Resveratrol inhibits transforming growth factor-β-induced proliferation and differentiation of ex vivo human lung fibroblasts into myofibroblasts through ERK/Akt inhibition and PTEN restoration

The authors investigated the role of resveratrol (RV), a natural poliphenolic molecule with several biological activities, in transforming growth factor-β (TGF-β)-induced proliferation and differentiation of ex vivo human pulmonary fibroblasts into myofibroblasts. The effects of RV treatment were evaluated by analyzing TGF-β-induced α-smooth muscle actin (α-SMA) expression and collagen production, as well as cell proliferation of both normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts. Results demonstrate that RV inhibits TGF-β-induced cell proliferation of both normal and pathological lung fibroblasts, attenuates α-SMA expression at both the mRNA and protein levels, and also inhibits intracellular collagen deposition. In order to understand the molecular mechanisms, the authors also investigated the effects of RV treatment on signaling pathways involved in TGF-β-induced fibrosis. The authors show that RV inhibited TGF-β-induced phosphorylation of both extracellular signal-regulated kinases (ERK1/2) and the serine/threonine kinase, Akt. Moreover, RV treatment blocked the TGF-β-induced decrease in phosphatase and tensin homolog (PTEN) expression levels.     

Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance

It is generally recognized that lipid peroxides play an important role in the pathogenesis of several diseases and that sulfhydryl groups are critically involved in cellular defense against endogenous or exogenous oxidants. Recent evidence indicates that lipid peroxides directly participate in induction of cytoprotective proteins, such as heat shock proteins (Hsps), which play a central role in the cellular mechanisms of stress tolerance. Heme oxygenase (HO) is a stress protein that has been implicated in defense mechanisms against agents that may induce oxidative injury, such as endotoxins, cytokines and heme and its induction represents a common feature in a number of neurodegenerative diseases. In the present report we studied regional distribution of heme oxygenase (HO) activity and protein expression, together with that of Hps70, in brain of C57BL6 mice. Endogenous lipid peroxidation was investigated on the basis of the analysis of ultra weak chemiluminescence, hydro peroxides and lipid soluble fluorescent products, and compared to the regional distribution of thiols, antioxidant enzymes and trace metals. Our results show that levels of HO activity and expression of inducible Hsp70 and the ratio of GSH/GSSG in the different brain regions examined were positively correlated with the content of peroxides. Substantia Nigra was the brain area exhibiting the highest levels of HO-2, constitutive and inducible Hsp70, GSSG, peroxides, iron, and calcium, in contrast with the lowest content in GSH, GSH/GSSG ratio and glutathione reductase activity, compared to the other cerebral regions examined. Among these, cortex showed the lowest levels of HO-2, Hsp70, GSSG and peroxides that were associated with the highest levels of GSH and GSH/GSSG ratio. These data support the hypothesis that the glutathione redox state and basal peroxides can directly participate in the signaling pathways of heat shock protein expression and hence of stress tolerance.     

Robot-assisted Gastrectomy for Gastric Cancer: Current Status and Technical Considerations

Background

Robot-assisted gastrectomy has been reported as a safe alternative to the conventional laparoscopy or open approach for treating early gastric carcinoma. To date, however, there are a limited number of published reports available in the literature.

Methods

We assess the current status of robotic surgery in the treatment of gastric cancer, focusing on the technical details and oncological considerations.

Results

In gastric surgery, the biggest advantage of robotic surgery is the ease and reproducibility of D2-lymphadenectomy. Reports show that even the intracorporeal digestive restoration is facilitated by use of the robotic approach, particularly following total gastrectomy. Additionally, the accuracy of robotic dissection is confirmed by decreased blood loss, as reported in series comparing robot-assisted with laparoscopic gastrectomy. The learning curve and technical reproducibility also appear to be shorter with robotic surgery and, consequently, robotics can help to standardize and diffuse minimally invasive surgery in the treatment of gastric cancer, even in the later stages. This is important because the application of minimally invasive surgery is limited by the complexity of performing a D2-lymphadenectomy. The potential to reproduce D2-lymphadenectomy, enlarged resections, and complex reconstructions provides robotic surgery with an important role in the therapeutic strategy of advanced gastric cancer.

Conclusions

While published reports have shown no significant differences in surgical morbidity, mortality, or oncological adequacy between robot-assisted and conventional laparoscopic gastrectomy, more studies are needed to assess the indications and oncological effectiveness of robotic use in the treatment of gastric carcinoma. Herein, the authors assess the current status of robotic surgery in the treatment of gastric cancer, focusing on the technical details and oncological considerations.     

A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases

OBJECTIVE: To assess outcome after a 2-stage hepatectomy procedure (TSHP) combined with portal vein embolization (PVE) in the treatment of patients with unresectable multiple and bilobar colorectal liver metastases (MBCLM). BACKGROUND: Patients with MBCLM are often considered for palliative chemotherapy only, due to too small future remnant liver (FRL). Recently, right hepatectomy with simultaneous left liver wedge resections after previous right PVE has been reported in a curative intent. However, the growth of metastatic nodules in FRL after PVE can be more rapid than that of the nontumoral remnant hepatic parenchyma. Therefore, metastases located in the FRL should be ideally resected before PVE. Then, a right (or extended right) hepatectomy can be safely performed during a second-stage hepatectomy. Therefore, we analyzed our experience with the use of TSHP combined with PVE in treatment of MBCLM. PATIENTS AND METHODS: Between December 1996 and April 2003, 33 patients with unresectable MBCLM were selected for a TSHP. A right or an extended right hepatectomy was planned after treatment of left FRL metastases to achieve a curative resection. The first-stage hepatectomy consisted in a clearance of the left hemiliver by resection or radiofrequency destruction of metastases of the left FRL. Subsequently, a right PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the left hemiliver. Finally, a second-stage hepatectomy was planned to resect the right liver metastases. RESULTS: There was no operative mortality. Post-PVE morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33 patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%, respectively, in the 25 patients in whom the TSHP was completed. CONCLUSIONS: In selected patients with initially unresectable MBCLM, a TSHP combined with PVE can be achieved safely with long-term survival similar to that observed in patients with initially resectable liver metastases.     

Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy

Acrodermatitis continua of Hallopeau (ACH) consists of a relapsing pustular eruption of the distal portions of hands and feet. We described a case of a 9-year-old boy affected by ACH, successfully treated with targeted ultraviolet B 311 nm phototherapy, which seems to be an effective and safe therapy for this condition.     

Evaluation of plasma oxidative stress,with or without antioxidant supplementation,in superficial partial thickness burn patients: a pilot study

Background: Oxidative stress is one of the main causes of pathophysiological alterations observed during burn injury. The present pilot study aimed to determine whether a specific oral antioxidant supplementation could in any way influence free radical blood values in patients affected by superficial partial thickness burns.

Materials and methods: Plasma oxidants and plasma antioxidant capacity were analysed in 20 superficial partial thickness burn patients for a 2-week period; patients were randomly divided into two groups, one of which was supported with a specifically designed oral antioxidant formula (Squalene 100?mg, Vitamin C 30?mg, Coenzyme Q10 10?mg, Zinc 5?mg, Beta Carotene 3.6?mg, Bioflavonoids 30?mg, Selenium 55?mcg) administered daily, starting from the day of admission, for the whole study period.

Results: No significant differences were found in plasma oxidants and plasma antioxidant capacity between the two groups of patients.

Conclusions: These results did not reflect any significant benefits of an antioxidant oral supplementation at usual dosages when considering oxidative plasmatic values of superficial partial thickness burn patients.