Sudden vision loss in a mucopolysaccharidosis I patient receiving enzyme replacement therapy

A 25-year-old female was referred for short stature and joint deformities. Except for previous corneal transplantation, her medical history was unremarkable. Initial physical examination revealed the presence of a coarse facies, short neck, kyphosis, restricted joint movements and deformities, and cardiac murmur besides a normal intellect. Urine glycosaminoglycan levels were high, and blood enzyme assay indicated significantly low alpha-L-iduronidase levels. Mucopolysaccharidosis I (MPS I) was diagnosed and prompted the onset of enzyme replacement therapy (ERT), which significantly improved articular complaints, while cardiac pathology remained stable. At the eighteenth month of ERT, sudden vision loss developed. She spontaneously recovered her vision in a month. MPS I is a progressive disease, in which tissue accummulation of heparan and dermatan sulphate result from defective activity or lack of alpha-L-iduronidase. ERT in MPS I usually presents favourable outcomes or at least stabilization of symptoms. This present case qualifies as the first report ofa MPS I patient developing sudden vision loss under ERT. We suggest that further research studies are warranted for defining the efficiency and possible limitations of ERT.     

The effects of different adhesive agents on the shear bond strength of a self-adhesive resin cement

Purpose: To compare the clinical success of a self-adhesive resin cement used in combination with different adhesive bonding systems with that of a conventional dual-cure resin cement. Methods: The study was performed with 136 freshly extracted molars embedded in acrylic resin blocks and 136 IPS e.max Press discs. Teeth and discs were randomly divided into four equal groups and cemented together using either RelyX ARC (ARC), RelyX Unicem (Unicem), RelyX Unicem+Adper-Prompt L-pop (L-pop), or RelyX and Unicem+Total-etch (Total-etch). Shear bond strength measurements were obtained before and after thermocycling. Following bond testing, the surfaces of one sample per subgroup (thermocycled and non-thermocycled), were assessed using scanning electron microscopy (SEM). Results: Among the non-thermocylced subgroups, ARC exhibited the highest bond strength values, followed by Total Etch, Unicem and L-pop. ARC also exhibited the highest bond strength values among the thermocycled subgroups, followed by Unicem, Total-etch, and L-pop. SEM analysis clearly revealed the negative effects of thermo-cycling on the mechanical properties of adhesive agents. Conclusions: RelyX Unicem may be preferable in many cases because of its simplified application and reduced technique-sensitivity.     

Mechanism of extracellular ubiquitination in the mammalian epididymis

Posttranslational modification by ubiquitination marks defective or outlived intracellular proteins for proteolytic degradation by the 26S proteasome. The ATP-dependent, covalent ligation and formation of polyubiquitin chains on substrate proteins requires the presence and activity of a set of ubiquitin activating and conjugating enzymes. While protein ubiquitination typically occurs in the cell cytosol or nucleus, defective mammalian spermatozoa become ubiquitinated on their surface during post-testicular sperm maturation in the epididymis, suggesting an active molecular mechanism for sperm quality control. Consequently, we hypothesized that the bioactive constituents of ubiquitin-proteasome pathway were secreted in the mammalian epididymal fluid (EF) and capable of ubiquitinating extrinsic substrates. Western blotting indeed detected the presence of the ubiquitin-activating enzyme E1 and presumed E1-ubiquitin thiol-ester intermediates, ubiquitin-carrier enzyme E2 and presumed E2-ubiquitin thiol-ester intermediates and the ubiquitin C-terminal hydrolase PGP 9.5/UCHL1 in the isolated bovine EF. Thiol-ester assays utilizing recombinant ubiquitin-activating and ubiquitin-conjugating enzymes, biotinylated substrates, and isolated bovine EF confirmed the activity of the ubiquitin activating and conjugating enzymes within EF. Ubiquitinated proteins were found to be enriched in the defective bull sperm fraction and appropriate proteasomal deubiquitinating and proteolytic activities were measured in the isolated EF by specific fluorescent substrates. The apocrine secretion of cytosolic proteins was visualized in transgenic mice and rats expressing the enhanced green fluorescent protein (eGFP) under the direction of ubiquitin-C promoter. Accumulation of eGFP, ubiquitin and proteasomes was detected in the apical blebs, the apocrine secretion sites of the caput epididymal epithelia of both the rat and mouse epididymal epithelium, although region-specific differences exist. Secretion of eGFP and proteasomes continued during the prolonged culture of the isolated rat epididymal epithelial cells in vitro. This study provides evidence that the activity of the ubiquitin system is not limited to the intracellular environment, contributing to a greater understanding of the sperm maturation process during epididymal passage.     

Motility and acrosomal integrity comparisons between electro-ejaculated and epididymal ram sperm after exposure to a range of anisosmotic solutions, cryoprotective agents and low temperatures

Effective ram sperm cryopreservation protocols, which would yield acceptable lambing rates following artificial insemination (AI), are currently lacking. The objectives of the current studies were to compare the effects of various anisosmotic conditions, cryoprotective agents (CPAs) and chilling on the motility and acrosomal integrity of electro-ejaculated and epididymal ram sperm. Three experiments were conducted. In experiment 1, ejaculated and epididymal ram sperm were exposed to 75, 150, 225, 600, 900 and 1200 milliosmolal (mOsm)/kg sucrose solutions, held for 5 min and then returned to isosmotic condition. Motility characteristics of sperm during exposure to each anisosmotic solutions and after returning to isosmotic conditions were determined. In experiment 2, ejaculated and epididymal ram sperm were exposed to 1 M glycerol (Gly), dimethyl sulfoxide (DMSO), ethylene glycol (EG) and propylene glycol (PG) for 5 min and then returned to isosmotic conditions. Motility characteristics of sperm samples during exposure to each CPA solution and after returning to isosmotic conditions were determined. In experiment 3, effects of various temperatures on motility characteristics of ejaculated and epididymal ram sperm were determined after exposing them to three different sub-physiologic temperatures (4, 10 and 22 °C) for 30 min and subsequently returning them to 37 °C. The motility of ejaculated ram sperm was significantly more affected from anisosmotic stress than was epididymal ram sperm (P < 0.05). While anisosmotic stress had no effects on acrosomal integrity of epididymal ram sperm, there was a significant reduction in acrosomal integrity for ejaculated ram sperm after the addition and removal of a 75 mOsm sucrose solution. The abrupt addition and removal of 1 M Gly, DMSO, EG or PG had no effect on the motility and acrosomal integrity of epididymal ram sperm (P > 0.05). However, there was a slight decrease in acrosomal integrity for ejaculated ram sperm after exposure to 1 M Gly, DMSO or EG (P > 0.05). Both epididymal and ejaculated ram sperm exhibited temperature-dependent loss of motility and acrosomal integrity (P < 0.05). However, ejaculated ram sperm was more sensitive to chilling stress than epididymal sperm (P < 0.05). In conclusion, the current data suggest that while epididymal ram sperm is extremely resilient to various cryobiologically relevant stress conditions, ejaculated ram sperm demonstrate greater sensitivity to such stressors. These findings should be taken into account when developing cryopreservation protocols for ejaculated and epididymal ram sperm.     

Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor

It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling. One receptor subtype, which has been suggested to be involved in this regulation, is the P2Y2 receptor (P2Y2R). In the present study, we investigated the effect of P2Y2R overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces. Both mineral apposition rate and thickness of the endocortical osteoid layer were higher in the P2Y2R-Tg rats. μCT analysis showed reduced trabecular thickness and structural model index in P2Y2R-Tg rats. Femoral length was increased in the P2Y2R-Tg rats compared to Wt rats. In vitro, there was an increased formation of osteoclasts, but no change in total resorption in cultures from P2Y2R-Tg rats. The formation of mineralized nodules was significantly reduced in the osteoblastic cultures from P2Y2R-Tg rats. In conclusion, our study suggests that P2Y2R is involved in regulation of bone turnover, due to the effects on both osteoblasts and osteoclasts and that these effects might be relevant in the regulation of bone growth.     

Serotonin transporter gene polymorphisms and sertraline response in major depression patients

Major depression (MD) has a complex multifactorial etiology with genetic and environmental factors contributing to the disorder. As with all antidepressant treatments, there is variability in drug response due to heredity, generally focusing on genetic polymorphism of the drug-metabolizing transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered to be an interesting candidate in the mechanism of antidepressant drugs. In this study, we have focused on the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) related to sertraline responses. Our sample consisted of 64 unrelated Turkish subjects who strictly met DSM-IV and CGI scores. There was no significant difference between the frequency of the SS, LS, LL, 9/10, 10/10, 9/12, 10/12, and 12/12 genotypes and responses to sertraline. However, the number of patients can be increased and different drugs can be studied in order to find a specific pharmacogenetic relation.     

Effect of pericardial fluid pro-inflammatory cytokines on hemodynamic parameters

We investigated the effects of pro-inflammatory cytokines of pericardial fluid on hemodynamic parameters in patients undergoing coronary artery surgery. Seventy-eight patients were included in the study and they were allocated to three groups: group 1, stable angina pectoris (SAP, n = 15); group 2, unstable angina pectoris (USAP, n = 34); group 3, post-myocardial infarction (PMI, n = 29). Pericardial fluid and arterial blood samples were obtained from all patients and interleukin (IL)-1beta, IL-2 receptor, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) levels were measured. Pericardial IL-1beta concentration (pg/mL) was significantly higher in the USAP group (26.6 +/- 10.9) compared to the SAP (5.0 +/- 0.1) and PMI (5.8 +/- 1.0) groups. IL-2R, IL-6, IL-8 and TNF-alpha concentrations of pericardial fluid were significantly higher than serum in all groups; difference was more prominent in the PMI group compared to the SAP and the USAP groups. Serum IL-1beta concentrations (pg/mL) were significantly higher in the USAP group (21.8 +/- 3.4) compared to the SAP group (5.0 +/- 0.1) and the PMI group (5.4 +/- 1.6). Cardiac index (CI) before opening the pericardial sac was found to be lower in the USAP group (1.6 +/- 0.3 L/min/m2) compared to the SAP (2.2 +/- 0.5 L/min/m2) and the PMI (2.1 +/- 0.5 L/min/m2) groups (p = 0.028 and p = 0.011, respectively). In the USAP group, there was a relationship between reduction of CI and increase of IL-1beta levels in serum and pericardial fluid.     

Topographic mapping of the superior transverse scapular ligament: a cadaver study to facilitate suprascapular nerve decompression

Division of the superior transverse scapular ligament for decompression of suprascapular nerve entrapment can be curative. However, the superior transverse scapular ligament can be difficult to locate, and large incisions are often required. This study was designed to determine the topographic coordinates of the superior transverse scapular ligament to permit reproducible surgical localization and reduce incision size. In 20 cadavers, the superior transverse scapular ligament was identified through a superior approach. Measurements were obtained from the superior transverse scapular ligament to external landmarks. The superior transverse scapular ligament was located 1.3 +/- 0.3 cm (+/- SD) posterior to the posterior border of the clavicle and 2.9 +/- 0.8 cm from the acromioclavicular joint in a two-dimensional surface plane. The depth of the superior transverse scapular ligament from the skin surface was 3.9 +/- 0.7 cm. An incision (mean length, 6.3 +/- 0.7 cm) derived from a novel system of planning marks facilitated access to the superior transverse scapular ligament. The authors conclude that the superior transverse scapular ligament can be located consistently through an incision located on the superior aspect of the shoulder on the basis of palpable topographic landmarks. The superior approach permits small incision size and the maintenance of local muscle anatomic integrity.     

Increased expression of angiogenic markers in patients with seasonal allergic rhinitis

BACKGROUND: Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis. OBJECTIVE: We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. METHODS: Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immunohistochemical analysis methods (HSCORE, MVD and VSD).Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. CONCLUSION: There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR.