ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury

The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4−/−, Adamts5−/−, and wt mice but not in the sham-operated group. By contrast Adamts4−/− and Adamts5−/− mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4−/− mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4−/− or Adamts5−/− mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI

Frequency of Stent Placement after Ureteroscopic Lithotripsy in a University and a State Hospital

Objective: The aim of this study was to compare frequen­cy of ureteral stent placement after ureteroscopic litho­tripsy in a university and a state hospital of two different cities, which are endemic in terms of stone and often ure­terolithotripsy was performed for urolithiasis treatment. Methods: The patients who applied in to urology clinic of Inonu University Turgut Ozal Medical Center (TOMC) and urology clinic of Osmaniye State Hospital (OSH) between January 2014 and May 2014 were evaluated retrospec­tively. The patients who underwent ureteroscopic lithotrip­sy due to ureteral stone, were evaluated stone locations, stone sizes, grades of pelvicaliectasia and ureteral stent placement status. Results: About 92 patients were enrolled into the study from the both hospital. After the endoscopic ureteral stone treatment, Double J stent was placed in 85 patients in TOMC (92.3%) and 82 patients in OSH (89.1%). Stent im­plantation rate in the university hospital was higher than the state hospital but this was not statistically significant. There was a statistically meaningful difference in mean operative time between the 2 groups. Conclusion: Double J stent placament is recently per­formed too often after the endoscopic ureteral stone treat­ment. According to our study, university hospitals have a higher rate of incidence of double j stent placement ac­cording to state hospitals. It can be reason for that, uni­versity hospitals as the last line treatment centers, more complicated cases that refer to these centers. But in this matter, prospective, multicenter and larger series studies are needed

A practical scoring system to predict mortality in patients with perforated peptic ulcer

Conclusion: Because the new system consists only age and routinely measured two simple laboratory tests (albumin and BUN), its application is easy and prediction power is satisfactory. Verification of this new scoring system is required by large scale multicenter studies

Percutaneous Nephrolithotomy for Paediatric Stone Disease

We evaluated the outcomes and complications occurring following percutaneous nephrolithotomy (PCNL) procedures performed in paediatric patients. There were 291 paediatric patients (293 renal units) included in the current study and who underwent PCNL in our clinic between March 1999 and December 2014. We evaluated stone burden, duration of surgery and complications, success (stone-free) rate, residual fragments and auxilliary procedures, and follow-up details. The stone-free rate following PCNL was 88.3%. Early postoperative complications included excessive bleeding and transfusion in nine patients, and prolonged urinary extravasation following removal of the nephrostomy tube and requiring JJ stent placement in eight patients. The mean time to catheter removal was 2.8 days and the mean hospitalisation time was 3.5 days. The aim of kidney stone treatment is to achieve minimal kidney damage with the highest success rate. Therefore, minimally invasive procedures are important in the paediatric age group where life expectancy is high. PCNL is a safe and effective procedure for the treatment of kidney stones in children

Percutaneous Nephrolithotomy and Complications: Our Experience with 3,003 Cases

We report the outcomes of 3,003 percutaneous nephrolithotomy (PCNL) procedures performed in our institution between March 1998 and December 2014. The PCNL procedures were performed under general anaesthesia. The ureteral catheter was installed in the supine position during cystoscopy under C-arm fluoroscopy guidance and, after turning the patient into the prone position, the kidney with stone was entered with a metal needle under fluoroscopy. The Amplatz renal dilator set was used (dilation or balloon renal dilator). The nephrostomy catheter was placed in the renal sheath. After completion of PCNL procedures, residual asymptomatic stones of 4 mm or less in size were considered clinically insignificant. Of the total number of patients, 2,699 (89.88%) achieved stone clearance. Bleeding requiring transfusion occurred in 186 cases (6.19%), of which 14 (0.47%) were treated with embolisation angiography. A double-J stent was inserted in 158 patients (5.26%). Pneumothorax occurred in 24 patients (0.80%) and colon perforation occurred in one patient (0.03%). In angiography, the bleeding site was not identified in one patient and open repair was performed. Mean duration of hospitalisation was 3.3 days and the nephrostomy tube was kept for a mean duration of 2.6 days

Antioxidant and anti-apoptotic effects of onion (Allium cepa) extract on doxorubicin-induced cardiotoxicity in rats

The aim of this study was to investigate the antioxidant and anti-apoptotic effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced cardiotoxicity. The rats in the ACE-pretreated group were given a daily dose of 1 ml ACE for 14 days. To induce cardiotoxicity, DOX (30 mg kg-1 body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. To date, no such studies have been performed on the cardioprotective and anti-apoptotic potential of ACE on DOX-induced cardiotoxicity. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in cardiomyocytes of the DOX-treated group with ACE therapy. The DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels, and increased activities of superoxide dismutase, glutathione and glutathione peroxidase in comparison with the DOX-treated group. Creatine kinase, creatine kinase MB, lactate dehydrogenase activities and cardiac troponin I levels were significantly decreased in the DOX + ACE group in comparison with the DOX group. These biochemical and histological disturbances were effectively attenuated on pretreatment with ACE. The present study showed that ACE may be a suitable cardioprotector against toxic effects of DOX. Copyright (C) 2011 John Wiley & Sons, Ltd

The effects of onion (Allium cepa) extract on doxorubicin-induced apoptosis in aortic endothelial cells

The aim of this study was to investigate the effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced apoptosis in aortic endothelial cells. The rats in the ACE-pretreated group were given a daily dose of 1ml ACE for 14days. To induce aortic endothelial cell apoptosis, DOX (30mgkg1 body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48h. To date, no such studies have been performed on antiapoptotic potential of ACE on DOX-induced apoptosis in aortic endothelial cells. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in aortic endothelial cells of the DOX-treated group with ACE therapy. DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels and increased levels of glutathione in comparison with the DOX-treated group. Data from our study show that prevention of endothelial cell apoptosis by ACE may contribute to the restoration of aortic endothelial dysfunction that is associated with DOX treatment. Copyright (c) 2011 John Wiley & Sons, Ltd

ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS)has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI. (c) 2013 Elsevier Ireland Ltd. All rights reserved

Bioassay-guided isolation, identification of compounds from <i>Origanum rotundifolium</i> and investigation of their antiproliferative and antioxidant activities

<p><b>Context:</b><i>Origanum</i> (Lamiaceae) has been used in food and pharmaceutical industries.</p> <p><b>Objective:</b> Isolation and identification of bioactive compounds from <i>Origanum rotundifolium</i> Boiss. and investigation of their antiproliferative and antioxidant activities.</p> <p><b>Materials and methods:</b> The aerial part of <i>O. rotundifolium</i> was dried and powdered (1.0 kg ±2.0 g) then extracted with hexane, ethyl acetate, methanol and water. Solvent (3 × 1 L) was used for each extraction for a week at room temperature. The aqueous extract was partitioned with ethyl acetate (3 × 1 L) to yield the water/EtOAc extract subjected to chromatography to isolate the active compounds. The structures of isolated compounds were elucidated by 1 D, 2 D NMR and LC-TOF/MS.</p> <p><b>Results:</b> Apigenin (<b>1</b>), ferulic acid (<b>2</b>), vitexin (<b>3</b>), caprolactam (<b>4</b>), rosmarinic acid (<b>5</b>), and globoidnan A (<b>6</b>) were isolated and identified. Globoidnan A (<b>6</b>), vitexin (<b>3</b>), and rosmarinic acid (<b>5</b>) revealed the excellent DPPH^• scavenging effect with IC₅₀ values of 22.4, 31.4, 47.2 μM, respectively. Vitexin (<b>3</b>) (IC₅₀ 3.6), globoidnan A (<b>6</b>) (IC₅₀ 4.6), apigenin (<b>1</b>) (IC₅₀ 8.9) and ferulic acid (<b>2</b>) exhibited more ABTS^•+ activity than standard Trolox (IC₅₀ 13.8 μg/mL). Vitexin (<b>3</b>) revealed the most antiproliferative activity against HeLa, HT29, C6 and Vero cells lines with IC₅₀ values of 35.6, 32.5, 41.6, 46.7 (μM), respectively.</p> <p><b>Discussion and conclusion:</b> Globoidnan A (<b>6</b>) has the most antioxidant effects on all assays. This has to do with the chemical structure of the compound bearing the acidic protons. Vitexin (<b>3</b>) could be a promising anticancer agent.</p