Effects of dietary copper and molybdenum on copper status, cytokine production, and humoral immune response of calves

Twenty-four male Holstein calves were used to determine the effects of dietary Cu and Mo on performance, Cu status, and immune function of calves. Calves were fed a milk replacer that was deficient in Cu for 8 wk and then were randomly assigned after weaning to one of four treatments: 1) control (no supplemental Cu or Mo), 2) 10 mg of Cu (from CuSO4)/kg of dry matter (DM) (Cu diet), 3) 5 mg of Mo (from Na2MoO4)/kg of DM (Mo diet), or 4) 5 mg of Cu (from CuSO4) and 5 mg of Mo (from Na2MoO4)/kg of DM (Cu + Mo diet). The basal diet was a semipurified diet that contained approximately 1.1 mg of Cu and 1.1 mg of Mo/kg of DM. Calves fed the Cu and Mo diets gained weight more efficiently than those fed the control and Cu + Mo diets during the 112-d study. By d 84 of the study, calves fed the Cu diet had higher plasma Cu concentrations and plasma ceruloplasmin activities than did calves fed the other three diets and had higher liver Cu concentrations on d 136. Plasma and liver Cu concentrations did not differ among calves fed the control, Mo, and Cu + Mo diets. At d 112, activity of Cu-Zn superoxide dismutase was lower in calves fed the Mo diet than in calves fed the Cu diet. Serum total antibodies to porcine erythrocytes (primary response) were lower in calves fed the Mo diet than in calves fed the Cu diet at 7, 14, and 21 d postinoculation. Production of tumor necrosis factor and interleukin-1 by isolated peripheral blood monocytes was not significantly affected by treatment. Although no differences were apparent in plasma or liver Cu concentrations among calves fed the control, Mo, and Cu + Mo diets, calves fed the Mo diet had a more severe Cu deficiency based on depressed humoral immune response and superoxide dismutase activity.     

Effects of dietary molybdenum on the metabolism of copper and molybdenum in young cattle

On separate occasions young cattle were injected intrarumenally with 99Mo or 64Cu or intravenously with 64Cu. The metabolism of the isotopes were compared to evaluate metabolic changes associated with molybdenum-induced copper deficiency. Molybdenum-99 metabolism was the same in both controls and experimental subjects. Marked differences in plasma kinetics were observed following intrarumenal 64Cu injection, with experimental animals displaying earlier plasma appearance and maintaining higher plasma levels than did controls. Similarly, higher plasma levels, more rapid plasma reappearance and greater fecal excretion were observed following intravenous injection of 64Cu in the experimental animals than in controls. A mechanism involving abnormal ceruloplasmin synthesis associated with the molybdenum-copper interaction is proposed.     

Effects of supplemental shade on thermoregulatory response of calves to heat challenge in a hutch environment

Holstein (n = 12) and Guernsey (n = 6) calves, housed in hutches, were used to evaluate the complex relationships among external environment, housing microclimate, and thermal status of calves. The study was conducted during the summer; 9 calves were housed in hutches under supplemental shade, and 9 calves were maintained in hutches under direct sunlight. Environmental and calf temperatures were measured twice daily at 0700 and 1500 h, which included determinations of air temperature, inner and outer surface temperatures of the hutch, rectal and skin temperatures of the calf, and respiration rate. Outer and inner surface temperatures of the hutch were lower under supplemental shade. Hutch air temperature was highly correlated with inner surface temperature and therefore was lower in the shaded environment. During the p.m. period, when heat stress was highest, calves housed in a shaded hutch environment had lower skin temperatures and respiration rates than did unshaded calves. Body temperature and respiration rates increased less for calves in shade than for calves in sun. These data define the relationship between the calf and the environment. Supplemental shade diminished the severity of heat stress experienced by calves that were housed in hutches during the summer.     

Effects of monosodium glutamate on blood neutrophils phagocytic activity and phagocytic response in mice

Previous researches of our laboratories (1945, 1946, 1947) have shown that direct electrical stimulation of the tubero-mammillary hypothalamic area in dogs enhances the blood neutrophils phagocytic activity and the phagocytosis exhibiting leukocytes percent. After electrolytic damage of the same area, phagocytic activity decreases and phagocytic response is suppressed (1985, 1988). In the present work, we performed in mice extensive chemical lesions of the arcuate nucleus, by means of the neonatal treatment with monosodium glutamate (MSG). The experiment was carried out on 23 new-born mice. 15 mice were injected with MSG (G group), the other 8, serving as control group, received isotonic saline solution (C group). The studied parameters were, in both groups, the weight evolution of the animals, the blood neutrophils and lymphocytes percentual variation and the neutrophils' phagocytic activity, tested in vitro, expressed through the number of bacteria engulfed by 100 neutrophils and through the phagocyting neutrophils percentage. Phagocytic activity was tested in whole heparinised blood, against E. coli. Phagocytic response was elicited by i.p. injecting 0.05 ml bacterial suspension and was tested four hours later. The results show that the arcuate nucleus has little influence upon maintaining basal phagocytic activity--that does not significantly decrease after its chemical damage--, but plays a decisive role in triggering the phagocytic response. The neonatal MSG treatment also determines a decrease of the blood lymphocytes percentage and induces obesity in up to 30 days old mice pups.     

Effects of concurrently administered copper and mercury on phagocytic cell activity and antibody levels in guinea pigs with experimental ascariasis

The dopamine (DA) D2/D3 antagonist (-)eticlopride (0.02, 0.05 and 0.1 mg/kg), dose-dependently increased immobility in the mouse tail-suspension test. Chronic treatment with the same compound (0.05, 0.1 mg/kg, x 14 days) produced a different effect, decreasing immobility when animals were tested 24 h after the last injection. The DA D3 agonist, 7-OH-DPAT, acutely administered before the same test, behaved biphasically, increasing and decreasing mice immobility at low (0.05 and 0.1 mg/kg) and high (1 and 2 mg/kg) doses, respectively. Chronically administered 7-OH-DPAT reduced the immobility time at 2 mg/kg but not at 0.1 mg/kg. These effects, coupled with measurements of locomotor activity and evaluation of mice behaviour in different conditions, are discussed in the light of putative DA involvement in depressive states and are considered as predicting antidepressant potential.     

Work capacity after iron treatment as a function of hemoglobin and iron deficiency

The relative importance of hemoglobin (Hb) and non-Hb iron for physical work capacity was studied in 45 adult male and female subjects, with a range of Hb and serum iron levels. Maximal work capacity, heart rate, venous blood lactate and serum protein were measured before and after 1 week of treatment with Imferon, i.v. Even though some non-Hb related effects on parameters indicative of maximal work capacity were found, the main factor was Hb related. Subjects with low Hb-high serum iron worked longer than ones with low Hb-low iron. When work performed was similar, the marginal Hb-low iron group had a higher blood lactate concentration than the high Hb-high iron and marginal Hb-high iron groups. The coefficient of correlation between serum iron and post-exercise lactate levels was -0.41 (p less than 0.05). Even though neither of these groups showed a Hb response within 1 week of iron treatment, the initial low serum iron groups had significantly lower heart rates at a given work load relative to subjects with high iron but with a similar Hb level. This occurred both at rest and during light to heavy exercise. These results suggest that a rather rapid benefit of iron treatment is gained in iron-deficient subjects with severe and moderate anemia which cannot be accounted for by Hb changes. Although the primary factor which affects the physical work capacity of iron-deficient anemic subjects seems to be the Hb level, there also seems to be a significant non-Hb related effect of iron treatment as well.     

Mitochondrial function as a determinant of recovery or death in cell response to injury

Many pathological conditions can be the cause or the consequence of mitochondrial dysfunction. For instance anoxia, which is initiated by a critical reduction of oxygen availability for mitochondrial oxidations, is followed by a wide variety of mitochondrial alterations. A crucial role in the evolution of cell injury is to be attributed to the direction of operation of the F0F1 ATPase, which may turn mitochondria into the major consumers of cellular ATP in the futile attempt to restore the proton electrochemical gradient. On the other hand, functional mitochondria can paradoxically accelerate or exacerbate cell damage. This concept is particularly relevant for the ischemic myocardium. Indeed, inhibition of the respiratory chain or addition of uncouplers of oxidative phosphorylation can both limit the extent of enzyme release in the intact heart and prevent the onset of irreversible morphological changes in isolated myocytes. From studies on different tissues in a variety of pathological conditions a general consensus emerges on the role of intracellular Ca2+ overload as a pivotal link between cellular alterations and mitochondrial dysfunction. Oxidative phosphorylation is reduced by a massive mitochondrial uptake of Ca2+, resulting in a vicious cycle whereby the reduced ATP availability is followed by a failure of the mechanisms which extrude Ca2+ from the sarcoplasm. In addition, the rise in [Ca2+]i could promote opening of the cyclosporin-sensitive mitochondrial permeability transition pore, leading to a sudden deltapsi(m) dissipation. Here, we review the changes in intracellular and intramitochondrial ionic homeostasis occurring during ischemia and reperfusion. In particular, we evaluate the potential contribution of the permeability transition pore to cellular damage and discuss the mechanisms which can determine the cellular fate from a mitochondrial point of view.     

The effect of dietary supplementation with copper sulfate or tribasic copper chloride on broiler performance, relative copper bioavailability, and dietary prooxidant activity

A new classification has been proposed for prophylactic antiradiation drugs, which are divided into three groups: radioprotectors, stimulators of radioresistance and the means of protection from internal irradiation. Depending on organs (systems) for the protection of which they are designed, radioprotectors in their turn are subdivided into myelo-, entero- and cerebroprotectors; stimulators of radioresistance (depending on the optimal regimens of their use to develop a higher resistance of the organism) are subdivided into drugs that are effective in single and repeated (course) use; the means of protection from internal irradiation are subdivided into the drugs that prevent incorporation of radioiodine by the thyroid gland, and into the drugs preventing absorption of radionuclides in the digestive tract. The main features that distinguish radioprotectors from stimulators of radioresistance are presented. The former are characterized by such properties as exhibiting the effect exquisitely when prophylactically administered in doses close to those of maximal tolerance, greatest effect against shortterm (pulse) irradiation, rapid development and short duration of the radioprotective action period, reduction in the effect in repeated use, etc. Stimulators of radioresistance rank below radioprotectors in their effect against short-term irradiation, however, unlike the latter, they exhibit their protective effect against a long-term (low dose rate) exposure as well under the conditions of both prophylactic and therapeutic use; their radioprotective action is more prolonged, they are distinguished for their low toxicity and lower the risk of delayed sequelae of irradiation, etc. Examples of the most typical members of each group of prophylactic antiradiation drugs are cited, data are presented which characterize their radioprotective activity, the role and place in the system of antiradiation protection of troops and population.     

Effects of pneumoperitoneum with carbon dioxide, argon, or helium on hemodynamic and respiratory function

In this study we investigated ob gene expression and plasma leptin levels in Psammomys obesus (the Israeli Sand Rat), a polygenic animal model of obesity and non-insulin-dependent diabetes mellitus. The ob gene was expressed exclusively in adipocytes of Psammomys obesus. DNA sequencing revealed a high degree of homology with other species (90% with mouse, 88% with rat and 79% with human). No ob gene sequence differences were found between lean and obese Psammomys obesus, and the codon 105 mutation found in ob/ob mice was not detected. Ob gene expression in Psammomys obesus correlated with body weight (r = 0.436, p < 0.001), percent body fat (r = 0.645, p < 0.001) and plasma insulin concentration (r = 0.651, p < 0.001). This is the first time that ob gene expression has been shown to increase steadily over a continuous wide range of body weight or plasma insulin in an animal model of obesity. Ob gene expression was significantly elevated in obese compared with lean Psammomys obesus (p < 0.05). No significant difference in ob gene expression was found between the four adipose tissue depots tested. Psammomys obesus plasma leptin levels correlated with body weight (r = 0.36, p < 0.05), percent body fat (r = 0.702, p < 0.01) and plasma insulin concentration (r = 0.735, p < 0.001). Plasma leptin concentrations were significantly increased in insulin-resistant animals independent of body weight. These results show that Psammomys obesus is an excellent animal model in which to study the ob gene and leptin, and confirm the importance of insulin as a significant factor in the regulation of leptin and ob gene expression.     

Influence of nutritional iron deficiency development on some aspects of iron, copper and zinc metabolism

The permanent fibrocyte-like fish cell line RTG-2 from rainbow trout (Oncorhynchus mykiss) gonads was investigated by means of light and scanning electron microscopy with respect to alterations as a consequence of sublethal exposure to 0, 1, 10, 16, 25, and 50 mg/liter 3,5-dichlorophenol (3,5-DCP) for 24 h. Control RTG-2 cells were spindle-like in shape and almost three times longer than wide. In subconfluent cultures, they displayed widely spread, flat leading lamellae and formed small groups. Along the edges of the cell protrusions, numerous retraction fibrils could be identified. Except for shallow ridges and small folds, the surface of untreated cells was completely smooth. Following exposure to 3,5-DCP, distinct dose-dependent alterations in cell shape, the appearance of surface blebs and invaginations, as well as progressive retraction of cell extensions could be observed from the lowest test concentration. Morphological changes could be correlated to suppression of lactate dehydrogenase and reduced neutral red retention capacity.     

Placental copper transport in rats: effects of elevated dietary zinc on fetal copper, iron and metallothionein

We hypothesized that the competition between zinc (Zn) and copper (Cu) during fetal accretion of copper could be discriminated at either the dam-to-placenta or placenta-to-fetus stage. This premise was tested by feeding dams a high Zn diet (1000 mg/kg, HZn) during the second half of gestation. One day before delivery, dams were anesthetized, fetuses removed and both maternal and fetal tissues and plasma obtained and assayed. Other rats were fed a normal Zn concentration diet (32.4 mg/kg, ND) throughout pregnancy. There were significantly lower fetal liver Cu concentrations and greater plasma Fe concentrations, but not plasma Cu concentrations or liver Fe concentrations in the HZn group. Both dam and fetal Zn liver concentrations were greater in the HZn than in the ND group. Plasma Cu levels were lower in the HZn-fed than in the ND-fed dams. Placental tissue from the HZn litters had a greater concentration of Zn and Fe than did the ND group, whereas no effect was noted for Cu concentration. Metallothionein (MT) levels were elevated in dam livers and placenta in the HZn group, but there were no differences in fetal liver MT. The dynamic assessment of placental transport was conducted by injecting 2.5 mg/kg Cu acetate intravenously into dams of both groups. Sequential samplings of dam and fetal blood and placentas were taken from 0 to 60 min. After the Cu bolus, there was a consistently higher plasma Cu concentration in the HZn than in the ND dams, but no alteration in the concentration of Cu in the placenta or fetal plasma. This study indicates that placental Cu uptake is not affected by a high Zn diet in the dam. In addition, the greater Zn concentration in the placenta of HZn than in ND litters results in abnormal fetal Cu, Fe and Zn concentrations, suggesting that an imbalanced maternal mineral consumption is deleterious to normal divalent metal accretion.     

Infectious morbidity and defects of phagocytic function in end-stage renal disease: a review

Infectious diseases remain among the most morbid events and are an important cause of death in ESRD. These events are related to an acquired immunodeficiency that progresses during the development of uremic retention, as part of the broader spectrum, displayed by the "uremic syndrome". A central role in the hose defense against bacterial infection is played by the phagocytic polymorphonuclear white blood cells, which are characterized by the capacity to ingest bacteria (phagocytosis), which is followed by the destruction of those bacteria (killing capacity). This article reviews the mechanisms of development and the potential causes that have been held responsible for this aspect of the defective immune function. The observed changes are attributed to alterations in receptor expression, although more convincing evidence points in the direction of metabolic functional disturbances, especially in the NAD(P)H-oxidase-dependent production of oxygen free radicals. The most important causative factors are: uremic toxicity, iron overload, renal anemia, dialyzer bioincompatibility, and the type of renal replacement therapy. It is concluded that the phagocytic defect in ESRD is multifactorial and that each factor should be managed by specific therapeutic approaches.     

Influence of cold or hyperbaric helium-oxygen environments on mouse response to a respiratory viral infection

In investigating the stress effects of chilling (2-3 degrees C) and hypothermia (2-3 degrees C drop in body core temperature mediated by exposure to hyperbaric helium-oxygen atmosphere) on mouse resistance to "influenza," it was noted that these stresses adversely affected the course of pulmonary infection produced by aerosols of the NWS strain of influenza virus. Comparatively, respiratory LD50 values for control animals were about 25 virus plaque-forming units (PFU) with median mortality occurring on day 13. The LD50 values for mice chilled at 2-3 degrees C were about 15 PFU with median mortality on day 7, and for mice exposed to hyperbaric helium, about 12 PFU with median mortality on day 6. Cold or hyperbaric stress impaired interferon production. Impairment was observed at 24 h but not at 12 h post-challenge and persisted for several days until mice became moribund.     

Effects of electrolytic bilateral symmetric lesions of the arcuate nucleus on the phagocytic activity and on the phagocytic response in rats

Previous researches of Cluj-Napoca laboratories of Physiology (Benetato, Baciu et al., 1945, 1946, 1947) demonstrated that direct electrical stimulation of the tubero-mammillary area in dogs increases, in the following hours, the blood polymorphonuclears phagocytic activity. By contrast, electrical damage of the same region produces a depression of the basal phagocytic activity and a blocking of the phagocytic response (Baciu et al., 1958, 1988). In the present research we assumed there is a stimulating effect of the arcuate nucleus, located in this area, on the phagocytic activity of blood neutrophils. We used an anodal current to stereotaxically induce lesion of the arcuate nucleus in six rats. A control group of six animals was used. Five days later, phagocytic response was induced with a Gram negative bacterial extract given i.v. The results demonstrated a decrease of the phagocytic activity from 164.31 +/- 17 bacteria engulfed by 100 neutrophils in controls, to 138 +/- 12.8 in the lesioned group p < 0.05. Phagocytic response after five hours appears depressed in the lesioned group (138 +/- 12.8 to 156.25 +/- 13.3, p < 0.05). Similar results were obtained after 24 hours. In control animals the response is very significant after 5 and 24 hrs., respectively, (p < 0.001). In conclusion, the arcuate nucleus is moderately involved in sustaining the basal phagocytic activity of blood neutrophils. It has an important role in phagocytic response.     

Effects of copper deficiency and copper loading on 67Cu in supernatants of rat organs

Eleven organs of the rat were studied 1 hr and 24 hr after the intravenous administration of 67CuCl2 and 67Cu-ceruloplasmin. The rats were normal, copper-deficient, or copper-laden. The amounts of stable copper and 67Cu in the whole organ and supernatant fractions, corrected for whole blood copper and 67Cu, were measured. The distribution of supernatant 67Cu was determined in three Sephadex G-100 chromatographic zones: Peak I (150,000 daltons), Peak II (31,000 daltons), and Peak III (11,000 daltons). All organs took up 67Cu from both sources, but there was a tendency for increased uptakes in copper-deficient rats and decreased uptake in copper-laden rats. Only lung, heart, and testis took up more 67Cu from 67Cu-ceruloplasmin than from 67CuCl2. Supernatant 67Cu tended to be in Peak I when the source was 67Cu-ceruloplasmin and in Peak II when the source was 67CuCl2. When 67Cu-ceroloplasmin was added to supernatant fractions in vitro, the 67Cu was in Peak I. However, when 67CuCl2 was added to supernatant fractions, Peak III predominated in kidney, brain, testis, and liver; Peak II predominated in none; and Peak I predominated in spleen, muscle, large and small bowel, stomach, lung, and heart. A high-molecular-weight copper-binding substance seems to be present in organ supernatant fractions.     

Effects of dietary magnesium deficiency in the rat: with special reference to ultrastructural examination

Epidemiologically, it has been suggested that dietary magnesium/calcium imbalance is associated with the risk of heart diseases. In the present study, the effects of magnesium deficiency and/or calcium over intake were investigated in rats. Male Sprague-Dawley rats were divided into 4 groups, and respectively fed basal diet (AIN-76) alone (Group 1), calcium-doubled AIN-76 diet (Group 2), magnesium-deficient AIN -76 diet (Group 3) and magnesium-deficient/calcium-doubled AIN-76 diet (Group 4) for 19 days. A biochemical assay using inductively coupled plasma showed that the magnesium concentrations of the femoral bone and serum were significantly (p < 0.001) lower in Groups 3 and 4 than in Group 1. The lipid peroxides of the heart in Group 4 and of the liver in Groups 3 and 4 were increased as compared to the Group 1 values although there was no statistical significance. Ultrastructurally, degenerative changes of organellas including mitochondria were observed in myocardial, liver and renal tubule cells of Groups 2-4. Severe degeneration such as disorganization, lysis and disarrangement of myofibrils was most evident in myocardial cells of Group 4. Our results thus suggest that dietary magnesium deficiency gives rise to retrogressive changes in some organs including the heart, and concurrent calcium overintake synergistically enhances the myocardial injury due to magnesium deficiency.     

乌山铜钼矿高次生铜矿石铜钼分离关键技术研究与应用

针对乌山铜钼矿矿石中次生铜矿物含量高,及其选矿厂设备选型配置、工艺流程结构不合理等问题,进行了技术研究和流程改造。通过对其工艺参数及技术条件的优化,对现场分离设备重新选型和设计,解决了流程无法实现连续稳定生产等突出问题,使设备选型和流程结构满足了生产要求,为铜钼成功分离奠定了良好的基础。经工艺流程的改造优化,铜钼分离钼精矿品位和钼回收率均达到投产以来最好水平,其中钼精矿品位累计为48.48%,累计含铜1.49%,钼回收率由改造前的30.58%提高到81.82%;且铜钼分离流程运行稳定,经济效益显著。     

电感耦合等离子体原子发射光谱法测定含铬镍生铁中镍铬锰磷钼铜钴

采用王水并滴加氢氟酸溶解含铬镍生铁样品,高氯酸冒烟,采用标准样品/控制样品制作校准曲线,测定过程采用内标法,实现了使用电感耦合等离子体原子发射光谱法(ICP-AES)测定含铬镍生铁中高镍、高铬以及锰、磷、钼、铜和钴等元素的测定。在仪器工作条件下,各元素校准曲线线性相关系数均大于0.999,其中镍元素线性相关系数达到0.999 9。方法中各元素的检出限为0.002 0～0.020 μg/mL。采用实验方法对含铬镍生铁实际样品中的镍、铬、锰、磷、钼、铜和钴含量进行测定,结果与国家标准化学分析方法基本一致,相对标准偏差(RSD,n=11)在0.53%～5.0%之间。     

Lack of Th1 or Th2 polarization of CD4+ T cell response induced by particulate antigen targeted to phagocytic cells

Viral haemorrhagic disease (VHD) of rabbits was introduced into Mexico from the United States of America in November 1988, following the importation of infected carcasses from China. In February 1989, the National System for Animal Health Emergencies was created, and an eradication programme was implemented at that time. The VHD virus was eradicated in 1992, by means of disease control procedures which included active epidemiological surveillance, publicity campaigns, slaughter, cleaning and disinfection of affected premises, the use of sentinel animals, serological monitoring and repopulation. The eradication programme involved the serological sampling of 39,727 rabbits (revealing an incidence of 1.4%) and the slaughter of 121,275 affected rabbits and rabbits at risk of exposure to infection. The final outbreak of the disease was recorded in April 1991. The country maintained strict epidemiological surveillance through serological testing, certification of premises free from the disease, and control of movement of animals and animal products. Mexico was declared free from the disease on 20 January 1993, becoming the first country to have eradicated VHD. The authors propose a model to evaluate the risk of introducing VHD through the importation of animals and animal products. A guide is provided to evaluate each branch of the relevant scenario tree and the principal criteria which indicate the event at each parameter.