RESUMEN
Efficacy and safety of testosterone gel 2% (TG) were evaluated in two phase 3, open-labelled, single-arm, multicentre studies (000023 and extension study 000077). Hypogonadal men having serum testosterone levels <300 ng/dl at two consecutive measurements were included. Study duration was 9 months (000023: 3 months; 000077: 6 months). Starting dose of TG (46 mg) was applied on upper arm/shoulder. The primary endpoint (000023) was responder rate (subjects with average 24-hour serum testosterone concentration 300-1050 ng/dl on Day 90). Study 000077 evaluated the safety of TG in patients rolling over from study 000023 over a period of 6 months. Of 180 subjects in 000023, 172 completed and 145 rolled over to 000077, with 127 completers. The responder rate was 85.5%. Fewer subjects in 000077 (12.7%) versus 000023 (31.8%) had maximum testosterone concentration (Cmax ) >1500 ng/dl, with no significant safety concerns. Significant improvements in sexual function and quality of life were noted in both studies. Subjects experienced few skin reactions without notable increases in prostate-specific antigen and haematocrit levels. TG was efficacious with an acceptable safety profile. Cmax >1500 ng/dl did not exhibit distinct impact on safety parameters. However, further optimisation of titration schema to reduce Cmax is warranted while maintaining the average steady state total testosterone concentration.
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Andrógenos/uso terapéutico , Terapia de Reemplazo de Hormonas/efectos adversos , Hipogonadismo/tratamiento farmacológico , Testosterona/uso terapéutico , Administración Cutánea , Adolescente , Adulto , Anciano , Andrógenos/administración & dosificación , Andrógenos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Testosterona/administración & dosificación , Testosterona/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Pharmacokinetics, pharmacodynamics and safety of a novel hydroalcoholic testosterone gel 2% (TG) were evaluated in phase II sequential dose escalation studies using 3 application sites (thigh, abdomen and shoulder/upper arm) and 2 application methods. Hypogonadal men (n = 40), 18-75 years, with serum testosterone <300 ng dl(-1) were included in both studies. Study 1 evaluated hand-applied multiple doses of TG 1.25, 2.50 and 3.75 ml (23, 46 and 70 mg of testosterone, respectively), once daily for 10 days to shoulder/upper arm. Study 2 evaluated applicator-applied (TG 1.25, 2.50 and 3.75 ml) versus hand-applied (TG 2.5 ml) doses, once daily for 7 days to shoulder/upper arm. Primary endpoint for both studies was responder rate (Cave testosterone levels between 298 and 1050 ng dl(-1) ). In Study 1 following multiple applications, >70% participants in each group were responders. Dose-dependent increase was observed in PK values for total testosterone, free testosterone and DHT. In Study 2, responder rate was dose proportional: 16.7%, 50.0% and 77.8% responders in TG 1.25, 2.50 and 3.75 ml groups respectively. The bioavailability was highest for the shoulder application. There was a significant improvement in almost all the domains of sexual functioning. Applicator-application was preferred over hand-application by majority of the participants. TG was found to be safe and well tolerated in hypogonadal men.
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Geles/farmacocinética , Geles/uso terapéutico , Hipogonadismo/tratamiento farmacológico , Testosterona/farmacocinética , Testosterona/uso terapéutico , Adolescente , Adulto , Anciano , Disponibilidad Biológica , Dihidrotestosterona/sangre , Geles/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Testosterona/efectos adversos , Testosterona/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To investigate the systemic renin-angiotensin system (RAS) in essential hypertensives (EH) and controls (C) after short- and long-term vitamin D receptor activation. DESIGN: Ten consecutive EH (under controlled low-salt diet) and 10 C underwent calcitriol administration (0.25 µg bid) for 1 week (Group A). Eighteen consecutive EH under angiotensin II receptor antagonist therapy received a single oral dose of 300,000 IU of cholecalciferol and were followed up for 8 weeks (Group B). METHODS: In basal conditions and at the end of the study (1 week in Group A and 8 weeks in Group B), plasma renin activity (PRA), plasma active renin, aldosterone, and angiotensin II were evaluated, as well as blood pressure, plasma 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH. RESULTS: In Group A, plasma 25(OH)D levels in EH and C were below the normal range, although lower levels were found in the former. No association between basal plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS components was observed either in the whole group or in the two subgroups. Calcitriol administration did not affect any RAS parameter either in EH or in C. In Group B, cholecalciferol significantly increased 25(OH)D and 1,25(OH)2D levels without interfering with the angiotensin II receptor antagonist-induced increase in RAS components. No correlation was found between plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS parameters before and after cholecalciferol administration. CONCLUSIONS: The present data suggest that, in our experimental conditions, vitamin D receptor activation is unable to influence systemic RAS activity.
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Antihipertensivos/administración & dosificación , Calcitriol/administración & dosificación , Hipertensión/tratamiento farmacológico , Receptores de Calcitriol/agonistas , Sistema Renina-Angiotensina/efectos de los fármacos , Vitamina D/administración & dosificación , Adulto , Aldosterona/sangre , Angiotensina II/sangre , Antagonistas de Receptores de Angiotensina/uso terapéutico , Dieta Hiposódica , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Renina/sangre , Renina/metabolismoRESUMEN
BACKGROUND: Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. AIM: To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. MATERIAL/ METHODS: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1±5.0 months) in 19 and 41 patients, respectively. RESULTS: As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m(2), p<0.0007; LV mass g/m(2.7), p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow- up were statistically significant (p<0.01) between groups. Basal LV mass/m(2.7) was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). CONCLUSIONS: Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system.
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Adenoma/epidemiología , Neoplasias de la Corteza Suprarrenal/epidemiología , Hiperplasia Suprarrenal Congénita/epidemiología , Hiperaldosteronismo , Hipertensión/epidemiología , Adenoma/cirugía , Neoplasias de la Corteza Suprarrenal/cirugía , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Adulto , Anciano , Aldosterona/sangre , Presión Sanguínea/fisiología , Fenómenos Fisiológicos Cardiovasculares , Estudios de Seguimiento , Humanos , Hiperaldosteronismo/tratamiento farmacológico , Hiperaldosteronismo/epidemiología , Hiperaldosteronismo/cirugía , Hipertrofia Ventricular Izquierda/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Testosterone gel formulations have become a popular testosterone replacement therapy in patients with hypogonadism since their advent in the year 2000. The gel formulations restore testosterone levels to mid-normal physiological levels (14-17.5 nmol/L) as early as within 24 h, and help alleviate the signs and symptoms of testosterone deficiency, thereby leading to an improved quality of life. Although testosterone gels have a favourable efficacy and safety profile as compared to injectable and patch formulations, risk of secondary exposure poses a challenge. Approved testosterone topical formulations include Tostrex® (Tostran® , Fortesta® ), Androgel® (Testogel® ), Testim® and Axiron® (solution), which have a favourable efficacy profile and positively impacted patient-reported outcome(s). Besides, Testavan, which is a 2% testosterone gel, is under registration in Europe and already approved in Australia in May 2017. Testavan uses a novel hydroalcoholic and highly viscous topical formulation. This product comes with a metered dose dispenser and a cap applicator that allows a hands-free application for precise dispensing and application. The present article provides a comprehensive review of pharmacokinetic, tolerability and safety profile of the testosterone gels available in the market along with the new 2% testosterone gel, Testavan.
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Terapia de Reemplazo de Hormonas/métodos , Testosterona/administración & dosificación , Administración Tópica , Geles , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Hipogonadismo/tratamiento farmacológico , Masculino , Testosterona/efectos adversos , Testosterona/farmacocinéticaRESUMEN
OBJECTIVES: To establish the prognostic role of clinical and demographic factors in a hospital-based cohort of MS patients categorized by age at clinical onset and clinical course. METHODS: Eighty-three patients with MS had a clinical onset of the disease in childhood (age <16 years; early-onset MS [EOMS]) and 710 in adult age (between 16 and 65 years; adult-onset MS [AOMS]). Patients were followed for a mean period of observation of 5 years. Univariate and multivariate analyses of clinical and demographic predictors for rapid progression and disability were performed using a stepwise Cox regression model with time-dependent covariates. RESULTS: In EOMS, the Expanded Disability Status Scale (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a longer disease duration. The probability to reach growth disability and progression was significantly lower in EOMS than in AOMS. Median times to reach EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but the age at both endpoints was significantly lower in EOMS. In EOMS and AOMS, an irreversible disability was related to a secondary progressive course, a sphincteric system involvement at onset, and an older age at onset (in EOMS only for the group >14 years); in AOMS, other unfavorable factors were a pyramidal involvement at onset and a high relapse frequency in the first 2 years. The risk of entering secondary progression was significantly influenced by a high number of relapses in EOMS and by a higher age at onset and a short interattack interval in AOMS. CONCLUSION: A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor.
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Esclerosis Múltiple/fisiopatología , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Italia/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Pronóstico , Tractos Piramidales/fisiopatología , Recurrencia , Análisis de SupervivenciaRESUMEN
The purpose of this study was to compare magnetic resonance imaging (MRI) features and proton MR spectroscopy (1H-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesion subtypes. Combined MRI and single-voxel 1H-MRS investigation was performed in 54 MS patients (47 relapsing remitting (RR) and seven secondary progressive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions were Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-contrast T(1)-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypointense on pre- and post-contrast T(1)-weighted scans). Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in 1H spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurological controls. MS lesions of RR patients were characterized by a significant increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No significant metabolite changes were found in lesions of SP patients. Gd enhancing plaques showed lactate signal with higher frequency (37.8%) than Gd unenhancing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p<0.01), and to Gd unenhancing lesions (p<0.05). In particular, there was evidence of a significant increase of Cho/Cr in pre-contrast T(1) hypointense Gd enhancing lesions (p<0.01 vs. controls). The Gd unenhancing lesions (p<0.01), in particular the T(1) hypointense group (p<0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates key pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T(1) hypointense lesions, may reflect increased membrane cell turnover. The T(1) hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/Cr. Nevertheless, the lack of statistical differences in NAA/Cr between plaque subgroups suggests that axonal impairment might occur even in the early stages.
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Ácido Aspártico/análogos & derivados , Axones/metabolismo , Axones/patología , Encéfalo/metabolismo , Encéfalo/patología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Adolescente , Adulto , Ácido Aspártico/metabolismo , Encéfalo/fisiopatología , Colina/metabolismo , Creatina/metabolismo , Femenino , Humanos , Ácido Láctico/metabolismo , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Degeneración Nerviosa/fisiopatología , TritioRESUMEN
The hallmark of chronic Chagas' disease cardiomyopathy (CCC) is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effectors of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996) Journal of Clinical Investigation, 98: 1709-1712). Recently, we have studied heart-infiltrating T cells at the functional level. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas' cardiomyopathy. The bulk of evidence points to a significant production of IFN-gamma and TNF-alpha which may be linked to T. cruzi-induced IL-12 production.
Asunto(s)
Cardiomiopatía Chagásica/inmunología , Citocinas/fisiología , Corazón/fisiopatología , Linfocitos T/patología , Animales , Modelos Animales de Enfermedad , Humanos , Interferón gamma , RatonesRESUMEN
PURPOSE: The effects of beta-blockers on severe heart failure are not well known. We investigated the effects of carvedilol (beta 1, beta 2, alpha 1-blocker) on symptoms, functional class (FC), and left ventricular function in patients with refractory heart failure. METHODS: We studied 21 patients, mean age 56 +/- 10 years, 9 in FC IV, e 12 in FC III (intermittently with class IV). The initial dosage was 6.25 mg, and it was increased progressively as tolerated. The mean dose was 42 +/- 11 mg. The patients were submitted to routine clinical evaluation, and electrocardiogram. We determined after 196 +/- 60 days of follow-up the left ventricular end diastolic dimension (by echocardiogram), and left ventricular ejection fraction (using MUGA). RESULTS: Carvedilol was well tolerated by 16 (76%) patients. One patient is in FC II during increment of the dosage. Eight patients were in FC I, and 7 in FC II at 196 +/- 60 days of follow-up. Heart rate decreased from 96 +/- 15 to 67 +/- 10 bpm (p < 0.0001), left ventricular end diastolic diameter from 73 +/- 13 to 66 +/- 12 mm (p < 0.009), and the left ventricular ejection fraction increased from 0.21 +/- 0.06 to 0.34 +/- 0.12 (p < 0.0003). CONCLUSION: Carvedilol may have beneficial effects on cardiac function, remodeling process, and FC. If tolerated, it seems to be a potential alternative option in the medical treatment of refractory heart failure. However, investigations are still necessary to clarify the long-term effects of carvedilol on this specific subgroup of patients.
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Antagonistas Adrenérgicos beta/uso terapéutico , Carbazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Propanolaminas/uso terapéutico , Función Ventricular/efectos de los fármacos , Carvedilol , Tolerancia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 microg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.
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Insuficiencia Cardíaca/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Caquexia/etiología , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Hormona de Crecimiento Humana/sangre , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Alcoholismo/epidemiología , Adulto , Factores de Edad , Anciano , Alcoholismo/complicaciones , Femenino , Enfermedades Gastrointestinales/etiología , Departamentos de Hospitales , Humanos , Medicina Interna , Italia , Hepatopatías Alcohólicas/epidemiología , Enfermedades Pulmonares/etiología , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Trastornos Nutricionales/complicaciones , Ocupaciones , Factores SexualesAsunto(s)
Trasplante de Corazón , Complicaciones Posoperatorias , Infecciones Bacterianas/etiología , Infecciones Bacterianas/prevención & control , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/terapia , Trasplante de Corazón/inmunología , Humanos , Cuidados Posoperatorios , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/prevención & control , Infección de la Herida QuirúrgicaRESUMEN
Multiple sclerosis (MS) onset is usually in adult life (age 20-40 years). Discordant data have been reported concerning the frequency of early onset MS (EOMS) that ranges from 2.7% to 5%, whereas there is a general agreement on prevalence of female sex, particularly after puberty. The initial symptoms in EOMS are frequently characterized by visual loss whereas the other functional systems are involved with a variable frequency. Literature data show that EOMS tends to have a relapsing-remitting course, a high rate of recovery from the initial attack, a long time interval between the first and second attacks and a slow progression rate. A poor prognosis is reported in a few cases of EOMS and seems to be related to number of relapses and to the delay between the first and second attacks.
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Esclerosis Múltiple/fisiopatología , Adolescente , Adulto , Edad de Inicio , Sistema Nervioso Central/fisiopatología , Niño , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Masculino , Pronóstico , Recurrencia , Factores SexualesRESUMEN
PURPOSE: To assess the role of 1H-magnetic resonance spectroscopy (MRS) in detecting biochemical abnormalities in neuronal migration disorders (NMDs). METHODS: We performed 1H-MRS studies on 17 brain NMD areas [five polymicrogyria, eight subcortical heterotopia, and four cortical dysplasia on magnetic resonance imaging (MRI)]. The study group consisted of 15 patients, all but one affected by partial epileptic seizures. Spectra were acquired from volumes of interest localized on NMDs and contralateral sides and compared with those obtained on gray and white matter of 18 neurologic controls. RESULTS: NMD lesions were characterized by lower N-acetylaspartate to creatine (NAA/Cr) and choline to Cr (Cho/Cr) ratios than those of the white (p = 0.002 and p = 0.004) and gray matter (p = 0.03 and p = 0.06) of neurologic controls. In addition, the normal-appearing contralateral sides to the NMD lesions showed a significant decrease of Cho/Cr ratio when compared with those of white (p = 0.003) and gray matter (p = 0.05) of neurologic controls. No relation was found between NAA/Cr decrease, EEG abnormalities, and NMD sides, or between NAA/Cr ratios, duration of epilepsy, and frequency of seizures. Lactate signal was detected in the spectra of four patients who had an epileptic seizure a short time before MR examination. CONCLUSIONS: NAA/Cr decrease may be related more to structural and functional alteration of the NMD sides than to epileptic activity in these lesions. Low Cho/Cr may be related to a more extensive diffuse hypomyelination than suggested by the MRI findings. An activation of anerobic glycolysis during and after seizures could account for the presence of lactate. These data confirm that H-MRS is an advanced technique that may provide useful biochemical information in vivo on neurobiologic processes underlying NMDs.
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Encéfalo/anomalías , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Encéfalo/metabolismo , Corteza Cerebral/anomalías , Corteza Cerebral/metabolismo , Humanos , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/metabolismoRESUMEN
One-third of all Trypanosoma cruzi -infected patients eventually develop chronic Chagas' disease cardiomyopathy (CCC), a particularly lethal inflammatory dilated cardiomyopathy, where parasites are scarce and heart-infiltrating mononuclear cells seem to be the effectors of tissue damage. Since T. cruzi is a major inducer of interleukin-12 production, the role of inflammatory cytokines in the pathogenesis of CCC was investigated. We assayed cytokine production by peripheral blood mononuclear cells (PBMC) from CCC and asymptomatic T. cruzi -infected (ASY) individuals, as well as by T cell lines from endomyocardial biopsies from CCC patients. PBMC from CCC and ASY patients produced higher IFN-gamma levels than normal (N) individuals in response to B13 protein and phytohaemagglutinin PHA; IFN-gamma high responders (> or =1 ng/ml) were 2-3 fold more frequent among CCC patients than ASY individuals. Conversely, IL-4 production in response to the same stimuli was suppressed among T. cruzi -infected patients. The frequency of PHA-induced IFN gammaproducing cells on PBMC was significantly higher among CCC than ASY and N individuals. IFN-gamma and TNF-alpha were produced by ten out of ten PHAstimulated T cell lines from CCC patients; IL-2 and IL-10 were produced by four out of ten and one out of ten lines, respectively; IL-4, IL-1alpha, IL-1beta, IL-6 and IL-12 were undetectable. Our results suggest that CCC and ASY patients may respond differentially to the IFN-gamma-inducing stimulus provided by T. cruzi infection. Given the T(1)-type cytokine profile of heart-infiltrating T cell lines from CCC patients, the ability to mount a vigorous IFN-gamma response may play a role on the differential susceptibility to CCC development.
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Cardiomiopatía Chagásica/inmunología , Interferón gamma/biosíntesis , Trypanosoma cruzi/inmunología , Adulto , Animales , Línea Celular , Movimiento Celular/inmunología , Cardiomiopatía Chagásica/patología , Enfermedad Crónica , Citocinas/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miocardio/inmunología , Miocardio/patología , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
OBJECTIVES: To evaluate the role of proton MR spectroscopy (1H-MRS) in detecting metabolic changes in diffuse or focal lesions in the brain of patients infected with HIV. METHODS: Sixty HIV seropositive patients (25 with HIV related encephalopathies, 20 with toxoplasmosis, eight with progressive multifocal leukoencephalopathies (PMLs), and seven with lymphomas) and 22 HIV seronegative neurological controls were examined with a combined MRI and 1H-MRS technique using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echo sequence, TE 135 ms) were acquired by single voxel, localised on focal lesions in toxoplasmosis, PML, lymphomas, and HIV encephalopathies and on the centrum semiovale of neurological controls. Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, and lipids were evaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios were calculated. RESULTS: A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV diagnostic groups in comparison with neurological controls (p<0.003), suggesting neuronal or axonal damage independent of brain lesion aetiology. However, the NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03) without between group differences. The presence of a lipid signal was more frequent in lymphomas (71%) than in other HIV groups (Fisher's test, p=0.00003). The presence of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be related to an increased membrane synthesis and turnover in tumour cells. A lactate signal (marker of inflammatory reaction), was found in all but one patient with PML lesions (75%), but had a lower incidence in the other HIV diagnostic groups (Fisher's test, p=0.00024). CONCLUSION: 1H-MRS shows a high sensitivity in detecting brain involvement in HIV related diseases, but a poor specificity in differential diagnosis of HIV brain lesions. Nevertheless, the homogeneous metabolic pattern that characterises PML suggests the usefulness of 1H-MRS as an adjunct to MRI in differentiating CNS white matter lesions, such as HIV encephalopathies, from PML.