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Standardization of A Physiologic Hypoparathyroidism Animal Model.

ABSTRACT: Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.

SUBMITTER: Jung SY

PROVIDER: S-EPMC5047647 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Standardization of A Physiologic Hypoparathyroidism Animal Model.

Jung Soo Yeon SY Kim Ha Yeong HY Park Hae Sang HS Yin Xiang Yun XY Chung Sung Min SM Kim Han Su HS

PloS one 20161003 10

Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), resp ...[more]

PMID: 27695051

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Project description:BackgroundWhen studying the association between treatment and a clinical outcome, a parametric multivariable model of the conditional outcome expectation is often used to adjust for covariates. The treatment coefficient of the outcome model targets a conditional treatment effect. Model-based standardization is typically applied to average the model predictions over the target covariate distribution, and generate a covariate-adjusted estimate of the marginal treatment effect.MethodsThe standard approach to model-based standardization involves maximum-likelihood estimation and use of the non-parametric bootstrap. We introduce a novel, general-purpose, model-based standardization method based on multiple imputation that is easily applicable when the outcome model is a generalized linear model. We term our proposed approach multiple imputation marginalization (MIM). MIM consists of two main stages: the generation of synthetic datasets and their analysis. MIM accommodates a Bayesian statistical framework, which naturally allows for the principled propagation of uncertainty, integrates the analysis into a probabilistic framework, and allows for the incorporation of prior evidence.ResultsWe conduct a simulation study to benchmark the finite-sample performance of MIM in conjunction with a parametric outcome model. The simulations provide proof-of-principle in scenarios with binary outcomes, continuous-valued covariates, a logistic outcome model and the marginal log odds ratio as the target effect measure. When parametric modeling assumptions hold, MIM yields unbiased estimation in the target covariate distribution, valid coverage rates, and similar precision and efficiency than the standard approach to model-based standardization.ConclusionWe demonstrate that multiple imputation can be used to marginalize over a target covariate distribution, providing appropriate inference with a correctly specified parametric outcome model and offering statistical performance comparable to that of the standard approach to model-based standardization.

Project description:Histoplasmosis is considered one of the most important endemic and systemic mycoses worldwide. Until now few molecular techniques have been developed for its diagnosis. The aim of this study was to develop and evaluate three real time PCR (qPCR) protocols for different protein-coding genes (100-kDa, H and M antigens) using an animal model. Fresh and formalin-fixed and paraffin-embedded (FFPE) lung tissues from BALB/c mice inoculated i.n. with 2.5x106 Histoplasma capsulatum yeast or PBS were obtained at 1, 2, 3, 4, 8, 12 and 16 weeks post-infection. A collection of DNA from cultures representing different clades of H. capsulatum (30 strains) and other medically relevant pathogens (36 strains of related fungi and Mycobacterium tuberculosis) were used to analyze sensitivity and specificity. Analytical sensitivity and specificity were 100% when DNAs from the different strains were tested. The highest fungal burden occurred at first week post-infection and complete fungal clearance was observed after the third week; similar results were obtained when the presence of H. capsulatum yeast cells was demonstrated in histopathological analysis. In the first week post-infection, all fresh and FFPE lung tissues from H. capsulatum-infected animals were positive for the qPCR protocols tested except for the M antigen protocol, which gave variable results when fresh lung tissue samples were analyzed. In the second week, all qPCR protocols showed variable results for both fresh and FFPE tissues. Samples from the infected mice at the remaining times post-infection and uninfected mice (controls) were negative for all protocols. Good agreement was observed between CFUs, histopathological analysis and qPCR results for the 100-kDa and H antigen protocols. We successfully standardized and validated three qPCR assays for detecting H. capsulatum DNA in fresh and FFPE tissues, and conclude that the 100-kDa and H antigen molecular assays are promising tests for diagnosing this mycosis.

Project description:ObjectivesIndividuals with chronic hypoparathyroidism may experience suboptimal medical care with high frequency of unplanned hospitalisation and iatrogenic harm. In 2015 the European Society for Endocrinology published consensus guidelines on the management of chronic hypoparathyroidism. We set out to audit compliance with these guidelines.MethodsUsing these recommendations as audit standards we worked with the Society for Endocrinology and Parathyroid UK to conduct a national audit of management of chronic hypoparathyroidism in the United Kingdom. Endocrine leads in 117 endocrine departments were invited to participate in the survey by completing a data collection tool on up to 5 sequential cases of chronic hypoparathyroidism seen in their outpatient clinics in the preceding 12 months. Data were collected on 4 treatment standards and 9 monitoring standards. Data on hospitalisations and Quality of Life monitoring were also collected.ResultsResponses were received from 22 departments giving a response rate of 19%, concerning 80 individual cases. The mean age of subjects was 48.4 years. The main findings were that the commonest cause of hypoparathyroidism was post surgical (66.3%). Treatments taken by the group included activated vitamin D analogues (96.3%), oral calcium salts (66.3%), vitamin D supplements (17.5%), thiazide diuretics (5%) and rhPTH1-34 (1.3%). Compliance with the audit standards varied between 98.8% and 60% for the treatment standards and between 91.3% and 20% for the monitoring standards. Some of the areas of weakness revealed include low rates of 24 h urinary calcium excretion monitoring, serum magnesium monitoring and low rates of renal imaging where indicated. In addition and importantly, 16.3% of subjects had experienced at least one hospital admission in the preceding 12 months.ConclusionWe conclude that further improvements in the UK national standard of management of chronic hypoparathyroidism should be made and that this will benefit both quality of life, morbidity and potentially mortality in this group of patients.

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Standardization of A Physiologic Hypoparathyroidism Animal Model.

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Standardization of A Physiologic Hypoparathyroidism Animal Model.

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