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Case Reports 2001; 22(1): 49-52 PubMed PMID: 11335880 Citation  Keywords:  Autoantibodies:analysis, Female, HLA-DR5 Antigen:genetics, Hepatitis C, Chronic:complications, Histocompatibility Testing, Humans, Interferon-alpha:adverse effects, Middle Aged, Thyroiditis, Autoimmune:genetics,.   

OBJECTIVES: The authors described a case of Hashimoto's disease during interferon-alpha (IFN-alpha) treatment for chronic viral C hepatitis in a patient with the specific genetic susceptibility associated with the thyroid disease.r />r /> RESULTS: A 60-year-old woman with chronic active viral C hepatitis (HCV genotype = 3a) started IFN-alpha therapy in November '96. Before treatment thyroid function tests were normal and anti-thyroid (anti-thyroglobulin and anti-thyroid peroxidase) Abs were negative. During IFN therapy, serum aminotransferases fell within the normal range and viremia (serum HCV-RNA) became negative after one year. After 20 months, the patient presented clinical features of primary hypothyroidism. Anti-thyroid Abs were found positive. Hormonal, ultrasonographic, radioiodine scanning and fine needle aspiration findings were consistent with the diagnosis of Hashimoto's thyroiditis. The tissutal typing of the patient showed the presence of Human Leukocyte Antigen (HLA) DRB1*11 gene (corresponding to DR5 antigen). IFN-alpha therapy was suspended and a treatment with l-T4 started. Chronic viral infection relapsed after the suspension of the IFN-alpha therapy.r />r /> CONCLUSIONS: This case report showed that the clinical appearance of Hashimoto's disease after IFN-alpha therapy for chronic C hepatitis in our patient was associated with a specific genetic predisposition (DR5) for this pathology. Further studies are necessary to evaluate whether the study of HLA antigens may be a very useful tool to detect the patients with a predisposition to develop autoimmune thyroiditis, in order to make a early diagnosis of thyroid disorders during the IFN-alpha treatment....

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Clinical Trial 2001; 22(1): 45-47 PubMed PMID: 11335879 Citation  Keywords:  Adult, Aged, Bone Neoplasms:secondary, Carcinoma:blood, Carcinoma, Hepatocellular:blood, Carcinoma, Non-Small-Cell Lung:blood, Carcinoma, Renal Cell:blood, Colorectal Neoplasms:blood, Disease Progression, Endothelial Growth Factors:blood, Female, Humans, .   

OBJECTIVES: The anticancer activity of the indole melatonin has been explained to be due to its immunomodulatory, anti-prolferative and anti-oxidant effects, whereas at present no data are available about its possible influence on the angiogenesis, which has been shown to be one of the main biological mechanisms responsible for tumor dissemination. Vascular endothelial growth factor (VEGF) is the most active angiogenic factor, and the evidence of abnormally high blood levels or VEGF has been proven to be associated with poor prognosis in cancer patients. To investigate the influence of melatonin on angiogenesis, in this preliminary study we have evaluated the effects of melatonin therapy on VEGF blood levels in advanced cancer patients.r />r /> MATERIAL & METHODS: The study included 20 metastatic patients, who progressed on previous conventional antitumor therapies and for whom no other effective treatment was available. Melatonin was given orally at 20 mg/day in the evening for at least 2 months. Serum levels of VEGF were measured by an enzyme immunoassay on venous blood samples collected at 15-day intervals.r />r /> RESULTS: The clinical response consisted of minor response (MR) in 2, stable disease (SD) in 6 and progressive disease (PD) in the remaining 12 patients. VEGF mean levels decreased on therapy, without, however, statistical differences with respect to the pre-treatment values. In contrast, by evaluating changes in VEGF levels in relation to the clinical response, non-progressing patients (MR + SD) showed a significant decline in VEGF mean concentrations, whereas no effect was achieved in progressing patients.r />r /> CONCLUSIONS: This study, by showing that melatonin-induced control or the neoplastic growth is associated with a decline in VEGF secretion, would suggest that the pineal hormone may control tumor growth at least in part by acting as a natural anti-angiogenic molecule, with a following opposition or angiogenesis-dependent cancer proliferation....

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Journal Article 2001; 22(1): 39-44 PubMed PMID: 11335878 Citation  Keywords:  Adult, Aged, Antiviral Agents:adverse effects, Comorbidity, Female, Follow-Up Studies, Hepatitis C, Chronic:drug therapy, Humans, Incidence, Interferon-alpha:adverse effects, Male, Middle Aged, Prevalence, Retrospective Studies, Risk Factors, Sex Distribu.   

OBJECTIVES: To clarify the relationship between interferon-alpha (IFN-alpha) therapy and autoimmune thyroiditis in chronic hepatitis C virus (HCV) infection, we investigated a selected number of patients without basal thyroid dysfunctions.r />r /> MATERIALS AND METHODS: 130 patients (average age: 20-70), with chronic HCV infection and without basal clinical and laboratory signs of autoimmune thyroiditis were divided into two groups: IFN-alpha treated (A) and untreated (B) patients. Group A received IFN-alpha (three million U.I./3 times a week) for six months; group B was followed for the same period. Thyroid peroxidase and thyroglobulin autoantibodies were measured by radioimmunoassay; thyroid function was measured by radioimmunoassay (free thyroxine and triiodothyronine) and immunoradiometric assay (thyroid stimulating hormone).r />r /> RESULTS: After a 6-month period, thyroid autoantibodies positivity was documented in 21.1% of group A and in 10.3% of group B patients, both statistically relevant (p<0.001 and p<0.011, respectively). The comparison between the two groups was not statistically relevant (p=0.142).r />r /> CONCLUSIONS: Our study showed a prevalence of de novo thyroid autoimmunity in chronic HCV patients treated with IFN-alpha, confirming previous data in literature. The lack of a significant difference between treated and untreated patients strongly suggests that the anti-thyroid autoimmune response is linked to the HCV infection itself. Moreover, IFN-alpha therapy probably does not represent a risk factor in renewing the autoimmune processes of the thyroid gland. Thyroid function and autoantibodies must be systematically monitored in patients with HCV infection, especially in female and IFN-alpha treated population, not only to verify the possible thyroid abnormalities but also to rule out concomitant autoimmune diseases....

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Journal Article 2001; 22(1): 33-37 PubMed PMID: 11335877 Citation  Keywords:  Adolescent, Adult, Animals, Chick Embryo, Complement System Proteins:metabolism, Embryo, Mammalian:abnormalities, Factor Analysis, Statistical, Female, Gestational Age, Humans, Maternal-Fetal Exchange, Models, Biological, Pregnancy:blood, Progesterone:blo.   

OBJECTIVE: In this paper the relation between progesterone levels and embryotoxic effect of serum complement was studied.r />r /> DESIGN: The aim of this study was to validate hypothesis that progesterone is strong inhibitor of complement embryotoxic action.r />r /> SETTING: We used chick embryo like an experimental model for evidence of our hypothesis. We treated chick embryos by sera acquired from healthy pregnant woman with physiologically elevated levels of progesterone and normal complement activity. We investigated embryotoxicity of these sera.r />r /> RESULT: We noticed a significant decrease of sera embryotoxicity inversely related to serum levels of progesterone. The main finding: The embryotoxicity of sera is reversally dependent on progesterone level.r />r /> CONCLUSIONS: These findings bring a new knowledge to the role of progesterone and complement system mainly in initial stages of pregnancy and in some cases of spontaneous abortions....

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Clinical Trial 2001; 22(1): 27-29 PubMed PMID: 11335876 Citation  Keywords:  Adult, Aged, Antineoplastic Agents, Phytogenic:administration & dosage, Antineoplastic Combined Chemotherapy Protocols:administration & dosage, Biomarkers, Tumor:blood, Bone Neoplasms:secondary, Breast Neoplasms:blood, Disease Progression, Female, Humans,.   

OBJECTIVES: Recent data have suggested that the efficacy of cancer chemotherapy does not depend only on tumor-related characteristics, but also on patient biological status, namely immune and endocrine functions. In particular, it has been shown that prolactin (PRL) is a growth factor for breast cancer, and abnormally high blood levels of PRL have been described in metastatic breast cancer patients. The present study was performed to evaluate the efficacy of chemotherapy with taxanes in relation to PRL blood levels in metastatic breast cancer.r />r /> MATERIAL & METHODS: The study included 20 metastatic breast cancer patients, who were treated with taxotere (100 mg/mq I.V. every 21 days) for at least 3 consecutive cycles. Serum levels of PRL were measured by RIA before the onset of treatment and at 21-days intervals.r />r /> RESULTS: The clinical response consisted of partial response (PR) in 6, stable disease (SD) in 7 and progressive disease (PD) in the remaining 7 patients. Abnormally high pre-treatment levels of PRL were seen in 7/20 patients. The percent of patients who had PD in response to chemotherapy was significantly high in patients with pre-treatment hyperprolactinemia than in those with normal blood levels of PRL before therapy.r />r /> CONCLUSIONS: This study shows that the evidence of abnormally high serum levels of PRL correlates with resistance to chemotherapy with taxanes in metastatic breast cancer. Therefore, a concomitant administration of anti-prolactinemic agents, such as bromocriptine, could enhance the efficacy of chemotherapy itself....

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Journal Article 2001; 22(1): 19-26 PubMed PMID: 11335875 Citation  Keywords:  Animals, Apoptosis, Basement Membrane:ultrastructure, Cell Movement, Cerebral Cortex:injuries, Cytoplasm:ultrastructure, Endothelium, Vascular:ultrastructure, Intercellular Junctions:ultrastructure, Macrophages:ultrastructure, Necrosis, Phagocytosis, Rats.   

OBJECTIVES: The effect of the traumatic injury of the cerebral cortex on the ultrastructure of the cerebrovascular junction was studied in rats. The aim of the present study is to describe the ultrastructural alterations in the cerebrovascular junction in rat cerebral cortex after traumatic injury. We were particularly interested in the alterations in endothelium, pericytes and the differentiated population of cerebral macrophages.r />r /> MATERIAL AND METHODS: The observations were conducted four days (group I-five animals) and seven days (group II-five animals) after induction of cortical trauma. Traumatic injury was induced in the fronto-temporal region of cerebral cortex in general anesthesia with 20 mg/kg ketamine hydrochloride.r />r /> RESULTS: In the first group we found the features of damage of the blood-brain barrier and migration of the morphological blood components to the perivascular space. The trauma caused necrosis and apoptosis within brain tissue. An important observation was the presence of numerous brain macrophages that participated in phagocytosis of damaged cellular elements. Additionally, we found an increase in the connective tissue ground substance around brain capillaries. In the second experimental group we noted an increased number of pericytes (1-3) near capillary walls. In some instances, the basement membrane surrounding the pericytes was interrupted and these cells were also located beyond the rim of the vessel wall. Some pericytes showed numerous phagolysosomes indicating that these cells belonged to perivascular macrophages. Moreover, we observed a population of phagocytes residing in close contact with neurons. These cells were different from the typical perivascular macrophages.r />r /> CONCLUSIONS: These observations indicate that the traumatic injury of the brain results in mobilization of a heterogeneous population of brain macrophages. This study indicates that different subpopulations of macrophages emerge in the region of traumatic brain damage, and that the morphology and dynamics of these phagocytes changes and depends on the time elapsed after the initial traumatic incident....

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Journal Article 2001; 22(1): 9-18 PubMed PMID: 11335874 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Aging:drug effects, Animals, Antioxidants:metabolism, Catalase:drug effects, Drosophila melanogaster, Free Radicals:metabolism, Humans, Lipid Peroxidation:drug effects, Melatonin:metabolism, Middle Aged, Oxidation-Reduction.   

OBJECTIVES: The review on our own data on the effect of the pineal peptide preparation Epithalamin on free radical processes in rodents and humans is presented in this paper.r />r /> RESULTS: The activity of Cu, Zn-superoxide dismutase (SOD) was found decreased in the brain of aged rats (30 months old) by 46.8% as compared to young animals. Concentration of Schiff's bases in the brain also went down with age (by 13.6%), while the level of dien conjugates (DC) and protein peroxidation (PPO) remained unchanged. General antioxidation activity (AOA) in the brain also remained stable with age. The liver of aged rats showed significant increase of Schiff's bases (by 27.1%) and PPO products (by 109.2%) and considerable decrease of SOD activity. The level of DC and general AOA in the liver remained unchanged with age. Considerable elevation of protein and lipid peroxidation products contents was registered in the blood serum of aged rats. At the same time, general AOA and SOD activity remarkably decreased. The results obtained evidence from both significant age-related alterations in the activity of free radical processes in animal organism and organic peculiarities of their dynamics. Application of peptide drug epithalamin suppressed significantly the intensity of peroxide chemoluminescence in the blood serum (2.8-fold) and lipid peroxide oxidation (LPO) expressed in the considerably decreased DC contents (4,1-fold). The contents of Schiff's bases showed only a tendency towards decrease (by 14.4%, p > 0.05) and PPO level remained unchanged. Epithalamin administration was followed by considerable (by 36.6%, p < 0.01) increase of general AOA and increased SOD activity (by 19.7%) in males. Epithalamin decreased significantly the contents of conjugated hydroperoxides and ketodienes in tissues of D.melanogaster females, increased catalase activity in drosophila males and females, and increased SOD activity in males of D.melanogaster by 41%. Humans reveal significant age-related decrease of antioxidation defence indices.r />r /> CONCLUSION: Epithalamin administration to patients with age-related pathology eliminates imbalance in prooxidation and antioxidation systems....

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Journal Article 2001; 22(1): 5-8 PubMed PMID: 11335873 Citation  Keywords:  Abortion, Spontaneous:prevention & control, Female, Fetal Death:prevention & control, Gestational Age, Humans, Infant Mortality, Infant, Newborn, Infant, Premature:physiology, Medical Laboratory Science:instrumentation, Obstetrics:trends, Pregnancy:physio.   

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