Lack of significant effect of coffee and caffeine on fluoride metabolism in rats

It has been reported that rat plasma fluoride (F) concentrations are higher by up to 100% when F is administered ig in coffee or a caffeine solution compared with when it is administered in water. It was hypothesized that the consumption of caffeinated beverages has contributed to the prevalence of dental fluorosis. The present studies were done to determine the physiological mechanisms for these effects. For approximately 2 h after F was administered in coffee, plasma F concentrations were higher than when administered in water, decaffeinated coffee, or a caffeine solution (3 mg/kg), but the intergroup differences were small and generally not statistically significant. The 4-hour plasma AUC values did not differ with statistical significance. There were no differences among the groups in the renal or extrarenal (skeletal) clearances of F, which suggested that the higher plasma F concentrations in the coffee groups may have been due to a slight and transient increase in absorption rate. The possibility that caffeine per se might elevate endogenous plasma F and calcium concentrations was excluded after caffeine (25 mg/kg) ig without F was given. In addition, the renal excretion, clearance, and fractional renal clearance of calcium did not differ among the groups. The results indicated that decaffeinated coffee and caffeine had no effect on F metabolism, whereas caffeinated coffee appeared to increase the initial absorption rate but not the 4-hour bio-availability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of ovariectomy on bone metabolism in very old rats

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 micrograms/kg BW/48 hours) or progesterone (P; 140 micrograms/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after ovx, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentrations and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.     

Impaired vitamin D metabolism and response in spontaneously diabetic GK rats

Several studies of diabetes mellitus patients have demonstrated abnormalities in calcium, phosphate and vitamin D metabolism. In an earlier study, the authors reported impaired renal processing of phosphate in spontaneously diabetic GK rats, an animal model of type II diabetes mellitus. In the present study, which represents an extension of the earlier study, vitamin D metabolism and response are examined in 20-week-old GK rats. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was found to be lower in GK rats than in Wistar rats. After intraperitoneal administration of 0.5 micrograms/kg 1,25-(OH)2D, serum calcium increased in GK rats, but not in Wistar rats, while serum phosphate remained unchanged in GK rats, but increased in Wistar rats. Although serum 1,25-(OH)2D rose abruptly in 3 h and decreased thereafter in both GK and Wistar rats, the decrease in serum 1,25-(OH)2D at 6 h was more marked in GK rats than in Wistar rats. Serum 24,25-dihydroxyvitamin D was consistently higher in GK rats than in Wistar rats. Northern blotting and dot blotting with use of a cDNA probe for the 24-hydroxylase gene showed an increased expression of the gene in the kidney of GK rats. These results demonstrate impaired vitamin D metabolism in GK rats. Increased activity of 24-hydroxylase, in addition to impaired phosphate metabolism, may play a role in impaired vitamin D metabolism in GK rats.     

Tissue specific-distribution and metabolism of vitamin A are affected by dietary protein levels in rats

The prevalence of human immunodeficiency virus (HIV) in adolescents is difficult to assess as few adolescents consent to testing. This prospective study characterized urban youth requesting HIV testing at two types of health settings, inner-city school-based and hospital-based clinics. Data were obtained on 1652 inner-city youths aged 13 to 19 years who consented to individualized HIV counseling and testing from January 1993 to January 1994. Identified risks for HIV included sexual activity, sexually transmitted disease (STD) history, and substance use by self-report during a confidential structured interview. Data were analyzed using chi-squared analysis. Of the 1652 youth who were counseled, 1602 were from hospital-based clinics. A total of 827 (50%) requested HIV testing. Females accounted for the majority of youth who underwent counseling (79%) and requested HIV testing (75%). However, once counseled, males were more likely to be tested. Risk factors differed by gender; females were more likely to report STDs and marijuana use, and males more likely to report alcohol and cocaine use. These results indicate a need to identify developmentally appropriate methods to educate and counsel youth about HIV that will lead to more youth willing to be tested. School-based clinics may provide easier access than traditional health models for confidential HIV services.     

Inhibitory effect of calcium-binding protein regucalcin on protein kinase activity in the nuclei of regenerating rat liver

PURPOSE: The purpose of this study was to compare the response in contractility of the right (RV) and left (LV) ventricle of the heart to beta-adrenergic stimulation using an echo planar MR technique. METHOD: In six sheep, RV and LV pressure-volume (P-V) relationships were constructed simultaneously using intraventricular pressures and volumes measured with echo planar MRI at rest and during dobutamine stress. Contractility changes were quantified by assessment of the end-systolic P-V relationship (ESPVR) and the preload recruitable stroke work (PRSW). RESULTS: Both the ESPVR the the PRSW showed a significant increase in contractility for both ventricles after dobutamine administration. The increase in contractility was significantly larger for the LV than for the RV, both measured wit the ESPVR (p < 0.0003) and the PRSW (p < 0.007). CONCLUSION: This study shows the usefulness of echo planar MRI to assess myocardial contractility of both ventricles simultaneously. Furthermore, the study shows that beta-adrenergic stimulation has a significantly greater positive inotropic effect on LV contractility than on RV contractility.     

Effect of vitamin D metabolites and analogs on renal and intestinal calbindin-D in the rat

The effects of endotoxin (20 mg kg-1 i.p.) on the mesenteric vascular responses to acetylcholine, bradykinin, sodium nitroprusside, and to transient occlusion of the superior mesenteric artery were examined in rats anesthetized with pentobarbitone. Mesenteric vasodilator responses to close arterial injections of acetylcholine and bradykinin were reduced at 1.5 h after endotoxin and almost abolished by 4 h; responses to sodium nitroprusside were unaffected. Occlusion of the superior mesenteric artery for 30, 60, or 120 s produced, on release of the occlusion, a time-dependent vasodilator response in the mesenteric circulation (post-occlusion hyperemia). This hyperemia was markedly reduced by nitro-L-arginine methyl ester (L-NAME); L-NAME did not modify acetylcholine-induced vasodilation. Endotoxin-pretreatment did not modify mesenteric post-occlusion hyperemia 1.5 h after administration but markedly reduced the response by 2.5 h. The administration of L-NAME to endotoxin-treated rats did not further attenuate the hyperemic responses. Mesenteric vasoconstrictor responses to phenylephrine were not modified by endotoxin, although systemic pressor responses to this agent were impaired. We concluded that endotoxin impairs endothelium and nitric oxide-dependent vasodilator responses in the mesenteric circulation.     

In vitro study of the effect of miglitol on carbohydrate digestion and intestinal metabolism in normal and non-insulin-dependent diabetic rats

The effect of miglitol was studied (20 mg/kg body weight), administered intraduodenally alone or together with maltose, on the absorption and intestinal metabolism of glucose during its translocation from the lumen of the intestine to the blood, using in vitro perfused preparations of complete small intestine-pancreas, proximal small intestine alone, or distal small intestine alone, isolated from normal and non-insulin-dependent diabetic rats. In the absence of a luminal administration of maltose in normal rats, the glucose uptake from the vascular perfusate was greater in the presence (0.52 +/- 0.04 mmol/h) than in the absence (0.39 +/- 0.02 mmol/h) of miglitol (p < 0.05). In diabetic rats, no significant variations were observed in glucose uptake from the vascular perfusate as an effect of miglitol, but the glucose uptake in the presence of this drug was significantly less (p < 0.05) than that observed in normal rats. Portal lactate was significantly greater (p < 0.05) in diabetic than in normal rats and, after administration of miglitol, rose in both normal and diabetic rats, the rise being significantly greater in normal than in diabetic rats (p < 0.01). When maltose was administered luminally (2 g/kg body weight), the values of portal glucose in both normal and diabetic rats were significantly less in the presence of miglitol in the complete as well as in the distal and proximal small intestine preparations (p < 0.05); the glucose uptake from luminal administered maltose was greater in the presence of miglitol in diabetic (p < 0.05) and in normal (p < 0.05) rats except in the complete small intestine of normal rats; and no significant differences were observed in portal lactate levels between normal and diabetic rats in the presence of miglitol. In conclusion, our results show that miglitol administered luminally at the doses employed here, as well as reducing the transport of glucose from the lumen of the intestine into the blood supply, significantly stimulate intestinal glucose metabolism.     

过量维生素E摄入对大鼠脂代谢的影响

目的:探讨摄入大剂量维生素E(VE)对大鼠脂代谢的影响,为VE摄入限量值的确定提供实验依据.方法:28只成年健康雌性Wistar大鼠随机分为正常对照组、低剂量VE组(400 mg·kg-1)、中剂量VE组(800 mg·kg-1)和高剂量VE组(1600 mg·kg-1),每天定时采用灌胃方法给予VE,定期根据体质量调整剂量,给药16 d后,经眼球采血,检测血清中总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白(HDL-C)等生化指标;处死大鼠取肝、肾、脾,计算上述脏器的脏体比.结果:与正常对照组比较,低、中和高剂量VE组大鼠饮水、进食量减少,状态及活动欠佳;与正常对照组和低剂量VE组比较,中、高剂量VE组大鼠体质量降低(P<0.05);与正常对照组比较,VE各剂量组大鼠肝/体比、肾/体比和脾/体比差异无统计学意义(P>0.05).与正常对照组比较,中、高剂量VE组大鼠血清中TC、TG和HDL-C水平均显著降低(P<0.05);与低剂量VE组比较,中、高剂量VE组TC、TG和HDL-C水平均显著降低(P<0.05);中、高剂量VE组之间比较差异无统计学意义(P>0.05).结论:大剂量VE抑制大鼠的生长,过量口服会降低体内HDL-C、TC和TG的合成,不利于脂代谢,提示不建议大量补充VE.     

Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein

A line of mice deficient in vitamin D binding protein (DBP) was generated by targeted mutagenesis to establish a model for analysis of DBP's biological functions in vitamin D metabolism and action. On vitamin D-replete diets, DBP-/- mice had low levels of total serum vitamin D metabolites but were otherwise normal. When maintained on vitamin D-deficient diets for a brief period, the DBP-/-, but not DBP+/+, mice developed secondary hyperparathyroidism and the accompanying bone changes associated with vitamin D deficiency. DBP markedly prolonged the serum half-life of 25(OH)D and less dramatically prolonged the half-life of vitamin D by slowing its hepatic uptake and increasing the efficiency of its conversion to 25(OH)D in the liver. After an overload of vitamin D, DBP-/- mice were unexpectedly less susceptible to hypercalcemia and its toxic effects. Peak steady-state mRNA levels of the vitamin D-dependent calbindin-D9K gene were induced by 1,25(OH)2D more rapidly in the DBP-/- mice. Thus, the role of DBP is to maintain stable serum stores of vitamin D metabolites and modulate the rates of its bioavailability, activation, and end-organ responsiveness. These properties may have evolved to stabilize and maintain serum levels of vitamin D in environments with variable vitamin D availability.     

The high affinity calcium-binding sites in the epidermal growth factor module region of vitamin K-dependent protein S

Vitamin K-dependent protein S, a cofactor of the anticoagulant enzyme-activated protein C, has four epidermal growth factor (EGF)-like modules, all of which have one partially hydroxylated Asp (EGF 1; beta-hydroxyaspartic acid) or Asn (EGF 2, 3, and 4; beta-hydroxyasparagine) residue. The three C-terminal modules have a typical Ca2+ binding sequence motif that is usually present in EGF modules with hydroxylated Asp/Asn residues. Using the chromophoric Ca2+ chelators Quin 2 and 5,5'-Br2BAPTA, we have now determined the Ca2+ affinity of recombinant fragments containing EGF modules 1-3, 1-4, 2-3, and 2-4. EGF modules 1-4 and 2-4 each contains two very high affinity Ca2+-binding sites, i.e. with dissociation constants ranging from 10(-10) to 10(-8) M in the absence of salt and from 10(-8) to 10(-6) M in the presence of 0.15 M NaCl. In contrast, in EGF 1-3 and EGF 2-3, the Ca2+ affinity is 2-4 orders of magnitude lower. EGF 4 thus appears to have the highest Ca2+ affinity, and furthermore it seems to influence the Ca2+ affinity of its immediate N-terminal neighbor EGF 3 by a factor of approximately 230. In addition, EGF 4 seems to influence the Ca2+ affinity of EGF 2 by a factor of approximately 25. The Ca2+ affinity of the binding sites in EGF modules 3 and 4 in fragments EGF 1-4 and EGF 2-4 is 10(3)-10(5)-fold higher than in the corresponding isolated modules, implying important contributions to the Ca2+ affinity of each module from interactions with neighboring modules. This difference is much higher than the approximately 10-fold difference previously found in similar comparisons of EGF modules from fibrillin. However, the modules studied in protein S and fibrillin appear to have the similar Ca2+ ligands. The structural basis for the difference in Ca2+ affinity is not yet understood.     

Effectiveness of estradiol in preventing and reversing obesity induced by ovariectomy and high-caloric diet in female rats.

Four experiments with 77 female Holtzman rats examined the effects of estradiol benzoate (EB) on food intake, body weight (BW), ano-nasal length, and BW/body length ratio in ovariectomized (OVX) and intact Ss maintained on control or high-fat diets and of OVX and intact Ss that had been reduced by deprivation. EB was highly effective in preventing the increase in food intake, BW, and ano-nasal growth after OVX; it was relatively ineffective in reversing BW gain after OVX. However, when ano-nasal length was also considered, BW was effective in returning OVX Ss to an appropriate BW for their increased ano-nasal length. Intact Ss fed a high-caloric diet did not exhibit an increased rate of ano-nasal growth, which indicates that the skeletal growth that occurred after OVX was not simply a result of increased food intake. It is concluded that EB modulates food intake and BW by multiple mechanisms, one of which is by modulating skeletal growth. The nature of the effect of EB on BW of intact Ss suggests that this effect occurs by still another mechanism. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fetal thymus development in vitamin D deficient rats

A specifically designed handpiece has been developed for ultrasonic dissection of tissues and organs during minimal-access surgery. The experimental prototype has been evaluated in major endoscopic operations on the esophagus, colon, and rectum (n = 19). The benefits documented by this initial experience include increased dissection efficiency of extensive fibroareolar attachments, safe exposure of major vascular pedicles (especially those located in mesocolic fat), greatly reduced risk of major hemorrhage, and decreased operating time.     

Experimental nephrolithiasis in rats: the effect of ethylene glycol and vitamin D3 on the induction of renal calcium oxalate crystals

Using ethylene glycol (EG) and vitamin D3 as crystal-inducing diet (CID) in rats, we investigated the effect of the dosage of EG on the generation of chronic calcium oxalate (CaOx) nephrolithiasis. We collected weekly 24 hour urines and measured herein the amount of oxalate, calcium, glycosaminoglycans (GAG's), creatinine, protein, alkaline phosphatase (AP), gamma-glutamyl transpeptidase (gamma-GT), and N-acetyl-beta-glucosaminidase (NAG). The potential of these urines to inhibit crystal growth and agglomeration was also evaluated. After four weeks, the kidneys were screened by histology and radiography for the presence of CaOx crystals and the amount of kidney-associated oxalate was biochemically measured. Using 0.5 vol.% EG, only a part of the rats showed CaOx deposition in the renal cortex and/or medulla, without obvious differences between Wistar and Sprague-Dawley (SD) rats. If a dietary EG concentration of 0.75, 1.0, or 1.5 vol.% was used, the amount of kidney-associated oxalate was proportionally higher and CaOx crystal formation was consistently found in all rats. Most crystals were encountered in the cortex, whereas in the medulla and the papillary region, crystals were only occasionally detected. From these data, we conclude that in the chronic rat model, based on EG and vitamin D3, a consistent deposition of CaOx crystals is obtained using a EG concentration of at least 0.75%.     

The effect of certain vitamin deficiencies on hepatic drug metabolism

There is increasing evidence that the liver microsomal drug metabolizing system is affected by various vitamins such as ascorbic acid, riboflavin, and alpha-tocopherol. In regard to ascorbic acid deficiency there is a decrease in the quantity of hepatic microsomal electron transport components such as cytochrome P-450 and NADPH-cytochrome P-450 reductase, as well as decreases in a variety of drug enzyme reactions such as N-demethylation, O-demethylation, and steroid hydroxylation. In addition, young animals given high supplements of vitamin C have increased quantities of electron transport components and overall drug metabolism activities. Kinetic studies indicate no change in the apparent Km of N-demethylase, O-demethylase or hydroxylase for drug substrates in animals depleted or given high amounts of the vitamin. However, there are qualitative changes in both type I and II substrate-cytochrome P-450 binding. Ascorbic acid is not involved in microsomal lipid peroxidation or in any qualitative or quantitative change in phosphatidylcholine. Replenishing vitamin C-deficient animals with ascorbic acid required 3 to 7 days for the electron transport components and drug metabolism activities to return to normal levels. Induction with phenobarbital and 3-methylcholanthrene is not impaired in the deficient animal since drug metabolism activities are induced to the same extent as normal controls; however, the administration of delta-aminolevulinic acid, a precursor of heme synthesis, to deficient animals caused an increase in the quantity of cytochrome P-450. The effects of riboflavin deficiency on electron transport components and drug metabolism activities have been noted only in adult animals after prolonged periods of deficiency. Decreases in drug metabolism activities occur with both type I (aminopyrine and ethylmorphine) and type II (aniline) substrates. As was found with ascorbic acid deficiency, drug enzyme induction occurred to the same extent with phenobarbital in deficient and normal animals. In addition, it required from 10 to 15 days for the drug metabolism activities to return to normal levels when deficient animals were replenished with riboflavin. The effect of vitamin E on drug metabolism is specific in N-demethylase activities decrease while O-demethylase activities are not affected in the deficient state. This vitamin differs from ascorbic acid and riboflavin in that several laboratories have reported no quantitative decrease in cytochrome P-450, although there are some reports that it and delta-aminolevulinic acid dehydratase are lowered quantity of cytochrome in E-deficient animals. The effect of vitamin E, if any, on the P-450 is unresolved; an important question that requires further clarification. As with ascorbic acid there is no difference in the apparent Km of N-demethylase enzymes for varous substrates and the protective effect of vitamin E does not appear to be one of an antioxidant inhibiting microsomal lipid peroxidation.     

Distribution and metabolism of F6-1,25(OH)2 vitamin D3 and 1,25(OH)2 vitamin D3 in the bones of rats dosed with tritium-labeled compounds

26,26,26,27,27,27-Hexafluo-1,25(OH)2 vitamin D3, the hexafluorinated analog of 1,25(OH)2 vitamin D3, has been reported to be several times more potent than the parent compound regarding some vitamin D actions. The reason for enhanced biologic activity in the kidneys and small intestine appears to be related to F6-1,25(OH)2 vitamin D3 metabolism to ST-232, 26,26,26,27,27,27-hexafluoro-1 alpha, 23S,25-trihydroxyvitamin D3, a bioactive 23S-hydroxylated form that is resistant to further metabolism. Since F6-1,25(OH)2 vitamin D3 is considered to prevent osteoporotic decrease in bone mass by suppressing bone turnover, we here compared the distribution and metabolism of [1 beta-3H]F6-1,25(OH)2 vitamin D3 and [1 beta-3H]1,25(OH)2 vitamin D3 in bones of rats by autoradiography and radio-HPLC. In the dosed groups, radioactivity was detected locally in the metaphysis, the modeling site in bones. As compared with the [1 beta-3H]1,25(OH)2 vitamin D3 case, [1 beta-3H]F6-1,25(OH)2 vitamin D3 was significantly retained in this site, and moreover, it mainly persisted as unchanged compound and ST-232. These findings indicate that the reason for the higher potency of F6-1,25(OH)2 vitamin D3 than 1,25(OH)2 vitamin D3 in bones are linked with increased distribution and reduced metabolism.     

Effect of vitamin D deficiency and 1,25-dihydroxyvitamin D3 on metabolism and D-glucose transport in rat cerebral cortex

We previously demonstrated that feeding rats Steenbock and Black's rickets-inducing diet produces remarkable changes in the metabolic pattern of the intestinal mucosa, kidney, and liver and in some membrane transport systems of intestinal mucosa and kidney. 1,25-Dihydroxyvitamin D3 administration to rachitic rats did not always prove to be effective in restoring normal values. We have now investigated the effect of 1,25-dihydroxyvitamin D3 on the levels of some metabolites in rat cerebral cortex, on the activity of some enzymes, and on the transport of 2-deoxy-D-glucose and D-glucose in synaptosomes. Our experiments were carried out on three rat groups: control, rachitic, and rachitic treated with 1,25-dihydroxyvitamin D3. The decrease in phosphorus content and the increase in citrate concentration observed in rachitic rat cerebral cortex were corrected by 1,25-dihydroxyvitamin D3 treatment. The activity of acetylcholinesterase, glucose-6-phosphate dehydrogenase, and acyl phosphatase significantly increased in rachitic rat synaptosomes, as well as NAD(+)-dependent isocitrate dehydrogenase in cerebral cortex mitochondria; the administration of 1,25-dihydroxyvitamin D3 to rachitic rats restored enzyme levels to normal. The transport of 2-deoxy-D-glucose and D-glucose in rachitic rat synaptosomes was lower than in the control group and returned to control values in consequence of 1,25-dihydroxyvitamin D3 treatment. The results reported here support the hypothesis of a participation of 1,25-dihydroxyvitamin D3 in some aspects of cerebral cortex metabolism.     

Lack of effect of spaceflight on bone mass and bone formation in group-housed rats

As part of an experiment to study the role of corticosteroids in bone changes during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs) aboard the space shuttle Columbia (STS-78). Control rats were group housed in a similar manner in ground-based AEMs or standard vivarium cages. Adrenal hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed a lack of significant changes in bone mass and bone formation in these animals. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were nearly the same in flight and ground-based rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation rate was found to be identical in flight and ground-based rats. The results indicate that, under conditions of group housing in AEMs, spaceflight has minimal effects on bone mass and bone formation in rapidly growing rats. These findings emphasize the need to investigate the importance of rat age, strain, and especially housing conditions for studies of the skeletal effects of spaceflight.