THE SMALL INTESTINE IN VITAMIN D DEPENDENT RICKETS

PEDIATRICS ◽  
1970 ◽  
Vol 45 (3) ◽  
pp. 364-373
Author(s):  
Richard Hamilton ◽  
Joan Harrison ◽  
Donald Fraser ◽  
Lngeborg Radde ◽  
Rachel Morecki ◽  
...  

We have demonstrated impaired intestinal absorption of calcium in a child with active vitamin D dependent rickets (hereditary pseudovitamin D deficiency rickets) at a time when the patient had normal anti-rachitic activity in her serum. Calcium absorption improved greatly in response to vitamin D, administered in the massive dosage that was necessary to heal the rachitic lesions. Phosphorus absorption may have been slightly impaired in the same patient, but no other absorptive defect was found. We studied intestinal function in five additional patients after they had been placed on vitamin D therapy. No abnormalities were found. In these treated patients, calcium absorption was not measured. Duodenal mucosa studied by light and electron microscopy was normal in all patients. Future investigation of intestinal transport of calcium in these patients should help to explain the pathogenesis of this disease.

Author(s):  
Brynn E. Marks ◽  
Daniel A. Doyle

AbstractThe widespread use of supplemental vitamin D has dramatically reduced the incidence of rickets. While generally considered a safe practice, there is potential for toxicity in patients with idiopathic infantile hypercalcemia (IIH). Inadequate 24-hydroxylase-enzyme activity renders these individuals unable to degrade active vitamin D, resulting in hypercalcemia due to increased intestinal calcium absorption, decreased renal calcium excretion, and increased osteoclastic bone activity. Clinicians should be aware that even therapeutic doses of vitamin D can prove harmful for patients with


2016 ◽  
Vol 101 (6) ◽  
pp. 2313-2324 ◽  
Author(s):  
John P. Bilezikian ◽  
Maria Luisa Brandi ◽  
Natalie E. Cusano ◽  
Michael Mannstadt ◽  
Lars Rejnmark ◽  
...  

Abstract Context: Conventional management of hypoparathyroidism has focused upon maintaining the serum calcium with oral calcium and active vitamin D, often requiring high doses and giving rise to concerns about long-term consequences including renal and brain calcifications. Replacement therapy with PTH has recently become available. This paper summarizes the results of the findings and recommendations of the Working Group on Management of Hypoparathyroidism. Evidence Acquisition: Contributing authors reviewed the literature regarding physiology, pathophysiology, and nutritional aspects of hypoparathyroidism, management of acute hypocalcemia, clinical aspects of chronic management, and replacement therapy of hypoparathyroidism with PTH peptides. PubMed and other literature search engines were utilized. Evidence synthesis: Under normal circumstances, interactions between PTH and active vitamin D along with the dynamics of calcium and phosphorus absorption, renal tubular handing of those ions, and skeletal responsiveness help to maintain calcium homeostasis and skeletal health. In the absence of PTH, the gastrointestinal tract, kidneys, and skeleton are all affected, leading to hypocalcemia, hyperphosphatemia, reduced bone remodeling, and an inability to conserve filtered calcium. Acute hypocalcemia can be a medical emergency presenting with neuromuscular irritability. The recent availability of recombinant human PTH (1–84) has given hope that management of hypoparathyroidism with the missing hormone in this disorder will provide better control and reduced needs for calcium and vitamin D. Conclusions: Hypoparathyroidism is associated with abnormal calcium and skeletal homeostasis. Control with calcium and active vitamin D can be a challenge. The availability of PTH (1–84) replacement therapy may usher new opportunities for better control with reduced supplementation requirements.


1981 ◽  
Vol 195 (3) ◽  
pp. 685-690 ◽  
Author(s):  
T Shinki ◽  
N Takahashi ◽  
C Miyaura ◽  
K Samejima ◽  
Y Nishii ◽  
...  

The effect of cholecalciferol and its metabolites on ornithine decarboxylase activity was investigated in the duodenal mucosa of vitamin D-deficient chicks. The duodenal ornithine decarboxylase activity decreased in animals fed a vitamin D-deficient diet and its retarded activity was increased dose-dependently by a single injection of cholecalciferol. Among various metabolites of cholecalciferol tested, 1 alpha, 25-dihydroxycholecalciferol [ 1 alpha, 25 (OH)2D3] was the most potent stimulator. Stimulation of the enzyme activity was detected as early as 2h after intravenous administration of 1 alpha, 25 (OH)2D3 and a maximal value was attained at 6 h. The maximal value was 27 times higher than the control. In addition, treatment with 1 alpha 25 (OH)2D3 affected the duodenal content of polyamines. The content of putrescine increased to a value of three times that of the control 6 h after the hormone administration. The spermidine content did not change appreciably. The enhancement of duodenal ornithine decarboxylase activity by 1 alpha, 25 (OH)2D3 occurred in parallel with the enhancement of calcium absorption, which was first detected 3 h after the hormone administration. The enhancement appeared to be tissue-specific. It was observed in every intestinal segment, but was highest in the duodenum. Enzyme activity in other tissues was not influenced appreciably by 1 alpha, 25 (OH)2D3. These results clearly indicate that the duodenal biosynthesis of polyamines is regulated by 1 alpha, 25 (OH)2D3, suggesting the possibility that duodenal ornithine decarboxylase may be involved in the calcium absorption mechanism.


2019 ◽  
Vol 244 (12) ◽  
pp. 1040-1052 ◽  
Author(s):  
Mohammadhossein Hassanshahi ◽  
Paul H Anderson ◽  
Cyan L Sylvester ◽  
Andrea M Stringer

Vitamin D activity is associated with the modulation of a wide variety of biological systems, in addition to its roles in calcium homeostatic mechanisms. While vitamin D is well known to promote gastrointestinal calcium absorption, vitamin D also plays a role in attenuating and/or preventing the progression of several gastrointestinal diseases including Crohn’s disease, ulcerative colitis, and colorectal cancer, and may also play a role in chemotherapy-induced intestinal mucositis. The pro-differentiation, immunomodulatory, and anti-inflammatory effects of vitamin D, which has been reported in numerous circumstances, are key potential mechanisms of action in the prevention of gastrointestinal disorders. While the debate of the effectiveness of vitamin D to treat bone pathologies continues, the clinical importance of vitamin D therapy to prevent gastrointestinal disorders should be investigated given current evidence, using both nutritional and pharmaceutical intervention approaches. Impact statement The non-skeletal functions of vitamin D play an important role in health and disease. The anti-inflammatory properties and maintenance of intestinal function fulfilled by vitamin D impact other systems in the body though downstream processing. This review provides insight into the mechanisms underpinning the potential benefits of vitamin D in both maintaining intestinal homeostasis and associated diseased states.


2009 ◽  
Vol 297 (6) ◽  
pp. G1193-G1197 ◽  
Author(s):  
Sara Balesaria ◽  
Sonia Sangha ◽  
Julian R. F. Walters

Calcium absorption by the intestine is necessary for bone mineralization. Much has been learned about this process and the role of vitamin D metabolites in gene transcription from animal studies, but the molecular mechanisms in humans are less well understood. We have used samples of normal human duodenal mucosa, obtained at endoscopy, to investigate the effects of the vitamin D metabolites, 1α-dihydroxycholecalciferol [1,25(OH)2D3] and 25-hydroxycholecalciferol (25OHD), on transcripts on genes involved in calcium absorption and vitamin D metabolism. TRPV6 transcripts were significantly higher after incubation for 6 h with 1,25(OH)2D3 (10−9 mol/l) than after control incubations (median difference 3.1-fold, P < 0.001). Unexpectedly, TRPV6 expression was also higher (2.4-fold, P < 0.02) after incubation with 25OHD (10−7 mol/l). Transcripts for the calcium-ATPase, PMCA1, were significantly higher with 1,25(OH)2D3; CYP24 transcripts were reliably detected after incubation with either metabolite, but calbindin-D9k transcripts were unaffected. The response of TRPV6 to 25OHD and the expression of transcripts for CYP27B1, the 25OHD-1α-hydroxylase, were significantly correlated ( r = 0.82, P < 0.02). Basal duodenal expression of TRPV6 and CYP27B1 were significantly associated ( r = 0.72, P < 0.001) in a separate previously reported series of subjects. Multiple regression analysis of the associations with basal duodenal TRPV6 expression identified CYP27B1 expression and serum 1,25(OH)2D as major factors. Expression of the CYP27B1 protein was demonstrated immunohistochemically in duodenal mucosa. This study has shown that human duodenal TRPV6, PMCA1, and CYP24 transcripts respond rapidly to 1,25(OH)2D3 and provides evidence suggesting that local duodenal production of 1,25(OH)2D3 by 25OHD-1α-hydroxylase may have a role in human calcium absorption.


2021 ◽  
Vol 10 (7) ◽  
pp. 1378
Author(s):  
Dalal S. Ali ◽  
Karel Dandurand ◽  
Aliya A. Khan

Background: Hypoparathyroidism is an uncommon endocrine disorder. During pregnancy, multiple changes occur in the calcium-regulating hormones, which may affect the requirements of calcium and active vitamin D during pregnancy in patients with hypoparathyroidism. Close monitoring of serum calcium during pregnancy and lactation is ideal in order to optimize maternal and fetal outcomes. In this review, we describe calcium homeostasis during pregnancy in euparathyroid individuals and also review the diagnosis and management of hypoparathyroidism during pregnancy and lactation. Methods: We searched the MEDLINE, CINAHL, EMBASE, and Google scholar databases from 1 January 1990 to 31 December 2020. Case reports, case series, book chapters, and clinical guidelines were included in this review. Conclusions: During pregnancy, rises in 1,25-dihydroxyvitamin D (1,25-(OH)2-D3) and PTH-related peptide result in suppression of PTH and enhanced calcium absorption from the bowel. In individuals with hypoparathyroidism, the requirements for calcium and active vitamin D may decrease. Close monitoring of serum calcium is advised in women with hypoparathyroidism with adjustment of the doses of calcium and active vitamin D to ensure that serum calcium is maintained in the low-normal to mid-normal reference range. Hyper- and hypocalcemia should be avoided in order to reduce the maternal and fetal complications of hypoparathyroidism during pregnancy and lactation. Standard of care therapy consisting of elemental calcium, active vitamin D, and vitamin D is safe during pregnancy.


Author(s):  
Odell T. Minick ◽  
Hidejiro Yokoo ◽  
Fawzia Batti

Vacuolated cells in the liver of young rats were studied by light and electron microscopy following the administration of vitamin A (200 units per gram of body weight). Their characteristics were compared with similar cells found in untreated animals.In rats given vitamin A, cells with vacuolated cytoplasm were a prominent feature. These cells were found mostly in a perisinusoidal location, although some appeared to be in between liver cells (Fig. 1). Electron microscopy confirmed their location in Disse's space adjacent to the sinusoid and in recesses between liver cells. Some appeared to be bordering the lumen of the sinusoid, but careful observation usually revealed a tenuous endothelial process separating the vacuolated cell from the vascular space. In appropriate sections, fenestrations in the thin endothelial processes were noted (Fig. 2, arrow).


Author(s):  
John H. L. Watson ◽  
John L. Swedo ◽  
M. Vrandecic

The ambient temperature and the nature of the storage fluids may well have significant effects upon the post-implantation behavior of venus autografts. A first step in the investigation of such effects is reported here. Experimental conditions have been set which approximate actual operating room procedures. Saphenous veins from dogs have been used as models in the experiments. After removal from the dogs the veins were kept for two hours under four different experimental conditions, viz at either 4°C or 23°C in either physiological saline or whole canine arterial blood. At the end of the two hours they were prepared for light and electron microscopy. Since no obvious changes or damage could be seen in the veins by light microscopy, even with the advantage of tissue specific stains, it was essential that the control of parameters for successful grafts be set by electron microscopy.


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