Search PubMed⌕ Search

Biomedical subjects

M Denda

Publications and source records attributed to M Denda.

48 records · Page 3Linked to original sources

1,25-dihydroxyvitamin D3 and 22-oxacalcitriol prevent the decrease in vitamin D receptor content in the parathyroid glands of uremic rats.

Decreased content of the 1,25-dihydroxyvitamin D3 receptor (VDR) in parathyroid glands from patients and animals with chronic renal failure has been implicated in the pathogenesis of secondary hyperparathyroidism. In these studies, we examined the regulation of VDR by 1,25-dihydroxyvitamin D3 (1,25-D3) and 22-oxacalcitriol (OCT) in parathyroid glands of uremic rats. After eight weeks of renal failure, VDR content in parathyroid glands of uremic rats was decreased (400 +/- 42 vs. 729 +/- 47 fmol/mg protein in normal control rats, P < 0.05) and strongly correlated with serum 1,25-D3 levels (r = 0.829, P = 0.0001). Treatment with either 1,25-D3 or OCT prevented the decrease in VDR. We conclude that low serum 1,25-D3 levels, at least in part, account for the decrease in VDR content in parathyroid glands of uremic rats and that treatment with 1,25-D3 or OCT prevents this decrease ameliorating the development of secondary hyperparathyroidism.

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↗

Plasma pentosidine levels in uremic patients before and after hemodialysis.

Pentosidine, a fluorescent cross-link, is one of the advanced glycosylation end-products. It accumulates in human tissues, plasma and urine in diabetic and uremic patients. Using SP-Sephadex C-25 in the pretreatment for reversed-phase HPLC, we determined pentosidine levels in plasma before and after hemodialysis using cuprophane membranes from 18 patients (9 diabetic, 9 nondiabetic) with end-stage renal disease, as well as examined the hemodialysis efficiency of plasma pentosidine. We also measured beta 2-microglobulin levels in plasma before and after hemodialysis. The values of plasma pentosidine did not significantly change after hemodialysis. Also, plasma beta 2-microglobulin was not removed by hemodialysis. Hemodialysis efficiency of plasma pentosidine and beta 2-microglobulin was nil. In addition, there was a significant correlation between plasma levels of pentosidine and beta 2-microglobulin before hemodialysis in 116 uremic patients. The results indicated that hemodialysis could not eliminate pentosidine from plasma; therefore, pentosidine retention by the diseased kidney might be a major cause of elevated levels of pentosidine with uremia.

Arginine↗

The effect of menopause on biochemical markers and ultrasound densitometry in healthy females.

Urinary pyridinoline (pyr) and deoxypyridinoline (dpyr) are new markers for bone resorption, and serum osteocalcin reportedly indicates osteoblastic activity. Recently, a new ultrasound bone densitometer instrument has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index. The effects of menopause on biochemical markers and ultrasound densitometry were investigated in 40 healthy females, 36-39 years, with regular menstruation, and in 117 healthy perimenopausal females, 47-57 years, who were divided into a premenopausal group and a postmenopausal group. Significantly elevated values of pyr, dpyr, and serum osteocalcin were found for the postmenopausal group as a whole compared with the premenopausal group. We examined postmenopausal groups 48-57 years of age stratified into 2-year intervals (within 2 years of the menopause, 2-4 years postmenopause and 4-6 years postmenopause). Elevated values of urinary pyr, dpyr, and serum osteocalcin were evident even in the first 2 years postmenopause compared with the premenopausal group, and these higher values were exhibited until 6 years after menopause. We found a significant decrease in SOS, BUA, and stiffness index of the postmenopausal group as a whole, compared with those of the premenopausal group. SOS, BUA, and stiffness index of the group within 2 years of menopause significantly decreased compared with those of the premenopausal group. The Z-scores of the increase in biochemical markers and the decrease in stiffness index in the postmenopausal group were approximately 0.7-1.3 compared with the premenopausal group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stratum corneum lipid morphology and transepidermal water loss in normal skin and surfactant-induced scaly skin.

Stratum corneum lipid morphology was evaluated using attenuated total reflectance infrared spectroscopy (ATR-IR) in normal skin and surfactant-induced scaly skin to evaluate skin barrier function. To evaluate the degree of order of the intercellular lipid alkyl chain conformation, we measured the wavenumbers (frequency shifts) of the symmetrical and asymmetrical C-H stretching vibrations observed at approximately 2850 cm-1 and 2920 cm-1, respectively. There was a correlation between the wave-number and transepidermal water loss in normal skin. However, no difference was observed in surfactant-induced scaly skin from the baseline value in the wavenumbers of the C-H vibrations. These results suggest that in normal skin, lipid morphology plays an important role in the barrier function of the stratum corneum. However, the decline in barrier function in scaly skin is not due to conformational disorder of the lipid alkyl chain.

Adult↗

Age- and sex-dependent change in stratum corneum sphingolipids.

We measured six stratum corneum sphingolipid species (ceramides 1-6) in 26 males and 27 females, and found a significant change in their percentage composition only among female subjects of different age groups. There was a significant increase in ceramide 1 and 2 with a corresponding decrease in ceramide 3 and 6 from prepubertal age to adulthood. Thereafter the ratio of ceramide 2 to total sphingolipids decreased with age in contrast to ceramide 3 which showed an increase. Such a pattern of change in the aging population is different from that observed in scaly skin experimentally induced by tape stripping. The present results suggest a significant influence of female hormones on the composition of stratum corneum sphingolipids. Moreover, the different patterns of change in sphingolipid composition of stratum corneum lipids between scales from inflammatory skin and those from aged skin also suggest that epidermal biosynthesis of sphingolipids is influenced by epidermal proliferative activity.

Adolescent↗

Quantification of the cross-link pentosidine in serum from normal and uremic subjects.

Pentosidine is a fluorescent cross-link compound that accumulates in human tissues from uremic and diabetic patients. Using SP-Sephadex C-25 pretreatment before reversed-phase HPLC, we developed a method for quantifying pentosidine in the acid hydrolysate of serum. We examined concentrations of pentosidine in serum from 98 patients with end-stage renal disease requiring hemodialysis and from 33 normal control subjects. The mean (+/- SD) concentration of pentosidine was significantly greater in serum from uremic patients than that from control subjects (1267 +/- 695 nmol/L vs 77 +/- 40 nmol/L, P = 0.0001). There was a significant correlation between serum pentosidine concentrations and age in control subjects (r = 0.453, P < 0.01), but not in uremic patients. Serum pentosidine significantly increased with the duration of hemodialysis treatment (r = 0.272, P < 0.05). The greater pentosidine concentrations in uremic patients may be caused by the increased synthesis of pentosidine (perhaps because of the retention of pentosidine precursors), by the retention of pentosidine molecule itself in end-stage renal failure, or both.

Adolescent↗

[A clinical multivariate study on bone change after parathyroidectomy in patients with renal osteodystrophy].

This study investigated the changes of bone lesions after parathyroidectomy (PTX) in patients with renal osteodystrophy. Fifty-eight patients (mean age 43.7 +/- 8.4 years and mean duration of hemodialysis 120.9 +/- 32.1 months), who were resistant to medical treatments, were studied. Total PTX was followed by massive administration of alfacalcidol on these patients. The clinical symptoms, hematological findings, radiographic findings and second metacarpal bone density during the first 2 years following PTX were studied. After the operation, the clinical symptoms, hematological findings as well as radiographic findings improved in all of the patients and the density of the second metacarpal bone increased in 37 out of 40 patients. From these results we concluded that total PTX followed by massive administration of active vitamin D was effective in improving bone lesions and bone mineral density on patients with renal osteodystrophy.

Adult↗

Stratum corneum sphingolipids and free amino acids in experimentally-induced scaly skin.

Stratum corneum sphingolipids are of particular importance in maintaining the water permeability barrier of mammalian epidermis. Free amino acids also play an important role in water retention in the stratum corneum. To clarify the way in which these substances affect scaly skin, stratum corneum sphingolipids and free amino acids collected from artificially-induced scaly skin were analysed. Scaly skin was induced by tape stripping. The total amount of sphingolipids was quantified by gas chromatography and five of sphingolipid fractions were isolated and quantified by thin-layer chromatography. Free amino acids were analysed using a high-speed amino analyser. The total amount of sphingolipid in scaly skin did not differ statistically from that in control skin. However, a significant change in the distribution of the five sphingolipid species was observed in scaly skin and the total amount of amino acids was decreased in scaly skin. These results suggest that the distribution of these five types of sphingolipid and the total amount of amino acids are responsible for scaly skin.

Adult↗

Topical application of ionic polymers affects skin permeability barrier homeostasis.

We previously demonstrated that the external electric potential affected skin barrier homeostasis. On the other hand, topical application of an ionic polymer formed a diffusion electric double layer on the surface of the skin. Thus, we evaluated effects of topical application of ionic polymers on the damaged skin barrier. Application of a nonionic polymer did not affect barrier recovery. Application of sodium salts of anionic polymers accelerated barrier recovery, while that of cationic polymers delayed it. Topical application of a sodium-exchange resin accelerated barrier recovery, but application of a calcium-exchange resin had no effect even when the resins had the same structure. Application of a chloride-exchange resin delayed barrier recovery. Topical application of ionic polymers influenced skin barrier homeostasis.

Administration, Cutaneous↗