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Defects in the biochemistry of collagen in diseases of connective tissue.

The collagens are the major structural glycoproteins of connective tissues. A unique primary structure and a multiplicity of post-translational modification reactions are required for normal fibrillogenesis. The post-translational modifications include hydroxylation of prolyl and lysyl residues, glycosylation, folding of the molecule into triple-helical conformation, proteolytic conversion of precursor procollagen to collagen, and oxidative deamination of certain lysyl and hydroxylysyl residues. Any defect in the normal mechanisms responsible for the synthesis and secretion of collagen molecul

Ciprofibrate, clofibric acid and respective glycinate derivatives. Effects of a four-week treatment on male lean and obese Zucker rats.

Fibrates are widely prescribed in hyperlpidemic patients to prevent atherosclerosis. Their therapeutic use, however, can be associated with adverse effects like gastrointestinal disorders, myalgia, myositis and hepatotoxicity. In rodents large doses can even cause hepatocellular carcinoma. Additionally, interactions with the biotransformation of other compounds at the cytochrome P450 (CYP) system have been observed. Thus, the discovery of new substances or derivatives with less side effects is of great interest. In the present study the influence of a four-week daily oral administration of 2 m

Sustained local application of low-dose epidermal growth factor on steroid-inhibited colonic wound healing.

BACKGROUND/PURPOSE: The effects of locally administered low-dose epidermal growth factor in a steroid-inhibited wound healing were investigated in a rat model. METHODS: Long-acting release of epidermal growth factor was enabled using microspheres embedded in gelatin sponge. Study groups consisted of 60 rats with 10 in each: colonic anastomosis only (C), plus pure gelatin sponge (CG), plus epidermal growth factor loaded sponge (CE), colonic anastomosis and steroid (S), plus gelatine sponge (SG), and plus epidermal growth factor-loaded gelatine sponge (SE) groups. Bursting pressure and wound hy

A novel thyroid hormone receptor-beta mutation, not anticipated to occur in resistance to thyroid hormone, causes variable phenotypes.

Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable tissue hyposensitivity to thyroid hormones and is linked to mutations in the thyroid hormone receptor-beta (TRbeta) gene. We report here for the first time in vivo the mutation R429W (CCG-->TCG) located in the exon 10. The artificial mutant obtained in vitro displayed a normal T(3)-binding affinity and transactivation function. Therefore, it was thought to produce little, if any, clinical effect and to escape to clinical detection. The present report is at least in part discordant with this prediction since the prop

Natural history of malignant bone disease in breast cancer and the use of cumulative mean functions to measure skeletal morbidity.

BackgroundBone metastases are a common cause of skeletal morbidity in patients with advanced cancer. The pattern of skeletal morbidity is complex, and the number of skeletal complications is influenced by the duration of survival. Because many patients with cancer die before trial completion, there is a need for survival-adjusted methods to accurately assess the effects of treatment on skeletal morbidity.MethodsRecently, a survival-adjusted cumulative mean function model has been generated that can provide an intuitive graphic representation of skeletal morbidity throughout a study. This model

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… Baseline variables considered included age (< 50 or ≥ 50 years old), time from diagnosis of cancer to study entry (years), time from diagnosis of metastases to study entry (years), urinary hydroxyproline/creatinine ratio, serum bone-specific alkaline phosphatase (BALP) level (in units/L), Brief Pain … Hydroxyproline/creatinine ratio (centered) and positive progesterone-receptor status were the only variables to significantly correlate with overall survival in both univariate ( p = 0.001 and p = 0.022, respectively) and full multivariate analyses ( p = 0.001 and p = 0.050, respectively). …

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

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… Hydroxyproline (OHP) Hydroxyproline (OHP), an amino acid formed from the post-translational hydroxylation of proline, constitutes 12–14% of the total amino acid content of mature collagen [ 31 ]. … Hydroxyproline metabolism by the rat kidney: Distribution of renal enzymes of hydroxyproline catabolism and renal conversion of hydroxyproline to glycine and serine Metabolism 1985 34 955 961 10.1016/0026-0495(85)90145-3 3930916 33. Inoue H. Date Y. Kohashi K. Yoshitomi H. Tsuruta Y. …

Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy.

Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K(ATP)) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel K(ATP) channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evid

Lipid peroxidation products do not activate hepatic stellate cells.

Lipid peroxidation (LPO) is known to be associated with liver fibrosis in chronic liver injury. However, direct effects of the products of LPO on liver fibrogenesis are still not clear. In this study, we examined the LPO products, such as malondiladehyde (MDA), 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), and 15-keto-13,14-dihydro-PGF(2alpha) (15-keto-PGF(2alpha)), on the activation of hepatic stellate cells (HSCs) in vivo and in vitro. Carbon tetrachloride (CCl(4)) was given orally to rats twice a week for 8 weeks. Corn oil was given daily to rats for 8 weeks. CCl(4) induced both free-r

Pentoxifylline downregulates profibrogenic cytokines and procollagen I expression in rat secondary biliary fibrosis.

BACKGROUND: The trisubstituted methylxanthine derivative pentoxifylline inhibits hepatic stellate cell proliferation and collagen synthesis in vitro. The antifibrotic effect of pentoxifylline in a suitable in vivo model of chronic liver fibrogenesis remains to be tested. METHODS: Groups of adult rats (n=20-23) received oral pentoxifylline at a dose of 8 mg/kg/day from week 1 to week 6, and 16 mg/kg/day from week 1 to week 6 or week 4 to week 6 after complete bile duct occlusion. Animals who underwent sham operation that received 16 mg/kg/day pentoxifylline and untreated rats with bile duct oc

[Effects of Dendrobium huoshanense polysaccharide in inhibiting intestinal fibrosis in ulcerative colitis via macrophage IL-36α pathway].

This study investigated the intervention effects and mechanisms of Dendrobium huoshanense polysaccharide(DHP) on intestinal fibrosis in mice with dextran sulfate sodium(DSS)-induced chronic ulcerative colitis(UC). A chronic UC mouse model was established by administering 2% DSS in drinking water for 56 days. Male C57BL/6J mice were randomly divided into a normal group, a model group, a low-dose DHP(50 mg·kg~(-1)) group, and a high-dose DHP(200 mg·kg~(-1)) group. Disease activity index(DAI), colon length, histopathological changes( HE and sirius red staining), hydroxyproline( HYP) content, and …

Buyanghuanwu decoction (BYHWD) attenuates hepatic fibrosis in CCl4-induced mice by regulating bile acid metabolism through activating PPARα.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyanghuanwu decoction (BYHWD), a classical Traditional Chinese Medicine (TCM) formula, has been widely used … Serum biochemical indicators, histopathological staining (H&E, Masson and Sirius red), and hepatic hydroxyproline content were used to assess hepatic injury and fibrosis. Hepatic stellate cell (HSC) activation and TGF-β/Smad signaling pathway, and hepatic inflammation were detected by qPCR, Western blot, immunohistochemistry, immunofluorescence, and arachidonic …

Luteolin ameliorates cornea stromal collagen degradation and inflammatory damage in rats with corneal alkali burn.

Corneal alkali burn (AB) is a blindness-causing ocular trauma commonly seen in clinics. An excessive inflammatory reaction and stromal colla … feration and apoptosis were assessed by CCK-8 assay and flow cytometry respectively. Measurement of hydroxyproline (HYP) in culture supernatants was used to quantify the amount of collagen degradation. Plasmin activity was also assessed. ELISA or real-time PCR was used to detect the production of matrix metalloproteinases (MMPs), IL-8, IL-6 and monocyte chemotac …

[Kiwi fruit essence reduces radiation-induced lung injury by down-regulating TNF-α and PDGF-B in rats].

Objective To observe the role of tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-B (PDGF-B) in kiwi fruit essence-mediate … es were isolated for HE and Masson staining to evaluate alveolitis and pulmonary fibrosis (PF). The hydroxyproline (HYP) content in lung tissues was detected. The mRNA and protein expression of pulmonary TNF-α and PDGF-B were determined by quantitative real-time PCR and immunohistochemistry. Results Compared with the model group, treatment with 60 and 240 mg/kg …

Total alkaloids of bulbus of Fritillaria cirrhosa alleviate bleomycin-induced inflammation and pulmonary fibrosis in rats by inhibiting TGF-β and NF-κB signaling pathway.

BACKGROUND: Bulbus of Fritillaria cirrhosa is a medicinal and edible plant that has the functions of clearing away heat and moisturizing the … y for 21 days. During this period, the body weight changes of the rats were measured, the levels of hydroxyproline (HYP) and inflammatory factors were measured in the collected serum, and the histological analysis of the lung tissue was performed by staining technology. Western blotting and quantitative Polymerase Chain Reaction (qPCR) were used to assess the pr …

Plasma amino acid profiling improves predictive accuracy of adverse events in patients with heart failure.

AIMS: The clinical outcome of heart failure (HF) is complicated by the presence of multiple comorbidities including malnutrition and cachexi … no acids being associated with adverse events were 3-methylhistidine (3-Me-His), β-alanine, valine, hydroxyproline, and tryptophan. Multivariate Cox-proportional hazard analyses indicated that a high 3-Me-His concentration and low β-alanine and valine concentrations were independently associated with adverse events. When HF patients were divided according to the …

Effects of particulate matter from straw burning on lung fibrosis in mice.

OBJECTIVE: To investigate the impacts of particulate matter 2.5 (PM2.5) from straw burning on the acute exacerbation of lung fibrosis in mic … GF-β in peripheral serum were not significantly different in the BLM+PM2.5 and BLM+air groups. Lung hydroxyproline contents increased as the exposure to PM2.5 increased and were significantly higher after four-week than after one-week exposure (P=0.019). Exposure to PM2.5 did not affect the survival of normal mice (100%) but reduced the survival of mice with BLM …

Is clinical expressiveness of Paget's disease of bone decreasing?

Recent data have suggested secular changes implying a current trend toward decreased clinical severity of Paget's disease of bone (PD). To t … n bone scan uptake, was determined by using the index proposed by Coutris. Alkaline phosphatase and hydroxyproline excretion levels were determined in blood and urine, respectively. Baseline characteristics were recorded on a purpose-designed computerized database. The proportion of males (47% in group I vs. 65% in group II; p = 0.007) and the mean (+/-SD) age a …