Effect of IGF-I on total serum antioxidant status in cirrhotic rats.
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Animals↗
Biomedical subjects
A Castilla
Publications and source records attributed to A Castilla.
Opioid peptides and immunodysfunction in patients with major depression and anxiety disorders.
To assess cell-mediated immunity in depression and anxiety disorders and to elucidate whether immunodysfunction might be related to a high opioid activity, a prospective study of patients with major depression (n = 34) or anxiety disorders (n = 21) was performed. Cellular immunity tests, the in vitro effects of naloxone on monocytes, and beta-endorphin plasma levels were investigated. Peripheral blood mononuclear cells and some monocyte parameters were determined by flow cytometry. Natural killer (NK) cell activity was studied by cytotoxicity, gamma-interferon production by a standard bioassay, monocytic phagocytosis by ingestion of Candida albicans and latex, and blastogenesis by stimulation with phytohaemaglutinin. In major depression and anxiety: 1) a marked reduction in the number of monocytes that ingested particles and expressed cytoskeletal intermediate filaments and surface structures (CR1 receptors and HLA-DR antigens); 2) a monocytosis that was not able to normalize the count of functioning monocytes; 3) an in vitro correction of the monocyte dysfunction by naloxone; 4) a decrease in NK cell number and activity; and 6) an anergy to candidin and tuberculin and a diminished lectin-induced blastogenesis were observed. Some of these immune changes correlated closely with plasma beta-endorphin abnormally high in all the cases. In conclusion, a naloxone-reversible monocyte dysfunction, associated to decreased NK activity and cell-mediated hypersensitivity, was found together with high of beta-endorphin plasma levels. In addition, results suggest that these immunological alterations may be useful in the clinical management of patients with these psychiatric diseases.
Adolescent↗
Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon.
alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hepatitis B virus occult infection in subjects with persistent isolated anti-HBc reactivity.
The aim of this study was to investigate the presence of hepatitis B virus occult infection in asymptomatic subjects with persistent anti-HBc reactivity but no other hepatitis B virus serological markers, including HBsAg, anti-HBs, IgM anti-HBc and HBV-DNA. For this purpose we used both polymerase chain reaction assays in sera and immunohistochemistry for HBsAg and HBcAg in liver biopsy specimens. Twenty-four cases were studied: 15 were drug abusers or homosexuals (eight with normal alanine aminotransferase levels) and nine were heterosexuals with raised alanine aminotransferase levels (> 45 U/l) but with no history of blood transfusion or ethanol intake (< 80 g daily). In all but five cases, liver biopsy was performed in subjects with persistent elevated alanine aminotransferase levels. In 10 out of 24 cases (41.66%) hepatitis B virus infection was demonstrated by polymerase chain reaction or immunohistochemistry, and when results from both procedures were available (n = 11) hepatitis B virus infection was detected in 63.63% of the subjects. The only clinical feature associated with HBV infection was the presence of persistent elevated alanine aminotransferase levels (p < 0.05). In conclusion, persistent isolated anti-HBc reactivity may be a relatively common serologic pattern for hepatitis B virus occult infection, at least in patients with chronic liver disease.
Base Sequence↗
Randomised trial of lymphoblastoid alpha-interferon in chronic hepatitis C. Effects on inflammation, fibrogenesis and viremia.
Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities became normal during treatment in 30 of 36 (83.3%) treated patients, but in only 1 out of 36 (2.7%) non-treated cases (p < 0.001). However, a reactivation of the disease during the interferon course was observed in 12 patients after a mean of 5.58 +/- 1.55 months of therapy, and a post-treatment relapse was observed in 5 additional cases. The remaining 13 patients (36%) had sustained normalization of the aminotransferase levels for 15.27 +/- 10.34 months (range 3-30) after discontinuation of interferon, thus representing a long-term sustained remission of the disease. Knodell's histological activity index decreased in all treatment patients, except for 3 non-responders (91.5%), but in only 9 of 36 non-treated cases (25%) (p < 0.001). Procollagen type III peptide levels normalized in most cases (83%) with a sustained response. A significant decrease in the detection of hepatitis C virus RNA was observed in patients with a sustained response (p < 0.05). Anti-interferon antibodies were only detected in one non-responder. Thus, interferon diminishes inflammatory and fibrogenic activity in the majority of patients with chronic hepatitis C and abolishes viremia in most of the patients with a sustained response.
Adult↗
Human fibrogenesis and transforming growth factor beta-1.
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Collagen↗
Histological outcome of chronic hepatitis C treated with a 12-month course of lymphoblastoid alfa interferon.
To assess the effect of long-term alfa interferon therapy (12 months) on liver histology of chronic hepatitis C, we studied 61 treated patients, and compared their outcome with 28 untreated cases followed as controls. A liver biopsy was taken from all patients, before (month 0) and after the completion of the treatment or the control period (month 12). A third liver specimen taken at month 24 was available in 29 treated cases. Liver biopsies were blindly graded following Knodell's method. In 33 out of the 61 treated patients (54.1%), aminotransferase levels became normal shortly after starting therapy and remained within normal values until the end of treatment (sustained response). Nine (27%) sustained responders relapsed after interferon discontinuation, while the remaining 24 (73%) continued with normal aminotransferase values during follow-up (16.8 +/- 9.9 months). All histological parameters, except fibrosis, improved significantly after 12 months of therapy (periportal necrosis, month 0: 2.7 +/- 1.0, month 12: 1.6 +/- 1.1, p < 0.0001; lobular damage, month 0: 2.5 +/- 1.1, month 12: 1.4 +/- 0.9, p < 0.0001; portal inflammation, month 0: 3.6 +/- 0.5, month 12: 3.0 +/- 0.9, p < 0.0001). Histological improvement was especially marked in patients who did not relapse, although those who relapsed and partial responders also improved. Overall histological diagnoses improved in most patients. A sustained response to interferon was predicted by high periportal and lobular scores, and by a low fibrosis score on the pretreatment liver biopsy. At 24 months, histological improvement persisted in patients without posttreatment relapse, while liver inflammation had returned to pretreatment levels in the remaining cases.
Adult↗
Lymphoblastoid alpha-interferon for chronic hepatitis C: a randomized controlled study.
Forty patients with chronic hepatitis C (CHC) were included in an open randomized controlled trial of lymphoblastoid alpha-interferon (L-IFN) versus no treatment. Twenty patients entered each group, and features of therapy and control cases were similar. L-IFN was given in low doses (1.5-4.5 megaunits) for 1 yr. In 16 of 20 patients treated with L-IFN (80%), but in only one of 20 nontreated cases (0.5%; p < 0.001), amino-transferase activities became normal. In four patients there was a reactivation of the disease during treatment after 4, 5, 6, and 8 months with normal aminotransferase levels. A posttherapy reactivation of hepatitis was observed in four additional cases after 1, 1, 1, and 3 months of follow-up. The other eight patients (40%) continued with normal aminotransferase levels for 1.52 +/- 0.74 (range, 1-2.1) yr after IFN doses were discontinued. In all treated patients except two nonresponders, but in only one of 20 nontreated cases (p < 0.001), Knodell's histological activity index decreased. Procollagen type III aminoterminal peptide levels did not change significantly in nontreated and nonresponder patients, diminished slightly in patients with a transient response, and normalized in cases with a long-standing response, suggesting that this serum test may be a reliable marker for monitoring response to IFN therapy in patients with CHC. Finally, L-IFN treatment induced significant increments in CD4/CD8 index, phytohemagglutinin-induced blastogenesis, and natural killer activity. This study shows that L-IFN diminish inflammatory and fibrogenic activity in most patients with CHC. In 40% of patients treated in this trial, a long-standing remission of the disease was observed.
Adult↗
alpha-Interferon therapy for hepatitis C virus chronic infection with mixed cryoglobulinemia.
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Cryoglobulinemia↗
[Monocytic dysfunction by opioid peptides in patients with major depression].
BACKGROUND: Patients with depression present immunodepression and it has been proposed that, in these patients, endogenous opioid peptides may be mediators between the dysfunction of the central nervous system and immune alterations. METHODS: The function and the surface markers of monocytes were studied in 15 patients with major unipolar depression and in 24 healthy controls by biological trials of phagocytosis of Candida albicans and latex particles and immunofluorescence with monoclonal antibodies. RESULTS: Most of the patients studied (86%) presented monocytic dysfunction characterized by diminished phagocytic activity and a decrease in the expression of intermediate filaments of vimentin of the cytoskeleton and membrane molecules (CR1, receptor for the Fc fraction of the IgG and HLA DR antigens). Incubation of the patients monocytes with naloxone led to the disappearance of monocytic alterations in most of the patients. CONCLUSIONS: Patients with major unipolar depression present a high opioid tone which has consequences in the function of the immune system.
Adult↗
[Detection of hepatitis B virus DNA in serum by gene amplification in patients with chronic hepatitis B and in patients chronic hepatitis C].
BACKGROUND: The polymerase chain reaction (PCR) constitutes important methodological progress for detecting the presence of viral nucleic acids when these are found in small quantities in serum or tissues. The aim of this study was the use of PCR to detect DNA of the hepatitis B virus (HBV) in patients with chronic HBsAg positive hepatitis (HC-B) and in patients with chronic non A non B hepatitis with antibodies against the virus of hepatitis C (anti-HCV) positive (HC-C). METHODS: The DNA of the HBV was determined with PCR in the serum of 40 patients with HC-B and in 15 with HC-C. Moreover, the presence of anti-HCV was studied in the patients with HC-B. RESULTS: The presence of DNA of the HBV was detected by PCR in 69% of the HC-B patients presenting HBeAg positive and DNA of the HBV negative by simple hybridization as well as in 50% of the patients with HBeAg negative, anti-HBe positive and DNA of HBV negative by simple hybridization. In addition, DNA of HBV was detected by PCR in 27% (4/15) of the subjects with HC-C, three of whom had anti-HBc antibodies. On the other hand, 20% of the patients with HC-B had anti-HCV. Anti-HCV positivity was associated to a greater hypertransaminasemia in patients with HC-B in a non replicative phase. CONCLUSIONS: PCR is a sensitive method for detecting viral replication. Its use permits the detection of low DNA concentrations of the HBV in a low but appreciable percentage of chronic negative HBsAg hepatitis. Coinfection by the B and C viruses of hepatitis is not exceptional and explains hypertransaminasemia in some HC-B in a non replicative phase.
DNA, Viral↗
Detection of hepatitis C virus antibodies with new recombinant antigens: assessment in chronic liver diseases.
A new serological assay to detect antibodies against hepatitis C, based on a recombinant protein (BHC10) which incorporates structural and non-structural viral antigens, was tested in 67 healthy subjects and 409 patients with various forms of liver disease. Results were compared with the current assay based on the recombinant non-structural viral antigen c100 and with the recently introduced second-generation assay, Ortho2. None of the healthy subjects was positive by any of the assays. In patients with chronic non-A, non-B hepatitis the prevalence of anti-BHC10 was 96.8%, higher than anti-c100 (83.3%, p less than 0.001) and similar to Ortho2 (94.3%). False-positive results were less frequently found when BHC10 was used. These findings show that assays incorporating structural and non-structural antigens provide higher sensitivity to detect hepatitis C virus infection and they define an almost exclusive role of hepatitis C virus in the genesis of chronic non-A, non-B hepatitis.
Adolescent↗
[Surface T-lymphocyte markers and monocyte dysfunction in the chronic fatigue syndrome].
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Adult↗
Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy.
BACKGROUND: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation of unknown pathogenesis. Transforming growth factor (TGF) beta 1 induces the production of extracellular matrix proteins by liver cells and has been implicated in the pathogenesis of hepatic fibrosis in laboratory animals. TGF alpha is a hepatocyte mitogen that participates in liver regeneration. METHODS: Using Northern blot analysis, we studied the expression of TGF beta 1 messenger RNA (mRNA) in liver specimens from 42 patients with chronic hepatitis and cirrhosis and 12 subjects with either normal or fatty livers. The results were correlated with measurements of procollagen Type I mRNA in liver tissue, procollagen Type III peptide in serum, and the degree of histologic injury. We also investigated whether TGF alpha mRNA would be detectable in biopsy specimens of livers with proliferative activity. RESULTS: TGF beta 1 mRNA expression correlated closely with the expression of procollagen Type I mRNA (r = 0.94) and serum procollagen Type III peptide (r = 0.89) and with the histologic activity index (r = 0.73). All patients with increased fibrogenic activity (serum procollagen Type III peptide level, greater than 11.9 micrograms per liter) had increased levels of TGF beta 1 mRNA (2 to 14 times the levels in the control group or in patients with normal fibrogenic activity), and both TGF alpha and H3 histone (a marker of DNA synthesis) mRNAs were detectable in patients with regenerative nodules. Six of eight patients with hepatitis C treated with interferon alfa for one year had sustained clinical responses with normalization of serum procollagen Type III peptide and aminotransferase activity. All these patients had normal levels of TGF beta 1 mRNA in liver specimens obtained at the end of the year. CONCLUSIONS: TGF beta 1 may have an important role in the pathogenesis of fibrosis in patients with chronic liver disease, and TGF alpha expression may be associated with liver regeneration in these patients.
Adult↗
Effects of TGF-beta s in the liver: cell proliferation and fibrogenesis.
TGF-beta 1 is a potent inhibitor of hepatocyte proliferation in vivo and in culture and an inducer of fibrogenesis. It is produced by non-parenchymal cells in normal, regenerating, neoplastic and pre-neoplastic liver. TGF-beta 2 and beta 3 are also found in liver non-parenchymal cells and the amounts of their mRNAs increase during liver regeneration. TGF-beta 2 has similar effects to TGF-beta 1. Membranes from normal adult rat liver bind TGF-beta 1 with kinetics consistent with the presence of a single high affinity binding site; membranes from livers that have been regenerating for 12-72 hours show high affinity binding sites not detected in livers of normal or sham-operated rats. Affinity labelling of membranes from normal and regenerating liver shows two receptor proteins with Mr 85,000 and 65,000. In contrast, a prominent band corresponding to a binding protein of Mr 280,000 is detected in membrane preparations of cultured liver epithelial cells. Although modulation of TGF-beta 1 receptors occurs during liver regeneration, it has not been possible to determine which receptor is responsible for the TGF-beta 1 effects in hepatocytes. Other studies have demonstrated a significant correlation between TGF-beta 1 mRNA expression and various indicators of fibrogenesis in patients with chronic liver disease. Thus in animals and humans TGF-beta 1 appears to play a major role in the pathogenesis of fibrosis in chronic liver disease.
Animals↗
[Type 6 human herpes virus and chronic asthenic syndrome].
Chronic asthenia syndrome has been associated with Epstein-Barr virus (EBV). To investigate the possible role in this syndrome of human herpesvirus type 6 (HHV-6), a new herpesvirus discovered in 1986, we performed a serological study of 44 patients diagnosed of chronic asthenia syndrome and 50 controls. Fifty healthy controls (34%) and 44 patients (54.5%) had positive serological tests for HHV-6. This difference was significant (p less than 0.05). The rate of positive serological studies for CMV and EBV was higher in healthy controls (n = 50) than in patients (n = 37) (96% vs 67.7% for CMV [p less than 0.001] and 92% vs 78.4% for EBV [non significant difference]). We conclude that HHV-6 may play a role in the pathogenesis of chronic asthenia syndrome. In our group of patients there were no significant differences in the presence of anti EBV capsid antibodies.
Antibodies, Viral↗
Monocyte disorder causing cellular immunodeficiency: a family study.
We report a familial type of monocyte dysfunction not recognized previously. This disorder was observed in a young adult man with a long clinical history of recurrent, self-limited episodes of cryptogenic fever accompanied by digestive and respiratory symptoms and repeated oral and skin infections. Lectin-induced lymphocyte transformation was reduced and skin tests revealed anergy to tuberculin and candidin. Monocytes from this patient exhibited markedly diminished expression of cytoskeletal vimentin intermediate filaments, HLA-DR antigens and immunological receptors for IgG Fc and C3b. These abnormal monocytes demonstrated impaired phagocytosis and reduced accessory cell function on PHA-mediated lymphocyte activation. Release of soluble lymphocyte-activating factors by these cells was found to be defective. Lymphocytes from the patient responded appropriately to lectin in the presence of normal monocytes. Two family members of the proband presented similar monocyte defects although they only manifested minor clinical symptoms. This syndrome underlines the interest of testing monocyte markers and function in subjects with clinical manifestations of immunodeficiency.
Adult↗
[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon].
Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.
Adult↗