Intraperitoneal treatment with S100B enhances hippocampal neurogenesis in juvenile mice and after experimental brain injury

Background

Neurogenesis is documented in adult mammals including humans, is promoted by neurotrophic factors, and constitutes an innate repair mechanism following brain injury. The glial neurotrophic protein S100B is released following various types of brain injuries, enhances hippocampal neurogenesis and improves cognitive function following brain injury in rats when applied intrathecally. The present study was designed to elucidate whether the beneficial effect of S100B on injury-induced neurogenesis can be confirmed in mice when applied intraperitoneally (i.p.), and whether this effect is dose-dependent.

Methods

Male juvenile mice were subjected to a unilateral parietal cryolesion or sham injury, and treated with S100B at 20nM, 200nM or vehicle i.p. once daily. Hippocampal progenitor cell proliferation was quantified following labelling with bromo-deoxyuridine (BrdU, 50 mg/KG i.p.) in the germinative area of the dentate gyrus, the subgranular zone (SGZ), on day 4 as well as on cell survival and migration to the granular cell layer (GCL) on day 28. Progenitor cell differentiation was assessed following colabelling with the glial marker GFAP and the neuronal marker NeuN.

Results

S100B enhanced significantly the early progenitor cell proliferation in the SGZ as well as cell survival and migration to the GCL, and promoted neuronal differentiation. While these effects were predominately dose-dependent, 200nM S100B failed to enhance the proliferation in the SGZ on day 4 post-injury.

Conclusion

We conclude that S100B participates in hippocampal neurogenesis after injury at lower nanomolar concentrations. Therefore S100B may serve as a potential adjunct treatment to promote neuroregeneration following brain damage.     

Quantitative assessment and determinants of suture-holding capacity of human pancreas

Background

Hard pancreas is welcome by surgeons performing resective pancreatic surgery, because it is believed to offer better suture holding capacity (SHC), thus decreasing the risk for a postoperative leak. However, neither the actual SHC of pancreatic tissue in humans nor its determinants have been studied.

Methods

We directly measured SHC for polydioxanone 5–0 suture and tissue hardness at the pancreatic isthmus in 53 human pancreata using a dynamometer and a durometer. A histologic score based on fibrosis grade, fat content, pancreatic duct size, and signs of chronic pancreatitis was calculated for every sample. We tested the hypothesis that SHC of the pancreas was proportional to tissue hardness, and evaluated the role of different possible histomorphologic determinants of SHC.

Results

Suture-holding capacity correlated perfectly with tissue hardness (r = 0.98; P < 0.001; 95% confidence interval, 0.96–0.99). The histologic score showed a stronger correlation with both parameters than any single histologic parameter. The SHC of transductal sutures was significantly higher than that of pure transparenchymal sutures. The SHC and hardness were significantly lower in patients who developed a clinically relevant pancreatic fistula postoperatively.

Conclusions

A mixture of histomorphologic features of human pancreas determines its tissue hardness and SHC. Involvement of the main pancreatic duct in the suture line appears to increase the mechanical strength of the pancreatic anastomosis.     

Physicians’ awareness of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer carcinomatosis

Background

Recent trials have shown that cytoreductive surgery and heated intraperitoneal chemotherapy (S+HIPEC) for colorectal cancer carcinomatosis (CRC-C) leads to 5-year, disease-free survival rates of more than 30%. Since these data represent a substantial change in the management of CRC-C, the objectives of this study were to determine physicians’ awareness of S+HIPEC for CRC-C and physician characteristics predictive of awareness of S+HIPEC for CRC-C.

Methods

This study was a mailed, cross-sectional survey of general surgeons and medical oncologists in Ontario.

Results

The response rate was 44.0% (214 of 487). Most respondents were men and younger than 50 years. There was an even split between those at academic and community hospitals. Overall, 46% of respondents were aware of S+HIPEC for CRC-C, and multivariate analysis showed that there were no physician characteristics predictive of awareness of S+HIPEC for CRC-C.

Conclusion

Physician awareness of S+HIPEC for CRC-C is low. Therefore, strategies to improve patient and physician knowledge about S+HIPEC for CRC-C are important to ensure appropriate treatment for patients.     

Temporary Right Ventricular Mechanical Support in High‐Risk Left Ventricular Assist Device Recipients Versus Permanent Biventricular or Total Artificial Heart Support

Early planned institution of temporary right ventricular assist device (RVAD) support with the CentriMag (Levitronix LLC, Waltham, MA, USA) in left ventricular assist device (LVAD) recipients was compared with permanent biventricular assist device (BVAD) or total artificial heart (TAH) support. Between 2007 and 2011, 77 patients (age range: 25–70 years) with preoperative evidence of biventricular dysfunction (University of Pennsylvania score >50; University of Michigan score >5) were included. Forty‐six patients (38 men; median age 54.5 years, range: 25–70 years) underwent LVAD placement combined with temporary RVAD support (group A); in 31 patients (25 men; median age 56.7 years, range: 28–68 years), a permanent BVAD or TAH implantation (group B) was performed. Within 30 days, 12 patients from group A (26.08%) and 14 patients from group B (45.1%) died on mechanical support (P = 0.02). Thirty patients (65.2%) in group A were weaned from temporary RVAD support and three (6.5%) underwent permanent RVAD (HeartWare, Inc., Framingham, MA, USA) placement. A total of 26 patients (56.5%) were discharged home in group A versus 17 (54.8%) in group B (P = 0.56). Three patients (8.5%) received heart transplantation in group A and six (19.3%) in group B (P = 0.04). In group A, 90‐day and 6‐month survival was 54.3% (n = 25) versus 51.6% (n = 16) in group B (P = 0.66). In group A, 1‐year survival was 45.6% (n = 21) versus 45.1% (n = 14) in group B (P = 0.81). The strategy of planned temporary RVAD support in LVAD recipients showed encouraging results if compared with those of a similar permanent BVAD/TAH population. Weaning from and removal of the temporary RVAD support may allow patients to be on LVAD support only despite preoperative biventricular dysfunction.     

Long-Term Bone Density Evaluation in Cerebrotendinous Xanthomatosis: Evidence of Improvement after Chenodeoxycholic Acid Treatment

Cerebrotendinous xanthomatosis (CTX) is known to be associated with osteoporosis and a higher incidence of bone fractures. However, the underlying pathogenesis is still unknown, and the effects of long-term replacement therapy with chenodeoxycholic acid (CDCA) on bone mineral density (BMD) have not been fully investigated. We studied 11 CTX patients aged 13–43 years. We performed dual-energy X-ray absorptiometry and assessed serum cholestanol and 25-hydroxyvitamin D (25-OHD) concentrations both at the time of diagnosis and after long-term treatment with CDCA. At baseline, we found low BMD in nine patients, cholestanol elevation in all subjects, and 25-OHD decrease in nine. After a mean follow-up time of 30 months (range 24–36), no substantial clinical changes including bone fractures occurred; and we detected a significant increase of both planar and volumetric BMD as well as normalization of plasma cholestanol levels and increase of serum 25-OHD. Densitometric improvement following CDCA introduction was not correlated to changes of biochemical parameters. Our study confirms the presence of low bone mass in CTX and demonstrates that long-term CDCA treatment increases bone mineral content. In this respect, improvement of vitamin D intestinal absorption secondary to bile acid restoration could play an important role. Moreover, our data strongly suggest the utility of periodic bone density evaluation in CTX patients.     

Analysis of the interfacial micromorphology and bond strength of adhesive systems to Er:YAG laser-irradiated dentin

This study evaluated the effects of different parameters of dentin irradiation with erbium-doped yttrium aluminum garnet (Er:YAG) laser on bond strength to dentin and analyzed the ultramorphological characteristics of resin–laser-irradiated dentin interfaces using a transmission electron microscope (TEM). Dentin surfaces were abraded with SiC paper (600 grit) or Er:YAG laser-irradiated (120/4, 140/6, 180/4, or 200/6 mJ/Hz). Three adhesive systems were tested: Single Bond Plus (3M ESPE), Clearfil Protect Bond (Kuraray Med.), and Clearfil Tri-S Bond (Kuraray Med.). Treatments were performed over flat dentin surfaces of human third molars. Specimens were stored in distilled water for 1 week or 6 months and prepared for a microtensile bond strength test and interfacial ultrastructure for analysis. Microtensile bond strength data (n?=?5) were analyzed with three-way analysis of variance. Irradiation with Er:YAG laser did not reduce the bond strength values for self-etching adhesives even after 6 months of water storage. The hybrid layer formation was observed only when the adhesives were applied to non-irradiated dentin (control group). Nanoleakage occurred in all resin–dentin interfaces using Single Bond Plus for both periods. Nanoleakage pattern and bond strength of self-etching adhesives to dentin were less affected by Er:YAG laser irradiation and by the 6-month storage in water than was those of the etch-and-rinse adhesive. TEM analysis revealed no hybridization when dentin was laser-irradiated. Clinical significance: Minimally invasive caries removal has been proposed. Nevertheless, bonding mechanisms to lased dentin are not entirely described. Knowing the interaction between the treated dentin and bonding agents and its behavior over time is of utmost importance for new technologies. Regarding that, two-bottle self-etching adhesive system provided a more consistent evidence of its better behavior when bonding to lased substrate.