The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits

We have compared the hemorrhagic and antithrombotic effects of a low molecular weight (LMW) heparin fraction and standard heparin in rabbits. Similar LMW heparin fractions have antithrombotic effects when tested in animals, but their hemorrhagic effects relative to standard heparin have not been established. Standard porcine mucosal heparin (mol wt 15,000 daltons) was depolymerized by nitrous acid to a low molecular weight fraction (mol wt 4600 daltons). Using equal USP units, the standard and Dep LMW heparin were compared in vitro, ex vivo, and in vivo. In vitro, when diluted in rabbit plasma, the Dep LMW heparin at equivalent anti-Xa activity showed less prolongation of thrombin clotting times or activated partial thromboplastin times. Ex vivo, platelets from rabbits treated with the Dep LMW heparin showed less inhibition of collagen-induced aggregation. The relative hemorrhagic properties of the two heparins were compared in vivo in rabbits using a sensitive blood loss assay, and the antithrombotic properties were compared in a thrombin-induced venous stasis model. By using an optimal threshold heparin dose in each test system, it was possible to demonstrate that equal USP units of Dep LMW heparin caused less blood loss but showed greater antithrombotic activity than standard heparin.     

Should we abandon regional anesthesia in open inguinal hernia repair in adults?

Inguinal hernia repair is a common worldwide surgical procedure usually done in the outpatient setting. The purpose of this systematic review is to make an evidence-based meta-analysis to determine the possible benefits of regional (neuraxial block) anesthesia compared to general anesthesia in open inguinal hernia repair in adults. Cochrane Library, Medline, EMBASE, CINAHL, SCI-EXPANDED, SCOPUS as well as trial registries, conference proceedings and reference lists were searched. Only randomized controlled trials (RCT) that compare neuraxial block (spinal or/and epidural) anesthesia (NABA) and general anesthesia (GA) were included. Main outcome measures were postoperative complications, urinary retention and postoperative pain. Seven RCTs were included in this review. A total of 308 patients were analyzed with 154 patients in each group. Overall complications were evenly distributed in NABA and in GA group [OR 1.17, 95 % CI (0.52–2.66)]. Urinary retention was statistically less frequent in GA group compared to NABA group [OR 0.25, 95 % CI (0.08–0.74)]. Movement-associated pain score 24 h after surgery was significantly lower in NABA group [SMD 5.59, 95 % CI (3.69–7.50)]. Time of first analgesia application was shorter in GA group [SMD 8.99, 95 % CI 6.10–11.89]. Compared to GA, NABA appears to be a more adequate technique in terms of postoperative pain control. However, when GA is applied, patients seem to have less voiding problems.     

Pulp chamber temperature rise during curing of resin-based composites with different light-curing units.

AIMS: The purpose of the present study was to measure the intrapulpal temperature rise occurring during polymerisation of different shades of resin-based composites (RBCs), and two light-emitting diode (LED) units. METHODS: Seventy non-carious permanent molars, that had been extracted for orthodontic purposes and stored in 2% thymol for not more than four months, were selected. Patient age range was 11-18 years. Standard cavity preparation with standardised remaining dentine thickness and placement of thermocouples (TCs) was prepared using a novel split-tooth technique. Cavities were filled with one of two shades of RBC (A2 and C4, Filtek Z250, 3M ESPE, Seefeld, Germany), and cured with two LED high-intensity units (Elipar Freelight2, 3M ESPE, Seefeld, Germany; Bluephase, Ivoclar Vivadent, Schaan, Liechtenstein) and a conventional halogen light-curing unit (LCU) (Prismetics Lite 2, Dentsply, Weybridge, Surrey, UK) as a control. RESULTS: Pulp temperature rises during bonding [A2 results: H;2.67/0.48:E;5.24/1.32;B;5.99/1.61] were always greater than during RBC curing [A2 results: 2.44/0.63;E3.34/0.70;B3.38/0.60], and these were significant for both LED lights but not for the halogen control, irrespective of shade (Mann-Whitney test: 95% confidence limits). Temperature rises were at times in excess of the values normally quoted as causing irreversible pulp damage. Pulp temperature rises during bonding were higher with the LED lights than with the halogen control. There was no significant difference in temperature rise between the two LED lights when bonding but there was a significant difference between the two LED lights and the halogen control LCUs (Kruskal-Wallis Test: 95% confidence limits). CONCLUSIONS: The results support the view that there is a potential risk for heat-induced pulpal injury when light-curing RBCs. The risk is greater during bonding and with high energy, as compared to low-energy output systems. As the extent of tolerable thermal trauma by the pulp tissues is unknown, care and consideration should be given to the choice of LCU and the exposure time when curing RBCs, and especially during bonding.     

Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats

Glioblastomas (GBMs) are aggressive brain tumours with a dismal prognosis, despite combined surgery, radio- and chemotherapy. Close to 90?% of all GBMs harbour a deregulated PI3K pathway, which is essential in regulating central cellular functions such as proliferation, cell growth, motility and survival. Thus, PI3K represents a potential target for molecular therapy in GBM. We investigated the anti-tumour efficacy of the PI3K inhibitor buparlisib (NVP-BKM120) in GBM cell lines in vitro and in vivo, when treatment was initiated after MRI-confirmed tumour engraftment. We found that buparlisib inhibited glioma cell proliferation in a dose dependent manner, demonstrated by MTS assay, manual cell count and BrdU incorporation. A dose dependent increase in apoptosis was observed through flow cytometric analysis. Furthermore, by immunocytochemistry and western blot, we found a dose dependent inhibition of Akt phosphorylation. Moreover, buparlisib prolonged survival of nude rats harboring human GBM xenografts in three independent studies and reduced the tumours’ volumetric increase, as determined by MRI. In addition, histological analyses of xenograft rat brains showed necrotic areas and change in tumour cell nuclei in buparlisib-treated animals. The rats receiving buparlisib maintained their weight, activity level and food- and water intake. In conclusion, buparlisib effectively inhibits glioma cell proliferation in vitro and growth of human GBM xenografts in nude rats. Moreover, the compound is well tolerated when administered at doses providing anti-tumour efficacy. Thus, buparlisib may have a future role in glioma therapy, and further studies are warranted to validate this compound for human use.     

Surface antigenic determinants on human pluripotent and unipotent hematopoietic progenitor cells

RFB-1 is a monoclonal antibody previously shown to react with granulocyte-monocyte progenitors (CFU-GM) and immature lymphoid cells in human bone marrow. RFB-HLA-DR is a monoclonal antibody that reacts with HLA-DR (la-like) antigens. The present study shows that the bone marrow subset reactive with both RFB-1 and RFB-HLA-DR contains all the cells that give rise to mixed hematopoietic colonies (derived from CFU- GEMM; a pluripotent human progenitor cell) as well as to megakaryocytic (megakaryocyte-CFU-derived) and erythropoietic (derived from erythroid burst-forming units, BFU-E) colonies, as shown by fluorescence- activated cell sorting and complement-mediated cytotoxicity. These results indicate that CFU-GEMM, BFU-E, and megakaryocyte-CFU express RFB-1 and la-like antigens. RFB-1 antigen is also expressed on erythroid colony-forming units (CFU-E). RFB-1 and RFB-HLA-DR are useful reagents in the study of hematopoietic stem cells.     

Continual systemic infusion of lidocaine provides analgesia in an animal model of neuropathic pain

We examined whether continual constant-rate infusion of lidocaine would provide analgesia during the initial post-injury phase in the chronic constriction injury model of neuropathic pain. Male Sprague-Dawley rats were divided into control and ligated groups and infused with saline or lidocaine (0.15, 0.33, 0.67, and 1.3mg/kg/h) via subcutaneously implanted Alzet((R)) osmotic minipumps. Thermal withdrawal latencies were obtained prior (Day 0) and 3 days after loose sciatic ligation and pump implantation surgery. Ligated animals receiving lidocaine at 0.67 or 1.3mg/kg/h exhibited no change in withdrawal latency on Day 3 after surgery, indicating that lidocaine at these doses prevented the development of thermal hyperalgesia as a sign of neuropathic pain. In contrast, ligated animals treated with saline or lidocaine at 0.15 or 0.33mg/kg/h exhibited hyperalgesia on Day 3 after surgery, indicating that these lower doses of lidocaine failed to provide analgesia. Control animals treated with saline or any of the lidocaine doses exhibited no change in withdrawal latencies between Day 0 and Day 3. In a separate group of ligated animals, lidocaine infusion (0.67mg/kg/h) that was started 24h after sciatic ligation surgery reversed the already present thermal hyperalgesia. Average plasma lidocaine concentrations were 0.11, 0.36, and 0.45microg/ml for animals receiving 0.33, 0.67 and 1.3mg/kg/h of lidocaine, respectively. These results suggest that continual systemic infusion of lidocaine prevents or reverses the development of neuropathic pain following chronic constriction injury. These results add to the increasing body of evidence supporting the therapeutic value of preemptive and post-operative lidocaine administration for the relief of neuropathic pain.     

Remaining unreacted methacrylate groups in resin-based composite with respect to sample preparation and storing conditions using micro-Raman spectroscopy

The aim of this study was to measure degree of conversion (DC) of resin-based composites (RBCs) using micro-Raman spectroscopy followed by different sample preparation procedures and storing conditions. Ninety samples of Tetric EvoCeram (Ivoclar Vivadent, Schaan, Liechtenstein) were prepared in standardized molds and cured with a high powered LED light-curing unit, bluephase (Ivoclar Vivadent, Schaan, Liechtenstein) for 20 s. Samples were allocated to eight groups. DC of groups 1 and 2 was recorded without or after polishing. DC in groups 3 and 4 was recorded from vertically sectioned samples versus "split" samples. DC in groups 5-8 was recorded after storing samples at room temperature and humidity, in 90 +/- 2% humidity at 37 +/- 1 degrees C, distilled water at 37 +/- 1 degrees C or buffered incubation medium (BIM) at 37 +/- 1 degrees C for 24 h. Mean values of DC in polished and unpolished samples were 63.6% (+/-3.2%) and 54.7% (+/-5.2%), respectively (p < 0.0001). There was no significant difference in DC after sample-sectioning (p > 0.05). Significantly higher DC values were obtained after storing samples in BIM (76.8% +/- 2.1%) than in distilled water (59.7% +/- 5.7%), extreme humidity (60.3% +/- 3.9%) or in room conditions (63.6% +/- 3.2%) (p < 0.001). DC of an RBC measured by micro-Raman spectroscopy may be affected by differences in sample preparation and storing conditions, making it difficult to extrapolate data from in vitro studies into clinically relevant information.     

Treatment of children with neurogenic bladder dysfunctions using dynamic nero-electrostimulation(DENS) and M-Cholinolytic therapy

【Objective】 To investigate effects of combined usage of dynamic neuro-electric stimulation(DNES) and M-cholynolytic therapy(oxybutynin) upon manifestations of neurogenic bladder dysfunctions(NBD) in children.【Method】 Urodynamics examination included registration of extemporaneous urinary excretion,urofluometry,and retrograde cytometry in horizontal and vertical position by example of urodynamic system(UDS) ACS 180 Plus(MENFIS BioMed.,USA).In accordance to severity of clinician manifestations,three groups of patients have been defined(27-highest one,49-middle and 51 low levels).Dynamic neuro-electrostimulation(DNES) procedures were conducted using the"DiaDNES-PKM"device(Russian Federation).The children were exposed to juxtaspinal stimulation on S1-S3 level-altogether 10 sessions have been performed.Oxybutynin(driptan) was used in dosage of 2.5 mg per diem.【Result】It was established that combined usage of DNES and oxybutynin in the group with highest severity caused the reduction of manifestations by 3.1 times while separately given DNES and basic therapy were followed by 34.1% and 28.0% reduction correspondently.Meanwhile,DNES and oxybutynin reduced severity in patients with pronounced disturbances by 7.5 times.Combined usage of oxybutynin and DNES in severely manifested NBD increased the effective volume of bladder by 2.3 times.Also significant reduction of both intrabladder pressure(by 48.0%) and compliance of the bladder(by 4.8 times) were detected under condition of combined usage of DNES and oxybutynin.All mentioned indices were modified to less extent in case of separate usage of DNES or oxybutynin when compared with the one registered after the combined their usage(P <0.05).【Conclusion】Combined usage of DENS and oxybutinin(driptan) is effective in most severe cases in children suffered from neurogenic overactive bladder.