ABSTRACT
BACKGROUND: Combination therapy with pegylated interferon, ribavirin and a first-generation NS3/4A protease inhibitor, telaprevir or boceprevir, is the new strategy for treatment of genotype 1 chronic hepatitis C virus infection. This combination improves therapeutic efficacy but it also increases the risk of adverse events. OBJECTIVE: The aim of the study was to analyze frequency and severity of dermatological adverse events during protease inhibitor-based therapy and to evaluate the risk factors for their development. PATIENTS AND METHODS: This is a retrospective study of 109 patients with genotype 1 chronic hepatitis C treated with boceprevir (n=33) or telaprevir (n=76) based triple therapy. A logistic regression for relationship between clinical, demographic and laboratory factors and cutaneous adverse events was performed. RESULTS: Dermatological adverse events (skin rash, pruritus, anorectal paresthesia) occurred in both treatments (boceprevir and telaprevir) with similar frequency: 28% in telaprevir and 21% in boceprevir. In patients treated with telaprevir, men were more predisposed to develop skin rashes compared to women (OR 4,1 p=0,014) and age above 45 years was associated with occurrence of pruritus in men (OR 8,16 p=0,014). Being a female, coexistence of autoimmune thyroiditis and advanced liver fibrosis were independent factors predisposing to development of anorectal paresthesia (OR 4,13 p=0,041, OR 4,25 p=0,029, OR 4,54 p=0,018 respectively) in this group. In patients treated with boceprevir, coexistence of autoimmune thyroiditis predisposed to skin rashes (OR 10,22 p=0,017) and being a female predisposed to pruritus (OR11,2 p=0,033). The adverse events occurred after a mean time of 8,6 (range 1-24) weeks after initiation of therapy. CONCLUSIONS: In patients with chronic hepatitis C who received the triple therapy, the anorectal paresthesias were observed only in patients treated with telaprevir. The predisposing factors for this adverse event were: female gender and advanced liver fibrosis. The risk factors for other dermatological adverse were: 1) being a male over 45 years, for skin rashes and pruritus (for telaprevir), 2) coexistence of autoimmune thyroiditis for skin rashes (for boceprevir), 3) being a female, for pruritus (for boceprevir).
ABSTRACT
OBJECTIVES: Observing the changes of activity of some lysosomal enzymes in blood serum of female rabbits subjected to injection of 10 microg of ghrelin/kg of body weight. METHODS: In the blood serum the activity of cathepsins D and L, alanine aminopeptidase, acid phosphatase, lysosomal lipase and lysosomal esterase was determined. RESULTS: As a result of ghrelin injection the activity of all the enzymes examined in blood serum increased markedly. CONCLUSION: Changes of lysosomal enzymes activities in the blood serum caused by the effects of ghrelin should be regarded as the response of the lysosomal system.
Subject(s)
Hydrolases/blood , Lysosomes/enzymology , Peptide Hormones/pharmacology , Acid Phosphatase/blood , Animals , CD13 Antigens/blood , Cathepsin D/blood , Cathepsin L , Cathepsins/blood , Cysteine Endopeptidases/blood , Esterases/blood , Female , Ghrelin , Homeostasis/drug effects , Homeostasis/physiology , Lipase/blood , RabbitsABSTRACT
MALDI-TOF mass spectrometry, 1H NMR spectrometry, the continuous variation method and molecular modeling by MM3 calculation confirmed our earlier studies showing that gonadotropin-releasing hormone (GnRH) forms complex with copper(II) ion with the binding ratio 1:1. The copper(II) complex formed at physiological pH has a square planar configuration and GnRH complexes with nickel(II) and cobalt(II) ions are less stable than that of copper(II).
Subject(s)
Gonadotropin-Releasing Hormone/chemistry , Metals, Heavy/chemistry , Animals , Copper/chemistry , Nickel/chemistry , Nuclear Magnetic Resonance, Biomolecular , Protons , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
OBJECTIVES: Changes in the activity of alanine aminopeptidase, leucine aminopeptidase and cathepsins D and L in the liver and kidney of male and female of mice, injected with 0.4 IU/kg b.w. insulin for 4 and 8 days. METHODS: The homogenates of the liver and kidney were taken for examination. The activity of alanine aminopeptidase, leucine aminopeptidase and cathepsins D and L has been determined according to [1] method. RESULTS: The activity of alanine aminopeptidase, leucine aminopeptidase, cathepsins D and L in the liver and kidney of male and female of mice decreased in effect of insulin injections for 4 and 8 days. CONCLUSION: The changes of enzyme activities showed a stimulating effect of the insulin injection on the labilization of lysosomal membranes. The range of the reaction remained in a relationship with the kind of the organ, the type of enzyme, time over which insulin introduced operates in the organism, and with the sex.
Subject(s)
Insulin/physiology , Lysosomes/enzymology , Peptide Hydrolases/metabolism , Animals , Blood Glucose/analysis , CD13 Antigens/metabolism , Cathepsin D/metabolism , Cathepsin L , Cathepsins/metabolism , Cysteine Endopeptidases , Down-Regulation , Female , Kidney/enzymology , Leucyl Aminopeptidase/metabolism , Liver/enzymology , Male , Mice , Random AllocationABSTRACT
OBJECTIVES: Changes in the activity of cathepsin D and L, alanine aminopeptidase, leucine aminopeptidase, N-acetyl-beta-glucosaminidase, lysosomal arylesterase and lysosomal lipase in the liver and kidney of unselected and selected mice, subjected to 7.5 mg/kg b.w. of hydrocortisone injection for 4 and 8 days. METHODS: The homogenates of the liver and kidney were subjected to differentiated centrifuging and determination of studied enzymes. RESULTS: Injection of hydrocortisone caused an increase in the activity of all investigated lysosomal enzymes in the liver and kidney of mice. CONCLUSION: The reactions of selected mice were stronger in comparison with unselected ones. The highest increase in the activity investigated enzymes was observed after 8 days of hydrocortisone injection.
