Blood-Brain Barrier Permeability of Asiaticoside,Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (P_app) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10^?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.     

Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Assessment of Ventricular Septal Volume and Mass before and after Myectomy in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy. In patients resistant to medical management, myectomy is the surgical procedure of choice to reduce the symptoms of left ventricular outflow obstruction. Two‐dimensional transesophageal echocardiography (2DTEE) has become part of the operative procedure by decreasing the incidence of postoperative complications. However, because of the three‐dimensional geometry of left ventricular outflow tract, it is unable to comprehensively assess the location and severity of the obstruction and to provide accurate guidance during myectomy. In this study, 10 patients with HCM underwent live/real time three‐dimensional transesophageal echocardiography (3DTEE) intra‐operatively to measure the volume of the resected septum. This volume correlated well with the volume of the resected septal muscle directly obtained using a graduating cylinder containing water (r = 0.9, P < 0.000). 3DTEE may be potentially used as an adjunct to guide the surgeon in performing an adequate myectomy with a lower incidence of residual obstruction and complications such as an iatrogenic ventricular septal defect.     

Silicone pneumonitis,diffuse alveolar hemorrhage and acute respiratory distress syndrome from gluteal silicone injections

Fatal complications from illegal cosmetic injection of nonmedical-grade liquid silicone (polydimethylsiloxane) by unlicensed providers are becoming more common. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis and diffuse alveolar hemorrhage. Prompt and aggressive management with high-dose steroids and lung-protective ventilation strategies to minimize acute respiratory distress syndrome (ARDS) can be lifesaving. We present the case of a patient presenting with abdominal pain and shortness of breath who quickly developed respiratory failure. The patient recently had received bilateral gluteal silicone injections from an unlicensed provider.     

Developments in the field of allergy in 2011 through the eyes of Clinical and Experimental Allergy

As in previous years, we felt it would be of value to our readership to summarize the new information provided by the authors who have published in Clinical and Experimental Allergy in 2011 and set this in the context of recent advances in our understanding of the pathogenesis and management of allergic disease in all its many manifestations. In 2011, about 210 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, guidelines, letters, book reviews and of course at the heart of the journal, papers containing original data. As before, this review is divided into sections based on the way the journal is structured, although this year we have grouped together all the papers dealing with mechanisms of allergic disease, whether they involve patients (clinical mechanisms), pure in vitro studies (basic mechanisms) or animal models (experimental models), as we felt this was a more coherent way to deal with the subject. In the field of asthma and rhinitis, the relationship between airway inflammation and airway dysfunction was of perennial interest to investigators, as were phenotypes and biomarkers. Aspirin hypersensitivity appeared in studies in several papers and there was new interest in asthma in the elderly. The mechanisms involved in allergic disease describe advances in our understanding of T cell responses, the relationship between inflammation and disease, mast cell and basophil activation, steroid resistance and novel therapies. In the section dealing with epidemiology, studies seeking to identify risk factors for allergic disease including vitamin D are prominent, as once again are studies investigating gene–environment interactions. The clinical allergy section focuses on drug allergy, food allergy and immunotherapy. The area of oral immunotherapy for food allergy is well covered and we were grateful to Stephen Durham for guest editing an outstanding special issue on immunotherapy in the centenary year of Leonard Noon's pioneering work. Lastly, in the field of allergens, the interest in component‐resolved diagnosis continues to grow and there are also articles describing important novel cultivars and the effect of food processing on the allergenic properties of foods. Another terrific year, full of important and high‐quality work,which the journal has been proud to bring to the allergy community.     

Clinicopathological significance of PTEN and bcl2 expressions in oral squamous cell carcinoma

A high frequency of mutations at the PTEN locus has been noticed in carcinoma of oral. However, the role of PTEN alternations and its association with outcome variables in the genesis of oral carcinoma is not understood fully. The purpose of our study was to examine the impact of PTEN and Bcl2 in the genesis of Squamous cell carcinoma of oral. Total numbers of 60 histopathologically confirmed cases of Squamous Cell Carcinoma and 15 cases of inflammatory lesion of oral specimens were studied. We assessed PTEN and bcl2 overexpression by the use of anti-PTEN and anti-bcl2 antibody through immunohistochemistry as directed by the manufacturer. There was progressive loss of PTEN expression from inflammatory lesion to OSCC (p<0.05). Significant differences were found for PTEN expression between inflammatory lesion and OSCC. The difference in expression pattern of PTEN in gender did not reach statistical significance (p>0.05). The expression of bcl2 was found to be restricted to tumor cells in well and moderately differentiated tumors. The intense expression of bcl2 was observed throughout the tumor cell in poorly differentiated tumors.The Overexpression of bcl2 and loss of PTEN expression were correlated to poor differentiation, lymph node involvement and late stages. Thus, alteration of PTEN and bcl2 is likely an important molecular event in pathogenesis and carcinogenesis of oral carcinoma.     

Acute pancreatitis induced thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown cause with an estimated incidence of one case per million. The disease is characterized by a pentad of symptoms: Thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, renal dysfunction, and fever. It causes thrombosis in the microvasculature of several organs, producing diverse manifestations. Acute pancreatitis (AP) is a well-described consequence of TTP. Acute pancreatitis triggering TTP is uncommon.