Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: impact of alpha-tocopherol.

Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (α-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of α-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg(-1)day(-1) of PCB (i.p.); Group III rats were treated with 2 mg kg(-1)day(-1) of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg(-1)day(-1) of α-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H(2)O(2)) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-α and ER-ß in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-α expressions were significantly decreased while H(2)O(2) generation, LPO, ER-ß were increased in PCB-exposed animals. Simultaneous supplementation of α-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that α-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction.

Oxidative stress modulates membrane bound ATPases in brain regions of PCB (Aroclor 1254) exposed rats: protective role of alpha-tocopherol.

Polychlorinated biphenyls (PCBs) are a class of widely dispersed and environmentally persistent organic compounds. PCBs exhibit a wide range of toxicological effects including neurotoxicity. Vitamin E (alpha-tocopherol) is an important lipid soluble antioxidant placed in a special region of membranes. Large amounts of energy are required to maintain the signaling activities of the cells in the central nervous system (CNS). Membrane proteins that control ion gradients across organellar and plasma membranes appear to be particularly susceptible to oxidation-induced changes. The aim of this study was to determine the protective role of vitamin E on Aroclor 1254 induced modulation in membrane bound ATPases in brain regions of rats. One group of rats received corn oil as vehicle for 30days as control. The other group of rats were administered Aroclor 1254 at a dose of 2mgkg(-1) bwday(-1) intraperitoneally for 30days. One group of rats received vitamin E (50mgkg(-1) bwday(-1)) orally simultaneously with Aroclor 1254 for 30days. After 30days, the animals were euthanized and the brain was dissected to hypothalamus and hippocampus to determine the following parameters. Hydrogen peroxide (H2O2), Lipid peroxidation (LPO) and the activities of Na+K+-ATPase, Ca2+-ATPase and Mg2+-ATPase were determined. Reduced glutathione (GSH) level was also determined. Activities of all the enzymes were decreased while an increase in H2O2 and LPO were observed in selected brain regions of PCB treated animals. Simultaneous vitamin E treatment in PCB exposed animals restored all the parameters significantly. These results suggest that oxidative stress is involved in the inhibitory effect of PCB (Aroclor 1254) on membrane bound ATPases in selected brain regions. alpha-tocopherol acts against PCB induced neurotoxicity by decreasing oxidative stress.

Ameliorative effect of vitamins (alpha-tocopherol and ascorbic acid) on PCB (Aroclor 1254) induced oxidative stress in rat epididymal sperm.

The aim of this study was to investigate the possible protective role of vitamins on PCB (Aroclor 1254)-induced spermiotoxicity using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups, each group consists of six animals. The control group received corn oil, the second group of rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. The third group of rats were treated with Aroclor 1254 along with alpha-tocopherol (50 mg/kg of bw/day) for 30 days, while the fourth group of rats were treated with Aroclor 1254 along with ascorbic acid (100 mg/kg bw/day) orally for 30 days. Twenty-four hours after the last treatment, control and experimental animals were killed by decapitation. Sperm was collected from the cauda epididymal region and its count and motility were detected. Sperm was sonicated and used for the estimation of reactive oxygen species (ROS) [hydroxyl radical (HO(*)) and hydrogen peroxide (H(2)O(2))], non-enzymic antioxidants [alpha-tocopherol, ascorbic acid and reduced glutathione (GSH)], activity of enzymic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST)] and lipid peroxidation (LPO). The result of this experiment shows that PCB significantly decreases the level of alpha-tocopherol, ascorbic acid and GSH and the activities of SOD, CAT, GPx, GR and GST with elevated levels of ROS and LPO. In addition, decreased epididymal sperm motility and count were observed. Simultaneous supplementation with alpha-tocopherol and ascorbic acid restored these parameters to that of normal range. In conclusion, alpha-tocopherol and ascorbic acid exhibited protective effect on sperm by inhibiting PCB-induced ROS generation.

Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats.

BACKGROUND: PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Vitamin C is well known as an outstanding antioxidant. We determined the protective role of ascorbate on hypothalamic antioxidant system of Aroclor 1254 exposed rats. METHODS: The rats were injected Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received vitamin C (100 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Twenty-four hours after last treatment, the animals were killed and hypothalamic region was separated from brain tissue. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and vitamin C were estimated. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and acetylcholine esterase (AchE) activity were determined. Serum gonadotropins such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed. RESULTS: Activities of SOD, CAT, GPx, GR, AchE and the concentration of vitamin C were decreased while an increase in H(2)O(2) and LPO were observed in hypothalamus of PCB treated animals. LH and FSH concentrations were also decreased in serum of PCB exposed animals. Vitamin C administration retrieved all the parameters significantly except serum hormonal profiles. CONCLUSION: PCB induces oxidative stress in hypothalamus by decreasing the activities of antioxidant enzymes, which can be protected by vitamin C treatment.

Effects of vitamin supplementation on PCB (Aroclor 1254)-induced changes in ventral prostatic androgen and estrogen receptors.

The objective of this study was to determine the impact of the polychlorinated biphenyl (PCB) Aroclor 1254 and vitamin C and E on ventral prostatic testosterone and estradiol receptor concentration. A group of 30 rats were treated with Aroclor 1254 [2 mg/kg body weight (bwt) /day/ip] for 30 days; 10 rats were treated as Aroclor 1254 control. The remaining 20 rats were subdivided into the following two subgroups of 10 animals each. One group was given vitamin C (500 mg/kg bwt/day/oral) for 10 days, whereas the other group was given vitamin E (50 mg/kg bwt/day/oral) for 10 days. Separate controls were also maintained. Ventral prostatic androgen and estrogen receptor concentration in all the groups were quantified. Serum hormonal profiles such as total T3, T4, TSH, testosterone, and estradiol were also estimated in all the groups. Ventral prostatic zinc content and serum zinc concentration were also determined in all the groups. Aroclor 1254 exposure decreased the concentration of both receptors. Decreased serum total T3, T4, testosterone, estradiol, and increased TSH were observed after Aroclor 1254 exposure. Serum and tissue zinc levels were also decreased. Administration of vitamin C or E restored both the receptor concentration and the serum hormone levels with the exception of estradiol. Administration of vitamin C or E restored zinc levels. Vitamin E was more sensitive on ventral prostatic androgen receptors and zinc levels, including serum, in PCB-exposed rats.

Calcium, magnesium and phosphorus in the nutrition of the newborn.

Several factors have been suggested to contribute to inadequate bone mineralization in infants. Calcium and phosphorus intakes in preterm infants are below the intrauterine accretion rates. Calcium retention is influenced by the types of calcium salts used and by alterations in dietary phosphorus, fat and carbohydrates. Dietary intakes of vitamin D, and modifications in the protein base of infant formula, e.g., soy base vs cow milk base, may impact bone mineralization. The major hormonal mechanisms involved in the regulation of bone mineralization are parathyroid hormone, calcitonin and vitamin D. From recent animal studies, it has been suggested that parathyroid hormone related peptide (PTH-rp) may also play a role in perinatal calcium homeostasis.

Bone mineral metabolism in full-term infants fed human milk, cow milk-based, and soy-based formulas.

OBJECTIVE: To study the hypothesis that ingestion of a modified soy-based formula with an improved mineral suspension system may result in bone mineral content similar to that observed in infants fed human milk or cow milk-based formulas. DESIGN: Prospective, self-selected group of infants fed human milk randomized between the two formula-fed groups. SETTING: University-based hospital nursery and follow-up. PARTICIPANTS: Fifty-six normal, healthy, full-term infants, free of major malformations or disorders, including 17 infants fed human milk, 19 infants fed a cow milk-based formula, and 20 infants fed a soy protein formula were followed up to 6 months' postnatal age. The soy-based formula studied was modified to improve the suspendability of the minerals. INTERVENTIONS: Infants were fed human milk or the study formula for the first 4 months, at which time beikost was permitted. Infants fed human milk received vitamin supplementation to provide 400 IU of vitamin D per day. MEASUREMENTS: Anthropometric variables, serum calcium, magnesium, phosphorus, alkaline phosphatase, and parathyroid hormone levels were measured at enrollment, and at 8, 16, and 24 to 26 weeks' postnatal age. Bone mineral content at the distal third radius site was measured with single photon absorptiometry at these times. Growth in the infants did not differ significantly among the groups. There was no significant difference in serum calcium, magnesium, alkaline phosphatase, or parathyroid hormone concentrations among the infants during the study. Serum phosphorus was significantly lower at 8 weeks in the group fed human milk than in that fed the cow milk-based formula. Bone mineral content at 16 and 24 to 26 weeks was higher in the group fed the soy-based formula than in that fed human milk, and bone width was also higher at 16 weeks in the infants fed the soy-based formula. CONCLUSIONS: Improving the suspendability of the mineral system in the soy formula results in bone mineralization in infants fed the soy-based formula similar to that measured in infants fed human milk and cow milk-based formula. We suggest that the suspendability of the minerals used is an important variable in the interpretation of the effect of feedings on the bone mineral status of infants.

KAP study on mothers of children with Down syndrome.

We evaluated 50 mothers of children with Down syndrome attending Genetic Clinic of the Institute of Child Health and Hospital for Children, Madras, with special reference to their knowledge, belief and attitudes in the care of these children. After evaluation, they were educated individually and in groups with demonstration, picture cards and pamphlets, on the causation, expected health problems, developmental potential of Down syndrome and the ways and means to help the child to attain the maximum developmental potential. They were taught on preventive aspects of Down syndrome as well. Re-evaluation was done after three months, and considerable improvement was noted in the mother's knowledge, and attitude towards bringing up such a child. The mothers also showed an improvement in the skills in providing developmental enrichment to these children. Thus this study has formulated a programme in the management of such children, which can be practised on any population, anywhere, especially, in rural areas, and by less affluent folk, with poor educational background.

PIP: Between May-October 1989, physicians selected 50 mothers of low socioeconomic and educational background with Down Syndrome (DS) children who attended the Genetic Clinic at the Institute of Child Health and Hospital for Children in Madras, India for a study to evaluate their knowledge, attitude, and practices. The study consisted of a preevaluation, education and genetic counseling, and reevaluation at 3 months. Only 18% of the mothers knew that their children had DS. Physicians had diagnosed it at birth in these cases. Most mothers (62%) came to the hospital because they had noticed developmental delay. Most (64%) did not know what caused DS. 36% believed DS occurred due to various prenatal events including poor diet, weakness, injury, abortifacients, abdominal pain, vomiting, and long birth intervals. Family tended to blame the mothers for the child's disability which evoked social and emotional problems. When 52% learned of their children's handicap, they suffered depression. 80% did not know that their children required special care. Once learning this, however, most mothers (88%) wanted either themselves or someone else to care for their children. 96% breast fed their children and weaned them properly. 90% of the children had received immunizations. After genetic counseling and health education, all mothers understood their children's condition. 75% worked with their children at home doing passive exercises and developing their vocabulary. The rearing practices of the DS children were the same as those of the normal children. The mothers learned via the health education and genetic counseling that family planning and amniocentesis could prevent the birth of a DS child. The health education and genetic counseling program improved mothers knowledge, attitude, and practices toward child-rearing practices of DS children. This program can be duplicated among poor and illiterate parents in rural areas.

Effect of intravenous calcium infusions on serum chemistries in neonates.

In 36 newborn infants admitted to the Children's Hospital of Oklahoma, we studied the hypotheses that intravenous bolus infusions of Ca as calcium gluconate over 10 min may (a) result in acute metabolic acidosis, (b) increase serum osmolality, (c) increase serum free bilirubin, and (d) decrease serum phosphorus concentrations. All infants received 18 mg/kg of elemental calcium, as either a 5 or 10% solution of calcium gluconate. Blood ionized calcium (iCa) rose significantly with i.v. bolus Ca infusion (p less than 0.005) and blood pH and serum P declined significantly (p less than 0.05) with i.v. bolus Ca infusion in infants. Serum free bilirubin was not significantly altered. Serum osmolality rose significantly from baseline with bolus infusion of Ca as a 10% calcium gluconate solution and did not change significantly with bolus infusion of a diluted 5% solution. In neonates, intravenous bolus calcium infusion (a) decreases blood pH, (b) infusion of 10% but not 5% calcium gluconate increases serum osmolality, (c) serum free bilirubin concentrations were not altered, and (d) serum phosphorus concentrations were decreased.

Hypercalcitoninemia and hypocalcemia in acutely ill children: studies in serum calcium, blood ionized calcium, and calcium-regulating hormones.

We studied the hypotheses that serum calcium and blood ionized calcium would be low in acutely ill children and would rise with clinical improvement. In 15 children admitted to the pediatric intensive care unit, the blood ionized calcium level was 4.45 +/- 0.06 mg/dl (1.11 +/- 0.015 mmol/L) on entry versus 5.17 +/- 0.03 mg/dl (1.29 +/- 0.01 mmol/L) in control subjects (p less than 0.005), rose significantly on days 2 and 3, and was 5.12 +/- 0.04 mg/dl (1.28 +/- 0.01 mmol/L) at discharge (p less than 0.005). Changes in serum calcium level were similar, whereas serum magnesium and phosphorus levels were normal and did not change. Basal serum parathyroid hormone concentrations were elevated, rose further during the study, and were normal at discharge. Serum parathyroid hormone levels correlated inversely with blood ionized calcium levels, indicating that compensatory hyperparathyroidism occurs with low blood ionized calcium concentrations. Basal serum calcitonin values were evaluated on entry and decreased with clinical improvement. Serum calcitonin levels correlated significantly with low blood ionized calcium levels, indicating that hypercalcitoninemia may play a role in the pathogenesis of hypocalcemia in these children. Urine calcium excretion was not increased in the four children studied. We speculate that with clinical improvement, a rise in serum parathyroid hormone levels and a decline in serum calcitonin levels may help restore normocalcemia in these acutely ill children.

Effect of mineral supplementation of human milk on bone mineral content and trace element metabolism.

We studied the effect of feeding mineral fortified human milk to preterm infants (birth weight less than or equal to 1500 gm). Serum concentrations of calcium, magnesium, phosphorus, zinc, cooper, alkaline phosphatase, and parathyroid hormone were determined, and bone mineral content was measured, in infants fed unfortified human milk (group 1), fortified human milk (group 1), fortified human milk (group 2), and a "humanized," mineral-enriched premature infant formula (group 3). Serum calcium, magnesium, phosphorus, zinc, copper, and parathyroid hormone concentrations did not differ significantly among the groups studied. Serum alkaline phosphatase concentrations increased significantly only in the infants fed unfortified human milk, and bone mineral content in this group was significantly lower than in formula-fed infants.

Calcium, phosphorus, magnesium, and calcitonin concentrations in the serum and cerebrospinal fluid of children.

Mineral metabolism in the cerebrospinal fluid (CSF) of children is poorly understood. Recent reports have suggested a neuroregulatory role for calcitonin. We examined the hypotheses that in children (1) CSF levels of calcium and phosphorus might be low, (2) CSF levels of magnesium might be higher than serum levels of magnesium, and (3) immunoreactive calcitonin might be present in the CSF. We examined serum and CSF samples of 45 children, aged 8 days to 16 years, undergoing spinal taps for suspected meningitis or as part of leukemia therapy. Both serum and CSF levels of calcium correlated with those of magnesium. There was no correlation for CSF levels vs serum levels of calcium, magnesium, or phosphorus. The CSF levels of calcium and phosphorus were lower than the serum levels of these elements, but the CSF levels of magnesium were higher than the serum levels of magnesium. Calcitonin was detected in the CSF of 8% of samples assayed (range, 14 to 175 ng/L [14 to 175 pg/mL]). Two of these five samples had bacteriologically proven meningitis, and two samples were from patients less than 2 months of age. The CSF levels of calcitonin did not correlate with the serum levels of calcitonin. Thus, in children CSF levels of calcium and phosphorus are low, CSF levels of magnesium are higher than the serum levels, and the level of immunoreactive calcitonin is usually not present in the CSF but possibly is elevated in meningitis and early infancy.

Early neonatal hypocalcemia in extremely preterm infants. High incidence, early onset, and refractoriness to supraphysiologic doses of calcitriol.

Nineteen preterm infants born at or before 32 weeks of gestation were studied to determine the dose of calcitriol that would be effective in the prophylaxis of early neonatal hypocalcemia (serum calcium level, less than 7.0 mg/dL [less than 1.75 mmol/L]). In these infants the course of early neonatal hypocalcemia was not modified by calcitriol administration. Serum 1,25-dihydroxyvitamin D level rose in response to intramuscular administration of calcitriol. The incidence of hypocalcemia in these infants was 37% by 12 hours, 83% by 24 hours, and 89% by 36 hours. Thus, in extremely preterm infants, the incidence of early neonatal hypocalcemia is higher and the onset earlier than in larger preterm infants; furthermore, in these infants the hypocalcemia is refractory even to high doses of calcitriol.

Decline in serum calcium, magnesium, and phosphorus values with oral glucose in normal neonates: studies of serum parathyroid hormone and calcitonin.

In 10 normal term infants aged 52 +/- 2.5 hours, serum calcium, magnesium, phosphorus, ionized calcium, parathyroid hormone, and calcitonin were studied at 0, 1/2, 1, and 2 hours after administration of 1.77 +/- 0.08 gm/kg glucose orally over 20 minutes. In response to glucose administration, serum glucose concentration rose and serum P, Ca, and Mg concentrations fell. Serum PTH concentration rose significantly, and blood ionized Ca and pH were unaltered. Serum calcitonin was elevated, as compared with adult values, and did not change. We suggest that in neonates, as in adults, oral ingestion of glucose lowers serum Ca, Mg, and P, and a compensatory rise in serum PTH concentration maintains blood ionized Ca concentration.

Late infantile tetany and secondary hyperparathyroidism in infants fed humanized cow milk formula. Longitudinal follow-up.

Five full-term infants with birth weights appropriate for gestational age presented with hypocalcemic tetany at 5 to 9 days of age. All infants had been fed Similac 20, a cow milk formula. Initial mean serum calcium (Ca), phosphorus (P), and magnesium (Mg) levels of the tetanic infants were 6.8, 9.5, and 1.6 mg/dL, respectively. The mean serum parathyroid hormone (PTH) level was elevated at 79 mu LEq/mL (adult normal values, less than or equal to 57 mu LEq/mL). Following restoration of normocalcemia with Ca supplements, feeding was reinstituted with Similac 20 in two infants and Similac PM 60/40 in three infants. Serum biochemical and hormonal values were compared with those of 18 exclusively breast-fed infants followed up from three weeks to six months and 14 Similac 20-fed full-term infants followed up from one week to six months. In tetanic infants, serum Ca concentrations became elevated (10.4 +/- 0.05 mg/dL; mean +/- SEM) by six weeks (vs 9.2 +/- 0.3 mg/dL in breast-fed infants) (P less than .001) and serum Mg concentrations (2.26 +/- 0.01 mg/dL) by four weeks (vs 1.92 +/- 0.07 mg/dL in breast-fed infants) (P less than .01). Mean serum P concentrations declined progressively. Mean serum PTH concentrations were elevated and ranged from 74 to 143 mu LEq/mL at two to 16 weeks (vs mean 28 to 35 mu LEq/mL in breast-fed infants (P less than .0001). In 14 formula-fed-nontetanic full-term infants, serum PTH concentrations were intermediate between formula-fed-tetanic and breast-fed infants, mean serum Ca concentrations ranged from 10.2 to 10.4 mg/dL, and mean serum P concentrations declined from 8.3 to 7.1 mg/dL. We speculate that acute hypocalcemic tetany in the study infants was induced by the relatively high P load in cow milk formulas (vs human milk); with the continued P load, secondary hyperparathyroidism continued, maintaining P, Ca, and Mg homeostasis.

The development of pseudohypoparathyroidism. Involvement of progressively increasing serum parathyroid hormone concentrations, increased 1,25-dihydroxyvitamin D concentrations, and 'migratory' subcutaneous calcifications.

The hormonal changes in the development of pseudohypoparathyroidism ( PSH ) have not, to our knowledge, been previously reported. The male sibling of a child with PSH was studied for 2 1/2 years. At 1 year of age he had generalized subcutaneous calcifications that subsequently migrated over his body. At 3 years of age and over a six-month period, serum calcium levels fell; serum phosphorus, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations increased. There was no calcemic, phosphaturic, or urinary cyclic adenosine monophosphate response to PTH. The concentration of serum PTH was suppressed by infusion of calcium and doubled with edetic acid infusion, indicating that the parathyroids were sensitive to changes in calcium levels. Thus, increasing PTH and increased 1,25-(OH)2D concentrations occur in the development of PSH . Migratory skin calcifications may occur. We speculate that increasing the serum PTH level reflects increasing compensatory parathyroid production to overcome a progressive PTH receptor defect and serves, with increased 1,25-(OH)2D concentrations, to prevent severe falls in serum calcium concentrations in the early stage of the disease.

Stability of calcium and phosphorus in neonatal parenteral nutrition solutions.

The solubility and stability of Ca and P in a parenteral nutrition solution is defined. In this study we demonstrate that high levels of Ca and P can be attained in parenteral nutrition solutions suitable for use in neonates. The efficacy and safety in neonates, however, will require specific study.