Safety and efficacy of brachial approach for coronary angiography and percutaneous coronary intervention.

BACKGROUND: There are many percutaneous coronary approaches. The most commonly used one is the radial artery because of its lowest risk of adverse vascular events. However, it could not be an option in some situations as congenital radial artery hypoplasia and spasm. In these cases, the second most common access is the femoral artery. The current literature over the brachial artery access is controversial. Thus, the aim of this study was to verify the brachial artery approach's effectiveness and safety. RESULTS: We studied 300 patients who underwent elective coronary angiography and angioplasty in our institution with failed radial access between August 2022 and February 2023. They were classified into two groups; 150 patients with brachial access and 150 with femoral access. Access, procedural and fluoroscopy times were recorded. All patients were examined carefully immediately after the procedure and before discharge to assess any complications. Left brachial access was used more frequently than left femoral access (32.7% vs. 22.7%, P = 0.05), but no significant difference noted regarding right sided or bilateral access. Procedure time, fluoroscopy time, and contrast volume did not significantly differ (P = 0.19, 0.06 and 0.1 respectively). However, brachial group had shorter access time (2.6 ± 1.1 vs. 3.4 ± 0.7 min, P = 0.05) and hospital stay (3.5 ± 1.1 vs. 5.9 ± 1.3 days, P < 0.001). Regarding major and minor complications (especially hematomas), they were significantly less in the brachial arm (P = 0.04 and P = 0.05, respectively). CONCLUSIONS: Brachial access is a safe, efficient and non-inferior to the femoral route for coronary intervention whenever radial access is not an option.

Pro-Apoptotic Activity of Epi-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis.

Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, epi-obtusane, previously isolated from Aplysia oculifera, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential -12.3 ± 2.3), and the antiproliferative potential of epi-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. Epi-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of epi-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases.

Co-administration of Thymoquinone and Propolis in Liposomal Formulations as a Potential Approach for Treatment of Acetic Acid-Induced Ulcerative Colitis: Physiological and Histopathological Analysis.

A severe form of autoimmune-mediated inflammatory bowel disease (IBD) is termed as ulcerative colitis (UC) which ultimately results in significant mucosal damage and ulceration. Herbal remedies may be employed as an alternative for treatment of UC instead of conventional medications such as Sulfasalazine. Promising natural remedies for the treatment of IBD, including colitis, are propolis extract (PP) and thymoquinone (TQ). This study is aimed at assessing the potential of liposomal formulations of TQ and Egyptian PP in combination therapy on improving their therapeutic efficacy against ulcerative colitis in order to maximize the potential of their beneficial clinical effects. Clinical, biochemical, and histological evaluations of colonic mucosal damage and inflammation were evaluated. The results exhibited a significant increase in tissue MDA, TNFα, and nitrite levels with activation of caspase-3 in the acetic acid-induced colitis group, which is predominantly downregulated in the treatment groups. The prepared formulations of TQ and PP revealed liposomal vesicles in a nanoscale size (192 ± 20.3 and 98.2 ± 20.3 nm, respectively) and accepted stability indicated with a zeta potential of 19.3 ± 0.11 and 17.1 ± 0.25 mV, respectively. They showed an entrapment efficiency of 85.3 ± 12.6% and 69.3 ± 11.8%, respectively. At comparable doses, combination therapy with thymoquinone liposomes and propolis liposomes considerably outperformed free TQ and free PP in reducing inflammation of UC as shown in the present study by clinical, biochemical, and histological evaluations.

Diterpenoids profile of the marine sponge Chelonaplysilla erecta and candidacy as potential antitumor drugs investigated by molecular docking and pharmacokinetic studies.

The Chelonaplysilla genus possesses a numerous bioactive diterpenes with anti-inflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC50 value 16.5 ± 0.8 µg/mL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC50 = 2.8 ± 0.03 µg/mL). Among the dereplicated compounds, macfarlandin F (16) and pourewanone (25) demonstrated the highest potential with co-crystallized ligand 63 O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications.

Network Pharmacological Analysis of the Red Sea Sponge Hyrtios erectus Extract to Reveal Anticancer Efficacy of Corresponding Loaded Niosomes.

In this study, the LC-HRMS-assisted chemical profiling of Hyrtios erectus sponge led to the annotation of eleven major compounds (1-11). H. erectus-derived crude extract (HE) was tested in vitro for its antiproliferative activity against three human cancer cell lines, Hep-G2 (human liver cancer cell line), MCF-7 (breast cancer cell line), and Caco-2 (colon cancer cell line), before and after encapsulation within niosomes. Hyrtios erectus extract showed moderate in vitro antiproliferative activities towards the studied cell lines with IC50 values 18.5 ± 0.08, 15.2 ± 0.11, and 13.4 ± 0.12, respectively. The formulated extract-containing niosomes (size 142.3 ± 10.3 nm, PDI 0.279, and zeta potential 22.8 ± 1.6) increased the in vitro antiproliferative activity of the entrapped extract significantly (IC50 8.5 ± 0.04, 4.1 ± 0.07, and 3.4 ± 0.05, respectively). A subsequent computational chemical study was performed to build a sponge-metabolite-targets-cancer diseases network, by focusing on targets that possess anticancer activity toward the three cancer types: breast, colon, and liver. Pubchem, BindingDB, and DisGenet databases were used to build the network. Shinygo and KEGG databases in addition to FunRich software were used for gene ontology and functional analysis. The computational analysis linked the metabolites to 200 genes among which 147 genes related to cancer and only 64 genes are intersected in the three cancer types. The study proved that the co-occurrence of compounds 1, 2, 3, 7, 8, and 10 are the most probable compounds possessing cytotoxic activity due to large number of connections to the intersected cytotoxic genes with edges range from 9-14. The targets possess the anticancer effect through Pathways in cancer, Endocrine resistance and Proteoglycans in cancer as mentioned by KEGG and ShinyGo 7.1 databases. This study introduces niosomes as a promising strategy to promote the cytotoxic potential of H. erectus extract.

An In Vitro and In Silico Study of the Enhanced Antiproliferative and Pro-Oxidant Potential of Olea europaea L. cv. Arbosana Leaf Extract via Elastic Nanovesicles (Spanlastics).

The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC50 values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC50 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC50 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.

Regional differences in presentation characteristics, use of treatments and outcome of patients with cardiogenic shock: Results from multicenter, international registry.

BACKGROUND: Concurrent evidence about cardiogenic shock (CS) characteristics, treatment and outcome does not represent a global spectrum of patients and is therefore limited. The aim of this study was to investigate these regional differences. METHODS: To investigate regional differences in presentation characteristics, treatments and outcomes of patients treated with all types of cardiogenic shock (CS) in a single calendar year on a multi-national level. Consecutive patients from 19 tertiary care hospitals in 13 countries with CS who were treated between January 1, 2018 and December 31, 2018 were enrolled in this study. RESULTS: In total, 699 cardiogenic shock patients were included in this study. Of these patients, 440 patients (63%) were treated in European hospitals and 259 (37%) were treated in Non-European hospitals. Female patients (P<0.01) and patients with a previous myocardial infarction (P=0.02) were more likely to present at Non-European hospitals; whereas older patients (P=0.01) and patients with cardiogenic shock due to acute heart failure (P<0.01) were more likely to present at European hospitals. Vasopressor use was more likely in Non-European hospitals (P=0.04), whereas use of mechanical circulatory support (MCS) was more likely in European hospitals (P<0.01). Despite adjustment for relevant confounders, 30-day in-hospital mortality risk was comparably high in CS patients treated in European vs. Non-European hospitals (hazard ratio 1.08, 95% CI 0.84-1.39, P=0.56). CONCLUSION: Despite marked heterogeneity in characteristics and treatment of CS patients, including fewer use of MCS but more frequent use of vasopressors in Non-European hospitals, 30-day in-hospital mortality did not differ between regions.

Cytotoxic Potential, Metabolic Profiling, and Liposomes of Coscinoderma sp. Crude Extract Supported by in silico Analysis.

INTRODUCTION: Sponge-Coscinoderma sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable. METHODOLOGY: In the present study, the metabolomic profiling of Coscinoderma sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). Coscinoderma-derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively). RESULTS: The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds 1-15) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC50 values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC50 values ranged from 1.7 to 4.1 µg/mL). DISCUSSION: Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.

Novel predictors and adverse long-term outcomes of No-reflow phenomenon in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

OBJECTIVES: The no-reflow phenomenon occurs in 25% of patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and may be associated with adverse outcomes. The aim of our study was to detect novel predictors of no-reflow phenomenon and the resulting adverse long term outcomes. METHODS: We enrolled 400 STEMI patients undergoing primary PCI; 228 patients had TIMI flow 3 after PCI (57%) and the remaining 172 patients had TIMI flow <3 (43%). Fibrinogen to albumin ratio (FAR), high sensitive C-reactive protein to albumin ratio (CAR), and atherogenic index of plasma (AIP) were calculated. Long term mortality and morbidity during 6 months follow up were recorded. These data were compared among both groups. RESULTS: In multivariate regression analysis, old age (OR = 1.115, 95% CI: 1.032-1.205, P = 0.006), higher troponin level >5.6 ng/mL (OR = 1.040, 95% CI: 1.001-1.080, P = 0.04), diabetes mellitus (OR = 4.401, 95% CI: 1.081-17.923, P = 0.04) and heavy thrombus burden (OR = 16.915, 95% CI: 5.055-56.602, P < 0.001) could be considered as predictors for the development of no-reflow. Interestingly, CAR >0.21, FAR >11.56, and AIP >0.52 could be considered as novel powerful independent predictors (OR = 3.357, 95% CI: 2.288-4.927, P < 0.001, OR = 4.187, 95% CI: 2.761-6.349, P < 0.001, OR = 16.794, 95% CI: 1.018-277.01, P = 0.04, respectively). Higher long term mortality (P < 0.001) and heart failure (P < 0.001) was also strongly related to incidence of no-reflow. CONCLUSION: No-reflow could be attributed to novel predictors as CAR, FAR, and AIP. This phenomenon was associated with long term adverse events as higher mortality and pump failure.

Short- and long-term prognostic value of right ventricular function in patients with first acute ST elevation myocardial infarction treated by primary angioplasty.

INTRODUCTION: Limited data are known about the prognostic value of right ventricle (RV) function in patients with first acute ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the prognostic value of RV dysfunction in predicting both in-hospital and long-term outcomes in these patients, irrespective of the site of necrosis. METHODS: We enrolled 502 consecutive patients with first acute STEMI treated with primary angioplasty and underwent echocardiography within 48 hours of admission. RV function was evaluated by RV myocardial performance index (RVMPI), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), pulsed tissue Doppler S' wave velocity, and RV global longitudinal strain (RVGLS) of the free wall. The occurrence of in-hospital major adverse cardiac events (MACE) and 1-year survival rate were recorded. RESULTS: In MACE group, RVFAC, TAPSE, and RV S' wave velocity were lower. However, RVMPI, RVGLS, and TR Vmax. were higher than MACE free group (P < .001). In multivariable analysis adjusted for other variables that predicted adverse outcomes, RVFAC < 35% (P < .001), TAPSE < 17 mm (P < .001), RVGLS > -17% (P < .001), RV S' wave velocity < 9.5 cm/s (P = .02), RVMPI > 0.43 (P < .001), and TR Vmax. > 2.8 m/s (P = .01) were strong independent predictors of in-hospital MACE. Lower 1-year survival was noted in patients with RV dysfunction, documented by these cutoffs values. CONCLUSION: RV dysfunction, evidenced by multiparametric echocardiography, is predictive for adverse in-hospital outcomes, and lower 1-year survival rate in first acute STEMI regardless of the site of necrosis.

Flavonoids of Salvadora persica L. (meswak) and its liposomal formulation as a potential inhibitor of SARS-CoV-2.

Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant extract and its liposomal formulation were shown to inhibit SARS-CoV-2 in an in vitro A549 cell line culture and a RT-PCR test almost as well as the FDA-approved anti-COVID-19 agent, remdesivir. Encapsulation within liposomal formulation led to a highly significant increase in the percentage of inhibition of viral replication from 38.09 ± 0.83 to 85.56 ± 1.12% in a flavonoid mixture and its liposomal preparation, respectively, and this figure approached that obtained for remdesivir (91.20 ± 1.71%). Preliminary tests were also performed, including a total flavonoid assay, a molecular docking study, a 3CL-protease inhibition assay and a cytotoxicity study. It was worthy to find a cheap, readily available, safe natural source for promising anti-SARS-CoV-2 agents, that leak their phytochemicals into the aqueous saliva during regular use as a brushing agent.

Human monocyte-derived macrophages: Pathogenetic role in plaque rupture associated to systemic inflammation.

BACKGROUND: Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. METHODS: Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having "round" or "spindle" morphology. RESULTS: Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008). CONCLUSIONS: MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation.

Low Plasma Adiponectin Levels Are Associated With Vulnerable Plaque Features in Patients With Acute Coronary Syndrome: An Optical Coherence Tomography Study.

BACKGROUND: Vulnerable plaques are the primary cause of acute coronary syndrome (ACS). The association between in-vivo plaque vulnerability and adiponectin levels in ACS still remains to be determined. OBJECTIVE: The purpose of this study was to investigate the correlation between adiponectin levels and vulnerable plaque features in ACS patients. METHODS: We enrolled 107 ACS patients admitted to our institution; 83 with Non-ST elevation ACS (NSTE-ACS) and 24 with ST-elevation myocardial infarction (STEMI). Adiponectin levels were measured in these patients. Coronary angiography and subsequent optical coherence tomography (OCT) analysis of culprit lesions were performed. RESULTS: Adiponectin level was lower in patients with complex angiographic lesions, compared to those with non-complex lesions (7.13 ± 3.04 vs. 8.94 ± 2.84 µg/ml, P = 0.002). Adiponectin level was lower in patients with plaque rupture (PR), micro-thrombi, and thin cap fibroatheroma (TCFA), compared to those with non-vulnerable features (7.19 ± 2.95 vs 8.79 ± 3.02 µg/ml, P = 0.007 & 7.29 ± 2.97 vs 8.44 ± 3.09 µg/ml, P = 0.04 and 4.76 ± 0.65 vs 9.74 ± 2.35 µg/ml, P < 0.001 µg/ml respectively). There was a significant negative correlation between adiponectin levels and lipid rich plaque extent and maximum lipid arc (r = -0.05, P < 0.001 & r = -0.03, P = 0.03, respectively). However, a significant positive correlation was observed between adiponectin levels and fibrous cap thickness (r = 0.95, P < 0.001). CONCLUSION: Low adiponectin levels were associated with complex angiographic lesions and vulnerable plaque features in ACS patients, where there was a significant correlation between it and PR, TCFA, and lipid rich plaque.

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19.

The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The optimized formulation parameters were as follow: LMC of 60 mM, CH% of 20% and DL of 5 mg/ml. At those values the E.E% and released % were 70.112% and 81.801%, respectively with nanosized particles (117 ± 11 nm). Docking studies revealed that Rutin and Caffeic acid phenethyl ester showed the highest affinity to both targets. Results showed a significant inhibitory effect of the optimized liposomal formula of Propolis against COVID-3CL protease (IC50 = 1.183 ± 0.06) compared with the Egyptian propolis extract (IC50 = 2.452 ± 0.11), P < 0.001. Interestingly, the inhibition of viral replication of COVID-19 determined by RT_PCR has been significantly enhanced via encapsulation of propolis extract within the liposomal formulation (P < 0.0001) and was comparable to the viral inhibitory effect of the potent antiviral (remdesivir). These findings identified the potential of propolis liposomes as a promising treatment approach against COVID-19.

Modified Spraying Technique and Response Surface Methodology for the Preparation and Optimization of Propolis Liposomes of Enhanced Anti-Proliferative Activity against Human Melanoma Cell Line A375.

Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box-Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to "wrap" them will be minimized.

Biological profile of monocyte-derived macrophages in coronary heart disease patients: implications for plaque morphology.

The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability. Macrophages from coronary plaques are not available, and monocyte-derived macrophages (MDMs) are usually considered as a surrogate. We compared the MDM profile obtained from coronary artery disease (CAD) patients and healthy subjects, and we evaluated the association between CAD MDM profile and in vivo coronary plaque characteristics assessed by optical coherence tomography (OCT). At morphological analysis, MDMs of CAD patients had a higher prevalence of round than spindle cells, whereas in healthy subjects the prevalence of the two morphotypes was similar. Compared to healthy subjects, MDMs of CAD patients had reduced efferocytosis, lower transglutaminase-2, CD206 and CD163 receptor levels, and higher tissue factor (TF) levels. At OCT, patients with a higher prevalence of round MDMs showed more frequently a lipid-rich plaque, a thin-cap fibroatheroma, a greater intra-plaque macrophage accumulation, and a ruptured plaque. The MDM efferocytosis correlated with minimal lumen area, and TF levels in MDMs correlated with the presence of ruptured plaque. MDMs obtained from CAD patients are characterized by a morpho-phenotypic heterogeneity with a prevalence of round cells, showing pro-inflammatory and pro-thrombotic properties. The MDM profile allows identifying CAD patients at high risk.

Dexmedetomidine Compared to Remifentanil Infusion as Adjuvant to Sevoflurane Anesthesia during Laparoscopic Sleeve Gastrectomy.

OBJECTIVES: Evaluation of postoperative (PO) analgesic effects of intraoperative (IO) Dexmedetomidine (DEX) compared to remifentanil (REMI) infusions during sevoflurane anesthesia for laparoscopic gastric sleeve surgery. PATIENTS AND METHODS: One hundred and thirty-two patients with body mass index >35 kg.m-2 and ASA Grades II or III were randomly divided into group R received REMI infusion (6-18 µg.kg-1.h-1) and Group D received DEX infusion (0.2-0.5 µg.kg-1.h-1) after tracheal intubation till before stoppage of inhalational anesthetic. Heart rate and mean arterial pressure were noninvasively monitored during and after surgery. Emergence time, time until postanesthetic care unit transfer, and total operating room (OR) time was recorded. PO shoulder-tip pain and wound pain scores were recorded and rescue analgesia was provided as 50 mg pethidine intramuscular injection. Occurrence of PO nausea and vomiting (PONV) and frequency of the need for antiemetic therapy were recorded. Primary study outcome was the ability of the study infusions to reduce consumption of PO pethidine down to one dose during 24-hr PO. RESULTS: IO use of REMI or DEX infusion allowed hemodynamic control to surgical stresses with nonsignificant difference between both infusions. REMI infusion insured significantly rapid recovery and short OR times but required larger volume of sevoflurane during surgery and proper PO follow-up for pain and PONV. DEX infusion significantly improved control of PO pain with a larger number of patient requested rescue analgesia only once, reduced the dose of PO analgesia, reduced the frequency of PONV, and the need for antiemetic therapy. CONCLUSION: REMI or DEX infusion as IO adjuvant to general anesthesia is appropriate option to achieve hemodynamic control of surgical stresses and to improve perioperative outcomes. REMI infusion may be preferred for its induced rapid recovery and short OR time, whereas DEX infusion may be chosen for its improved control of PO pain and reduction of PO analgesia and frequency of PONV.

Not all plaque ruptures are born equal: an optical coherence tomography study.

AIMS: Plaque rupture (PR) represents the most common substrate of coronary thrombosis, in at least 50% of cases. Chronic low grade inflammation is a common background for atherosclerosis development; however, increased plaque inflammation may predispose by itself to PR. In the last decade, studies performed by optical coherence tomography (OCT) have allowed to establish the severity of plaque inflammation by assessing macrophage infiltration (MØI). Our retrospective study aimed at assessing the role of plaque inflammation in PR among patients with acute coronary syndrome (ACS) using OCT. METHODS AND RESULTS: We enrolled 56 patients with ACS exhibiting PR at the site of the culprit stenosis identified by OCT. Patients were divided into two cohorts according to the presence of MØI at OCT analysis, defined as signal-rich, distinct, or confluent punctate regions that exceed the intensity of background speckle noise. Serum high-sensitivity C-reactive protein (CRP) was measured on admission by latex-enhanced immunophelometric assay. Thirty-seven (66%) patients had MØI at the site of PR, whereas 19 (34%) patients had no evidence of MØI. Patients with MØI showed a higher rate of CRP values >3 mg/dL as compared with those without MØI (92% vs. 47%, P = 0.004). In contrast, patients without MØI had a higher prevalence of hypertension compared with those with MØI (89% vs. 59%, P = 0.021). Furthermore, the group with MØI exhibited a significantly higher rate of lipid-rich plaques (86% vs. 50%, P = 0.008), a higher rate of multifocal disease (59% vs. 10%, P < 0.001), and an MØI in both culprit and remote lesions (97% vs. 0%, P < 0.001) compared with those without MØI. At multivariate analysis, CRP value >3 mg/dL was the only independent predictor of MØI in the culprit plaque (OR 8.72, 95% CI 1.78-41.67, P= 0.007). CONCLUSIONS: In conclusion, PR can be caused by predominant inflammatory or non-inflammatory mechanisms, over a common low-grade chronic inflammatory background well known from pathology observations.

Data on the lipoprotein (a), coronary atherosclerotic burden and vulnerable plaque phenotype in angiographic obstructive coronary artery disease.

Lipoprotein Lp(a) represents an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden and lipid rich plaques prone to rupture in patients with acute coronary syndrome (ACS) still remains unknown. These data aim to investigate the association among serum Lipoprotein(a) (Lpa) levels, coronary atherosclerotic burden and features of culprit plaque in patients with ACS and obstructive CAD. For his reason, a total of 500 ACS patients were enrolled for the angiographic cohort and 51 ACS patients were enrolled for the optical coherence tomography (OCT) cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index, whereas OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. In the angiographic cohort, Lp(a) was a weak independent predictor of Sullivan score (p<0.0001), stenosis score (p<0.0001) and extent index (p<0.0001). In the OCT cohort, patients with higher Lp(a) levels (>30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (P=0.02), a wider lipid arc (p=0.003) and a higher prevalence of thin-cap fibroatheroma (p=0.004).

Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease.

BACKGROUND: Lipoprotein Lp(a) has been shown to be an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden in patients with ACS is largely unknown, as well as the association of Lp(a) with lipid rich plaques prone to rupture. AIM: We aim at assessing CAD burden by coronary angiography and plaque features including thin cap fibroatheroma (TCFA) by optical coherence tomography (OCT) in consecutive patients presenting with acute coronary syndrome (ACS) and obstructive CAD along with serum Lp(a) levels. METHODS: This study comprises an angiographic and an OCT cohort. A total of 500 ACS patients (370 men, average age 66 ± 11) were enrolled for the angiographic cohort and 51 ACS patients (29 males, average age 65 ± 11) were enrolled for the OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index. OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. RESULTS: In the angiographic cohort, at multivariate analysis, Lp(a) was a weak independent predictor of Sullivan score (p < 0.0001), stenosis score (p < 0.0001) and extent index (p < 0.0001). In the OCT cohort, patients with higher Lp(a) levels (≥ 30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (67% vs. 27%; P = 0.02), a wider lipid arc (135 ± 114 vs 59 ± 111; P = 0.03) and a higher prevalence of TCFA (38% vs. 10%; P = 0.04). CONCLUSIONS: Among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis.