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Biomedical subjects

Moshe Laudon

Publications and source records attributed to Moshe Laudon.

9 recordsLinked to original sources

Melatonin reduces night blood pressure in patients with nocturnal hypertension.

PURPOSE: Nocturnal hypertension is associated with a high risk of morbidity and mortality. A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients. We therefore studied the potency of melatonin to reduce nighttime blood pressure (BP) in treated hypertensive patients with nocturnal hypertension. PATIENTS AND METHODS: Thirty-eight treated hypertensive patients (22 males, mean age 64+/-11 years) with confirmed nocturnal hypertension (mean nighttime systolic BP >125 mm Hg), according to repeated 24-hour ambulatory blood pressure monitoring (ABPM), were randomized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks. A 24-hour ABPM was then performed. RESULTS: Melatonin treatment reduced nocturnal systolic BP significantly from 136+/-9 to 130+/-10 mm Hg (P=.011), and diastolic BP from 72+/-11 to 69+/-9 mm Hg (P=.002), whereas placebo had no effect on nocturnal BP. The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo (P=.01), and was most prominent between 2:00 AM and 5:00 AM (P=.002). CONCLUSIONS: Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension. Thus, an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension.

Adult↗

Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy.

PURPOSE: Melatonin, which is produced by the pineal gland at night, is an endogenous sleep regulator. Both sleep disorders and impaired melatonin production are common among the elderly. We examined the excretion of the major melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged >or=55 years and its relation with the subsequent response to melatonin therapy. METHODS: We studied 517 insomnia patients, along with 29 age-matched and 30 younger healthy volunteers. Nocturnal urinary 6-sulfatoxymelatonin excretion was assessed between 10 pm and 10 am. Three hundred and ninety-six of the insomnia patients were treated for 2 weeks with placebo and for 3 weeks with 2 mg per night of controlled-release melatonin, of which 372 provided complete datasets. Clinical response, assessed with the Leeds Sleep Evaluation Questionnaire, was defined as an improvement of 10 mm or more on the visual analog scales. RESULTS: Mean (+/- SD) 6-sulfatoxymelatonin excretion was lower in the insomnia patients (9.0 +/- 8.3 microg per night) than in volunteers of the same age (18.1 +/- 12.7 microg per night, P <0.05) and in younger volunteers (24.2 +/- 11.9 microg per night, P <0.05). About 30% of patients (112/372) excreted <or=3.5 microg of sulfatoxymelatonin per night, which is considered to be lower than normal for this age group. These "low excretors" had a significantly higher response to melatonin replacement therapy (58% [65/112] vs. 47% [122/260], P <0.05). CONCLUSION: Low nocturnal melatonin production is associated with insomnia in patients aged 55 years or older, and identifies patients who are somewhat more likely to respond to melatonin replacement.

Aged↗

Cross-cultural validation of the Leeds sleep evaluation questionnaire (LSEQ) in insomnia patients.

The Leeds sleep evaluation questionnaire (LSEQ) is a standardized self-reporting instrument comprising ten 100 mm visual analogue scales that pertain to the ease of getting to sleep (GTS), quality of sleep (QOS), ease of awakening from sleep (AFS) and alertness and behaviour following wakefulness (BFW). Although the LSEQ has been used in a variety of populations, published psychometric data on insomnia patients are limited. The LSEQ reliability and construct validity was evaluated in 396 French insomnia patients aged 55 years and over, who were treated with placebo (2 weeks) and melatonin (3 weeks). The results supported LSEQ internal consistency, reliability and construct validity with minor differences from those of the original English version. Then the internal consistency of the LSEQ was evaluated in 257 insomnia patients (age 20-80 years) in France and Israel who, following a 1 week placebo baseline, were randomized to placebo or melatonin treatment for 3 weeks. Cronbach's alpha and Pearson's r correlation coefficients for placebo and drug treatment conditions (p<0.001 for all) supported LSEQ internal consistency in different treatment and age groups and in different languages. It is concluded that the consistency, reliability and validity of the four LSEQ domains allows them to be singled out as independent outcome variables in cross cultural sleep research and clinical practice in adult and elderly patients with insomnia.

Aged↗

Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour.

This study aimed to explore the effects of melatonin on sleep, waking up and well being in subjects with varying degrees of seasonal or weather-associated changes in mood and behaviour. Fifty-eight healthy adults exhibiting subsyndromal seasonal affective disorder (s-SAD) and/or the negative or positive type of weather-associated syndrome (WAS) were randomised to either 2 mg of sustained-release melatonin or placebo tablets 1-2 h before a desired bedtime for 3 weeks. Outcome measures were changes from baseline in sleep quality, sleepiness after waking, atypical depressive symptoms and health-related quality of life by week three. Early morning salivary melatonin concentrations were measured at baseline and treatment cessation in all subjects. Melatonin administration significantly improved the quality of sleep (P=0.03) and vitality (P=0.02) in the subjects with s-SAD, but attenuated the improvement of atypical symptoms and physical parameters of quality of life compared to placebo in the subjects with WAS, positive type.

Adult↗

Impaired nocturnal melatonin secretion in non-dipper hypertensive patients.

BACKGROUND: Melatonin plays a role in the biologic regulation of circadian rhythms, including sleep. Melatonin has also been shown to modulate vascular smooth muscle tone and to induce hemodynamic effects in humans. OBJECTIVE: To evaluate whether melatonin plays a role in the circadian rhythm of blood pressure in hypertensive patients. METHODS: Sixteen elderly patients with essential hypertension were evaluated. Patients were defined as either dippers (DIP, n = 8) or non-dippers (NDIP, n = 8) according to the nocturnal change in the mean arterial pressure (MAP). 6-Sulfatoxymelatonin (6-SMT), the main melatonin metabolite, was determined by enzyme-linked immunosorbent assay (ELISA) in two separate urine collections, one in the daytime and one during the night. RESULTS: Both groups of DIP and NDIP hypertensives were comparable in regard to age and sex. During the night, the mean arterial pressure decreased by 10.3 +/- 2.2% in the DIP and increased by 7.5 +/- 1.7% in the NDIP group (p < 0.01). Daily 6-SMT was comparable in DIP (3.28 +/- 0.87 microg/12 h) and NDIP (2.31 +/- 0.68 microg/12 h) (p = 0.39). However, while the DIP presented the physiological nocturnal increase in urinary 6-SMT (mean 8.19 +/- 1.68 microg/ 12 h), this surge of melatonin production was missing in NDIP in whom nocturnal urinary 6-SMT concentrations were not significantly different from daily levels (mean 2.56 +/- 0.79 microg/12 h). The nocturnal change in urinary 6-SMT excretion was positively correlated to the nocturnal change in MAP (R = 0.54; p = 0.031). CONCLUSIONS: NDIP hypertensive patients differ from DIP hypertensives by having an impaired nocturnal melatonin secretion. Thus, melatonin may play a role in the circadian rhythm of blood pressure in hypertensive patients.

Aged↗

Melatonin rhythms in stroke patients.

Very little is known regarding melatonin's circadian rhythm in stroke patients. We compared urinary-sulfatoxymelatonin (6-SMT), its major metabolite, in 11 extensive cortical and seven deep or lacunar stroke patients on day 3 or 4 and day 10 post-stroke. Urinary 6-SMT and creatinine measured every 4 h for 24 h starting at 06:00 h significantly fluctuated during the day in both types of stroke and did not differ between day 3 or 4 and day 10 post-stroke. However, in extensive cortical lesions, a delay in the 6-SMT excretion was observed in the first post-stroke days compared to day 10. We conclude that circadian oscillator is preserved in extensive cortical as well as in deep and lacunar strokes. Extensive cortical stroke might delay the melatonin surge during the first post-stroke days.

Age Factors↗

Melatonin production in infants.

This study investigated the relationships of the excretion of the melatonin metabolite, 6-sulfatoxymelatonin, to prenatal, natal, and postnatal variables and its possible relation to psychomotor development. nocturnal urinary excretion of 6-sulfatoxymelatonin was studied over a 13-hour period in 355 term infants at 8 weeks of age (n = 320) and 16 weeks of age (n = 96). data on a variety of perinatal factors including pregnancy course, delivery, early postnatal course, birth weight, medical problems, growth (length, weight, and head circumference), and psychomotor development were collected at 1, 3, 6, 9, 12, and 18 months. the relationship between nocturnal 6-sulfatoxymelatonin excretion at 8 and 16 weeks of age and these factors was investigated and analyzed. 6-sulfatoxymelatonin levels at 16 weeks of age were significantly lower in infants with abnormal vs normal development at 3 months of age (7.27 + 1.44 vs 7.97 + 1.06, p = 0.05) as well as at 6 months of age (7.15 + 1.29 vs 7.95 + 1.10, p = 0.04). no other significant relation was evident among growth, perinatal complications, medical problems, and 6-sulfatoxymelatonin excretion at 8 weeks of age and at 16 weeks of age. low melatonin excretion in the first weeks of life correlates with delayed psychomotor achievements at 3 and 6 months of age. this association suggests a causal or predictive link between melatonin and neurodevelopment in infants.

Analysis of Variance↗

Massage therapy by mothers enhances the adjustment of circadian rhythms to the nocturnal period in full-term infants.

The objective of this study was to investigate the effect of massage therapy on phase adjustment of rest-activity and melatonin secretion rhythms to the nocturnal period in full-term infants. Rest-activity cycles of infants (measurement 1, n = 16) were measured by actigraphy before and after 14 days of massage therapy (starting at age 10 [+/-4] d) and subsequently at 6 and 8 weeks of age. 6-Sulphatoxymelatonin excretion was assessed in urine samples at 6, 8, and 12 weeks of age (measurement 2, n = 21). At 8 weeks the controls revealed one peak of activity at approximately 12 midnight (11 p.m.-3 a.m.) and another one at approximately 12 noon (11 a.m.-3 p.m.), whereas in the treated group, a major peak was early in the morning (3 a.m.-7 a.m.) and a secondary peak in the late afternoon (3 p.m.-7 p.m.). At 12 weeks, nocturnal 6-sulphatoxymelatonin excretions were significantly higher in the treated infants (1346.38 +/- 209.40 microg/night vs 823.25 +/- 121.25 microg/night, respectively; <.05). It is concluded that massage therapy by mothers in the perinatal period serves as a strong time cue, enhancing coordination of the developing circadian system with environmental cues.

Adaptation, Physiological↗

Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system.

OBJECTIVES: The preliminary applications of the psychoneuroimmunological knowledges to the treatment of human diseases have confirmed the possibility to amplify IL-2-dependent anticancer immunity by the pineal hormone melatonin (MLT) or by opioid antagonist, such as naltrexone (NTX), which act by activating TH1 lymphocytes or suppressing TH2 lymphocytes, respectively. At present, however, there are no data about the immunobiological effects of a concomitant administration of both MLT and NTX on IL-2-induced anticancer immunity. This preliminary study was carried out to evaluate whether the association of NTX may further enhance the lymphocytosis induced by the neuroimmunotherapy with IL-2 plus MLT. MATERIALS & METHODS: The study included 14 consecutive untreatable metastatic solid tumor patients. According to a cross-over randomized study, the patients were treated during two consecutive immunotherapeutic cycles at 21-day intervals with IL-2 plus MLT alone or with IL-2 plus MLT plus NTX. IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, MLT was given orally at 20 mg /day in the evening every day, and NTX was given orally at 100 mg in the morning every next day. For the immune evaluation, venous blood samples were drawn before the onset of treatment and at weekly intervals. RESULTS: Lymphocyte mean number significantly increased after both IL-2 plus MLT and IL-2 plus MLT plus NTX. However, the concomitant administration of NTX induced a significantly higher increase in lymphocyte mean number with respect to that achieved with IL-2 plus MLT alone. In contrast, the increase in eosinophil mean number was significantly higher on IL-2 plus MLT alone. CONCLUSIONS: This preliminary study shows that the association of NTX further amplifies the lymphocytosis obtained by IL-2 plus MLT. Since the lymphocytosis represents the most important favourable prognostic variable predicting the anticancer efficacy of IL-2 immunotherapy, it is probable that a cancer neuroimmunotherapy with IL-2 plus both MLT and NTX to activate TH1 and suppress TH2 cells respectively, may deserve more promising results in the treatment of human neoplasms according to the psychoneuroimnunological knowledge.

Adjuvants, Immunologic↗