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1.
Hum Brain Mapp ; 44(2): 612-628, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36181510

RESUMEN

Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.


Asunto(s)
Núcleos Talámicos , Sustancia Blanca , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Núcleos Talámicos/diagnóstico por imagen , Tálamo , Envejecimiento , Imagen por Resonancia Magnética/métodos
2.
Drug Alcohol Depend ; 220: 108509, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33453503

RESUMEN

The extant literature supports the involvement of the thalamus in the cognitive and motor impairment associated with chronic alcohol consumption, but clear structure/function relationships remain elusive. Alcohol effects on specific nuclei rather than the entire thalamus may provide the basis for differential cognitive and motor decline in Alcohol Use Disorder (AUD). This functional MRI (fMRI) study was conducted in 23 abstinent individuals with AUD and 27 healthy controls to test the hypothesis that functional connectivity between anterior thalamus and hippocampus would be compromised in those with an AUD diagnosis and related to mnemonic deficits. Functional connectivity between 7 thalamic structures [5 thalamic nuclei: anterior ventral (AV), mediodorsal (MD), pulvinar (Pul), ventral lateral posterior (VLP), and ventral posterior lateral (VPL); ventral thalamus; the entire thalamus] and 14 "functional regions" was evaluated. Relative to controls, the AUD group exhibited different VPL-based functional connectivity: an anticorrelation between VPL and a bilateral middle temporal lobe region observed in controls became a positive correlation in the AUD group; an anticorrelation between the VPL and the cerebellum was stronger in the AUD than control group. AUD-associated altered connectivity between anterior thalamus and hippocampus as a substrate of memory compromise was not supported; instead, connectivity differences from controls selective to VPL and cerebellum demonstrated a relationship with impaired balance. These preliminary findings support substructure-level evaluation in future studies focused on discerning the role of the thalamus in AUD-associated cognitive and motor deficits.


Asunto(s)
Abstinencia de Alcohol , Alcoholismo/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adulto , Estudios de Casos y Controles , Disfunción Cognitiva/diagnóstico por imagen , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
3.
Neurology ; 96(2): e171-e181, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33028664

RESUMEN

OBJECTIVE: To evaluate the role of blood pressure (BP) as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after endovascular treatment (EVT). METHODS: Patients treated in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP), and procedural BP trend, compared to LA. Second, we assessed the association between BP and functional outcome (modified Rankin Scale [mRS]) with multivariable regression. Lastly, we evaluated whether BP explained the effect of CS on mRS. RESULTS: In 440 patients with available BP data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%), and a more negative BP trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common odds ratio [acOR] per 10% drop 0.87, 95% confidence interval [CI] 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95% CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95% CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95% CI 0.42-0.92). CONCLUSIONS: Large BP drops are associated with worse functional outcome. However, BP drops do not explain the worse outcomes in the CS group.


Asunto(s)
Anestesia Local/métodos , Presión Sanguínea/fisiología , Isquemia Encefálica/cirugía , Sedación Consciente/métodos , Procedimientos Endovasculares/métodos , Monitorización Neurofisiológica Intraoperatoria/métodos , Accidente Cerebrovascular Isquémico/cirugía , Anestesia Local/efectos adversos , Presión Sanguínea/efectos de los fármacos , Isquemia Encefálica/epidemiología , Isquemia Encefálica/fisiopatología , Sedación Consciente/efectos adversos , Procedimientos Endovasculares/efectos adversos , Humanos , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/fisiopatología , Países Bajos/epidemiología , Estudios Prospectivos , Sistema de Registros
4.
J Neuroimmune Pharmacol ; 14(3): 436-447, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30741374

RESUMEN

Neuropathy, typically diagnosed by the presence of either symptoms or signs of peripheral nerve dysfunction, remains a frequently reported complication in the antiretroviral (ART)-treated HIV population. This study was conducted in 109 healthy controls and 57 HIV-infected individuals to investigate CNS regions associated with neuropathy. An index of objective neuropathy was computed based on 4 measures: deep tendon ankle reflex, vibration sense (great toes), position sense (great toes), and 2-point discrimination (feet). Subjective neuropathy (self-report of pain, aching, or burning; pins and needles; or numbness in legs or feet) was also evaluated. Structural MRI data were available for 126/166 cases. The HIV relative to the healthy control group was impaired on all 4 signs of neuropathy. Within the HIV group, an objective neuropathy index of 1 (bilateral impairment on 1 measure) or 2 (bilateral impairment on at least 2/4 measures) was associated with older age and a smaller volume of the cerebellar vermis. Moderate to severe symptoms of neuropathy were associated with more depressive symptoms, reduced quality of life, and a smaller volume of the parietal precuneus. This study is consistent with the recent contention that ART-treated HIV-related neuropathy has a CNS component. Distinguishing subjective symptoms from objective signs of neuropathy allowed for a dissociation between the precuneus, a brain region involved in conscious information processing and the vermis, involved in fine tuning of limb movements. Graphical Abstract In HIV patients, objective signs of neuropathy correlated with smaller cerebellar vermis (red) volumes whereas subjective symptoms of neuropathy were associated with smaller precuneus (blue) volumes.


Asunto(s)
Mapeo Encefálico , Vermis Cerebeloso/fisiopatología , Infecciones por VIH/complicaciones , Imagen por Resonancia Magnética , Lóbulo Parietal/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Adulto , Anciano , Vermis Cerebeloso/diagnóstico por imagen , Depresión/etiología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Infecciones por VIH/psicología , Humanos , Pierna/inervación , Masculino , Persona de Mediana Edad , Neuralgia/diagnóstico por imagen , Neuralgia/etiología , Neuralgia/fisiopatología , Neuralgia/psicología , Tamaño de los Órganos , Percepción del Dolor , Parestesia/diagnóstico por imagen , Parestesia/etiología , Parestesia/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Trastornos de la Percepción/diagnóstico por imagen , Trastornos de la Percepción/etiología , Trastornos de la Percepción/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/psicología , Calidad de Vida , Reflejo Anormal , Autoinforme , Trastornos Somatosensoriales/diagnóstico por imagen , Trastornos Somatosensoriales/etiología , Trastornos Somatosensoriales/fisiopatología , Tálamo/diagnóstico por imagen , Vibración
5.
Chirurg ; 81(11): 1005-12, 2010 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-20552152

RESUMEN

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) offers patients with peritoneal cancer of various origins the chance of a relevant increase in life expectancy. These cases are very complex from a medical viewpoint and very expensive from an economical aspect. An analysis of case cost calculations was performed to find out whether this procedure can on average be carried out cost-effectively by a maximum care university. MATERIALS AND METHODS: All cases from 2008 in which HIPEC was carried out were analyzed. The types of main diagnosis, secondary diagnoses, procedures, times from incision to suture and hospital stay were analyzed. On the basis of the case costs the proceeds and marginal returns were calculated from the diagnosis-related groups (DRGs) and additional remuneration when applicable. The causes of positive and negative marginal returns were explained using the InEK cost matrix. RESULTS: In 18 patients there were 9 different main diagnoses and 7 different "main procedures" (from a surgical perspective the most resource intensive procedures) and a total of 10 different DRGs were identified in the grouping algorithm. With an average of 2 operations (range 1-7) per patient the summed incision-to-suture time was 423 min (170-962 min). The patients stayed on average 6.4 days (1.3-17.6 days) in intensive care. The average case cost was 21,072€ (range 8,657-55,904€) and the proceeds 20,474€ (6,333-37,497€). Each case had on average a debit balance of 598€ (range from 11,843€ profit balance to 18,407€ debit balance) with an assumed base rate of 2,786€. The causes for positive or negative marginal profits were mostly operating times, incision-to-suture times and duration of intensive care. CONCLUSIONS: The proceeds showed on average a deficit of only 3% compared to the costs. The operating times must be decreased by optimization particularly of the preoperative approach. Interventions should be carried out in one stage only and the intraoperative connecting and waiting times should be reduced in order to reduce the incision-to-suture times.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional/economía , Grupos Diagnósticos Relacionados/economía , Hipertermia Inducida/economía , Programas Nacionales de Salud/economía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/economía , Adulto , Anciano , Análisis Costo-Beneficio , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/economía , Alemania , Humanos , Infusiones Parenterales/economía , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/economía , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Tasa de Supervivencia
6.
Chirurg ; 78(5): 462, 464-6, 468, 2007 May.
Artículo en Alemán | MEDLINE | ID: mdl-17310355

RESUMEN

BACKGROUND: New demands and possibilities of collaboration between hospitals and private practices in Germany have appeared, now that the way has been opened legally. A poll was conducted to analyse the current status of collaboration between outpatient gastroenterologists and hospital surgical departments and to identify possible future collaborations. MATERIALS AND METHODS: One thousand twenty-six private practices specialising in endoscopy were found by contacting the Association of Statutory Health Insurance Physicians and additional internet research. Of these, 50% were randomly selected (513 private practices) and contacted by mail with anonymous questionnaires about cooperation with their clinical partners. Two hundred three (39.6%) practices responded, of which 200 could be analysed. RESULTS: Of all practices reached, 75% considered the cooperation with clinics very valuable or even exceptional. Still, almost half (46%) suggested necessary improvements in these collaborations. Around a third of all contacted colleagues were already involved in projects following integrated care models. In about 80% of all participants, the main interest in integrated models was specified to be common therapy planning. CONCLUSION: The data analysis of this study shows a substantial interest of private-practice gastroenterologists in close collaboration with hospitals. It is now up to the hospitals to open contracts with their medical outpatient partners.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/legislación & jurisprudencia , Conducta Cooperativa , Endoscopía Gastrointestinal , Gastroenterología/legislación & jurisprudencia , Programas Nacionales de Salud/legislación & jurisprudencia , Servicio de Cirugía en Hospital/legislación & jurisprudencia , Servicios Contratados/legislación & jurisprudencia , Prestación Integrada de Atención de Salud/legislación & jurisprudencia , Alemania , Humanos , Tiempo de Internación/legislación & jurisprudencia , Práctica Privada/legislación & jurisprudencia , Encuestas y Cuestionarios
7.
Artículo en Inglés | MEDLINE | ID: mdl-16556492

RESUMEN

Type and composition of polyunsaturated fatty acids (PUFAs) are suspected to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 PUFAs on tumour growth, liver metastasis and concentration of prostaglandins (PG) and leukotrienes (LT) in experimental ductal pancreatic adenocarcinoma. Ninety male hamsters were randomised into six groups (Gr.) (n=15). While Gr. 1-3 were healthy control groups, Gr. 4-6 weekly received subcutaneous injections of 10mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1 and 16 all animals were fed with a standard diet with a raw fat content of 2.9%. In week 17 Gr. 1-6 were allocated to three types of diets: Gr. 1: standard high fat (=SHF diet, rich in n-6 PUFAs)/Gr. 2: FISH-OIL (rich in n-3 PUFAs)/Gr. 3: SMOF (=mixture of n-3, n-6 and n-9 PUFAs)/Gr. 4: BOP+SHF/Gr. 5: BOP+SMOF/Gr. 6: BOP+FISH-OIL. After 32 weeks all animals were sacrificed and pancreas as well as liver were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1alpha, PGE(2)) and LT were measured. FISH-OIL decreased number of macroscopically visible pancreatic tumours (Gr. 4-6: 54.5% vs. 45.5% vs. 9.1%, P<0.05) as well as incidence of liver metastasis (Gr. 4-6: 90.9% vs. 72.7% vs. 36.4%, P<0.05). Furthermore concentration of PGF(1)(alpha), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1)(alpha) and PGE(2) were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of LT was significantly lower than in non-metastatic hepatic tissue as well as in Gr. 4 and Gr. 5. FISH-OIL decreased number of visible pancreatic tumours and incidence of histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of LT compared to extrametastatic hepatic tissue.


Asunto(s)
Ácidos Grasos Insaturados/farmacología , Leucotrienos/metabolismo , Neoplasias Hepáticas/secundario , Hígado/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Prostaglandinas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Cricetinae , Grasas Insaturadas en la Dieta/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Dinoprost/química , Dinoprost/metabolismo , Dinoprostona/química , Dinoprostona/metabolismo , Ácidos Grasos Insaturados/metabolismo , Masculino , Páncreas/citología , Páncreas/metabolismo
8.
Neuroimage ; 31(1): 228-39, 2006 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-16466677

RESUMEN

A statistical model is presented that combines the registration of an atlas with the segmentation of magnetic resonance images. We use an Expectation Maximization-based algorithm to find a solution within the model, which simultaneously estimates image artifacts, anatomical labelmaps, and a structure-dependent hierarchical mapping from the atlas to the image space. The algorithm produces segmentations for brain tissues as well as their substructures. We demonstrate the approach on a set of 22 magnetic resonance images. On this set of images, the new approach performs significantly better than similar methods which sequentially apply registration and segmentation.


Asunto(s)
Teorema de Bayes , Encefalopatías/diagnóstico , Encéfalo/patología , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Imagen por Resonancia Magnética/estadística & datos numéricos , Artefactos , Mapeo Encefálico , Ventrículos Cerebrales/patología , Dominancia Cerebral/fisiología , Humanos , Modelos Estadísticos , Tálamo/patología
9.
Int J Colorectal Dis ; 21(1): 57-63, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15864609

RESUMEN

BACKGROUND AND AIMS: Acute pancreatitis often requires parenteral nutrition. Thus, we analyzed, using a randomized trial, whether different fatty acids in parenteral nutrition influence lipidperoxidation and histopathology in acute pancreatitis in rats. MATERIALS AND METHODS: Seventy-five male Sprague-Dawley rats were randomized into five groups (gr.) (n=15). Gr. 1 underwent a laparotomy followed by saline infusion, gr. 2-5 received intraductal glycodeoxycholic acid (GDOC) followed by intravenous cerulein. Six hours after induction of pancreatitis (IOP), gr. 2 received saline infusion, while gr. 3 was infused with standard lipovenous (rich in [n-6] polyunsaturated fatty acids (PUFA)), gr. 4 received ClinOleic (rich in [n-9] PUFA), while gr. 5 was infused with Omegaven (rich in [n-3] PUFA) for 18 h. After 24 h, all animals were sacrificed and the pancreas was determined histopathologically according to the severity of pancreatitis. Furthermore, pancreatic lipidperoxidation (TBARS) and activity of lipid production protective enzymes superoxide dismutase (SOD) and gluthationperoxidase (GSHPx) were analyzed. RESULTS: Omegaven infusion reduced the severity of histopathologic changes in acute pancreatitis and decreased lipidperoxidation (TBARS) in pancreatic tissue samples. Furthermore, pancreatic activity of SOD was increased. However, standard PUFA and ClinOleic infusion did not influence the severity of pancreatitis and lipidperoxidation. CONCLUSION: Parenteral nutrition high in n-3 PUFA seems to be superior to compositions of n-6 or n-9 PUFA in the treatment of acute hemorrhagic pancreatitis in rats.


Asunto(s)
Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Peroxidación de Lípido/efectos de los fármacos , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Pancreatitis Aguda Necrotizante/patología , Animales , Modelos Animales de Enfermedad , Ácidos Grasos Insaturados/farmacología , Inmunohistoquímica , Infusiones Intravenosas , Masculino , Pancreatitis Aguda Necrotizante/mortalidad , Nutrición Parenteral Total , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Sensibilidad y Especificidad , Tasa de Supervivencia , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
10.
Artículo en Inglés | MEDLINE | ID: mdl-16226437

RESUMEN

BACKGROUND: Type and composition of dietary fat intake is supposed to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 polyunsaturated fatty acids (PUFA) on oxidative stress (lipidperoxidation) and tumour growth in ductal pancreatic cancer. METHODS: Ninety male hamsters were randomized into 6 groups (gr.) (n=15) and allocated to 3 main dietary categories: gr. 1 and 2 received a standard high fat diet (SHF, rich in n-6 PUFA), while gr. 3 and 4 were fed with a diet containing a mixture of n-3, n-6 and n-9 PUFA (SMOF) and gr. 5 and 6 had free access to a diet rich in n-3 PUFA (FISH-OIL). Gr. 1, 3 and 5 received weekly subcutaneous (s.c.) injections of 10 mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight in order to induce ductal pancreatic adenocarcinoma. Healthy control gr. 2, 4 and 6 were treated with 0.5 ml 0.9% sodium chloride s.c. After 32 weeks all animals were sacrificed. Removed pancreata were weighed and analysed histologically and biochemically. Activities of glutathionperoxidase (GSH-Px), superoxiddismutase (SOD) and levels of lipidperoxidation were measured in samples of pancreatic carcinoma as well as in tumour-free pancreatic tissue. RESULTS: While different diets did not significantly alter the overall incidence of histologically proven pancreatic adenocarcinoma, the number of macroscopically visible tumours was decreased in the FISH-OIL-gr. CONCLUSION: Different diets did not significantly influence the incidence of histologically proven pancreatic adenocarcinoma. However, administration of a diet rich in n-3 PUFA (FISH-OIL) resulted in a decrease of macroscopically visible tumours, thus indicating its beneficial effects in respect to attenuation of tumour growth.


Asunto(s)
Carcinoma Ductal Pancreático/patología , Grasas Insaturadas en la Dieta/farmacología , Nutrición Enteral , Estrés Oxidativo/efectos de los fármacos , Neoplasias Pancreáticas/patología , Animales , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/mortalidad , Cricetinae , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos Insaturados/farmacología , Aceites de Pescado/química , Aceites de Pescado/farmacología , Glutatión Peroxidasa/metabolismo , Ácido Linoleico/análisis , Ácido Linoleico/farmacología , Masculino , Mesocricetus , Nitrosaminas/administración & dosificación , Nitrosaminas/toxicidad , Ácido Oléico/análisis , Ácido Oléico/farmacología , Aceite de Oliva , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/mortalidad , Aceites de Plantas/química , Aceites de Plantas/farmacología , Distribución Aleatoria , Aceite de Soja/química , Aceite de Soja/farmacología , Superóxido Dismutasa/metabolismo , Tasa de Supervivencia , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Triglicéridos/química , Triglicéridos/farmacología
11.
Pancreatology ; 6(1-2): 96-102, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16327286

RESUMEN

OBJECTIVES: Effects of polyunsaturated fatty acids (PUFA) on carcinogenesis are discussed controversially. Thus, tumor growth seems to be influenced by type and composition of fat dietary; however, the pathomechanism is still unknown. Therefore, we investigated the impact of different PUFAs on liver metastasis and hepatic lipid peroxidation in a solid model of ductal pancreatic cancer in Syrian hamsters. METHODS: 90 male hamsters were randomized into 6 groups (n = 15). Accordingly groups 2, 4 and 6 received 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly by subcutaneous injection for 12 weeks in order to induce ductal pancreatic cancer, while groups 1, 3 and 5 were treated with 0.5 ml 0.9% sodium chloride. All hamsters received a standard fat diet (SFD) rich in n-6 PUFA for 16 weeks (2.9% fat). Afterwards, groups 1 and 2 had free access to SFD, while groups 3 and 4 were given a diet enriched with n-3, n-6 and n-9 PUFA (SMOF) and groups 5 and 6 were fed a diet high in n-3 PUFA (FISH-OIL). After 32 weeks all hamsters were sacrificed in order to determine incidence of pancreatic carcinoma and liver metastasis. Furthermore hepatic activities of glutathionperoxidase (GSH-Px) and superoxiddismutase (SOD) as well as levels of lipidperoxidation were analyzed intra- and extrametastatically. RESULTS: The incidence of liver metastasis was decreased in the FISH-OIL tumor group compared to the SFD and SMOF groups. However, GSH-Px activity was not influenced by different diets. Extrametastatic hepatic SOD activity did not differ between all groups, while intrametastatic hepatic SOD activity in the SFD-BOP group was increased. In the FISH-OIL-BOP and the SMOF-BOP group intrametastatic SOD activity was lower than in non-metastatic hepatic tissue. Furthermore levels of hepatic lipid peroxidation were decreased in the tumor groups treated with fish oil and SMOF compared to the SFD group. Comparing intra- and extrametastatic TBARS concentration there was no difference in the SFD-BOP and the SMOF-BOP groups, while in the FISH-OIL-BOP group intrametastatic TBARS concentration was increased. CONCLUSION: Conclusively, fish oil reduced the incidence of liver metastasis in experimental ductal pancreatic cancer. Maybe this effect is caused by an increase of intrametastatic hepatic lipid peroxidation.


Asunto(s)
Carcinógenos , Grasas de la Dieta/farmacología , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas/secundario , Hígado/metabolismo , Nitrosaminas , Neoplasias Pancreáticas/metabolismo , Animales , Cricetinae , Dieta , Glutatión Peroxidasa/metabolismo , Neoplasias Hepáticas/patología , Masculino , Mesocricetus , Aceite de Oliva , Neoplasias Pancreáticas/patología , Aceites de Plantas/química , Aceite de Soja/química , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
12.
Pancreatology ; 5(4-5): 403-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15985764

RESUMEN

BACKGROUND/AIMS: Antioxidative vitamins are known to inhibit metastasis. Therefore we evaluated the impact of vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) on liver metastasis in a model of ductal pancreatic adenocarcinoma in hamster. METHODS: One hundred and twenty male Syrian hamsters were randomized into 8 groups (Gr.) (n = 15). Gr. 1-4 were given 0.5 ml normal saline subcutaneously (s.c.) weekly, whereas Gr. 5-8 received 10 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body weight s.c. for 3 months for tumor induction. In the 13th week Gr. 2 and 6 were administered retinol, Gr. 3 and 7 received ascorbic acid and Gr. 4 and 8 were given alpha-tocopherol orally. No treatment was performed in Gr. 1 and 5. After 24 weeks animals were sacrificed, pancreas and liver were histologically determined. Activities of glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD) and concentration of thiobarbituric-acid-reactive substances (TBARS) were analyzed in hepatic tissue. RESULTS: Retinol and alpha-tocopherol decreased the incidence of liver metastases (44.4 vs. 86.7%, p < 0.05). The number and size of liver metastases were significantly reduced by retinol. Activities of GSH-Px and SOD were increased and concentration of TBARS was decreased in NML and LiMe by all vitamins. CONCLUSION: Obviously, antioxidative vitamins prevent oxidative stress in hepatocytes. This may be one mechanism decreasing liver metastasis in pancreatic cancer in the present trial.


Asunto(s)
Antineoplásicos/uso terapéutico , Antioxidantes/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Administración Oral , Animales , Ácido Ascórbico/uso terapéutico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/secundario , Cricetinae , Modelos Animales de Enfermedad , Glutatión Peroxidasa/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Masculino , Mesocricetus , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Nitrosaminas , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Vitamina A/uso terapéutico , Vitamina E/uso terapéutico
13.
Br J Ophthalmol ; 87(10): 1238-40, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14507757

RESUMEN

AIM: To examine the ciprofloxacin susceptibility of 106 Pseudomonas aeruginosa eye isolates from the United Kingdom, Denmark, India, the United States, and Australia, and to determine the molecular mechanisms of resistance. METHODS: Ciprofloxacin susceptibility was tested by an agar dilution method; genomic DNA corresponding to the quinolone target genes gyrA and parC, and the regulatory genes mexR and nfxB controlling drug efflux systems, was amplified by PCR and sequenced; multilocus enzyme electrophoresis was performed to examine the genetic relation among resistant strains. RESULTS: Three out of 90 keratitis isolates (3.3%), one from the United Kingdom and two from India, exhibited MIC values of 16 mg/l or 32 mg/l. The UK isolate had a mutation in gyrA (Thr83Ile), whereas the two Indian isolates showed mutations in both gyrA (Thr83Ile) and parC (Ser87Leu). The remaining isolates from keratitis, endophthalmitis, contact lens associated red eye (CLARE), and contact lens storage cases showed MIC values below 1 mg/l. Several allelic forms of gyrA and a single variation in the mexR gene product were detected in 10 ciprofloxacin susceptible strains. CONCLUSIONS: The vast majority of eye isolates of P aeruginosa from European countries are fully susceptible to ciprofloxacin and the concentration of ciprofloxacin eye drops used for local treatment (3000 mg/l) exceeds MIC values for strains recorded as resistant. Mutations in more than one target gene were associated with higher MIC values.


Asunto(s)
Antiinfecciosos/uso terapéutico , Ciprofloxacina/uso terapéutico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Queratitis/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , ADN Bacteriano/genética , Farmacorresistencia Bacteriana/genética , Infecciones Bacterianas del Ojo/genética , Genes Bacterianos , Humanos , Queratitis/microbiología , Mutación/genética , Análisis de Secuencia de ADN
14.
Ann Nutr Metab ; 43(2): 121-6, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10436311

RESUMEN

BACKGROUND: alpha-Linolenic acid (ALA) has been shown to have a promoting effect on pancreatic carcinogenesis. The purpose of this study was to evaluate the influence of ALA on liver metastases in a model of BOP-induced pancreatic ductular carcinoma in the Syrian golden hamster. METHODS: While the control group (group V) received a standard diet low in fat (soya oil, 3 w/v) without ALA, groups I-IV were fed a diet high in fat (soya oil 25 w/v) with increasing percentages of ALA (2.5, 5, 7.5 and 10%) for 16 weeks. RESULTS: No significant differences in mean body weight and pancreas weight were found between the groups. But significant differences (p = 0.0001) were observed in the mean weight of the resected liver. Treatment with BOP alone resulted in the induction of well-differentiated ductal pancreatic adenocarcinoma in 91%, while all groups treated with different amounts of ALA had induction of 100%. The incidence of liver metastases differed significantly between the groups. The incidence of liver metastases in group I (2.5% ALA) was 18%, in group II (5% ALA) 27%, in group III (7.5% ALA) 50%, and in group IV (10% ALA) 91%. Moreover, the diameter of liver metastases increased significantly according to ALA supplementation (p = 0.001). CONCLUSION: The results indicate that dietary ALA increases liver metastases in BOP-initiated pancreatic cancer.


Asunto(s)
Grasas Insaturadas en la Dieta/farmacología , Neoplasias Hepáticas/secundario , Nitrosaminas/toxicidad , Neoplasias Pancreáticas/patología , Ácido alfa-Linolénico/farmacología , Animales , Carcinógenos/toxicidad , Cricetinae , Incidencia , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Mesocricetus , Mutágenos/toxicidad , Neoplasias Pancreáticas/inducido químicamente
16.
Fertil Steril ; 63(1): 63-70, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7805926

RESUMEN

OBJECTIVE: To determine the immunoglobulin (Ig) A subclass distribution of antibodies in the serum and cervical mucus (CM) of infertile women and to evaluate the effect of an IgA1 protease on the removal of sperm-bound antibodies. METHODS: Twenty infertile women with antisperm antibodies in serum (n = 10) or in CM (n = 10) were recruited for this study. Monoclonal antibodies to human IgA1 and IgA2 were conjugated to immunobeads and the IgA subclass distribution of antisperm antibodies was determined for positive serum and CM samples. The effect of an IgA1 protease (isolated from Neisseria meningitidis strain HF13) on sperm-bound antibodies was evaluated by immunobead binding. RESULTS: In serum, IgA1 subclass antisperm antibodies predominated (89%) when compared to IgA2 (11%). In CM IgA1 accounted for 62% and IgA2 accounted for 38% of the total IgA antisperm antibodies. Enzyme treatment was able to reduce dramatically the amount of serum IgA antibodies bound to sperm from 88% to 10%. Similarly, a significant reduction in CM antisperm antibodies was observed after enzymatic treatment with no loss in sperm motility. CONCLUSION: Cervical mucus antisperm antibodies have a higher proportion of IgA2 subclass suggesting a local production of IgA. Specific IgA1 protease treatment is capable of reducing the amount of immunobead-detectable IgA on sperm. Hamster sperm penetration assays are ongoing to determine if this treatment might improve sperm penetration rates with antibody positive sperm.


Asunto(s)
Anticuerpos/clasificación , Inmunoglobulina A/análisis , Inmunoglobulina A/clasificación , Infertilidad Femenina/inmunología , Péptido Hidrolasas/farmacología , Serina Endopeptidasas , Espermatozoides/inmunología , Anticuerpos/análisis , Bromelaínas/farmacología , Medios de Cultivo/química , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/clasificación , Masculino
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