Search NEL Online

Journal Article 2001; 22(2): 121-127 PubMed PMID: 11335888 Citation  Keywords:  Body Constitution, Body Mass Index, Bone and Bones:metabolism, Circadian Rhythm, Collagen:analysis, Collagen Type I, Female, Humans, Melatonin:analysis, Middle Aged, Obesity:metabolism, Osteoporosis, Postmenopausal:prevention & control, Peptide Fragments:.   

BACKGROUND: Few experimental and clinical studies show that melatonin (MEL) can play a significant part to modulate circadian bone metabolism. On this basis it was suggested that MEL secretion which altered during 24-h in obese women could be of importance to regulate bony mass defect after menopause.

OBJECTIVE: The aim of the study was to prove if there were any connection between changes in 24-h profile of serum MEL levels and circadian metabolism of type I collagen in postmenopausal women with visceral obesity.

METHODS: The relationship of 24-h profile of salivary MEL and circadian metabolism of type I collagen (as assessed by measuring saliva concentrations of carboxyterminal propeptide of type I procollagen--PICP and cross-linked carboxyterminal telopeptide of type I collagen--ICTP) was investigated in 26 women with visceral obesity (33.5 < BMI < 42.1 kg/m(2)) and 18 healthy volunteers with correct body mass (21 < BMI < 24.5 kg/m(2); 0.73 < WHR < 0.76). The specimens were collected at subjects' home at 3 h intervals during a 24 h span. The age range of all subjects was 52-60 years.

RESULTS: In all the obese women studied a tendency to suppress circadian levels of tested biochemical markers of bone metabolism was observed (especially regarding ICTP); those alterations were accompanied by substantial increment in MEL concentrations during the day. Significant and negative correlation was found between values of acrophase MEL and PICP rhythms and both amplitude and acrophase of MEL and ICTP rhythms.

CONCLUSION: Our results confirm hypothesis that alterations in MEL concentrations might have a protective effect against postmenopausal loss of bone mass....

Read abstract  Full text PDF

Journal Article 2001; 22(2): 109-117 PubMed PMID: 11335887 Citation  Keywords:  Adult, Circadian Rhythm, Duodenal Ulcer:metabolism, Humans, Male, Melatonin:biosynthesis, Middle Aged, Remission Induction,.   

UNLABELLED: OBJECTIVES. This work was designed to study melatonin (M) production levels in duodenal ulcer (DU) patients in the exacerbation and remission stages and in DU patients with a different course of DU in the exacerbation and remission stages.

METHODS: DU patients (15 men aged 20 to 45, mean age 34,2 +/- 1,1 years) were studied. The control group included 11 healthy volunteers (men aged 20-45, mean age 32,5 +/- 1,4 years). M was measured by RIA-method using H(3)-labeled M in daily urine collected at 3-hour intervals (8 portions per day). Mathematical processing was carried out using ANOVA, Student's t-test, and cosinor analysis. Differences at p< or = 0,05 were considered to be significant.

RESULTS: A strong disturbance of M secretion in DU patients both in the exacerbation and remission stages and a direct correlation between the degree of M production disturbance and severity of clinical course of DU were revealed.

CONCLUSION: The obtained results suggest that circadian rhythms of M production are altered in DU patients. M was supposed to be involved in the pathogenesis of DU....

Read abstract  Full text PDF

Journal Article 2001; 22(2): 101-108 PubMed PMID: 11335886 Citation  Keywords:  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine:pharmacology, Animals, Apoptosis:drug effects, Brain:cytology, Cell Count, Corpus Striatum:cytology, DNA Fragmentation, Dopamine Agents:pharmacology, Male, Melatonin:pharmacology, Mesencephalon:cytology, Mice, .   

OBJECTIVES: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces a Parkinsonian-type syndrome in animals which is similar to Parkinson's disease in humans. MPTP toxicity partially depends on the production of free radicals which in turn play a key role in the apoptotic death of neurons. In the present study melatonin, a potent free radical scavenger with antiapoptotic properties, was given to determine whether it would reduce oxidative stress in mice treated with MPTP.

MATERIALS AND METHODS: Male mice were given MPTP with or without melatonin and the brain was studied either 6h, 24h, 7 days or 15 days after the last MPTP injection.

RESULTS: The results show that melatonin counteracted in vivo MPTP-induced apoptosis in midbrain neurons at 6 and 24 h after MPTP treatment, and partially prevented apoptosis at 7 and 15 days after MPTP administration. MPTP treatment also produced time-dependent cell damage, whereas melatonin reduced the percentage of damaged cells at all time points, the effect being most evident at 15 days after treatment. Moreover, melatonin counteracted MPTP-dependent DNA fragmentation in the midbrain and striatum at 7 and 15 days after drug administration.

CONCLUSION: These results support a role for melatonin in protecting neurons against MPTP toxicity in vivo, and suggest that its antiapoptotic action is one of the mechanisms by which melatonin protects neuronal cells from neurotoxic insults....

Read abstract  Full text PDF

Journal Article 2001; 22(2): 93-99 PubMed PMID: 11335885 Citation  Keywords:  Alcoholism:complications, Animals, Autoradiography, Cell Division:drug effects, Ethanol:administration & dosage, Leydig Cells:drug effects, Male, Rats, Rats, Sprague-Dawley, Seminiferous Tubules:drug effects, Spermatogonia:drug effects, Testicular Disease.   

OBJECTIVES: Considering the possibility that alcoholism induces gonadal dysfunction, the present work was designed to investigate the morphophysiology of rat testes submitted to experimental alcoholism.

METHODS: Male Sprague-Dawley rats weighing 150+/-5 gm were chronically given 40% ethanol solution at a dose of 3 g/kg body weight for 30 days. (3)H-thymidine autoradiographic investigations and histological studies were carried out to determine the proliferative activity and/or different stages of spermatogenesis in the seminiferous tubule cycle and Leydig cells.

RESULTS: The 3H-thymidine autoradigraphic investigation revealed that there was a significant inhibition in the proliferative activity of the spermatogonia in all stages of the seminiferous tubule cycle in the alcohol-treated rats versus controls as indicated by the values of (3)H-labelling indices. The histological and numerical investigations indicated that the alcohol-treated rats presented testicular lesions including a significant decrease in the diameter of the seminiferous tubules, the number of different germ cells in all stages of the seminiferous tubule cycle and the presence of degenerative germ cells. In addition, there was a significant decrease in the number of Leydig cells.

CONCLUSION: The present work suggests the deleterious effects of alcohol on the testes. These effects may be due to the effect of alcohol on the gonadotrophic cells of the pituitary gland and/or directly on the seminiferous tubules and Leydig cells....

Read abstract  Full text PDF

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.

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.

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....

Read abstract  Full text PDF

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.

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.

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.

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....

Read abstract  Full text PDF

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.

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).

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).

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....

Read abstract  Full text PDF

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.

DESIGN: The aim of this study was to validate hypothesis that progesterone is strong inhibitor of complement embryotoxic action.

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.

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.

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....

Read abstract  Full text PDF