Monozygotic twins with Alzheimer's disease of 8 years duration were studied. The onset of the disease differed by about 6 months between twins and was characterized by a primary impairment of memory function. Clinical evaluation at the time of diagnosis indicated a similar cognitive and neuroimaging alteration in both patients, as well as a similar neuropsychologic impairment. A possible genetic origin of the disease was suggested by a similar disease suffered by the mother. Patients were initially treated with vitamin E (800 I.U./day). Starting at approximately the same time (about 3 years ago), they received 50 mg/day thioridazine because of the behavioral and sleep disorder. One of the patients was treated with melatonin (6 mg orally) at bed time daily for 36 months. Evolution of the disease in the melatonin-treated patient indicated a milder impairment of memory function, with substantial improvement of sleep quality and reduction of sundowning. This led to discontinuance (after 3 months) of thioridazine treatment. Present clinical evaluation indicated a difference in functional stage of the disease between the twins (Functional Assessment Tool For Alzheimer's Disease, FAST), with a score of 5 in the twin who received melatonin and of 7b in the twin who did not receive it. Since experimental data on melatonin in animals indicated its antioxidant, antiapoptotic, and beta-amyloid-decreasing activity, the hypothesis that melatonin has a beneficial effect in Alzheimer's disease patients should be considered.

Heat production and isovolumetric pressure development (P) were measured simultaneously in the arterially perfused rat ventricle. The time course of the calorimetric signal that follows a contraction could be decomposed into four components of energy released. Three of these components (H1, H2, and H4) were pressure independent, only H3 correlated with either P or the pressure-time integral (PtI) (r > 0.78, n = 36, P < 0.01). The dimensionless slope of the regression of H3 on P was 0.24 (an index of muscle economy) and the absence of O2 (N2 replacement) decreased it to 0.178 suggesting that 26% of H3 is related to oxidative metabolism. H4 was the most affected by the lack of O2 in the perfusate. It decreased to 16% in the first beat under N2 without change in P or in H1, H2 or H3, and disappeared (1.6 +/- 1.0 mJ.g-1) in the fourth contraction under N2 (while P, H1, H2 and H3 remained over 64% of their control values). H4 was activated during the first 1-3 beats after a quiescent period and remained active for several seconds (even in the absence of subsequent stimulation) as if the basal metabolism had been increased to a new steady level. H1 and H2 were dependent on the extracellular Ca. The magnitudes of both H1 (1.8 +/- 0.2 mJ.g-1) and H2 (2.7 +/- 0.2 mJ.g-1) were similar to those reported for the fast and slow components of activation heat in skeletal muscle. If twin stimuli are applied (200 ms apart), additional energy is released (+3.0 +/- 0.3 mJ.g-1) that can be decomposed in two components similar to those identified as H2 and H3. The magnitude of H1, its absence in the twin contraction and its Ca dependency suggest an association with Ca-binding processes (mainly Troponin C). The presence of an H2 component during the twin contraction, its magnitude and Ca dependence gives support to a relationship between H2 and Ca removal processes.

In an open pilot study on the efficacy of melatonin in the treatment of sleep disorders, patients with sleep disturbances alone, patients with sleep disturbances and signs of depression and patients with sleep disorders and dementia received 3 mg melatonin p.o. for 21 days, at bed time. After 2–3 days of treatment, melatonin significantly augmented sleep quality and decreased the number of awakening episodes in patients with sleep disturbances associated or not with depression. Estimates of next-day alertness improved significantly only in patients with primary insomnia. Agitated behavior at night (sundowning) decreased significantly in dementia patients. In a second retrospective study, 14 Alzheimer’s disease (AD) patients received 9 mg melatonin daily for 22–35 months. A significant improvement of sleep quality was found, while there were no significant differences between initial and final neuropsychological evaluation (Functional Assessment Tool for AD, Mini-Mental). The results indicate that melatonin can be useful to treat sleep disturbances in elderly insomniacs and AD patients.

The consequences of an extrasystole (ES) on cardiac muscle’s energetics and Ca2+ homeostasis were investigated in the beating heart. The fraction of heat release related to pressure development (pressure dependent) and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricle. The heat release by a contraction showed two pressure-independent components (H1 and H2) of short evolution and a pressure-dependent component (H3). The additional heat released by ES was decomposed into one pressure-independent ([Formula: see text]) and one pressure-dependent ([Formula: see text]) component with time courses similar to those of control components H2 and H3. ES also induced the potentiation of pressure development (P) and heat release during the postextrasystolic (PES) beat. The slope of the linear relationship between pressure-dependent heat and pressure maintenance was similar in control, ES, and PES contractions (0.08 ± 0.01, 0.10 ± 0.02, and 0.08 ± 0.01 mJ ⋅ g−1 ⋅ mmHg−1 ⋅ s−1, respectively). The potentiation of H2 (heat component related with Ca2+ removal processes) in PES was equal to [Formula: see text] at 0.3, 0.5, 1, and 2 mM Ca2+, suggesting that the extra amount of Ca2+ mobilized during ES was recycled in PES. Pretreatment with 1 mM caffeine to deplete sarcoplasmic reticulum Ca2+ content inhibited both the mechanical and energetic potentiation of PES. However, the heat released and the pressure developed during ES were not changed by sarcoplasmic reticulum depletion. The results suggest that 1) the source of Ca2+ for ES would be entirely extracellular, 2) the Ca2+ entered during ES is accumulated in the sarcoplasmic reticulum, and 3) the Ca2+ stored by the sarcoplasmic reticulum during ES induces an increased contribution of this organelle during PES compared with the normal contraction.