Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users.

OBJECTIVES: To determine whether six days recombinant human growth hormone (rhGH) in an abstinent anabolic-androgenic steroid (AAS) group had any cardiovascular and biochemical effects compared with a control group. METHODS: Male subjects (n=48) were randomly divided, using a single blind procedure into two groups: (1) control group (C) n=24, mean+/-SD, age 32+/-11 years; height 1.8+/-0.06m; (2) rhGH using group (0.058IUkg(-1)day(-1)) (GH) n=24, mean+/-SD, age 32+/-9 years; height 1.8+/-0.07m. Physiological responses, anthropometry, arterial pulse wave velocity (APWV), blood pressure (BP), heart rate (HR), peak oxygen uptake (VO(2) peak) and biochemical indices were investigated. RESULTS: Body mass index, fat-free mass index and VO(2) peak significantly increased while body fat significantly decreased within GH (all P<0.017). Insulin like growth factor-I significantly increased within GH (P<0.017) and compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum homocysteine, high sensitivity C-reactive protein, thyroid stimulating hormone and tetra-iodothyronine (T(4)), significantly decreased within GH (all P<0.017). T(4) significantly decreased compared with C (P<0.05). Arterial pulse wave velocity, peak and recovery systolic and diastolic BP, significantly decreased compared with C (P<0.05). Resting HR and rate pressure product (RPP) significantly increased compared with C (P<0.05). CONCLUSION: The findings of this study suggest that short term use of rhGH may have beneficial effects on endothelial function and specific inflammatory markers of cardiovascular disease in abstinent AAS users, but may have an adverse effect on the cardiovascular system, as evidenced by the increase in resting RPP.     

Are the results of electrophysiological study different in patients with a pre-excitation syndrome, with and without syncope?

AIMS: Syncope in Wolff-Parkinson-White (WPW) syndrome may reveal an arrhythmic event or is not WPW syndrome related. The aim of the study is to evaluate the results of electrophysiological study in WPW syndrome according to the presence or not of syncope and the possible causes of syncope. METHODS AND RESULTS: Among 518 consecutive patients with diagnosis of WPW syndrome, 71 patients, mean age 34.5 +/- 17, presented syncope. Transoesophageal electrophysiological study in control state and after isoproterenol infusion was performed in the out-patient clinic. Atrioventricular re-entrant tachycardia (AVRT) was more frequently induced than in asymptomatic patients (n = 38, 53.5%, P < 0.01), less frequently than in those with tachycardia; atrial fibrillation (AF) and/or antidromic tachycardia (ATD) was induced in 28 patients (39%) more frequently (P < 0.05) than in asymptomatic patients or those with tachycardia. The incidence of high-risk form [rapid conduction over accessory pathway (AP) and AF or ATD induction] was higher in syncope group (n = 18, 25%, P < 0.001) than in asymptomatic subjects (8%) or those with tachycardias (7.5%). Maximal rate conducted over AP was similar in patients with and without syncope, and higher in patients with spontaneous AF, but without syncope. Results were not age-related. CONCLUSION: Tachycardia inducibility was higher in patients with syncope than in the asymptomatic group. The incidence of malignant WPW syndrome was higher in patients with syncope than in asymptomatic or symptomatic population, but the maximal rate conducted over AP was not higher and another mechanism could be also implicated in the mechanism of syncope.     

Comprehensive Treatment of Periorbital Region with Hyaluronic Acid

The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients.Maintaining a youthful and pleasant appearance of the face in today’s culture impacts quality of life in many patients. The facial contour remodeling is being revolutionized by new nonsurgical techniques.Facial aging is a complex and dynamic process. All people age differently as a result of imbalance, disharmony, and disproportion of the aging process between the overlying soft tissue and the underlying bony frameworks.1 The upper periorbital subunit is one of the first facial regions to show signs of aging, and even minor changes in its structure and volume can distort the perceived emotions and health of patients.2 An aesthetic and youthful upper periorbital subunit is characterized by a well-defined brow of appropriate height and shape, fullness of the upper periorbit, a crisp and well-defined upper eyelid crease, minimal skin excess, and good skin quality.3,4In the aging process of this facial area, one group of patients displays signs of aging due predominantly to soft tissue ptosis of the upper eyelid, requiring surgical excision. Another group presents with volume depletion of the soft tissue and bony resorption of the orbit. The loss of septal support, leading to brow prolapse and an exacerbation of upper eyelid fullness and congestion, can also contribute to the aging process. This appearance is characterized by deflation of the upper eyelid as well as hollowing and visibility of the supraorbital bony rim, leading to a sunken, hollow, and skeletonized orbit, which can make the patient appear sickly, anorexic, and old. In recent years, modern facial rejuvenation surgery has evolved toward volume restoration in addition to tissue suspension.2Comprehensive analysis of both soft tissue and bony structural changes are essential for the periorbital rejuvenation. Surgical procedures and office-based nonsurgical procedures form an important basis for periorbital rejuvenation, including cosmeceuticals, chemical peels, laser and light treatments, neurotoxins, and fillers. Improved understanding of the pathophysiology of aging and technical advancements in nonsurgical techniques has enabled us to achieve better and more comprehensive improvement for patients.5     

Interactions between chromosomes, microfilaments and microtubules revealed by the study of small GTPases in a big cell, the vertebrate oocyte

Meiotic divisions during oogenesis in higher eukaryotes are extremely asymmetric giving rise to one gamete, the oocyte, and two polar bodies. In most species, this asymmetric partitioning relies on the eccentric positioning of meiotic spindles. Recent work performed in mouse and frog oocytes has suggested the involvement of small GTPases, such as Cdc42, Rac and Ran both in the control of spindle organization and positioning. The present review summarizes these findings that shed light on the molecular mechanisms by which small GTPases control asymmetric cell divisions in vertebrate oocytes.     

Streamlined ion torrent PGM-based diagnostics: BRCA1 and BRCA2 genes as a model

To meet challenges in terms of throughput and turnaround time, many diagnostic laboratories are shifting from Sanger sequencing to higher throughput next-generation sequencing (NGS) platforms. Bearing in mind that the performance and quality criteria expected from NGS in diagnostic or research settings are strikingly different, we have developed an Ion Torrent''s PGM-based routine diagnostic procedure for BRCA1/2 sequencing. The procedure was first tested on a training set of 62 control samples, and then blindly validated on 77 samples in parallel with our routine technique. The training set was composed of difficult cases, for example, insertions and/or deletions of various sizes, large-scale rearrangements and, obviously, mutations occurring in homopolymer regions. We also compared two bioinformatic solutions in this diagnostic context, an in-house academic pipeline and the commercially available NextGene software (Softgenetics). NextGene analysis provided higher sensitivity, as four previously undetected single-nucleotide variations were found. Regarding specificity, an average of 1.5 confirmatory Sanger sequencings per patient was needed for complete BRCA1/2 screening. Large-scale rearrangements were identified by two distinct analyses, that is, bioinformatics and fragment analysis with electrophoresis profile comparison. Turnaround time was enhanced, as a series of 30 patients were sequenced by one technician, making the results available for the clinician in 10 working days following blood sampling. BRCA1/2 genes are a good model, representative of the difficulties commonly encountered in diagnostic settings, which is why we believe our findings are of interest for the whole community, and the pipeline described can be adapted by any user of PGM for diagnostic purposes.     

Unique neuromyelitis optica pathology produced in naïve rats by intracerebral administration of NMO-IgG

Animal models of neuromyelitis optica (NMO) are needed for elucidation of disease mechanisms and for testing new therapeutics. Prior animal models of NMO involved administration of human anti-aquaporin-4 immunoglobulin G antibody (NMO-IgG) to rats with pre-existing neuroinflammation, or to naïve mice supplemented with human complement. We report here the development of NMO pathology following passive transfer of NMO-IgG to naïve rats. A single intracerebral infusion of NMO-IgG to adult Lewis rats produced robust lesions around the needle track in 100 % of rats; at 5 days there was marked loss of aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP) and myelin, granulocyte and macrophage infiltration, vasculocentric complement deposition, blood–brain barrier disruption, microglial activation and neuron death. Remarkably, a distinct ‘penumbra’ was seen around lesions, with loss of AQP4 but not of GFAP or myelin. No lesions or penumbra were seen in rats receiving control IgG. The size of the main lesion with loss of myelin was greatly reduced in rats made complement-deficient by cobra venom factor or administered NMO-IgG lacking complement-dependent cytotoxicity (CDC) effector function. However, the penumbra was seen under these conditions, suggesting a complement-independent pathogenesis mechanism. The penumbra was absent with NMO-IgG lacking both CDC and antibody-dependent cellular cytotoxicity (ADCC) effector functions. Finally, lesion size was significantly reduced after macrophage depletion with clodronate liposomes. These results: (i) establish a robust, passive-transfer model of NMO in rats that does not require pre-existing neuroinflammation or complement administration; (ii) implicate ADCC as responsible for a unique type of pathology also seen in human NMO; and (iii) support a pathogenic role of macrophages in NMO.