Carbonic anhydrase enzymes for regulating mast cell hematopoiesis and type-2 inflammation: a patent evaluation (WO2017/058370)

Introduction: Activity modulators of carbonic anhydrases hold great potential for several therapeutic applications against ophthalmologic and neurological disease, cancer, and infectious diseases. The involvement of carbonic anhydrase in the regulation of mast cell response opens new ways for the treatment of mastocytosis, allergic inflammation, and parasite infection.

Areas covered: The application claims the use of carbonic anhydrase activity modulators (inhibitors or activators) for treating allergic disease, bacterial infection, fungal infection, viral infection, mastocytosis, or mast cell–mediated inflammation.

Expert opinion: Although there is a lack of essential biological data, this patent proposes a new type of applications for carbonic anhydrase inhibitors and deserves further studies. This may lead to new advances in the field of carbonic anhydrase with potential therapeutic implications in the management of type-2 inflammation.     

The quantified patient: a patient participatory culture

The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient’s Quantified Self can be directly monitored and remotely accessed by health care professionals.     

Variation management by functional tolerance allocation and manufacturing process selection

The imperfections of the manufacturing process lead to functional characteristics degradation, and therefore product quality. To ensure a certain level of product quality, the synthesis of tolerance (tolerance design) aims to determine the acceptable limits of the characteristics of parts, assemblies... The allocation or synthesis of functional tolerances is an important step in the design process which takes place generally during the detailed design and greatly impacts the design of the manufacturing process, manufacturing and product control. That is why it is important, when functional tolerances are quantified, to take into account their impacts on the manufacturing cost and product quality. These two concepts (manufacturing cost and product quality) are usually considered as conflicting goals. The proposed approach aims to allocate the functional tolerances that provide the best ratio between functional performances and manufacturing cost. It is based on the “Key Characteristics” approach, developed by Boeing coupled with an activities approach. This optimization is carried out by a genetic algorithm. The process selection is performed by a constraint satisfaction algorithm. Finally, the impacts of process choices are assessed with the Monte Carlo simulation which calculates the behavior and quality of the resulting product.     

Expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver tissue

Background/Aims: The objective of the present study was to analyze the expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver slices, which preserve the normal microenvironment of liver cells.Methods: Rat liver slices were maintained in culture for 15 min to 24 h and examnied for ICAM-1 expression by immunohistochemistry and Western blotting in basal conditions and after stimulation with 1000 IU/ml interferon-γ (IFNγ), 1000 IU/ml tumor necrosis factor-α (TNFα) and 50 μg/ml endotoxin. Immunohistochemical results were evaluated using a semiquantitative scoring system.Results: In uncultured slices, ICAM-1 was not detected on hepatocytes. In unstimulated liver slices maintained in organotypic culture, ICAM-1 was induced at the surface of scattered hepatocytes (score at 15 min, 0.33±0.47 and at 24 h, 1.17±0.69). After 4 h of stimulation, a significant increase in ICAM-1 expression by hepatocytes and adjacent sinusoidal cells, but not by intra-hepatic biliary epithelial cells, was observed for IFNγ (score: 2.35±0.47) and endotoxin (score: 2.67±0.47), but not with TNFα (score: 0.66±0.47). After 24 h of stimulation, a further increase in the extent of ICAM-1 expression by hepatocytes was observed for IFNγ (score: 3.67±0.47) and endotoxin (score: 4.0±0.0), and a significant overexpression of ICAM-1 by hepatocytes was detectable after treatement with TNFα (score: 3.67±0.47).Conclusions: In rat liver organotypic cultures, TNFα, IFNγ and endotoxin induce the expression of ICAM-1 in hepatocytes and adjacent sinusoidal endothelial cells, but not in portal tracts.     

Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echocardiography for the detection of patent foramen ovale in stroke patients.

AIMS: The comparison of three imaging methods to determine which is the most accurate and reliable for the detection of right-to-left shunt. METHODS AND RESULTS: One hundred and seven patients who were hospitalized for stroke underwent: a transthoracic echocardiography (TTE) using second harmonic, a transcranial Doppler (TCD) and a transesophageal echocardiography (TEE) from August 2003 to April 2004. All studies were recorded on a videotape and were studied by a physician blinded to the study. With TTE and TEE, we found 44 (41%) patent foramen ovales. All contrast tests were positive with TCD for these 44 patients. For two patients, the contrast test was positive only with TTE and TCD. We found four false negative contrast tests with TTE. Among the 63 patients who had a negative contrast test with TEE and TTE, the results were the same with TCD for 59 of them; we were not able to determine a cause for the four positive tests. CONCLUSION: This study confirms that transesophageal echocardiography has limitations in the diagnosis of patent foramen ovale. In this study, the negative predictive value of transcranial Doppler was excellent. Therefore, this examination is able to exclude a patent foramen ovale with a high level of confidence.     

Effects of vitamin D in the elderly population: current status and perspectives

Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case–control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.