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Biomedical subjects

N Zisapel

Publications and source records attributed to N Zisapel.

107 records · Page 6Linked to original sources
PubMed1975

Nuclear-magnetic-resonance studies of carboxypeptidase B. Binding of inhibitors to the manganese enzyme.

Longitudinal and transverse proton relaxation rates of water in solutions of porcine manganese carboxypeptidase B have been measured in the presence of various competitive inhibitors by pulse nuclear magnetic resonance (NMR) spectrometry. The inhibition constant of Mn-carboxypeptidase activity by L-argininic acid and acetyl-L-arginine was in agreement with the equilibrium constant obtained by the NMR method, indicating similar and specific binding of the inhibitors to the active site of the manganese enzyme. Titration of the water boound to the metal ion revealed the presence of one water molecular which could be displaced from the sphere of the managenese ion by various inhibitors. The structural features of the inhibitors required for this displacement as well as the mode of interaction is described.

Animals↗
PubMed1975

On the interaction of esters and peptides with carboxypeptidase B.

The specificity of porcine carboxypeptidase B towards basic and non-basic substrates was studied by employing several esters of phenyllactate. The structure of these depsipeptides complement exactly those of the corresponding phenylalanyl oligopeptide substrates. These non-basic ester-peptide pairs as well as the basic ester-peptide pair of arginyl derivatives, permits the direct comparison of the pH dependencies of the kinetic constants for the hydrolysis of those substrates by carboxypeptidase B. The data is interpreted in terms of three specific ionizing groups located at the active site of the enzyme. The mode and extent of inhibition of the hydrolysis of a specific substrate by another substrate was characterized kinetically. These results are discussed in relation to a proposed model for esterolytic and proteolytic action of carboxypeptidase B.

Animals↗
PubMed1973

The role of a tyrosyl residue in the mechanism of action of carboxypeptidase B: luminescence studies.

The luminescence spectra of carboxypeptidase B indicate specific differences between the zinc and apoenzyme due to the state of tyrosyl residues presumably at the active site. These differences disappear when enzyme-substrate or enzyme-inhibitor complexes are formed, suggesting that they may reflect the interaction of a tyrosyl residue in the native enzyme with the catalytically essential zinc atom. An interpretation of the role of that tyrosyl residue in the mechanism of action of carboxypeptidase B is presented.

Animals↗
PubMedDate not supplied

Improvement of sleep quality by controlled-release melatonin in benzodiazepine-treated elderly insomniacs.

Benzodiazepines are widely used in the elderly population for the initiation of sleep. However, very frequently, complaints about poor sleep maintenance persist despite benzodiazepine treatment. Melatonin, a hormone produced by the pineal gland at night, is involved in the regulation of the sleep/wake cycle. Melatonin production decreases with age and can also be inhibited by benzodiazepines. We have recently reported on the association between insomnia and impaired melatonin output in the elderly. In the present study we have investigated the efficacy of melatonin replacement therapy in improving sleep in 21 elderly subjects who have been taking benzodiazepines and had low melatonin output. In a randomized, double-blind, crossover designed study the subjects were treated for three weeks with 2 mg per night of controlled-release melatonin and for 3 weeks with placebo, 2 h before desired bedtime with a 1-week washout period between treatment periods. Subjects' sleep was assessed by wrist actigraphy. Melatonin treatment significantly increased sleep efficiency and total sleep time and decreased wake after sleep onset, sleep latency, number of awakenings and fragmental index, as compared to placebo. The results of our study indicate that melatonin replacement therapy can improve sleep quality in the elderly and that the beneficial effects are augmented in the presence of benzodiazepines.

Clinical Trial↗
PubMedDate not supplied

Seasonal thermogenic acclimation of diurnally and nocturnally active desert spiny mice.

Diurnally active golden spiny mice (Acomys russatus) and nocturnal common spiny mice (Acomys cahirinus) coexist in hot rocky deserts of Israel. Diurnal and nocturnal activities expose these species to different climatic conditions. Nonshivering thermogenesis (NST) capacity of individuals of both species immediately upon removal from the field exhibited seasonal changes, with no significant interspecific difference. Colony-reared mice of either species transferred in the laboratory from long to short photoperiod increased NST capacity, though to a lesser extent than observed in the seasonal acclimatization. The underlying biochemical mechanisms of short photoperiod acclimation differed between the species. In both Cytochrome-c oxidase (Cox) activity was higher in short as compared to long photoperiod. In short-photoperiod-acclimated A. cahirinus uncoupling protein (UCP) content in brown adipose tissue (BAT) was significantly higher than in long photoperiod, while in A. russatus there was no significant change. In A. russatus there was a significant increase in lipoprotein lipase (LPL) activity in BAT in short-photoperiod-acclimated individuals, while in A. cahirinus LPL activity was high under both acclimations. The low LPL activity in brown adipose tissue of desert-adapted A. russatus may facilitate lipid uptake in white adipose tissue, an advantage in desert conditions where food is scarce and irregularly distributed in space and time.

Acclimatization↗
PubMedDate not supplied

Prospects of the clinical utilization of melatonin.

This review summarizes the present knowledge on melatonin in several areas on physiology and discusses various prospects of its clinical utilization. Ever increasing evidence indicates that melatonin has an immuno-hematopoietic role. In animal studies, melatonin provided protection against gram-negative septic shock, prevented stress-induced immunodepression, and restored immune function after a hemorrhagic shock. In human studies, melatonin amplified the antitumoral activity of interleukin-2. Melatonin has been proven as a powerful cytostatic drug in vitro as well as in vivo. In the human clinical field, melatonin appears to be a promising agent either as a diagnostic or prognostic marker of neoplastic diseases or as a compound used either alone or in combination with the standard cancer treatment. Utilization of melatonin for treatment of rhythm disorders, such as those manifested in jet lag, shift work or blindness, is one of the oldest and the most successful clinical application of this chemical. Low doses of melatonin applied in controlled-release preparation were very effective in improving the sleep latency, increasing the sleep efficiency and rising sleep quality scores in elderly, melatonin-deficient insomniacs. In the cardiovascular system, melatonin seems to regulate the tone of cerebral arteries; melatonin receptors in vascular beds appear to participate in the regulation of body temperature. Heat loss may be the principal mechanism in the initiation of sleepiness caused by melatonin. The role of melatonin in the development of migraine headaches is at present uncertain but more research could result in new ways of treatment. Melatonin is the major messenger of light-dependent periodicity, implicated in the seasonal reproduction of animals and pubertal development in humans. Multiple receptor sites detected in brain and gonadal tissues of birds and mammals of both sexes indicate that melatonin exerts a direct effect on the vertebrate reproductive organs. In a clinical study, melatonin has been used successfully as an effective female contraceptive with little side effects. Melatonin is one of the most powerful scavengers of free radicals. Because it easily penetrates the blood-brain barrier, this antioxidant may, in the future, be used for the treatment of Alzheimer's and Parkinson's diseases, stroke, nitric oxide, neurotoxicity and hyperbaric oxygen exposure. In the digestive tract, melatonin reduced the incidence and severity of gastric ulcers and prevented severe symptoms of colitis, such as mucosal lesions and diarrhea.

Adjuvants, Immunologic↗
PubMedDate not supplied

The use of melatonin for the treatment of insomnia.

The pineal product melatonin is involved in the regulation of the sleep/wake cycle in humans. In blind individuals and in people travelling through time zones, melatonin rhythms are sometimes unsynchronized with the diel cycle, and nocturnal sleep may be disturbed. Low or distorted melatonin rhythms have repeatedly been reported in middle aged and elderly insomniacs. Melatonin administration effectively synchronized the sleep wake cycle in blind individuals and in subjects suffering from jet lag and advanced sleep onset in subjects suffering from delayed sleep phase syndrome. In elderly insomniacs, melatonin replacement therapy significantly decreased sleep latency, and/or increased sleep efficiency and decreased wake time after sleep onset. In addition, melatonin substitution facilitated benzodiazepine discontinuation in chronic users. These data show an association between melatonin rhythm disturbances and difficulties to promote or maintain sleep at night. Specific melatonin formulations may be useful to treat circadian-rhythm-related sleep disorders and age-related insomnia.

Aged↗
PubMedDate not supplied

Concurrent inactivation of calcium dependent phosphorylation and neurotransmitter release in cultured rat brain neurons.

Depolarization of cultured rat brain neurons preloaded with 3H-dopamine provokes a transient (t 1/2 = 9.6 sec), Ca(2+)-dependent release of the labeled neurotransmitter from cells. In parallel, the amount of 32Pi incorporated into a protein of apparent molecular weight of 43,000 increased whereas the phosphorylation of a protein with an apparent molecular weight of 55,000 daltons decreased. The time course of the change in phosphorylation pattern was examined. The depolarization-induced phosphorylation of the 45,000 protein and dephosphorylation of the 55,000 dalton protein consisted of an initial, rapidly terminating phase (t 1/2 = 5 sec), and of a slow, Ca(2+)-independent phosphorylation of both proteins which persisted during maintained depolarization. The depolarization-evoked changes in the neuronal protein phosphorylation were dependent on the extracellular Ca2+ concentration (half saturation at 0.4-0.5 mM Ca2+). These data indicate that the entry of Ca2+ into the depolarized cells induces rapid phosphorylation-dephosphorylation activities. These processes terminate within 10 sec, concurrently with the depression of neurotransmitter release.

Animals↗
PubMedDate not supplied

Pinealectomy but not melatonin supplementation affects the diurnal variations in 125I-melatonin binding sites in the rat brain.

The distribution of melatonin binding sites in synaptosomal preparations from five brain areas of sham-operated and pinealectomized young male rats (maintained in a 14 h light: 10 h darkness cycle; lights on at 5.00 h) was recorded at 10.00, 18.00 and 24.00 h, 18 days after surgery, using 125I-melatonin as a probe. The densities of 125I-melatonin binding sites in the medulla-pons, hippocampus and hypothalamus of the pinealectomized rats, exhibited clear diurnal variations. However, the densities of binding sites in these brain areas at 18.00 h were lower in the pinealectomized animals than at the other times of day tested, whereas in the sham-operated controls, the binding at 18.00 h was higher than at the other times of day. No diurnal variations were evident in the midbrain and cerebellum of the pinealectomized animals. The apparent affinities of the binding sites toward the ligand in the various brain areas were similar in the pinealectomized and sham-operated animals and did not significantly vary at any of the times recorded. Oral supplementation of melatonin to the rats via drinking water had no effect on the diurnal variations in 125I-melatonin binding in the pinealectomized rat brain. The results indicate that the diurnal variations in 125I-melatonin binding sites in the rat brain are not generated by the pineal but are affected by removal of the gland.

Animals↗