Melatonin ameliorates the sleep disorder induced by surgery under sevoflurane anaesthesia in aged mice.

Post-operative sleep disorders induce adverse effects on patients, especially the elderly, which may be associated with surgery and inhalational anaesthetics. Melatonin is a neuroendocrine regulator of the sleep-wake cycle. In this study, we analysed the alterations of post-operative sleep in aged melatonin-deficient (C57BL/6J) mice, and investigated if exogenous melatonin could facilitate entrainment of circadian rhythm after laparotomy under sevoflurane anaesthesia. The results showed that laparotomy under sevoflurane anaesthesia had a greater influence on post-operative sleep than sevoflurane alone. Laparotomy under anaesthesia led to circadian rhythm shifting forward, altered EEG power density and delta power of NREM sleep, and lengthened REM and NREM sleep latencies. In the light phase, the number of waking episodes tended to decline, and wake episode duration elevated. However, these indicators presented the opposite tendency during the dark phase. Melatonin showed significant efficacy for ameliorating the sleep disorder and restoring physiological sleep, and most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist.

Effect of endurance training on diurnal rhythms of superoxide dismutase activity, glutathione and lipid peroxidation in plasma of pinealectomized rats.

Melatonin deficit is characterized by disturbed circadian rhythms of many physiological and biochemical parameters including markers of oxidative stress. Moderate endurance training exerts protection against oxidative stress. In the present study, we aimed to explore the impact of endurance treadmill training on disturbed rhythmic fluctuations of some markers of oxidative stress in pinealectomized rats. Animals were divided into four groups: sham-operated sedentary rats (sham-sed), a sham group with exercise (sham-ex), pinealectomized sedentary rats (pin-sed) and pin rats with exercise (pin-ex). Animals were sacrificed by decapitation at 4-h intervals for biochemical analysis of plasma melatonin and markers of oxidative stress. The activity of superoxide dismutase (SOD) and the levels of glutathione (GSH) and lipid peroxidation demonstrated diurnal variations in the sham-sed group. The peak values of SOD were detected during the dark period that coincided with the peak plasma levels of melatonin in the sham-sed rats. The malondialdehyde (MDA) levels also showed a tendency to a progressive raise during the dark period. Pinealectomy was characterized by a remarkable melatonin deficit in plasma of sedentary rats, compromised fluctuations with decreased SOD activity and increased lipid peroxidation. While endurance training was unable to restore the melatonin deficit, it partly prevented the oxidative stress at selected time points in the pinealectomised rats. Our findings indicate the important role of endurance training against oxidative stress both in physiological conditions and melatonin deficit.

Melatonin deficiency at tissue level: a possible aetiological factor in nasal polyposis.

OBJECTIVE: The aim of this study was to examine whether melatonin is involved in the pathogenesis of nasal polyposis. METHOD: This study included 29 patients with nasal polyposis and undergoing functional endoscopic sinus surgery. As a control group, 26 patients who had been operated on for a deviated nasal septum and concha bullosa were enrolled. Samples were taken from the nasal polyp tissue and from the resected middle concha bullosa mucosa of the control group. Serum samples were taken from all patients. RESULTS: It was found that the tissue and serum melatonin levels in the nasal polyp group were significantly lower compared with the tissue and serum melatonin levels in the control group. CONCLUSION: In nasal polyposis, the melatonin level in the serum and tissue is lower than in individuals without polyposis. This deficiency may play a role in the pathogenesis of nasal polyposis.

The Role of Melatonin in Oxidative Stress, DNA Damage, Apoptosis and Angiogenesis in Fetal Eye under Preeclampsia and Melatonin Deficiency Stress.

Aim: The aim of this study was to investigate the possible mechanisms of ocular damage induced by pinealectomy (PNX) and preeclampsia (PE), and to determine the cellular and molecular effects of melatonin treatment on oxidative stress, DNA damage, molecular chaperone responses, induction of apoptosis and angiogenesis in the fetal eye of both PNX and PNX+PE animals. Material and Methods: We analysed therapeutic potential of melatonin on fetal eye damage in PNX and PNX+PE animals using Malondialdehyde (MDA), Random Amplified Polymorphic DNA (RAPD), qRT-PCR and Western blot assays. Results: Our study presents three preliminary findings: (a) in fetal eye tissues, PNX and PNX+PE significantly induce oxidative damage to both DNA and protein contents, leading to a dramatic increase in caspase-dependent apoptotic signalling in both mitochondrial and death receptor pathways; (b) the same conditions trigger hypoxia biomarkers in addition to significant overexpression of HIF1-α, HIF1-ß, MMP9 and VEGF genes in the fetal eye; (c) finally, melatonin regulates not only the expression of genes encoding antioxidant enzymes and increase in DNA damage as well as lipid peroxidation but also limits programmed cell death processes in the fetal eye of PNX and PNX+PE animals . Furthermore, melatonin can relatively modulate genes in the HIF1 family, TNF-α and VEGF, thus acting as a direct anti-angiogenic molecule. In conclusion, both PNX and PNX+PE induce ocular damage at both cellular and molecular levels in fetal eye tissue of rats. Conclusion: Our results clearly indicate the potential of melatonin as a preventative therapeutic intervention for fetal ocular damage triggered by both PNX and PNX+PE.

Low serum melatonin levels are associated with erectile dysfunction

ABSTRACT Objective: Melatonin is a hormone secreted from the pineal gland and has anti-oxidative and anti-inflammatory effects. Oxidative stress is considered as an important factor in the etiology of erectile dysfunction (ED), and in many experimental models, positive results have been obtained with melatonin treatment. This study aimed to measure serum melatonin levels in ED patients and to investigate the possible relationship between ED and melatonin levels. Materials and Methods: Sixty-two patients diagnosed with mild, moderate or severe ED according to the five-item International Erectile Function Index (IIEF-5) and 22 healthy individuals were included in the study. The serum melatonin levels, anthropometric data, and other biochemical and hormonal parameters of all the subjects were recorded. Detailed anamnesis was also obtained in terms of diabetes, hypertension, cardiovascular diseases, smoking status, and alcohol use. Results: The serum melatonin level was found 34.2±13.3 ng/dL in the mild ED group, 33.3±14.7 ng/dL in the moderate ED group, 34.8±17.2 ng/dL in the severe ED group, and 44.6±16.5 ng/dL in the control group. The serum melatonin levels were significantly lower in all ED groups compared to the control group (p=0.019). There was no significant difference in the serum melatonin levels between the three ED groups. Diabetes, hypertension, cardiovascular diseases, smoking and alcohol use were not significantly different between the ED groups (p>0.05). Conclusion: We consider that if our findings are supported by further studies with larger populations, the measurement of the serum melatonin level may have a future role in the diagnosis and treatment of ED.

Low serum melatonin levels are associated with erectile dysfunction.

OBJECTIVE: Melatonin is a hormone secreted from the pineal gland and has anti-oxidative and anti-inflammatory effects. Oxidative stress is considered as an important factor in the etiology of erectile dysfunction (ED), and in many experimental models, positive results have been obtained with melatonin treatment. This study aimed to measure serum melatonin levels in ED patients and to investigate the possible relationship between ED and melatonin levels. MATERIALS AND METHODS: Sixty-two patients diagnosed with mild, moderate or severe ED according to the five-item International Erectile Function Index (IIEF-5) and 22 healthy individuals were included in the study. The serum melatonin levels, anthropometric data, and other biochemical and hormonal parameters of all the subjects were recorded. Detailed anamnesis was also obtained in terms of diabetes, hypertension, cardiovascular diseases, smoking status, and alcohol use. RESULTS: The serum melatonin level was found 34.2±13.3 ng/dL in the mild ED group, 33.3±14.7 ng/dL in the moderate ED group, 34.8±17.2 ng/dL in the severe ED group, and 44.6±16.5 ng/dL in the control group. The serum melatonin levels were significantly lower in all ED groups compared to the control group (p=0.019). There was no significant difference in the serum melatonin levels between the three ED groups. Diabetes, hypertension, cardiovascular diseases, smoking and alcohol use were not significantly different between the ED groups (p>0.05). CONCLUSION: We consider that if our findings are supported by further studies with larger populations, the measurement of the serum melatonin level may have a future role in the diagnosis and treatment of ED.

Characterization of the relations between morphology and physiological status of the pineal gland in connection with the somatic development level in turkeys reared in Romania / Caracterização das relações entre morfologia e estado fisiológico da glândula pineal em conexão com o nível de desenvolvimento somático em perus criados na România

This research started from the premises of the existence of some possible relationships between indole and pineal peptide hormones and the somatic development, with participation of hypothalamic-pituitary complex. Experimental factors, which were the subject of the present paper, influenced the dynamics of corporal mass and fodder consumption, leading to the occurrence of some important structural modifications at the level of pineal gland. The exposure of the individuals to continuous light (photic pinealectomy) produces increases in corporal mass, showing the involvement of the pineal gland in neuro-endocrine-metabolic reactions, which contributes to the maintenance of homeostatic balance, including somatic ones. Biological material was represented by a number of 50 individuals belonging to B.U.T. Big 6 hybrid, reared on soil, on a permanent litter, which could assure the expanding of knowledge area regarding the relation between rearing technology, modulation of some microclimate parameters and growing performances. Were also realised cytometric and hystometric muscular determinations.

A pesquisa começou a partir da premissa de que provavelmente existam relações entre indol e hormônios peptídicos pineal e o desenvolvimento somático, com a participação do complexo hipotálamo-hipófise. Fatores experimentais que foram objeto do presente trabalho influenciaram a dinâmica da massa corporal e o consumo de forragem, o que leva à ocorrência de algumas modificações estruturais importantes no nível da glândula pineal. A exposição dos indivíduos à luz contínua (Pinealectomia photic) leva ao aumento de massa corporal, mostrando o envolvimento da glândula pineal em reações neuroendócrino metabólicas, inclusive somáticas, que contribuem na manutenção do equilíbrio homeostático. O material biológico foi representado por um número de 50 indivíduos pertencentes a MAS Big híbrido 6, criados em solo, em uma ninhada permanente, o que poderia garantir a expansão da área de conhecimento a respeito da relação entre a tecnologia de criação, modulação de alguns parâmetros microclimáticos e performances de crescimento. Também foram realizadas por citometria e histometria determinações musculares.

Melatonin administration alters nicotine preference consumption via signaling through high-affinity melatonin receptors.

RATIONALE: While it is known that tobacco use varies across the 24-h day, the time-of-day effects are poorly understood. Findings from several previous studies indicate a potential role for melatonin in these time-of-day effects; however, the specific underlying mechanisms have not been well characterized. Understanding of these mechanisms may lead to potential novel smoking cessation treatments. OBJECTIVE: The objective of this study is examine the role of melatonin and melatonin receptors in nicotine free-choice consumption METHODS: A two-bottle oral nicotine choice paradigm was utilized with melatonin supplementation in melatonin-deficient mice (C57BL/6J) or without melatonin supplementation in mice proficient at melatonin synthesis (C3H/Ibg) compared to melatonin-proficient mice lacking both or one of the high-affinity melatonin receptors (MT1 and MT2; double-null mutant DM, or MT1 or MT2). Preference for bitter and sweet tastants also was assessed in wild-type and MT1 and MT2 DM mice. Finally, home cage locomotor monitoring was performed to determine the effect of melatonin administration on activity patterns. RESULTS: Supplemental melatonin in drinking water significantly reduced free-choice nicotine consumption in C57BL/6J mice, which do not produce endogenous melatonin, while not altering activity patterns. Independently, genetic deletion of both MT1 and MT2 receptors in a melatonin-proficient mouse strain (C3H) resulted in significantly more nicotine consumption than controls. However, single genetic deletion of either the MT1 or MT2 receptor alone did not result in increased nicotine consumption. Deletion of MT1 and MT2 did not impact taste preference. CONCLUSIONS: This study demonstrates that nicotine consumption can be affected by exogenous or endogenous melatonin and requires at least one of the high-affinity melatonin receptors. The fact that expression of either the MT1 or MT2 melatonin receptor is sufficient to maintain lower nicotine consumption suggests functional overlap and potential mechanistic explanations.

[Role of transcription nuclear factor kB in mechanisms impairing oxidative metabolism in rats brain under chronic hypomelatoninemia].

The experiment carried out on 20 Wistar male rats weighing 180-220 g was designed to study the effect of NF-κB activation on the free radical oxidation and bioenergy processes in the brain under modeled chronic hypomelatoninemia (animals were exposured to steady illumination at a dose of 1500 lux for 55 days). It has been shown the intraperitoneal administration (daily for the last 7 days of steady illumination) of nuclear factor κB (NF-κB) activation inhibitor II - JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1,2-diamine) in a dose of 1 mg/kg of animal's body wt is accompanied with a significant reduction in ·Ðž2 production by mitochondria and NADPH oxidase of leukocytes, by the formation of secondary LPO products, increased activity of superoxide dismutase and catalase, AO potential, ATP content and energy quotient. It might be concluded the disturbances resulting in the above mentioned processes in the brain under steady hypomelatoninemia are of NF-κB-dependent nature.

Melatonin influences on steroidogenic gene expression in the ovary of pinealectomized rats.

OBJECTIVE: To analyze the expression of genes related to steroidogenesis in the ovary of pinealectomized rats. DESIGN: Experimental research. SETTING: University research laboratory. ANIMAL(S): Thirty female adult rats. INTERVENTION(S): Administration of vehicle (GI), pinealectomy with vehicle (GII), or pinealectomy with melatonin replacement (10 µg/night) for 60 consecutive days (GIII), then euthanasia after 2 months of treatment, ovary collection complementary DNA microarray analyses, confirmatory quantitative reverse-transcriptase polymerase chain reaction analyses, and immunohistochemical analyses for localizing steroidogenesis changes in the ovary. MAIN OUTCOME MEASURE(S): Biologic molecular study followed by immunohistochemical analysis. RESULT(S): The changes in the expression of CYP11A1, CYP17A1, and CYP19A1 after pinealectomy (GII) compared with control (GI) showed the Cyp17a1 expression level increased in the theca interna and interstitial cells in the GII rats compared with the other groups. CONCLUSION(S): Melatonin deprivation (pinealectomy) or administration may influence the ovarian CYP17A1 expression and steroidogenesis.

Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model.

This study assessed the effect of melatonin deprival on ovarian status and function in sheep. Experimental procedures were carried out within two consecutive breeding seasons. Animals were divided into two groups: pinealectomised (n=6) and sham-operated (n=6). The completeness of the pineal gland removal was confirmed by the plasma concentration of melatonin. Ovarian status was monitored by ovarian ultrasonography for 1 year to study reproductive seasonality. Follicular and corpus luteal growth dynamics were assessed during an induced oestrous cycle. As the effects of melatonin on the ovary may also be mediated by its antioxidant properties, plasma Trolox equivalent antioxidant capacity (TEAC) was determined monthly for 1 year. Pinealectomy significantly extended the breeding season (310±24.7 vs 217.5±24.7 days in controls; P<0.05). Both pinealectomised and sham-operated ewes showed a well-defined wave-like pattern of follicle dynamics; however, melatonin deficiency caused fewer waves during the oestrous cycle (4.3±0.2 vs 5.2±0.2; P<0.05), because waves were 1 day longer when compared with the controls (7.2±0.3 vs 6.1±0.3; P<0.05). The mean area of the corpora lutea (105.4±5.9 vs 65.4±5.9 mm(2); P<0.05) and plasma progesterone levels (7.1±0.7 vs 4.9±0.6 ng/ml; P<0.05) were significantly higher in sham-operated ewes compared with pinealectomised ewes. In addition, TEAC values were significantly lower in pinealectomised ewes compared with control ones. These data suggest that melatonin, besides exerting its well-known role in the synchronisation of seasonal reproductive fluctuations, influences the growth pattern of the follicles and the steroidogenic capacity of the corpus luteum.

The expression of inflammatory cytokines on the aorta endothelia are up-regulated in pinealectomized rats.

This study was designed to investigate the effect of melatonin on the expression of aortic inflammatory cytokines and its underlying mechanisms in rats. Melatonin deficiency rats (Px, N = 16) were created by pinealectomy and were fed with normal diet for 16 weeks after the surgery, and compared with sham-operated rats (Con, N = 14). Serum lipid profile, glucose metabolism parameters, serum oxidative stress and inflammatory biomarkers were evaluated. The expression of inflammatory cytokines in the aorta endothelia was analyzed. To evaluate the signal transduction pathways of melatonin on the expression of cytokines, rat aortic endothelial cell lines (RAECs) were treated with melatonin, and their protein expressions of inflammatory cytokines and phosphorylation levels of relevant signal pathways were detected. At the 16th week after surgery in Px rats, their serum triglyceride, very low density lipoprotein cholesterol, free fatty acid and glucose levels were prominently elevated (all P < 0.05); serum oxidative stress biomarker malondialdehyde, serum inflammatory biomarkers oxidized low-density lipoprotein, tumor necrosis factor-α, interleukin-6 and C reactive protein were also significantly increased. Meanwhile, the expression of inflammatory cytokines: monocyte chemotactic protein-1 (MCP-1), vascular adhesion molecule 1 (VCAM-1) and matrix metalloproteinase-9 (MMP-9) of the aorta endothelia in Px rats were significantly up-regulated (all P < 0.05). In vitro, melatonin significantly decreased the expression of MCP-1, VCAM-1 and MMP-9 proteins, along with the suppression of phosphorylation levels of nuclear factor κB (NF-κB)/P65 and p38 mitogen-activated protein kinase (P38-MAPK) in RAECs. Melatonin deficiency elevates the serum inflammatory biomarkers and increases aortic inflammatory responses. Melatonin regulates these inflammatory responses by NF-κB and P38-MAPK involved pathways.

Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth.

The pineal hormone melatonin (MLT) has potent anti-breast cancer activity, its actions are heavily mediated via the MT1 receptor and subsequent modulation of downstream signaling pathways including cAMP/PKA, Erk/MAPK, p38, and Ca2+/calmodulin. Also, via the MT1 pathway, MLT can repress the transcriptional activity of some mitogenic nuclear receptors including ERα, GR, and RORα, while potentiating the activity of other receptors (RARα and RXRα) involved in differentiation, anti-proliferation, and apoptosis. A review of the literature supports the view that MLT, via its MT1 receptor, can suppress all phases of breast cancer including initiation, promotion, and progression. During the fifth and sixth decades of life, the production of MLT diminishes, concurrently with an increase in the incidence of breast cancer. Inasmuch as MLT has been demonstrated to have anti-cancer activity, we hypothesized that there may be a causal link between the reduction in MLT production in the pineal gland and the incidence of breast cancer which increases with age. We designed this study to establish whether a truly inverse relationship exists between tissue-isolated mammary tumor growth in young (2 months), adult (12 months), and old (20 months) female Buffalo rats and the decrease in both MLT and the MT1 receptor with age, such that a causal link could be found. Serum MLT levels were measured in both the light and dark phases. A significant 29% decrease in serum MLT levels, measured at the nocturnal peak, was found in the adult and senescent rats (75% decrease) in comparison to that in young rats. In young rats, the nocturnal pineal gland MLT content exceeded daytime levels by 19-fold compared to a sevenfold increase in old mice. Also, the MT1 receptor was found to be significantly lower in the nighttime and early morning in the senescent rat uterus as compared to uteri from young and adult rats. Analysis of the rate of growth in transplanted, tissue-isolated, mammary tumors induced by N-nitroso-n-methyl-urea (NMU) showed a significant increase in the senescent rats, but not in the young or adult rats Additionally, diminished response to the inhibitory action on tumor growth of exogenous MLT was noted in senescent rats such that tumor growth was suppressed by only 33% compared to 48% and 66% in adult and young rats, respectively. The diminution of the response of tumors to exogenous MLT was found to correlate with reduced MT1 receptor expression in senescent compared to young and adult rats. These data suggest that the observed age-associated enhanced growth of tumors is related to the much reduced levels of MLT and its receptor in aged animals which reduce the sensitivity of tumors to inhibition by exogenous MLT.

Experimental models of melatonin-deficient hypertension.

Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs.

Neurobiology, pathophysiology, and treatment of melatonin deficiency and dysfunction.

Melatonin is a highly pleiotropic signaling molecule, which is released as a hormone of the pineal gland predominantly during night. Melatonin secretion decreases during aging. Reduced melatonin levels are also observed in various diseases, such as types of dementia, some mood disorders, severe pain, cancer, and diabetes type 2. Melatonin dysfunction is frequently related to deviations in amplitudes, phasing, and coupling of circadian rhythms. Gene polymorphisms of melatonin receptors and circadian oscillator proteins bear risks for several of the diseases mentioned. A common symptom of insufficient melatonin signaling is sleep disturbances. It is necessary to distinguish between symptoms that are curable by short melatonergic actions and others that require extended actions during night. Melatonin immediate release is already effective, at moderate doses, for reducing difficulties of falling asleep or improving symptoms associated with poorly coupled circadian rhythms, including seasonal affective and bipolar disorders. For purposes of a replacement therapy based on longer-lasting melatonergic actions, melatonin prolonged release and synthetic agonists have been developed. Therapies with melatonin or synthetic melatonergic drugs have to consider that these agents do not only act on the SCN, but also on numerous organs and cells in which melatonin receptors are also expressed.

Nocturnal headache associated with melatonin deficiency due to a pineal gland cyst.

The cyclic nature of some of headache disorders is closely related to melatonin, which is secreted by the pineal gland. We report a 29-year-old male patient with a 2.5-year history of headaches that woke him in the middle of the night. These headaches were pulsatile and continued until sunrise. During these attacks he also suffered from allodynia over the scalp, bilateral conjunctival hyperemia, and nervousness. His brain MRI showed a 5mm by 4mm neuroepithelial cyst in the pineal gland. The peak plasma melatonin level that was measured at 2 am was 28 pg/mL. The patient underwent oral melatonin treatment (6 mg/day). After 1 month he experienced a 70% reduction in his symptoms. When the melatonin dosage was increased to 10mg/day he became headache-free, and 5 months after the treatment began, had no complaints. His 5-month follow-up plasma melatonin level at 2 am was 61 pg/mL. To our knowledge this is the first report of a patient with nocturnal headache associated with a low level of melatonin due to a neuroepithelial cyst in the pineal gland.

Pinealectomy affects bone mineral density and structure--an experimental study in sheep.

BACKGROUND: Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model. METHODS: Female sheep were arranged into four groups: Control, surgically ovariectomized (Ovx), surgically pinealectomized (Px) and Ovx+Px. Before and 6 months after surgery, iliac crest biopsies were harvested and structural parameters were measured using µCT. Markers of bone formation and resorption were determined. To evaluate long term changes after pinealectomy, bone mineral density (BMD) was analyzed at the distal radius at 0, 3, 9, 18 and 30 months. RESULTS: Cancellous bone volume (BV/TV) declined after 6 months by -13.3% Px and -21.5% OvxPx. The bone loss was due to increased trabecular separation as well as decreased thickness. The histomorphometric quantification and determination of collagen degradation products showed increased bone resorption following pinealectomy. Ovariectomy alone results in a transient bone loss at the distal radius followed by continuous increase to baseline levels. The bone resorption activity after pinealectomy causes a bone loss which was not transient, since a continuous decrease in BMD was observed until 30 months. CONCLUSIONS: The changes after pinealectomy in sheep are indicative of bone loss. Overall, these findings suggest that the pineal gland may influence bone metabolism and that pinealectomy can be used to induce bone loss in sheep.

[About entropy in ophthalmology]. / Consideratii asupra entropiei în oftalmologie.

Entropy is one of the most controversial ideas ever described. Clausius, who discovered this natural propriety in 1865, used this notion in order to define the conversion of energy. Out of a thermodynamic point of view, health is seen as a minimum of entropy and illness as a maximum.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

BACKGROUND: A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. OBJECTIVE: We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. PATIENT: The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. METHODS: A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. RESULTS: Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. CONCLUSION: In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

Shift work and cancer - considerations on rationale, mechanisms, and epidemiology.

This paper summarizes the rationale for, possible mechanisms of, and problems related to risk assessment of the association between shift work and cancer. The mechanisms by which circadian disruption may favor the induction and/or promotion of malignant tumors are complex and multifactorial. The multilevel endocrine changes caused by circadian disruption with melatonin suppression through light at night (LAN) lead to the oncogenic targeting of the endocrine-responsive breast in women and possibly the prostate in men. Repeated phase shifting with internal desynchronization may lead to defects in the regulation of the circadian cell cycle, thus favoring uncontrolled growth. Sleep deprivation leads to the suppression of immune surveillance that may permit the establishment and/or growth of malignant clones. The epidemiological studies published so far, although dealing with large cohorts and controlling for several personal confounders, have defined the exposure to shift and/or night work rather loosely and consequently do not allow for the proper assessment of the risk connected with circadian disruption.