A comparison of experimental compressive axial loading testing with a numerical simulation of topologically optimized cervical implants made by selective laser melting.

In recent years, the number of cervical interventions has increased. The stress shielding effect is a serious complication in cervical spine interventions. Topological optimization is based on finite element method structural analysis and numerical simulations. The generated design of cervical implants is made from Ti6Al4V powder by selective laser melting while the optimized cage is numerically tested for compressive axial loading and the results are compared with experimental measurement. Additive manufacturing technologies and new software possibilities in the field of structural analysis, which use the finite element method tools, help to execute implant topological optimization that is useful for clinical practice. The inner structures of the implant would be impossible to make by conventional manufacturing technologies. The resulting implant design, after modification, must fulfill strict application criteria for the area of cervical spine with respect to its material and biomechanical properties. The aim of this work was to alter the mechanical properties of the cervical intervertebral cage to address the clinical concern of the stress shielding effect by topological optimization. A methodology of cervical implant compressive axial loading numerical simulation was created, and subsequent experimental testing was done to obtain real material properties after a selective laser melting process. The weight of the optimized implant was reduced by 28.92 %. Results of the experimental testing and numerical simulation of topologically optimized design showed 10-times lower stiffness compared to the solid cage design, and the real yield strength of the optimized structure is 843.8 MPa based on experimental results.

The influence of the low-frequency magnetic fields of different parameters on the secretion of cortisol in men.

OBJECTIVES: The aim of this paper is to test the influence of long-term application of the low-frequency magnetic fields in magnetotherapy and magnetostimulation on cortisol secretion in men. MATERIALS AND METHODS: Patients were divided into three groups: 16 men underwent magnetotherapy and 20 men (divided into two groups) underwent magnetostimulation. Magnetotherapy - 2 mT induction, 40 Hz, bipolar square wave, was applied for 20 min to lumbar area. Magnetostimulation (Viofor Jaroszyk, Paluszak, Sieron (JPS) system, M2P2 program) was applied to 10 patients for 12 min each day. The third group (10 patients) underwent magnetostimulation (Viofor JPS system, M3P3) for 12 min each day using a different machine. All groups had 15 rounds of applications at approximately 10:00 a.m. with intermissions on the weekends. Blood serum was taken four times in a 24-hour period, before applications, the day after applications and a month later. Chemiluminescence micromethod was used to indicate hormone concentrations. Data was statistically analyzed with the analysis of variance (ANOVA) method. RESULTS: The statistically significant gains in the circadian cortisol profile at 4:00 p.m., be- fore and after application, were observed as a decrease in concentration during magnetotherapy. In magnetostimulation, with the M2P2 program, a significant increase in the cortisol concentration was observed in circadian profile at 12:00 p.m. one month after the last application. After magnetostimulation with the M3P3 program, a significant increase in concentration at 6:00 a.m. and a decrease in concentration at 12:00 p.m. were observed one month later. Statistically significant difference was demonstrated in the participants after the application of magnetotherapy and magnetostimulation with M3P3 program compared to the men submitted to magnetostimulation, with M2P2 program, at 4:00 p.m. after 15 applications. CONCLUSIONS: Biological hysteresis one month after magnetostimulation suggests long-term influence on the hypothalamo-hypophysial axis. The circadian curves of cortisol secretion a day after magnetotherapy and magnetostimulation with M3P3 program compared to magnetostimulation with M2P2 progam differs nearly by 100%, which proves that they show varied influence on cortisol secretion in men. All changes in the hormone concentration did not exceed the physiological standards of cortisol secretion, which suggests a regulating influence of magnetic fields on cortisol concentration rather than a strong stressogenic impact of magnetostimulation.

Luzindole but not 4-phenyl-2- propionamidotetralin (4P-PDOT) diminishes the inhibitory effect of melatonin on murine Colon 38 cancer growth in vitro.

OBJECTIVE: Our earlier studies have shown that MLT exerts the inhibitory effect on murine cancer via membrane and nuclear receptors. We have found that the antagonist of MT1 receptors does not diminish the antiproliferative effect of MLT on Colon 38 cells, and the contribution of MT2 receptors has been suggested to be responsible. Therefore, in the present study we have examined the influence of the 4-phenyl-2-propionamidotetralin (4P-PDOT), which is a selective antagonist of MT2 membrane receptor, and luzindole - an antagonist of both membrane receptors, on an oncostatic action of MLT. MATERIALS AND METHODS: The murine cancer cell line Colon 38 was used in the experiments. In 48 hrs cell culture the effects of MLT, 4P-PDOT and luzindole administered alone and MLT applied jointly with either 4P-PDOT or luzindole were examined. The growth of cancer cells was assessed using the modified colorimetric Mosmann method. RESULTS: Melatonin at both examined concentrations (10-7, 10-9 M) significantly decreased the viability of cancer cells. The selective antagonist of MT2 membrane receptor, namely 4P-PDOT and luzindole applied separately did not have an effect on the growth of Colon 38 cells. The addition of 4P-PDOT to MLT did not change the inhibitory effect of MLT, whereas luzindole given together with MLT diminished, but failed to block totally, the oncostatic properties of MLT. CONCLUSIONS: The obtained data and our previous studies conducted on Colon 38 cancer indicate that membrane melatonin receptors are not indispensable to the oncostatic action of melatonin and thus other pathways such as nuclear signaling and receptor-independent mechanism may be also involved.

Human sexuality and sex steroids.

Studies on human sexuality are considered to be extremely difficult. Moreover, their results appear often unclear and contradictory. Sexuality is perceived as the identity, feelings and behavior associated with sex. Different assumptions concerning its mechanisms are made by researchers in the field of neuroendocrinology, endocrinology and psychology, and their tests' results help to describe human sexuality. Since the second half of the 20th century efforts of describing sexuality have been made, but they are still imperfect. There are no current research methods which allow for separation of sexual functions or sex-related behavior in a human, and for their description. It should be remembered, however, that the very awareness of taking part in such examination can have meaningful impact on the tests' results. What is more, the patient's emotional state can also alter the results. In this paper, current results on sexual steroids' place in forming human sexuality and its role in an adult human being life are presented. The cognition of the complete role of testosterone, estradiol and progesterone in forming human sexuality is considered to be the challenge for researchers in the following years.

High repeatability of circadian prolactin rhythm assessment results in children.

OBJECTIVES: In normal conditions, prolactin (Prl) secretion manifests a circadian pattern. So far, there have only been but few studies, concerning intrasubject variability and repeatability of the circadian Prl secretion pattern, based on pulse analysis. It seems, that macroscopic analysis based on measurement of Prl concentration at nine time points every 3 hours during 24 hours is an appropriate method to assess Prl profile for clinical purposes. The aim of the study was to assess the repeatability of that circadian Prl secretion pattern in a group of short children without hormonal disorders. MATERIALS AND METHODS: The analysis comprised the results of two circadian Prl profiles, performed from 2 to 14 months in 23 prepubertal children (16 boys) with idiopathic short stature, aged: 10.3+/-2.4 yrs. RESULTS: There were no statistical differences between Prl concentrations at the same time points in the two consecutive profiles, but the comparison of Prl concentrations at 8:00 gave results which were close to the border of statistical significance (p=0.055), what indicated low repeatability of measurement results at that particular time point. There were no statistical differences between the values of particular parameters in macroscopic profile analysis in the first and in the second test. CONCLUSION: Circadian Prl profile, based on nine Prl concentration measurements, taken every 3 hours during one day, is characterized by high repeatability of the results and low intrasubject variability in children, despite the results of Prl concentration at 08:00 o'clock.

Circadian pattern of prolactin secretion in children with growth hormone deficiency and congenital organic lesions in the hypothalamic-pituitary region.

OBJECTIVES: Prolactin (Prl) secretion in children manifests circadian rhythm. The aim of the study was to assess circadian Prl pattern in children with growth hormone deficiency (GHD) and congenital organic disorders in the hypothalamic-pituitary region (HPR). MATERIAL AND METHODS: The analysis comprised 47 children (aged: 11.05+/-3.5 years) with GHD, divided (based on MRI) into subgroups: NORM (no disturbances in HPR); HP (pituitary hypoplasia) and PSIS (pituitary stalk interruption syndrome). The profile of circadian Prl secretion was determined, based on Prl measurements in serum every 3 hours during 24 hours. The macroscopic analysis of circadian Prl rhythm in particular groups was performed. The comparison group consists of 41 children (aged: 11.45+/-3.20 years) with idiopathic short stature (ISS). RESULTS: In GHD-HP, diurnal and nocturnal Prl concentrations were low but with the dispersion between them and with normal rhythm in most of cases. In GHD-PSIS, diurnal and nocturnal Prl concentrations were on the same level and the rhythm was not observed in most of cases. No significant differences were found in Prl secretions and Prl rhythm between GHD-NORM and ISS. The rhythm of Prl secretion was disturbed in: 72.7% of children with GHD-PSIS, 23.5% - with GHD-HP, 10.5% with GHD-NORM and 7.3% with ISS, only. CONCLUSIONS: Congenital organic lesions of HPR are associated with quantitative disorders and changes of the circadian pattern of Prl secretion. In children with GHD without organic lesions of HPR, the circadian rhythm of Prl secretion was not different from that with ISS.

Assessment of prolactin secretion in children: a profile of circadian prolactin secretion and the principles for interpreting it.

INTRODUCTION: Prolactin (Prl) is secreted in a circadian pattern, although no method of interpreting it has yet been established. The aim of the study was to assess Prl secretion in children on the basis of the Prl circadian profile and to establish principles for the interpretation of the results obtained by this method. MATERIAL AND METHODS: The analysis comprised 41 healthy short children (25 boys); aged 5.2-16.3 years, in whom hormonal disorders and chronic diseases had been excluded. The children were divided into prepubertal or pubertal subgroups. Serum Prl concentrations were measured every 3 hours for 24 hours. To assess the rhythm the parameters of macroscopic analysis were calculated and receiver operating characteristic (ROC) analysis was performed. The group for comparison consisted of 30 children aged 8.9-17.2 years with hyperprolactinaemia. RESULTS: In each subgroup significantly higher Prl concentrations were observed at night than by day. No statistical differences were noticed between the groups regarding Prl concentrations at particular time points or parameter values during circadian Prl rhythm evaluation. In the group analysed weak correlations were found between age and Prl peak and trough levels. On the basis of ROC analysis criteria for the existence of normal circadian Prl rhythm in children were established. CONCLUSIONS: 1. The presence of normal circadian Prl rhythm is observed if at least one of the following three criteria is fulfilled: amplitude >1.8779; X(n)/X(d) ratio >1.685; regression index <-0.4107. 2. No interpretation in relation to sex, age and stage of puberty is necessary for the circadian prolactin secretion rhythm in children.

Partial growth hormone deficiency (GHD) in children has more similarities to idiopathic short stature than to severe GHD.

INTRODUCTION: Assessment of growth hormone (GH) secretion is based on stimulation tests. Low GH peaks in stimulation tests, together with decreased insulin-like growth factor-I (IGF-I) secretion, confirm a diagnosis of GH deficiency (GHD). However, limitations in interpreting the test results and discrepancies between GH and IGF-I secretion in particular patients have both been reported. GH therapy should improve the prognosis of adult height (PAH). The aim of the study was to compare the deficit of height at diagnosis, IGF-I secretion and PAH in children with either decreased (in varying degrees of severity) or normal GH secretion in stimulation tests. MATERIAL AND METHODS: The analysis comprised 540 short children (373 boys, 167 girls), aged 11.7 +/- 3.2 years. In all the patients two GH stimulation tests were performed, IGF-I serum concentration was measured, bone age was assessed and PAH was calculated. According to the GH peak in the two stimulation tests, the patients were classified into the following groups: severe GHD (sGHD)--GH peak < 5 ng/mL (n = 44), partial GHD (pGHD)--GH peak 5-10 ng/mL (n = 190), idiopathic short stature (ISS)--GH peak at least 10 ng/mL (n = 306). RESULTS: A significantly greater deficit of height, lower IGF-I secretion and worse PAH were observed in sGHD than in both remaining groups, while all the differences between pGHD and ISS in the parameters analysed were insignificant. CONCLUSION: The results obtained indicate the necessity of applying another methods of qualifying short children for GH therapy other than GH stimulation tests with a cut-off value at a level of 10 ng/mL.

Structural abnormalities in the levator palpebrae superioris muscle in patients with congenital blepharoptosis.

BACKGROUND AND OBJECTIVE: To evaluate structural and ultrastructural abnormalities of the levator palpebrae superioris (LPS) complex in patients with congenital blepharoptosis. PATIENTS AND METHODS: Samples of the LPS complex were obtained from patients operated on for congenital blepharoptosis between 2000 and 2001 and studied under light microscopy (15 cases) and electron microscopy (9 cases). RESULTS: Findings of light microscopy evaluation of the LPS complex correlated closely with the clinical grading of congenital blepharoptosis-hypoplasia, decreased number and varying diameter of muscle fibers, and fibrous tissue hyperplasia in the endomysium and perimysium. The Müller's muscle preserved a normal appearance. Mild blepharoptosis revealed proliferation of collagen fibers on electron microscopy. Moderate blepharoptosis showed abnormal distribution of myofibrils and distortion of the tubular system and mitochondria in addition to the changes observed in mild blepharoptosis. Severe blepharoptosis showed mitochondria loss, cytoplasm thinning, and homogenous fiber areas in addition to the changes observed in mild and moderate blepharoptosis. CONCLUSIONS: The clinical degree of severity of congenital blepharoptosis correlates positively with the degree of histopathologic changes in the levator palpebrae superioris muscle.

Assessment of insulin-like growth factor-I serum concentration as a screening procedure in diagnosing children with short stature.

OBJECTIVES: Insulin-like growth factor-I (IGF-I) secretion is growth hormone (GH) dependent. However the data on using IGF-I assessment as a screening procedure in diagnosing GH deficiency are not consistent. The goal of the study was an analysis of the relations between GH secretion in stimulating tests and plasma IGF-I concentration. PATIENTS & METHODS: The analysis comprised 540 children with short stature in whom two standard GH stimulating tests (GHST) were performed, together with an assessment of plasma IGF-I concentration. The relationships between GH peak in both tests and IGF-I secretion were analysed. RESULTS: There was no correlation either between GH peaks in different tests or between GH and IGF-I secretion in particular patients. Moreover, both the mean IGF-I concentration was similar in the patients with normal and subnormal results of GHST and the mean GH peak in GHST presented similar in the groups of children with normal and decreased IGF-I secretion. CONCLUSIONS: Assessment of IGF-I secretion fails to be a screening procedure for the results of GHST. The lack of correlation between the results of two GHST should be taken into account when evaluating the significance of GHST and IGF-I assessment in diagnosing GH deficiency.

[Hormones of youth?]. / Hormony mlodosci?

Ageing is doubtless complicated, lifelong process regarding many body systems, including endocrine system. Human hormonal system changes with age. Although these changes concern secretion of many hormones, they are not unidirectional, there are hormones secretion of which is diminished, whereas secretion of the others is augmented or not changed with age. A possible role of hormones which are often termed "hormones of youth"(growth hormone, melatonin, and dehydroepiandrosterone) in the ageing process is discussed in the present article. Although some experimental and clinical data indicate that these hormones may play some role in the human ageing process, it appears from presented data that we are still far away from conclusion that, indeed, one (or more) of the discussed hormones could be considered as "hormone of youth", which may slow down ageing process. However, some symptoms of the quality of life improvement following administration of dehydroepiandrosterone, melatonin, and growth hormone may suggest that they may promote so called "successful aging".

Increased melatonin concentrations in children with growth hormone deficiency.

A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1-16.9 yr (mean +/- S.E.M. = 14.1 +/- 0.3 yr) with short stature (height SDS below -2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak > or = 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children.

Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects.

The disturbances in pro- and antioxidant balance may play an important role in the pathomechanism of aging. The pineal hormone melatonin, which exerts effective antioxidative properties, is suggested to be involved in the aging process. The aim of this study was to compare the oxidative stress in erythrocytes of healthy young adults and elderly people, and to determine the influence of melatonin supplementation on measured parameters in both examined groups. The malondialdehyde (MDA) and reduced glutathione levels as well as Cu-Zn superoxide dismutase (SOD-1), catalase, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR) activities in erythrocytes and morning serum melatonin concentration in 14 healthy young adults and 14 healthy elderly people at baseline and after the 30th day of melatonin (5 mg daily) supplementation were determined. A significant age effect on increasing the MDA level and decreasing SOD-1, GSH-Px and GR activities as well as melatonin concentration was observed. Melatonin supplementation resulted in a significant increase in melatonin concentration, SOD-1 and GR activities and a decrease in the MDA level in both examined groups. These data indicate an age-related augmentation of oxidative stress in erythrocytes and the improvement of erythrocytic antioxidative defense by melatonin administration. These results might suggest melatonin supplementation to prevent age-related diseases and to prolong the lifespan and improve the quality of life of elderly people.

Growth-inhibitory action of melatonin and thiazolidinedione derivative CGP 52608 on murine 16/C breast cancer cells.

OBJECTIVES: Melatonin may influence directly tumor cells through the specific binding sites. The best known melatonin binding sites are membrane receptors. Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR receptors in oncostatic action of melatonin on the breast cancer has been widely discussed. The aim of present study was to investigate effects of melatonin, the selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on growth of murine 16/C breast cancer cells. MATERIAL AND METHODS: The experiment was performed in vitro. The breast cancer cells were incubated for 2 days in the presence of melatonin, CGP 52608 (at concentrations of 10(-5)M, 10(-7)M, 10(-9)M, 10-(11)M ) and methotrexate (at concentrations of 0.25 and 0.125 microg/ml). The growth of cells was measured using the modified Mossman method. RESULTS: All examined compounds significantly inhibited the growth of cancer cells. The effects of MLT and CGP 52 608 were comparable with suppression caused by methotrexate. The significant differences of efficacy between two examined concentrations of methotrexate were not observed. CONCLUSION: The obtained data together with our previous results indicate that nuclear receptors RZR/ROR play an important, although not sufficiently recognized role in the oncostatic action of melatonin.

The effects of melatonin, N-acetylserotonin, and 6-hydroxymelatonin on the ultrastructure of the pinealocytes of the Syrian hamster (Mesocricetus auratus).

OBJECTIVES: The aim of this study was to examine the effects of melatonin as well as of its precursor (N-acetylserotonin) and metabolite (6-hydroxymelatonin) on the ultrastructure of the pinealocytes of the Syrian hamster. MATERIAL AND METHODS: The pineal glands of 2-month-old male Syrian hamsters were examined. The animals were divided into the following groups of four animals each: group 1 - melatonin treatment; group 2 - N-acetylserotonin treatment; group 3 - 6-hydroxymelatonin treatment (all substances given subcutaneously at doses of 25 microg per animal between 16.00 and 17.00 h daily for seven weeks). Group 4 was given solvent treatment only and served as controls. The animals were killed by decapitation between 09:00 and 10.00 h. Routine electron microscopical techniques were used to obtain quantitative data on pinealocyte ultrastructure. RESULTS: Melatonin administration did not influence the size of the hamster pinealocytes, whereas administration of N-acetylserotonin and 6-hydroxymelatonin caused a significant reduction in cell size in comparison to the melatonin-treated and control groups. There were changes in the relative volumes of the mitochondria, Golgi apparatus and lysosomes in the pinealocytes of the studied groups, while the volumes of granular endoplasmic reticulum and lipid droplets were unchanged. The dense-core vesicles were more numerous in the pinealocytes of the melatonin and 6-hydroxymelatonin-treated groups in comparison to those of animals treated with N-acetylserotonin or the controls. CONCLUSIONS: The changes observed in the ultrastructure of hamster pinealocytes indicate that administration of melatonin as well as of its precursor or metabolite influences the morphology of these cells and also, perhaps, their secretory activity.

Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL-2 production.

Human lymphocytes have recently been described as an important physiological source of melatonin (N-acetyl-5-methoxytryptamine), which could be involved in the regulation of the human immune system. On the other hand, stimulation of IL-2 production by exogenous melatonin has been shown in the Jurkat human lymphocytic cell line. Furthermore, both melatonin membrane and nuclear receptors are present in these cells. In this study, we show that the necessary machinery to synthesize melatonin is present and active in resting and stimulated Jurkat cells. Accordingly, we have found that cells synthesize and release melatonin in both conditions. Therefore, we investigated whether endogenous melatonin produced by Jurkat cells was involved in the regulation of IL-2 production. When melatonin membrane and nuclear receptors were blocked using specific antagonists, luzindole and CGP 55644, respectively, we found that IL-2 production decreased, and this drop was reverted by exogenous melatonin. Additionally, PHA activation of Jurkat cells changed the profile of melatonin nuclear receptor mRNA expression. A previous study showed that exogenous melatonin is able to counteract the decrease in IL-2 production caused by prostaglandin E2 (PGE2) in human lymphocytes via its membrane receptor. In our model, when we blocked the melatonin membrane receptor with luzindole, the inhibitory effect of PGE2 on IL-2 production was higher. Therefore, we have demonstrated the physiological role of endogenous melatonin in this cell line. These findings indicate that endogenous melatonin synthesized by human T cells would contribute to regulation of its own IL-2 production, acting as an intracrine, autocrine, and/or paracrine substance.

[Hyperprolactinemia: causes, diagnosis, and treatment]. / Hiperprolaktynemia: przyczyny, diagnostyka, leczenie.

The basic data on hyperprolactinemia (i.e. an excess of PRL above a reference laboratory's upper limits), the most common endocrine disorder of the hypothalamic-pituitary axis are given in this review. The following issues are discussed: regulation of prolactin (Prl) secretion, definition of hyperprolactinemia, its etiology and pathogenesis as well as its symptoms, diagnosis, and treatment (including medical and surgical therapy). It should be stressed that finding of elevated PRL serum concentrations constitute the beginning of diagnostic procedure and, after exclusion of physiologic, pharmacologic, and other organic causes of increased PRL levels, should be followed by detailed diagnosis including MRI. In patients in whom hyperprolactinemia has been confirmed the treatment with dopamine agonists (with prevalence of cabergoline, followed by quinagoline) is currently considered first-choice therapy. Surgery should be performed only in the patients resistant or intolerant to these agents, or in patients who refuse long-term therapy.

Decreased melatonin nocturnal concentrations in hemodialyzed patients.

OBJECTIVES: In spite of broad interest, intensive studies on function of melatonin have not yielded much information about relationships between this hormone and kidneys in health, and particularity, in disease. There are only a few studies dealing with melatonin concentrations in renal diseases, mainly performed in hemodialyzed patients with end-stage renal disease (ESRD). Moreover, the most melatonin assays were performed during the daytime, and the results are conflicting. Therefore, the aim of the present study was to determine the circadian melatonin profiles in patients ESRD before and after hemodialysis. MATERIAL AND METHODS: Thirty patients (19 males and 11 females) with ESRD undergoing dialysis, aged 22 to 64 years (mean+/-SEM: 49.1.0+/-1.9 years) were included in the study. The control group consisted of 20 healthy volunteers (13 males and 7 females) aged 35 to 55 years (mean+/-SEM: 46.2+/-1.4 years) matched according to sex and age. Blood samples were collected on the day preceding hemodialysis and one day following dialysis at 08:00, 12:00, 16:00, 20:00, 24:00, 02:00, 04:00, and 08:00 h. Melatonin concentration was measured by enzyme immunoassay. RESULTS: In patients with renal insufficiency undergoing dialysis mean melatonin nocturnal concentrations were significantly lower then those in healthy volunteers. The presence of the circadian rhythm in melatonin concentrations (although of significantly lower nocturnal amplitude) was detected only in 8 patients with renal failure undergoing hemodialysis, whereas in remaining 22 patients no such rhythm was found. Hemodialysis did not influence melatonin concentrations. CONCLUSIONS: The mechanism of depressed melatonin concentrations in hemodialyzed patients observed in our study remains unclear. However, it seems possible that decline in melatonin levels is due to impairment in adrenergic function that occurs in renal failure. Because the studies on the melatonin secretion in chronic renal failure bring about conflicting results, the relationship between renal diseases and melatonin secretion needs further investigations.

Serum melatonin circadian profiles in women suffering from cervical cancer.

Although there is an increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore, we decided to study the circadian melatonin rhythm in patients suffering from cervical cancer in different stages of progression and to compare them with those in subjects free from neoplastic disease. A total of 45 women were analyzed in this study. The subjects were divided into two groups. The first group consisted of 31 patients [mean age 52.1 +/- 1.8 yr (mean +/- S.E.M.), range 32-77 yr] with cervical cancer in various stages of the disease. The second group consisted of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/- S.E.M.), range 42-63] who served as the control group. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00, and 08:00 hours. Melatonin concentration was measured by immunoenzymatic method. There were significant differences in circadian melatonin profiles as well as in the area under curve among the two studied groups. Melatonin concentrations were significantly lower in cancer patients in comparison with healthy individuals. Taking into consideration stage of the cervical cancer significantly lower melatonin secretion has been found in all subgroups of patients in comparison with that of tumor-free control group. Additionally, nocturnal melatonin concentrations as well as area under curve were significantly lower in advanced stage of cancer (stages 3 and 4) in comparison with patients with preinvasive cancer (stage 0) at 24:00, 02:00, and 04:00 hours and patients with stage 1 disease at 02:00 and 04:00 hours. The results of the present study indicate that the presence of cervical cancer influences melatonin levels in women. Moreover, stage dependence in reduction of melatonin concentrations has been found.

Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system.

Since melatonin was first isolated in 1958 up to the last few years, this substance was considered a hormone exclusive to the pineal gland. Although melatonin has lately been identified in a large number of extrapineal sites, its potential biological actions have not yet been studied. This paper shows that human lymphocyte-synthesized melatonin plays a crucial role modulating IL-2/IL-2 receptor system because when blocking melatonin biosynthesis by the tryptophan hydroxylase inhibitor, parachlorophenylalanine, both IL-2 and IL-2 receptor levels fell, restoring them by adding exogenous melatonin. Moreover, we demonstrated that this endogenous melatonin interfered with the exogenous melatonin effect on IL-2 production. Melatonin exerted these effects by a receptor-mediated action mechanism because both IL-2 and IL-2 receptor expressions significantly decreased when lymphocytes were incubated in the presence of the specific membrane and/or nuclear melatonin receptor antagonists, luzindole, and/or CGP 55644, respectively. Finally, we made the real significance of the membrane melatonin receptors in this process clear, so prostaglandin E(2)-induced inhibition on IL-2 production increased when we blocked the membrane receptors using luzindole. In conclusion, these data show that endogenous melatonin is an essential part for an accurate response of human lymphocytes through the modulation of IL-2/IL-2 receptor system.