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1.
J Endocrinol Invest ; 46(5): 1009-1016, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36459368

RESUMEN

PURPOSE: To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. METHODS: Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007-2020) were retrospective evaluated. RESULTS: The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor's surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. CONCLUSION: This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed "one-size-fits-all model" is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.


Asunto(s)
Enfermedades del Sistema Endocrino , Endocrinología , Neoplasias , Adulto , Humanos , Niño , Adolescente , Adulto Joven , Estudios de Seguimiento , Estudios Retrospectivos , Enfermedades del Sistema Endocrino/epidemiología
2.
Rev. bras. plantas med ; 18(1,supl.1): 264-272, 2016. tab, graf
Artículo en Portugués | LILACS | ID: lil-782975

RESUMEN

RESUMO A preocupação com o tratamento do Diabetes mellitus (DM) leva a uma crescente busca por terapias alternativas, como o uso de plantas medicinais, entre as quais, destaca-se o uso de Handroanthus heptaphyllus (Mart.) Mattos (popular Ipê roxo). Neste estudo realizamos a investigação química da presença de compostos fenólicos em H. heptaphyllus e o efeito do tratamento com o extrato aquoso da casca desta planta em parâmetros bioquímicos e nos níveis de lipoperoxidação tecidual e plasmática em animais diabéticos. Metodologia: Ratos Wistar machos foram submetidos ao desenvolvimento do quadro de DM por meio da administração intraperitoneal (IP) de Aloxano monohidrato (150 mg/Kg IP). Após a confirmação de hiperglicemia (>200 mg dL-1), os animais foram distribuídos nos grupos Diabético (D; n=6) e Diabético Tratado (DT; n=6). O tratamento consistiu na administração diária do extrato aquoso da casca de H. heptaphyllus via oral (v.o.) (150mg/Kg v.o.) por quatro semanas. O extrato aquoso foi analisado qualitativamente por cromatografia de camada delgada. Resultados: A análise qualitativa do extrato aquoso da casca indicou a presença de compostos fenólicos da subclasse flavonoides. O tratamento com o extrato aquoso reduziu a glicemia de jejum a partir da 3ª semana de tratamento, melhorou a resposta glicêmica à sobrecarga de glicose, diminuiu os níveis de triglicerídeos e índice LDL (Triglicerídeos/HDL). Estes resultados sugerem o uso terapêutico do extrato aquoso das cascas de H. heptaphyllus no tratamento do DM.


ABSTRACT Alternative medicine for diabetes mellitus (DM) treatment represents a growing research area on the use of medicinal plants, of which Handroanthus heptaphyllus (mart.) Mattos (popularly known as purple ipe) is most prominent. In this study, we investigated the presence of phenolic compounds and the effects of treatment with aqueous extract of in H. heptaphyllus in biochemical profile in plasma and the levels of lipid peroxidation in tissues and plasma in diabetic animals. Male Wistar rats were induced to develop DM through intraperitoneal (IP) administration of alloxan monohydrate (150 mg/kg IP). Once hyperglycemia (>200 mg dL-1) was confirmed, the animals were divided into the Diabetic (D; n=6) and Treated Diabetic (TD; n=6) groups. The TD group received daily administration (150 mg/kg v.o.) of aqueous extract of H. heptaphyllus for four weeks. The aqueous extract was also analyzed qualitatively by layer chromatography. Qualitative analysis of the aqueous extract of the bark indicated the presence of phenolic compounds from the flavonoid subclass. The treatment with the aqueous extract reduced fasting blood glucose levels from the third week of treatment on, improved the glycemic response to the glucose tolerance test, and lowered the levels of triglycerides and the LDL index (triglycerides/HDL). These findings suggest therapeutic use of the aqueous extract of H. heptaphyllus bark in treating DM.


Asunto(s)
Ratas , Ratas/clasificación , Tabebuia/química , Compuestos Fenólicos/análisis , Plantas Medicinales/clasificación , Diabetes Mellitus/fisiopatología
3.
Neurosurg Rev ; 37(2): 321-9; discussion 329, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24526364

RESUMEN

The aim of this paper is to report on our ample experience with the medial cord to musculocutaneous (MCMc) nerve transfer. The MCMc technique is a new type of neurotization which is able to reanimate the elbow flexion in multilevel avulsive injuries of the brachial plexus provided that at least the T1 root is intact. A series of 180 consecutive patients, divided into four classes according to the quality of hand function, is available for a long-term follow-up after brachial plexus surgery. The patients enrolled for the study have in common a brachial plexus palsy showing multiple cervical root avulsive injuries at two (C5-C6), three (C5-C6-C7) and four (C5-C6-C7-C8) levels. The reinnervation of the musculocutaneous nerve is obtained via an end-to-end transfer from two donor fascicles located in the medial cord. The selected fascicles are those directed principally to the flexor carpi radialis, ulnaris and, to a lesser degree, the flexor digitorum profundus. Under normal anatomic conditions, they are located in the medial cord, and their site corresponds to the inverted V-shaped bifurcation between the internal contribution of the median nerve and the ulnar nerve. The technique has no failure and no complications when the hand shows a normal wrist and finger flexion and a normal intrinsic function. In case of suboptimal conditions of the hand, the technique has proved technically more challenging, but still with 67% satisfactory results. In the four-root avulsive injuries, however, this method shows its limitations and an alternative strategy should be preferred when possible. EMG analysis shows a reinnervation in both the biceps and the brachialis muscles, explaining the high quality of the observed results. Moreover, this technique theoretically offers the possibility of a "second attempt" at a more distal level in case of failure of the first surgery. This procedure is quick, safe, extremely effective and easily feasible by an experienced plexus surgeon. The ideal candidate is a patient harbouring a C5-C6 avulsive injury of the upper brachial plexus with a normally functioning hand.


Asunto(s)
Neuropatías del Plexo Braquial/cirugía , Plexo Braquial/cirugía , Articulación del Codo/cirugía , Codo/cirugía , Transferencia de Nervios , Anciano , Codo/inervación , Articulación del Codo/inervación , Electromiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Transferencia de Nervios/métodos , Resultado del Tratamiento , Nervio Cubital/fisiopatología , Nervio Cubital/cirugía
4.
Transplant Proc ; 45(7): 2785-7, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24034049

RESUMEN

Atypical hemolytic uremic syndrome (aHUS), which can recur after renal transplantation, is associated with poor graft outcomes. The underlying genetic defect, namely, mutations in genes coding for the complement factor H, I (CFI), or membrane cofactor protein, greatly impacts the risk of aHUS recurrence. We report here the case of a patient with chronic renal failure due to aHUS in which screening for complement mutations, performed before wait-listing for kidney transplantation, showed a never described previously heterozygous mutation in the exon II of the CFI gene. Specifically, this mutation leads to a substitution of cytosine for guanosine at nucleotide 148, resulting in the change at amino acid 50 from arginine to proline. Subsequently, he received a renal allograft from deceased donor. Good graft function was established immediately, without clinical features of aHUS. Due to a lack of data on this mutation, we avoided prophylactic treatment for aHUS but closely monitored biochemical markers of aHUS to treat a possible recurrence. Immunosuppressive treatment was based on basiliximab, tacrolimus, steroids, and mycophenolic acid. At the time of discharge the serum creatinine was 1.4 mg/dL. Ten months after transplantation the patient is doing well without evidence of aHUS. Our case suggested that a heterozygous mutation in exon II of the CFI gene was not associated with a risk of early post-transplant aHUs recurrence adding new knowledge on complement mutations implicated in aHUS post-transplant recurrences.


Asunto(s)
Factor I de Complemento/genética , Síndrome Hemolítico-Urémico/genética , Trasplante de Riñón , Mutación , Adulto , Síndrome Hemolítico Urémico Atípico , Humanos , Masculino , Recurrencia
5.
Neurobiol Aging ; 32(12): 2142-51, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20106550

RESUMEN

Alteration of key regulatory kinases may cause aberrant protein phosphorylation and aggregation in Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we investigated expression and phosphorylation status of glycogen synthase kinase 3 (GSK-3), protein kinase B (Akt) and tau protein in peripheral blood lymphocytes of 20 AD, 25 PD patients and 20 healthy controls. GSK-3 was increased in AD and PD patients. In these latter, GSK-3 levels were positively correlated with daily L-Dopa intake. Phosphorylated Akt expression was augmented in both groups; total Akt levels were increased only in AD patients and were positively correlated with disease duration and severity. Total and phosphorylated tau were increased only in AD, with phospho-tau levels being positively correlated with levels of total tau, Akt, and disease duration. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of specific kinases may, therefore, lead to the development of innovative biomarkers of neurodegeneration, particularly for AD.


Asunto(s)
Enfermedad de Alzheimer/enzimología , Glucógeno Sintasa Quinasa 3/biosíntesis , Leucocitos Mononucleares/enzimología , Enfermedad de Parkinson/enzimología , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas tau/biosíntesis , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Células Cultivadas , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Masculino
6.
G Ital Nefrol ; 26(2): 191-200, 2009.
Artículo en Italiano | MEDLINE | ID: mdl-19382075

RESUMEN

Whether or not to consider a uremic patient for retransplantation remains a matter of debate. Donor shortage and putative poor outcomes are the main cons, improved results in the last decade and a better survival (HR 0.50) with retransplantation than dialysis stand as pros. The percentage of patients waitlisted for retransplantation or already having been retransplanted is increasing (up to 20-30%) and the absolute contraindications are limited to rare conditions (loss of previous transplant due to anti-glomerular basement antibodies in Alport's syndrome, early recurrence of GNF or hemolytic uremic syndrome). When retransplantation is considered, however, careful screening for risk factors is mandatory, whether they are related to the previous graft or to the recipient's clinical features or the donor's demographics and immunological status. In the last decade the clinical outcomes of retransplantation have significantly improved. No difference in patient survival at the fifth year has been reported between first, second and third grafts. The kidney survival at the same interval is above 70% for the second graft and 65% for the third graft. Nephrectomy of a previous graft is not necessary if not for clinical reasons. As far as the maximum number of retransplants is concerned, most transplant centers (69%) set no clear-cut limit. In conclusion, also taking into account that many patients after graft failure ask for readmission to the waiting list (75% in our experience), we think the retransplantation option should always be evaluated.


Asunto(s)
Trasplante de Riñón , Supervivencia de Injerto , Humanos , Trasplante de Riñón/mortalidad , Pronóstico , Reoperación , Tasa de Supervivencia , Resultado del Tratamiento
7.
Neuroscience ; 155(3): 585-96, 2008 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-18621101

RESUMEN

In this report, we have assessed the behavioral responses of mice missing the Ppif gene (CyPD-KO), encoding mitochondrial cyclophilin D (CyPD). Mitochondrial CyPD is a key modulator of the mitochondrial permeability transition which is involved in the regulation of calcium- and oxidative damage-induced cell death. Behavioral screening of CyPD-KO mice (ranging between 4 and 15 months of age) was accomplished using a battery of behavioral paradigms which included testing of motor functions, exploratory activity, and anxiety/emotionality, as well as learning and memory skills. We found that, compared with wild-type mice, CyPD-KO mice were (i) more anxious and less explorative in open field and elevated plus maze and (ii) performed better in learning and memory of avoidance tasks, such as active and passive avoidance. However, the absence of CyPD did not alter the nociceptive threshold for thermal stimuli. Finally, deletion of CyPD caused also an abnormal accumulation of white adipose tissue resulting in adult-onset obesity, which was not dependent on increased food and/or water intake. Taken together, our results suggest a new fundamental role of mitochondrial CyPD in basal brain functions and body weight homeostasis.


Asunto(s)
Ansiedad/genética , Ansiedad/fisiopatología , Reacción de Prevención/fisiología , Ciclofilinas/deficiencia , Obesidad/genética , Obesidad/fisiopatología , Factores de Edad , Análisis de Varianza , Animales , Conducta Animal , Peso Corporal/genética , Peptidil-Prolil Isomerasa F , Modelos Animales de Enfermedad , Ingestión de Líquidos/genética , Ingestión de Alimentos/genética , Conducta Exploratoria/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora/fisiología , Umbral del Dolor/fisiología , Desempeño Psicomotor/fisiología
8.
J Mass Spectrom ; 40(12): 1618-25, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16320296

RESUMEN

The self-assembling of sodium bis (2-ethylhexyl) sulfosuccinate (AOT) in gas phase has been investigated by electrospray ionization- and matrix-assisted laser desorption/ionization mass spectrometry. Large surfactant clusters with an aggregation number close to that found in apolar media have been observed either as positive or negative ions. Moreover, the marked predominance of singly charged species as well as preliminary theoretical calculations strongly suggest an aggregate structure characterized by an internal hydrophilic core hosting the extra charge surrounded by an apolar shell constituted by the surfactant alkyl chains. This structure is similar to that of the more familiar reversed micelles formed when an appropriate surfactant is solubilized in apolar solvents. Finally, similar trends are observed independently either on the ionization technique or the polarity of the solvent used. This, together with the large dependence of the aggregation number on the flow rates, strongly indicates that self-assembling of the surfactant molecules occurs during the evaporation step.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 59(13): 3139-45, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14583289

RESUMEN

1H, 13C and 15N NMR spectra of eight 2-amino-N'-(aryl)-benzamidines and of the parent compound were recorded, and unequivocal chemical shift assignments through the use of COSY, 1H-J resolved, HETCOR and COLOC sequences were performed. 1H and 13C chemical shifts for the nuclei of the benzamidine aromatic ring were not affected by the substituents present at N'-phenyl group, while the substituent effects in the chemical shifts of the same nuclei of N'-phenyl ring were very similar to the ones reported for the corresponding monosubstituted benzenes, indicating that there is no interaction between the two aromatic rings. 15N NMR spectra (DEPT sequence) show just two hydrogenated nitrogen atoms, which confirm that the amino form is the most stable tautomer, but the observation of a sharp signal and two broad signals (15N decoupled spectra), and the corresponding broad signal for the =C-NH(2) protons (in the 1H spectra), indicates the occurrence of tautomerism between the amino and imino forms, observable for some of the studied benzamidines. Theoretical calculations lead to the conclusion that these compounds occur mostly as the amino tautomer with Z configuration, which is stabilized by hydrogen bonding.


Asunto(s)
Benzamidinas/química , Calorimetría , Espectroscopía de Resonancia Magnética/métodos , Modelos Teóricos , Conformación Molecular
10.
Mol Cell Biol ; 20(9): 3125-36, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10757797

RESUMEN

The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) and antiapoptotic (e.g., BCL-2 and BCL-X(L)) molecules. The cell death-regulating activity of BCL-2 members appears to depend on their ability to modulate mitochondrial function, which may include regulation of the mitochondrial permeability transition pore (PTP). We examined the function of BAX and BCL-X(L) using genetic and biochemical approaches in budding yeast because studies with yeast suggest that BCL-2 family members act upon highly conserved mitochondrial components. In this study we found that in wild-type yeast, BAX induced hyperpolarization of mitochondria, production of reactive oxygen species, growth arrest, and cell death; however, cytochrome c was not released detectably despite the induction of mitochondrial dysfunction. Coexpression of BCL-X(L) prevented all BAX-mediated responses. We also assessed the function of BCL-X(L) and BAX in the same strain of Saccharomyces cerevisiae with deletions of selected mitochondrial proteins that have been implicated in the function of BCL-2 family members. BAX-induced growth arrest was independent of the tested mitochondrial components, including voltage-dependent anion channel (VDAC), the catalytic beta subunit or the delta subunit of the F(0)F(1)-ATP synthase, mitochondrial cyclophilin, cytochrome c, and proteins encoded by the mitochondrial genome as revealed by [rho(0)] cells. In contrast, actual cell killing was dependent upon select mitochondrial components including the beta subunit of ATP synthase and mitochondrial genome-encoded proteins but not VDAC. The BCL-X(L) protection from either BAX-induced growth arrest or cell killing proved to be independent of mitochondrial components. Thus, BAX induces two cellular processes in yeast which can each be abrogated by BCL-X(L): cell arrest, which does not require aspects of mitochondrial biochemistry, and cell killing, which does.


Asunto(s)
Genes Fúngicos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas/química , Proteínas Proto-Oncogénicas/genética , Levaduras/genética , Apoptosis , Western Blotting , División Celular , Citometría de Flujo , Galactosa/metabolismo , Glucosa/metabolismo , Membranas Intracelulares/metabolismo , Mutación , Especies Reactivas de Oxígeno/metabolismo , Fracciones Subcelulares/metabolismo , Factores de Tiempo , Proteína X Asociada a bcl-2 , Proteína bcl-X
11.
Ann Oncol ; 11(11): 1445-9, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11142485

RESUMEN

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare malignant tumor and little is known about its clinical features and management. We report on a series of 19 pediatric patients managed over 20 years. PATIENTS AND METHODS: Primary conservative surgery was performed in all patients and was radical in nine, non-radical in three; seven patients underwent biopsy alone (3 unresectable tumors, 4 metastatic disease). In two cases radical surgery was performed after primary chemotherapy. Radiotherapy was delivered to 8 patients, chemotherapy to 15. RESULTS: After a median follow-up of 74 months, the five-year survival was 80% for the whole series, 91% for patients with localized disease, 100% for patients with tumor < or = 5 cm, and 31% for those > 5 cm; 16 of 19 patients were alive (12 of 12 with grossly-resected tumor in first continuous remission). Chemotherapy achieved two partial remission among seven evaluable patients. CONCLUSIONS: Pediatric ASPS has a more favorable prognosis than its adult counterpart. In this series, tumor size correlates with metastatic disease at onset and is the major factor influencing survival. Surgery is the mainstay of therapy. The effectiveness of adjuvant therapy remains to be established, though radiotherapy may be advisable in cases of inadequate surgery.


Asunto(s)
Sarcoma/epidemiología , Neoplasias de los Tejidos Blandos/epidemiología , Adolescente , Quimioterapia Adyuvante , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Italia/epidemiología , Escisión del Ganglio Linfático , Masculino , Estadificación de Neoplasias , Cuidados Paliativos , Radioterapia Adyuvante , Estudios Retrospectivos , Sarcoma/diagnóstico , Sarcoma/patología , Sarcoma/cirugía , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Neoplasias de los Tejidos Blandos/terapia , Resultado del Tratamiento
12.
Percept Mot Skills ; 87(1): 127-30, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9760637

RESUMEN

This study explored the issue of whether status and power differences are expressed in the way men and women hold hands. It was hypothesized that men's hands would be upper in heterosexual handholding couples significantly more often than women's. Also, to explore the possibility that height differences of handholding partners might affect handholding position, all handholding couples observed in this study were classified as couples with men and women of equal height or couples where either the men or women were taller. A total of 1,006 handholing couples were observed, and men's hands were significantly more likely to be the upper one in couples when men were taller than women and in couples where men and women were of equal height, suggesting that, while height does matter, it is less important for this handholding pattern than sex differences.


Asunto(s)
Mano/fisiología , Poder Psicológico , Conducta Social , Tacto/fisiología , Estatura , Femenino , Fuerza de la Mano/fisiología , Humanos , Masculino , Factores Sexuales
13.
Cardiovasc Drugs Ther ; 12(5): 431-7, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9926273

RESUMEN

The influence of the calcium antagonist gallopamil on the contractility of asynergic viable myocardium after acute myocardial infarction treated with thrombolysis was investigated by two-dimensional echocardiography. Sixteen patients with > or = 1 viable segment(s), identified during the low-dose phase (up to 10 micrograms/kg/min) of a dobutamine echocardiographic test (up to 40 micrograms/kg/min) performed 4-5 days after a first acute myocardial infarction, were given a gallopamil intravenous bolus (50 micrograms/kg) 12-24 hours later. Two-dimensional echocardiography was done before and 15 minutes after the bolus. A score index of 1 (normokinesis) to 4 (dyskinesis) and a 16-segment model were used. A segment was considered viable when a resting asynergy (score > or = 2) improvement of > or = 1 grade was seen during low-dose dobutamine. Follow-up echocardiograms were done 3-5 months later. A total of 30 viable segments were found; of these, 10 showed sustained improvement in contractility (group A) during high-dose dobutamine, while 20 exhibited a biphasic response returning to their basal contractile state (group B). After the gallopamil bolus, 9 of 10 group A segments improved their contractility, in comparison with 0 of 20 group B segments (P < .001). Infarct-related vessel significant (> or = 75%) coronary stenosis was present in the tributary vessel of 0 of 10 group A and of 20 of 20 group B segments (P < .001). At follow-up, 9 of 10 group A segments showed a spontaneous contractile improvement; of the 20 group B segments, 8 of 10 that underwent revascularization (7 angioplasty, 3 bypass graft) showed contractile improvement, in comparison with 0 of 10 segments not revascularized (P = .001). We conclude that gallopamil may reverse the contractile dysfunction of postischemic stunned myocardium in patients with acute myocardial infarction, whereas no effects are apparent on ischemic/hibernating myocardium.


Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Galopamilo/uso terapéutico , Corazón/efectos de los fármacos , Hibernación , Contracción Miocárdica/efectos de los fármacos , Aturdimiento Miocárdico , Dobutamina/uso terapéutico , Relación Dosis-Respuesta a Droga , Ecocardiografía , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Terapia Trombolítica
14.
Mol Cell Biochem ; 174(1-2): 181-4, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9309684

RESUMEN

Mitochondria possess an inner membrane channel, the permeability transition pore, which is inhibited by cyclosporin A (CsA) and by matrix protons. As suggested recently by our laboratory, pore closure by these inhibitors may be due to dissociation of mitochondrial cyclophilin (CyP-M), a matrix peptidyl-prolyl-cis-trans isomerase, from its putative binding site on the pore. Unbinding of CyP-M would follow a CsA-dependent or proton-dependent change in conformation of the CyP-M molecule. It is interesting that upon binding of CsA the enzymatic activity of CyP-M is inhibited, but it is not clear whether this event plays a role in pore inhibition. Here we report experiments designed to further test the role of CyP-M in pore function. Our results indicate that CyP-M-dependent and independent mechanisms of pore activation may exist, and that the peptidylprolyl-cis-trans-isomerase activity of CyP-M is not necessarily involved in pore modulation by CyP-M.


Asunto(s)
Mitocondrias Hepáticas/metabolismo , Isomerasa de Peptidilprolil/metabolismo , Animales , Ciclosporina/farmacología , Membranas Intracelulares/metabolismo , Canales Iónicos/efectos de los fármacos , Canales Iónicos/metabolismo , Canales Iónicos/ultraestructura , Mitocondrias Hepáticas/ultraestructura , Permeabilidad/efectos de los fármacos , Ratas
15.
J Biol Chem ; 271(4): 2185-92, 1996 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-8567677

RESUMEN

Mammalian mitochondria possess an inner membrane channel, the permeability transition pore (MTP), which can be inhibited by nanomolar concentrations of cyclosporin (CS) A. The molecular basis for MTP inhibition by CSA remains unclear. Mitochondria also possess a matrix cyclophilin (CyP) with a unique N-terminal sequence (CyP-M). To test the hypothesis that it interacts with the MTP, we have studied the interactions of CyP-M with rat liver mitochondria by Western blotting with a specific antibody against its unique N terminus. Although sonication in isotonic sucrose at pH 7.4 refraction sediments with submitochondrial particles at 150,000 x g. We show that the interactions of this CyP-M pool with submitochondrial particles are disrupted (i) by the addition of CSA, which inhibits the pore, but not of CSH, which does not, and (ii) by acidic pH condition, which also leads to selective inhibition of the MTP; furthermore, we show that the effect of acidic pH on CyP-M fully prevents the inhibitory effect of H+ on the MTP (Nicolli, A., Petronilli, V., and Bernardi, P. (1993) Biochemistry 32, 4461-4465). These data suggest that CyP-M inhibition by CSA and protons may be due to unbinding of CyP-M from its putative binding site on the MTP. A role for CyP-M in MTP regulation is also supported by a study with a series of CSA derivatives with graded affinity for CyP. We show that with each derivative the isomerase activity of CyP-M purified to homogeneity is similar to that displayed at inhibition of MTP opening, CyP-M (but not CyP-A) and decreased efficiency at MTP inhibition is obtained by substitution in position 8 while a 4-substituted, nonimmunosuppressive derivative is a as effective as the native CSA molecule, indicating that calcineurin is not involved in MTP inhibition by CSA.


Asunto(s)
Isomerasas de Aminoácido/metabolismo , Proteínas Portadoras/metabolismo , Ciclosporina/metabolismo , Membranas Intracelulares/química , Mitocondrias Hepáticas/química , Isomerasas de Aminoácido/química , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/química , Membranas Intracelulares/metabolismo , Mitocondrias Hepáticas/metabolismo , Datos de Secuencia Molecular , Péptidos/química , Péptidos/metabolismo , Isomerasa de Peptidilprolil , Permeabilidad , Ratas , Partículas Submitocóndricas/química , Partículas Submitocóndricas/metabolismo
17.
G Ital Cardiol ; 24(2): 123-30, 1994 Feb.
Artículo en Italiano | MEDLINE | ID: mdl-8013764

RESUMEN

BACKGROUND: The reversibility of regional dysfunction early after acute myocardial infarction may be obtained with inotropic adrenergic stimulation, in particular during low dose dobutamine infusion, suggesting the presence of viable myocardium. The aim of this study was to determine whether viable myocardium can be identified by two-dimensional echocardiography after an i.v. bolus of enoximone-positive inotropic non-adrenergic drug, phosphodiesterase III inhibitor as well as during dobutamine infusion, in patients with acute myocardial infarction. METHODS: Twelve male patients, aged 57 +/- 10 years and treated with rtPA (100 mg i.v. in 180 minutes) within the first 6 hours of a first anterior myocardial infarction were studied. All patients underwent a dobutamine infusion (5 and 10 mcg/kg/min, 5 minutes per dose) 4 +/- 1 days after entrance, followed by an enoximone bolus (1 mg/kg over 5 minutes) 1 hour later. Echocardiography was performed before dobutamine and enoximone, during dobutamine, 10 minutes after enoximone and at 6 +/- 2 months follow-up. A Wall Motion Score Index (WMSI) was calculated as recommended by the American Society of Echocardiography. All patients underwent coronarography on days 9-11 post-infarction. RESULTS: Improvement in regional function of basally asynergic segments occurred in 8 patients during dobutamine infusion, as well as after enoximone i.v. bolus, and in 1 patient only during dobutamine infusion. Both dobutamine and enoximone tests were found to be negative in the other 3 patients. A decrease of WMSI was observed with both dobutamine and enoximone tests (from 1.84 +/- 0.32 to 1.73 +/- 0.31; p = .002 with dobutamine; from 1.84 +/- 0.32 to 1.70 +/- 0.27; p = .0132 with enoximone) with concordant wall motion changes between two tests in 73/84 (87%; K = 0.61) basally asynergic segments. There were no complications occurred during the study. Of 8 patients with positive response for viable myocardium to both tests, 6 had a patent and 2 an occluded infarct-related artery. However, in the latter a collateral circulation toward necrotic area was present. At follow-up improvement in regional function of basally asynergic segments, with a decrease of WMSI (from 1.74 +/- 0.23 to 1.59 +/- 0.24; p < .05), was observed in 4 of 8 patients with viable myocardium detected by either dobutamine or enoximone. CONCLUSIONS: 1) Viable asynergic myocardium may be identified early after acute myocardial infarction by enoximone bolus, as carefully and safely as by dobutamine infusion; 2) transient recovery of post-ischemic myocardial dysfunction may be obtained independently of beta-receptor stimulation.


Asunto(s)
Dobutamina , Ecocardiografía Doppler , Enoximona , Infarto del Miocardio/diagnóstico , Anciano , Angiografía Coronaria , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen
18.
Am J Cardiol ; 70(4): 531-5, 1992 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-1642194

RESUMEN

The role of Frank-Starling law of the heart in determining the increase in cardiac output during exercise in humans is still controversial (e.g., the mechanisms responsible for the enhancement of left ventricular [LV] filling during the shortened diastolic interval). Ten weight lifters, 12 swimmers and 12 sedentary subjects who underwent maximal upright bicycle exercise testing were studied. First-pass radionuclide angiography was performed both at rest and at peak exercise using a multicrystal gamma camera. Compared with resting values, heart rate and cardiac index at peak exercise increased by 101 +/- 16 beats/min (p less than 0.001) and 6.7 +/- 2.8 liters/min/m2 (p less than 0.001) in weight lifters, by 96 +/- 9 beats/min (p less than 0.001) and 9.5 +/- 2 liters/min/m2 (p less than 0.001) in swimmers, and by 103 +/- 9 beats/min (p less than 0.001) and 7.3 +/- 1.8 liters/min/m2 (p less than 0.001) in sedentary subjects. Stroke volume increased by 20.5 +/- 9.8 ml/m2 (p less than 0.001) in swimmers only. End-diastolic volume at peak exercise did not change in weight lifters and in swimmers; it decreased by 8.2 +/- 8.6 ml/m2 (p less than 0.01) in sedentary subjects. A significant correlation was found between the decrease in end-systolic volume and the increase in peak rapid filling rate at peak exercise in all 3 groups (r = 0.65, p less than 0.05 in weight lifters; r = 0.59, p less than 0.05 in swimmers; r = 0.67, p less than 0.05 in sedentary subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Angiografía Coronaria/métodos , Ejercicio Físico/fisiología , Función Ventricular Izquierda/fisiología , Adulto , Corazón/diagnóstico por imagen , Hemodinámica , Humanos , Masculino , Cintigrafía , Deportes , Resistencia Vascular
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