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1.
J Endocrinol Invest ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904913

RESUMEN

BACKGROUND: People with metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) differ for the presence or absence of cardio-metabolic complications, respectively. OBJECTIVE: Based on these differences, we are interested in deepening whether these obesity phenotypes could be linked to changes in microbiota and metabolome profiles. In this respect, the overt role of microbiota taxa composition and relative metabolic profiles is not completely understood. At this aim, biochemical and nutritional parameters, fecal microbiota, metabolome and SCFA compositions were inspected in patients with MHO and MUO under a restrictive diet regimen with a daily intake ranging from 800 to 1200 kcal. METHODS: Blood, fecal samples and food questionnaires were collected from healthy controls (HC), and an obese cohort composed of both MHO and MUO patients. Most impacting biochemical/anthropometric variables from an a priori sample stratification were detected by applying a robust statistics approach useful in lowering the background noise. Bacterial taxa and volatile metabolites were assessed by qPCR and gas chromatography coupled with mass spectrometry, respectively. A targeted GC-MS analyses on SCFAs was also performed. RESULTS: Instructed to follow a controlled and restricted daily calorie intake, MHO and MUO patients showed differences in metabolic, gut microbial and volatilome signatures. Our data revealed higher quantities of specific pro-inflammatory taxa (i.e., Desulfovibrio and Prevotella genera) and lower quantities of Clostridium coccoides group in MUO subset. Higher abundances in alkane, ketone, aldehyde, and indole VOC classes together with a lower amount of butanoic acid marked the faecal MUO metabolome. CONCLUSIONS: Compared to MHO, MUO subset symptom picture is featured by specific differences in gut pro-inflammatory taxa and metabolites that could have a role in the progression to metabolically unhealthy status and developing of obesity-related cardiometabolic diseases. The approach is suitable to better explain the crosstalk existing among dysmetabolism-related inflammation, nutrient intake, lifestyle, and gut dysbiosis.

2.
Infection ; 52(4): 1607-1614, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38457094

RESUMEN

BACKGROUND: Tularaemia is a zoonotic disease caused by Francisella tularensis, a highly virulent bacterium that affects humans and small wild animals. It is transmitted through direct contact with infected animals or indirectly through contaminated soil, water or arthropod bites (e.g. ticks). Primary thoracic manifestations of tularaemia are infrequent and, therefore, a diagnostic challenge for clinicians. METHODS: We report six tularaemia cases with exclusively thoracic involvement diagnosed in a clinic for pulmonary diseases in Bavaria between 10/2020 and 02/2022. RESULTS: All patients lived or were active in rural areas, four reported a recent tick bite. All patients presented with thoracic lymphadenopathy and pulmonary tumours or consolidations; all underwent bronchoscopy with EBUS-TBNA of lymph nodes, three lung biopsies as well. Five patients showed inflammatory changes in the endobronchial mucosa. The main histological findings were necrotic epithelioid granulomas with remarkable granulocyte infiltration. All cases were identified by positive serology, five by PCR (here identification of F.t. ssp. Holarctica) from biopsy as well. As first-line therapy, oral ciprofloxacin was given (5/6); in 2/6 cases, a combination of quinolone-rifampicin was given. CONCLUSIONS: Pulmonary tularaemia may occur after tick bites and without extrathoracic manifestations. In patients who present with thoracic lymphadenopathy and pulmonary consolidations and who are exposed to increased outdoor activities, tularaemia should be included in the diagnostic pathway. Histologically, the presence of neutrophil-granulocyte infiltrations might help to distinguish tularaemia from other granulomatous infections, e.g. tuberculosis. The combination of quinolone-rifampicin rather than i.v. gentamicin reduced length of hospital stay in two patients.


Asunto(s)
Tularemia , Humanos , Tularemia/diagnóstico , Tularemia/tratamiento farmacológico , Tularemia/microbiología , Tularemia/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Antibacterianos/uso terapéutico , Adulto , Francisella tularensis/aislamiento & purificación , Linfadenopatía/microbiología , Linfadenopatía/patología , Linfadenopatía/etiología , Ciprofloxacina/uso terapéutico
3.
Nat Metab ; 4(4): 476-494, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35478031

RESUMEN

Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Tejido Adiposo/metabolismo , Animales , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidasas , Fibrosis , Inflamación/metabolismo , Resistencia a la Insulina/genética , Macrófagos/metabolismo , Ratones , Obesidad/metabolismo
5.
Biomed Res Int ; 2014: 980429, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24895638

RESUMEN

AIMS: We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). MATERIALS AND METHODOLOGY: We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17- ß -estradiol (17 ß -E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). RESULTS: In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. CONCLUSIONS: Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.


Asunto(s)
Líquido Folicular/metabolismo , Insulina/sangre , Leptina/metabolismo , Síndrome del Ovario Poliquístico/sangre , Adulto , Índice de Masa Corporal , Femenino , Humanos , Leptina/sangre , Inducción de la Ovulación
6.
J Biol Regul Homeost Agents ; 28(4): 775-82, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25620186

RESUMEN

Imoviral™ is a natural product formulation containing a mixture of uncaria, shiitake and ribes extracts. All ingredients are recognized as antioxidant, anti-inflammatory agent and immunomodulant. In order to evaluate the rational basis of extract mixture as immunomodulatory agent, we tested the effect of Imoviral™ formulation on macrophage response to lipopolysaccharide (LPS)-induced stress. The effect was evaluated as variation of reactive oxygen species (ROS) and prostaglandin E2 (PGE2) production and as cytokine gene expression. The extract did not affect cell viability up to 250 µg/ml. Treatment with extract (10-150 µg/ml) reduced ROS and PGE2 production as well as IL-8 and TNF-α gene expression. A pre-treatment with extract blunted LPS-induced production of ROS and PGE2, markers of oxidative and inflammatory stress, as well as the gene expression of all cytokines tested, indicators, in vitro, of immune response activation. In conclusion, we demonstrated that Imoviral™ formulation could be a useful tool to modulate the immune function, reducing the oxidative and inflammatory markers related to bacterial attack. Experimental data suggest that Imoviral™ extract mixture could also represent a preventive pharmacological strategy to enhance cell resistance to bacterial infections.


Asunto(s)
Uña de Gato , Citocinas/genética , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Ribes , Hongos Shiitake , beta-Glucanos/farmacología , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Estrés Oxidativo , Células U937
7.
Minerva Med ; 103(1): 13-21, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22278065

RESUMEN

AIM: Aim of this study was to evaluate the effects of phytocomplexes of Uncaria, Shiitake and Ribes in terms of viability and inflammatory response on immune cell-derived cultures. METHODS: Standardized extracts of Uncaria, Shitake and Ribes and their commercial formulation were tested on cell lines PBMC, U937 and macrophage. The activity was evaluated in terms of cell viability (MTT test), variations of oxidative marker release (ROS and PGE2) and modulatory effects on immune response (gene expression of IL-6, IL-8 and TNFα, RT-PCR). RESULTS: Cell viability was not affected by extracts, except subtle variations observed only at higher doses (>250 µg/mL). The extract mixture was well tolerated, with no effects on cell viability up to doses of 500 µg/mL. Pre-treatment of macrophages with subtoxic doses of the extracts reduced the basal release of oxidative markers and enhanced the cell response to exogenous oxidant stimulation, as revealed by ROS and PGE2 release reduction. The same treatment on macrophage resulted in a selective modulation of the immune response, as shown by an increase of IL-6 mRNA and, partially, IL-8 mRNA, while a reduction was observed for TNFα mRNA. CONCLUSION: Data confirm that extracts and their formulations can act as regulator of the immune system with mechanisms involving the oxidative stress and the release of selected proinflammatory cytokines.


Asunto(s)
Citocinas/metabolismo , Sistema Inmunológico/efectos de los fármacos , Fitoterapia/métodos , Preparaciones de Plantas/farmacología , Ribes , Hongos Shiitake , Uncaria , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Citocinas/genética , Dinoprostona/metabolismo , Combinación de Medicamentos , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Humanos , Sistema Inmunológico/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Estrés Oxidativo/inmunología , Estrés Oxidativo/efectos de la radiación , Preparaciones de Plantas/química , Especies Reactivas de Oxígeno/metabolismo , Ribes/química , Hongos Shiitake/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Células U937/efectos de los fármacos , Células U937/inmunología , Uncaria/química
8.
J Biol Regul Homeost Agents ; 25(1): 71-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21382275

RESUMEN

Recent studies underscore the importance of oxygen supply in bladder cancer. Tumour growth stimulates the production of vasoactive factors to increase oxygen delivery to tissues by vasodilatation. Any vasoconstrictor mediator could impair this vasodilatation reducing the oxygen supply. 8-Iso-PGF2 alpha is a potent vasoconstrictor agent. The aim of this work is to determine 8-Iso-PGF2 alpha release in healthy bladder mucosa and in superficial bladder cancer in order to investigate a pathophysiological vasoconstrictor answer of the superficial bladder cancer. The study was conducted on a sample of 12 patients; for every subject studied 8-Iso-PGF2 alpha release was assayed in healthy bladder mucosa and in superficial bladder tumour. 8-Iso-PGF2 alpha release was significantly reduced (p less than 0.001) in superficial bladder cancer compared with healthy bladder mucosa. The inhibition of the production of a powerful vasoconstrictor such as 8-Iso-PGF2 alpha in the vascular homeostatic mechanism of bladder cancer can represent a response of the tumor tending to contrast an antagonist effect of vasodilatation and the necessary to support the oxygen supply.


Asunto(s)
Dinoprost/análogos & derivados , Consumo de Oxígeno , Neoplasias de la Vejiga Urinaria/metabolismo , Vejiga Urinaria/metabolismo , Vasoconstrictores/metabolismo , Dinoprost/biosíntesis , Dinoprost/farmacología , Femenino , Humanos , Masculino , Membrana Mucosa/metabolismo , Membrana Mucosa/patología , Células Tumorales Cultivadas , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos
9.
J Biol Regul Homeost Agents ; 24(4): 441-6, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21122283

RESUMEN

Resveratrol (3,5,4-trihydroxystilbene), a viniferin polyphenolic compound, has been shown to have neuroprotective effects and we tested its possible antioxidant activity in young and aged rat brain, evaluating, in vitro, synaptosomal 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) production as a marker of oxidative stress. We found that in young rat brain synaptosomes resveratrol perfusion had no effect on basal 8-iso-PGF2alpha production, but quenched to basal levels the increased 8-iso-PGF2alpha production induced by hydrogen peroxide. On the other hand, in aged rats, resveratrol was able to decrease 8-iso-PGF2alpha production both basally and after hydrogen peroxide-induced oxidative stimulus. In conclusion, our findings show that the antioxidant effects of resveratrol in rat brain could play a neuroprotective role in aging, when the increased burden of oxidative stress is faced by defective antioxidant mechanisms.


Asunto(s)
Envejecimiento/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Isoprostanos/biosíntesis , Estilbenos/farmacología , Animales , Antioxidantes/farmacología , Dinoprost/análogos & derivados , Dinoprost/biosíntesis , Peróxido de Hidrógeno/toxicidad , Masculino , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Resveratrol , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo
10.
Int J Immunopathol Pharmacol ; 23(4): 1073-8, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21244756

RESUMEN

Nutrient composition, particularly the omega-6/omega-3 polyunsaturated fatty acids ratio, may differently affect inflammatory mediators production in tissues, which could be causally related to increased cancer incidence in obesity. We evaluated prostaglandin E(2) levels in male Wistar rat prostate, kidney and testicle tissues after 15 days of either a high fat, cafeteria-style diet (5.50 Kcal/g, 30 percent calories from fat, omega-6/omega-3 ratio 2.33) or a standard laboratory chow diet (3.35 Kcal/g, 3 percent calories from fat, omega-6/omega-3 ratio 0.56). In the cafeteria diet compared to standard laboratory diet rats, we found both an increase in weight gain and increased prostaglandin E(2) (PGE(2)) levels in prostate, kidney and testicle tissues. The increased levels of PGE(2) induced by the cafeteria diet could drive an inflammatory process leading to increased incidence of prostate, kidney and testicular cancer in overweight patients.


Asunto(s)
Grasas de la Dieta/administración & dosificación , Dinoprostona/biosíntesis , Riñón/metabolismo , Próstata/metabolismo , Testículo/metabolismo , Animales , Ciclooxigenasa 2/análisis , Masculino , Especificidad de Órganos , Ratas , Ratas Wistar
11.
Curr Med Chem ; 14(19): 2081-94, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17691949

RESUMEN

Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic disease characterized by hepatic inflammation and obliterative fibrosis, resulting in both intra- and extra-hepatic bile duct strictures. End-stage liver disease and bile duct carcinoma represent frequent complications. Incidence and prevalence of PSC in USA have been recently estimated as 0.9 per 100,000 person-years, and 1-6 per 100,000 person-years, respectively. Major diagnostic criteria include the presence of multifocal strictures, beadings of bile ducts, and compatible biochemical profile, once excluded secondary causes of cholangitis. Since the aetiology of PSC remains poorly defined, medical therapy is currently limited to symptom improvement and prolonged survival. Ursodeoxycholic acid (UDCA), corticosteroids and immunosuppressants have been proposed alone or in combination to improve the clinical outcome. In selected cases, surgical or endoscopic procedures need to be considered. Orthotopic liver transplantation (OLT) is at the moment the only definitive approach although disease relapse has been reported. In this article the state of the art in PSC treatment and future promises in this field are reviewed.


Asunto(s)
Colangitis Esclerosante/tratamiento farmacológico , Colangitis Esclerosante/cirugía , Corticoesteroides/uso terapéutico , Antibacterianos/uso terapéutico , Colagogos y Coleréticos/uso terapéutico , Colangitis Esclerosante/etiología , Humanos , Hipolipemiantes/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Ácido Ursodesoxicólico/uso terapéutico
12.
Vox Sang ; 91(2): 126-34, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16907873

RESUMEN

BACKGROUND AND OBJECTIVES: Stem cell collection is a standard procedure for the procurement of autologous grafts to rescue myelosuppression induced by high-dose treatments. Accurate prediction of collection yields may contribute to optimize planning and quality control of collection. MATERIALS AND METHODS: Data of 313 autologous haematopoietic stem cell (AHSC) evaluable collections performed in 208 patients with haematologic and non-haematologic neoplasms from seven centres were prospectively analysed to test the accuracy of yield predictions generated by a formula that required the input of peripheral blood (PB) CD34+ cell precount and desired PB volume to be processed. Data were matched in a standard linear regression, in a zero-point regression analysis and tested for prediction accuracy. Further 165 AHSC collections were analysed on a single-centre basis, using yield predictions as reference standards. RESULTS: Analysis showed high levels of correlation between measured collection yields (my) and predictions (py) (R = 0.85; P = 0.000000) as well as high degree of prediction accuracy (my vs. py at paired t-test: P = 0.114781; median my/py ratio = 1.23). Analysis of additional 165 AHSC collections on a single-centre basis showed that the analysed centres had 70% or more measured yields comprising the 0.6-1.8 interval of the my/py ratio. The observance of the 'efficiency' my/py interval assured collection quality control in these centres confirming the reliability of the method. CONCLUSIONS: This prediction method generates accurate and immediate yield predictions allowing collection planning and rapid efficiency control. As a consequence of our study, four centres out of seven use the described method to plan both leukapheresis number and single-procedure blood processing volume while the remaining three centres plan leukapheresis number on the basis of our predictions, maintaining a fixed single-procedure 200 ml/kg blood volume processing, according to their centre AHSC collection policy.


Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Leucaféresis/normas , Modelos Biológicos , Adolescente , Adulto , Anciano , Recuento de Células Sanguíneas/métodos , Niño , Preescolar , Femenino , Movilización de Célula Madre Hematopoyética/normas , Humanos , Italia , Cinética , Leucaféresis/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Trasplante Autólogo
13.
Int J Immunopathol Pharmacol ; 18(3): 497-502, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16164830

RESUMEN

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2alpha, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2 alpha is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2 alpha formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.


Asunto(s)
Carcinoma Basocelular/metabolismo , F2-Isoprostanos/análisis , Neoplasias Cutáneas/metabolismo , Piel/efectos de la radiación , Rayos Ultravioleta , Administración Tópica , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Carcinoma Basocelular/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/fisiopatología , Vitamina E/administración & dosificación , Vitamina E/uso terapéutico
14.
Int J Immunopathol Pharmacol ; 18(2): 201-12, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15888244

RESUMEN

Feeding and energy expenditures are modulated by the interplay of hormones and neurotransmitters in the central nervous system (CNS), where the hypothalamus plays a pivotal role in the transduction of peripheral afferents into satiety and feeding signals. Aminergic neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) are historically considered to play a key role, but a number of peptides are involved in finely tuning feeding regulation. This review summarizes the current understanding of the CNS mechanisms of orexigenic peptides, such as neuropeptide Y, orexins, and ghrelin, as well as anorectic peptides, such as leptin, neurotensin (NT), cocaine- and amphetamine regulated transcript (CART) peptide, thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), urocortin, amylin.


Asunto(s)
Regulación del Apetito/fisiología , Encéfalo/metabolismo , Sistema Nervioso Periférico/metabolismo , Animales , Encéfalo/fisiología , Metabolismo Energético/fisiología , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuropéptidos/metabolismo , Neurotransmisores/metabolismo , Hormonas Peptídicas/metabolismo , Sistema Nervioso Periférico/fisiología
15.
Gene ; 273(2): 285-93, 2001 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-11595175

RESUMEN

Mutations in the sedlin gene cause spondyloepiphyseal dysplasia tarda (SEDT), a rare X-linked chondrodysplasia. Affected males suffer short stature, deformation of the spine and hips, and deterioration of intervertebral discs with characteristic radiographic changes in the vertebrae. We have sequenced two full-length cDNA clones corresponding to the human sedlin gene. The longest cDNA is 2836 bp, containing a 218 bp 5' untranslated region, a 423 bp coding region, and a 2195 bp 3' untranslated region. The second cDNA does not contain exon 2, suggesting alternative splicing. Sedlin was finely mapped in Xp22.2 by Southern blot analysis on a yeast artificial chromosome/bacterial artificial chromosome map. Comparison of the cDNA sequence and genomic sequence identified six sedlin exons of 67, 142, 112, 147, 84, and 2259 bp. The corresponding introns vary in size from 339 to 14,061 bp. Splice site sequences for four of the five introns conform to the GT/AG consensus sequences, however, the splice site between exons 4 and 5 displays a rare non-canonical splice site sequence, AT/AC. Northern blot analysis showed expression of the sedlin gene in all human adult and fetal tissues tested, with the highest levels in kidney, heart, skeletal muscle, liver, and placenta. Four mRNA sizes were detected with the major band being 3 kb and minor bands of 5, 1.6, and 0.9 kb (the smallest product may reflect a sedlin pseudogene). Sedlin is expressed from both the active and the inactive human X chromosomes helping to explain the recessive nature and consistent presentation of the disease. Human sedlin shows homology to a yeast gene, which conditions endoplasmic reticulum/golgi transport. Characterization of the human sedlin cDNA and determination of the sedlin gene structure enable functional studies of sedlin and elucidation of the pathogenesis of SEDT.


Asunto(s)
Empalme Alternativo/genética , Proteínas Portadoras/genética , Compensación de Dosificación (Genética) , Proteínas de Transporte de Membrana , Osteocondrodisplasias/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , Mapeo Cromosómico , ADN Complementario/química , ADN Complementario/genética , Exones , Femenino , Feto/metabolismo , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Genes/genética , Humanos , Intrones , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ADN , Distribución Tisular , Factores de Transcripción , Cromosoma X/genética
16.
Peptides ; 22(6): 975-8, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11390028

RESUMEN

We have studied the neuromodulatory effects of three synthetic peptides, structurally related to chromatin-derived acidic peptides (ACPs): ACP-1 (Asp-Asp-Ser-Asp-Glu-Glu-Asn), corresponding to the C-terminal fragment of the largest subunit of eukaryotic RNA polymerase II; a more lipophilic derivative, ACP-2 (Ala-Ile-Ser-Pro-Asp-Asp-Ser-Asp-Glu-Glu-Asn); and its phosphorylated form ACP-3 (Ala-Ile-Ser-Pro-Asp-Asp-Ser(P)-Asp-Glu-Glu-Asn). Rat hypothalamic synaptosomes, loaded with [(3)H]norepinephrine or [(3)H]dopamine, were perfused with the above peptides, both basally and during a depolarizing stimulus. We have found: ACP-1 inhibited both dopamine and norepinephrine release; ACP-2 inhibited dopamine release, without affecting norepinephrine release; ACP-3 was almost ineffective, except for a weak dopamine inhibiting effect only at a higher concentration.


Asunto(s)
Catecolaminas/biosíntesis , Cromatina/metabolismo , Hipotálamo/metabolismo , Péptidos/química , Péptidos/metabolismo , Animales , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Norepinefrina/antagonistas & inhibidores , Fosforilación , Ratas , Ratas Wistar , Sinaptosomas/metabolismo
17.
Toxicol Lett ; 116(3): 231-6, 2000 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-10996485

RESUMEN

Nonhormonal antineoplastic therapy can affect the endocrine system with consequent effects on the growth of hormone-sensitive tumors. Amongst anthracycline antibiotics, we have found daunorubicin and epirubicin able to acutely stimulate prolactin (PRL) secretion both in vivo, in the rat, and in vitro, from rat anterior pituitary cell cultures. Despite a similar structure, doxorubicin showed no such activity. Considering the possible role of PRL in breast cancer cell proliferation, the effects of certain anthracyclines might be viewed as an adverse drug reaction involving the anterior pituitary gland.


Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Prolactina/fisiología , Animales , Daunorrubicina/toxicidad , Relación Dosis-Respuesta a Droga , Doxorrubicina/toxicidad , Epirrubicina/toxicidad , Masculino , Prolactina/metabolismo , Ratas , Ratas Wistar
18.
Eur J Pharmacol ; 369(3): 299-304, 1999 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-10225366

RESUMEN

Leptin, an adipocyte-derived 16 kDa polypeptide hormone, has been found to regulate food intake and thermogenesis by modulating stimulatory and inhibitory pathways in the feeding circuitry of the hypothalamus, among which corticotropin releasing hormone (CRH). Nitric oxide (NO) and prostaglandins have been shown to be involved in both CRH neurosecretion and feeding regulation. We have investigated the role of NO, prostaglandin E2 and prostaglandin F2alpha as mediators of the hypothalamic effects of leptin and their possible involvement in leptin-stimulated CRH secretion. Using primary cultures of neonatal (5- to 6-day-old) rat hypothalamic cells, we confirmed that leptin (0.1-10 nM) stimulates CRH secretion. This effect was not blocked by L-N(G)-nitro-methyl-arginine (L-NAME, 100 microM), a NO-synthase competitive inhibitor; and leptin did not stimulate NO production. Cyclooxygenase inhibition by indomethacin (10 microM) did not modify leptin-induced CRH secretion, while leptin stimulated prostaglandin E2, and prostaglandin F2alpha secretion. In conclusion, leptin-induced hypothalamic CRH secretion is not modulated by NO-synthase- or cyclooxygenase-mediated mechanisms; leptin does not stimulate NO production, but it stimulates prostaglandin E2 and F2alpha production, which could add to the growing list of mediators of leptin signaling in the hypothalamus.


Asunto(s)
Hormona Liberadora de Corticotropina/metabolismo , Dinoprost/fisiología , Dinoprostona/fisiología , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Óxido Nítrico/fisiología , Proteínas/farmacología , Animales , Animales Recién Nacidos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Inhibidores de la Ciclooxigenasa/farmacología , Dinoprost/biosíntesis , Dinoprostona/biosíntesis , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Indometacina/farmacología , Leptina , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Ratas
19.
Rev Esp Cardiol ; 52(12): 1066-74, 1999 Dec.
Artículo en Español | MEDLINE | ID: mdl-10659653

RESUMEN

INTRODUCTION AND OBJECTIVES: The importance of the clinical presentation in the frequency and type of recurrences of ventricular arrhythmias in patients that received an automatic implantable defibrillator is not well known. The purpose of this study was to analyze the frequency and type of recurrences in patients with an old myocardial infarction that received an automatic implantable defibrillator with electrogram recording. METHODS AND RESULTS: We analyzed 100 patients classified in 3 groups according to their clinical presentation: Sustained Monomorphic Ventricular Tachycardia (VT Group n = 65), Cardiac Arrest (CA Group = 19), and Syncope (Syncope Group n = 16). There were no significant differences in the clinical variables among the different groups, nor in the inducibility of arrhythmia at the electrophysiologic study. In a follow-up 27 +/- 14 months, 54% of patients presented at last one episode of sustained ventricular arrhythmia. All recurrences except one were as sustained monomorphic ventricular tachycardia (776 episodes). 81% of episodes of sustained monomorphic ventricular tachycardia (630) were treated with antitachycardia pacing with an effectiveness of 89%. There were no differences in the probability of arrhythmic recurrence among groups but death probability was higher in the ventricular fibrillation group at 36 follow-up months (38% vs 7% and 12% in the sustained monomorphic ventricular tachycardia and syncope groups respectively, p = 0.0113). CONCLUSIONS: In the patients with an old myocardial infarction and malignant ventricular arrhythmias, most of recurrences are due to sustained monomorphic ventricular tachycardia independently of the clinical presentation. The antitachycardia pacing is not only effective in patients with documented sustained monomorphic ventricular tachycardia but also in those that are presented as cardiac arrest or syncope.


Asunto(s)
Arritmias Cardíacas/terapia , Desfibriladores Implantables , Infarto del Miocardio/complicaciones , Anciano , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiología , Desfibriladores Implantables/estadística & datos numéricos , Electrocardiografía/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Paro Cardíaco/diagnóstico , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Recurrencia , Síncope/diagnóstico , Síncope/etiología , Síncope/terapia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiología , Taquicardia Ventricular/terapia
20.
Hum Reprod ; 13(6): 1486-9, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9688377

RESUMEN

The aim of the present study was to evaluate the efficacy of low-dose versus high-dose aspirin in the prevention of postoperative adhesion formation. Forty New Zealand White rabbits were randomized into three groups: low-dose aspirin (1.7 mg/kg per day for 5 days starting on the day of surgery), high-dose aspirin (28.0 mg/kg per day), and controls. The rabbits underwent a standardized surgical injury on the ovary, uterine horn and abdominal wall on one side at laparotomy. On postoperative day 21, a second-look laparotomy was performed for the evaluation of postoperative adhesions. In five animals in each group, peritoneal fluid samples were collected at initial surgery, then through an additional 2 cm incision performed on postoperative day 3, and at second-look laparotomy. The peritoneal concentrations of thromboxane B2 and 6-keto-prostaglandin F1alpha (the stable hydrolysis product of prostacyclin) were measured by radioimmunoassay. At second-look laparotomy, the adhesion formation rate was 46% in the low-dose aspirin group, 77% in the high-dose group, and 100% in the control group. The adhesion score in the low-dose group was significantly lower (P < 0.01) than in the high-dose and control groups. Peritoneal thromboxane decreased significantly during treatment in both low-dose and high-dose aspirin groups, whereas prostacyclin decreased only in the high-dose group. Postoperative adhesion reduction observed in this study with low-dose aspirin treatment could be due to the selective inhibition of thromboxane over prostacyclin production.


Asunto(s)
Aspirina/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Trombosis/prevención & control , Tromboxanos/antagonistas & inhibidores , Músculos Abdominales/cirugía , Animales , Femenino , Ovario/cirugía , Conejos , Útero/cirugía
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