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Journal Article 2001; 22(4): 251-254 PubMed PMID: 11524632 Citation  Keywords:  Aging:physiology, Animals, Circadian Rhythm, Endocrine System Diseases:drug therapy, Female, Macaca mulatta, Melatonin:blood, Nervous System Diseases:drug therapy, Oligopeptides:therapeutic use, Osmolar Concentration,.   

UNLABELLED: The OBJECTIVE of this research was to investigate the regulatory effect of Epitalon on the production of melatonin and cortisol in senescent monkeys.

MATERIAL AND METHODS: We investigated the character of melatonin and cortisol secretion by immunoferment assay in Epitalon-administered female Macaca mulatta in different age periods.

RESULTS: Epitalon was proven to significantly stimulate melatonin synthesis in senescent monkeys in the evening, thereby normalising the circadian rhythm of cortisol secretion....

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Journal Article 2001; 22(3): 163-168 PubMed PMID: 11449190 Citation  Keywords:  Aged, Aged, 80 and over, Aging, Alzheimer Disease:blood, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Linear Models, Male, Memory, Middle Aged, Reference Values, Testosterone:blood,.   

OBJECTIVES: The purpose of this study was to determine whether the level of serum total testosterone (TT) was different in cases of Dementia of the Alzheimer's Type (DAT) than in controls.

SETTING AND DESIGN: We included 83 referred DAT cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford Project To Investigate Memory and Ageing.

METHODS: Information was obtained about potential confounds in the relation of DAT with testosterone, including age, gender, education, body mass index, smoking, (ab)use of alcohol, diabetes mellitus, endocrine therapy, and having undergone hysterectomy. TT was measured in non-fasting serum obtained between 10 and 12 a.m. using a competitive enzyme immunoassay.

RESULTS: Men with DAT (n=39) had lower levels (p =0.005) of total serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L). Lower TT was more likely in men with DAT, independent of potential confounds (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT levels between cases (n=44) and controls (n=62).

MAIN FINDINGS: Our results suggested that low TT may be a co-morbid feature of DAT in men. However, low TT levels could also exacerbate the disease.

CONCLUSIONS: Prospective longitudinal studies should investigate whether low TT levels precede or follow the onset of DAT (209 words)....

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Journal Article 2001; 22(2): 129-136 PubMed PMID: 11335889 Citation  Keywords:  Alkaline Phosphatase:blood, Animals, Biomarkers:analysis, Bone and Bones:metabolism, Calcium:urine, Circadian Rhythm, Collagen:blood, Collagen Type I, Disease Models, Animal, Female, Humans, Hydroxyproline:urine, Melatonin:blood, Osteoporosis, Postmenopau.   

BACKGROUND: Lately, there have been suggestions that bone mass changes occurring in postmenopausal women may remain related to melatonin.

OBJECTIVE: To assess the relationship between the dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in ovariectomized rats--a model of postmenopausal osteoporosis.

METHODS: Mature Wistar female rats were either ovariectomozed or underwent a sham operation. Following this they were killed at 02:00AM at weekly intervals for 8 weeks after surgery. Serum levels of MEL at death related to the chosen biochemical markers of bone formation (alkaline phosphatase--ALP; carboxyterminal propeptide of type I procollagen--PICP, both in serum) and resorption (cross-linked carboxyterminal telopeptide of type I collagen--ICTP in serum; hydroxyproline--HYP and total calcium--Ca, both excreted in urine).

RESULTS: In all ovariectomized rats changes of examined indices of bone tissue metabolism were found to be dynamic and statistically significant relative to the control group; however the changes were more pronounced regarding resorption markers. Following ovariectomy, the increase in ALP and PICP values was found to begin at the 4th and the 1st week, while that in ICTP, HYP and Ca at the 2nd, the 1st and the 1st week, respectively. The ALP and PICP values remained at a similar level until the end of observation, whereas ICTP, HYP and Ca gradually decreased. MEL levels were decreased during the 2nd week following surgery and slightly increased 2 weeks later. The serum MEL levels in the ovariectomized group were significantly and negatively correlated with serum ICTP and both urinary HYP and Ca levels.

CONCLUSION: Our findings in rats seem to corroborate the concept of secondary changes in MEL levels co-participating in the development of bone mass changes characteristic for postmenopausal osteoporosis....

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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....

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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.

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....

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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.

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.

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.

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 2018; 39(3): 196-204 PubMed PMID: 30431741 Citation  Keywords:  Adult, Aged, Antibodies, Monoclonal, Humanized:adverse effects, Antineoplastic Agents, Immunological:adverse effects, Autoimmune Diseases:chemically induced, Autoimmune Hypophysitis:chemically induced, Colitis:chemically induced, Female, Humans, Hydrocort.   

OBJECTIVES: Immune checkpoints inhibitors (ICI) represent a new therapy option for the treatment of several advanced tumors. However, this therapy has been linked to a spectrum of ICI related autoimmune (AI) adverse events. Some may be life threatening and their diagnosis is tricky. The aim of our study was to describe various imaging appearances of ICI related secondary hypophysitis and other coincidental AI diseases. MATERIAL AND METHODS: We included 28 patients (19 females, 9 men, mean aged 58±13 years), who were consecutively treated mostly for advanced stage melanoma by different ICI. All their CT/MRI records and clinical data were reviewed. RESULTS: We found 5 (18%) cases of endocrinology proven secondary hypophysitis; 2 cases of panhypopituitarism and 3 cases of central hypocortisolism. Four cases were MRI positive, 1 case was MRI negative. Three cases were accompanied by other AI diseases: 1 by hemorrhagic colitis and mesenterial lymphadenitis, 1 by AI pancreatitis and 1 by pneumonitis. On MRI pituitary gland was swollen in 3 cases, twice enhanced non-homogenously, once homogenously; infundibular enlargement was present in 2 cases. Those 3 cases reacted to glucocorticoid therapy by hypophyseal shrinkage. In 1 case of MRI positive hypophysitis, the pituitary gland was not enlarged, slightly nonhomogeneous with peripheral contour enhancement; no reaction to glucocorticoids was mentioned. CONCLUSION: Secondary hypophysitis is probably more common ICI related adverse event than reported in the literature. Its MRI appearance is variable. Most of our cases were in coincidence with other AI ICI related events that affected their clinical manifestations....

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Journal Article 2018; 39(3): 209-218 PubMed PMID: 30431738 Citation  Keywords:  Animals, Behavior, Animal, Blood-Brain Barrier:metabolism, Brain:diagnostic imaging, Brain Edema:etiology, Disease Models, Animal, Evans Blue, Intracranial Hypertension:etiology, Locomotion, Male, Myelin Sheath:pathology, Permeability, Rats, Rats, Wistar,.   

OBJECTIVES: This paper presents our own rat model of the cellular brain edema, induced by water intoxication (WI). The basic principle of the model is an osmotic imbalance in the cell membrane followed by an intracellular flow of sodium and simultaneous accumulation of water leading to the subsequent increase of BBB permeability. METHODS: The usefulness of the model was tested in precisely specified conditions whose results were clearly expressed. The procedure determined both how WI induces cellular edema as well as the disturbances caused by cellular edema. RESULTS: The evidence of existing cellular edema with increased BBB permeability was proved by intracellular accumulation of intravital dye with a large molecular size; increased brain-water content was confirmed by using the dry/wet weight method and by the decrease in CT density; the elevated intracranial pressure (ICP) due to the expanding volume was determined by continuous monitoring the ICP; the structural lesions were proved by identification of the myelin disintegration; and the impaired nervous functions was demonstrated by the of open field test method. CONCLUSION: Our experimental model can help the future studies of pathophysiology of cellular brain edema and is suitable for testing neuroprotective agents....

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