OBJECTIVE: To investigate the protective effects of procyanidin on periprosthetic osteolysis caused by tricalcium phosphate (TCP) wear particles in the mouse calvaria and its mechanism. METHODS: Forty-eight male ICR mice were randomly divided into sham group, TCP group, and procyanidin (0.2 mg/kg, 1 mg/kg, 5 mg/kg)-treated group (n=12). A periprosthetic osteolysis model in the mouse calvaria was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2 day post-operation, procyanidin (1 mg/kg, 5 mg/kg) was locally injected to the calvaria under the periosteum every other day. After 2 weeks, all the mice were sacrificed to collect the blood samples and the calvaria. Periprosthetic osteolysis and osteoclastogenesis in the mouse calvaria were observed by tartrate resistant acid phosphatase (TRAP) staining and HE staining. mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 in the periprosthestic bone tissue were examined by real-time fluorescence quantitative PCR. Serum contents of total anti-oxidation capacity (T-AOC) and MDA, and superoxide dismutase (SOD) activity were determined by chemical colorimetry. Protein expressions of autophagic biomarkers such as Beclin-1 and LC-3 in periprosthetic bone tissue of the calvaria were examined by Western blot. RESULTS: Compared with sham group, periprosthetic osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1, and serum MDA content were increased significantly in the TCP group (P＜0.05), whereas serum T-AOC level and SOD activity were decreased. The protein expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were both up-regulated markedly in the mouse calvaria of TCP group (P＜0.05). Compared with TCP group, osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 and serum MDA content were decreased obviously in the procyanidine group (P＜0.05), serum T-AOC level and SOD activity were increased, the expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were down-regulated obviously in the mouse calvaria of procyanidin group (P＜0.05). CONCLUSION Procyanidin has a protective effect of periprosthetic osteolysis caused by TCP wear particles in the mouse calvaia, its mechanism may be mediated by inhibition of oxidative stress and autophagy.
Animals ; Autophagy ; Biflavonoids ; pharmacology ; Calcium Phosphates ; adverse effects ; Catechin ; pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Osteolysis ; Oxidative Stress ; Proanthocyanidins ; pharmacology ; Prostheses and Implants ; adverse effects ; Random Allocation ; Skull

OBJECTIVE: To study whether tricalcium phosphate(TCP) wear particles cause injuries of periprosthetic osteocytes in the mouse calvaria, and to explain its molecular mechanism. METHODS: Thirty six-week(ICR)male mice were randomly divided into sham group, model (TCP) group and 3-methyladenine (3-MA) group. A murine calvarial model of osteolysis was established by 30 mg of TCP wear particles implantation over the periosteum around the middle suture of calvaria in mice. On the second postoperative day, the autophagy specific inhibitor 3-MA (1.0 mg/kg) was subcutaneously injected to the calvaria in the 3-MA-treated mice every other day. After 2 weeks, blood and the calvaria were obtained. Micro-CT was used to detect bone mineral density(BMD), bone volume fraction (BVF) and porosity number. HE staining and flow cytometry were performed to analyze the viability and apoptosis of periprosthetic osteocytes. The serum levels of dentin matrix protein 1(DMP-1) and sclerostin (SOST) were determined by ELISA. The proteins expressions of DMP-1, SOST, Beclin-1 and microtuble-associated protein 1 light chain 3 (LC-3) were detected by Western blot in the calvaria osteocytes. RESULTS: Compared with the sham group, the mice in the TCP group showed that a significant decrease in the viability of periprosthetic osteocytes, but obvious increases in number of osteocytes death and osteocytes apoptosis (<0.05), and in serum level and protein expression of SOST; significant decreases in serum level and protein expression of DMP-1 (<0.05), and remarkable up-regulation of autophagy-related factors beclin-1 and the conversion of LC3-Ⅱ from LC3-I in the calvaria osteocytes. Compared with TCP group, the mice in the 3-MA group showed that injuries of calvaria osteocytes were obviously aggravated, and osteocytes apoptosis was significantly increased (<0.05). CONCLUSIONS TCP wear particles can cause injuries of periprosthetic osteocytes via activation of apoptosis and autophagy, which promotes osteolysis around the prosthesis osteolysis and joint aseptic loosening.
Animals ; Apoptosis ; Beclin-1 ; metabolism ; Bone Density ; Calcium Phosphates ; adverse effects ; Extracellular Matrix Proteins ; metabolism ; Glycoproteins ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Microtubule-Associated Proteins ; metabolism ; Osteocytes ; pathology ; Osteolysis ; Prostheses and Implants ; adverse effects ; Skull

BACKGROUND/AIMS: Performance of polyethylene glycol solution (PEG) is often unsatisfactory as bowel preparation agent for colonoscopy. In order to provide equivalent efficacy with better patient tolerance, sodium phosphate tablet (SPT) has been developed. This study was carried out to compare the efficacy and compliance of two bowel preparation methods: PEG with ascorbic acid (PEGA) vs. SPT preparation. METHODS: A multicenter, randomized controlled trial was performed. Primary efficacy variable was overall quality of colon cleansing assessed by Boston bowel preparation scale (BBPS) during colonoscopy. Patient's satisfaction and adverse events were evaluated by means of symptom questionnaire completed by each patient immediately before colonoscopy. RESULTS: A total of 189 patients were randomly assigned to undergo pre-colonoscopic bowel preparation with either SPT (n=96) or PEGA (n=93). Overall BBPS score was 8.3+/-1.12 in the SPT group and 8.4+/-0.96 in the PEGA group (p=0.441). Among the 189 patients, 90 had polyps (47.6%) and 50 had adenomas (26.5%). The polyp/adenoma detection rate was 54.2% (n=52)/27.1% (n=26) for SPT group and 40.9% (n=38)/25.8% (n=24) for PEGA group (p=0.079 and 0.790, respectively). More number of patients were unable to take the prescribed dose of PEGA compared with the SPT regimen (8.6% vs. 2.0%, p=0.045). Overall satisfaction score was 7.9+/-1.63 in the SPT group and 7.4+/-1.53 in the PEGA group (p=0.022). CONCLUSIONS: Degree of colon preparation, polyp/adenoma detection rate and adverse effect were similar between SPT group and PEGA group. Patient compliance and satisfaction were greater in the SPT group.
Abdominal Pain/etiology ; Adenoma/pathology ; Adult ; Ascorbic Acid/*therapeutic use ; Cathartics/adverse effects/*therapeutic use ; Colonic Polyps/pathology ; *Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Nausea/etiology ; Patient Satisfaction ; Phosphates/*therapeutic use ; Polyethylene Glycols/*therapeutic use ; Surveys and Questionnaires

The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2 ± 3.2 and 10.5 ± 2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6 ± 5.9 and 24.8 ± 6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.
Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Lanthanum ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Parathyroid Hormone ; analysis ; Phosphates ; blood ; Pruritus ; blood ; drug therapy ; etiology ; Renal Dialysis ; adverse effects ; methods ; Treatment Outcome ; Vascular Calcification ; blood ; drug therapy

Although renal calcium crystal deposits (nephrocalcinosis) may occur in acute phosphate poisoning as well as type 1 renal tubular acidosis (RTA), hyperphosphatemic hypocalcemia is common in the former while normocalcemic hypokalemia is typical in the latter. Here, as a unique coexistence of these two seperated clinical entities, we report a 30-yr-old woman presenting with carpal spasm related to hypocalcemia (ionized calcium of 1.90 mM/L) due to acute phosphate poisoning after oral sodium phosphate bowel preparation, which resolved rapidly after calcium gluconate intravenously. Subsequently, type 1 RTA due to Sjogren's syndrome was unveiled by sustained hypokalemia (3.3 to 3.4 mEq/L), persistent alkaline urine pH (> 6.0) despite metabolic acidosis, and medullary nephrocalcinosis. Through this case report, the differential points of nephrocalcinosis and electrolyte imbalances between them are discussed, and focused more on diagnostic tests and managements of type 1 RTA.
Acidosis, Renal Tubular/*diagnosis/etiology ; Acute Disease ; Adult ; Antibodies, Antinuclear/blood ; Calcium Gluconate/therapeutic use ; Chronic Disease ; Female ; Humans ; Hydrogen-Ion Concentration ; Hypocalcemia/*chemically induced/complications/drug therapy ; Nephrocalcinosis/complications/*diagnosis/ultrasonography ; Parotid Gland/ultrasonography ; Phosphates/*adverse effects ; Salivary Glands/radionuclide imaging ; Sjogren's Syndrome/complications/*diagnosis/metabolism ; Submandibular Gland/ultrasonography

PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy. The purpose of this study was to determine whether measurement of intact parathyroid hormone (i-PTH) level in thyroidectomy patients could predict hypocalcemia. MATERIALS AND METHODS: We performed a prospective study of patients undergoing total thyroidectomy. Serum concentration of i-PTH, total calcium (Ca), ionized calcium (Ca2+), phosphate (P), magnesium (Mg), and albumin were measured preoperatively and at 0 hour, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours postoperatively. RESULTS: 108 patients were recruited to the study. A total of 50 patients (46%) experienced hypocalcemia. The serum i-PTH concentration was linearly related to the time of measurement, while concentrations of P, Mg, albumin, Ca, and Ca2+ were not. We compared odds ratios, and found that the concentration of i-PTH at 6 hours post operation was the most closely related to the occurrence of hypocalcemic symptom. On ROC analysis using i-PTH level at 6 hours, an i-PTH level of 10.6 mg/dL was found to maximize both sensitivity and specificity at the same time point. CONCLUSION: We found that i-PTH was a predictor of hypocalcemia, and that the earliest predictor of hypocalcemic symptoms was an i-PTH concentration lower than 10.6 mg/dL obtained 6 hours after total thyroidectomy.
Calcium/blood ; Humans ; Hypocalcemia/*diagnosis ; Magnesium/blood ; Odds Ratio ; Parathyroid Hormone/*blood ; Phosphates/blood ; Postoperative Complications/blood/*diagnosis ; Prospective Studies ; Serum Albumin ; Thyroidectomy/*adverse effects

BACKGROUND/AIMS: The aim of this study was to compare polyethylene glycol (PEG) 4 L, split method of PEG 4 L and PEG 2 L plus sodium phosphate (NaP) in the aspect of bowel preparation quality, safety, patients' compliance and preference. METHODS: Total 249 subjects were prospectively enrolled and received bowel preparation for colonoscopy from August to October in 2010; PEG 4 L (93 subjects), split method of 4 L PEG (74 subjects) and PEG 2 L plus NaP 90 mL group (82 subjects). To investigate the completion, preference for bowel preparation and safety, a questionnaire survey was conducted before colonoscopy. RESULTS: There were no significant intergroup differences in the aspect of completion of preparation, cecal intubation time and success rate. Satisfaction and preference were higher in PEG 2 L plus NaP 90 mL and split method of 4 L PEG compared with PEG 4 L. In the aspect of the bowel preparation quality PEG 4 L showed significantly higher quality in the morning colonoscopy (p<0.001). However, in the afternoon colonoscopy PEG 2 L plus NaP 90 mL showed better result than PEG 4 L (p=0.009). Hyperphosphatemia was most frequently observed in PEG 2 L plus NaP 90 mL, but no severe adverse events occurred (p<0.001). CONCLUSIONS: PEG 4 L showed better result than split method of 4 L PEG or PEG 2 L plus NaP 90 mL in the aspect of bowel preparation quality and safety.
Adult ; Aged ; Cathartics/adverse effects/*pharmacology ; Colon/anatomy & histology/*drug effects ; Colonoscopy ; Female ; Humans ; Hyperphosphatemia/etiology ; Male ; Middle Aged ; Patient Compliance ; Phosphates/adverse effects/*pharmacology ; Polyethylene Glycols/adverse effects/*pharmacology ; Prospective Studies ; Questionnaires ; Time Factors

Adefovir dipivoxil, an acyclic nucleoside analogue, has been approved for the treatment of patients with chronic hepatitis B. This agent is efficacious particularly in those who have developed lamivudine resistance. The report according to hypophosphatemia induced by low dose adefovir therapy is very rare. We report one case in which osteomalacia with hypophosphatemia developed in a patient with chronic hepatitis B on adefovir dipivoxil at a low dose, 10 mg daily. A 66-year-old man, who had been taking adefovir for more than 4 years due to lamivudine resistance, presented with muscle weakness and bone pain in both thighs. After 3 years of adefovir therapy, hypophosphatemia and elevated serum alkaline phosphatase levels had been noted. A bone scan showed multiple hot uptakes. All the image findings and clinical symptoms, such as bone pain and muscle weakness were improved after correcting the hypophosphatemia with oral phosphorous supplementation.
Adenine/adverse effects/*analogs & derivatives/therapeutic use ; Aged ; Alkaline Phosphatase/blood ; Antiviral Agents/*adverse effects/therapeutic use ; DNA, Viral/blood ; Dietary Supplements ; Hepatitis B, Chronic/*drug therapy ; Humans ; Hypophosphatemia/*chemically induced/complications ; Liver Cirrhosis/diagnosis ; Male ; Osteomalacia/*diagnosis/etiology ; Phosphates/blood ; Phosphonic Acids/*adverse effects/therapeutic use ; Whole Body Imaging

Matrix metalloproteinase-9 (MMP-9) may play an important role in emphysematous change in chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality and morbidity worldwide. We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, attenuates emphysematous change and MMP-9 induction in the lungs of rats exposed to cigarette smoke. However, it remained uncertain how cigarette smoke induced MMP-9 and how simvastatin inhibited cigarette smoke-induced MMP-9 expression in alveolar macrophages (AMs), a major source of MMP-9 in the lungs of COPD patients. Presently, we examined the related signaling for MMP-9 induction and the inhibitory mechanism of simvastatin on MMP-9 induction in AMs exposed to cigarette smoke extract (CSE). In isolated rat AMs, CSE induced MMP-9 expression and phosphorylation of ERK and Akt. A chemical inhibitor of MEK1/2 or PI3K reduced phosphorylation of ERK or Akt, respectively, and also inhibited CSE-mediated MMP-9 induction. Simvastatin reduced CSE-mediated MMP-9 induction, and simvastatin-mediated inhibition was reversed by farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP). Similar to simvastatin, inhibition of FPP transferase or GGPP transferase suppressed CSE-mediated MMP-9 induction. Simvastatin attenuated CSE-mediated activation of RAS and phosphorylation of ERK, Akt, p65, IkappaB, and nuclear AP-1 or NF-kappaB activity. Taken together, these results suggest that simvastatin may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of RAS in the signaling pathways, in which Raf-MEK-ERK, PI3K/Akt, AP-1, and IkappaB-NF-kappaB are involved.
1-Phosphatidylinositol 3-Kinase/metabolism ; Alkyl and Aryl Transferases/metabolism ; Animals ; Anticholesteremic Agents/pharmacology ; Cells, Cultured ; Enzyme Inhibitors/metabolism/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation, Enzymologic/*drug effects ; I-kappa B Kinase/antagonists & inhibitors/metabolism ; Macrophages, Alveolar/cytology/*drug effects/*enzymology ; Matrix Metalloproteinase 9/genetics/*metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Polyisoprenyl Phosphates/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Sesquiterpenes/metabolism ; Signal Transduction/physiology ; Simvastatin/*pharmacology ; Smoke/*adverse effects ; *Tobacco/adverse effects/chemistry

BACKGROUND/AIMS: Bowel preparation for colonoscopy remains an unpleasant experience because oral solutions have unpleasant tastes and may provoke abdominal pain, nausea, vomiting, and sleep disturbance. Duodenoscopic bowel preparation is an alternative method for patients who are unwilling to take oral preparation solution or for those who are supposed to have both gastroscopic and colonoscopic examination on the same day. We assessed the effectiveness and tolerance of duodenoscopic bowel preparation. METHODS: Patients in group OA (orally administered) ingested 45 mL of sodium phosphate (NaP) in the evening before the day of procedure and in the morning on the day of colonoscopy, whereas patients in group EA (endoscopically administered) were prepared for the procedure by duodenoscopic infusion of 90 mL of NaP diluted with 180 mL of water into the second portion of the duodenum. After 4 hours, we assessed the overall quality of colonic cleansing, using a range of excellent to inadequate. The patients completed a questionnaire on their preparation-associated symptoms, tolerance, and preference. RESULTS: In group EA, sleep disturbance (p<0.05) and nausea (p<0.05) occurred less frequently than in group OA. Overall, the tolerance rating for preparation was higher in group EA. However, the quality of colonic cleansing and cecum intubation time was not different between the two groups. Patients in group EA who had ingested NaP in the past preferred duodenoscopic bowel preparation. CONCLUSIONS: Duodenoscopic bowel preparation may play a role in colonic cleansing especially for patients who are scheduled to undergo gastroscopic and colonoscopic examination on the same day and for those who are unwilling to ingest NaP.
Administration, Oral ; Adult ; Aged ; Cathartics/*administration & dosage/adverse effects ; *Colonoscopy ; *Duodenoscopy ; Female ; Humans ; Image Enhancement ; Irrigation ; Male ; Middle Aged ; Phosphates/*administration & dosage/adverse effects/chemistry ; Questionnaires ; Treatment Outcome