The pineal gland and breast cancer: serum levels of melatonin in patients with mammary tumors and their relation to clinical characteristics

Several studies have suggested that the pineal gland hormone melatonin may influence the growth of breast cancer. The importance of melatonin blood concentrations in the clinical history of human breast cancer, however, has still to be defined. To further investigate this problem, we used a RIA method to assay serum levels of the pineal hormone in 74 untreated breast cancer patients, clinical stage T1-3 NO-2 MO, and in 46 age-matched healthy women as controls. Mean serum melatonin levels were significantly higher in patients than in controls. Melatonin concentrations were highest in breast cancer patients with the best prognosis (i.e. estrogen receptor-positive/node-negative cases). Mean levels of melatonin were significantly higher in estrogen receptor-positive patients than in the negative ones. They were also higher in node-negative than in node-positive cases, and in progesterone receptor-positive patients than negative ones, but none of these differences was statistically significant. No difference was observed in relation to menopausal status and to tumor histotype. These results suggest that melatonin plays a role in the hormone-dependency of human breast cancer.     

Serum melatonin levels and insomnia in patients with Machado-Joseph Disease

We previously reported a patient with Machado-Joseph Disease (MJD) who had severe insomnia and a low serum melatonin (MLT) level, and whose insomnia was alleviated by oral MLT replacement therapy. The aims of this study were to examine whether patients with MJD are likely to have insomnia, and whether there is a relationship between the degree of insomnia and the serum MLT level among patients with MJD. This study included 8 patients with MJD. A 58-year-old-patient with cervical spondylosis was also included in this study to check the condition of the test room for sleeping. All patients filled out the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J) questionnaire. We obtained blood samples at 12:00 and 24:00 hours to measure the MLT level. We checked the sleep condition of the patient once an hour and recorded the grade in sleep-logs: the grades of sleep condition were asleep, sleepy, or awake. Statistical analyses were performed to search for correlations between the PSQI score and the serum MLT level or actual sleep time using Spearman’s rank correlation coefficient. Seven of the 8 MJD patients had a total PSQI score of above 5.5 (cut-off level). The daytime MLT level (at 12:00 hours) was below 2.8 pg/mL in all 8 patients, whereas the mean night-time MLT level (at 24:00 hours) of the MJD patients (23.6 ± 17.5 pg/mL) was lower than that of the control patient (43.0 pg/mL) and also lower than the reported cut-off level among healthy people aged 30–50 years (55.5 pg/mL). There was a negative correlation between the total PSQI score and the serum MLT level among the MJD patients (P < 0.05). Our results show that a low serum MLT level may contribute to insomnia in patients with MJD.

     

Serum cytokine levels in patients with acute brucellosis and their relation to the traditional inflammatory markers

The number of clinical studies on gamma interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) in human brucellosis is limited. The present study was focused on IFN-gamma, TNF-alpha and IL-4 levels in acute brucellosis cases, in the acute phase and at the end of the treatment. The relation of these cytokines to traditional inflammation markers was also investigated. The study included 27 cases of acute brucellosis and 20 healthy volunteers who had no complaints. It was found that mean IFN-gamma and TNF-alpha levels, CRP (C-reactive protein) levels and ESR (erythrocyte sedimentation rate) values were significantly higher in acute brucellosis cases as compared to post-treatment values and values measured in the control group. In addition, IFN-gamma and TNF-alpha levels measured in the acute phase correlated with the increase in CRP levels and ESR values. Our results confirmed that IFN-gamma and TNF-alpha are involved in the pathophysiology of brucellosis and are closely related to the inflammatory activation of the disease. In view of the present findings, it is suggested that IFN-gamma and TNFalpha may be used for monitoring brucellosis.     

Serum levels of leptin in multiple myeloma patients and its relation to angiogenic and inflammatory cytokines

BACKGROUND: Leptin, apart from the regulation of food intake, has been implicated in hematopoiesis, the immune response and angiogenesis. Leptin has been found to be decreased in various hematological malignancies. In the present study leptin was measured in multiple myeloma (MM) patients before and after treatment and correlated with other angiogenic molecules and markers of disease activity. METHODS: Serum leptin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), interleukin-1 beta (IL-1beta), beta 2 microglobulin (beta2M) and C-reactive protein (CRP) were measured in 62 newly diagnosed MM patients, 22 of whom obtaining disease stabilization after treatment. The same parameters were measured in 20 healthy controls. Disease stage was defined according to the Durie-Salmon criteria. RESULTS: Leptin, VEGF, b-FGF, IL-1beta, and beta2M were significantly higher in newly diagnosed MM patients than in controls (p<0.05). VEGF, b-FGF, IL-1beta, beta2M, CRP but not leptin increased with advancing stage of disease (p<0.01). All parameters decreased significantly following treatment (p<0.001). Although IL-1beta correlated positively with VEGF, beta2M, b-FGF and CRP, leptin did not correlate with any of the measured parameters. CONCLUSION: Leptin serum levels do not reflect disease severity in MM. However, there seems to be a decrease in leptin following treatment, which may be associated with an alteration in the metabolic state or the chemokine milieu.     

Serum levels of VEGF and VEGF-C in patients with endometrial cancer

Endometrial cancer (EC) is the most common type of uterine cancer. A dualistic model of endometrial tumorigenesis serves as a useful way of categorizing these cancers in terms of both etiology and clinical behavior. There are two types of EC: type I and type II. Type I is so-called estrogen-dependent, and appears mostly in pre- and perimenopausal women, it is well differentiated and therefore has a better prognosis. Type II EC is estrogen-independent, diagnosed mostly in postmenopausal women, thin and fertile women, or in women with normal menstrual cycles. It is aggressive and has a worse prognosis than type I. The aim of this study was to evaluate the relationship between the pretreatment serum levels of VEGF and VEGF-C and the outcome of EC patients. A total of 98 patients treated between 1999 and 2003 were included in this study. Circulating VEGF and VEGF-C levels were determined using ELISA kits. VEGF levels among the 76 patients with type I, and the 22 patients with type II EC were significantly higher than those found in the healthy control subjects (p?相似文献   

Serum zinc and angiotensin-converting enzyme levels in patients with lung cancer

Forty-two patients with lung cancer and 72 healthy subjects were studied in order to determine a possible relationship between serum zinc and angiotensin-converting enzyme (ACE), a peptidyl dipeptide hydrolase. Serum zinc levels were 105 +/- 21 micrograms/dl in control subjects and 50 +/- 19 micrograms/dl in patients, and angiotensin-converting enzyme activity was 296 +/- 28 U/l in the former and 240 +/- 55 U/l in the latter using hippurylglycylglycine as a substrate. The findings obtained show that the decreased levels of angiotensin-converting enzyme may be related to decreased serum zinc levels and that the primary defect may be the zinc deficiency in these patients.     

Plasma BDNF levels vary in relation to body weight in females

Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted.     

Localization and dynamics of Mel1a melatonin receptor in the ovary of carp Catla catla in relation to serum melatonin levels

We studied the localization, sub-cellular distribution and daily rhythms of a 37 kDa melatonin receptor (Mel_1aR) in the ovary to assess its temporal relationship with the serum melatonin levels in four different reproductive phases in carp Catla catla. Our immunocytochemical study accompanied by Western blot analysis of Mel_1aR in the ovary revealed that the expression of this 37-kDa protein was greater in the membrane fraction than in the cytosol. Ovarian Mel_1aR protein peaked at midnight and fell at midday in each reproductive phase. Conversely, serum melatonin levels in the same fish demonstrated a minimum diurnal value at midday in all seasons, but a peak at midnight (during pre-spawning, spawning, and post-spawning phases) or at late dark phase (during preparatory phase). In an annual cycle, band intensity of Mel_1aR protein showed a maximum at night in the spawning phase and a minimum in the post-spawning phase, demonstrating an inverse relationship with the levels of serum melatonin. Our data provide first evidence of the presence of Mel_1a melatonin receptor in carp ovary and offer interesting perspectives especially for the study of the mechanisms of the control of its rhythmicity and its response to external factors.     

子宫内膜异位症患者血清VEGF和CRP水平变化及其相关性

目的：探讨子宫内膜异位症患者血清血管内皮生长因子（VEGF）和C-反应蛋白（CRP）的水平变化及其相关性。方法：采用ELISA的方法测定30例III～Ⅳ期子宫内膜异位症患者（其中增生期13例、分泌期17例）和22例非子宫内膜异位症患者（其中增生期10例、分泌期12例）血清VEGF和CRP的水平,并分析两者相关性。结果：子宫内膜异位症组分泌期血清VEGF水平明显高于对照组（P〈0．05）;子宫内膜异位症组增生期血清CRP水平明显高于对照组（P〈0．05）;子宫内膜异位症组增生期和分泌期血清VEGF与CRP水平存在显著的正相关（F0．52,P〈0．05;r=0．44,P〈0．05）。结论：子宫内膜异位症患者血清VEGF、CRP水平的升高说明了过度血管生成和异常炎症反应是子宫内膜异位症的显著特征。     

Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical markers

A 6-mo longitudinal study of 48 hemodialysis patients (HPs) with chronic renal failure was performed. Three blood samplings were done. Samples of whole blood from each patient were collected during hemodialysis sessions after passing through the artificial kidney. Zinc and copper levels were measured by atomic absorption spectrometry. Additionally, 36 biochemical indexes were evaluated during the study. Fifty-two healthy matched controls were also considered. Mean serum zinc and copper concentrations in HPs were significantly decreased (Zn) and increased (Cu), when compared with healthy controls (p<0.01). Zinc concentrations found in the first and second blood samplings from patients were significantly lower than those measured for the third sampling (p<0.01). The etiology of chronic renal failure influenced the statistically serum Zn levels of patients (p<0.05). Serum copper levels of HPs were significantly diminished by the existence of secondary associated diseases (p<0.01). Uric acid and parathyroid hormone, and total-cholesterol and glutamic-pyruvic-transaminase levels were significantly (p<0.05) and linearly related with serum zinc and copper concentrations, respectively. From all of indexes, creatinine, direct bilirubin, magnesium, calcium, parathyroid hormone, transferrin, and albumin were statistically modified along the longitudinal study (p<0.05). Transferrin serum levels were significantly diminished in the third blood sampling, indicating the tendency toward anemia in the patients. This result is reinforced by low levels of biochemical and hematological indexes related with iron body staus.     

Serum levels of interleukin-2 in cancer patients: preliminary considerations

In order to investigate the production of interleukin-2 (IL-2) in human neoplasms, we determined IL-2 and soluble IL-2 receptors (sIL-2R) in serum from 18 patients with lymphoma and 28 patients with solid tumors, with (15 cases) or without (13 cases) metastases. As controls, 58 healthy subjects were evaluated. Low levels of IL-2 were not observed in patients with lymphoma or limited solid tumor but abnormally low concentrations of IL-2 were seen in 4/15 metastatic solid tumors, associated with abnormally high values of sIL-2R. This preliminary study confirms in vivo the reduced IL-2 production in metastatic solid neoplasms, previously documented in vitro.     

Determination of whole body circadian phase in lung cancer patients: melatonin vs. cortisol

Background: A quantifiable and reliable technique for the determination of body circadian phase applicable to non-laboratory studies would allow the evaluation of circadian dysregulation. In this study we evaluated feasible methodologies to individualize whole body circadian phase in lung cancer patients. Methods: Cortisol and melatonin serum levels were measured in blood samples collected every 4 h for 24 h from eleven male controls and nine men suffering from non-small cell lung cancer. Circadian rhythmicity was evaluated and the 4-hourly fractional variations (FV) were calculated to evaluate the dynamics of the rise and fall in serum levels. Results: Overall cortisol serum levels were higher in cancer patients (p < 0.001), and lower for melatonin, but not significantly (p = 0.261). Original serum levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values at night for melatonin and near awakening for cortisol. Using all data after normalization to percent of individual mean, ANOVA detected a significant time-effect (p < 0.001) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) in each group. Overall fractional variation (FV) levels were lower for cortisol in cancer patients and higher for melatonin, but these differences were not significant. FV levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values prior to darkness onset for melatonin and near mid-dark for cortisol. ANOVA also detected a significant time-effect (p < 0.002) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) for FV in each group, with maximal FV preceding maximal serum levels by ～3 h for melatonin and ～5 h for cortisol. Conclusions: A chronobiological evaluation of serum levels and fractional variations for cortisol and especially melatonin is a valuable methodology to define body circadian phase in lung cancer patients. It is possible to describe the complex process of hormone secretion with a methodology that allows the definition of both temporal characteristics and dynamic components. Impact: This kind of analysis might be useful in the study of hormone secretion(s) in cancer patients and other diseases and to guide therapeutic interventions. While lung cancer patients may have a negative prognostic value based upon stage and/or other hormonal aspects of their hypothalamus–pituitary–thyroid–adrenal axis function, patients that nevertheless maintain circadian rhythmicity in key body rhythm markers may still be eligible candidates for a chronotherapeutic approach of treatment(s).     

Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans

Circadian rhythms of core body temperature and melatonin are commonly used as phase markers of the circadian clock. Melatonin is a more stable marker of circadian phase when measured under constant routine conditions. However, little is known about the variability of these phase markers under less controlled conditions. Moreover, there is little consensus about the preferred method of analysis. The objective of this study was to assess various methods of calculating melatonin and temperature phase in subjects with regular sleep schedules living in their natural environment. Baseline data were analyzed from 42 healthy young subjects who were studied on at least two occasions. Each hospital admission was separated by at least 3 weeks. Subjects were instructed to maintain a regular sleep schedule, which was monitored for 1 week before admission by sleep logs and actigraphy. Subjects spent one habituation night under controlled conditions prior to collecting baseline temperature and melatonin measurements. The phase of the melatonin rhythm was assessed by 9 different methods. The temperature nadir (Tmin) was estimated using both Cleveland and Cosine curve fitting procedures, with and without demasking. Variability between admissions was assessed by correlation analysis and by the mean absolute difference in timing of the phase estimates. The relationship to sleep times was assessed by correlation of sleep onset or sleep offset with the various phase markers. Melatonin phase markers were more stable and more highly correlated with the timing of sleep than estimates of Tmin. Of the methods for estimating Tmin, simple cosine analysis was the least variable. In addition, sleep offset was more strongly correlated with the various phase markers than sleep onset. The relative measures of melatonin offset had the highest correlation coefficients, the lowest study-to-study variability, and were more strongly associated with sleep timing than melatonin onsets. Concordance of the methods of analysis suggests a tendency for the declining phase of the melatonin profile to be more stable and reliable than either markers of melatonin onset or measures of the termination of melatonin synthesis.     

Serum endocan levels in relation to traditional and non-traditional anthropometric indices in adult population

BackgroundAssociation between endocan and nontraditional anthropometric indices, as distinct cardiovascular disease risk factors, has not been examined in previous studies. Endocan is a novel inflammation biomarker with its higher levels involved in cardiometabolic diseases development. Taking into consideration that obesity is an independent risk factor for many cardiometabolic diseases, we aimed to explore the relationship between endocan levels and novel anthropometric indices [i.e., body adiposity index (BAI), cardiometabolic index (CMI), a body shape index, body roundness index, conicity index, lipid accumulation product index and visceral adiposity index] and traditional ones [i.e., waist circumference, hip circumference, body mass index, waist-to-height ratio and waist-to-hip ratio] in adult population.MethodsA total of 177 participants were included. Anthropometric indices and biochemical parametres were measured.ResultsUnivariate regression analysis demonstrated positive correlations of endocan and almost all anthropometric data. To explore independent associations of endocan and anthropometric parameters, the Model which fulfilled criteria for ordinal regression testing was created. Adjusted odds for BAI given in the Model (OR=1.120, 95% CI 1.036-1.212, P=0.004), demonstrated that a rise in BAI by 1 unit increased the probability of higher endocan concentration by 12%. As well, a rise in CMI for 1 unit, increased the probability for higher endocan levels for 2.6 times (OR=2.599, 95% CI 1.006-6.712, P=0.049). A total of 20.1% of variation in endocan levels could be explained by this Model.ConclusionsNon-traditional obesity indices, BAI and CMI independently correlated with higher serum endocan levels in adult population.     

Thermoregulatory effects of melatonin in relation to sleepiness

Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonin-induced sleepiness occurs in parallel with reduction in the thermoregulatory set-point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set-point. In addition, an orthostatic challenge can partially block the melatonin-induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine-tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as "nature's soporific", it can also serve as nature's nocturnal vascular modulator.     

Thermoregulatory effects of melatonin in relation to sleepiness

Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonin‐induced sleepiness occurs in parallel with reduction in the thermoregulatory set‐point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set‐point. In addition, an orthostatic challenge can partially block the melatonin‐induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine‐tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as “nature's soporific”, it can also serve as nature's nocturnal vascular modulator.     

Serum concentrations of interleukin-8 in relation to different levels of alcohol consumption

Serum levels of interleukin-8 (IL-8) are increased in patients with alcoholic hepatitis and correlate with disease severity. The present study was aimed at investigating serum IL-8 levels in relation to different levels of alcohol consumption. Serum IL-8 was measured in (a) 459 individuals randomly selected from the general adult population, including 221 alcohol abstainers, 140 light drinkers (1-140 g/week), 53 moderate drinkers (141-280 g/week), and 45 heavy drinkers (>280 g/week), as well as (b) 137 alcoholics admitted to the hospital. The proportion of individuals with abnormally high (>10 pg/mL) IL-8 levels increased with alcohol use from 5.9% in abstainers to 10.7% in light, 13.2% in moderate, and 17.8% in heavy drinkers (P=0.004). This proportion was exceedingly high in alcoholics admitted to the hospital (70.1%, P<0.001 with respect to all other categories). Extremely high (>100 pg/mL) IL-8 levels were only observed among alcoholics, and were more frequent in females than in males (23.5% versus 9.7%, P=0.03) in spite of lower alcohol consumption among the former. These data indicate that the effect of alcohol on serum IL-8 levels begins with light-to-moderate drinking and is dose-dependent. Females may be more prone than males to develop extremely high IL-8 levels after heavy alcohol intake.