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Biomedical subjects

H Zucker

Publications and source records attributed to H Zucker.

At least 19 recordsLinked to original sources

Vitamin D metabolites prevent vertebral osteopenia in ovariectomized rats.

The present study investigated the prophylactic effects of vitamin D metabolites and vitamin D metabolite combinations on static and dynamic, tetracycline-based, histomorphometric parameters in the axial skeleton of ovariectomized rats. Forty-three Fischer-344 rats (10 weeks old, 130 g each body weight, BW) were either bilaterally ovariectomized (OVX) or sham-operated (SHAM). The rats were allocated into the following groups: SHAM; OVX; OVX + 7.5 ng 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]/rat/day; OVX + 15 ng 1 alpha,24R,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3]/rat/day; OVX + 75 ng 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3]/rat/day; OVX + 7.5 ng 1,25(OH)2D3/rat/day + 15 ng 1,24,25(OH)3D3/rat/day; OVX + 7.5 ng 1,25(OH)2D3/rat/day + 75 ng 24,25(OH)2D3/rat/day. The vitamin D metabolites were fed orally starting 4 weeks after surgery. Urine and blood samples were collected 12 and 16 weeks postovariectomy, respectively. Sixteen weeks after surgery, all rats were sacrificed, and the first lumbar vertebrae were processed undecalcified for histomorphometric analysis. Ovariectomy induced a highly significant reduction (P less than 0.001) of cancellous bone mass in the secondary spongiosa of the lumbar vertebral body. The bone loss in OVX rats was accompanied by a distinct elevation of all histomorphometric parameters of bone formation and resorption. 1,25(OH)2D3 and both vitamin D metabolite combinations significantly raised serum calcium levels and prevented the bone loss by inhibiting the increased bone resorption in OVX rats. In the applied dosage, 1,24,25(OH)3D3 and 24,25(OH)2D3 alone were ineffective in preserving the cancellous bone of the lumbar vertebra in OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Individual differences in the vitamin A metabolism of the order Carnivora--a review].

Vitamin A transport in blood of most species in the order carnivora is fundamentally different from other animals and man. Very high levels of vitamin A in blood plasma of canines and mustelides are due to a high percentage of retinyl esters. These esters (basically retinyl palmitate and stearate) are transported nonspecifically bound to lipoproteins with very-low and low density lipoproteins representing the major fractions (about 70% of total vitamin A esters). A high percentage of retinyl esters could also be found in the families Ursidae, Procyonidae, Viverridae and Felidae in which total vitamin A in blood was low. In man and rat severe signs of vitamin A intoxication can be observed due to a similarly high percentage of nonspecifically bound vitamin A esters. No clinical or clinical-chemical signs of vitamin A intoxication were observed in the animals investigated. Because vitamin A esters are transported by lipoproteins, their blood levels are readily affected by dietary vitamin A supply as it is known to be the case for vitamin E. Furthermore, canines seem to be the only ones that excrete vitamin A as retinol and retinyl esters (basically retinyl palmitate) under physiological conditions with the urine. These fat-soluble metabolites of vitamin A are bound to a protein with a molecular weight between 50,000 and 125,000 Da which shows characteristics of a lipoprotein when subjected to ultracentrifugation or selective precipitation. Higher levels of vitamin A in organs and tissues, as well as the excretion of vitamin A with the urine, might be a consequence of the nonspecific binding of large amounts of retinyl esters to lipoproteins in blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Osteopenia caused by ovariectomy in young female rats and prophylactic effects of 1,25-dihydroxyvitamin D3.

Young female rats were subjected to either bilateral ovariectomy or sham operation. One group of ovariectomized (ovx) animals was treated with the vitamin D metabolite 1,25(OH)2D3 after surgery. The effects of ovariectomy and 1,25(OH)2D3 treatment on different markers of bone formation (serum alkaline phosphatase, serum bone gla protein) and bone resorption (fasting urinary hydroxyproline) were determined. All rats were euthanized at 7 weeks post ovariectomy and their first lumbar vertebra were processed undecalcified for quantitative bone histomorphometry. A significant decrease in cancellous bone mass was noted in ovx compared with sham-operated rats. This bone loss was associated with increased biochemical markers of bone formation and bone resorption. Furthermore, ovariectomy led to elevated osteoblast perimeter and osteoid parameters as well as an increased osteoclast number. These data indicate that young growing rats develop osteopenia 7 weeks after ovariectomy which goes along with an accelerated bone turnover. Bone gla-protein, alkaline phosphatase and hydroxyproline can be useful markers in studies with ovx rats. Treatment with 1,25(OH)2D3 led to a lowered urinary hydroxyproline excretion and a significant decrease of osteoclast number whereas histomorphometrical indices of bone formation were nearly unchanged. Cancellous bone mass increased significantly in ovx rats treated with 1,25(OH)2D3 compared with non-treated rats. These results suggest that 1,25(OH)2D3 has a prophylactic effect with regard to bone loss in ovx rats which refers to a diminished bone resorption in the high bone turnover condition of ovx animals.

Animals

Vitamin A in the urine of carnivores.

Vitamin A levels (retinol equivalents) in the urine of canines were between 423 ng/ml (dog) and 6304 ng/ml (silver fox). Neither vitamin A nor vitamin E was found in the urine of herbivores, omnivorous and rodents. No vitamin A but low levels of vitamin E were detected in cats. Vitamin A in the urine was present as retinol and retinyl esters (basically retinyl palmitate/oleate). The total excretion of vitamin A represented 15 to 63% of the daily uptake in dogs, while less than 4% of vitamin E was excreted. Results after precipitation and ultracentrifugation indicate that similar carrier proteins may exist for retinol, retinyl esters and alpha-tocopherol in the urine. The biological significance of this phenomenon is discussed with regard to the high concentrations of retinyl esters in the blood plasma of carnivores bound to lipoproteins.

Animals

Temperature sensitivity of Ca currents in chick sensory neurones.

We have investigated the effects of temperature on the Ca currents of chick sensory neurones. Raising the temperature from 17 to 37 degrees C, caused low-threshold (LVA, T) and high-threshold (HVA, L and N) Ca currents to show a marked amplitude increase and a drastic acceleration of their activation-inactivation gatings. Compared to HVA channels, the LVA type showed a weaker temperature sensitivity. Its average Q10 values were closer to those of other voltage-operated ion channels: 1.7 (permeability), 1.9 (activation) and 2.2 (inactivation). Alternatively, the activation kinetics and peak permeability of HVA Ca channels showed maximal Q10 values of about 5 and 2.8, respectively. HVA channel deactivation was less sensitive to temperature (Q10 1.8). Inactivation of these channels was slow and monoexponential between 17 and 22 degrees C, but faster and double exponential above 30 degrees C, uncovering a fast temperature-sensitive decaying phase. The size and rate of decay of this component decreased with increasing membrane depolarizations and persisted at holding potentials positive to -80 mV, suggesting the involvement of temperature-sensitive Ca-mediated processes in the mechanism of HVA channel inactivation. Our data are consistent with the view that heating from 17 to 37 degrees C causes both an increased probability of Ca channels to open and a drastic acceleration of their activation-inactivation kinetics.

Animals

The majority of vitamin A is transported as retinyl esters in the blood of most carnivores.

1. In canines and mustelides total vitamin A was 10-50 times higher compared to other species due to a high amount of retinyl esters (40-99% of total vitamin A) in blood plasma. The dominant vitamin A ester was in most species retinyl stearate. 2. In Ursidae, Procyonidae, Viveridae and Felidae, total vitamin A was much lower. When present, however, retinyl esters also represented 10-65% of total vitamin A in plasma. 3. Only retinol was detected in plasma of the family, Hyaenidae, and the suborder, Pinnipedia. 4. In maned wolf cubs it was found that retinol, retinyl esters and alpha-tocopherol increased with the age of the animals, reaching values comparable to adult animals at the age of 5 months.

Aging

Effect of feeding on vitamin A concentrations in blood plasma of dogs.

The effects of different concentrations of vitamin A in food as well as different food compositions on serum vitamin A levels in dogs were investigated. Contrary to current knowledge for all other species, vitamin A levels in dogs were clearly affected by the daily vitamin A supply as well as the type of food. This behavior, similar to that of vitamin E, can be explained by the fact that dogs and other carnivores transport most of their vitamin A in blood as retinyl esters (mainly retinyl stearate) bound to lipoproteins. The differences in the retinyl ester pattern between vitamin A in liver and in blood indicates that the mobilization of vitamin A from the liver involves selective mechanism. The possible importance of nonspecific, lipoprotein-bound vitamin A esters in the blood of dogs is discussed.

Animal Feed

Na+ currents through low-voltage-activated Ca2+ channels of chick sensory neurones: block by external Ca2+ and Mg2+.

1. Whole-cell currents through low-voltage-activated (LVA) Ca2+ channels carried by monovalent cations were studied in chick dorsal root ganglion (DRG) cells. 2. With 120 mM [Na+] on both sides of the membrane and [Ca2+]o less than or equal to 100 microM, the currents reversed at 0 mV. Their half-times of activation and inactivation were strictly voltage-dependent and decreased to near-constant values of 0.6-0.85 and 40 ms, respectively, at positive membrane potentials. The longer activation times were observed with [Ca2+]o greater than or equal to 50 microM. 3. The selectivity of the Ca2+ channel for monovalent ions with reference to internal Na+ was evaluated from the reversal potential. The Li+ and Na+ permeabilities were similar. The permeability ratios of K+ and Rb+ were 0.45, and 0.33 for Cs+. 4. Micromolar increases in [Ca2+]o produced small voltage shifts of half-times of activation (less than or equal to +3 mV at 10 microM and +10 mV at 500 microM), but strongly depressed the Na+ current. The Ca2(+)-induced block of Na+ current satisfied a 1:1 stoichiometry with an apparent KD of 1.8 microM at -20 mV. The block was, however, relieved with more positive and negative potentials, with KDs of 55 and 8.5 microM at +90 and -110 mV, respectively. 5. Relaxation time constants of block and unblock of Na+ currents through the LVA Ca2+ channel were measured on step changes to and from membrane potentials at which pronounced Ca2(+)-induced block occurred. 6. At -20 mV, the time constants of block decreased with micromolar increase in [Ca2+]o in line with a blocking rate coefficient of 1.9 x 10(8) M-1 s-1, but settled to values of 0.18 ms at [Ca2+]o beyond 50 microM. The Na+ currents were unblocked with time constant (tau u) of around 0.25 ms at strongly positive and negative membrane potentials at 22 degrees C. 7. Tau u failed to show any obvious dependence on [Ca2+]o up to the millimolar range. This finding contradicts suggestions that removal of the block occurs in a [Ca2+]o-dependent manner as a result of an increased probability of Ca2+ ion mobilization by repulsive forces with increased Ca2+ occupation of the channel. 8. The time course of unblock of Na+ currents was strongly temperature-dependent showing a Q10 of 2.5 for tau u. 9. The voltage dependence of the Na+ current block by Ca2+ ions is best accounted for by a single, centrally located Ca2+ binding site.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Histomorphometric analysis of the rat proximal tibial metaphysis by "linear scanning".

Twenty-four female Sprague-Dawley rats (10 weeks old, 200g BW) were either sham-operated (n = 6) or ovariectomized (ovx). Ovx rats were divided into 3 groups (n = 6 each): ovx; ovx + 1,25-(OH)2D3; ovx + 1,25(OH)2D3 + 1,24,25-(OH)3D3. The vitamin D metabolites were fed orally starting the day after surgery. After 7 weeks all rats were sacrificed and the proximal tibiae were processed undecalcified for quantitative histomorphometry. Conventional histomorphometric analysis of the distal zone (greater than 1 mm from the growth cartilage) of the tibial metaphysis revealed a dramatic loss of cancellous bone mass in ovx rats. Both 1,25(OH)2D3 and the combination of 1,25(OH)2D3 with 1,24,25(OH)3D3 prevented the bone loss in the distal zone in ovx animals. Measurements in the proximal zone (less than 1 mm from the growth cartilage) of the tibial metaphysis were performed with a newly developed technique that utilizes the advantages of automatic image analysis, and that we propose to name "linear scanning". This method revealed a significantly decreased hard tissue mass at about 100 microns and within 800 to 950 microns distance from the growth plate in ovx rats. However, ovx rats reached normal amounts of hard tissue within 250 to 450 microns from the growth plate. The results obtained by linear scanning suggest that the obvious loss of cancellous bone mass in the distal zone of the tibial metaphysis in growing ovx rats is not a consequence of structural changes in the proximal zone.

24,25-Dihydroxyvitamin D 3

Ascorbic acid in a New World monkey family: species difference and influence of stressors on ascorbic acid metabolism.

Like other simian primates, the New World monkey Callithrix jacchus, marmoset, and Saguinus fuscicollis, tamarin, require ascorbic acid as an essential nutrient. For adult marmosets, a daily intake of 15 mg/kg metabolic body weight was found to be necessary to obtain a serum level above the kidney threshold. A survey of the serum ascorbic acid level of marmosets and tamarins in a breeding colony resulted in a vast divergence between the two species, indicating a higher ascorbic acid requirement for tamarins. Unaccustomed trial conditions or additional stressors resulted in a higher catabolism of ascorbic acid to CO2 in both species, measured with 14C labeled material, compared to a higher rate of renal excretion when the animals were accustomed to the metabolic cage. These isotope excretion studies suggest a different metabolic behavior of ascorbic acid in the two species. This is supposedly caused by a higher sensitivity of the tamarins when subjected to the same conditions as marmosets.

Animals

The protein requirement of adult marmosets: nitrogen balances and net protein utilization of milk proteins, soy protein, and amino acid mixtures.

Nitrogen balance studies were conducted in adult male marmosets (Callithrix jacchus) using purified and semipurified diets with protein levels between 0% and 7%. Daily nitrogen loss in a state of prolonged protein free nutrition was 131 +/- 16 mg/kg body weight0.75. Zero nitrogen balance resulted from mean daily intake of 261 mg nitrogen/kg0.75 when high quality protein sources were used. Very low protein intake or the lack of arginine and histidine in an amino acid mixture induced coprophagy. It is concluded that the protein requirement of adult marmosets is very similar to the protein requirement of adult humans (based on metabolic body weight). About 6-7% high quality protein, based on dry matter, suffice to avoid a negative nitrogen balance in all individuals.

Amino Acids

Voltage-dependent and calcium-dependent inactivation of calcium channel current in identified snail neurones.

1. The dependence of Ca2+ current inactivation on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) was studied in TEA-loaded, identified Helix neurones which possess a single population of high-voltage-activated Ca2+ channels. During prolonged depolarization, the Ca2+ current declined from its peak with two clearly distinct phases. The time course of its decay was readily fitted by a double-exponential function. 2. In double-pulse experiments, the relationship between the magnitude of the Ca2+ current and the amount of Ca2+ inactivation was not linear, and considerable inactivation was present, even when conditioning pulses were to levels of depolarization so great that Ca2+ currents were near zero. Similar results were obtained when external Ca2+ was replaced by Ba2+. 3. In double-pulse experiments, hyperpolarization during the interpulse interval served to reprime a portion of the inactivated Ca2+ current for subsequent activation. The extent of repriming increased with hyperpolarization, reaching a maximum between -130 and -150 mV. The effectiveness of repriming hyperpolarizations was considerably increased when Ca2+ was replaced by Ba2+. 4. A significant fraction of inactivated Ca2+ channels can be recovered during hyperpolarizing pulses lasting only milliseconds. If hyperpolarizing pulses were applied before substantial inactivation of Ca2+ current, Ca2+ channels remained available for activation despite considerable Ca2+ entry. 5. The relationship between [Ca2+]i and inactivation was investigated by quantitatively injecting Ca2+-buffered solutions into the cells. The time course of Ca2+ current inactivation was unchanged at free [Ca2+] between 1 x 10(-7) and 1 x 10(-5) M. From 1 x 10(-7) to 1 x 10(-9) M, inactivation became progressively slower, mainly due to a decrease of the amplitude ratio (fast/slow) of the two components of inactivation, which fell from about unity to near zero at 1 x 10(-9) M. In double-pulse experiments, recovery from inactivation was enhanced in neurones that had been injected with Ca2+ chelator. 6. We conclude that inactivation of Ca2+ channels in these neurones depends on both [Ca2+]i and membrane potential. The voltage-dependent process may serve as a mechanism to quickly recover inactivated Ca2+ channels during repetitive firing despite considerable Ca2+ influx. 7. The results are discussed in the framework of a model which is based on two states of inactivation, INV and INCA, which represent different conformations of the inactivating substrate, and which are both reached from a lumped state of activation (A). Inactivation leads to high occupancy of INV during depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Synergistic effects of vitamin D metabolites.

The vitamin D3 metabolites 1 alpha,24R,25- and 1 alpha,25S,26-trihydroxy vitamin D3 and their combinations with 1 alpha,25-dihydroxy vitamin D3 were tested for antirachitic activity in rats, chicken and Japanese quails. The trihydroxylated compounds were found to increase the activity of 1 alpha,25-dihydroxy vitamin D3. Since this synergistic effect is restricted to calcium absorption and bone formation while bone calcium mobilization is unchanged, the combined administration might improve calcium balance. These findings raise the possibility of a more efficient therapy of vitamin D-dependent diseases with limited amounts of 1 alpha,25-dihydroxy vitamin D3.

Animals

Coprophagy in marmosets due to insufficient protein (amino acid) intake.

In the course of experiments to study the minimal protein requirement of common marmosets by nitrogen balance methods, coprophagy was observed. It occurred in most animals fed diets either with a protein content below 6% or lacking histidine/arginine. The protein level of 6% had previously been evaluated as being the minimal protein requirement for maintenance of marmosets.

Animals

Concentrations of vitamin A, beta-carotene and vitamin E in individual bovine follicles of different quality.

The degree of atresia of the follicle had no influence on the intrafollicular concentrations of beta-carotene, vitamin E and cholesterol. This might result from the passive transfer of these substances from blood to follicular fluid bound to high density lipoproteins. However, concentrations of vitamin A in follicular fluid were significantly (P less than 0.001) influenced by follicle quality, with highest concentrations (0.32 microgram/ml) in non-atretic follicles and lowest values (0.15 microgram/ml) in greatly atretic follicles. The higher concentrations of vitamin A in healthy follicles might be due to a local conversion of beta-carotene into vitamin A in follicular structures. By influencing hormone and protein synthesis, vitamin A may have a potential for local modulation of follicular development and therefore be one of the factors controlling recruitment, selection and growth of the dominant follicle in cattle.

Animals

Endogenous N-excretion and minimal protein requirement for maintenance of the common marmoset (Callithrix jacchus).

The protein requirement for maintenance of the marmoset Callithrix jacchus was investigated by factorial calculation via the N balance technique. Six adult male marmosets were fed a protein-free pelleted diet for 22 days. When a low protein diet (6%) was fed in the preperiod, only 7 days were necessary and when fed a higher protein diet (18%) 10 days were necessary to reach a minimum of N excretion during protein depletion. Body weight losses averaged 11% and food intake was 21% lower in the protein free period. The average endogenous urine N (EUN) was 62.1 mg N and endogenous fecal N (EFN) 49.2 mg N/kg W0.75. Body surface losses (BSN) were assumed to be 20 mg N/kg W0.75. The total endogenous loss of 131.3 mg N/kg W0.75 is similar to that of other species. Net protein utilization (NPU) of well balanced proteins, determined near the N equilibrium, was 51.8%. The calculated net protein requirement amounts to 313.6 mg N/kg W0.75, which corresponds to a dietary protein content of 6% in a diet of high caloric density, (about 19-20 MJ/kg dry matter) when the food intake is 3.3% of body weight.

Animal Nutritional Physiological Phenomena