Dexmedetomidine regulates inflammatory molecules contributing to ventilator-induced lung injury in dogs

Background

Dexmedetomidine reduced mortality and inhibited the inflammatory response during endotoxemia in rats. The aim of this study was to clarify the effect of dexmedetomidine-regulating inflammation on a noninfectious, ventilator-induced lung injury (VILI) in dogs.

Methods

Thirty healthy Beagles weighing between 8 and 12 kg were randomly divided into five groups: control group (group C, n = 6), mechanical ventilation (group MV, n = 6), and three different doses of dexmedetomidine group (group DEX1–3, n = 6). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 15 breaths/min; FiO₂ 0.5). Group DEX received intravenous Dex 20 min before endotracheal intubation (0.5, 1.0, and 2.0 μg/kg Dex was infused within 20 min and then a maintenance dose of 0.5, 1.0, and 2.0 μg/kg/h Dex was infused intravenously). Arterial blood samples were obtained from femoral artery at base state, MV1h, MV2h, and MV4h for blood gas analysis. After being mechanically ventilated for 4 h, dogs were killed and the levels of pulmonary inflammatory response and polymorphonuclear neutrophils (PMNs) count in bronchoalveolar lavage fluid were evaluated.

Results

Histologic findings of the MV, DEX1, DEX2, and DEX3 groups revealed severe, moderate, mild, and normal to minimal inflammation, respectively. Myeloperoxidase level, PMNs/alveoli ratio, nuclear factor-κB messenger RNA (mRNA), tumor necrosis factor-alpha mRNA, and inducible nitric oxide synthase mRNA expression in lung tissues of the DEX2 and DEX3 were significantly lower than those of the MV group. Partial pressures of oxygen was decreased significantly at MV4h as compared with the baseline. There was no statistical significance in partial pressures of oxygen between MV and DEX2 group as well as between group MV and group DEX3.

Conclusions

Dexmedetomidine could mitigate pulmonary inflammatory response induced by VILI in dogs.     

Reduction of alkaline reflux gastritis and marginal ulcer by modified Braun enteroenterostomy in gastroenterologic reconstruction after pancreaticoduodenectomy

Background

The incidence of alkaline reflux gastritis (ARG) after pancreaticoduodenectomy (PD) is high. Although Braun enteroenterostomy (BEE) may reduce ARG, BEE may result in marginal ulcers (MUs) due to the additional anastomotic stoma. We conducted this study to compare clinical outcomes of using a modified BEE (MBEE) with traditional gastrojejunostomy (TGJ), by inducting a purse-string suture instead of an additional anastomotic stoma.

Materials and methods

All 62 patients underwent standard PD at the Department of Hepatobiliopancreatic Surgery of West China Hospital between January 1, 2008 and January 31, 2012. Demographics, perioperative and postoperative factors, and follow-up morbidity were compared in those patients who underwent MBEE (n = 32, three patients were lost to follow-up) to those who underwent TGJ (n = 30, nine patients were lost to follow-up).

Results

Patients who underwent the MBEE experienced a decrease in total morbidity including ARG and MUs, relative to those who underwent TGJ (24.1% versus 58.3%, P = 0.011). With regard to the MBEE group, the total ARG rate was statistically significantly lower compared with the TGJ group (13.8% versus 37.5%, P = 0.046). In addition, the incidence of MUs was reduced.

Conclusions

In patients undergoing PD, the MBEE was safely performed with significantly more patients having reduced incidence of ARG and related sequela compared with those who underwent TGJ. These results support further study of patients undergoing gastroenterostomy after resection of the distal stomach in larger, randomized studies.     

shRNA-mediated GSTP1 gene silencing enhances androgen-independent cell line DU145 chemosensitivity

Purpose

Design short hairpin RNA (shRNA) interference sequence to silence glutathione S-transferase P1 (GSTP1) gene of androgen-independent prostate cancer cell line DU145, and then to explore its effect on sensitivity to chemotherapeutics.

Methods

Target sequence was picked up to form the shRNA. DU145 cell was divided into five groups according to the shRNA added for transfection: shRNA255, shRNA554, shRNA593, negative-shRNA and blank group. Fluorescence microscope was used to pick up the shRNA with the highest transfection ratio. Western blotting and RT-PCR were taken to pick up the shRNA with the best gene silencing result. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and terminal de-oxynucleotidyl transferase-mediated dUTP nick end-labeling assay were used to detect survival ratio and apoptosis ratio of DU145 administered of fluorouracil (5-FU) or paclitaxel (PA) at different concentrations before and after shRNA transfection.

Results

Three different shRNA oligonucleotides (shRNA255; shRNA554; shRNA593) targeting the coding sequence of GSTP1 mRNA and one negative control shRNA were constructed. The transfection ratio of shRNA554 (76.2 ± 0.68 %) was higher than that of shRNA255 (63.3 ± 1.04 %) (P < 0.01) or shRNA593 (72.7 ± 0.33 %) (P < 0.01). After transfection of shRNA554, the mRNA and protein of level were the lowest, P < 0.01. The survival ratio of DU145 administered with 5-FU of different concentrations (30, 60, 120, 240 μg/ml) declined after transfection (P < 0.01). Besides, the apoptosis ratio increased after transfection (P < 0.01). Similarly the survival ratio of DU145 administered with PA of different concentrations (0.2, 2, 10, 20 μg/ml) declined (P < 0.01) and the apoptosis ratio increased (P < 0.01) after transfection.

Conclusions

The gene GSTP1 silence via shRNA transfection to androgen-independent prostate cancer cell line DU145 enhances the sensitivity to chemotherapeutics.     

癫痫与心脏自主神经功能障碍

目的：分析癫痫患者发作期和发作间期自主神经功能障碍与癫痫患者突然意外死亡的关系。 资料来源：应用计算机检索Medline数据库1985-01／2004-12期间的相关文章限定文章语言种类为英文，检索词”epilepsy and autonomic”和“seizure and autonomic”。 资料选择：对资料进行初审，纳入标准：①癫痫和癫痫发作与自主神经功能状态关系。②癫痫突然意外死亡。 资料提炼：共收集到符合上述要求的文献45篇，排除27篇重复性内容。18篇符合纳入标准：其中16篇关于癫痫和癫痫发作与自主神经功能障碍，2篇关于自主神经功能障碍与癫痫患者突然意外死亡的关系。 资料综合：癫痫和癫痫发作均可引起心脏自主神经功能障碍，无论部分性发作还是全身性发作癫痫患者发作期和发作间期都存在自主神经功能障碍。而心脏自主神经功能障碍与心律失常尤其是恶性心律失常的发生密切相关。 结论：癫痫患者发作期和发作间期心脏自主神经功能障碍引发的恶性心率失常可能是癫痫患者发生突然意外死亡的重要原因。     

Effect of psychological stress on the structure of the temporomandibular joint and the expression of MMP-3 and TIMP-3 in the cartilage in rats

Our aim was to observe the effects of psychological stress on the structure of the temporomandibular joint (TMJ), and to evaluate the expression of matrix metallopeptidase-3 (MMP-3) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in condylar chondrocytes in rats. The rats were divided into 3 groups of 12 according to the duration of psychological stress: 3 weeks or 6 weeks, and 6 weeks of recovery. A fourth group of 12 rats was used as controls. Each rat was evaluated by the open-field test and the weight measured. The results confirmed psychological stress in 24 of the 36 rats (67%). The tissues of the TMJ were stained with haematoxylin and eosin and pathological changes were studied under a light microscope. MMP-3 and TIMP-3 expression was investigated using the SP kit. The experimental groups showed thinning of articular cartilage, shedding of collagen fibres, cracks in the articular discs, and other structural changes that were aggravated with time, from three weeks to six weeks. The 6-week recovery group showed an improvement in these changes, which indicated the initiation of joint repair. The MMP-3 expression rate correlated with the degree of joint lesion, while the TIMP-3 rate showed an opposite trend and was highest in the 6-week recovery group. Our findings clearly indicate that psychological stress may play an important part in the development of TMJ diseases in rats; further studies should be made to extrapolate the results to other models before clinical use.     

Experimental research on the relationship between fit accuracy and fracture resistance of zirconia abutments

Objectives

The purpose of the study was to investigate the correlation between fit accuracy and fracture resistance of zirconia abutments, as well as its feasibility for clinical applications.

Methods

Twenty self-made zirconia abutments were tested with 30 Osstem GSII implants. First, 10 Osstem GSII implants were cut into two parts along the long axis and assembled with the zirconia abutments. The microgaps between the implants and the zirconia abutments were measured under a scanning electron microscope. Second, the zirconia abutments were assembled with 20 un-cut implants and photographed before and after being fixed with a central screw of 30-N cm torque. The dental films were measured by Digora for Windows 2.6 software. Then the fracture resistance of zirconia abutments was measured using the universal testing machine at 90°. All results were analyzed using SPSS13.0 software.

Results

The average internal-hexagon microgaps between the implants and zirconia abutments were 19.38 ± 1.34 μm. The average Morse taper microgap in the implant–abutment interface was 17.55 ± 1.68 μm. The dental film showed that the Morse taper gap in the implant–abutment interface disappeared after being fixed with a central screw of 30-N cm torque, and the average moving distance of the zirconia abutments to the implants was 0.19 ± 0.02 mm. The average fracture resistance of zirconia abutments was 282.93 ± 17.28 N. The internal-hexagon microgap between the implants and zirconia abutments was negatively related to the fracture resistance of the abutments (r₁ = −0.97, p < 0.01). The Morse taper microgap in the implant–abutment interface was negatively related to the fracture resistance of the abutments (r₂ = −0.84, p < 0.01).

Conclusions

The microgap between implant and abutment was negatively related to the fracture resistance of the abutment, while the internal-hexagon microgap has better correlation than the Morse taper microgap. The closure of microgap is helpful to improve the fracture resistance of zirconia abutments. The fracture resistance of zirconia abutments can satisfy the clinical application.