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1.
Biomed Res Int ; 2014: 716538, 2014.
Article in English | MEDLINE | ID: mdl-25535614

ABSTRACT

The purpose of the current review was to determine the efficacy of alendronate for preventing collapse of femoral head in adult patients with nontraumatic avascular osteonecrosis of femoral head (ANFH). Five randomized controlled trials (RCTs) involving 305 hips were included in this review, of which 3 studies investigated alendronate versus control/placebo and the other 2 studies compared the combination of alendronate and extracorporeal shockwave therapy (ESWT) with ESWT alone. Our results suggested that even the patients with extensive necrosis encountered much less collapse in the alendronate group than control group. In these RCTs, their data also indicated a positive short- and middle-term efficacy of alendronate treatment in joint function improvement and hip pain diminishment. With the presence of the outlier study, only insignificant overall efficacy of alendronate could be observed with substantial heterogeneities. In addition, we did not find any additive benefits of alendronate in combination with ESWT for preventing collapse compared to ESWT alone. In conclusion, there is still lack of strong evidence for supporting application of alendronate in adult patients with nontraumatic ANFH, which justified that large scale, randomized, and double-blind studies should be developed to demonstrate the confirmed efficacies, detailed indication, and optimized strategy of alendronate treatment.


Subject(s)
Alendronate/therapeutic use , Bone Density Conservation Agents/therapeutic use , Femur Head/injuries , Osteonecrosis/drug therapy , Femur Head/drug effects , Femur Head/physiopathology , Humans , Lithotripsy , Osteonecrosis/physiopathology , Treatment Outcome
2.
Med Sci Monit ; 20: 2439-47, 2014 Nov 26.
Article in English | MEDLINE | ID: mdl-25424061

ABSTRACT

Osteonecrosis or avascular osteonecrosis (AVN) of the femoral head is a devastating multifactorial disease that affects 20 000 persons each year in the United States. The purpose of this systematic review was to determine the efficacy and safety of alendronate for adult AVN during short- and long-term follow-up. Electronic databases were searched for randomized or nonrandomized clinical trials, cohort, case-control studies, and series of cases in which alendronate was used for treatment of adult AVN of the femoral head. Relevant articles with adequate data on reduction of pain, improvement of articular function, slowing of bone collapse progression, or need for total hip arthroplasty (THA) were included after applying inclusion and exclusion criteria. Eight articles involving 788 hips with evidence level 1b to 3b were included in this systematic review. Most studies suggested a positive short-term efficacy of alendronate treatment in reducing pain, improving articular function, slowing of bone collapse progression, and delaying the need for THA for adult AVN patients. The favorable long-term results were also presented in those treated patients after 10-year follow-up. In addition, there were no severe adverse effects associated with alendronate treatment observed during short- and long-term follow-up, and most of the included studies suggested use of alendronate in early AVN with small necrotic lesion to achieve better outcomes. The findings support consideration of alendronate use for adult AVN, particularly with early stage and small necrotic size. The lack of large-scale, randomized, and double-blind studies justifies new studies to demonstrate the detailed indication and the optimized strategy of alendronate treatment. Level of evidence: Level 3a.


Subject(s)
Alendronate/therapeutic use , Femur Head Necrosis/drug therapy , Adolescent , Adult , Aged , Alendronate/adverse effects , Demography , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome , Young Adult
4.
J Surg Res ; 189(1): 89-95, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24679696

ABSTRACT

BACKGROUND: Protein phosphatase type 2A (PP2A) can downregulate c-Jun N-terminal kinase (JNK) expression in monocytes stimulated by lipopolysaccharide. However, this effect has not been evaluated in patients with sepsis. We sought to determine whether PP2A/JNK pathway is involved in sepsis and whether PP2A expression can be associated with patient outcome. MATERIALS AND METHODS: We measured PP2A, c-Jun, and JNK protein as well as PP2A and c-Jun messenger RNA in monocytes from trauma patients with (n = 24) or without (n = 22) sepsis 1 and 7 d after major trauma and from healthy volunteers (n = 15) by Western blotting and quantitative real-time polymerase chain reaction. Patient outcomes, including intensive care unit length of stay, Sequential Organ Failure Assessment score, and Multiple Organ Dysfunction score were compared between groups. Correlations between PP2A and c-Jun/JNK expression as well as patient outcomes were analyzed. Receiver operating characteristic analysis was performed to determine the diagnostic efficiency of PP2A for sepsis. RESULTS: PP2A protein and messenger RNA expression were significantly higher in septic patients compared with nonseptic patients or healthy volunteers. Conversely, the expressions of JNK and c-Jun were significantly reduced in septic patients and correlated inversely with PP2A expression. Furthermore, PP2A expression was positively associated with LOS, Sequential Organ Failure Assessment and Multiple Organ Dysfunction score at day 1 and day 7. Receiver operating characteristic curve yielded a high sensitivity (87.5%) of PP2A in discriminating septic versus nonseptic patients. CONCLUSIONS: PP2A may serve as a negative regulator of the JNK pathway and a biomarker for sepsis.


Subject(s)
JNK Mitogen-Activated Protein Kinases/genetics , Monocytes/enzymology , Protein Phosphatase 2/genetics , Proto-Oncogene Proteins c-jun/genetics , Sepsis/enzymology , Adolescent , Adult , Aged , Biomarkers/metabolism , Case-Control Studies , Female , Gene Expression Regulation, Enzymologic , Healthy Volunteers , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System/genetics , Male , Middle Aged , Monocytes/pathology , Prospective Studies , Protein Phosphatase 2/metabolism , Proto-Oncogene Proteins c-jun/metabolism , ROC Curve , Sepsis/pathology , Young Adult
5.
Int Immunopharmacol ; 17(2): 329-35, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23856614

ABSTRACT

Overproduction of nitric oxide (NO) and matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). In present study, we investigated whether vorinostat can inhibit the catabolic effects of IL-1ß in vitro, especially the inhibition of MMPs and inducible nitric oxide synthase (iNOS) through the attenuation of nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase (MAPK) pathways in human chondrocytes. Human OA chondrocytes were either left untreated or treated with various concentrations of vorinostat followed by incubation with IL-1ß (5ng/mL). Effects of vorinostat on IL-1ß-induced gene and protein expression of iNOS, MMP-1, MMP-13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) were verified by quantitative real time-PCR and Western blot analysis. Production of NO, MMP-1, MMP-13 and TIMP-1 released in culture supernatant was estimated using commercially available kits. The roles of NF-κB and MAPK pathways in the regulation of targeted genes and the mechanism involved in vorinostat mediated modulation of these genes were determined by Western blot using specific antibodies. We found that vorinostat down-regulated iNOS, MMP-1 and MMP-13 expression and up-regulated TIMP-1 expression in human OA chondrocytes. In addition, the release of NO, MMP-1 and MMP-13 secreted from IL-1ß stimulated chondrocytes was also suppressed by vorinostat. Interestingly, vorinostat selectively inhibited IL-1ß-induced p38 and ERK1/2 activation without affecting JNK activation. Furthermore, we observed that vorinostat inhibited NF-κB pathway by suppressing the degradation of I-κBα and attenuating NF-κB p65 translocation to the nucleus. These results suggest that vorinostat may be a promising therapeutic agent for the prevention and treatment of OA.


Subject(s)
Cell Nucleus/metabolism , Chondrocytes/drug effects , Histone Deacetylase Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Active Transport, Cell Nucleus/drug effects , Aged , Cells, Cultured , Chondrocytes/immunology , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Interleukin-1beta/immunology , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 13/metabolism , Middle Aged , Nitric Oxide Synthase Type II/metabolism , Osteoarthritis/immunology , Phosphorylation , Signal Transduction/drug effects , Tissue Inhibitor of Metalloproteinase-1/metabolism , Vorinostat , p38 Mitogen-Activated Protein Kinases/metabolism
6.
Chin J Traumatol ; 16(3): 176-7, 2013.
Article in English | MEDLINE | ID: mdl-23735553

ABSTRACT

We report electroversion in treatment of atrial fibrillation (AF) and atrioventricular nodal reentry tachycardia (AVNRT) in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury. At first, the patient sustained respiratory failure and weak cough reflex, thereafter repeated bronchoscopy was used to aspirate the sputum as well as control the pneumonia, which resulted in arrhythmia (AF and AVNRT). Two doses of intravenous amiodarone failed to correct the arrhythmia. After restoration of sinus rhythm by electroversion, he was successfully weaned from mechanical ventilation and discharged from the intensive care unit without recurrent arrhythmia.


Subject(s)
Atrial Fibrillation/complications , Atrial Fibrillation/therapy , Electric Countershock , Spinal Cord Injuries/complications , Wolff-Parkinson-White Syndrome/complications , Bronchoscopy , Cervical Vertebrae/injuries , Electrocardiography , Humans , Male , Middle Aged , Respiration, Artificial
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