Evaluation of Anticancer Potential of Flavones from Rhamnus alaternus against B16F10 Melanoma Cells.

Melanoma has become an important health problem and new treatment have become an imperative medical need. Therefore, the finding and identification of natural product with less toxic effects, capable of promoting melanoma cell death have become an important goal of research in oncotherapy. In this study, we want to investigate the anticancer activity of an enriched total oligomers flavonoids (TOF) extract of R. alaternus in melanoma cells. First, TOF was exhibited to be rich in flavones. We revealed that this extract reduced proliferation and increased of sub-G1 and S phase cells built-up in B16-F10 cells in a dose-related manner. Moreover, In Vivo, TOF reduced tumor volume and weight with percentages of inhibition of 92.4% and 92.9%, respectively. R. alaternus was also found to be effective in reducing the level of pro-inflammatory cytokine IL-6 during metastasis. Level of TH1 cytokine, such as IL-2, was significantly enhanced by TOF treatment. Indeed, the histological examination of the tumor revealed the absence of mitoses and the presence of numerous melanin pigmented macrophage cells in the R. alaternus extract-treated group that could be explained by the induction of macrophage activation and by the arrest of the cell cycle in the Sub-G1 and S phases.

Effect of Six-Minute Walk Test and Incremental Exercise on Inspiratory Capacity, Ventilatory Constraints, Breathlessness and Exercise Performance in Sedentary Male Smokers without Airway Obstruction.

We investigated physiological responses and exercise capacity in sedentary young smokers during sub-maximal and maximal test and its impact on dyspnea and exercise intolerance. Fifty sedentary male smokers and non-smokers (age: 24 ± 1 years., weight: 71 ± 9 kg, height: 177.3 ± 4.8 cm, body mass index: 22.6 ± 2.5 kg/m2) underwent two visits with pulmonary function tests, breathing pattern, and inspiratory capacity measurement at rest and during sub-maximal and maximal exercise. Smokers show reduced exercise capacity during six minutes walk test (6-MWT) with decreased walked distance (p < 0.001) and inspiratory capacity (p < 0.05). During cardiopulmonary exercise test (CPET), smokers had higher minute ventilation VE for a given submaximal intensity (p < 0.05) and lower minute ventilation at maximal exercise (p < 0.001). End expiratory lung volume was significantly lower in sedentary smokers at rest (p < 0.05), at ventilatory threshold during exercise (p < 0.05), but not during peak exercise. End inspiratory lung volume was significantly lower in smokers at rest (p < 0.05) and ventilatory threshold (p < 0.05). Cigarette smoking alters lung function during submaximal and maximal exercise. This alteration is manifested by the development of dynamic hyperinflation contributing to exercise capacity limitation.

From deficiency to handicap in the respiratory field: lung function tests (LFT) norms and quality of life (QOL) questionnaires validated for the Tunisian population.

OBJECTIVE: The objective of this literature review is to gather all the LFT norms available for the Tunisian population, as well as QDV questionnaires specific to chronic respiratory patients that have been validated in Tunisia. METHODS: This review included a literature search using the PubMed and Sciencedirect databases. The reference lists of the retrieved English/French articles were searched for any additional reference. Specific research has been carried out for each stage of the natural evolution of chronic diseases. For LFT used in the exploration of deficiency, the key-words were ("respiratory function test" OR "spirometry" OR "plethysmography" OR "exhaled fraction of oxide nitric" OR "lung diffusion" OR "peak nasal inspiratory flow" OR "Lung age") AND ("Tunisia" OR "North Africa") AND ("reference equation" OR "reference value" OR "standard reference"). For LFT used in the exploration of incapacity, the key-words were ("exercise test" OR "maximal oxygen uptake" OR "cardiorespiratory test" OR "six minute walk distance" OR "six-minute walk distance" OR "6-minute walk distance" OR "six-min walk distance" OR "6-min walk distance" OR "six minute walking distance" OR "six-minute walking distance" OR "6MWD") AND ("Tunisia" OR "North Africa") AND ("reference equation" OR "reference value" OR "standard reference"). For the QOL questionnaires used in pneumology, the key-words were: ("quality of life" OR "QOL") AND ("respiratory" OR "pulmonology") AND ("Tunisia" OR "North Africa"). RESULTS: As part of deficiency exploration, 11 Tunisian norms are available. As part of incapacity exploration, three Tunisian norms are available for the 6-minute walk test. Only one QOL questionnaire specific to chronic respiratory patients has been validated in Tunisia. CONCLUSION: Despite its richness, the Tunisian "bank" of norms for LFT and QOL questionnaires has yet to be enriched.

The Ventilatory and Diffusion Dysfunctions in Obese Patients with and without Obstructive Sleep Apnea-Hypopnea Syndrome.

Objective: To analyze the ventilatory and alveolar-capillary diffusion dysfunctions in case of obesity with or without an OSAS. Methods: It is a cross-sectional study of 48 obese adults (23 OSAS and 25 controls). Anthropometric data (height, weight, and body mass index (BMI)) were collected. All adults responded to a medical questionnaire and underwent polysomnography or sleep polygraphy for apnea-hypopnea index (AHI) and percentage of desaturation measurements. The following lung function data were collected: pulmonary flows and volumes, lung transfer factor for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FeNO). Results: Obesity was confirmed for the two groups with a total sample mean value of BMI = 35.06 ± 4.68 kg/m2. A significant decrease in lung function was noted in patients with OSAS compared with controls. Indeed, when compared with the control group, the OSAS one had a severe restrictive ventilatory defect (total lung capacity: 93 ± 14 vs. 79 ± 12%), an abnormal DLCO (112 ± 20 vs. 93 ± 22%), and higher bronchial inflammation (18.40 ± 9.20 vs. 31.30 ± 13.60 ppb) (p < 0.05). Conclusion: Obesity when associated with OSAS increases the severity of pulmonary function and alveolar-capillary diffusion alteration. This can be explained in part by the alveolar inflammation.

Defining and grading an obstructive ventilatory defect (OVD): 'FEV1/FVC lower limit of normal (LLN) vs. Z-score' and 'FEV1 percentage predicted (%pred) vs. Z-score'.

An obstructive ventilatory defect (OVD) is defined by a low forced expiratory volume/'forced/slow' vital capacity (FEV1/FVC) (e.g. 70%), moderate (60-69%), moderately severe (50-59%), severe (35-49%), and very severe (<35%) and GLI (FEV1 Z-score): mild (≥ -2.0), moderate (-2.0 to -2.5), moderately severe (-2.5 to -3.0), severe (-3.0 to -4.0), and very severe (<-4.0). The frequencies of OVD were 14.4% (ATS/ERS method) and 10.5% (GLI method) (p < 0.05). Among the 103 participants having an OVD according to the two methods, the severity classification was mild (34.95% vs. 37.86%, p < 0.05), moderate (25.24% vs. 18.45%, p < 0.05), moderately severe (23.30% vs. 15.53%, p = 0.144), severe (9.71% vs. 20.39%, p < 0.05), and very severe (6.80% vs. 7.77%, p = 0.785), respectively for the ATS/ERS and GLI classifications. The two OVD definitions were not exchangeable. Moreover, the two grading severity systems misclassified the OVD grades.

A reappraisal of small- and large-fiber damage in carpal tunnel syndrome: New insights into the value of the EMLA test for improving diagnostic sensitivity.

OBJECTIVES: To reappraise the respective involvement of small- and large-fiber damage in carpal tunnel syndrome (CTS) and to determine the diagnostic sensitivity of autonomic tests compared to conventional nerve conduction study (NCS). METHODS: Thirty-two manual workers complaining of at least unilateral CTS were enrolled. They underwent clinical interview and completed the symptom severity scale of the Boston CTS Questionnaire (sssBCTQ) and the Neuropathic Pain Symptom Inventory (NPSI). In addition, transcarpal NCS was performed to investigate large sensory and motor fibers of the median nerve, while small autonomic fibers were assessed by recording sympathetic skin reflexes (SSR) at the palm and by grading skin wrinkling in response to eutectic mixture of local anesthetic (EMLA) cream application at the pulp of the index finger. For each neurophysiological variable, sensitivity and specificity values for the diagnosis of CTS were calculated and clinical correlations were studied. RESULTS: Among 64 hands examined, 36 were clinically symptomatic, while 22 were clinically asymptomatic and served as controls. Among all the neurophysiological variables studied, only the values of transcarpal sensory nerve conduction velocity and the EMLA test grade were found to be more altered in clinically symptomatic hands, with also a trend towards prolonged distal motor latency. Overall, for the diagnosis of clinically symptomatic CTS, NCS, SSR, and the EMLA test had a sensitivity of 66.7%, 22.2%, and 69.4%, respectively, and a specificity of 72.7%, 90.9%, and 50%, respectively. Combining NCS and the EMLA test led to a sensitivity of 88.9% and a specificity of 45.4%. The sssBCTQ (r=-0.34, P=0.009) and the total NPSI score (r=-0.41, P=0.001) correlated to a more altered EMLA test grade, but not to any NCS or SSR variables. In symptomatic hands, burning sensation was associated with more severe small-fiber lesion, while other pain and sensory symptoms were rather found to be reduced in case of large-fiber damage, evidenced by NCS alteration. CONCLUSIONS: This study confirms the discrepancy between conventional NCS results and clinical presentation of CTS, but still suggests a major involvement of Aß fibers in the positive sensory symptoms of CTS, excepting burning sensation. On the other hand, the EMLA test was found to correlate with clinical data and to be able to improve sensitivity of neurophysiological investigation in diagnosing CTS.