PURPOSE: In hemodialysis patients with secondary hyperparathyroidism, intravenous administration of calcitriol became widely utilized. In CAPD patients, however, the intravenous administration of calcitriol is not practical. The purpose of the present study was to determine the effect and safety of intraperitoneal (IP) calcitriol pulse therapy in CAPD patients. METHODS: All patients undergoing CAPD between January 2006 and January 2007 and willing to give informed consent were eligible. Inclusion criteria were age greater 18 years, on CAPD for at least 6 months, and secondary hyperparathyroidism (intact PTH >300 pg/mL). Intraperitoneal calcitriol was given by direct infusion into the dialysate (2.0 microgram) twice per week. If hypercalcemia (>10.5 mg/dL) and hyperphosphatemia (>6.5 mg/dL) developed, the patients were excluded from study. RESULTS: Eighteen patients were enrolled into the study. Among them, 16 patients completed the study period. After IP calcitriol for 3 months, there was a significant drop of iPTH level from the pretreatment level of 490+/-234 pg/mL to the level of 318+/-315 pg/mL (p<0.05). There were no definite hypercalcemia during the study period, and only 1 patient was excluded from study due to hyperphosphatemia. CONCLUSION: In CAPD patients, IP calcitriol pulse therapy is effective in treating secondary hyperparathyroidism, and that IP calcitriol pulse therapy is associated with a low incidence of hypercalcemia and hyperphosphatemia.
Administration, Intravenous ; Calcitriol ; Humans ; Hypercalcemia ; Hyperparathyroidism, Secondary ; Hyperphosphatemia ; Incidence ; Informed Consent ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Renal Dialysis

Secondary hyperparathyroidism is a major complication in ESRD patients undergoing dialysis. In hemodialysis patients with secondary hyperparathyroidism, intravenous administration of paricalcitol became widely utilized. In CAPD patients, however, the intravenous administration of paricalcitol which requires frequent visits to the clinic is not practical. The subject of this study was one CAPD patient with secondary hyperparathyroidism. He had already received oral calcitriol pulse therapy for 6 months and thereafter refused parathyroidectomy and intravenous paricalcitol which required frequent visits to the hospital. Furthermore, paricalcitol capsule is not yet introduced in Korea. Consequently, intraperitoneal paricalcitol therapy was tried whereby the patient was taught how to inject the paricalcitol (5 ug) directly into the dialysate for three times per week before bedtime. Blood samples for measurement of intact parathyroid hormone (iPTH), serum ionized calcium, serum phosphate, serum total alkaline phosphatase levels were obtained at baseline and after 1, 2, 3 and 4 months of treatment. After usage of intraperitoneal paricalcitol for 2 months, there was a significant decrease in iPTH level. In conclusion, intraperitoneal paricalcitol therapy might be effective for suppressing iPTH in CAPD patients with secondary hyperparathyroidism. A large-scale and long-term study must be conducted for safety and clinical effect.
Administration, Intravenous ; Alkaline Phosphatase ; Calcitriol ; Calcium ; Dialysis ; Ergocalciferols ; Humans ; Hyperparathyroidism, Secondary ; Injections, Intraperitoneal ; Kidney Failure, Chronic ; Korea ; Parathyroid Hormone ; Parathyroidectomy ; Peritoneal Dialysis, Continuous Ambulatory ; Renal Dialysis

BACKGROUND/AIMS: This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 microg) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 +/- 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.
Administration, Oral ; Age Factors ; Aged ; Alendronate/administration & dosage/*adverse effects ; Bone Density Conservation Agents/administration & dosage/*adverse effects ; Calcitriol/administration & dosage/*adverse effects ; Drug Combinations ; *Endoscopy, Digestive System ; Esophagus/*drug effects/pathology ; Female ; Gastric Mucosa/*drug effects/pathology ; Humans ; Middle Aged ; *Postmenopause ; Predictive Value of Tests ; Republic of Korea ; Sex Factors ; Tablets, Enteric-Coated ; Time Factors ; Treatment Outcome ; Vitamins/administration & dosage/*adverse effects

To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5 mg/(kg.d) is safe and efficacious.
Adolescent ; Adult ; Aged ; Androgens ; administration & dosage ; Anemia, Refractory ; drug therapy ; Anemia, Refractory, with Excess of Blasts ; drug therapy ; Calcitriol ; administration & dosage ; therapeutic use ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Recombinant Proteins ; Treatment Outcome

To determine the effect of exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] combined with induced parturition on calcium (Ca) metabolism, cows received a single intramuscular injection of 1,25(OH)2D3 and prostaglandin F2alpha (PGF2alpha) closely before calving. Ten late-pregnant, multiparous Holstein cows were assigned to 1,25(OH)2D3 group (five treated with both 1,25(OH)2D3 and PGF2alpha) and control group (five treated with PGF2alpha). 1,25(OH)2D3 group showed an increase in plasma Ca concentration around parturition, whereas control group revealed a decrease in plasma Ca level. Plasma Ca concentration in 1,25(OH)2D3 group were significantly higher than that in control group during .0.5 to 3 days after parturition.
Animals ; Calcitriol/*pharmacology ; Calcium/blood/*metabolism ; Cattle/*metabolism ; Dinoprost/*pharmacology ; Drug Administration Schedule/veterinary ; Female ; Injections, Intramuscular/veterinary ; Magnesium/blood ; Parturient Paresis/prevention&control ; Parturition/blood/*metabolism ; Phosphorus/blood ; Pregnancy ; Statistics, Nonparametric

OBJECTIVETo investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model.

METHODRat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay.

RESULTThe rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P<0.05). The levels of urinary calcium and serum BALP in rats of maximum rPTH(1-84) injection group (160 µg/kg) were higher than those of normal control group (P<0.05). The rats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus concentration compared with normal control group (P<0.05). The amount of urinary calcium also exceeded the other groups (P<0.05), but no with significant difference in BMD of bilateral femoral bone and lumbar vertebra between negative control group and normal control group (P>0.05).

CONCLUSIONCalcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and increase BMD, but can not correspondingly decrease the phosphorus concentration and increase the excretion of calcium in urine.

Absorptiometry, Photon ; Alkaline Phosphatase ; blood ; Animals ; Bone Density ; Calcitriol ; administration & dosage ; Calcium ; blood ; urine ; Disease Models, Animal ; Femur ; Hormone Replacement Therapy ; Humans ; Hypothyroidism ; drug therapy ; Lumbar Vertebrae ; Parathyroid Glands ; surgery ; Parathyroid Hormone ; administration & dosage ; therapeutic use ; Phosphorus ; blood ; Rats ; Recombinant Proteins ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the association of polymorphisms of start codon (Fok I site) and CDX2 binding site in vitamin D receptor gene (VDR) concerned with the effect of calcium supplementation on bone mineral density (BMD) and bone turnover markers of postmenopausal women.

METHODSTwo hundreds unrelated postmenopausal women of Han ethnicity in Shanghai were randomly divided into 2 groups of 100 women: high calcium group (1000 mg element calcium and 400 units of vitamin D were given daily for 12 months) and low calcium group (300 mg element calcium and 300 units of vitamin D were given daily for 12 months). BMD and bone turnover markers were measured at baseline and 12 months after calcium supplementation. VDR gene Fok I and CDX2 polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific multiplex PCR, respectively.

RESULTSOne hundred and seventy-one women completed 12-month study period. The frequency of VDR Fok I genotypes was 48.0 % for Ff, 31.0 % for FF, and 21.0 % for ff, and the frequency of CDX2 genotypes was 56.7 % for AG, 25.7% for GG, and 17.6% for AA. The frequencies distribution of Fok I and CDX2 alleles in the entire population or in two subgroups all followed the Hardy-Weinberg equilibrium. No significant difference of baseline BMD and bone turnover markers in Fok I genotypes or CDX2 genotypes was observed in the entire population or in two subgroups. Moreover, regardless of calcium supplementation given for 12 months, no significant association was found between Fok I or CDX2 polymorphisms and the endpoint values or percentage changes of any BMD and bone turnover markers in either high calcium group or low calcium group.

CONCLUSIONThere is no significant relationship between VDR gene Fok I or CDX2 polymorphisms and the effect of high or low doses calcium supplementation on BMD and bone turnover markers in Shanghai postmenopausal women of Han ethnicity.

Aged ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Calcium, Dietary ; administration & dosage ; therapeutic use ; Codon, Initiator ; genetics ; Dietary Supplements ; Drug Therapy, Combination ; Female ; Gene Frequency ; Genotype ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Postmenopause ; drug effects ; Receptors, Calcitriol ; genetics ; Vitamin D ; administration & dosage ; therapeutic use ; Vitamins ; administration & dosage ; therapeutic use

This study was aimed to examine whether a combination of all-trans retinoic acid (ATRA), 1, 25-dihydroxyvitamin D(3) and androgen possesses the therapeutic value for the MDS-refractory anemia (MDS-RA), and to analyze the mechanisms in detail. 62 cases receiving a scheme of combination of ATRA, 1, 25-dihydroxyvitamin D(3) and androgen (group A) were monitored. The remaining 33 cases (group B) were provided with vitamin supplementation, chalybeate drugs, and one or two of the combination. Bone marrow aspiration and biopsy were performed for collecting the specimens at the baseline and afterwards. The conditions of the patients were monitored by means of weekly complete blood counts and the monthly examination, including toxicity test, physical examination, electrocardiography, and biochemistry panel. The results showed that after treating for 8 weeks in group A, 4 out of 62 patients showed complete remission and 12 patients showed partial remission according to the defined response criteria, and 43 patients (69.35%) showed hematological improvement (HI). The further treatment for 16 out of 62 patients (25.81%), 13 failures (10 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(5)) with a median survival interval of 26.25 months, were observed and interrupted for some reasons. However, partial remission was observed only in 3 patients in group B, and HI amounted to 51.51%. Furthermore, the disease progression was observed in 12 out of 33 patients (36.36%) with a median survival interval of 16 months, 9 failures (including 6 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(4)). The overall ratios of survival for 3 and 5 years in group A, which received the combination, reached to 69.24% and 53.72% respectively, in comparison with 52.23% and 31.34% in the patients of group B (log-rank, P = 0.016). The following requirements, if were met, would be significant for prognosis: the combination regiment, no transformation, children, no complication, female, 90-120 g/L of hemoglobin concentration, normal cellular bone marrow and uni-cytopenias (P < 0.05). Moreover, Cox regression showed that therapy, transformation and age are all the independent factors (P < 0.05). It is concluded that the combination of above mentioned 3 drugs may be effective and safe treatment for the patients with MDS-RA. Its relevant mechanisms can be involved in the combination, that elicits a wide range of pharmacological effects, such as differentiation, anti-tumor-promotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Androgens ; administration & dosage ; therapeutic use ; Anemia, Refractory ; blood ; drug therapy ; Blood Cell Count ; Calcitriol ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; drug therapy ; Retrospective Studies ; Survival Analysis ; Time Factors ; Treatment Outcome ; Tretinoin ; administration & dosage ; therapeutic use

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

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.
Administration, Intranasal ; Animals ; Anti-Allergic Agents ; Calcitriol ; Cell Proliferation ; Dendritic Cells ; Eosinophils ; Flow Cytometry ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lymph Nodes ; Lymphocytes ; Major Histocompatibility Complex ; Mice ; Models, Animal ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Vitamin D