ABSTRACT
BACKGROUND: Hepatitis C virus (HCV) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease, particularly following renal transplantation. METHODS: In order to assess the efficacy and tolerance of interferon (IFN) in the treatment of chronic hepatitis C in haemodialysis (HD) patients and their clinical course following renal transplantation, a multicentre, randomized, open-label study was conducted to compare IFN therapy vs a control group. RESULTS: Nineteen HCV RNA-positive patients received 3 x 10(6) U of IFN s.c., three times a week (post-HD), and 17 HCV RNA-positive patients were assigned to the control group. Tolerance to IFN therapy was good in nine patients, while treatment was discontinued in the other 10 due to the occurrence of side effects. HCV RNA was negative at the end of treatment in 14 out of 19 patients (74%) receiving IFN and in one patient (5%) in the control group. Six out of the 14 patients who initially responded to IFN therapy had a virological relapse (43%). Eight patients (42%) remained HCV RNA-negative, three of them until the day that renal transplantation (RT) was performed (7, 12 and 27 months, respectively), as did five patients on HD during the follow-up (27+/-5 months). Eight out of the nine patients (89%) who completed therapy were HCV RNA-negative at the end of treatment, and seven of them (78%) remained HCV RNA-negative during the follow-up on dialysis (21+/-8 months). Mean transaminase (ALT) values were significantly decreased following IFN therapy, while no changes were observed during the follow-up period in the control group. Fifteen patients (10 in the treatment group and five in the control group) underwent RT. Three patients in the treatment group were HCV RNA-negative at RT, and one of them had a virological relapse 20 months after RT, while the other two remained HCV RNA-negative at 3 months and 24 months after RT, respectively. In contrast to the control group, transaminase (ALT) remained within normal limits in all patients in the treatment group. Finally, during the post-RT follow-up, the transaminase mean values were significantly lower in treated patients vs patients in the control group (P<0.05). CONCLUSIONS: It is concluded that the biochemical and virological response to IFN therapy is good in HD patients. In addition, IFN therapy appears to exert a beneficial effect on the course of liver disease following RT, regardless of the virological response. Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects, these disappeared following discontinuation of therapy. Therefore, IFN therapy is advisable for HCV-infected dialysis patients who are candidates for RT.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Kidney Transplantation , Renal Dialysis , Adult , Alanine Transaminase/blood , Antiviral Agents/adverse effects , Female , Hepacivirus/genetics , Hepatitis C, Chronic/blood , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Middle Aged , Postoperative Period , RNA, Viral/analysis , Recombinant Proteins , Reference Values , Treatment OutcomeABSTRACT
Se determinaron los parámetros farmacocinéticos en el estado estacionario (C máx), (T máx) (C mín), ABCot) y concenttración de la formulacion en el estado estacionario (C ) calculada como (ABC/t) en 10 pacientes asmáticos moderados o severos, que recibían tratamiento en intercrisis con teofilina de liberación sostenida Aristegui 300 mg, a la dosis de 9 mg/kg de peso/día (cada 12 horas). Se comprobó a partir de los resultados que la administración de la formulación de teofilina retard Aristegui 300 mg a la dosis empleada fue suficiente para mantener niveles séricos del fármaco dentro del rango terapéutico durante el intervalo de dosificación
Subject(s)
Theophylline/pharmacokinetics , Delayed-Action PreparationsABSTRACT
Se determinaron los parámetros farmacocinéticos en el estado estacionario (C max),(T máx), (C min),(ABC ) y concentración de la formulación en el estado estacionario (C ) calculada como (ABC/T) en 10 pacientes asmáticos moderados o severos, que recibían tratamiento en intercrisis con teofilina de liberación sostenida Aristegui 300 mg, a la dosis de 9 mg/kg de peso/día (cada 12 horas). Se comprobó a partir de los resultados que la administración de la formulación de teofilina retard Aristegui 300 mg a la dosis empleada fue suficiente para mantener niveles séricos del fármaco dentro del rango terapéutico durante el intervalo de dosificación (AU)
Subject(s)
Theophylline , PharmacokineticsABSTRACT
Results on the anatomy of ventromedial hypothalamic outputs, together with the temporal aspects of electrophysiological studies, predict that for reproductive behavior control sex steroids alter hypothalamic protein synthesis and transport of proteins to the dorsal midbrain. We have studied labeled proteins arriving in the dorsal midbrain after local microinjection of tritiated amino acids to the ventromedial hypothalamus. Estrogen treated and control ovariectomized female rats are significantly different in this respect, and in particular some proteins appear to be synthesized or transported in greater amounts in the estrogen treated animals. Physical characterization of these proteins and comparisons under a variety of endocrine conditions will suggest whether their synthesis could be part of the mechanism by which ovarian steroids affect behavior.
Subject(s)
Estradiol/pharmacology , Hypothalamus, Middle/metabolism , Nerve Tissue Proteins/metabolism , Periaqueductal Gray/metabolism , Amino Acids/metabolism , Animals , Castration , Female , Nerve Tissue Proteins/biosynthesis , RatsABSTRACT
Rat axial muscle previously has not been studied histochemically. We were interested in determining the fiber composition and fiber distribution in rat lateral longissimus (LL), the large epaxial dorsiflexor muscle active during sexual posturing in the female rat and to determine if estrogen replacement in ovariectomized rats would affect the histochemical profile. Staining for ATPase after acid preincubation at pH 4.5, pH 4.35, and after alkaline preincubation at pH 9.4 and staining for NADH-TR revealed that rat LL contains the three major types of fibers present in most mammalian hind limbs: fast-twitch glycolytic (FG); fast-twitch oxidative-glycolytic (FOG); and slow-twitch oxidative (SO). The muscle contains predominantly FG fibers; SO fibers are segregated superficially from L2--L6 where they comprise from 11 to 18% of the fiber population, and in an oxidative compartment in the medial deep region of L5 where they comprise 62% of all fibers. In the medial deep region of L5 most of the remaining fast fibers also contain oxidative enzyme. Spindles are most highly concentrated in this oxidative region of L5. Estrogen treatment did not affect the relative number, distribution, or diameter of the three muscle fiber types in rat LL. The concentration of SO and FOG fibers and spindles localized in the region of the lumbosacral joint is discussed by contrasting forceful movements (e.g., rump elevation during sexual behavior) with normal postural regulation.
