Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.

NPK in treated wastewater irrigation: Regional scale indices to minimize environmental pollution and optimize crop nutritional supply.

Treated wastewater (TWW) is increasingly used for agricultural irrigation, and often contains higher concentrations of the major plant nutrients N, P, and K than freshwater, reducing the need for agricultural fertilization. However, excessive inputs of nutrients to cropping systems can be harmful to crops and the environment. The present study developed and employed six novel indices to assess the sustainability of TWW-irrigation and spatio-temporal trends in NPK loads to TWW-irrigated fields. Three indices relate to regional analysis of TWW-irrigation sustainability: the 'Environmental sustainability' index measures the TWW compliance with environmental irrigation standards; a 'Nutritional sustainability' index assesses whether the TWW satisfy crop fertilization requirements; a 'Basin nutrient surplus' index measures deviations of N or P loads to river basins from allowed levels. Three additional indices assess the environmental impact, potential loss of nutrients and fit of a given TWW for fertilization recommendations. We employed these indices to analyze a decade-long high spatio-temporal resolution data of TWW quality from Israel on a basin scale, for six TWW-irrigated plantation crops. The results reveal that in high-sensitivity hydrological areas, TWW is generally above the environmental standard for N and P; the TWW with lowest nutrient content is irrigated in low-sensitivity areas, leading to a reduced potential for utilization of nutrients in TWW. While the N irrigation standard (25 mg L-1) does not exceed the nutritional requirements of most analyzed crops, the P standard (5 mg L-1) results in excess fertilization for all analyzed crops. Therefore, environmental and nutritional sustainability of TWW-irrigation can be increased by diverting high-quality TWW to high-sensitivity areas and vice versa. Furthermore, development of local environmental standards will allow maximizing TWW NPK utilization in low-sensitivity areas, increasing nutritional sustainability. The indices presented in this study provide a tool to help maximize the nutritional benefits of TWW while minimizing its environmental impact.

Reducing salinity of treated waste water with large scale desalination.

Agriculture, the largest global water consumer, accounts for ~70% of freshwater use thereby considerably influencing water availability. The use of treated wastewater [TWW] for agricultural irrigation has been suggested as a possible solution to help mitigate water scarcity without disrupting food production. However, despite the benefits of TWW irrigation, it is often characterized by high salinity that can reduce crop performance and damage soil structure. In Israel, over 50% of the water used for irrigation is TWW, and a third of the produced TWW undergoes soil aquifer treatment [SAT], i.e., infiltration and percolation to groundwater through the soil before utilization for irrigation. In parallel, seawater desalination provides about 80% of the urban and industrial sector water use. These developments in Israel's water economy during the last three decades, accompanied by extensive governmental monitoring, enabled us to harness high-resolution nation-wide datasets to study the effects of the large-scale introduction of desalination and SAT on TWW quality and salinity in particular. The analyses revealed that large-scale desalination considerably reduced the salinity of TWW to levels similar to freshwater (up to 70% and 60% for Cl and Na, respectively). However, sodium absorption ratio remained unchanged due to the concurrent reductions of Na, Ca and Mg. Mg was reduced to levels that can potentially harm both crops and human health, while B concentrations increased to levels of possible toxicity to crops, suggesting the need for stringent requirements in the post-treatment process. Salinity of groundwater was increased by SAT in the long-term, but was reduced after the introduction of desalination. The results, encompassing almost three decades of water monitoring, suggest that high-quality TWW with a significant portion of desalinated base-water can provide groundwater salinity remediation services.

Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in zebrafish.

Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic complex was [Cu(Valp)2Bipy], in which the LC50 was 0.22 µM at 48 h post fertilization (HPF) and 0.12 µM at 96 HPF, followed by [Zn(Valp)2Bipy] (LC50 = 10 µM). These same metallodrugs ([Cu(Valp)2Bipy] 10 mM/kg and [Zn(Valp)2Bipy] 30 mM and 100 mM/kg) displayed superior activity, thus reducing the seizure intensity by approximately 20 times compared to sodium valproate (175 mM/kg). Overall, [Cu(Valp)2Bipy] showed the best anticonvulsant effects. However, because of the toxicity of copper, [Zn(Valp)2Bipy] is considered the most promising anticonvulsant for future studies.

Evaluation of zinc effect on cadmium action in lipid peroxidation and metallothionein levels in the brain.

Cadmium (Cd) is a known hepato- and nephrotoxic pollutant and zinc (Zn) metalloproteins are important targets of Cd. Hence, the administration of Zn may mitigate Cd toxic effects. However, the interaction of Cd and Zn has been little investigated in the brain. Previously, we reported a protective effect of Zn on mortality caused by Cd in rats. Here, we tested whether the protective effect of Zn could be related to changes in brain Zn-proteins, metallothionein (MT) and δ-aminolevulinate dehydratse (δ-ALA-D). Male adult rats were daily administered for 10 days with Zn (2 mg kg-1), Cd (0.25 and 1 mg kg-1) and 0.25 mg kg-1 of Cd plus Zn and 1 mg kg-1 of Cd plus Zn. The body weight loss, food intake deprivation, and mortality occurred in 1 mg kg-1 of Cd, but Zn co-administration did mitigate these effects. The brain Zn content was not modified by treatment with Cd, whereas cerebral Cd levels increased in animals exposed to Cd. The administration of 0.25 mg kg-1 of Cd (with or without Zn) induced lipid peroxidation and decreased MT concentration, but 2 mg kg-1 of Zn and 1 mg kg-1 of Cd did not change these parameters. Brain δ-ALA-D was not modified by Cd and/or Zn treatments. Since the co-administration of Zn did not attenuate the changes induced by Cd in the brain, our results suggest that the protective effect of Zn on impairments caused by Cd in animal status is weakly related to a cerebral interaction of these metals.

Anxiolytic effects of diphenyl diselenide on adult zebrafish in a novelty paradigm.

Anxiety-related disorders are frequently observed in the population. Because the available pharmacotherapies for anxiety can cause side effects, new anxiolytic compounds have been screened using behavioral tasks. For example, diphenyl diselenide (PhSe)2, a simple organoselenium compound with neuroprotective effects, has demonstrated anxiolytic effects in rodents. However, this compound has not yet been tested in a novelty-based paradigm in non-mammalian animal models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on the behavior of adult zebrafish under novelty-induced stress. The animals were pretreated with 0.1, 0.25, 0.5, and 1µM (PhSe)2 in the aquarium water for 30min. The fish were then exposed to a novel tank, and their behavior was quantified during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration-dependent manner. At 0.01 and 0.25µM, (PhSe)2 did not elicit effects on fish behavior. At 0.5µM, moderate behavioral side effects (e.g., lethargy and short episodic immobility) were noted. At the highest concentration tested (1µM), dramatic side effects were observed, such as burst behavior and longer periods of immobility. The results were confirmed by spatiotemporal analysis of each group. Occupancy plot data showed dispersed homebase formation in the 0.25µM (PhSe)2-treated group compared with the control group (treated with 0.04% DMSO). Furthermore, animals treated with 0.25µM (PhSe)2 showed a reduction in latency to enter the top and spent more time in the upper area of the tank. These data suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of anxiety evoked by novelty.

Seizures induced by pentylenetetrazole in the adult zebrafish: a detailed behavioral characterization.

Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.

Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats.

Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different rat models. However, these studies are controversial and the majority has primarily analyzed activity parameters. Therefore, the aim of the present study was to evaluate locomotor and exploratory behavior in bile duct-ligated (BDL) rats to explore the spatial and temporal structure of behavior. Adult female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure and exhibited a decrease in total distance traveled, increased total immobility time, smaller number of rearings, longer periods in the home base area and decreased percentage of time in the center zone of the arena, when compared to the control rats. Moreover, the performance of the BDL rats was not different from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior.

Behavioral effects of taurine pretreatment in zebrafish acutely exposed to ethanol.

Taurine (TAU) is an amino sulfonic acid that plays protective roles against neurochemical impairments induced by ethanol (EtOH). Mounting evidence shows the applicability of zebrafish for evaluating locomotor parameters and anxiety-like behavioral phenotypes after EtOH exposure in a large scale manner. In this study, we assess the effects of TAU pretreatment on the behavior of zebrafish in the open tank after acute 1% EtOH (v/v) exposure (20 and 60 min of duration) and on brain alcohol contents. The exposure for 20 min exerted significant anxiolytic effects, which were prevented by 42, 150, and 400 mg/L TAU. Conversely, the 60-min condition induced depressant/sedative effects, in which the changes on vertical activity were associated to modifications on the exploratory profile. Although all TAU concentrations kept locomotor parameters at basal levels, 150 mg/L TAU, did not prevent the impairment on vertical activity of EtOH[60]. Despite the higher brain EtOH content detected in the 60-min exposure, 42, 150, and 400 mg/L TAU attenuated the increase of alcohol content in EtOH[60] group. In conclusion, our data suggest that both protocols of acute EtOH exposure induce significant changes in the spatio-temporal behavior of zebrafish and that TAU may exert a preventive role by antagonizing the effects induced by EtOH possibly due to its neuromodulatory role and also by decreasing brain EtOH levels. The hormetic dose-response of TAU on vertical exploration suggests a complex interaction between TAU and EtOH in the central nervous system.

Physical exercise reverses glutamate uptake and oxidative stress effects of chronic homocysteine administration in the rat.

The influence of physical exercise on the effects elicited by homocysteine on glutamate uptake and some parameters of oxidative stress, namely thiobarbituric acid-reactive substances, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, as well as enzymatic antioxidant activities, superoxide dismutase, catalase and glutathione peroxidase in rat cerebral cortex were investigated. Wistar rats received subcutaneous administration of homocysteine or saline (control) from the 6th to 29th day of life. The physical exercise was performed from the 30th to 60th day of life; 12 h after the last exercise session animals were sacrificed and the cerebral cortex was dissected out. It is shown that homocysteine reduces glutamate uptake increases thiobarbituric acid-reactive substances and disrupts enzymatic antioxidant defenses in cerebral cortex. Physical activity reversed the homocysteine effects on glutamate uptake and on antioxidant enzymes activities; although the increase in thiobarbituric acid-reactive substances was only partially reversed by exercise. These findings allow us to suggest that physical exercise may have a protective role against homocysteine-induced oxidative imbalance and brain damage to the glutamatergic system.

Differences in spatio-temporal behavior of zebrafish in the open tank paradigm after a short-period confinement into dark and bright environments.

The open tank paradigm, also known as novel tank diving test, is a protocol used to evaluate the zebrafish behavior. Several characteristics have been described for this species, including scototaxis, which is the natural preference for dark environments in detriment of bright ones. However, there is no evidence regarding the influence of "natural stimuli" in zebrafish subjected to novelty-based paradigms. In this report, we evaluated the spatio-temporal exploratory activity of the short-fin zebrafish phenotype in the open tank after a short-period confinement into dark/bright environments. A total of 44 animals were individually confined during a 10-min single session into one of three environments: black-painted, white-painted, and transparent cylinders (dark, bright, and transparent groups). Fish were further subjected to the novel tank test and their exploratory profile was recorded during a 15-min trial. The results demonstrated that zebrafish increased their vertical exploratory activity during the first 6-min, where the bright group spent more time and travelled a higher distance in the top area. Interestingly, all behavioral parameters measured for the dark group were similar to the transparent one. These data were confirmed by automated analysis of track and occupancy plots and also demonstrated that zebrafish display a classical homebase formation in the bottom area of the tank. A detailed spatio-temporal study of zebrafish exploratory behavior and the construction of representative ethograms showed that the experimental groups presented significant differences in the first 3-min vs. last 3-min of test. Although the main factors involved in these behavioral responses still remain ambiguous and require further investigation, the current report describes an alternative methodological approach for assessing the zebrafish behavior after a forced exposure to different environments. Additionally, the analysis of ethologically-relevant patterns across time could be a potential phenotyping tool to evaluate the zebrafish exploratory profile in the open tank task.

Homocysteine alters glutamate uptake and Na+,K+-ATPase activity and oxidative status in rats hippocampus: protection by vitamin C.

In the present study we investigate the effect of homocysteine on glutamate uptake, Na+,K+-ATPase, enzymatic antioxidant defenses, as well as reactive species levels in hippocampus of rats. The influence of vitamin C, a classic antioxidant, on the effects elicited by homocysteine was also tested. Results showed that chronic hyperhomocysteinemia decreased glutamate uptake and the activities of Na+,K+-ATPase, catalase and superoxide dismutase in hippocampus of rats. Reactive species levels were increased by chronic homocysteine administration. Concomitant administration of vitamin C significantly prevented these alterations caused by homocysteine. According to our results, it seems possible to suggest that the reduction in glutamate uptake and Na+,K+-ATPase activity may be mediated by oxidative stress, since vitamin C prevented these effects. We suggest that the administration of antioxidants should be considered as an adjuvant therapy to specific diet in homocystinuria.

Sodium and chloride exclusion and retention by non-grafted and grafted melon and Cucurbita plants.

The effects of grafting on Na and Cl(-) uptake and distribution in plant tissues were quantified in a greenhouse experiment using six combinations of melon (Cucumis melo L. cv. Arava) and pumpkin (Cucurbita maxima Duchesne×Cucurbita moschata Duchesne cv. TZ-148): non-grafted, self-grafted, melons grafted on pumpkins, and pumpkins grafted on melons. Total Na concentration in shoots of plants with pumpkin or melon rootstocks was <60 mmol kg(-1) and >400 mmol kg(-1), respectively, regardless of the scion. In contrast, shoot Cl(-) concentrations were quite similar among the different scion-rootstock combinations. Na concentrations in exudates from cut stems of plants with a pumpkin rootstock were very low (<0.18 mM), whereas those in the exudates of plants with melon rootstocks ranged from 4.7 mM to 6.2 mM, and were quite similar to the Na concentration in the irrigation water. Root Na concentrations averaged 11.7 times those in the shoots of plants with pumpkin rootstocks, while in plants with melon rootstocks, values were similar. Two mechanisms could explain the decrease in shoot Na concentrations in plants with pumpkin rootstocks: (i) Na exclusion by the pumpkin roots; and (ii) Na retention and accumulation within the pumpkin rootstock. Quantitative analysis indicated that the pumpkin roots excluded ∼74% of available Na, while there was nearly no Na exclusion by melon roots. Na retention by the pumpkin rootstocks decreased its amount in the shoot by an average 46.9% compared with uniform Na distribution throughout the plant. In contrast, no retention of Na could be found in plants grafted on melons.

Hyperhomocysteinemia reduces glutamate uptake in parietal cortex of rats.

In the present study we evaluated the effect of acute and chronic homocysteine administrations on glutamate uptake in parietal cortex of rats. The immunocontent of glial glutamate transporter (GLAST) and sodium-dependent glutamate/aspartate transporter (GLT-1) in the same cerebral structure was also investigated. For acute treatment, neonate or young rats received a single injection of homocysteine or saline (control) and were sacrificed 1, 8, 12 h, 7 or 30 days later. For chronic treatment, homocysteine was administered to rats twice a day at 8 h interval from their 6th to their 28th days old; controls and treated rats were sacrificed 12 h, 1, 7 or 30 days after the last injection. Results show that acute hyperhomocysteinemia caused a reduction on glutamate uptake in parietal cortex of neonate and young rats, and that 12h after homocysteine administration the glutamate uptake returned to normal levels in young rats, but not in neonate. Chronic hyperhomocysteinemia reduced glutamate uptake, and GLAST and GLT-1 immunocontent. According to our results, it seems reasonable to postulate that the reduction on glutamate uptake in cerebral cortex of rats caused by homocysteine may be mediated by the reduction of GLAST and GLT-1 immunocontent, leading to increased extracellular glutamate concentrations, promoting excitotoxicity.

Growth management of vetiver (Vetiveria zizanioides) under Mediterranean conditions.

In spite of the advantages of Vetiver grass in light of environmental aspects, this plant is not used in the Mediterranean region. The objectives of the present study were: (i) to elucidate growth parameters and establishment of Vetiver under Mediterranean conditions suitable for its various environmental applications; and (ii) to develop management practices for growing vetiver under Mediterranean conditions. In greenhouse experiments conducted under controlled conditions it was found that, in general, increasing the minimum/maximum temperatures to 21-29 degrees C significantly increased plant height. In the Mediterranean region, this range of air temperatures is obtained mainly during the summer, from June to September. For air temperatures up to 15-23 degrees C the effect of day length on plant height was insignificant, whereas in air temperature >15-23 degrees C, the plant heights under long day conditions were significantly higher than under short day. The number of sprouts per plant increased exponentially with increasing air temperature, and was not significantly affected by the day length at any air temperature range. In open fields, the heights of irrigated vetiver plants were significantly higher than those of rain-fed plants. It was concluded that, once they were established, vetiver plants could survive the dry summer of the Mediterranean region under rain-fed conditions, but they would be shorter than under irrigation. Cutting or burning of the plant foliage during the spring did not improve the survival of vetiver during the dry summer. In order to obtain fast growth of vetiver and to increase the possibility of its using the rainwater, the plants should be planted in the winter, during February and March. However, under this regime, the vetiver plant cannot be used as a soil stabilizer during the first winter, because the plant is still small. In contrast, under irrigation it is advantageous to plant vetiver at the beginning of the summer; the plant then has sufficient time to grow and develop before the beginning of the winter, so that its effect as a soil stabilizer in the following wet winter could be maximal. It was found that vetiver could grow in a wide range of substrates, such as: sandy soil, loamy sand, clay soil, crushed limestone, sandy clay loam, and tuff/peat mixture.

Soil microvariations as a source of variability in the wild: the case of secondary metabolism in Origanum dayi post.

The volatile components of Origanum dayi Post were analyzed in 10 wild populations grown in a limited area. ANOVA tests showed no significant differences among the compositions of plants that grew in different locations, which suggests that differences in composition are of genetic origin and do not spring from environmental variation. However, the use of new statistical methods (such as use of the correlation coefficient, r, as a parametric value) revealed that, despite their reduced range of variation, most of the 22 soil properties (SPs) measured correlated with the composition of the volatile components. This analysis also indicated that the main volatile components were modified in parallel in response to SP variations. It is concluded that variations in soil properties affected the composition of volatile components in O. dayi, and that the main influencing factors were soil microelement contents and texture. This study highlights the need for highly sensitive statistical tools to determine the actual influence of environmental factors in natural environments, especially when their range of variation is small.

Effect of divalent cations on the formation and stability of myosin subfragment 1-ADP-phosphate analog complexes.

Myosin belongs to the family of motor proteins. Its interaction with actin coupled with hydrolysis of ATP is the molecular basis of muscle contraction. The head segment of myosin, called subfragment 1 (S1), contains the distinct binding sites for ATP and actin and responsible for the ATPase activity. The rate-limiting step of the ATP hydrolysis is the dissociation of the S1-MgADP-Pi complex which is accelerated by actin. The substitution of Pi with phosphate analogs (PA), such as vanadate (Vi) or beryllium fluoride (BeF(x)), highly stabilizes the complex. We studied the role of the divalent cations in the ATPase activity and in the formation and decomposition of PA-containing stable complexes by substituting Mg2+ with Fe2+, Mn2+, Ni2+, Co2+, and Ca2+. These metal ions supported the actin activation of S1 ATPase and affected the obtained kinetic parameters, Km and V(max). The ATPase activity of S1 in the absence of actin increased with the increasing ionic radius of the metal (Me) ions. These ions also substituted for Mg2+ in the formation of the stable ternary S1-MeADP-PA complexes, which cannot be generated in the absence of divalent cations. Upon formation of stable ternary complexes, S1 reversibly loses its ability to catalyze the hydrolysis of ATP. The formation of the complexes can be followed by monitoring the disappearance of the ATPase activity. The rate of the complex formation depends on the divalent cation present and decreases in the order Mn > Fe > Ni > Co > Mg and Ca > Mn > Fe > Mg > Co in the Vi- and BeF(x)-containing complexes, respectively. The ATPase activity of S1 is recovered upon addition of actin, which causes the decomposition of the complex. The spontaneous decomposition of the complexes was studied in the presence of ethylenediaminetetraacetic acid (EDTA), which chelates the metal divalent cations released from the complex and prevents its reformation. The rate of decomposition was assessed by monitoring the recovery of the ATPase activity of S1 in the presence of EDTA. The rate of decomposition of the Vi- and BeF(x)-containing complexes follows the order Mn > Fe > Co > Mg > Ni and Ca >> Mn > Fe > Co > Mg, respectively. The rate of decomposition increases with the increasing ionic radius of the metal ions, similarly as observed in the case of ionic radius dependence of the ATPase activity. On the basis of this similarity, it is assumed that the decomposition of the complexes consists of two steps, the first step being the very slow release of PA followed by a rapid dissociation of MeADP from S1. The stability of the complexes has been calculated from the formation and decomposition rates. Except in the case of Mg, the stabilities of the BeF(x) complexes are higher than those containing Vi. The results indicate that the metal cations have a significant role in maintaining the proper structure of the transient state complex in the myosin-catalyzed ATP hydrolysis.

Male breast cancer in Israel: selected epidemiological aspects.

The 17-yr incidence of male breast cancer was analyzed from data of the Israel Cancer Registry for Jews and non-Jews, and for the Jewish subgroups of European/American-born and Asian/African-born. The 187 observed cases among Jewish males in Israel were compared with the 194 cases reported in the U.S. Third National Cancer Survey and with female breast cancer rates for the same period. Results show that the dependence of male breast cancer (MBC) on the female rate seems to exist in both countries. The disputed observation of a higher rate of MBC among Jews is supported by the higher rates of MBC in Israel than in the USA. Data on the laterality and histological features of MBC are presented. The series included eight cases among non-Jews (Arabs). The on going survey of the Israel Cancer Registry revealed four families in which both husband and wife had breast cancer and one family with breast cancer in both father and son.