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Abstract Background The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to mantain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations. Methods In ten healthy male volunteers (age range 45-66) and ten male patients with untreated non small cell lung cancer (age range 46-65) we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared. Results A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8bright, CD8dim, CD16, TcRδ1 and δTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4) showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8bright, TcRδ1 and δTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. Conclusion The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system

Abstract Background Immunosenescence is a process that affects all cell compartments of the immune system and the contribution of the immune system to healthy aging and longevity is still an open question. Lymphocyte subpopulations present different patterns of circadian variation and in the elderly alteration of circadian rhythmicity has been evidenced. The aim of our study was to analyze the dynamics of variation of specific cytotoxic lymphocyte subsets in old aged subjects. Methods Lymphocyte subpopulation analyses were performed and cortisol serum levels were measured on blood samples collected every four hours for 24 hours from fifteen healthy male young-middle aged subjects (age range 36-55 years) and fifteen healthy male old aged subjects (age range 67-79 years). Results In healthy young-middle aged subjects CD20 were higher and at 06:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16 correlated positively with γδTCR+ cells At 18:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16+ correlated positively with γδTCR+ cells and a clear circadian rhythm was validated for the time-qualified changes of CD3+, CD4+, CD20+, CD25+ and HLA-DR+ cells with acrophase during the night and for the time-qualified changes of CD8+, CD8+ bright, CD8+ dim, CD16+ and γδTCR+ cells with acrophase during the day. In old aged subjects CD25, DR+ T cells and cortisol serum levels were higher, but there was no statistically significant correlation among lymphocyte subpopulations and a clear circadian rhythm was evidenced for time-qualified changes of CD3+ and CD25+ cells with acrophase during the night and for the time-qualified changes of CD8+ cells and cortisol with acrophase during the day. Conclusion Our study has evidenced aging-related changes of correlation and circadian rhythmicity of variation of cytotoxic lymphocyte subpopulations that might play a role in the alteration of immune system function in the elderly.

The CD4+ T helper/inducer and the CD8+ T suppressor/cytotoxic are major lymphocyte subsets that play a key role in cell-mediated immunity. Aging-related changes of immune function have been demonstrated. The purpose of this study is to analyze the dynamics of variation of these specific lymphocyte subsets in the elderly. In our study cortisol and melatonin serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from fifteen healthy young middle-aged subjects (age range 36-55 years) and fifteen healthy elderly male subjects (age range 67-79 years). A clear circadian rhythm was validated for the time-qualified changes of CD3+ and CD4+ cells with acrophase at night and for the time-qualified changes of CD8+ cells with acrophase at noon in young middle-aged subjects and for the time-qualified changes of CD3+ cells with acrophase at night and for the time-qualified changes of CD8+ cells with acrophase at noon in elderly subjects. No clear circadian rhythm was validated for the time-qualified changes of CD4+ cells in elderly subjects. No statistically significant correlation among lymphocyte subsets was found in elderly subjects. In elderly subjects CD3+ lymphocyte percentage was higher in the photoperiod and in the scotoperiod and cortisol serum level were higher in the scotoperiod in respect to young middle-aged subjects. In the elderly there is an alteration of circadian rhythmicity of T helper/inducer lymphocytes and this phenomenon might contribute to the aging-related changes of immune responses.

Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.

Aim: The nervous, endocrine and immune systems are connected by shared neurotransmitters, hormones and cytokines. The function of these systems shows patterns of circadian rhythmicity and a number of age-related changes in the 24-h hormonal and non-hormonal rhythms have been found in older human beings. The aim of this study was to evaluate integration among the nervous, endocrine and immune systems in the elderly., Methods: Cortisol and melatonin serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every 4 h for 24 h from 15 healthy young-middle-aged subjects (range 36-55 years, mean age±standard error [SE] 44.08±1.76) and 15 healthy old-aged subjects (range 67-79 years, mean age±SE 68.52±1.27)., Results: There was a statistically significant difference between the groups in the observed values of CD20 (total B cells higher in young-middle-aged subjects, P=0.02), CD25 (activated T cells with expression of the α-chain of interleukin-2 receptor, higher in elderly subjects, P=0.04) and DR+ T cells (activated T cells higher in elderly subjects, P=0.01). There were different correlations among lymphocyte subpopulations and hormone serum levels in young and middle-aged subjects in compared to old-aged subjects. In the group of young-middle-aged subjects, a clear circadian rhythm was validated for the time-qualified changes of all the factors studied. In the group of elderly subjects, a clear circadian rhythm was validated for the nyctohemeral changes of CD3 (with a phase delay of 3 h), CD8, CD4/CD8 ratio, CD16, CD25 (in opposite phase), cortisol (with a phase delay of 1 h) and melatonin., Conclusion: The results of the current study show that aging is associated with enhanced responsiveness of the T-cell compartment, impairment of B-cell compartment and alterations in temporal architecture and correlations of neuroendocrine-immune parameters., (© 2010 Japan Geriatrics Society.)

Lymphocyte subpopulations present circadian variation of some of their subsets, this variation may influence magnitude and expression of the immune responses and may be related to the variation of neuro-endocrine humoral factors. In our study cortisol, melatonin, TRH, TSH, FT4, GH, IGF1 and IL2 serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from 11 healthy male subjects aged 38-55 years. A clear circadian rhythm was validated for cortisol serum levels, CD8, CD16, TcRδ1 with acrophase in the morning and at noon, and for melatonin, TRH, TSH, GH, CD3, CD4, CD4/CD8 ratio, HLA-DR, CD20 and CD25 with acrophase at night. Changes of serum levels of FT4, IGF1 and IL2 did not show circadian rhythmicity. In the photoperiod (06.00-18.00h) and in the scotoperiod (18.00-06.00h) there were significant correlations among the lymphocyte subpopulations and humoral factors studied. The results show that specific lymphocyte subsets present different profiles of nyctohemeral changes and different timed relationships with neuro-endocrine hormones.

Background: Reciprocal influences and bidirectional connections among the nervous, endocrine and immune systems, mediated by shared neuroendocrine hormones, chemo/cytokines and binding sites contribute to the maintainment of body homeostasis. The hypothalamus-pituitary axis may play an immunomodulating role and influence cellular immune responses by releasing various hormones and neuropeptides into the blood with direct modulatory action on the immune effectors, or by regulating the hormonal secretion of peripheral endocrine glands. Aging is associated with changes in immune function. The aim of this study was to evaluate circadian variations of some endocrine and immune factors in the elderly., Materials and Methods: Serum levels of cortisol, melatonin, thyrotropin-releasing hormone (TRH), thyroid stimulating hormone (TSH), free thyroxine (FT(4)), growth hormone (GH), insulin-like growth factor (IGF) 1 and interleukin (IL) 2 were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from ten healthy young and middle-aged individuals (age 35-54 years) and from ten healthy elderly individuals (age 65-76 years)., Results: There was a statistically significant difference between the groups in the observed values of CD20 and TSH serum levels (higher in the young and middle-aged) and CD25 and DR(+) T-cells (higher in the elderly). In the group of young and middle aged subjects, a clear circadian rhythm was validated for the time-qualified changes of all the factors studied, with the exception of FT(4), IGF1 and IL2. In the group of elderly individuals, a number of rhythms and correlations with neuroendocrine hormones were absent or altered., Conclusion: The results of the current study evidence aging-associated decrease of peripheral B-cell compartment, increase of activated T-cell compartment, decrease of hypophyseal thyrotropin secretion, altered circadian rhythmicity and altered hormone-immune cell correlations.

Background: Numerous interactions exist among the nervous, endocrine, and immune systems, mediated by neurotransmitters, hormones, and cytokines. Melatonin may modulate the integrated functions of a unique neuro-immune-endocrine system. Neoplastic diseases may be linked to progressive loss of integration among these systems. We investigated whether there are differences among healthy elderly people and elderly people suffering from lung cancer at different stages of disease in 24-hour melatonin and cortisol secretory profiles., Material/methods: In seventeen healthy subjects (mean age +/-S.E.: 68.8+/-1.92 years), seventeen patients with stage I and II lung cancer (mean age: 67.2+/-0.80), seventeen patients with stage III and IV lung cancer (mean age: 69.5+/-2.26), melatonin and cortisol serum levels were measured in blood samples collected every four hours for 24 hours. The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated., Results: The circadian rhythm of melatonin was present in all the groups, but serum levels were decreased in the subjects suffering from lung cancer (P<0.05). In these patients, cortisol serum levels were increased (not in a significant way), with a loss of the circadian rhythm of secretion. The melatonin/cortisol ratio was decreased in stage III and IV cancer patients (P<0.05)., Conclusions: The progressive decrease of melatonin secretion and altered cortisol secretion pattern with advancing stage of neoplastic disease may be an expression of a gradual alteration of the integrated function of the neuro-endocrine system in lung cancer patients.

Objective: Melatonin plays a role in the regulation of biological rhythms, body temperature presents circadian variations with lower levels during nighttime, when melatonin levels are very high, and thyroid hormones influence shiver independent thermogenesis. We have investigated on possible interactions between the hypothalamic-pituitary-thyroid axis and melatonin in the control of body temperature in humans., Methods: Peripheral blood samples for thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free-thyroxine (FT4), melatonin levels determination and body temperature measurements were obtained every four hours for 24-hours starting at 0600 h in a controlled temperature and light-dark environment from ten healthy males, aged 38-65 (mean age +/-s.e. 57.4+/-3.03, mean body mass index +/-s.e. 25.5+/-0.75). We calculated fractional variation and correlation on single time point hormone serum levels and tested whether the time-qualified data series showed consistent pattern of circadian variation., Results: A statistically significant difference was evidenced for the fractional variation of daytime TSH serum levels (0600 h-1000 h vs. 1000 h-1400 h, p=0.01, 1000 h-1400 h vs. 1400 h-1800 h, p=0.0001, 1400 h-1800 h vs. 1800 h-2200 h, p=0.001) and for the fractional variation of FT4 serum levels at 1800 h-2200 h vs. 2200 h-0200 h (p=0.02). FT4 serum levels correlated positively with TRH serum levels at 1000 h (r=0.67, P=0.03) and at 1400 h (r=0.63, p=0.04), negatively with TSH serum levels at 2200 h (r=-0.67, p=0.03), negatively with melatonin serum levels at 2200 h (r=-0.64, p=0.04) and at 0200 h (r=-0.73, p=0.01). TRH serum levels correlated positively with TSH serum levels at 0200 h (r=0.65, p=0.04) and at 0600 h (r=0.64, p=0.04). Body temperature correlated positively with FT4 serum levels at 1000 h (r=0.63, p=0.04) and negatively with melatonin serum levels at 0200 h (r=-0.64, p=0.04). A clear circadian rhythm was validated for body temperature (with acrophase in the morning) and melatonin, TRH and TSH secretion (with acrophase at night), while FT4 serum level changes presented ultradian periodicity (with acrophase in the morning)., Conclusion: Changes of TSH serum levels are smaller and those of FT4 are greater at night, when melatonin levels are higher, so that the response of anterior pituitary to hypothalamic TRH and of thyroid to hypophyseal TSH may be influenced by the pineal hormone that may modulate the hypothalamic-pituitary-thyroid axis function and influence the circadian rhythm of body temperature.

Subclinical hypothyroidism is characterized by normal serum levels of free thyroxine and triiodothyronine with increased serum levels of thyroid-stimulating hormone (TSH) without symptoms. We evaluated by thoracic electrical bioimpedance cardiography the hemodynamic pattern of 38 patients with subclinical hypothyroidism, before and after 6-month therapy with levo(L)-thyroxine. We have not evidenced statistically significant differences for cardiac index, cardiac frequency and vascular peripheral resistances. TSH levels were decreased in a statistically significant way. Results obtained in our study show that hemodynamic pattern is not changed after hormone therapy in patients affected by subclinical hypothyroidism.

Interstitial lung diseases (ILD) are an heterogeneous group of inflammatory diseases characterized by an anatomical distortion of peripheral airways and interstitium, determined by a first stage of alveolitis and a following stage of fibrosis. Natural history of several ILD is characterized by slow and progressive destruction of alveolar-capillary functional units, often with respiratory failure and death. For their smoldering evolution and not specificity of symptoms (exertional dyspnea and cough) ILD may remain not diagnosed and not treated for a long time.

Melatonin was not considered for a long time in medical culture and scientific research for the difficulties encountered in study protocols and for the obscure relevance in clinical practice. Today the pineal hormone has reached a great popularity, may be not strictly corresponding to the important role played in the regulation of many system function and the commercial diffusion has become extremely wide in some countries.

Background: A number of qualitative and quantitative changes in hormonal secretion pattern have been found in subjects suffering from neoplastic disease. The aim of this study was to evaluate the presence of alterations in neuro-endocrine system function and in the pattern of endocrine secretion in patients with lung cancer., Methods: Cortisol, melatonin, growth hormone (GH), insulin-like growth factor I (IGF-I), thyrotropin-releasing hormone (TRH), thyroid-stimulating-hormone (TSH), and free thyroxine (FT4) serum levels were measured on blood samples collected every four hours for 24 hours from ten healthy old subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve and mean diurnal and nocturnal levels were compared and the presence of circadian rhythmicity was evaluated., Results: When hormone levels were expressed as area under the curve GH levels were higher (p=0.004) and IGF-I levels were lower (p=0.006) in patients with lung cancer than in normal subjects. The evaluation of melatonin/cortisol ratio in all subjects showed a significant difference between the control group and the group of cancer patients (p<0.05). When we compared mean diurnal levels (mean of 06.00-10.00-14.00h) GH levels were higher (p<0.0001) and IGF I levels were lower (p<0.0001) in cancer patients; when we compared mean nocturnal levels (mean of 18.00-22.00-02.00h) cortisol (p=0.03), TRH (p=0.02), and GH (p=0.001) levels were higher in cancer patients, while melatonin (p=0.04), TSH (p=0.04) and IGF I (p<0.0001) levels were higher in control subjects. A clear circadian rhythm was validated for time related changes of cortisol, melatonin, TRH, TSH and GH in control subjects and for time related changes of melatonin in cancer patients., Conclusion: These data suggest that lung cancer patients show alterations of hormone secretion and neuroendocrine system function.

The finding of intracardiac masses is very uncommon. In this patient the early clinical picture was characterized by neurologic signs and symptoms as mild forgetfulness, blurred vision, a sensation of imbalance, anorexia, weight loss. Brain magnetic resonance imaging showed multiple metastatic lesions, computed tomography of the chest, abdomen and pelvis showed intraatrial masses and whole body nuclear scanning evidenced bone lesion. It was not possible to find the primary tumor by other instrumental or laboratory exams. Transesophageal echocardiography showed a mass originating from interatrial septum, with atrial invasion and risk of embolization from the left atrium. The patient was transferred to the operating room for cardiac surgery, the mass at risk for embolization was resected and the specimen consisted of fibrous and fibrino-necrotic tissue infiltrated by poorly differentiated adenocarcinoma. The patient received brain and bone radiotherapy and chemotherapy with cisplatin and vinorelbin.

Nodular regenerative hyperplasia of the liver is characterized by multiple and usually small nodules of hyperplastic hepatocytes surrounded by compressed atrophic liver cells. Given the small size of nodules and the preserved framework, the imaging techniques often show a normal liver and blind percutaneous biopsy is misinterpreted. The Authors report two cases of nodular regenerative hyperplasia diagnosed by ultrasound and percutaneous echoguided biopsy.

The protective role of large spontaneous portosystemic shunts in oesophageal varices bleeding due to portal hypertension in liver cirrhosis is still debated. A series of 20 consecutive patients with haemodynamically efficient collaterals involving the para-umbilical-epigastric venous route (evaluated by Echo-Doppler flowmetry) is reported. All patients presented absent or mild oesophageal varices at endoscopy. During a mean follow-up period of 23.5 months, no patient developed large varices or experienced variceal bleeding. Hepatic encephalopathy was present in 35% of patients. Haemodynamically efficient spontaneous portosystemic shunts may protect cirrhotic patients from the risk of oesophageal varices forming and bleeding. The diversion of large amounts of blood from portal to systemic circulation correlates with the higher trend of hepatic encephalopathy in these patients.

In the last 10 years, interest about the employment of bile acids, especially of ursodeoxycholic acid (UDCA), in the treatment of chronic liver diseases has increased. The mechanism has not been completely explained yet, but this agent has been thought to act mainly by making bile less toxic for the liver cells, reducing the fraction of hydrophobic detergent bile acids. UDCA is effective in decreasing serum concentrations of liver enzymes in chronic liver diseases, especially in those associated with cholestasis. This effect discloses new perspectives about the employment of this agent, even in association with other drugs, i.e. interferon; however, further investigations will be necessary in order to standardize the use of UDCA in the treatment of chronic liver diseases.

A case of an isolated recurrent cardiac hydatidosis with multiple intrapericardial cysts is presented. The patient, who underwent 2 previous surgical resection of intramyocardial and pericardial hydatid cysts, presented with atypical chest pain. The ECG and the perfusion scintigraphy with 201-thallium showed a previous lateral myocardial infarction. The diagnosis of recurrent cardiac hydatidosis was made by two-dimensional echocardiography and computed tomography and was confirmed by clinical and biochemical findings.

In the "24-hour Cross Country Ski Race of Pinzolo" skiers attempt to cover as long as possible distances within 24 hours. Cardiac and metabolic changes of 6 volunteer cross country skiers, aging 29 to 39 years, participating to the individual competition, were analysed. All skiers had negative clinical examination and resting standard 12-lead ECG, except for one who had a midsystolic click on auscultation suggesting the presence of mitral valve prolapse. They were submitted to 48-hour Holter monitoring (HM) going from 3:00 p.m. of the day before the race up to one hour after the end of competition. The period of HM going from 3 p.m. of the day before to 1.00 p.m. of the day of race (one hour before the start) was utilized as control as concerns arrhythmias, ST-T wave and QT interval changes observed during the period of competition. In all 6 skiers, standard 12-lead ECG was again recorded on completion of race. The following serum indexes were obtained in basal conditions and within one hour after the end of race: electrolytes (Na+, K+), Myoglobina (MG) and the enzymes GOT, GPT, LDH, CK and CK-MB. Complete urine analysis was also obtained before and immediately after the race. The distance covered by the skiers ranged from 189 to 260 Km, except for the skier with systolic click who covered 95.7 Km within 12 hour and then retired from the race for acute pain of knee.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a case of ankylosing spondylitis associated with hairy cell leukemia. This is the second observed case (I3) of ankylosing spondylitis with a B-type lymphoproliferative disorder which allows us to make some observations about the pathogenesis of these rare diseases.