<Emphasis Type="Italic">N</Emphasis>-(2-Hydroxyphenyl)acetamide: a Novel Suppressor of RANK/RANKL Pathway in Collagen-Induced Arthritis Model in Rats

RANKL and RANK are potential contributors of inflammatory cascade in human and animal model of arthritis. The current study aims to investigate the effect of N-(2-hydroxyphenyl)acetamide (NA-2) on regulation of RANKL pathway in collagen-induced arthritis (CIA) model in rats. CIA was induced using bovine type II collagen in female Wistar rats. The clinical parameters, level of pro-inflammatory and oxidative stress markers were measured to determine the progression of the disease. The mRNA level of RANKL and RANK and downstream mediators of inflammation i.e. c-fos, c-jun, NF-κB and Akt were analysed in spleen tissue using real-time PCR. Immunohistochemical analysis of iNOS, pAkt and c-Fos was also done in spleen tissue. Treatment with NA-2 and indomethacin showed increase in body weight and significant reduction in paw volume and arthritic score (p < 0.0001). Marked reduction in the level of oxidative stress markers, NO, PO and GSH (p < 0.0001), and pro-inflammatory markers, IL-1β (p < 0.0001) and TNF-α (p < 0.01), was also observed. Likewise, NA-2 and indomethacin treatment also significantly suppressed the mRNA expression of RANKL, RANK, c-fos, c-jun, NF-κB (p < 0.0001) and Akt (p < 0.01) and protein expression of iNOS, pAkt and c-Fos (p < 0.0001) compared to the arthritic control group. Our findings suggest that NA-2 is an antiarthritic agent acting in a pleiotropic manner in CIA rats by not only reducing the clinical signs of arthritis, inflammatory cytokines and free radical production but also attenuating the RANK/RANKL signaling pathway.     

Mechanical stimuli enhance simultaneous differentiation into oesophageal cell lineages in a double‐layered tubular scaffold

The tissue‐engineered oesophagus serves as an alternative and promising therapeutic approach for long‐gap oesophageal replacement. This study proposes an advanced in vitro culture platform focused on construction of the oesophagus by combining an electrospun double‐layered tubular scaffold, stem cells, biochemical reagents, and biomechanical factors. Human mesenchymal stem cells were seeded onto the inner and outer surfaces of the scaffold. Mechanical stimuli were applied with a hollow organ bioreactor along with different biochemical reagents inside and outside of the scaffold. Electrospun fibres in a tubular scaffold were found to be randomly and circumferentially oriented for the inner and outer surfaces, respectively. Amongst the two types of mechanical stimuli, the intermittent shear flow that can simultaneously cause circumferential stretching due to hydrostatic pressure, and shear stress caused by flow on the inner surface, was found to be more effective for simultaneous differentiation into epithelial and muscle lineage than steady shear flow. Under these conditions, the expression of epithelial markers on the inner surface was significantly observed, although it was minimal on the outer surface. Muscle differentiation showed the opposite expression pattern. Meanwhile, the mechanical tests showed that the strength of the scaffold was improved after incubation for 14 days. We have developed a potential platform for tissue‐engineered oesophagus construction. Specifically, simultaneous differentiation into epithelial and muscle lineages can be achieved by utilizing the double‐layered scaffold and appropriate mechanical stimulation.     

Selecting a Surgical Modality to Treat a Splenic Hydatid Cyst: Total Splenectomy or Spleen-Saving Surgery?

Aim

We analyzed the outcomes and effectiveness of surgical treatments and clinical manifestations of splenic hydatid cysts.

Patients and Methods

Between 2000 and 2011, we retrospectively reviewed the cases of 11 patients who were operated on for a splenic hydatid cyst. The demographic features, medical history, physical examinations, biochemical and serological tests, imaging modalities, and surgical treatment of the patients were noted.

Results

The mean patient age was 36.45?years (range, 20?C66?years). While isolated splenic hydatid disease was present in five patients, other abdominal hydatid cysts were accompanied by a splenic hydatid cyst in six patients. Left upper abdominal pain was present in seven (64%) patients, whereas four (36%) patients were asymptomatic. Eight patients (72.72%) had undergone a total splenectomy and three (27.28%) had undergone spleen-preserving surgery. Postoperative complications developed in four (36%) patients at 5?C15?days postoperatively.

Conclusion

Management of a splenic hydatid cyst is not consensual. Total splenectomy is optimal because it provides definitive treatment. However, spleen-preserving surgery is the preferred treatment in selected patients. The choice of technique depends on the localization, number, and size of hydatid cysts, and the absence or presence of other hydatic organ cysts.     

Red blood cell rheological properties in various rat hypertension models

Red blood cell (RBC) properties were proposed to play role in the development of hypertension (HT). This study aimed at investigating the alterations of RBC deformability and aggregation, in various models of HT in rats. The following four models of HT were developed in rats: one kidney-one clip HT (1K-1C HT), two kidney-one clip HT (2K-1C HT), deoxycorticosterone acetate (DOCA) induced HT (15 mg/kg, 2 times/week, sc) and N-nitro L-arginine methyl ester (L-NAME) induced HT (50 mg/kg/day, 10 weeks, ip). The blood samples were obtained from abdominal aorta, under ether anesthesia, after a period of 10 weeks of increased blood pressure. RBC deformability was determined by ektacytometry. RBC aggregation was measured in autologous plasma and 0.5% dextran 500, using a photometric rheoscope. Plasma fibrinogen concentration was determined by Clauss method. The mean blood pressure in all four HT models were about 140 mmHg, on the day of sampling, compared to approximately 110 mmHg in the control group. RBC deformability was found to be significantly decreased in the L-NAME model of HT. RBC aggregation in autologous plasma was significantly higher than control in 2K-1C, L-NAME and DOCA models, DOCA HT model being the most effective in altering the RBC aggregation. Plasma fibrinogen values were found to be higher than control in 2K-1C and L-NAME HT models, but not in DOCA HT. These results confirm that RBC rheological properties might be altered in HT. It can also be suggested that these alternations may not simply be the result of the vascular effects of HT, but may play role in the development of HT, as the alterations in different HT models were not the same, although the length and magnitude of increased blood pressure were similar.