Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group

Background and aim: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. Methods: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. Results: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p &lt; 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P &lt; 0.001). Conclusion: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas “in-situ thrombosis” seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.</p

Development of new synthetic methodologies for accessing heterocyclic molecules and evaluation of their biological properties in cancer and neurodegenerative diseases

Les hétérocycles constituent une grande famille de composés organiques possédant un grand intérêt biologique et industriel. Afin d’obtenir des structures hétérocycliques variées et élargir leur domaine d’application, le développement de nouvelles approches synthétiques efficaces est devenu un défi important dans les laboratoires de recherche. Le travail présenté dans ce mémoire s'inscrit dans cette perspective et aborde de nouvelles méthodologies efficaces et durables pour accéder aux molécules hétérocycliques à visée thérapeutique. Dans une première partie, une méthodologie basée sur un réarrangement dioxa-[1,3]-sigmatropique [3,3] assisté par irradiations micro-ondes a permis d’élargir le scope en carbamates allyliques linéaires et d’aboutir par la suite aux dérivés d’oxazinanedione. Dans une deuxième partie, un réarrangement sigmatropique [3,3] d’allyle cyanate/isocyanate a été appliqué aux carbamates allyliques pour accéder aux dérivés d’imidazolidinedione. Enfin, la synthèse des dérivés 2-alkyl et 2-arylimidazolones, inspirés du produit naturel la leucettamine B, est exposée dans ce manuscrit. Elle met en jeu une stratégie synthétique multicomposant assistée par micro-ondes. Les dérivés d’imidazolone obtenus ont montré des activités anticancéreuses intéressantes contre les lignées cellulaires MCF-7 et HepG2. De même, ils ont montré un effet thérapeutique potentiel sur un modèle de maladie d’Alzheimer induit aux poissons zèbre.Heterocycles constitute an important family of organic compounds having a great biological and industrial interest. In order to obtain various heterocyclic structures and widen their field of application, the development of new effective synthetic approaches has become an important challenge in research laboratories.The work presented in this thesis is within this perspective and highlights new efficient and sustainable methodologies for accessing bioactive heterocyclic molecules. In a first part, a methodology based on a [1,3]-dioxa-[3,3]-sigmatropic rearrangement assisted by microwave irradiations made it possible to extend the scope of linear allylic carbamates and subsequently to lead to oxazinanedione derivatives. In a second part, an allyl cyanate/isocyanate [3,3]-sigmatropic rearrangement was applied to allylic carbamates to access imidazolidinedione derivatives. Finally, the synthesis of 2-alkyl and 2-arylimidazolone derivatives, inspired by the natural product leucettamine B, is presented in this manuscript. It involves a microwave-assisted multicomponent synthetic strategy. The obtained imidazolone derivatives showed interesting anticancer activities against the MCF-7 and HepG2 cell lines. Likewise, they have shown a potential therapeutic effect against an induced model of Alzheimer's disease in zebrafish

Microwave-assisted synthesis of new 2-aryl and 2-alkylimidazolones and evaluation of their in vitro anticancer activity and their in vivo toxicity on zebrafish embryos

International audienceHerein we describe the synthesis of five new 2-aryl and 2-alkylimidazolone derivatives via an effective one-pot synthetic strategy assisted by microwave irradiations which allowed us to access the desired product in a reduced time reaction compared to the thermal heating and a slightly better yield (48% compared to 45%). The new imidazolone derivatives were evaluated for their anticancer activity in vitro against MCF-7, MDA-MB-231 and HepG2 cell lines. The results showed good cytotoxic effects for some of these derivatives on both MCF-7 and HepG2 cell lines in the range of 5.7-11.3 mu M. Among the synthesized derivatives, 2ab and 2b showed the strongest activity with IC50 values of 7 and 5.7 mu M (MCF-7) and 6.2 and 8.6 mu M (HepG2), respectively. The cytotoxic activities of these derivatives were moderate compared to those of doxorubicin. However, this product showed higher toxicity in vivo on the development of zebrafish embryos than the synthesized imidazolones. These derivatives at high concentrations exhibited some morphological abnormalities on the embryos

Microwave-Assisted 1,3-Dioxa-[3,3]-Sigmatropic Rearrangement of Substituted Allylic Carbamates: Application to the Synthesis of Novel 1,3-Oxazine-2,4-dione Derivatives

International audienceIn a first instance, the effect of the microwave irradiation on the 1,3-Dioxa-[3,3]-sigmatropic rearrangement of aryl allylic carbamates was investigated. Under these new conditions, the reaction acceleration was clearly highlighted compared to conventional heating conditions. Depending on the electronic nature of substituents on the aromatic group, this type of rearrangement can be faster with similar or improved yields. Due to this experimental improvement, the diversity of aryl allylic carbamates able to undergo this rearrangement in a reasonable reaction time (30 min.) and with acceptable to high yields was greatly extended. Finally, an original synthetic way involving this microwave-assisted process to access new six-membered heterocyclic structures such as (E)-5-arylidene-1,3-oxazinane-2,4-diones was developed from Morita-Baylis-Hillman (MBH) adducts showing the interest of this molecular rearrangement approach. DFT and Fragment Distortion studies showed in general polar transition structures and connected high deformation and interaction energies with lower activation barriers

Risk factors and quality of life of dyslipidemic patients in Lebanon: A cross-sectional study

The main objective of this study was to identify the risk factors of dyslipidemia and measure its impact on patients’ quality of life (QOL). Secondary objectives were to determine the percentage of dyslipidemia and assess the predictive factors affecting patients’ QOL. A cross-sectional study was conducted in a sample of Lebanese population. A standardized questionnaire was developed to assess the QOL using the Short form-36 (SF-36) score. A total of 452 individuals were interviewed, of which 59.5% were females. The mean age was 43.3 ± 15.6 years, and 24.8% had dyslipidemia. The results show a lower overall QOL score among dyslipidemic patients compared with controls (57.9% and 76.5%, respectively; p < 0.001). Waterpipe smoking [adjusted odds ratio (ORa) = 4.113, 95% confidence interval (CI): 1.696–9.971, p = 0.002], hypertension (ORa = 3.597, 95% CI: 1.818–7.116, p < 0.001), diabetes (ORa = 3.441, 95% CI: 1.587–7.462, p = 0.002), cigarette smoking (ORa = 2.966, 95% CI: 1.516–5.804, p = 0.001), and passive smoking (ORa = 2.716, 95% CI: 1.376–5.358, p = 0.004) were significantly associated with dyslipidemia in individuals older than 30 years. A higher overall QOL score (p = 0.013) was observed in patients treated with statins in comparison with other lipid-lowering medications. In addition to clinical and economical consequences, dyslipidemia may have a significant impact on patients’ QOL. Further research is needed to confirm the impact of treatment on dyslipidemic patients’ QOL in order to maximize the overall benefits of therapy

Factors affecting medication adherence in Lebanese patients with chronic diseases

Background: Non-adherence to prescribed medications represents an obstacle toward achieving treatment goals. This problem is more pronounced in patients with chronic illness.Objective: To identify the extent of adherence in Lebanese outpatients with chronic diseases, and to suggest possible predictors of non-adherence in this population. The secondary objective was to assess if medication adherence affects patients' quality of life.Methods: A questionnaire was administered face-to-face to a sample of Lebanese adults visiting the external clinics at two Tertiary Care Hospitals in Beirut. The level of adherence was assessed using the 8-item Morisky Medication Adherence Scale which was first validated. The health-related quality of life (HRQoL) of patients was measured using the EQ-5D. Linear regression and logistic regression analyses examined possible predictors of adherence.Results: Out of the 148 patients included in this study, 42.6% were classified as adherent. In the univariate analyses, statistically significant predictors of high adherence included good physician-patient relationship (p=0.029) and counseling (p=0.037), a high level of HRQoL (p<0.001), and a high level of perceived health (p<0.001). Predictors of low adherence included a declining memory (p<0.001), anxiety/depression (p=0.002), little drug knowledge (p<0.001), and postponing physician appointments (p<0.001). The multivariate analyses revealed similar results. In the linear regression, the most powerful predictor of non-adherence was the disbelief that the drug is ameliorating the disease (beta=0.279), however, in logistic regression, patient who were willing to skip or double doses in case of amelioration/deterioration were found to be 7.35 times more likely to be non-adherent than those who were not (aOR=0.136, 95%CI: 0.037-0.503).Conclusion: The findings of this study reassure the view that patients should be regarded as active decision makers. Patient education should be regarded as a cornerstone for treatment success. Additional studies as well are needed to test the practicability and effectiveness of interventions suggested to enhance adherence

Evaluation of medication adherence in Lebanese hypertensive patients

Controlling hypertension is essential in cardiovascular diseases. Poor medication adherence is associated with poor disease outcomes, waste of healthcare resources, and contributes to reduced blood pressure control. This study evaluates treatment adherence to antihypertensive therapy in Lebanese hypertensive patients by estimating the proportion of adherent hypertensive patients using a validated tool and investigates what factors predict this behavior. A questionnaire-based cross-sectional study was conducted on a random sample of 210 hypertensive outpatients selected from clinics located in tertiary-care hospitals and from private cardiology clinics located in Beirut. Adherence level was measured using a validated 8-item Modified Morisky Medication Adherence Scale (MMMAS). Among 210 patients, 50.5% showed high adherence, 27.1% medium adherence, and 22.4% low adherence to medication. Mean MMMAS score was 6.59 ± 2.0. In bivariate analyses, having controlled blood pressure (p = 0.003) and taking a combination drug (p = 0.023) were predictors of high adherence. Forgetfulness (p < 0.01), complicated drug regimen (p = 0.001), and side effects (p = 0.006) were predictors of low adherence after multiple liner regression. Logistic regression results showed that calcium channel blockers (p = 0.030) were associated with increased adherence levels. In conclusion, developing multidisciplinary intervention programs to address the factors identified, in addition to educational strategies targeting healthcare providers, are necessary to enhance patient adherence