Accuracy of continuous glucose monitoring in the hospital setting: an observational study.

Aims/hypothesis: Continuous glucose monitoring (CGM) improves glycaemic outcomes in the outpatient setting; however, there are limited data regarding CGM accuracy in hospital.

Methods: We conducted a prospective, observational study comparing CGM data from blinded Dexcom G6 Pro sensors with reference point of care and laboratory glucose measurements during participants' hospitalisations. Key accuracy metrics included the proportion of CGM values within ±20% of reference glucose values >5.

Rapid cloning, expression, and functional characterization of paired αβ and γδ T-cell receptor chains from single-cell analysis.

Transgenic expression of antigen-specific T-cell receptor (TCR) genes is a promising approach for immunotherapy against infectious diseases and cancers. A key to the efficient application of this approach is the rapid and specific isolation and cloning of TCRs. Current methods are often labor-intensive, nonspecific, and/or relatively slow.

Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM). However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection.

Virus-like particle-induced protection against MRSA pneumonia is dependent on IL-13 and enhancement of phagocyte function.

The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases.

Effects of calcitriol, seocalcitol, and medium-chain triglyceride on a canine transitional cell carcinoma cell line.

Background: Transitional cell carcinoma (TCC) in dogs is associated with high morbidity and mortality. Calcitriol and its analog seocalcitol, combined with medium-chain triglyceride (MCT), have potential for the treatment of this disease.

Materials And Methods: TCC cells were treated with calcitriol or seocalcitol, alone or combined with MCT.

Emerging drugs in psoriasis.

Psoriasis is a relatively common, chronic skin disease affecting 1-2% of the population in the developed countries. It is an inflammatory, autoimmune skin disorder characterised by an accelerated rate of epidermal proliferation and disordered differentiation. Since our last review in 1999, considerable progress has been made in understanding the immunopathogenesis of this disease, and new drugs have become available for its treatment.

Synthesis of novel hapten derivatives of 1alpha,25-dihydroxy-vitamin D3 and its 20-epi analogue.

Hapten derivatives of 1alpha,25-dihydroxyvitamin D(3) and its 20-epimer were synthesized and conjugated to a carrier protein for raising polyclonal antibodies. The haptens were linked through spacers at C-16, thereby exposing both the A-ring and the side chain of the molecules, to maximize antibody specificity. The spacers were introduced via stereoselective hydroboration of 16-ene intermediates as the key step.

Synthesis and testing of 2alpha-modified 1alpha,25-dihydroxyvitamin D(3) analogues with a double side chain: marked cell differentiation activity.

The 2alpha-methyl-, 2alpha-(3-hydroxypropyl)-, and 2alpha-(3-hydroxypropoxy)-derivatives of the 'double side chain' analogue of 1alpha,25-dihydroxyvitamin D(3) were synthesized using Trost A-ring/CD-ring connective strategy. Regarding the requisite A-ring building blocks, a new, high yield and stereoselective route to the 2alpha-methyl compound starting from D-glucose was developed. All three new analogues showed potent HL-60 cancer cell differentiation activity.

Polyclonal antibodies to EB1089 (seocalcitol), an analog of 1alpha,25-dihydroxyvitamin D(3)*.

A hapten derivative of EB1089 [1(R),3(S),25-trihydroxy-26,27-dimethyl-9,10-seco-24-homocholesta-5(Z),7(E),10(19),22(E),24(E)-pentaene], a side-chain analog of 1alpha,25-dihydroxyvitamin D(3), was synthesized for raising antibodies with a high specificity for EB1089. The A-ring moiety of EB1089 was replaced in the hapten by a linker for conjugation to a protein. Three polyclonal antibodies were obtained by immunizing rabbits with a BSA-conjugate of the hapten.

Novel side chain analogs of 1alpha,25-dihydroxyvitamin D(3): design and synthesis of the 21,24-methano derivatives.

The syntheses of the new 21,24-methano derivatives of 1alpha,25-dihydroxyvitamin D(3) [viz. 1(S),3(R)-dihydroxy-17(R)-(1',4'-cis-(4'-(1'-hydroxy-1'-methylethyl)-cyclo-hexyl))-9,10-seco-androsta-5(Z),7(E),10(19)-triene (MC 2108) and its (1',4'-trans)-isomer (MC 2110)] are described. The key step is the establishment, by Diels-Alder reaction on a CD-ring side chain diene intermediate prepared from vitamin D(2), of a 1,4-disubstituted cyclohexene moiety in the side chain.

Potent suppression of the parathyroid glands by hydroxylated metabolites of dihydrotachysterol(2).

Background: Dihydrotachysterol(2), a licensed pharmaceutical, is hydroxylated to 25-hydroxydihydrotachysterol(2) (25(OH)DHT(2)) and 1 alpha,25-dihydroxydihydrotachysterol(2) (1 alpha,25(OH)(2)DHT(2)) in man. We have compared the biological activity of these metabolites with calcitriol and the 'non-calcaemic' analogue, 22-oxacalcitriol (OCT) in bovine parathyroid cell cultures and in rats.

Methods: The effect of each sterol on parathyroid hormone (PTH) secreted by primary bovine parathyroid cells was measured.

Evidence for the activation of vitamin D compounds in the skin by side-chain hydroxylation.

KH 1060 is the 20-epi-22-oxa-24a-homo-26,27-dimethyl analogue of the natural hormone, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). We have previously shown that after topical application in hairless mice both KH 1060 and 1 alpha,25(OH)2D3 cause epidermal hyperproliferation. MC 1582 differs from KH 1060 by the lack of hydroxyl group in the side chain which is required for receptor binding.

The vitamin D analog, KH1060, is rapidly degraded both in vivo and in vitro via several pathways: principal metabolites generated retain significant biological activity.

Vitamin D analogs are valuable drugs with established and potential uses in hyperproliferative disorders. Lexacalcitol (KH1060) is over 100 times more active than 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3], as judged by in vitro antiproliferative and cell differentiating assays. The underlying biochemical reasons for the increased biological activity of KH1060 are unknown, but are thought to include 1) metabolic considerations in addition to explanations based upon 2) enhanced stability of KH1060-liganded transcriptional complexes.

Metabolism of the vitamin D analog EB1089 by cultured human cells: redirection of hydroxylation site to distal carbons of the side-chain.

1(S),3(R)-dihydroxy-20(R)-(5'-ethyl-5'-hydroxy-hepta-1'(E),3' (E)-dien-1'-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene (EB1089) is a novel synthetic analog of 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D3] with potential for use in the treatment of hyperproliferative disorders. It has an altered side-chain structure compared to 1,25-(OH)2D3, featuring 26,27 dimethyl groups, insertion of an extra carbon atom (24a) at C-24, and two double bonds at C-22,23 and C-24,24a. In vitro metabolism of EB1089 was studied in a human keratinocyte cell model, HPK1A-ras, previously shown to metabolize 1,25-(OH)2D3.

Different mechanisms of hydroxylation site selection by liver and kidney cytochrome P450 species (CYP27 and CYP24) involved in vitamin D metabolism.

A series of homologated 1 alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 molecules with one to three extra carbons in the side chain were used to examine the substrate preferences and hydroxylation site selection mechanisms of the liver vitamin D3-25-hydroxylase (CYP27) and the target cell 25-hydroxyvitamin D3-24-hydroxylase (CYP24). Cultured and transfected cell models, used as sources of these hydroxylases, gave 23-, 24-, 25-, and 27-hydroxylated metabolites which were identified by their high performance liquid chromatography and GC-MS characteristics. Lengthening the side chain is tolerated by each cytochrome P450 isoform such that 25-hydroxylation or 24-hydroxylation continues to occur at the same rate as in the native side chain, while the site of hydroxylation remains the same for the liver enzyme in that CYP27 continues to hydroxylate at C-25 and C-27 (minor) despite the two-carbon-atom extension.

Trends in tobacco use.

The production and use of tobacco have been accepted parts of the American life-style for over 500 years. Tobacco use in the United States has gone through many stages over the years. The present article reviews the trends of tobacco use over the last 100 years and the public health strategies recently initiated to control tobacco use and promote public health.

Increased biological activity of 20-epi-1,25-dihydroxyvitamin D3 is due to reduced catabolism and altered protein binding.

The 20-epi series of vitamin D3 analogs has been shown to be made up of more potent inducers of cell differentiation than calcitriol in vitro. Using 20-epi-1 alpha,25-dihydroxyvitamin D3 (MC 1288), we attempted to rationalize this increased biological activity by examining several parameters including the binding affinity of the analog for the plasma binding globulin (DBP) and the target cell vitamin D receptor (VDR), as well as attempting to measure the rate at which MC 1288 is metabolized. MC 1288 was found to be metabolized 36 times more slowly than its epimer 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3), forming several metabolites which were analogous to metabolites of 1,25-(OH)2D3 formed in the side chain oxidation pathway.

In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models.

Calcipotriol (MC903) is a side chain analog of the vitamin D hormone calcitriol, containing a 22-23 double bond, a 24(S)-hydroxyl function, and carbons 25, 26, and 27 incorporated into a cyclopropane ring which has been developed for treating psoriasis. The in vitro metabolism of calcipotriol was studied in two keratinocyte cell models, HPK1A and HPK1A-ras. Calcipotriol was initially converted into the 24-ketone (MC1046) and its 22,23-hydrogenated derivative (MC1080), metabolites observed in osteosarcoma, kidney, and hepatoma cell lines.

A dialogue on analogues Newer vitamin-D drugs for use in bone disease, psoriasis, and cancer.

Many new analogues of the vitamin-D hormone, 1 alpha,25-dihydroxy-vitamin D(3) [1 alpha,25-(OH)(2)D(3); calcitriol], have emerged that can mimic its various actions in classic calcium transport systems and/or in the regulation of cell proliferation and cell differentiation. Though some of these analogues have accentuated activity in cell differentiation assays in vitro, they lack appreciable "calcemic" activity in vivo, leading to the name "noncalcemic analogues." Several of these analogues are promising candidates for use in treatment of psoriasis and in tumor suppression, one of them, calcipotriol, being already widely approved for the former indication.

Removable partial denture framework try-in.

Removable partial denture frameworks must fit accurately to function properly and not cause injury to remaining teeth or soft tissue. This article presents a logical method and rationale for seating a removable partial denture framework and a review of several disclosing media used in the try-in procedure.