Evaluation of SAR for Amphotericin B Derivatives by Artificial Neural Network

Purpose: This study was designed to investigate the role of several descriptive structure-activity features in the antifungal drug, amphotericin B and analyze them by artificial neural networks. Method: Artificial neural networks (ANN) based on the back-propagation algorithm were applied to a structure-activity relationship (SAR) study for 17 amphotericin B derivatives with antifungal and membrane directed activity. A series of modified ANN architectures was made and the best result provided the ANN model for prediction of antifungal activity using the structural and biologic property descriptors. Results: The best architecture, in terms of cycles of calculation was 12-15-2. Among the most important factors were biological descriptors that correlated best with the model produced by ANN. Among the chemical and structural descriptors, positive charge on Y substitution was found to be the most important, followed by lack of availability of free carboxyl and parachor. Conclusion: This model is found to be useful to elucidate the structural requirements for the antifungal activity and can be applied in the design and activity prediction of the new amphotericin B derivatives. Keywords: Amphotericin B, SAR, Artificial Neural Network. > Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 517-52

Antimicrobial peptides of the vaginal innate immunity and their role in the fight against sexually transmitted diseases

Some antimicrobial peptides (AMPs) are produced in the vaginal innate immune system and play an important role in protecting this organ against pathogenic agents. Moreover, sexually transmitted diseases have become a major problem in human societies and are rapidly spreading. The emergence of antibiotic-resistant microbes (superbugs) can pose a major threat to human societies and cause rapid spread of these diseases. Finding new antimicrobial compounds to fight superbugs is therefore essential. It has been shown that AMPs have good potential to become new antibiotics. The most important AMPs in the vaginal innate immune system are defensins, secretory leucocyte protease inhibitors, calprotectin, lysozyme, lactoferrin and elafin, which play an important role in host defence against sexually transmitted infections, modulation of immune responses and anticancer activities. Some AMPs, such as LL-37, magainin 2 and nisin, show both spermicidal and antimicrobial effects in the vagina. In this summary, we will discuss vaginal AMPs and continue to address some of the challenges of using peptides to control pathogens that are effective in sexually transmitted diseases. © 2019 The Author(s

Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post stroke

Abstract Background Stroke remains one of the leading causes of long-term disability worldwide, and the development of effective restorative therapies is hindered by an incomplete understanding of intrinsic brain recovery mechanisms. Growing evidence indicates that the brain extracellular matrix (ECM) has major implications for neuroplasticity. Here we explored how perineuronal nets (PNNs), the facet-like ECM layers surrounding fast-spiking interneurons, contribute to neurological recovery after focal cerebral ischemia in mice with and without induced stroke tolerance. Methods We investigated the structural remodeling of PNNs after stroke using 3D superresolution stimulated emission depletion (STED) and structured illumination (SR-SIM) microscopy. Superresolution imaging allowed for the precise reconstruction of PNN morphology using graphs, which are mathematical constructs designed for topological analysis. Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery (tMCAO). PNN-associated synapses and contacts with microglia/macrophages were quantified using high-resolution confocal microscopy. Results PNNs undergo transient structural changes after stroke allowing for the dynamic reorganization of GABAergic input to motor cortical L5 interneurons. The coherent remodeling of PNNs and their perforating inhibitory synapses precedes the recovery of motor coordination after stroke and depends on the severity of the ischemic injury. Morphological alterations in PNNs correlate with the increased surface of contact between activated microglia/macrophages and PNN-coated neurons. Conclusions Our data indicate a novel mechanism of post stroke neuroplasticity involving the tripartite interaction between PNNs, synapses, and microglia/macrophages. We propose that prolonging PNN loosening during the post-acute period can extend the opening neuroplasticity window into the chronic stroke phase. Graphical Abstrac

A Rare Case Report of Saddle Embolism in the Abdominal Aorta Following Acute Myocardial Infarction

Background and Objective: Systemic embolism can be one of the unfortunate side effects of left ventricular thrombus following acute heart infarction, and its timely diagnosis and treatment is very important. In this report, a patient with saddle embolism in the abdominal aorta due to the complete separation of the left ventricular thrombus following acute anterior infarction is presented. Case Report: The patient is a 60-year-old man who referred to the emergency room complaining of severe retrosternal chest pain, nausea and cold sweats. In the ECG, he had ST segment elevation in leads V1-V5, and with the diagnosis of acute anterior infarction with ST segment elevation (acute anterior STEMI), he underwent primary angioplasty with stent placement (Primary PCI) on the left anterior descending artery. In transthoracic echocardiography three days later, a large thrombus was seen in the apex of the left ventricle. Seven days after stent implantation, the patient experienced severe pain and paraplegia of the lower limbs. In Doppler ultrasound, bilateral iliac artery occlusion was seen. Despite treatment with aspirin, clopidogrel, and anticoagulants, the left ventricular thrombus was embolized to the bifurcation of the abdominal aorta and caused bilateral acute ischemia of the lower limbs. The patient underwent emergency embolectomy and was discharged one week later with a stable condition and two antiplatelets and warfarin. Three months later, warfarin was discontinued. Conclusion: According to this case report, abdominal aortic saddle embolism following acute myocardial infarction may rarely be seen. Paying attention to clinical symptoms, careful examination and quick diagnosis and treatment can improve the prognosis. In any patient with a left ventricular thrombus following an acute myocardial infarction, the possibility of systemic embolism should be considered

8-Iodo-5,7-dimeth­oxy-4-methyl-2H-chromen-2-one

In the title compound, C12H11IO4, the C and O atoms of both meth­oxy groups lie very close to the mean plane of the six C atoms of the benzene ring. The O and C atoms of the group lying closest to the I atom are 0.012 (3) and 0.022 (4) Å, respectively, out of the mean plane. For the other meth­oxy group, the corresponding distances are 0.020 (3) and 0.078 (4) Å. In the crystal, there are only very weak inter­molecular C—H⋯O hydrogen bonds and O⋯I contacts [3.080 (2) Å]. The mol­ecules are approximately parallel to (100), forming a layered structure

Prognostic value of nonangiogenic and angiogenic growth patterns in non-small-cell lung cancer

An essential prerequisite of nonangiogenic growth appears to be the ability of the tumour to preserve the parenchymal structures of the host tissue. This morphological feature is visible on a routine tissue section. Based on this feature, we classified haematoxylin and eosin-stained tissue sections from 279 patients with non-small-cell lung cancer into three growth patterns: destructive (angiogenic; n=196), papillary (intermediate; n=38) and alveolar (nonangiogenic; n=45). A Cox multiple regression model was used to test the prognostic value of growth patterns together with other relevant clinicopathological factors. For overall survival, growth pattern (P=0.007), N-status (P=0.001), age (P=0.020) and type of operation (P=0.056) were independent prognostic factors. For disease-free survival, only growth pattern (P=0.007) and N-status (P<0.001) had an independent prognostic value. Alveolar (hazard ratio=1.825, 95% confidence interval=1.117-2.980, P=0.016) and papillary (hazard ratio=1.977, 95% confidence interval=1.169-3.345, P=0.011) growth patterns were independent predictors of poor prognosis. The proposed classification has an independent prognostic value for overall survival as well as for disease-free survival, providing a possible explanation for survival differences of patients in the same disease stage

6,8-Diiodo-5,7-dimeth­oxy-4-methyl­coumarin

In the title compound, C12H10I2O4, the meth­oxy groups are twisted considerably with respect to the plane of the aromatic ring [CH3—O—C—C torsion angles = −85.9 (3) and −92.8 (3)°]. In the crystal, mol­ecules are linked by weak C—H⋯O hydrogen bonds and O⋯I contacts [3.194 (2) Å]

Impact of Tube Bundle Placement on the Thermal Charging of a Latent Heat Storage Unit

The melting process of a multi-tube’s thermal energy storage system in the existence of free convection effects is a non-linear and important problem. The placement of heated tubes could change the convective thermal circulation. In the present study, the impact of the position of seven heat exchanger tubes was systematically investigated. The energy charging process was numerically studied utilizing liquid fraction and stored energy with exhaustive temperature outlines. The tubes of heat transfer fluid were presumed in the unit with different locations. The unit’s heat transfer behavior was assessed by studying the liquid fraction graphs, streamlines, and isotherm contours. Each of the design factors was divided into four levels. To better investigate the design space for the accounted five variables and four levels, an L16 orthogonal table was considered. Changing the location of tubes could change the melting rate by 28%. The best melting rate was 94% after four hours of charging. It was found that the tubes with close distance could overheat each other and reduce the total heat transfer. The study of isotherms and streamlines showed the general circulation of natural convection flows at the final stage of melting was the most crucial factor in the melting of top regions of the unit and reduces the charging time. Thus, particular attention to the tubes’ placement should be made so that the phase change material could be quickly melted at both ends of a unit.</jats:p