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Journal Article 2002; 23(Suppl 1): 20-23 PubMed PMID: 12019347 Citation  Keywords:  Aged, Alzheimer Disease:complications, Antioxidants:therapeutic use, Circadian Rhythm:drug effects, Clinical Trials as Topic, Humans, Melatonin:therapeutic use, Sleep Wake Disorders:drug therapy,.   

: About 45% of Alzheimer's disease (AD) patients have disruptions in their sleep and sundowning agitation. Since melatonin secretion is greatly inhibited in AD patients we have used melatonin to treat sleep disorders in AD patients since 1995. In a first study [21] we reported, in 7 out of 10 dementia patients treated with melatonin (3 mg p.o. at bed time), a decreased sundowning. In a second study [22] we examined 14 AD patients who received 9 mg melatonin daily for 22 to 35 months, observing a significant improvement of sleep quality with stabilization of behavioral and cognitive parameters. In a third study [23] we reported two monozygotic twins with AD and similar cognitive impairment, one of them receiving 6 mg melatonin at bedtime daily for 3 years. Melatonin treatment improved sleep quality and suppressed sundowning. We now report the effect of melatonin (4-month-long treatment with 6 mg/day) in 45 AD patients with sleep disturbances. Melatonin improved sleep and suppressed sundowning, an effect seen regardless of the concomitant medication employed to treat cognitive or behavioral signs of AD. Melatonin treatment seems to constitute a selection therapy to ameliorate sundowning and to slow evolution of cognitive impairment in AD patients....

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Clinical Trial 2002; 23(Suppl 1): 17-19 PubMed PMID: 12019346 Citation  Keywords:  Aged, Aged, 80 and over, Antioxidants:pharmacology, Blood Cell Count, Dehydroepiandrosterone Sulfate:blood, Estradiol:blood, Female, Humans, Hydrocortisone:blood, Melatonin:pharmacology, Pilot Projects, Sleep:drug effects, Sleep Wake Disorders:drug therap.   

OBJECTIVES: The role of melatonin is aging is still under debate. Therefore, an open pilot study on the effects of melatonin administration on some sleep parameters, routine hematological and biochemical parameters, and concentrations of hormones was performed in elderly women.

SUBJECTS AND METHODS: The study was performed on 14 women (volunteers), aged from 64 to 80 years (mean age 71+/-4.6 years). Melatonin (2 mg daily at 19:00 h) was administered during 6 months. Before and after melatonin treatment the peripheral venous blood samples were taken in the morning (approx. at 08:00 h) after the overnight fast. The total blood count, glucose, total cholesterol, LDL, HDL, and triglycerides were estimated by routine laboratory methods. The serum concentrations of the following hormones were determined: 17-beta-estradiol, dehydroepiandrosterone sulfate (DHEAS), cortisol, and somatomedin C (IGF-I). Additionally, before and after 6 months of melatonin therapy the investigated subjects answered to a questionnaire dealing with sleep parameters and self-estimation of general health status.

RESULTS: In 35.7% of investigated subjects an improvement in general sleep quality and in such sleep parameters as sleep initiation, sleep latency, number of awakenings episodes, wake time after sleep onset, was observed. A significant decrease of estradiol concentrations was observed after 6 months of the melatonin treatment in comparison to initial levels. IGF-I was found to be slightly but significantly increased after the 6 months melatonin therapy. Cortisol levels did not change significantly, during the melatonin treatment. DHEAS concentrations increased after melatonin therapy. Moreover, a tendency towards a higher DHEAS/cortisol ratio was found after 6 months of treatment. Melatonin treatment did not influence significantly either the parameters of total blood count or glucose and serum lipids levels.

CONCLUSIONS: On the basis of this preliminary open study it seems that melatonin administration may be beneficial for elderly subjects....

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Journal Article 2002; 23(Suppl 1): 14-16 PubMed PMID: 12019345 Citation  Keywords:  Aging:physiology, Animals, Circadian Rhythm:physiology, Humans, Melatonin:physiology, Pineal Gland:physiology,.   

: Although many theories relating the pineal secretory product melatonin to aging have been put forward, the role of this agent in the aging process is not clear. However, there are several reasons to postulate a role for melatonin in this process. Melatonin levels fall gradually over the life-span. Melatonin is a potent free radical scavenger. Melatonin deficiency is related to suppressed immunocompetence. In at least one animal model melatonin supplementation increased life-span although several other studies have failed. The aging process is multifactorial, and no single element seems to be of basic importance. It seems, however, that although melatonin can not be univocally recognized as a substance delaying aging, some of its actions may be beneficial for the process of aging. However, the precise role of melatonin in the aging process remains to be determined....

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Journal Article 2002; 23(Suppl 1): 9-13 PubMed PMID: 12019344 Citation  Keywords:  Aged, Animals, Humans, Jet Lag Syndrome:drug therapy, Melatonin:pharmacology, Sleep:drug effects, Sleep Initiation and Maintenance Disorders:drug therapy,.   

: In elderly insomniacs, melatonin treatment decreased sleep latency and increased sleep efficiency. This is particularly marked in Alzheimer's disease (AD) patients. Melatonin is effective to reduce significantly benzodiazepine use. In addition, melatonin administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from delayed sleep phase syndrome or jet lag. Urinary levels of 6-sulphatoxymelatonin decrease with age and in chronic diseases like AD or coronary heart disease. The effect of melatonin on sleep is probably the consequence of increasing sleep propensity (by inducing a fall in body temperature) and of a synchronizing effect on the circadian clock (chronobiotic effect)....

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Journal Article 2002; 23(Suppl 1): 3-8 PubMed PMID: 12019343 Citation  Keywords:  Animals, Antioxidants:pharmacology, Free Radical Scavengers:pharmacology, Free Radicals:adverse effects, Humans, Melatonin:pharmacology,.   

: Endogenously produced metabolites of ground state oxygen are highly reactive and destructive to intracellular and extracellular molecules. The resulting damage, referred to as oxidative stress, leads to molecular and cellular dysfunction. The destruction of essential macromolecules by oxygen-based reactants is the basis of some diseases and is believed to be involved in the processes of aging. Free radical scavengers and antioxidants neutralize and/or metabolically remove reactive species from cells before they carry out their destructive activities. Melatonin is a highly ubiquitous direct free radical scavenger and indirect antioxidant. This brief report summarizes the interactions of melatonin with reactive species and identifies the resulting products. The paper also defines the melatonin antioxidant cascade wherein not only melatonin but at least one of the products, i.e., N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, formed as a result of melatonin scavenging hydrogen peroxide is also a potent scavenger. The review summarizes the data which shows that melatonin is not only a pharmacologically useful free radical scavenger but that it functions in this capacity at physiological concentrations as well. Finally, this report identifies high oxidative stress situations in humans where melatonin has proven effective in reducing the severity of the disease state. In the last decade there have been hundreds of publications documenting melatonin's protective actions against a vast array of conditions, e.g., ischemia/reperfusion injury, toxin exposure, lipopolysaccharide exposure, etc., where free radical damage is a component of the condition....

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Journal Article 2002; 23(2): 170-187 PubMed PMID: 12011804 Citation  Keywords:  Authorship, Humans, Neuroendocrinology:trends, Neuroimmunomodulation, Periodicals as Topic:trends,.   

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Journal Article 2002; 23(2): 155-160 PubMed PMID: 12011802 Citation  Keywords:  Aged, Aged, 80 and over, Alzheimer Disease:blood, Estradiol:blood, Estrone:blood, Female, Folic Acid:blood, Humans, Logistic Models, Mental Status Schedule, Testosterone:blood,.   

OBJECTIVES: In vitro and in vivo animal studies suggest that sex steroids, such as estrogens and testosterone, could protect the brain. However, estrogen replacement therapy (ERT) for Alzheimer's disease (AD) in women has not been successful. We hypothesised that the lack of effect of ERT might be related to an interaction between estrogens and some other factor(s) associated with AD.

DESIGN, SETTING AND METHODS: We analysed total estrogen (TE) and testosterone (TT) levels in women diagnosed with AD and controls of the Oxford Project To Investigate Memory and Ageing. Because estradiol (TE2) after the menopause is largely derived from estrone (TE1), we computed the ratio TE2/(TE1+TE2) and a total steroid index (TT+TE2+TE1).

RESULTS: Women with AD (n=66) had significantly higher levels of TE2 (27+/-13 vs. 21+/-13) and a higher TE2/(TE1+TE2) ratio. Stepwise logistic regression analyses showed that the TE2/(TE1+TE2) ratio was the main sex steroid predictor for AD (O.R.=1.06, 95% C.I.=1.01-1.11, p<0.01). Multiple regression analyses revealed that dementia severity was associated with an interaction between the TE2/(TE1+TE2) ratio and serum folate (B=4.59 (SE=1.48), beta=1.22, 95% C.I.=1.62-7.56, p<0.005). None of the other potential mediators of this association (body mass index, sex hormone binding globulin, homocysteine levels, ApoE genotype, smoking, diabetes, blood pressure) was significant.

MAIN FINDINGS: A high ratio of estradiol to total estrogens is associated with AD but, in subjects with a high ratio, the dementia severity was lower in those with high serum folate levels.

CONCLUSIONS: If this association is causal, then supplementation with folic acid might be considered in future studies on ERT in AD....

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Journal Article 2002; 23(2): 133-140 PubMed PMID: 12011799 Citation  Keywords:  Biomarkers, Bites and Stings:complications, Child, Creatine Kinase:blood, Creatine Kinase, MB Form, Female, Heart Diseases:etiology, Humans, Interleukin-8:blood, Isoenzymes:blood, L-Lactate Dehydrogenase:blood, Male, Myocardium:metabolism, Scorpion Venoms.   

OBJECTIVES: (1) To investigate the significance of assessment of serum levels of cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside other biomarkers of myocardial injury in scorpion envenomed children. (2) To find the correlation between these biochemical indices with clinical status, prognosis and outcome of these cases.

METHODS: Forty-one children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with fifteen apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination, full blood count and arterial blood gases analysis. According to severity of scorpion envenomation, 17 children had manifestations of severe envenomation and clinical signs of toxic myocarditis (severe cases), 14 children had moderate manifestations of envenomation without clinical evidence of carditis (moderate cases) and 10 cases showing only mild symptoms of envenomation (mild cases). The serum levels of cTnI and IL-8 beside the enzymatic activities of creatine phosphokinase (CPK), CPK-MB isoenzyme (CPK-MB) and lactate dehydrogenase (LDH) were determined once for mild cases and controls on admission and twice for severe and moderate cases on admission and after 24 hrs. The measurements of electrocardiography (ECG), echocardiographic measurement of % fractional shortening of left ventricule (%SF), left ventricular ejection fraction (LVEF) and cardiac chambers dilatation were done for severe and moderate cases.

RESULTS: All the envenomed victims showed significantly higher mean values of CPK, CPK-MB, LDH, and IL-8 on admission in comparison to control group. cTnI was not detectable in the sera of control group as well as patients with mild envenomation. The mean values of CPK, CPK-MB, LDH, and IL-8 were significantly higher in severe cases while only IL-8 and CPK-MB were significantly higher in moderate cases in comparison with mild cases. The mean values of IL-8, cTnI, CPK, CPK-MB and LDH were significantly higher in severe cases both on admission and on follow-up comparing with moderate cases. The case fatality rate was 12.5% and all were from severe cases with toxic myocarditis (5/41=12.5%). The non-survivors victims showed significant higher mean values of only cTnI on admission and both cTnI and IL-8 on follow up in comparison to the survivors. Significant reduction of % SF and LVEF were noticed among the non-survivors in comparison to survivors. The cTnI showed 100% specificity and sensitivity for diagnosis of myocardial injury in relation to Echo finding in the envenomed victims. In severe cases, cTnI was positively correlated with IL-8 while negatively correlated with %SF and LVEF.

CONCLUSION: it may be suggested that cTnI is the most specific marker for diagnosis of myocardial injury in scorpion envenomation, which is almost associated with skeletal muscle injury. Other biochemical markers did not show such specificity. Also, IL-8 may be involved in the pathogenesis of myocardial injury of scorpion envenomation. Both cTnI and IL-8 may be useful to forecast the fatal outcome in scorpion envenomation....

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