An antibody‐free strategy for screening putative HDM2 inhibitors using crude bacterial lysates expressing GST‐HDM2 recombinant protein

Targeting the interaction of p53 with its natural inhibitor MDM2 by the use of small synthetic molecules has emerged as a promising pharmacological approach to restore p53 oncosuppressor function in cancers retaining wild‐type p53. The first critical step in the experimental validation of newly synthesized small molecules developed to inhibit MDM2‐p53 interaction is represented by the evaluation of their efficacy in preventing the formation of the MDM2‐p53 complex. This can be achieved using the in vitro reconstructed recombinant MDM2‐p53 complex in cell‐free assays. A number of possible approaches have been proposed, which are however not suitable for screening large chemical libraries, due to the high costs of reagents and instrumentations, or the need of large amounts of highly pure recombinant proteins. Here we describe a rapid and cheap method for high‐throughput screening of putative inhibitors of MDM2‐p53 complex formation – based on the use of GST‐recombinant proteins – that does not require antibodies and recombinant protein purification steps from bacterial cell lysates. Copyright © 2013 John Wiley & Sons, Ltd.     

Arthroscopic treatment of acute acromioclavicular joint dislocation with double flip button

The ideal treatment for acute acromioclavicular joint dislocation is still controversial, both in terms of indications and surgical technique. The clinical and radiographic outcomes of 16 patients affected by acute AC joint dislocation (type III–V) and arthroscopically treated with a coracoclavicular double flip button are presented. Despite the excellent clinical results both in terms of Constant score (mean 97 points) and patient satisfaction, at a mean follow-up of 31 months the radiographs showed partial loss of reduction due to distal migration of the flip button within the upper third of the clavicle in one-fourth of the cases. The technique presented here proved to be safe and minimally invasive while delivering good aesthetic results and allowing for the treatment of associated lesions. Furthermore, the technique could benefit from more advanced retention devices, which ought to reduce or avoid migration of the flip buttons.     

Primary mammary focus of malignant non-Hodgkin's lymphoma. Apropos of 10 cases

The authors describe 10 cases of malignant non-Hodgkin's lymphoma in a mammary site in women aged 38 to 82 years. The clinical examination and the sometimes suggest an adenocarcinomatous lesion, thus leading to a useless surgical exeresis. An initial histological study provides the diagnosis. A complete assessment of extension allows an accurate staging and the refinement of the therapeutic schedule. Exclusive radiation therapy seems to be justified in low-malignancy forms remaining strictly confined to the breast. For the high- and medium-malignancy forms, the essential weapon is chemotherapy, which seems to improve the duration and rate of remission.     

Role of p27 in Prostate Carcinogenesis

The cyclin dependent kinase inhibitor p27 binds to and inhibits preferentially S-phase kinases thereby halting cell cycle progression. Loss of p27 expression has been shown to be associated with aggressive behavior in a variety of human epithelial tumors including prostate cancer. In this review, the role of p27 in cell cycle progression as well as its regulation by the ubiquitin-proteasome pathway are discussed. The experimental evidence pointing to the role of p27 as a tumor suppressor gene is outlined. The data generated to date on the prognostic significance of loss of p27 protein expression in human prostate cancers are summarized. Finally, the implications of the changes in p27 expression which occur as a result of androgen ablation in normal and neoplastic prostate are discussed.     

EFFECTS OF RATION/SIZING DRUG TREATMENT OF PATIENTS WITH EPILEPSY AND MENTAL RETARDATION

Eighty patients with epilepsy and mental retardation were observed for a mean period of 12.5 months to assess the effects of 'rationalisation' of their drug treatment on both epilepsy and behaviour. Anticonvulsant drugs were modified to provide the best seizure control with the lowest toxicity, and psychotropic drugs also were monitored and modified if necessary to obtain the best results. At the end of the follow-up period the number of anti-epileptic drugs had fallen from 1.84 to 1.05 per patient. On admission to the study 47 patients were being treated with 85 psychotropic drugs: at the end of the follow-up 44 patients were taking 63 drugs. Seizures were significantly reduced in 16 of 39 patients with unsatisfactory control on admission to the study. Among 41 patients with initial satisfactory control, only 16 had relapse of seizures. Behavior did not change significantly.     

Echocardiographic approach in a new left ventricular assist device: Impella Recover 100.

Echocardiographic evaluation represents a basic tool for the treatment of patients undergoing ventricular assist device implant. Impella Recover 100 is a new left intraventricular assist device proposed for short-term mechanical circulatory support to be implanted without cardiopulmonary bypass. We report our experience with echocardiographic monitoring on a patient with ischemic cardiomyopathy who underwent Impella Recover 100 implant as a bridge to heart transplant. During the surgical procedure echocardiography had an essential role for anatomic evaluation of the heart and correct intraventricular positioning of the device. Moreover, during the whole period of assistance, echocardiography contributed to assessment of patient-device interaction and to check the device when malfunction was suggested.     

Efficacy of Zofenopril vs. Irbesartan in Combination with a Thiazide Diuretic in Hypertensive Patients with Multiple Risk Factors not Controlled by a Previous Monotherapy: A Review of the Double-Blind,Randomized “Z” Studies

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18–24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (?0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the recommendations of current guidelines.