.3%), necrosis (42.8%, 21.4%, 21.4%), and perforation (50%, 25%, 25%). A significantly higher risk of strangulation was noticed in incarcerated hernias than all the other obstruction causes. CONCLUSION: Absence of passage of flatus and/or feces and abdominal distension are the most common symptoms and physical finding of patients with acute mechanical bowel obstruction, respectively. Adhesions, hernias, and large bowel cancer are the most common causes of obstruction, as well as of bowel ischemia, necrosis, and perforation. Although an important proportion of these patients can be nonoperatively treated, a substantial portion requires immediate operation. Great caution should be taken for the treatment of these patients since the incidence of bowel ischemia, necrosis, and perforation is significantly high.
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Obstrucción Intestinal/etiología , Perforación Intestinal/etiología , Intestinos/patología , Isquemia/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hernia Abdominal/complicaciones , Humanos , Neoplasias Intestinales/complicaciones , Obstrucción Intestinal/patología , Obstrucción Intestinal/terapia , Intestinos/irrigación sanguínea , Masculino , Persona de Mediana Edad , Necrosis/patología , Estudios Prospectivos , Adherencias Tisulares/complicaciones , Resultado del TratamientoRESUMEN
Hydatid disease, although endemic mostly in sheep-farming countries, remains a public health issue worldwide, involving mainly the liver. Intrabiliary rupture is the most frequent complication of the hepatic hydatid cyst. Endoscopy is advocated, preoperatively, to alleviate obstructive jaundice caused by intracystic materials after a frank rupture and is also a useful and well-established adjunct in locating postoperative biliary fistulas. Endoscopic retrograde cholangiography with sphincterotomy has been successful as the sole and definitive means of treatment of intrabiliary ruptured hydatid cysts. A case of an elderly woman with frank rupture is presented, where the rupture was definitively managed endoscopically in conjunction with sphincterotomy to remove the intrabiliary obstructive daughter cysts and to achieve decontamination of the biliary tree. Endoscopic retrograde cholangiography provided an excellent diagnostic and therapeutic modality in the present case and, thus, it should be considered as definitive treatment in similar cases especially if surgical risk is anticipated to be high.
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Enfermedades de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Equinococosis Hepática/cirugía , Esfinterotomía Endoscópica , Anciano de 80 o más Años , Enfermedades de los Conductos Biliares/etiología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Equinococosis Hepática/diagnóstico por imagen , Femenino , Humanos , Rotura EspontáneaRESUMEN
A 60-years old male was admitted to our department for investigation of constipation and hypogastric discomfort intensified during defecation of a few weeks duration. The cause proved to be a rectal carcinosarcoma that was treated by abdominoperineal resection and postoperative chemo-radiotherapy. The patient died 6 months later due to hepatic failure, showing evidence of disseminated disease. In general colonic carcinosarcomas constitute a rare category of malignant neoplasms whose nature is still incompletely understood. No specific treatment guidelines exist. Surgery is the mainstay of treatment and regardless of the addition of adjuvant therapy the prognosis is very poor. Systematic genetic analysis may be the clue for understanding the pathogenesis of these mysterious tumors.
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Carcinosarcoma/diagnóstico , Neoplasias del Recto/diagnóstico , Biomarcadores/análisis , Carcinosarcoma/química , Carcinosarcoma/patología , Carcinosarcoma/terapia , Terapia Combinada , Humanos , Inmunohistoquímica , Queratinas/análisis , Masculino , Persona de Mediana Edad , Neoplasias del Recto/química , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Proteína p53 Supresora de Tumor/análisisRESUMEN
AIM: To determine the mechanical properties of anastomotic colonic tissue in experimental settings and therefore give a measure of wound healing. METHODS: Thirty-six male Wistar rats were used as experimental models of anastomotic tissue integrity. On the 5th post-operative day, the tensile strength was measured by application of an axial force, providing a quantitative measure of anastomotic dehiscence and leakage. RESULTS: Diagrams of the load as a function of the time [P = P (t)] and of the displacement also as a function of time [Delta s = Delta s (t)] were recorded for each test, permitting the design of the load versus the displacement diagram and thus providing significant data about the critical values of anastomotic failure. Quantitative data were obtained concerning the anastomotic strength of both control specimens (healthy rats), as well as specimens from non-healthy rats for comparison. CONCLUSION: This experimental model provides an excellent method of measuring anastomotic strength. Despite the relative small number of specimens used, this method provides an accurate way of measuring wound repair. More experimental measurements need to be performed to correlate emerging tensile strength values to anastomotic failure.
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Colon/fisiología , Colon/cirugía , Cicatrización de Heridas/fisiología , Anastomosis Quirúrgica/métodos , Animales , Masculino , Modelos Animales , Modelos Teóricos , Ratas , Ratas Wistar , Dehiscencia de la Herida Operatoria/fisiopatología , Dehiscencia de la Herida Operatoria/prevención & control , Resistencia a la Tracción/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: Hippocampus-dependent memory involves the activity of sharp wave ripples (SWRs), which are thought to participate in the process of memory consolidation. The hippocampus contains high levels of endogenous opioids and of µ-opioid receptors (MORs). Here, we have assessed the role of MOR agonists in the modulation of SWRs. EXPERIMENTAL APPROACH: Using recordings of extracellular potentials from the CA1 field of rat hippocampal slices, we examined the pharmacological actions of morphine, DAMGO and fentanyl on SWRs and on network excitability and paired-pulse inhibition. KEY RESULTS: All three MOR agonists (1 nM-10 µM) significantly increased the amplitude of sharp waves and the occurrence of SWR sequences, but reduced the initiation of episodes of SWRs. Fentanyl was most potent in producing these effects and morphine the least. Interestingly, although SWRs were reduced by relatively high concentrations (≥100 nM) of all agonists, they were significantly enhanced by very low concentrations of morphine (5-10 nM). Morphine and DAMGO at moderate-to-high concentrations increased network excitability and reduced inhibition. Furthermore, DAMGO suppressed inhibition more readily than it increased excitation, whereas morphine suppressed inhibition only at high concentrations. These drug effects were reversed by the MOR antagonists naloxone and CTOP. CONCLUSIONS AND IMPLICATIONS: We found that the SWRs were significantly modulated by three MOR agonists and that the SWRs were very sensitive to subtle changes in the excitation/inhibition balance induced by MOR agonists. Such modulation might underlie the effects of these agonists on hippocampus-dependent memory.
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Región CA1 Hipocampal/efectos de los fármacos , Receptores Opioides mu/agonistas , Analgésicos Opioides/farmacología , Animales , Región CA1 Hipocampal/fisiología , Encefalina Ala(2)-MeFe(4)-Gli(5)/farmacología , Potenciales Evocados/efectos de los fármacos , Fentanilo/farmacología , Técnicas In Vitro , Masculino , Morfina/farmacología , Ratas , Ratas Wistar , Receptores Opioides mu/fisiologíaRESUMEN
A convenient and facile synthesis, in silico docking studies and in vitro biological evaluation of N-substituted 5-butylimidazole derivatives as potent Angiotensin II (ANG II) receptor type 1 (AT1) blockers (ARBs) has been reported in the current study. Our efforts have been directed towards the development of an efficient synthetic route allowing the facile introduction of substituents on the imidazole ring. In particular, a series of imidazole based compounds bearing the biphenyl moiety at the N - 1 position, a halogen atom at the C-4 and polar substituents such as hydroxymethyl, aldo or carboxy group at the C-2 position were designed and synthesized. These compounds were evaluated for binding to human AT1 receptor and for ANG II antagonism in vitro on isolated rat uterus. Among them, 5-butyl-1-[[2'-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-2-carboxylic acid (30) exhibited higher binding affinity compared to the other analogues tested (-log IC(50) = 8.46). The latter analogue was also found to be the most active in the rat uterotonic test (pA(2) = 7.83). Importantly, the binding affinity was higher to that of losartan (-log IC(50) = 8.25) indicating the importance of carboxy group at the C-2 position. Experimental findings are in good agreement with docking studies, which were undertaken in order to investigate ligand/AT1 receptor interactions.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/síntesis química , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Descubrimiento de Drogas , Imidazoles/síntesis química , Imidazoles/farmacología , Simulación del Acoplamiento Molecular , Receptor de Angiotensina Tipo 1/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/química , Bloqueadores del Receptor Tipo 1 de Angiotensina II/metabolismo , Animales , Técnicas de Química Sintética , Femenino , Células HEK293 , Humanos , Imidazoles/química , Imidazoles/metabolismo , Técnicas In Vitro , Concentración 50 Inhibidora , Conformación Proteica , Ratas , Ratas Wistar , Receptor de Angiotensina Tipo 1/química , Contracción Uterina/efectos de los fármacos , Útero/efectos de los fármacos , Útero/fisiologíaRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the impact of ATLS(®) on trauma mortality in a non-trauma system setting. ATLS represents a fundamental element of trauma training in every trauma curriculum. Nevertheless, there are limited studies in the literature as for the impact of ATLS training in trauma mortality, especially outside the US. DESIGN: This is a prospective observational study. The primary end point was to investigate factors that affect mortality of trauma patients in our health care system. We performed a multivariate analysis for this purpose and we identified ATLS certification as a predictor of overall mortality. Following this finding we stratified patients according to the severity of injury as expressed by the ISS score and we compared outcome between those treated by an ATLS certified physician and those treated by non-certified ones. MAIN OUTCOME MEASURES: Trauma volume and demographics of trauma patients, factors that affect mortality of traumatized patients and mortality between patients treated by ATLS(®) certified and non-certified physicians. RESULTS: In total, 8862 trauma patients were included in the analysis. The majority of trauma patients (5988, 67.6%) were treated by a general surgeon, followed by those treated by an orthopedic surgeon (2194, 24.8%). There were 446 deaths in the registry but, 260 arrived dead in the Emergency Department and were excluded from the analysis. Multivariate analysis of the 186 deaths that occurred in the hospital revealed age, high ISS score, low GCS score, urban location of injury, neck injury and ATLS(®) certification as factors predisposing to mortality. Cross tabulation of ATLS(®) certification and ISS of the trauma patients shows that those treated by certified physicians died more often in all subcategories of ISS score (p<0.05). CONCLUSIONS: In Greece, with no formal trauma system implementation, ATLS(®) certified physicians achieve worse outcomes than their non-certified colleagues when managing trauma patients. We believe that these findings must be interpreted in the context of the National health care system. There is considerable room for improvement in our country, and further analysis is required.
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Certificación , Resucitación , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Médicos , Estudios Prospectivos , Resucitación/educaciónRESUMEN
PURPOSE: To present the initial Greek experience with vacuumassisted breast biopsy (VABB) in the diagnosis of nonpalpable solid mammographic lesions without microcalcifications. MATERIALS AND METHODS: We performed 83 VABB procedures (using a Fischer table and 11-guage Mammotome probes) in an 18- month period on women with nonpalpable solid breast tumors. We performed VABB procedures on women with breast imaging reporting and data system (BI-RADS) categories 3 and 4. VABB procedures excised more than 24 cores. RESULTS: Eighty-three women with nonpalpable lesions identified on mammography were evaluated; 42.2% were BI-RADS category 3, and 57.8% were BI-RADS 4. Of all solid tumors excised, 83.1% were benign, 3.6% were precursor lesions, and 13.3% of the lesions were malignant. No underestimation occurred. Clinically important hematoma developed in 4.8% of cases. CONCLUSION: VABB is an effective method for the diagnosis of nonpalpable solid lesions because of the lack of underestimation, although it is technically more difficult to focus on lesions without microcalcifications than those with microcalcifications on the Fischer table.
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Biopsia con Aguja/instrumentación , Biopsia con Aguja/métodos , Neoplasias de la Mama/patología , Glándulas Mamarias Humanas/patología , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Grecia , Humanos , Mamografía/métodos , Persona de Mediana Edad , Sensibilidad y Especificidad , VacioRESUMEN
INTRODUCTION: Primary splenic angiosarcoma is a rare neoplasm of vascular origin carrying a very poor prognosis, partly due to its high metastatic potential. This disease presents frequently with splenic rupture and hemorrhage. We report the case of a 17-year-old woman who presented with rupture of a primary splenic angiosarcoma. CASE PRESENTATION: The patient presented with diffuse abdominal pain and distention. Clinical examination revealed severe tenderness in the left upper abdominal quadrant, a palpable abdominal mass, and hemodynamic instability with a systolic arterial blood pressure of 75 mmHg and heart rate of 135 beats per minute. Blood tests revealed anemia (hemoglobin 7.0 g/dl) and thrombocytopenia (platelets 70 x 109/liter). After initial fluid resuscitation and stabilization, abdominal ultrasound and computed tomography were performed, revealing a large quantity of intraperitoneal free fluid, an enlarged spleen, and a heterogeneous low-density signal within the splenic parenchyma, which showed varying degrees of contrast enhancement. At laparotomy a huge (weight 1530 g, diameter 19 cm) actively bleeding spleen was identified and splenectomy was performed. Histopathology showed a primary splenic angiosarcoma. After an uneventful recovery, the patient was discharged on the sixth postoperative day. CONCLUSION: Primary splenic angiosarcoma is rare. Although this malignancy is usually encountered in advanced age, there have been a few reported cases among younger patients. The case reported here presented with splenic rupture, was treated by laparotomy and splenectomy, and the patient is disease free 16 months after surgery.