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Biomedical subjects

C Ritter

Publications and source records attributed to C Ritter.

At least 37 records · Page 2Linked to original sources

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Dietary phosphorus (P) restriction is known to ameliorate secondary hyperparathyroidism in renal failure patients. In early renal failure, this effect may be mediated by an increase in 1,25-(OH)2D3, whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH)2D3 and serum ionized calcium (ICa). In this study, we examined the effects of dietary P on serum PTH, PTH mRNA, and parathyroid gland (PTG) hyperplasia in uremic rats. Normal and uremic rats were maintained on a low (0.2%) or high (0.8%) P diet for 2 mo. PTG weight and serum PTH were similar in both groups of normal rats and in uremic rats fed the 0.2% P diet. In contrast, there were significant increases in serum PTH (130 +/- 25 vs. 35 +/- 3.5 pg/ml, P < 0.01), PTG weight (1.80 +/- 0.13 vs. 0.88 +/- 0.06 microg/gram of body weight, P < 0.01), and PTG DNA (1.63 +/- 0.24 vs. 0.94 +/- 0.07 microg DNA/gland, P < 0.01) in the uremic rats fed the 0.8% P diet as compared with uremic rats fed the 0.2% P diet. Serum ICa and 1,25-(OH)2D3 were not altered over this range of dietary P, suggesting a direct effect of P on PTG function. We tested this possibility in organ cultures of rat PTGs. While PTH secretion was acutely (30 min) regulated by medium calcium, the effects of medium P were not evident until 3 h. During a 6-h incubation, PTH accumulation was significantly greater in the 2.8 mM P medium than in the 0.2 mM P medium (1,706 +/- 215 vs. 1,033 +/- 209 pg/microg DNA, P < 0.02); the medium ICa was 1.25 mM in both conditions. Medium P did not alter PTH mRNA in this system, but cycloheximide (10 microg/ml) abolished the effect of P on PTH secretion. Thus, the effect of P is posttranscriptional, affecting PTH at a translational or posttranslational step. Collectively, these in vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH)2D3.

Analysis of Variance↗

Weight, self-esteem, ethnicity, and depressive symptomatology during pregnancy among inner-city women.

The relationship of weight and self-esteem to depressive symptomatology was examined among 36 African American and 96 European American pregnant inner-city women. Lower self-esteem and higher deviations from medically ideal weight predicted increased dysphoria during the 3rd trimester for European American women, but only lower self-esteem predicted increased dysphoria for African American women. These results support the hypothesis that African Americans are less likely than European Americans to experience negative psychological repercussions of greater weight. Consistent with findings among nonpregnant middle-class samples, these results extend the association between heavier weight and increased risk for psychological distress to pregnant women of European American descent.

Adolescent↗

Rat calcium-sensing receptor is regulated by vitamin D but not by calcium.

Parathyroid hormone (PTH) secretion is regulated by extracellular calcium acting through a cell surface calcium receptor (CaR). We have examined the potential regulation of the CaR in the parathyroid glands (PTG) and kidney by calcium and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Rats fed vitamin D-deficient (-D) diets containing 0.02, 0.4, or 2.0% Ca had a wide range of serum ionized Ca (2.5-5.2 mg/dl) and PTH (22-590 pg/ml) concentrations. PTG CaR mRNA did not vary significantly with ionized calcium or PTH, indicating that hypocalcemia and hyperparathyroidism may not alter CaR expression. However, PTG CaR mRNA was 40% lower in the -D rats than in age-matched rats fed a vitamin D-replete (+D) diet (P < 0.002). Repletion of -D rats with 1,25-(OH)2D3 produced a dose-dependent increase in PTG CaR mRNA. Treatment of +D rats with 100 ng of 1,25-(OH)2D3 increased CaR mRNA by 33% (P < 0.05) and 54% (P < 0.002) in the PTG and by 89% (P < 0.02) and 91% (P < 0.02) in the kidney in two independent experiments. PTG CaR peaked at 16 h (150% of control, P < 0.05) after 1,25-(OH)2D3 administration but returned to normal by 24 h. This upregulation of CaR expression by 1,25-(OH)2D3 may be involved in the suppressive effects of vitamin D compounds on PTH secretion.

Animals↗

A new glucose sensor for use in whole blood.

Existing electrochemical glucose sensors are either single use sensors produced in mass fabrication technologies or rather big sensors for multiple use with membranes to be changed frequently. Single use means no sensor maintenance but has the disadvantage that quality control measurements cannot be done with the same sensor used for the sample. Generally also the cost per test is relatively high. Multiple use sensors give the possibility of closer quality control and they are generally cheaper than the single use sensors for higher sample frequency but have the disadvantage of frequent need of remembraning. This often means special training and is a health risk due to sensor contamination by biological fluids. We combined the advantages of both principles meaning that we developed a new glucose sensor for multiple use in an essentially planar technology - thus being able to be produced very cheap. The underlying basic working principle is using glucose oxidase and detecting hydrogen peroxide. Due to the carbon base of the sensor it has a large surface area and therefore a very high sensitivity (microamps range at biological glucose concentrations) although the sensor itself is very small needing only about 10 microL of sample. The sensor shows a linear range of up to 40 mmol/L, a life time in use of far more than 1000 human serum samples and correlation coefficients between plasma and whole blood of r = 0.99. Interferences are well within clinical acceptability. Thus we conclude that this sensor works well in undiluted human body fluids and due to the very cheap production processes the whole sensor can be exchanged when it is old thus eliminating any need for remembraning or special maintenance.

Blood Glucose↗

More on the measurement of ionized magnesium in whole blood.

Current technology has made it possible to measure ionized magnesium with user-friendly ion selective electrode technology. Although this technology has not reached a perfect status literature shows that it can be used in clinical routine especially in serum. This paper deals with issues concerning the measurement of ionized magnesium in whole blood. To measure in whole blood apart from an instrument with good general performance data an adequate sample treatment is especially critical. We tested a number of different sample containers and found that they interfere in different degrees with the magnesium determination. In some cases this is due to silicone giving falsely high ionized magnesium values which may be twice the real value and even higher. Another problem is the heparinization of the sample. We found that different heparins may alter the result in a different way. The well known complexing capability of heparin may lead to a reduction of the ionized magnesium within the sample and thus to false low results. But some heparins cause elevated results. The reason for this may be zinc. Test procedures to check the quality of anticoagulants are given. Due to these procedures sample containers could be found which do not interfere with the determination of ionized magnesium in whole blood - thus making the measurement possible. All these factors indicate that the measurement of ionized magnesium really needs a very well defined sample handling - otherwise false results may arise. This is not only true for the measurement of whole blood but also for plasma or even for "so called serum" as there might be a sample container within the chain from patient to the instrument which is unsuitable- and thus will alter the result.

Humans↗

The effects of role socialization on the initiation of cocaine use: an event history analysis from adolescence into middle adulthood.

This research examines three relatively unexplored questions about the effects of role socialization on the initiation of cocaine use: (1) What are the effects of adult social roles on the initiation of cocaine use? (2) What are the effects of the life-course timing of entry into adult social roles on the initiation of cocaine use? and (3) What are the effects of life-course timing of the initiation of other drugs -- on the initiation of cocaine use? The data used in these analyses are from a national probability sample of men born between 1944 and 1954, inclusive (N = 1,933). Results indicate that the marital role was the only role which demonstrated a significant effect on the initiation of cocaine use. We find that either early or late entry into the marital role reduces its effect to nonsignificance. The timing of entry in the drug use roles indicates that the later the initiation of drug use the greater the odds of cocaine initiation. Results are discussed in light of the role socialization and developmental perspectives.

Adult↗

Modelling mortality and morbidity of newborns.

Data of 10,514 singleton births collected over a ten year period at a single hospital are analysed and models linking birthweight and gestational age with mortality and morbidity defined by low Apgar scores are constructed and compared. Based on these models, charts of mortality and morbidity are drawn and compared with common charts of birthweight centiles. Classification rules for newborns at risk are defined by iso-mortality contours, marginal birthweight centiles, and birthweight centiles adjusted by gestational age, respectively, and compared using receiver operating characteristic (ROC) curves. The results suggest that, as far as neonatal mortality is concerned, classification rules based on simple marginal birthweight centiles perform almost as well as iso-mortality contours and considerably better than birthweight centiles adjusted for gestational age.

Apgar Score↗

Loss of calcium responsiveness in cultured bovine parathyroid cells is associated with decreased calcium receptor expression.

Suppression of PTH secretion by extracellular calcium is mediated by a plasma membrane calcium receptor (CaR). However, primary cultures of bovine parathyroid cells are known to quickly lose their responsiveness to extracellular calcium. The present study was designed to determine if the loss of calcium responsiveness is due to changes in CaR expression. In primary monolayer cultures of parathyroid cells, calcium-mediated suppression of PTH was still evident after 24 hours in culture but was completely absent after 6 days. This was preceded by a 75% drop in CaR mRNA content within 24 hours. CaR mRNA levels remained low for the 6-day culture. Earlier time points, examined in parathyroid cell suspensions, showed a 70% drop in CaR mRNA by 4 hours after collagenase-dispersion of the glands and an 85% drop after 24 hours. The decreased expression of CaR mRNA was not influenced by altering medium serum, calcium, or 1,25-dihydroxyvitamin D3. Our results indicate that the loss of responsiveness of cultured parathyroid cells to calcium is due to decreased CaR mRNA and, presumably, CaR protein expression.

Animals↗

A new analog of calcitriol, 19-nor-1,25-(OH)2D2, suppresses parathyroid hormone secretion in uremic rats in the absence of hypercalcemia.

The active metabolite of vitamin D, calcitriol (1 alpha,25-(OH)2D3), suppresses parathyroid hormone (PTH) gene transcription. Although 1 alpha,25-(OH)2D3 is effective in suppressing secondary hyperparathyroidism (SH) in uremic patients, the mandatory use of large amounts of calcium salts to control serum phosphorus may preclude, in some patients, the use of ideal therapeutic doses of 1 alpha,25-(OH)2D3 because of hypercalcemia. We have studied a new analog of calcitriol, 19-nor-1 alpha,25-(OH)2D2, that possesses low calcemic and phosphatemic activity. Uremic rats received vehicle, 1 alpha,25-(OH)2D3 (2.0, 4.0, or 8.0 ng/rat) or 19-nor-1,25-(OH)2D2 (8.0, 25 or 75 ng/rat) intraperitoneally (IP) every other day for a period of 8 days. Pretreatment and posttreatment values of intact PTH were measured. The normal values for rat intact-PTH were 22 +/- 4.2 pg/mL and for ionized calcium (ICa) 4.77 +/- .07 mg/dL. The only dose of 1 alpha,25-(OH)2D3 that achieved a significantly, suppressed PTH (P < 0.01) was the 8.0 ng/rat. PTH decreased from 202 +/- 31 to 90 +/- 20 pg/mL. However, ICa increased from 4.81 +/- 0.08 to 5.08 mg/dL from uremic control (P < 0.02). Conversely, all doses of 19-nor-1,25-(OH)2D2 were effective in suppressing PTH, and none produced an elevation in ICa that was significantly different from that of vehicle-treated uremic rats. The maximum effect was achieved with the 75 ng/rat dose, which decreased PTH from 193 +/- 49 to 53 +/- 16 pg/mL (a decrease in 72.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Depression prevalence and incidence among inner-city pregnant and postpartum women.

A sample of 192 financially impoverished, inner-city women was assessed for clinical depression twice during pregnancy and once postpartum. At the first and second antepartum interviews, respectively, 27.6% and 24.5% of the women were depressed, controlling for pregnancy-related somatic symptoms. Postpartum depression was found among 23.4% of women. These rates are about double those found for middle-class samples. Particularly heightened risk for antepartum depression was found among single women who did not have a cohabiting partner. African American and European American women did not differ in rates of depression. Antepartum depression was a weak but significant risk factor for postpartum depression.

Adolescent↗

The roles of calcium and 1,25-dihydroxyvitamin D3 in the regulation of vitamin D receptor expression by rat parathyroid glands.

Expression of the vitamin D receptor (VDR) in the parathyroid glands is decreased in secondary hyperparathyroidism associated with chronic renal failure by undefined mechanisms. In the present study, we examined the effects of hyperparathyroidism and dietary calcium and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on the expression of VDR in rat parathyroid glands. Vitamin D-deficient rats were maintained on diets containing 0.02% Ca (-D, LCD), 0.4% Ca (-D, NCD), or 2.0% Ca (-D, HCD) for 6 weeks. Serum ionized Ca (ICa) in the rats on the three diets ranged from 2.5-5.2 mg/dl. Serum PTH ranged from 22-590 pg/ml and correlated inversely with ICa (r = -0.835; P < 0.001). Rats with the highest ICa had normal PTH values, suggesting that vitamin D deficiency per se does not lead to hyperparathyroidism. VDR messenger RNA (mRNA) levels in the parathyroid glands correlated positively with ICa (r = 0.845; P < 0.001) and negatively with PTH (r = -0.716; P < 0.001). VDR mRNA levels in the rats fed the -D, HCD were 6 times higher than those receiving -D, LCD and the same as those in rats fed a normal (Purina) diet. Thus, prevention of hyperparathyroidism with high dietary calcium prevented the drop in VDR expression. Treatment of the rats on all three diets with 0, 25, or 100 ng 1,25-(OH)2D3, ip, 48 and 12 h before death dose dependently increased ICa and decreased PTH, as expected, and also increased parathyroid gland VDR mRNA. This coordinate regulation of VDR mRNA by calcium and 1,25-(OH)2D3 was also observed in the kidney, but intestinal VDR mRNA was not stimulated by dietary calcium or 1,25-(OH)2D3. Analysis of covariance for parathyroid gland VDR mRNA and ICa for the three doses of 1,25-(OH)2D3 revealed no significant independent effect of 1,25-(OH)2D3 on VDR mRNA, suggesting that the up-regulation of VDR expression by 1,25-(OH)2D3 in the parathyroid glands may be mediated primarily by increasing serum calcium.

Animals↗

Machine milking of dairy goats during lactation: udder anatomy, milking characteristics, and blood concentrations of oxytocin and prolactin.

Forty-four goats were milked and milk flow recorded without or with 1 min manual prestimulation in early, mid and late lactation. Ultrasound measurements of cross sections of the whole mammary gland were performed in a water bath. In additional experiments with 15 goats, milk flow was recorded and frequent blood samples were taken for the determination of oxytocin and prolactin concentrations. Milk yield increased from the first to the third lactation and decreased markedly during the course of lactation. Average and peak milk flow rates were closely related to the actual milk yield. The ultrasound cisternal area was 27.4 +/- 1.5% of the entire udder half cross section. Milking characteristics were scarcely different without or with prestimulation, although oxytocin was released within 30 s after the start of prestimulation, whereas oxytocin concentrations without prestimulation increased only after the start of milking. Concentrations of prolactin were higher during July and August than in April, and increased similarly with or without prestimulation during milking. In contrast to dairy cows, prestimulation and an opportune release of oxytocin during milking does not significantly influence the course of milk flow in goats, and this is probably because large amounts of cisternal milk allow milk ejection to be induced only after the start of milking without causing bimodal or otherwise reduced milk flow.

Animals↗

Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture.

1,25-dihydroxyvitamin D3[1,25(OH)2D3] suppresses parathyroid hormone (PTH) gene transcription. Recent evidence suggests that retinoid X receptors are involved in 1,25(OH)2D3-mediated transcriptional events. However, little data exists for a role of retinoids in parathyroid function or in PTH expression. In the present study, we observed that all-trans- or 9-cis retinoic acid suppressed the release of PTH from bovine parathyroid cell cultures. Both retinoids were remarkably potent with significant decreases evident at 10(-10) M and a maximally suppressive effect (approximately 65%) at 10(-7) M. All-trans-retinol was considerably less potent in this system. The effect was not evident until 12 h, suggesting that retinoids did not affect the rapid secretion of preexisting PTH stores. PreproPTH mRNA levels were also suppressed by retinoic acid and the retinoid potencies were similar to those observed in the secretion studies. Combined treatment with 10(-6) M retinoic acid and 10(-8) M 1,25(OH)2D3 more effectively decreased PTH secretion and preproPTH mRNA than did either compound alone. These data indicate that retinoic acid: (a) elicits a bioresponse in bovine parathyroid cells; (b) attenuates PTH expression at the protein and mRNA levels, and (c) acts independently of 1,25(OH)2D3 in the control of PTH expression.

Animals↗

The mechanism for the disparate actions of calcitriol and 22-oxacalcitriol in the intestine.

22-Oxacalcitriol (OCT) is one of several new analogs of vitamin D that retain many of the therapeutically useful properties of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], but have much less calcemic activity. In the present study we examined the actions of OCT on intestinal calcium absorption and calbindin D9k mRNA in vitamin D-deficient rats. After ip injection of OCT (1 microgram/kg), calcium absorption increased significantly by 2 h and was maximal at 4 h (2.5-fold above control), but returned to pretreatment levels by 16 h. In contrast, the same dose of 1,25-(OH)2D3 caused a 3-fold increase in calcium absorption, which lasted more than 48 h. The transient effect of OCT on calcium absorption was also observed when the analog was infused at a dose of 1 micrograms/kg.day for 3 days. At the end of the infusion period, calcium absorption was 3-fold higher than that in vehicle-infused controls, but fell to pretreatment levels by 24 h after removing the minipumps. The time courses for induction of calbindin D9k mRNA were similar for OCT and 1,25-(OH)2D3, with no change observed until more than 4 h after injection. However, calbindin mRNA levels returned to pretreatment values more rapidly in the OCT-treated rats. Consistent with these findings, we observed that a 1 microgram/kg dose of [3H] OCT was completely cleared by 4-6 h after injection. This was paralleled by a loss of [3H]OCT associated with the intestinal vitamin D receptor. The rapid clearance of OCT is probably due to its low affinity for the serum vitamin D-binding protein. This low affinity would also be expected to allow greater accessibility to target cells. In support of this, we found that higher amounts of OCT than 1,25-(OH)2D3 were associated with the intestinal vitamin D receptor after the injection of several doses of these tritiated ligands. In summary, our results indicate that the pharmacokinetic properties of OCT are responsible at least in part for its low calcemic activity. Furthermore, comparison of the transient elevation of calcium absorption by OCT with its more prolonged effects on PTH and calbindin D9k indicates that each action of vitamin D compounds has a distinct biological half-life. The short circulating half-life of OCT can exploit these differences to provide a therapeutic advantage in the treatment of vitamin D-responsive diseases.

Animals↗