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Biomedical subjects

M Denda

Publications and source records attributed to M Denda.

At least 37 records · Page 2Linked to original sources
PubMed1999

Some magnesium salts and a mixture of magnesium and calcium salts accelerate skin barrier recovery.

The effects of four different magnesium salts on the cutaneous barrier recovery rate after barrier disruption were evaluated. We spread an aqueous solution of each salt on the flank skin of hairless mice, occluded the area with a plastic membrane for 20 min, and then left the skin surface to dry. All of the magnesium salts, except magnesium bis(dihydrogen phosphate), accelerated barrier repair. We next estimated the effects of magnesium chloride aqueous solutions which contained calcium chloride at different molar ratios. When the calcium to magnesium ratio was lower than 1, the mixture accelerated barrier repair. The application of an aqueous solution of 10 mM magnesium chloride and 10 mM calcium chloride was found to hasten the barrier recovery more effectively than a solution of 10 mM magnesium chloride. These results suggest that the effects of these metal ions are different depending on the counter ion and/or the method of application.

Animals↗
PubMed1998

Loss of water from the stratum corneum induces epidermal DNA synthesis in hairless mice.

Many clinical studies have shown that low humidity has a deleterious effect on skin, but the mechanisms involved are poorly understood. To clarify the changes that occur in skin, we examined epidermal cell proliferation in mice kept in a dry (relative humidity < 10%) or a moist (relative humidity > 90%) environment. In animals exposed to low humidity, epidermal DNA synthesis started to increase within 12 h, reaching twice the original level, and the increased level was maintained for up to 5 days. The transepidermal water loss (TEWL) of mice kept for 12 h in the dry environment was the same as that of mice kept in the moist environment, but the skin conductance was lower. The increase in epidermal DNA synthesis following exposure to the dry environment was inhibited by topical application of petrolatum. It is concluded that loss of water from the stratum corneum induces epidermal cell proliferation within 12 h, and this change occurs in the absence of apparent cutaneous barrier dysfunction.

Animals↗
PubMed1998

Dry condition affects desquamation of stratum corneum in vivo.

We examined whether a dry condition actually induces scaly skin in vivo. Hairless mice were kept in a high humidity condition or a low humidity condition and skin changes were examined. Scales appeared on the backs of mice kept for 3 days under the dry condition. The weight of stratum corneum (SC) was increased at this point, and these alterations were not accompanied with hyperproliferation of the nucleated cell layer of the epidermis. A decrease of desmosomal degradation was observed, though, desquamation-related enzyme activity was not altered. The regulation mechanism of desquamation is not yet clear, however, in vitro experiments suggest that the water content in SC is an important factor. The water content of SC was decreased in the dry condition. These results indicate that a dry environment perturbs desmosome degradation in intact SC by decreasing the water content of SC, and the consequent impairment of desquamation in normal skin in vivo may lead to the induction of a scaly skin surface.

Animals↗
PubMed1998

Immobilization-induced and crowded environment-induced stress delay barrier recovery in murine skin.

To examine the effect of stress on skin homeostasis, cutaneous barrier recovery was measured in rate exposed to immobilization stress after tape stripping or sodium dodecyl sulphate treatment. The barrier function was evaluated by measuring transepidermal water loss. Barrier recovery was delayed in rats exposed to stress in comparison with untreated controls. This tendency was observed in both male and female animals. The delay in barrier recovery was blocked by application of the sedative drugs diazepam and chlorpromazine. The barrier recovery rate in mice which were kept at a high population density (10 animals per cage) for 2 weeks was slower than that in mice kept at lower population densities (five animals or one animal per cage). These animal models could be useful for objectively quantifying the influence of stress on the cutaneous function.

Animals↗
PubMed1998

Cholesterol sulfate inhibits proteases that are involved in desquamation of stratum corneum.

We previously reported that desmosomes play a key role in the adhesion of corneocytes, and their digestion by two types of serine proteases leads to desquamation. Patients with recessive X-linked ichthyosis show hyperkeratosis attributable to desmosomes, associated with an increased content of cholesterol sulfate (CS) and an increased thickness of stratum corneum. In this study, therefore, we examined the possibility that CS provokes the abnormal desquamation, acting as a protease inhibitor. Scaling was induced on mice after topical application of chymostatin and leupeptin. Visible scale was also observed on mice after topical application of CS. We found that the stratum corneum thickness of CS-treated mice was increased in comparison with that of vehicle-treated mice. The thickness of the epidermis and the labeling index with proliferating cell nuclear antigen from CS-treated mice was almost the same as that from vehicle-treated mice. Moreover, in the stratum corneum of CS-treated mice, the content of desmosomes was higher than that in vehicle-treated mice. CS also inhibited the protease-induced cell dissociation of human stratum corneum sheets. In vitro, CS competitively inhibited both types of serine protease: the Ki for trypsin was 5.5 x 10(-6) M and that for chymotrypsin was 2.1 x 10(-6) M. These results indicate that CS retards desquamation by acting as a protease inhibitor. Thus, accumulation of stratum corneum in recessive X-linked ichthyosis may be a result of the inhibition by excessive CS of proteases involved in the dissolution of desmosomes, required for desquamation of the stratum corneum.

Animals↗
PubMed1998

Exposure to a dry environment enhances epidermal permeability barrier function.

Previous studies have suggested that transepidermal water movement may play an important role in epidermal homeostasis and barrier repair. Here we analyzed cutaneous barrier function, epidermal morphology, and lipid content of the stratum corneum in hairless mice maintained in a high relative humidity (RH > 80%) versus low humidity (RH < 10%) environment for 2 wk. Basal transepidermal water loss was reduced by 31% in animals maintained in a dry versus humid environment. Moreover, the number of lamellar bodies in stratum granulosum cells, the extent of lamellar body exocytosis, and the number of layers of stratum corneum increased in animals kept in a dry environment. Furthermore, the dry weight of the stratum corneum and the thickness of the epidermis also increased in a dry environment. In addition, total stratum corneum lipids increased but lipid analysis revealed no significant differences in lipid distribution. Lastly, barrier recovery following either acetone treatment or tape stripping was accelerated after prolonged prior exposure to a dry environment, while conversely, it was delayed by prior exposure to a humid environment. These studies demonstrate that environmental conditions markedly influence epidermal structure and function, and suggest mechanisms by which the environment could induce or exacerbate various cutaneous disorders.

Animals↗
PubMed1998

Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses.

Although seasonal changes in humidity are thought to exacerbate various skin diseases, whether these flares can be attributed to prolonged exposure to extremes in environmental humidities has not been studied systematically. We recently showed that prolonged exposure to high versus low humidities induced profound changes in epidermal structure and permeability barrier homeostasis. Therefore, we asked here whether comparable extremes in humidity could initiate not only homeostatic, but also potentially pathophysiologic alterations. We showed first that exposure to low humidity increases epidermal DNA synthesis in normal murine epidermis. Moreover, exposure to a low humidity for 48 h further amplifies the DNA synthetic response to barrier disruption, resulting in marked epidermal hyperplasia. Additionally, exposure to a dry environment for 48 h prior to barrier disruption results in dermal mast cell hypertrophy, degranulation, as well as histologic evidence of inflammation. To demonstrate the role of changes in external moisture on these phenomena, we applied either an occlusive, water-impermeable plastic membrane, Petrolatum, or a nonocclusive humectant, both to nonperturbated and to perturbed skin. All three forms of treatment prevented the epidermal hyperplasia and dermal mast cell hypertrophy and degranulation induced by exposure to low humidity. These studies indicate that (i) exposure to changes in environmental humidity alone induces increased keratinocyte proliferation and markers of inflammation, and (ii) that these changes are attributable to changes in stratum corneum moisture content. Finally, these studies provide evidence that changes in environmental humidity contribute to the seasonal exacerbations/amelioration of cutaneous disorders, such as atopic dermatitis and psoriasis, diseases which are characterized by a defective barrier, epidermal hyperplasia, and inflammation.

Acetone↗
PubMed1998

Recessive x-linked ichthyosis: role of cholesterol-sulfate accumulation in the barrier abnormality.

Cholesterol sulfate is a multifunctional sterol metabolite, produced in large amounts in squamous keratinizing epithelia. Because patients with recessive x-linked ichthyosis display not only a 10-fold increase in cholesterol sulfate, but also a 50% reduction in cholesterol, we assessed here whether cholesterol sulfate accumulation and/or cholesterol deficiency produce abnormal barrier function in recessive x-linked ichthyosis. Patients with recessive x-linked ichthyosis display both an abnormal barrier under basal conditions, and a delay in barrier recovery after acute perturbation, which correlate with minor abnormalities in membrane structure and extensive lamellar-phase separation. Moreover, both the functional and the structural abnormalities were corrected by topical cholesterol. Yet, topical cholesterol sulfate produced both a barrier abnormality in intact skin and extracellular abnormalities in isolated stratum corneum, effects largely reversed by coapplications of cholesterol. Together, these results suggest that cholesterol sulfate accumulation rather than cholesterol deficiency is responsible for the barrier abnormality. Despite the apparent importance of cholesterol sulfate-to-cholesterol processing for normal barrier homeostasis, neither steroid sulfatase activity nor mRNA levels are upregulated following acute perturbations. These results demonstrate both a potential role for cholesterol sulfate-to-cholesterol processing in normal permeability barrier homeostasis, and that basal levels of steroid sulfatase are sufficient to accommodate acute insults to the permeability barrier.

Administration, Topical↗
PubMed1998

The relationship between pentosidine and hemodialysis-related connective tissue disorders.

Dialysis-related amyloidosis (DRA), such as destructive spondyloarthropathy (DSA) and carpal tunnel syndrome (CTS), occurs in the connective tissues of patients on long-term hemodialysis (HD). Recently, it was suggested that advanced glycation end products (AGEs) and beta2-microglobulin (beta2m) modified with AGEs are related to DRA. The aim of this study is to elucidate whether serum levels of pentosidine, which is an AGE, relate to the occurrence of DRA in patients with long-term HD. 127 end-stage renal failure patients, with DSA or CTS and undergoing HD, were examined. Serum pentosidine was measured by the HPLC method with column switching. Beta2m and intact parathyroid hormone (i-PTH) were measured. Pentosidine levels were significantly elevated in the DSA, CTS, and DRA groups (patients in the DRA group had either DSA and/or CTS). There were no significant differences in the beta2m and i-PTH levels between any group. The duration of HD did not correlate with either pentosidine or beta2m levels, but did with i-PTH. Receiver-operating characteristic (ROC) analysis was performed to examine the discriminatory ability of pentosidine, beta2m, and i-PTH for DRA. The area under the ROC curve was the greatest for pentosidine. Serum beta2m levels were not related with the occurrence of DRA. The fact that serum pentosidine was higher in DRA than in non-DRA indicates that it has potential as an indicator of the occurrence of DRA in long-term HD patients.

Adult↗
PubMed1998

Modification of LC phenotype and suppression of contact hypersensitivity response by stress.

BACKGROUND: Stress is thought to exacerbate a number of diseases, some of which are skin disorders. Epidermal Langerhans' cells play a major role in cutaneous immune reactions. OBJECTIVE: The effects of two types of stress on the cutaneous immune system were to be assessed in mice. METHODS: Mice received stress by immobilization or housing at various population densities. Epidermal sheets were stained for I-A molecules (a member of class II major histocompatibility complex) and analyzed with a confocal-laser- scanning microscope. Contact hypersensitivity reaction to 2,4,6-trinitrochlorobenzene was elicited in mouse ears. RESULTS: The cell density, intensity of I-A expression, and number of dendrites were decreased as the population density increased. Elicitation of contact hypersensitivity was suppressed in mice that received either population or immobilization stress. Increased I-A expression and number of dendrites were observed in adrenalectomized compared to sham-operated mice. The population-dependent suppression of contact hypersensitivity reaction was not observed in adrenalectomized mice. After incubation with serum from mice that received either immobilization stress or population stress, the expression of I-A molecules on a XS52 Langerhans' cell-like cell line was reduced. CONCLUSION: Stress affected the cutaneous immune system. There were indications that adrenergic hormones played a role in the regulation of the system.

Adrenalectomy↗
PubMed1998

Characteristics of biochemical markers in patients with metabolic bone disorders.

Biochemical markers of bone turnover are expected to have some different characteristics among bone metabolic disorders. We compared bone formation markers: serum total alkaline phosphatase (s-Alp), serum osteocalcin (s-OC) and serum carboxy-terminal propeptide of type I collagen (s-PICP); and bone resorption markers: serum carboxy-terminal telopeptide of type I collagen (s-ICTP), urinary pyridinoline (u-Pyr) and urinary deoxypyridinoline (u-Dpyr) to examine which marker is the most suitable and reliable to evaluate bone turnover in patients with osteoporosis (n = 29), osteomalacia (n = 10), primary hyperparathyroidism (n = 6) and renal osteodystrophy (n = 21). The value of s-Alp in the osteomalacia group was significantly higher than those in the normal control group and the osteoporosis group (p < 0.001), and T-score of s-Alp was significantly higher than those of s-OC and s-PICP in the osteomalacia group. The values of u-Pyr and u-Dpyr in the primary hyperparathyroidism group were significantly higher than those in the other groups (p < 0.001). S-PICP, which are not dependent upon renal function, was much higher in the renal osteodystrophy group than in all other groups. In the osteoporosis group, T-score of s-ICTP was significantly higher than those of s-OC. Thus, s-Alp was a good marker in osteomalacia, u-Pyr and u-Dpyr in primary hyperparathyroidism, s-PICP in renal osteodystrophy, and s-ICTP in osteoporosis.

Adult↗
PubMed1997

Epidermal injury stimulates prenylation in the epidermis of hairless mice.

Isoprenylation is the covalent attachment of isoprenyl groups, intermediates of the cholesterol biosynthesis pathway, to carboxyl terminal cysteine residues of proteins. Numerous proteins are isoprenylated including small GTP binding proteins, trimeric G proteins, and nuclear lamins, and these prenylated proteins regulate a variety of cell functions, including cell growth, cytokinesis, and differentiation. Here, we quantitated protein prenylation and determined which proteins are prenylated in the epidermis of hairless mice by radiolabeling with 3H-mevalonolactone following acute or chronic epidermal injury. In normal epidermis, four major radiolabeled bands, with molecular weights of 17-26, 48, 54, and 68 kDa, were observed. The levels of each of these bands increased by 24-63% 16 h following acute epidermal injury induced by topical acetone treatment or tape stripping, returning to normal by 24 h. On 2D gel electrophoresis, there were no major differences between the patterns of labeling following barrier disruption. Subacute epidermal injury induced by either acetone or tape stripping twice a day for 7 days and chronic injury induced by feeding an essential fatty acid-deficient (EFAD) diet, also resulted in a significant increase in protein prenylation. As with an acute injury, SDS-PAGE and 2D gel electrophoresis did not reveal marked differences in the pattern of protein prenylation. These results demonstrate that the prenylation of proteins in the epidermis is stimulated by injury, suggesting that one or more of these prenylated species may be important in epidermal proliferation or differentiation.

Alkyl and Aryl Transferases↗
PubMed1997

A new analog of 1,25-(OH)2D3, 19-NOR-1,25-(OH)2D2, suppresses serum PTH and parathyroid gland growth in uremic rats without elevation of intestinal vitamin D receptor content.

We have previously reported that 19-nor-1,25-(OH)2D2, a new analog of 1,25-(OH)2D3, suppresses parathyroid hormone (PTH) secretion in uremic rats in the absence of hypercalcemia or hyperphosphatemia. In the current study, we examined the effect of 19-nor-1,25-(OH)2D2 on parathyroid gland growth and intestinal vitamin D receptor (VDR) content. After induction of uremia by 5/6 nephrectomy, rats were divided into five experimental groups and received intraperitoneal injections of vehicle, 1,25-(OH)2D3 (2 or 6 ng/rat), or 19-nor-1,25-(OH)2D2 (25 or 100 ng/rat) three times a week for 8 weeks. Twelve normal rats received vehicle and served as the normal control group. During the course of the study, rats were maintained on a 1.0% calcium and 0.8% phosphorus diet. The higher dose of 1,25-(OH)2D3, 6 ng, significantly decreased PTH from 52.7 +/- 10.2 pg/mL in the uremic control group to 25.7 +/- 6.7 pg/mL (P < 0.01). This dose of 1,25-(OH)2D3, however, increased serum levels of both ionized calcium (4.71 +/- 0.05 to 4.85 +/- 0.06 mg/dL; P < 0.05) and phosphorus (4.34 +/- 0.30 to 6.67 +/- 0.63 mg/dL; P < 0.01). Both doses of 19-nor-1,25-(OH)2D2 decreased serum PTH as effectively as 1,25-(OH)2D3 without changes in serum calcium or phosphorus. The 100-ng dose of 19-nor-1,25-(OH)2D2 decreased PTH to 20.7 +/- 3.1 pg/mL (P < 0.01) and suppressed parathyroid gland growth by more than 50%. Both doses of 19-nor-1,25-(OH)2D2 also decreased endogenous 1,25-(OH)2D3 levels compared with uremic control rats (25 ng:30.4 +/- 2.0, P < 0.05, and 100 ng:27.9 +/- 3.2, P < 0.01, v 48.4 +/- 6.6 pg/mL). The 6-ng dose of 1,25-(OH)2D3 elevated intestinal VDR content (138.5 +/- 20.0 fmol/mg protein) compared with animals receiving both doses of 19-nor-1,25-(OH)2D2 (25 ng:84.0 +/- 11.9, P < 0.05, and 100 ng:78.4 +/- 10.9, P < 0.01). This was probably attributable to the marked decrease in endogenous 1,25-(OH)2D3 levels caused by both doses of 19-nor-1,25-(OH)2D2 because intestinal VDR correlated directly with serum 1,25-(OH)2D3 (r = 0.963; P = 0.008). Thus, 19-nor-1,25-(OH)2D2 appears to exert a selective action on the parathyroid glands compared with the intestine. Its low calcemic and phosphatemic properties may result from the decreased endogenous 1,25-(OH)2D3 levels that lead to a reduction in intestinal VDR. This selectivity makes this analog ideal for the treatment of secondary hyperparathyroidism.

Animals↗
PubMed1997

trans-4-(Aminomethyl)cyclohexane carboxylic acid (T-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans.

Because wounding the epidermis increases proteolytic activity and because disorders associated with barrier dysfunction have elevated protease activity, we studied the effect of protease inhibitors on the time course of barrier recovery and on the development of epidermal hyperplasia induced by repeated injury. After injuries to the epidermis produced by tape stripping, acetone treatment, or detergent (SDS) treatment that disrupt the barrier, a single application of 5% tranexamic acid [4-(aminomethyl)cyclohexane carboxylic acid, t-AMCHA], a well known anti-plasmin reagent, accelerated barrier recovery in both hairless mouse and human skin. In contrast, neither aminocaproic acid nor aminobutyric acid, inactive analogs of t-AMCHA, affected the time course of barrier recovery. Several trypsin-like serine protease inhibitors, e.g., leupeptin, TLCK, and PMSF, also accelerated barrier repair. In contrast other types of protease inhibitors, e.g., EDTA, pepstatin, N-ethylmaleimide, chymostatin, and TPCK, did not accelerate barrier recovery. We next evaluated the effects of daily topical application of t-AMCHA on epidermal hyperplasia, induced by repeated tape stripping or acetone treatment for 7 d. The degree of hyperplasia, quantified by the measurement of epidermal thickness, was reduced in both models by repeated applications of t-AMCHA. Finally, proteolytic activity in both human and mouse epidermis increased 1-2 h after epidermal injuries that disrupt the barrier. These results demonstrate that the inhibition of plasmin, a serine protease, accelerates barrier recovery and inhibits the epidermal hyperplasia induced by repeated barrier disruption, perhaps by decreasing the extent of attendant epidermal injury.

Animals↗
PubMed1997

Short-term effect of parathyroidectomy on biochemical markers in primary and secondary hyperparathyroidism.

This study has been carried out in order to evaluate several bone metabolic markers after parathyroidectomy in patients with primary hyperparathyroidism (PHP) and secondary hyperparathyroidism (SHP). The subjects studied were 6 patients with PHP (5 females, 1 male, aged 64-83 years) and 5 patients with SHP on chronic maintenance hemodialysis with skeletal symptoms (2 females, 3 males, aged 57-67 years). In PHP, serum alkaline phosphatase (ALP) and procollagen type I carboxy-terminal propeptides (PICP) levels showed a trend to increase gradually after parathyroidectomy, changes which were statistically significant (ALP, p = 0.0375; PICP, p = 0.0006). The serum bone Gla protein (BGP) level showed no significant change throughout the pre- and postoperative periods (p = 0.7512). Urinary pyridinoline (Pyr.) and deoxypyridinoline (DPyr.) levels showed rapid decreases after parathyroidectomy (Pyr.; p = 0.0014, DPyr., p = 0.0087). In SHP, individual values of serum ALP in 3 patients with complete parathyroid resection and 1 patient with incomplete parathyroid resection showed a tendency to increase. Individual values of serum BGP and PICP increased after parathyroidectomy in 3 patients with complete parathyroid resection but not in the 2 patients with incomplete parathyroid resection. Individual values of the serum carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) level showed no certain trend. The results obtained after surgery indicate that there is a positive uncoupling of the two processes of bone remodeling, and serum PICP and urinary pyridinium cross-links are good specific markers for the evaluation of potential recovery of bone damage after parathyroidectomy.

Aged↗
PubMed1996

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↗
PubMed1996

Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure.

Several studies have suggested that phosphorus (P) restriction, independent of serum levels of ionized calcium and 1,25-(OH)2D3, may prevent parathyroid hyperplasia and secondary hyperparathyroidism in patients and animals with chronic renal failure. A direct role of phosphorus in the pathogenesis of these abnormalities is, however, still controversial. Thus, studies were performed to examine the direct role of phosphorus on the development of these abnormalities. Female Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation. The animals were then divided into two dietary groups (High-P: 0.8% P diet, Low-P: 0.2% P diet). Six to eight rats per group per time-point were killed at the following intervals: 0, 1, 2, and 4 days, and 1, 2, 3, and 4 weeks. Serum intact parathyroid hormone (PTH) levels in uremic rats fed the high-P diet increased 1 day after nephrectomy, and high levels persisted for the duration of the study. Parathyroid gland growth in uremic rats fed the high-P diet was apparent within 2 days of uremia and increased nearly twofold by 2 weeks. These abnormalities, however, did not develop in uremic rats fed the low-P diet. Serum P levels in uremic rats fed the high-P diet were significantly higher than those of uremic rats fed the low-P diet, but there was no significant difference in serum ionized calcium or 1,25-(OH)2D3 levels. These results demonstrate that phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure, and that phosphorus restriction prevents these abnormalities independent of changes in serum ionized calcium and 1,25-(OH)2D3.

Animals↗