HEPSIN inhibits cell growth/invasion in prostate cancer cells

Expression of HEPSIN, a type II transmembrane serine protease in prostate cancer (CaP), has been highlighted by several studies analyzing CaP-specific gene expression alterations by cDNA microarray. Evaluations of the biological functions of HEPSIN in CaP cells are warranted for better assessment of its utility as a biomarker and/or therapeutic target. In stable clones of PC-3/HEPSIN transfectants, there was a dramatic reduction in the cell growth, cell invasion, and soft agar colony formation. A higher proportion of PC-3/HEPSIN cells were in the G(2)-M phase of the cell cycle, and there was also an increase in the cell population undergoing apoptosis. Preliminary analysis of HEPSIN transfections into LNCaP and DU145 cells further revealed cell growth-inhibitory effects. These results underscore that exogenous HEPSIN expression negatively regulates cell growth in metastatic CaP cell lines. Although the cause of the biological consequence of HEPSIN overexpression in primary CaP remains to be determined, the negative cell growth-regulatory effects of HEPSIN in metastatic CaP cells reported here have unraveled possible cellular and molecular mechanisms underlying observations that link decreased/loss of HEPSIN expression with poor prognosis of CaP.     

The use of a bioactive skin substitute decreases length of stay for pediatric burn patients

BACKGROUND: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA). This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children. METHODS: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n = 20). These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy. Standard therapy consisted of application of antimicrobial ointments and hydrodebridement. The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS. Data were analyzed using the student's t test. RESULTS: Data for age, percent TBSA burn and LOS are reported as means +/- SEM. The children who received standard therapy were 2.99 +/- 0.7 years compared with those receiving TransCyte were 3.1 +/- 0.8 years. There was no difference between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 +/- 1.4% TBSA versus TransCyte, 12.7 +/- 1.3% TBSA. There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group. Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%). Children treated with TransCyte had a statistically 6 significant decreaed LOS compared with those receiving standard therapy, 5.9 +/- 0.9 days versus 13.8 +/- 2.2 days, respectively (P =.002). CONCLUSIONS: This is the first study using TransCyte in children. The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS. This new approach to pediatric burn care is effective and improves the quality of care for children with burns.     

Laparoscopic Cardial Calibration and Gastropexy for Treatment of Patients with Reflux Esophagitis: Pathophysiological basis and Result

Laparoscopic antireflux surgery is the gold standard procedure for treatment of patients with reflux esophagitis. The current results of the laparoscopic approach are absolutely comparables with the results obtained during the open surgery era. The Nissen, Nissen-Rossetti, or Toupet techniques are the more frequently used. We have performed cardial calibration and posterior gastropexy or Nissen fundoplication by the open approach with similar results. The purpose of this article is to present the anatomo-physiological basis for employing cardial calibration and posterior gastropexy in patients with reflux esophagitis. This study includes 108 symptomatic patients, 12 of them with associated extraesophageal manifestations ( posterior laryngitis). Endoscopic mild or moderate esophagitis was confirmed in 83 patients, Barrett’s esophagus in 12 patients, and type I or II hiatal hernia in 13 patients. All patients were also submitted to manometry, 24 hour intraesophageal pH monitoring, and barium swallow before and after surgery. Follow-up ranged from 12 to 36 months. There were no conversion, major intraoperative, or postoperative complications; nor were there any deaths. Postoperative dysphagia was present in 5% of cases. Symptomatic recurrence of reflux was observed in 10.3% and endoscopic presence of esophagitis in 12.3% of cases . Lower esophageal sphincter pressure increased significantly after surgery, even in patients with endoscopic recurrence. 24-hour intraesophageal monitoring improved after surgery, except in patients with objective recurrence of esophagitis. In conclusion, laparoscopic cardial calibration with posterior gastropexy presents comparable results to those reported after Nissen fundoplication and therefore could be another excellent therapeutic option in patients with reflux esophagitisThis paper was accepted for presentation as a free paper oral presentation for the last World Congress of ISS-SIC (cancelled).     

Molecular systematics of several cyclophyllid families (Cestoda) based on the analysis of 18S ribosomal DNA gene sequences

The sequences of the 18S small subunit ribosomal DNA of five species of cyclophyllidean cestodes from the families Davaineidae, Anoplocephalidae and Dilepididae were determined. A species of tetrabothridid was also sequenced. These 18S sequences were combined with other available eucestode sequences in GenBank. From the 1,838 sites in the alignment, 375 bp (20%) were excluded from the analysis due to alignment issues inferred by manual inspection. Phylogenetic trees were obtained by maximum parsimony, neighbour-joining distance and maximum likelihood methods. Analyses showed that Cyclophyllidea is monophyletic and separate from Tetrabothrius spp. Lyruterina nigropunctata, which is now included in the family Paruterinidae, is more closely related to davaineids of the genus Raillietina than Pseudidiogenes nana (Davaineidae). P. nana and Choanotaenia infundibulum (Dilepididae) derive from the Davaineidae (or Raillietininae). The two species of Taenia (T. parva and T. pisiformis) formed a monophyletic sister group to the Davaineidae and Anoplocephalidae. The systematics of the Paruterinidae have been problematic and our results suggest a review of this family including other species with paruterine organ located in other families. The position of the Idiogeninae as a subfamily in the Davaineidae is also reviewed.     

alpha 1d Adrenoceptor signaling is required for stimulus induced locomotor activity

alpha 1 Adrenergic receptors mediate a variety of physiological responses and have been well studied in the cardiovascular and peripheral nervous system. However, their role in the central nervous system remains ill defined because of the lack of highly specific ligands to the alpha1 receptor subtypes. Here, we have employed gene targeting to elucidate the role of alpha 1d receptors in vivo. In addition to disrupting function, the insertion of the lacZ gene into the alpha 1d receptor locus enabled the specific identification of cells expressing the alpha 1d gene. These cells are localized in the cortex, hippocampus, olfactory bulb, dorsal geniculate and ventral posterolateral nuclei of the thalamus. Behaviorally, the alpha 1d(-/-) mice show normal locomotor activity during the subjective day, or resting phase of their cycle. However, during subjective night, or active phase, wheel-running activity is significantly reduced in mutant mice. Furthermore, these mice show a reduction in exploratory rearing behavior in a novel cage environment. Lastly, alpha 1d(-/-) mice show reduced hyperlocomotion after acute amphetamine administration. Together, these data reveal the functional importance of alpha 1d adrenoceptors in mediating a variety of stimulus-induced changes in locomotor behaviors. While the sensitivity of noradrenergic neurons to environmental stimuli has been well documented, our data demonstrate that at least some of these post-synaptic responses are mediated by alpha 1d adrenergic receptors.     

Equol is more active than soy isoflavone itself to compete for binding to thromboxane A(2) receptor in human platelets

Introduction

Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific mechanism by which this action occurs has not been established. The aim of this study was to investigate the inhibitory effect of soy-isoflavones and the metabolite of daidzein, equol, on agonist-induced platelet responses dependent on thromboxane A₂ (TxA₂) receptor.

Material and methods

Competitive radioligand binding assay was used to screen for affinity of these compounds to the TxA₂ receptor. The effect of equol on platelet activation, evaluate through of release of the ATP, by analogs of TxA₂ was analyzed. The effect of equol on platelet aggregation was investigated with ADP, U46619 (a TxA₂ mimic) and the calcium ionophore A23187.

Results

The data showed that aglycone isoflavones and equol bind to TxA₂ receptor in the µmol/L range, whereas their glucoside derivates had very low binding activity for this receptor. Under equilibrium conditions, the following order of the relative affinity in inhibiting [³H]-SQ29585 binding was: equol > genistein > daidzein > glycitein ? genistin, daidzin, glycitin. Equol interaction was reversible and competitive for labeled-SQ29548 with not apparent decrease in the number of TxA₂ binding sites. In addition, from platelet activation studies, equol effectively inhibited ATP secretion elicited by the TxA₂ analog U46619. On the other hand, equol inhibited the platelet aggregation induced by U46619 and A23187, while it failed to inhibit that induced by ADP.

Conclusions

The aglycone isoflavones from soy, and particularly equol, have been found to have biological effects attributable to thromboxane A₂ receptor antagonism. These findings may help elucidate how dietary isoflavone modulate platelet function and explain why soy-rich foods are claimed to have beneficial effects in the prevention of thrombotic events.     

Evaluation of the Radiological Gastric Capacity and Evolution of the BMI 2–3 Years After Sleeve Gastrectomy

Background  Sleeve gastrectomy is a restrictive procedure for treatment of obese patients with different body mass index (BMI) and presents good results in terms of a reduction of percentage of excess weight loss and BMI. There is no consensus which is the optimal technique regarding to the diameter of the gastric tube, but a capacity of 100–120 ml has been suggested. In this prospective study, we compare the gastric capacity evaluated with barium sulfate or computer-aided tomography (CAT) scan early and 24 months after operation compared to the changes in body weight and BMI reduction in a small group of 15 consecutive patients submitted to sleeve gastrectomy. Methods  Fifteen successive obese patients submitted to laparoscopic sleeve gastrectomy were included. They were studied in order to measure the residual gastric capacity with barium sulfate and CAT scan early (3 days) and late (2 years) after surgery. Results  The early postoperative gastric volume was 108 ± 25 ml (80–120 ml) and 116.2 ± 78.24 assessed with barium sulfate and CAT scan, respectively. The gastric capacity at the late control increased to 250 ± 85 and 254 ± 56.8 assessed with the same techniques. However, patients remained stable with a BMI close to 25 without regain of weight at least at the time of observation. Conclusions  Gastric capacity can increase late after sleeve gastrectomy even after performing a narrow gastric tubulization. It is very important to measure objectively residual gastric volume after sleeve gastrectomy and its eventual increase in order to determine the late clinical results and to indicate eventual strategy for retreatment.     

Isolation of <Emphasis Type="Italic">Balamuthia mandrillaris</Emphasis> from urban dust,free of known infectious involvement

The free-living amoeba Balamuthia mandrillaris can cause fatal encephalitis in humans and other mammals. The organism is associated with soils, and soil exposure has been identified as a risk factor for this pathogen. However, B. mandrillaris has been isolated only once from soils believed to be the source of the infection in child from California, USA who died of Balamuthia amoebic encephalitis and once from another unrelated soil source. We report for a third time the isolation of B. mandrillaris from the environment and for the second time its isolation from a sample not known to be involved with pathogenicity. We have established the new clonal B. mandrillaris strain (ID-19) in axenic media. The identity of our isolate was originally by morphology using a light microscope and this has been confirmed by 16S rRNA gene PCR. The new strain ID-19 groups with others of the species. The fact that our isolate came from dust particles deposited on surfaces from the air in an urban environment may suggest that it is not just soil exposure that constitutes a risk factor for Balamuthia infection. This is the first report of this organism from Iran.