ADAM8 enhances osteoclast precursor fusion and osteoclast formation in vitro and in vivo

ADAM8 expression is increased in the interface tissue around a loosened hip prosthesis and in the pannus and synovium of patients with rheumatoid arthritis, but its potential role in these processes is unclear. ADAM8 stimulates osteoclast (OCL) formation, but the effects of overexpression or loss of expression of ADAM8 in vivo and the mechanisms responsible for the effects of ADAM8 on osteoclastogenesis are unknown. Therefore, to determine the effects of modulating ADAM expression, we generated tartrate‐resistant acid phosphatase (TRAP)–ADAM8 transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout (ADAM8 KO) mice. TRAP‐ADAM8 mice developed osteopenia and had increased numbers of OCL precursors that formed hypermultinucleated OCLs with an increased bone‐resorbing capacity per OCL. They also had an enhanced differentiation capacity, increased TRAF6 expression, and increased NF‐κB, Erk, and Akt signaling compared with wild‐type (WT) littermates. This increased bone‐resorbing capacity per OCL was associated with increased levels of p‐Pyk2 and p‐Src activation. In contrast, ADAM8 KO mice did not display a bone phenotype in vivo, but unlike WT littermates, they did not increase RANKL production, OCL formation, or calvarial fibrosis in response to tumor necrosis factor α (TNF‐α) in vivo. Since loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced OCL formation in response to TNF‐α, these results suggest that ADAM8 may be an attractive therapeutic target for preventing bone destruction associated with inflammatory disease. © 2011 American Society for Bone and Mineral Research.     

The Relationship Between Polyethylene Wear and Periprosthetic Osteolysis in Total Hip Arthroplasty at 12 Years in a Randomized Controlled Trial Cohort

Background

Polyethylene acetabular components are common in hip arthroplasty. Highly cross-linked polyethylene (HXLPE) has lower wear than ultra-high molecular weight polyethylene (UHMWPE). Evidence suggests that wear particles induce inflammation causing periprosthetic osteolysis contributing to implant loosening with wear rates of 0.05 mm/y were considered safe. We aimed to compare incidence and volume of periacetabular osteolysis between HXLPE and UHMWPE using computed tomography.

Change in contraceptive choices and the effect of education on use of contraception at the family planning clinic of Şişli Etfal Training and Research Hospital,Istanbul, Turkey

Objective?To investigate change in contraceptive use and the effect of education on fertility and contraceptive attitudes at our family planning clinic.

Methods?For this retrospective review, medical charts from ?i?li Etfal Training and Research Hospital Family Planning Center were obtained. Records were evaluated for 2514 women in 1997 and 2268 women in 2002.

Results?During the 6-year period studied, significant decreases occurred in the number of births, elective abortions, gravidity and number of living children (p?<?0.001). When the patterns of method use were compared, use of intrauterine devices and of coitus interruptus diminished whereas pill and condom use increased. Parallel with the rise in educational level, intrauterine device use declined whereas pill and condom use rose significantly (p?<?0.001).

Conclusion?The sociocultural and educational levels of women affect their contraceptive choices. Policies aimed at raising the socioeconomic and educational level of women should be supported to prevent maternal and fetal complications as a result of unwanted pregnancies.     

Cine cardiac imaging using black‐blood steady‐state free precession (BB‐SSFP) at 3T

Purpose

To propose a new black‐blood (BB) pulse sequence that provides BB cine cardiac images with high blood‐myocardium contrast. The proposed technique is based on the conventional steady‐state free precession (SSFP) sequence.

Materials and Methods

Numerical simulations of the Bloch equation were conducted to compare the resulting signal‐to‐noise ratio (SNR) to that of conventional BB imaging, including the effects of changing the imaging flip angle and heart rates. Simulation results were verified using a gel phantom experiment and five normal volunteers were scanned using the proposed technique.

Results

The new sequence showed higher SNR and contrast‐to‐noise ratio (CNR) (≈100%) compared to the conventional BB imaging. Also, the borders of the left ventricle (LV) and right ventricle (RV) appear more distinguishable than the conventional SSFP. We were also able to cover about 80% of the cardiac cycle with short breath‐hold time (≈10 cardiac cycles) and with reasonable SNR and CNR.

Conclusion

Based on an SSFP conventional sequence, the new sequence provides BB cines that cover most of the cardiac cycle and with higher SNR and CNR than the conventional BB sequences. J. Magn. Reson. Imaging 2009;30:94–103. © 2009 Wiley‐Liss, Inc.     

Autograft soaking in vancomycin reduces the risk of infection after anterior cruciate ligament reconstruction

Purpose

To determine whether the bathing of an anterior cruciate ligament (ACL) autograft in vancomycin reduces the rate of infection following an ACL reconstruction.

Methods

Retrospective analysis of all ACL reconstructions over an 8-year period in two University Hospitals. In the initial 4-year period, all patients were operated on under classical antibiotic intravenous prophylaxis (group 1). Over the last 4-year period, this prophylaxis was supplemented with presoaking of the autograft (group 2). Presoaking was performed with sterile gauze previously saturated with a vancomycin solution (5 mg/ml).

Results

There were 810 and 734 patients in group 1 and 2, respectively. Fifteen cases of knee joint infections were identified in the series (0.97 %). All of these infections occurred in group 1, representing a rate of infection of 1.85 % in comparison with 0 % in group 2 (p < 0.001).

Conclusions

Autograft presoaking with vancomycin in combination with classical intravenous antibiotic prophylaxis reduced the rate of knee joint infection following an ACLR in comparison with antibiotic prophylaxis alone. This technique could be of relevance in daily clinical practice to prevent infection after ACLR.

Level of evidence

Case control study, retrospective comparative study, Level III.

     

Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt

ObjectivesTo examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men.Materials and methodsWe used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively.ResultsThe study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women.ConclusionsThese findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt.     

Management of osteonecrosis of proximal tibia using trabecular osteonecrotic rods

Osteonecrosis of the knee is a well-described cause of acute knee pain. It can lead to significant functional impairment, rapid arthritic joint changes and subsequent collapse. Several hypotheses exist different treatment options are used ranging from conservative management to joint arthroplasty. The majority of cases involve the distal femoral condyle and to a much lesser extent the medial tibial plateau.We are presenting a rare case of osteonecrosis of the proximal tibia affecting the lateral tibial condyle in 44 years old Caucasian male which was treated successfully using osteonecrotic tantalum rods with 26 month follow-up.     

Erectile dysfunction in testicular cancer patients treated with chemotherapy

Information on male potency in testicular cancer (TC) patients treated with chemotherapy is insufficient. We aimed to assess the levels of depression and anxiety symptoms, sexual function and gonodotrophins. Participants (n = 27) were identified and recruited from the genitourinary services of two medical centres, one in Inonu University and the other in the Firat University. All patients are TC patients treated with chemotherapy after unilateral orchiectomy. Participants completed follow-up assessments after the completion of the chemotherapy regimen. Serum luteinising hormone, follicle-stimulating hormone and testosterone levels were determined after blood samples had been taken in the morning after an overnight fast. International Index of Erectile Function (IIEF-15) was also used to evaluate erectile dysfunction (ED) score. Beck Depression and Beck Anxiety Scale were used to assess psychological symptoms. The findings indicated that men treated with chemotherapy had significantly different IIEF-15 and Beck Anxiety scores compared with men who did not receive chemotherapy. But no statistically significant difference was determined in the serum gonodotrophin levels and depression score between the two groups. It is concluded that patients with TC undergoing chemotherapy have greater risk than normal men for ED, independently of the gonodotrophin's level.     

In vitro permeation of diclofenac sodium from novel microemulsion formulations through rabbit skin

In order to increase topical penetration of the nonsteroidal anti‐inflammatory drug, diclofenac sodium, new microemulsion formulations were prepared to increase drug solubility and in vitro penetration of the drug. The influence of dimethyl sulfoxide and propylene glycol were also investigated as enhancers on the in vitro penetration of diclofenac sodium using Franz diffusion cells using excised dorsal rabbit skin. Factorial randomized design was performed to analyze the results of in vitro permeation studies. Microemulsions prepared with isopropyl alcohol were superior to those prepared with propanol. Enhancers had different effects depending on the formulation. Propylene glycol was superior to dimethyl sulfoxide when incorporated into isopropyl alcohol microemulsion, whereas dimethyl sulfoxide was superior to propylene glycol in propanol microemulsions. There were no observable histopathological differences between the skin of the control group and the treated groups at the light microscope level due to swelling of the skin tissue. The present study shows that microemulsion formulations containing isopropyl alcohol as co‐surfactant and propylene glycol as enhancer represent a promising approach for a topical vehicle for diclofenac sodium. Drug Dev. Res. 65:17–25, 2005. © 2005 Wiley‐Liss, Inc.     

Improved solubility and dissolution rate of piroxicam using gelucire 44/14 and labrasol

Piroxicam is a nonsteroidal anti-inflammatory drug that is characterized by low solubility-high permeability. The present study was designed to improve the dissolution rate of piroxicam at the physiological pH's through its increased solubility by preparing semi-solid dispersions of drug using Gelucires and Labrasol. These excipients are essentially characterized by their melting points and HLB (hydrophilic-lipophilic balance) values. The dissolution tests of the preparations were performed in the media with different pH's. Differential scanning calorimetry (DSC), were used to examine the interaction between piroxicam and excipients. Gelucire 44/14 and Labrasol at the concentration of 15% w/v in water provided 20- and 50-fold increase in the solubility of piroxicam, respectively. The semi-solid dispersion containing 1/20 of drug/excipient mixture (20% Gelucire 44/14 and 80% Labrasol in w/w) produced the dissolution not less than 85% of piroxicam within 30 min in each dissolution media (simulated gastric fluid (SGF), pH 1.2; phosphate buffers, pH 4.5 and 6.8; and water). DSC analysis of this semi-solid dispersion indicated that there was no chemical reaction between the drug and excipients, and that a solid-state solution of piroxicam with excipient formed.