Assessment of Stool DNA Markers to Detect Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: A Multi-site Case-control Study.

Background And Aims: The FDA-approved multitarget stool-DNA [mt-sDNA] test is a successful colorectal cancer [CRC] screening tool in average-risk individuals but is not indicated for patients with inflammatory bowel disease [IBD]. We determined the performance of the mt-sDNA assay without the haemoglobin component [mt-sDNAHgb-] in patients with IBD, while measuring sensitivity for colorectal cancer and advanced colorectal neoplasia [ACRN].

Methods: This was a multi-centre, proof-of-concept investigation in persons aged 18-84 years with a diagnosis of IBD, or primary sclerosing cholangitis [PSC] with IBD.

A New 1,25 Dihydroxy Vitamin D Analog with Strong Bone Anabolic Activity in OVX Rats with Little or no Bone Resorptive Activity.

A new 1α,25-dihydroxy vitamin D analog (2-methylene-22(E)-(24R)-22-dehydro-1α,24,25-trihydroxy-19-norvitamin D or WT-51) has been tested as a possible therapeutic for osteoporosis. It is 1/10th as active as 1,25(OH) D in binding affinity for the vitamin D receptor but is at least 200 times more active than 1,25(OH) D and equal to that of 2MD (2-methylene-19-nor-(20S)-1α,25(OH) D , an analog previously tested in postmenopausal women), in supporting bone formation by isolated osteoblasts in culture. However, in contrast to 2MD, it is virtually inactive on bone resorption in vivo.

Telehealth with remote blood pressure monitoring for postpartum hypertension: A prospective single-cohort feasibility study.

Objective: Investigate feasibility of telehealth with remote blood pressure monitoring for management of hypertension in postpartum women at risk of severe hypertension after hospital discharge.

Methods: In a single-center, prospective single-cohort feasibility study, women with hypertension in pregnancy participated in a postpartum telehealth intervention for blood pressure management after discharge. The primary feasibility outcome measures were recruitment and retention through 6 weeks postpartum.

Pharmacokinetics of a New Oral Vitamin D Receptor Activator (2-Methylene-19-Nor-(20S)-1α,25-Dihydroxyvitamin D) in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism on Hemodialysis.

Background: 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D (DP001 or 2MD) is a novel, potent 1α-hydroxylated vitamin D analog that binds to the vitamin D receptor and suppresses parathyroid hormone synthesis and secretion with potential for an improved safety profile compared to existing active vitamin D analogs. The purpose of this study was to evaluate the pharmacokinetics of DP001 given orally after hemodialysis.

Methods: DP001 (550 ng) was given orally to 11 hemodialysis patients with secondary hyperparathyroidism after each dialysis session (3 times/week) for 4 weeks.

2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial.

Background: Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented.

Use of 2MD, a Novel Oral Calcitriol Analog, in Hemodialysis Patients with Secondary Hyperparathyroidism.

Background: Use of existing therapies for secondary hyperparathyroidism (SHPT), such as calcitriol or paricalcitol, is frequently limited by the development of hypercalcemia. 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD; DP001) is a novel and a more potent vitamin D receptor activator (VDRA) that more selectively localizes in the parathyroid gland, and has a wider therapeutic margin in the uremic rat model than calcitriol and paricalcitol.

Design, Setting, Participants, And Measurements: Hemodialysis patients were enrolled and dosed with 110, 220, 330, 440, or 550 ng of 2MD orally thrice weekly for 4 weeks.

Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women.

Background: The use of 1α-hydroxylated vitamin D therapy to control secondary hyperparathyroidism in renal failure patients has been a success story, culminating with the demonstration of increased life expectancy in patients treated with these compounds. However, hypercalcemic episodes have been a recurrent problem with these therapies and have resulted in the added use of calcium mimetics. Clearly there is good reason to search for improved vitamin D therapy.

Diaminobutane (DAB) dendrimers are potent binders of oral phosphate.

Reduction of blood phosphorus is a critical component in the management of secondary hyperparathyroidism in chronic kidney disease patients. In addition to dialysis treatment and dietary phosphorus restriction, oral phosphate binders are often consumed with meals to reduce the availability of food phosphorus. Several oral phosphate binders are approved for use in chronic kidney disease patients, but all have practical limitations because of toxicity, poor efficacy, or high cost.

Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus.

1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the biologically active form of vitamin D, is widely recognized as a modulator of the immune system as well as a regulator of mineral metabolism. The objective of this study was to determine the effects of vitamin D status and treatment with 1,25(OH)(2)D(3) on diabetes onset in non-obese diabetic (NOD) mice, a murine model of human type I diabetes. We have found that vitamin D-deficiency increases the incidence of diabetes in female mice from 46% (n=13) to 88% (n=8) and from 0% (n=10) to 44% (n=9) in male mice as of 200 days of age when compared to vitamin D-sufficient animals.

Regulation of the murine renal vitamin D receptor by 1,25-dihydroxyvitamin D3 and calcium.

Renal vitamin D receptor (VDR) is required for 1,25-dihydroxyvitamin D3-[1,25(OH)2D3]-induced renal reabsorption of calcium and for 1,25(OH)2D3-induced 1,25(OH)2D3 24-hydroxylase. The long-term effect of vitamin D and dietary calcium on the expression of renal VDR was examined in the nonobese diabetic mouse. Vitamin D-deficient and vitamin D-replete mice were maintained on diets containing 0.

Vitamin D and autoimmune diabetes.

The biologically active form of vitamin D, 1,25(OH)(2)D(3), is a potent modulator of the immune system as well as a regulator of bone and mineral metabolism. Vitamin D-deficiency in infancy and vitamin D receptor gene polymorphisms may be risk factors for insulin-dependent Diabetes mellitus (IDDM). 1,25(OH)(2)D(3) and its analogs significantly repress the development of insulitis and diabetes in the non-obese diabetic (NOD) mouse, a model of human IDDM.