Hybrid approach to postmyocardial infarction ventricular septal defect repair

Postinfarction ventricular septal rupture is a rare and devastating complication of myocardial infarction. Despite attempts at acute surgical and percutaneous defect closure, morbidity and mortality remain high. Herein, we describe a hybrid surgical and catheter-based approach to defect closure in a 63-year-old woman with postinfarction ventricular septal rupture and cardiogenic shock.     

Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model

Delayed treatment of stroke with recombinant tissue plasminogen activator (r‐tPA) induces overexpression of matrix metalloproteinase 9 (MMP‐9) which leads to breakdown of the blood–brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r‐tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA‐treated (500 mg/kg; 5 hr after stroke) rats, r‐tPA‐treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r‐tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP‐9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r‐tPA‐treated animals, AA alone (p < 0.001) or in combination with r‐tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r‐tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP‐9 (p < 0.05 versus control; p < 0.01 versus r‐tPA) and brain oedema (p < 0.001) when compared to either the control or the r‐tPA‐treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r‐tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r‐tPA in stroke therapy.     

Cdc42: Role in Cancer Management

Contribution of Cdc42, a member of Rho family, has been characterized for the beginning of variety of cellular responses including cellular transformation, cell division, cell invasion, migration, invadopodia formation, enzyme activity, filopodia formation, and cell polarity in cells. Deregulation of Cdc42 can alter the normal functioning of the cells, responsible for the initiation of signaling pathways and is correlated with several pathogenic processes such as cancer. Therefore, maintaining the level of Cdc42 and its effectors in cells, tumor progression can be controlled. Therefore, it can be suggested that deeper understanding about the Cdc42 contribution in cancer cell progression at molecular level can approach to the development of Cdc42 inhibitors in cancer management.     

New Approach for Using of Mentha longifolia L. and Citrus reticulata L. Essential Oils as Wood-Biofungicides: GC-MS,SEM, and MNDO Quantum Chemical Studies

Background: Fungi growing on wood cause deterioration of stored food materials or discoloration of the wood itself, and the search for new and safe bioagents is recently needed. Methods: Essential oils (EOs) from aerial parts from Mentha longifolia L. and Citrus reticulata L., analyzed by gas chromatography-mass spectrometry (GC-MS), were tested for their antifungal activity by the vapor method against four common fungi, Aspergillus flavus, A. niger, A. fumigatus, and Fusarium culmorum, and confirmed by SEM examination as the oils applied on wood samples. Results: The most abundant compounds identified in the EO from M. longifolia were menthone and eucalyptol; in C. reticulata EO, they were β-caryophyllene, β-caryophyllene oxide, and β-elemene. EOs from M. longifolia and C. reticulata, at 500 and 250 µL/mL, showed potent antifungal activity against A. flavus and A. fumigatus, with 100% fungal mycelial inhibition growth (FMIG). C. reticulata and M. longifolia EOs, at 125 µL/mL, observed FMIG values of 98% and 95%, respectively, against A. fumigatus. M. longifolia EO, at 500 and 250 µL/mL, showed potent activity against A. niger, with 100% FMIG. F. culmorum completely inhibited (100% FMIG) EOs from M. longifolia and C. reticulata applied at 500 µL/mL. Pinus roxburghii Sarg. Wood, treated with M. longifolia at 125 µL/mL, showed inhibition zone values of 7.33 and 21.33 mm against A. flavus and A. niger, respectively. Conclusions: Both oils possessed good wood-biofungicide activity with the vapor method, as clearly shown by the SEM examination. These activities suggest their possible use as natural wood preservatives.     

Synthesis and biological study of acridine-based imidazolium salts

A new series of acridine based imidazolium salts was synthesized and evaluated for in vitro cytotoxicity against human cancer cell lines by an MTT assay. The synthesis applied a coupling of imidazoles with 9-chloroacridines, which originated from an Ullmann condensation of a 2-chloro-benzoic acid with an aniline. The target compounds were obtained in high yields. The DPPH assay indicated considerable antioxidant activity for target compounds with simple and short alkyl chains on the imidazole, while increasing chain length and the introduction of an additional π-electron system in most cases reduced the activity. All compounds exhibited low biotoxicity against non-cancerous cell lines, whereas a few compounds showed promising anticancer activity. Unlike for the reference drugs Tamoxifen and Paclitaxel, the anticancer activity of acridine imidazolium ions is specific for only selected cancer types. Reasonable fluorescent behaviour of the products provide potential for visualization of the distribution of active drugs in tissue.

A series of acridine-based imidazolium salts was synthesized and studied on cytotoxicity against human cancer cell lines.     

Characterization of reactive intermediates formation in dacomitinib metabolism and bioactivation pathways elucidation by LC-MS/MS: in vitro phase I metabolic investigation

Dacomitinib (DCB) is a second generation irreversible tyrosine kinase inhibitor (TKI) that is claimed to overcome the disadvantages of the resistance developed by the first line epidermal growth factor receptor (EGFR) TKIs. In the current study, metabolites of phase I for DCB were systematically explored. DCB reactive metabolites were also investigated in rat liver microsomes in presence of potassium cyanide or methoxylamine that were employed as capturing agents for iminium reactive intermediates and aldehyde, respectively, to form stable complexes which can be detected by LC-MS/MS. As a result, four in vitro phase I metabolites were observed with major pathway of piperidine ring hydroxylation. Additionally, two potentially reactive intermediates, one aldehyde and one iminium ions were characterized. Two different pathways of bioactivation were ultimately proposed.

Dacomitinib (DCB) is a second generation irreversible tyrosine kinase inhibitor (TKI) that is claimed to overcome the disadvantages of the resistance developed by the first line epidermal growth factor receptor (EGFR) TKIs.     

Does prior immunization with measles,mumps, and rubella vaccines contribute to the antibody response to COVID-19 antigens?

Background: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. Objective: To assess the cross-protection induced by prior measles, mumps and rubella (MMR) vaccinations against COVID-19. Methods: The antibody responses to MMR and tetanus vaccines were determined in 53 patients affected with SARS-CoV2 infection and 52 age-matched healthy subjects. Serum levels of antibodies specific for NP and RBD of SARS-CoV2 were also determined in both groups of subjects with ELISA. Results: Our results revealed significant differences in anti-NP (p <0.0001) and anti-RBD (p <0.0001) IgG levels between patients and healthy controls. While the levels of rubella- and mumps specific IgG were not different in the two groups of subjects, measles-specific IgG was significantly higher in patients (p <0.01). The serum titer of anti-tetanus antibody, however, was significantly lower in patients compared to healthy individuals (p <0.01). Conclusion: Our findings suggest that measles vaccination triggers those B cells cross-reactive with SARS-CoV2 antigens leading to the production of increased levels of measles-specific antibody.     

Epicardial Versus Endocardial Pacemakers in the Pediatric Population: A Comparative Inquiry

Background: Most children in need of cardiac pacemakers remain dependent on the function of the permanent from childhood to adulthood. We sought to evaluate and compare the function between epicardial and endocardial pacemakers in pediatric groups with different conditions. Methods: Between 2012 and 2018, this single-canter study evaluated 44 pediatric patients with indications for epicardial or endocardial pacemakers. Results: The 2 groups, at a median age of 5 (0.1–16) years, were compared concerning the characteristics of the leads used (n = 80: bipolar, unipolar, steroid-eluting, and non–steroid-eluting), survival data, and complications. The reason for pacemaker implantation was congenital complete heart block in 11 (25%) cases and postoperative heart block in 33 (75%) cases. The commonest congenital heart disease accompanied by postoperative block was the ventricular septal defect. In the endocardial lead group, the mean ventricular pacing threshold immediately after the implantation and during the follow-up was less than that in the epicardial lead group (0.75 vs. 0.81 V; P = 0.01 and 0.8 vs. 2.4 V; P = 0.001). During the follow-up, the mean battery longevity was better in the endocardial group (last visit: 6.7 endocardial vs. 3.3 years epicardial). Lead failure was commoner in the epicardial pacemaker, and chronic high-pacing threshold pattern was seen in 14 patients in this group. After 3 years, freedom from lead failure was 94% and 63% in the endocardial and epicardial leads. Conclusions: Pacemakers with endocardial bipolar steroid-eluting leads showed better lead characteristics regarding survival and battery longevity than epicardial pacemakers without these lead characteristics. An appropriate pacemaker type should be selected based on the patient’s condition.