OBJECTIVETo observe the clinical results of proximal femoral nail anti-rotation (PFNA) combined with zoledronic acid injection in the treatment of osteoporotic intertrochanteric fractures in the elderly.

METHODS60 elderly patients with osteoporotic intertrochanteric fractures were diagnosed using a dual energy X-ray bone density instrument. Patients were randomly divided into treatment or control groups (30 cases in each group). Patients in both groups were treated by closed/open reduction and internal fixation using PFNA. In the treatment group, patients received one zoledronic phosphonic acid injection of 5 mg/100 ml via intravenous drip, in addition to 600 mg of Caltrate D (qd) and 0.25 mg of alpha ossification alcohol (qd). The control group received 600 mg of Caltrate D (qd) and 0.25 mg of alpha ossification alcohol (qd). The oral drugs were administered for 12 months. Bone pain relief was observed, and changes in the bone mineral density (BMD) of the lumbar and health-side hip were recorded. Clinical results were evaluated using the Visual Analogue Scale (VAS), Harris joint function score, and Osteo- porosis Quality of Life Scale (OQOLS).

RESULTSCompared with the control group, bone pain symptoms were significantly alleviated (p < 0.05) in the treatment group. In the treatment and control groups, both between-group and within-group differences in BMD were significantly increased in L1e4, femoral neck and trochanter (p < 0.05). No significant differences were found between the two groups in regard to the involved hip or the total rate of improvement at the end of the follow-up period, although cases in the treatment group had higher OQOLS scores than those of the controls (p = 0.04). Cases in the treatment group healed more quickly than those in the control group [(13 ± 3.2) weeks vs (15 ± 4.6) weeks, p = 0.02]. During the follow-up period, cases in the treatment group had no new fractures, whereas 2 new cases of hip fracture and 2 cases of distal radial fractures were observed among the controls.

CONCLUSIONZoledronic acid injection combined with PFNA is a favorable treatment option for the elderly patients with osteoporotic intertrochanteric fracture. It can effectively relieve bone pain, increase bone density, improve quality of life, reduce the occurrence of new fractures and promote fracture healing.

Aged ; Aged, 80 and over ; Bone Density ; Bone Nails ; Combined Modality Therapy ; Diphosphonates ; administration & dosage ; Female ; Hip Fractures ; psychology ; therapy ; Humans ; Imidazoles ; administration & dosage ; Injections ; Male ; Middle Aged ; Osteoporotic Fractures ; psychology ; therapy ; Quality of Life

BACKGROUNDSystemic administration of bisphosphonates has shown promising results in the treatment of osteonecrosis of the femoral head (ONFH). However, few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH. The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH.

METHODSThis experimental study was conducted between October 2014 and June 2015. Forty-five rabbits underwent simulated ONFH surgery. Immediately following surgery, they were divided into three groups: model (untreated, n = 15), HA (treated with HA alone, n = 15), and HA + ZOL (treated with HA soaked in a low-dose ZOL solution, n = 15). Histological, immunohistochemical, and quantitative analyses were performed to evaluate bone formation and resorption 2, 4, and 8 weeks after surgery.

RESULTSGross bone matrix and hematopoietic tissue formation were observed in the HA + ZOL group 4 weeks after surgery. The immunohistochemical staining intensities for 5-bromodeoxyuridine, runt-related transcription factor 2, osteocalcin, osteopontin, and osteoprotegerin were significantly higher in the HA + ZOL group than that in the model (P < 0.001, P< 0.001, P< 0.001, P< 0.001, and P = 0.018, respectively) and HA groups (P = 0.003, P = 0.049, P< 0.001, P = 0.020, and P = 0.019, respectively), whereas receptor activator of the nuclear factor-κB ligand staining intensity was significantly lower in the HA + ZOL group than that in the model and HA groups (P = 0.029 and P = 0.015, respectively) 4 weeks after surgery. No significant differences in bone formation or bone resorption marker expression were found between the three groups 2 or 8 weeks after surgery (P > 0.05).

CONCLUSIONSLocal administration of HA soaked in a low-dose ZOL solution increased new bone formation while inhibiting bone resorption in an animal model of ONFH, which might provide new evidence for joint-preserving surgery in the treatment of ONFH.

Animals ; Diphosphonates ; administration & dosage ; therapeutic use ; Durapatite ; administration & dosage ; therapeutic use ; Female ; Femur Head Necrosis ; drug therapy ; metabolism ; Imidazoles ; administration & dosage ; therapeutic use ; Immunohistochemistry ; Male

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.
Aged ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Aspartate Aminotransferases/blood ; Drug Administration Schedule ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics/isolation & purification ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Imidazoles/*therapeutic use ; Isoquinolines/*therapeutic use ; Liver/diagnostic imaging ; Liver Cirrhosis/complications ; Male ; Middle Aged ; RNA, Viral/blood ; Retrospective Studies ; Sulfonamides/*therapeutic use ; Treatment Outcome

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of butoconazole in human plasma. Human plasma samples of 0.2 μL were pretreated by a single step protein precipitation procedure and analyzed using a high performance liquid chromatography (HPLC) electrospray tandem mass spectrometer system. The compounds were eluted isocratically on an Inertsil ODS-SP column (100 mm×2.1 mm, 3 μm), ionized using a positive ion atmospheric pressure electrospray ionization source and analyzed using multiple reaction monitoring (MRM) mode. The ion transitions monitored were m/z 412.8→165.1 for butoconazole and m/z 453.4→230.3 for the internal standard. The chromatographic run time was 3.5 min per injection, with retention time of 2.47 min and 2.15 min for butoconazole and repaglinide, respectively. The method was validated to be linear over the range of 20 to 8000 pg/mL (r>0.999) by using a weighted (1/x(2)) quadratic regression. The mean recovery rate was more than 86.7%, and the intra- and inter-day precision of the quality control samples (QCs) was less than 8.3% and the accuracy ranged from 96.0% to 110.2%, which indicated that the quantitative method was reliable and accurate. The method is simple, rapid, and has been applied successfully to a pharmacokinetics study of butoconazole nitrate suppositories in healthy Chinese females.
Administration, Intravaginal ; Adult ; Antifungal Agents ; blood ; chemistry ; pharmacokinetics ; Calibration ; Chromatography, Liquid ; methods ; Female ; Humans ; Imidazoles ; administration & dosage ; blood ; pharmacokinetics ; Middle Aged ; Molecular Structure ; Reproducibility of Results ; Tandem Mass Spectrometry ; methods ; Time Factors ; Young Adult

Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and-mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infection has been initiated, which is hardly achievable through parenteral immunization. Given that effective delivery of vaccine materials into immune inductive sites is prerequisite for effective oral mucosal vaccination, M cell-targeting strategy is crucial in successful vaccination since M cells are main gateway for luminal antigen influx into mucosal lymphoid tissue. Here, we applied previously identified M cell-targeting ligand Co1 to VP1 of FMDV in order to test the possible oral mucosal vaccination against FMDV infection. M cell-targeting ligand Co1-conjugated VP1 interacted efficiently with M cells of Peyer's patch. In addition, oral administration of ligand-conjugated VP1 enhanced the induction of VP1-specific IgG and IgA responses in systemic and mucosal compartments, respectively, in comparison with those from oral administration of VP1 alone. In addition, the enhanced VP1-specific immune response was found to be due to antigen-specific Th2-type cytokine production. Collectively, it is suggested that the M cell-targeting strategy could be applied to develop efficient oral mucosal vaccine against FMDV infection.
Administration, Oral ; Animals ; Foot-and-Mouth Disease ; Foot-and-Mouth Disease Virus ; Imidazoles ; Immunity, Mucosal ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Lymphoid Tissue ; Nitro Compounds ; Phenobarbital ; Vaccination

In April 2010, pruritic symptoms were recognized in 3 privately-owned Siamese cats raised in Gwangju, Korea. Examination of ear canals revealed dark brown, ceruminous otic exudates that contain numerous live mites at various developmental stages. Based on morphological characteristics of adult mites in which caruncles were present on legs 1 and 2 in adult females and on legs 1, 2, 3, and 4 in adult males while the tarsus of leg 3 in both sexes was equipped with 2 long setae, the mite was identified as Otodectes cynotis. Ten ear mite-free domestic shorthaired cats were experimentally infected with O. cynotis to evaluate the efficacy of 10% imidacloprid/1% moxidectin spot-on. Live mites were recovered from 1 of 10 treated cats on day 9 post-treatment (PT) while no live mites were observed from the ear canals of treated cats on days 16 and 30 PT. The efficacy of 10% imidacloprid/1% moxidectin spot-on on O. cynotis in cats was, therefore, 90% on day 9 and 100% on days 16 and 30 PT. This is the first report of otodectosis in 3 cats naturally infested with O. cynotis in Gwang-ju, Korea. Both natural and experimental infestations were successfully treated with 10% imidacloprid/1% moxidectin spot-on.
Acaricides/*administration & dosage ; Administration, Topical ; Animals ; Cat Diseases/*diagnosis/*drug therapy ; Cats ; Ear Diseases/diagnosis/drug therapy/veterinary ; Female ; Imidazoles/*administration & dosage ; Macrolides/*administration & dosage ; Male ; Mite Infestations/diagnosis/drug therapy/*veterinary ; Nitro Compounds/*administration & dosage ; Psoroptidae/*growth & development ; Republic of Korea ; Solutions/administration & dosage ; Treatment Outcome

OBJECTIVETo examine the effects of niacin on lysophosphatidylcholine (LPC)-induced intercellular adhesion molecule-1 (ICAM-1), and gained insight to the mechanisms.

METHODHuman umbilical vein endothelial cell line was cultured using Medium 200 medium in incubator at 37 °C and 5% CO2 condition.Experimental groups:(1) the negative control group:medium; (2) LPC different time groups:the medium added with 20 µmol/L final concentration of LPC, were cultured for 10 min and 8 h, 24 h; (3) LPC+ p38-mitogen-activated protein kinase (p38MAPK) inhibitor (SB203580) group:the medium added with 10 µmol/L p38MAPK inhibitor (SB203580) was cultured for 1 h, then human umbilical vein endothelial cells (HUVECs) added with the LPC were cultured for 10 min, 8 h and 24 h.(4) LPC+different niacin dose group:after separately adding with 0.25, 0.5, 1 mmol/L niacin, the cells were cultured for 18 h, then HUVECs added with the LPC were cultured for 10 min, 8 h and 24 h. Cell concentration in each group was 5×10(5)/ml, inoculated in 6-well plates, each well 1 ml. Detected by Western blot analysis of pp38MAPK, ICAM-1 protein content, real-time quantitative PCR to detect endothelial cell ICAM-1 mRNA expression, cell immunofluorescence to detect LPC-induced ICAM-1 protein expression.

RESULTIn LPC 24 h group, the expression of ICAM-1 protein was significantly increased 0.786 ± 0.02, the LPC+niacin group, ICAM-1 protein levels (0.487 ± 0.015) was significantly lower than the LPC 24 h group (P < 0.01), in LPC+SB203580 intervention group, ICAM-1 protein levels (0.461 ± 0.011) was significantly lower than that of the LPC 24 h group (P < 0.01), but did not reach the level of the control group. Adding LPC to culture for 10 min, phosphorylation of p38MAPK (pp38MAPK) reached its peak (0.47 ± 0.02), niacin could reduce the pp38MAPK (0.07 ± 0.02), SB203580 could also reduce its activity (0.11 ± 0.02). Adding LPC to culture for 8 h, ICAM-1 mRNA expression (8.16 ± 0.15) compared with the control group (1.00 ± 0.02) had a significant increase (t = 24.34, P < 0.01). Compared with the LPC 8 h, niacin reduced LPC-induced ICAM-1 mRNA expression (3.85 ± 0.14), and showed a dose-dependent manner (F = 8.06, P < 0.01), while SB203580 could not effectively reduce the ICAM-1 mRNA (8.09 ± 0.11).

CONCLUSIONNiacin prevented LPC-induced endothelial dysfunction by reducing expression of ICAM-1. These mechanisms appeared to be at least partly mediated by suppression of the pp38MAPK in endothelial cells. These pleiotropic effects of niacin may potentially contribute to the beneficial effects of risk reduction for atherosclerotic disease.

Atherosclerosis ; metabolism ; prevention & control ; Cell Adhesion ; drug effects ; Cells, Cultured ; Enzyme Inhibitors ; administration & dosage ; pharmacology ; Gene Expression Regulation ; drug effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Imidazoles ; administration & dosage ; pharmacology ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Lysophosphatidylcholines ; administration & dosage ; pharmacology ; Niacin ; administration & dosage ; pharmacology ; Pyridines ; administration & dosage ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

OBJECTIVETo study the inhibitory effect and toxicity of axitinib combined with 5-FU in nude mice bearing transplanted tumor of colon cancer LoVo cells.

METHODSNude mouse models bearing LoVo colon cancer xenograft were randomized into vehicle control group, untreated control group, axitinib-treated group, 5-FU-treated group and combined treatment group for corresponding treatments. The tumor dimensions, body weight and tumor weight were recorded, and the efficacy and toxicity were evaluated in terms of complete remission (CR), partial remission (PR), tumor growth delay (TGD), mortality rate and net body weight loss.

RESULTSThe combined treatment showed a significantly stronger efficacy than axitinib or 5-FU used alone. TGD of the combined treatment group was 16.73 days, longer than that of axitinib (8.53 days) and 5-FU (9.72 days) used alone. No mouse died during the treatments in the untreated control group, and 1 died in each of the other 4 groups. The mortality rate and weight loss were both less than 20%. One mouse had PR in axitinib-treated group and another in the combination treatment group. Axitinib, alone and in combination with 5-FU, reduced ABCG2 expression in the tumor tissue, and 5-FU has no such effect.

CONCLUSIONCombination of axitinib and 5-FU produces better antitumor effect than either drug used alone and is well tolerated in nude mice bearing colon cancer xenograft.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Colonic Neoplasms ; drug therapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Imidazoles ; administration & dosage ; Indazoles ; administration & dosage ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays

PURPOSE: We evaluated changes in bone mineral density and biochemical bone turn over markers resulting from intravenous administration of zoledronic acid for the purpose of increasing bone mineral density and decreasing bone turnover rate in patients who had received operative treatment after hip fracture. MATERIALS AND METHODS: We carried out a retrospective study of 34 patients who had received injections of zoledronic acid after surgical treatment for hip fracture from January 2009 to June 2010, with a follow up period of more than one year. We evaluated pre and post T-scores of DXA in spine, proximal femur and femoral neck along with biochemical bone metabolic markers, and we then analyzed each factor. RESULTS: T score was enhanced in all cases with pre T-score -4.2 and post T-score -3.3 revealing statistical significance (P<0.05). In addition, two biochemical bone turnover markers were observed to decrease in most patients. Three days after drug administration, 7 patients(20.6%) had minor adverse effects. There were no serious complications such as atrial fibrillation. CONCLUSION: No major adverse effects were observed, only minor ones in patients who had been injected with zoledronic acid for the prevention of osteoporotic fracture after surgical treatment for hip fracture. We confirmed the affirmative effects on changes in bone mineral density and biochemical bone turn over markers associated with the use of this drug.
Administration, Intravenous ; Bone Density ; Diphosphonates ; Femur ; Femur Neck ; Follow-Up Studies ; Hip ; Humans ; Imidazoles ; Osteoporosis ; Osteoporotic Fractures ; Retrospective Studies ; Spine

The in vivo muscarinic receptor binding of antimuscarinic agents (oxybutynin, solifenacin, tolterodine, and imidafenacin) used to treat urinary dysfunction in patients with overactive bladder is reviewed. Transdermal administration of oxybutynin in rats leads to significant binding of muscarinic receptors in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin shows significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M3 subtype. Oral tolterodine binds more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding of oral imidafenacin in rats is more selective and longer-lasting in the bladder than in other tissues such as the submaxillary gland, heart, colon, lung, and brain, suggesting preferential muscarinic receptor binding in the bladder. In vivo quantitative autoradiography with (+)N-[11C]methyl-3-piperidyl benzilate in rats shows significant occupancy of brain muscarinic receptors with the intravenous injection of oxybutynin, solifenacin, and tolterodine. The estimated in vivo selectivity in brain is significantly greater for solifenacin and tolterodine than for oxybutynin. Imidafenacin occupies few brain muscarinic receptors. Similar findings for oral oxybutynin were observed with positron emission tomography in conscious rhesus monkeys with a significant disturbance of short-term memory. The newer generation of antimuscarinic agents may be advantageous in terms of bladder selectivity after systemic administration.
Administration, Cutaneous ; Animals ; Autoradiography ; Benzhydryl Compounds ; Brain ; Colon ; Cresols ; Heart ; Humans ; Imidazoles ; Injections, Intravenous ; Lung ; Macaca mulatta ; Mandelic Acids ; Memory, Short-Term ; Mice ; Muscarinic Antagonists ; Phenylpropanolamine ; Positron-Emission Tomography ; Quinuclidines ; Rats ; Receptors, Muscarinic ; Salivation ; Solifenacin Succinate ; Submandibular Gland ; Tetrahydroisoquinolines ; Tolterodine Tartrate ; Urinary Bladder ; Urinary Bladder, Overactive