β-Asarone Exhibits Antifungal Activity by Inhibiting Ergosterol Biosynthesis in Aspergillus niger ATCC 16888

Fungi play an important role in the degradation of leather goods. Economics often influence the choice of fungicide, thus, search for highly effective and low cost fungicides is immensely important. The authors have screened antifungal activity of ten Indian traditional medicinal plants viz Acalypha fruticosa, Acalypha indica, Aegle marmelos, Adathoda vasika, Calotropis gigantea, Erythrina indica, Morinda citrifolia, Nerium oleander, Pithecellobium dulce, and Acorus calamus based upon their traditional knowledge and usage. Various solvent extracts and essential oils were screened for antifungal activity against Aspergillus niger. The antifungal potency was compared to untreated control and standard antifungal drugs itraconazole and voriconazole. The bioactive principle from highly active fragment was isolated and chemically characterized. The mode of action was determined by a range of studies that include the lesion of plasma membrane, ergosterol content in the plasma membrane, acidification of external medium, and mitochondrial dehydrogenase activity in A. niger ATCC 16888. Among the ten plants studied, A. calamus exhibited greater antifungal potency in comparison to untreated control and standard drugs itraconazole and voriconazole. The minimum inhibitory concentration of both methanolic extract and essential oil of A. calamus against A. niger ATCC 16888 is around 5 µg/ml. The authors identified β-Asarone as the bioactive principle of A. calamus using spectral studies viz ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy and gas chromatography coupled mass spectroscopy. The results indicate that β-Asarone interfere and reduces the ergosterol content in the plasma membrane of A. niger ATCC 16888 thus exert their antifungal activity.

     

Deep Brain Stimulation for Disorders of Memory and Cognition

The next several decades will see an exponential rise in the number of patients with disorders of memory and cognition, and of Alzheimer’s disease in particular. Impending demographic shifts, an absence of effective treatments, and the significant burden these conditions place on patients, caregivers, and society, mean there is an urgent need to develop novel therapies. Deep brain stimulation (DBS) is a neurosurgical procedure that is a standard-of-care for many patients with treatment-refractory Parkinson’s disease, dystonia, and essential tremor. DBS has proven to be an effective means of modulating activity in disrupted motor circuitry, and has shown promise as a modulator of other dysfunctional circuits, including for mood and anxiety disorders. The deficits in Alzheimer’s disease and other disorders of memory and cognition are also beginning to be thought of as arising from dysfunction in neural circuits. Such dysfunction may be amenable to modulation using focal brain stimulation. A global experience is now emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities.     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome

European Journal of Nuclear Medicine and Molecular Imaging - Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC),...     

Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia

We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45^+high cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8⁺ T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4⁺ T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were ∼50% fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.     

In Search of Potent 5‐HT6 Receptor Inverse Agonists

A series of non‐sulfonamide/non‐sulfone derived potent 5‐HT₆ receptor inverse agonists has been disclosed. Representative compound 9 ( K _i = 14 nm ) displayed selectivity against a set of family members as well as brain permeability 6 h post‐oral administration. In addition, the separated enantiomers of compound 9 displayed difference in activity indicating the influence of chirality on potency.     

A high-efficiency Cre/loxP-based system for construction of adenoviral vectors

Adenovirus (Ad) vectors provide a highly efficient means of mammalian gene transfer and are widely used for high-level protein expression in mammalian cells, as recombinant vaccines and for gene therapy. A commonly used method for constructing Ad vectors relies on in vivo homologous recombination between two Ad DNA-containing bacterial plasmids cotransfected into 293 cells. While the utility of this two-plasmid approach is well established, its efficiency is low owing to the inefficiency of homologous recombination. To address this, we have developed an improved method for Ad vector construction based on Cre-mediated site-specific recombination between two bacterial plasmids, each bearing a loxP site. Ad vectors are generated as a result of Cre-mediated site-specific recombination between the two plasmids after their cotransfection into 293 cells expressing Cre recombinase. The frequency of Ad vector rescue by Cre-mediated site-specific recombination is significantly higher (approximately 30-fold) than by in vivo homologous recombination. The efficiency and reliability of this method should greatly simplify and expedite the construction of recombinant Ad vectors for mammalian gene transfer. Ad vectors are commonly constructed by homologous recombination between two plasmids cotransfected into 293 cells. This method has numerous advantages but results in low numbers of plaques owing to inefficient recombination. We have developed an improved method based on Cre-mediated site-specific recombination, which results in vector rescue at frequencies approximately 30-fold higher than by homologous recombination. This method should greatly simplify and expedite the construction of recombinant Ad vectors for mammalian gene transfer.