Comparison between nafarelin acetate andd-Trp6-LHRH for temporary pituitary suppression in in vitro fertilization (IVF) patients: A prospective crossover study

Purpose Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 g/daily in their first cycle and received d-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their first cycle and received nafarelin in the second.Results Estradiol suppression was achieved by both d-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P=0.0005) and the length of administration of hMG required for ovarian stimulation (P=0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P=0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues.Conclusion Our results demonstrate that nafarelin acetate is comparable to d-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with fewer ampoules of hMG, administered for a shorter period of time, thus with a lesser cost.     

Inhibition of amyloid precursor protein processing by beta-secretase through site-directed antibodies

Amyloid-beta peptide (AbetaP) that accumulates in the Alzheimer's diseased brain is derived from proteolytic processing of the amyloid precursor protein (APP) by means of beta- and gamma-secretases. The beta-secretase APP cleaving enzyme (BACE), which generates the N terminus of AbetaP, has become a target of intense research aimed at blocking the enzyme activity, thus reducing AbetaP and, subsequently, plaque formation. The search for specific inhibitors of beta-secretase activity as a possible treatment for Alzheimer's disease intensified with the discovery that BACE may be involved in processing other non-APP substrates. The presence of the APP-BACE complex in early endosomes highlights the cell surface as a potential therapeutic target, suggesting that interference in APP-BACE interaction at the cell surface may affect amyloid-beta production. We present here a unique approach to inhibit AbetaP production by means of antibodies against the beta-secretase cleavage site of APP. These antibodies were found to bind human APP overexpressed by CHO cells, and the formed immunocomplex was visualized in the early endosomes. Indeed, blocking of the beta-secretase site by these antibodies interfered with BACE activity and inhibited both intracellular and extracellular AbetaP formation in these cells.     

Operative treatment of pelvic apophyseal avulsions in adolescent and young adult athletes: a follow-up study

Introduction

Pelvic apophyseal avulsion can limit young athletes’ performance for months and may result in permanent disability. Nonoperative treatment is most commonly preferred, while surgical management with reduction and fixation is reserved for selected cases. Our aim was to evaluate outcomes of operative management of pelvic apophyseal avulsions in a series of adolescents and young adult athletes.

Materials and methods

Operative room registries and medical records were reviewed to identify patients who received surgical treatment for pelvic apophyseal avulsions who were younger than 24 years and with a minimum of 12 month follow-up.

Results

Thirty-two patients (16.8 years ± 2.6) were identified. The most common avulsion sites were anterior inferior iliac spine (34.4%, N = 11) and ischial tuberosity (34.4%, N = 11). Other avulsions were five cases (15.6%) of the pubic apophysis, four cases (12.5%) of the anterior superior iliac spine apophysis and one case of the iliac crest apophysis. Seventeen cases (53.1%) underwent surgery early, i.e., during the first 3 months after the acute injury. Twenty-two cases (68.8%) involved reduction with internal fixation, and six cases (18.8%) involved resection of the fragment. Twenty-six athletes (81.3%, N = 26) reported good outcomes and were able to return to preinjury sports level. Six patients (18.8%) had moderate outcome and reported activity limitations during high-level sports. Large displacement (> 20 mm) or delayed (> 3 months) surgery was not associated with inferior outcomes (P = 0.690 and P = 0.392, respectively). Injury side (P = 0.61) or gender (P = 0.345) did not affect outcomes.

Conclusions

Operative management of pelvic apophyseal avulsion results in return to the preinjury sports level in more than 80% of the cases. However, while both acute surgery for large displacement and delayed intervention for failed nonoperative treatment are generally successful in improving sports function in these cases, comparative studies are required to refine criteria for surgery.

Level of evidence

Case series, IV.

     

Targeted drug-carrying bacteriophages as antibacterial nanomedicines

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of approximately 20,000 compared to the free drug.