Humans ; Warfarin/therapeutic use* ; Cytochrome P-450 CYP2C9/genetics* ; Anticoagulants/therapeutic use* ; Genotype ; Heart Valves ; China ; Apolipoproteins E/genetics* ; Dose-Response Relationship, Drug ; Receptors, Calcitriol/genetics*

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Calcifediol/blood* ; Calcitriol/therapeutic use* ; Clinical Trials as Topic ; Ergocalciferols/therapeutic use* ; Humans ; Male ; Prostatic Neoplasms/prevention & control* ; Signal Transduction ; Vitamin D/metabolism* ; Vitamin D Deficiency/epidemiology*

OBJECTIVETo investigate the changes in the mRNA and protein expression of high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB) in lung tissues of asthmatic mice and the interventional effect of vitamin D.

METHODSA total of 48 BALB/c mice were randomly divided into control group, asthma group, and 1,25-(OH)Dintervention group, with 16 mice in each group. An animal model of asthma was established, and lung tissue samples were taken in each group at weeks 1 and 2 of ovalbumin challenging. Conventional hematoxylin-eosin staining was used to measure airway wall thickness. Immunohistochemical staining was used to observe the expression of HMGB1, TLR4, and NF-κB in lung tissues. Quantitative real-time PCR and Western blot were used to investigate the changes in the mRNA and protein expression of HMGB1, TLR4, and NF-κB.

RESULTSAt weeks 1 and 2 of ovalbumin challenging, compared with the control group, the asthma group had a significant increase in airway wall thickness and the intervention group had a significant reduction compared with the asthma group (P<0.05). The asthma group had significantly higher mRNA expression of HMGB1, TLR4, and NF-κB in lung tissues than the control group, and the intervention group had significantly lower mRNA expression of TLR4 and NF-κB than the asthma group (P<0.05). At week 1 of ovalbumin challenging, there was no significant difference in the mRNA expression of HMGB1 between the intervention group and the asthma group (P>0.05). At week 2, the intervention group had a significant reduction in the mRNA expression of HMGB1 compared with the asthma group (P<0.05). At weeks 1 and 2 of ovalbumin challenging, the asthma group had significantly higher protein expression of HMGB1, TLR4, and NF-κB in lung tissues than the control group, and the intervention group had significantly lower expression than the asthma group (P<0.05). Airway wall thickness was positively correlated with the mRNA expression of HMGB1, TLR4, and NF-κB in lung tissues (r=0.804, 0.895, and 0.834; P<0.05).

CONCLUSIONSThe HMGB1/TLR4/NF-κB signaling pathway plays an important role in the pathogenesis of asthma, and an appropriate amount of 1,25-(OH)Dhas a regulatory effect on this pathway and may prevent the progression of asthma. Therefore, 1,25-(OH)Dis expected to become a new choice for the treatment of asthma.

Animals ; Asthma ; drug therapy ; etiology ; pathology ; Calcitriol ; therapeutic use ; Female ; HMGB1 Protein ; analysis ; physiology ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; analysis ; physiology ; Signal Transduction ; physiology ; Toll-Like Receptor 4 ; analysis ; physiology

BACKGROUNDTetracycline (TET) has been found to have both antibiotic and anti-inflammatory properties. The anti-inflammatory effect of topical TET on atopic dermatitis (AD) has not been reported. The purpose of this study was to explore the potential role of topical TET and its anti-inflammatory effects in a mouse model of AD.

METHODSThe 2% TET was applied topically to ears of MC903-induced AD-like BALB/c mice once a day. AD-like symptoms and severity were evaluated by assessing skin scoring of dermatitis, ear thickness, and frequency of scratching. Serum IgE and thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay. Western blot was used for analyzing the expressions of TSLP, protease-activated receptor 2 (PAR2), and nuclear factor-kappa B (NF-κB) in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of TSLP and inflammatory cytokines including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, and IL-1β in skin lesions.

RESULTSScoring of dermatitis (9.00 ± 0.63 vs. 6.67 ± 1.03, P = 0.001), ear thickness (0.44 ± 0.02 mm vs. 0.40 ± 0.03 mm, P = 0.018), and serum IgE level (421.06 ± 212.13 pg/ml vs. 244.15 ± 121.39 pg/ml, P = 0.047) were all improved in the 2% TET treatment group compared with AD group. Topical TET significantly reduced the serum level of TSLP (119.04 ± 38.92 pg/ml vs. 65.95 ± 54.61 pg/ml, P = 0.011) and both mRNA and protein expressions of TSLP in skin lesions compared with AD group (P = 0.003 and 0.011, respectively), and NF-κB and PAR2 expression in skin lesions were also suppressed (P = 0.016 and 0.040, respectively). Furthermore, expressions of inflammatory cytokines IL-4, IL-13, and TNF-α in skin lesions were down-regulated in 2% TET group compared with AD group (P = 0.035, 0.008, and 0.044, respectively).

CONCLUSIONSTopical TET exerted anti-inflammatory effects through suppression of TSLP and inflammatory cytokines in AD mouse model, suggesting TET as a potential agent for the topical treatment of AD in the future.

Administration, Topical ; Animals ; Calcitriol ; analogs & derivatives ; toxicity ; Cytokines ; Dermatitis, Atopic ; chemically induced ; drug therapy ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Mice ; Mice, Inbred BALB C ; Tetracyclines ; administration & dosage ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats.

METHODSType 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups: untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later.

RESULTSIn the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased (all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group (P<0.05), whereas the other parameters were significantly decreased (all P<0.05).

CONCLUSION1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.

Animals ; Blood Glucose ; analysis ; Calcitriol ; therapeutic use ; Diabetes Mellitus, Experimental ; blood ; complications ; Diabetes Mellitus, Type 2 ; blood ; complications ; Hypertrophy, Left Ventricular ; prevention & control ; Insulin ; blood ; Male ; Rats ; Rats, Wistar ; Receptors, Calcitriol ; analysis ; Streptozocin

OBJECTIVETo investigate the effects of 1,25-(OH)(2)D(3) on the airway remodeling and expression of high-mobility group box 1 (HMGB1) and Toll-like receptor 4 (TLR4) in the lungs among asthmatic mice.

METHODSThirty female mice (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)(2)D(3) intervention groups. An asthmatic mouse model was established by intraperitoneal injection and aerosol inhalation of ovalbumin. The intervention group was given 1,25-(OH)(2)D(3) by intraperitoneal injection 0.5 hour before each aerosol inhalation, while the control group used normal saline instead. The hematoxylin-eosin staining was used to observe the mouse airway structural changes. The mRNA and protein expression of HMGB1 and TLR4 was measured by RT-PCR and immunohistochemistry, respectively. Pearson correlation analysis was performed.

RESULTSThe asthma group had a significantly increased airway wall thickness compared with the control group (P<0.05); the intervention group had a significantly lower increase in airway wall thickness than the asthma group (P<0.05). The mRNA and protein expression of HMGB1 and TLR4 was significantly higher in the asthma group than in the control group (P<0.05); the mRNA and protein expression of HMGB1 and TLR4 in the intervention group was significantly lower than that in the asthma group, but still higher than that in the control group (P<0.05). A positive correlation was found between the protein expression of HMGB1 and TLR4 (P<0.01), and so was their mRNA expression (P<0.01).

CONCLUSIONSHMGB1 and TLR4 may be involved in asthmatic airway remodeling. 1,25-(OH)(2)D(3) can reduce the airway remodeling in asthmatic mice, which may be related to the downregulation of HMGB1 and TLR4 expression in the lungs of asthmatic mice.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; metabolism ; Calcitriol ; pharmacology ; therapeutic use ; Female ; HMGB1 Protein ; genetics ; Lung ; metabolism ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; analysis ; Toll-Like Receptor 4 ; genetics

OBJECTIVETo investigate the correlation between regulatory T (Treg) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] in relation to Treg cells.

METHODSFifty female BALB/c mice were randomly divided into five groups: the basal control (BAS), Sham, ovariectomy (OVX), OVX+diethylstilbestrol (OVX+DES), and OVX+1,25(OH)₂D₃. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cytometry and quantitative RT-PCR, respectively.

RESULTSIn comparison with the Sham group, a significant decrease was found in the OVX group in such indices as trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th). 1,25(OH)₂D₃and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRNA expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-treated group compared with those in the sham group. 1,25(OH)2D₃and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters.

CONCLUSIONThe decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25(OH)₂D₃is related to regulatory T cells.

Animals ; Bone Density Conservation Agents ; pharmacology ; therapeutic use ; Calcitriol ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; drug effects ; Mice ; Mice, Inbred BALB C ; Osteoporosis ; drug therapy ; Ovariectomy ; T-Lymphocytes, Regulatory ; drug effects

Biopsy ; Calcitriol ; therapeutic use ; Calcium ; therapeutic use ; Fanconi Syndrome ; diagnosis ; drug therapy ; Humans ; Immunosuppressive Agents ; therapeutic use ; Pilot Projects ; Prednisone ; therapeutic use

The metastatic calcification is defined as the deposition of calcium salt in normal tissue with an abnormal serum biochemical environment, such as chronic kidney disease, hyperparathyroidism, and hypercalcemia related with malignancy. Although the metastatic calcification can develop in any organs and tissues, presenting its symptoms and complications are rare. Thus a few cases have been reported. This case shows the metastatic calcification of the small intestine without any peritoneal and mesenteric vascular calcification which was early diagnosed by computed tomography and mesenteric angiography in a patient with abdominal pain, receiving continuous ambulatory peritoneal dialysis due to end stage renal disease. The clinician should early consider the metastatic calcification as differential diagnosis when unidentified calcifications are noted in simple abdominal X-ray such as in the present case, and promptly confirm it by using appropriate diagnostic tests in order to prevent its complications and progression.
Calcinosis/*diagnosis/drug therapy/etiology ; Calcitriol/therapeutic use ; Calcium/blood ; Calcium Carbonate/therapeutic use ; Calcium Channel Agonists/therapeutic use ; Humans ; Intestine, Small/*radiography ; Kidney Failure, Chronic/therapy ; Male ; Mesenteric Artery, Superior/radiography ; Middle Aged ; Peritoneal Dialysis, Continuous Ambulatory/*adverse effects ; Tomography, X-Ray Computed

Low level laser or light treatment on the various clinical condition is getting considerable attention now. However, there has been no report about the clinical effect of low level polarized polychromatic noncoherent light (LPPL) on the inflammatory skin disease. We experienced a case of acrodermatitis continua in a pregnant woman refractory to any conventional treatment including the most potent topical steroid. She was successfully treated with LPPL. LPPL could be a possible treatment modality producing substantial clinical result in inflammatory skin condition without any side-effect.
Acrodermatitis/*therapy ; Adult ; Calcitriol/analogs & derivatives/therapeutic use ; Female ; Humans ; Inflammation/therapy ; Light ; Phototherapy/*methods ; Pregnancy ; Pregnancy Complications ; Psoriasis/drug therapy ; Skin Diseases/*therapy