Nanosuspension-Based Drug Delivery Systems for Topical Applications.

Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.

Molecular characterization of an outbreak-involved Bacillus anthracis strain confirms the spillover of anthrax from West Africa.

BACKGROUND: Anthrax, a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, remains a major global public health concern, especially in countries with limited resources. Sierra Leone, a West African country historically plagued by anthrax, has almost been out of report on this disease in recent decades. In this study, we described a large-scale anthrax outbreak affecting both animals and humans and attempted to characterize the pathogen using molecular techniques. METHODS: The causative agent of the animal outbreak in Port Loko District, Sierra Leone, between March and May 2022 was identified using the nanopore sequencing technique. A nationwide active surveillance was implemented from May 2022 to June 2023 to monitor the occurrence of anthrax-specific symptoms in humans. Suspected cases were subsequently verified using quantitative polymerase chain reaction. Full-genome sequencing was accomplished by combining long-read and short-read sequencing methods. Subsequent phylogenetic analysis was performed based on the full-chromosome single nucleotide polymorphisms. RESULTS: The outbreak in Port Loko District, Sierra Leone, led to the death of 233 animals between March 26th and May 16th, 2022. We ruled out the initial suspicion of Anaplasma species and successfully identified B. anthracis as the causative agent of the outbreak. As a result of the government's prompt response, out of the 49 suspected human cases identified during the one-year active surveillance, only 6 human cases tested positive, all within the first month after the official declaration of the outbreak. The phylogenetic analysis indicated that the BaSL2022 isolate responsible for the outbreak was positioned in the A.Br.153 clade within the TransEuroAsian group of B. anthracis. CONCLUSIONS: We successfully identified a large-scale anthrax outbreak in Sierra Leone. The causative isolate of B. anthracis, BaSL2022, phylogenetically bridged other lineages in A.Br.153 clade and neighboring genetic groups, A.Br.144 and A.Br.148, eventually confirming the spillover of anthrax from West Africa. Given the wide dissemination of B. anthracis spores, it is highly advisable to effectively monitor the potential reoccurrence of anthrax outbreaks and to launch campaigns to improve public awareness regarding anthrax in Sierra Leone.

Phosphodiesterase 10A deactivation induces long-term neurological recovery, Peri-infarct remodeling and pyramidal tract plasticity after transient focal cerebral ischemia in mice.

The phosphodiesterase (PDE) superfamily comprises enzymes responsible for the cAMP and cGMP degradation to AMP and GMP. PDEs are abundant in the brain, where they are involved in several neuronal functions. High PDE10A abundance was previously observed in the striatum; however its consequences for stroke recovery were unknown. Herein, we evaluated the effects of PDE10A deactivation by TAK-063 (0.3 or 3 mg/kg, initiated 72 h post-stroke) in mice exposed to intraluminal middle cerebral artery occlusion. We found that PDE10A deactivation over up to eight weeks dose-dependently increased long-term neuronal survival, angiogenesis, and neurogenesis in the peri-infarct striatum, which represents the core of the middle cerebral artery territory, and reduced astroglial scar formation, whole brain atrophy and, more specifically, striatal atrophy. Functional motor-coordination recovery and the long-distance plasticity of pyramidal tract axons, which originate from the contralesional motor cortex and descend through the contralesional striatum to innervate the ipsilesional facial nucleus, were enhanced by PDE10A deactivation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed a set of dopamine receptor-related and neuronal plasticity-related PDE10A targets, which were elevated (e.g., protein phosphatase-1 regulatory subunit 1B) or reduced (e.g., serine/threonine protein phosphatase 1α, ß-synuclein, proteasome subunit α2) by PDE10A deactivation. Our results identify PDE10A as a therapeutic target that critically controls post-ischemic brain tissue remodeling and plasticity.

Coil embolization for successful treatment of perforation of chronically occluded proximal coronary artery.

We describe a case of a coronary artery perforation involving the proximal right coronary artery that was successfully managed by percutaneous coil embolization. In the setting of a chronic coronary artery occlusion, this demonstrates the successful use of thrombogenic platinum alloy coils for a large proximal vessel perforation which has not been described previously.

Dilation of the coronary sinus on echocardiogram: prevalence and significance in patients with chronic pulmonary hypertension.

BACKGROUND: Although rarely seen in healthy patients, the coronary sinus (CS) is often visualized on echocardiography in patients with right-sided heart disease. However, the prevalence of this finding and its relation to right-sided heart structure and pressure remains undefined. METHODS: We examined the transthoracic echocardiograms of 43 consecutive patients referred for the evaluation of pulmonary hypertension (26 men, 17 women) with a mean age of 53 +/- 15 years (range 21 to 82 years). Structural abnormalities of the tricuspid valve were absent. All patients underwent right heart catheterization within 48 hours of their echocardiogram, which revealed the following pressures: mean pulmonary artery (50 mm Hg, range 31 to 84 mm Hg) and right atrial (RA) (mean 10, range 1 to 24 mm Hg). Echocardiograms were analyzed for CS size (identified as the smallest diameter of a circular structure in the left atrioventricular groove in the parasternal long-axis view), as well as RA and right ventricular (RV) sizes. The presence and severity (grades 1 through 3) of tricuspid regurgitation (TR) were also recorded. RESULTS: The CS was visualized in 35 (81%) of 43 patients, and measurements ranged from 0.4 to 1.6 cm (mean 0.8 cm). No difference in RA size, RV size, TR grade, RA pressure (RAP), RV pressure (RVP), mean pulmonary artery pressure (PAP), or pulmonary vascular resistance (PVR) was observed between patients with a visualized and nonvisualized CS. Coronary sinus size correlated significantly with RA size (r = 0.60, P <.001) and pressure (r = 0.59, P <.001), but not with RV size, degree of TR, RVP, PAP, or PVR. Nineteen of 35 patients with a visualized CS underwent pulmonary artery thromboendarterectomy (PTE), and their CS size and RAP were unchanged (0.8 cm and 12 mm Hg, respectively, preand post-PTE; both P = NS [not significant]), though a decrease was observed in other measurements: RA size (4.2 versus 4.8 cm, P =.02), RV size (4.2 versus 5.1 cm, P =.0004), mean PAP (37 versus 72 mm Hg, P <.0001), and PVR (230 versus 899 mm Hg, P <.0001). CONCLUSIONS: Coronary sinus dilation was observed in 81% of a selected group of patients with pulmonary hypertension in the absence of structural disease of the tricuspid valve. Coronary sinus dilation is related to RAP and RA size, but not to RV size, degree of TR, RVP, PA pressure, or PVR. Once dilated, CS size does not change shortly after decreases of RA size, RV size, or PA pressure produced by PTE.

Ethanol treatment inhibits mesoderm cell spreading in the gastrulating chick embryo.

Gastrulating chick embryos in culture were treated with ethanol solutions, following which the mesoderm cells migrating from the primitive streak were examined by scanning electron microscopy. Morphometric analysis of cell shape showed that mesoderm cells from treated embryos were significantly more rounded and therefore less well spread than controls, and showed fewer filopodial contacts with the overlying basement membrane. This result was only obtainable for cells leading the migration from the primitive streak, since the following cells in the mesodermal mass apparently did not show this difference. The ethanol concentration required to obtain a reliable effect was 5%, while lower concentrations produced highly variable results. The mesoderm cells were also examined for their in vitro responsiveness to ethanol by investigating their adhesiveness and cytoskeleton. No effect was observed on cell-glass adhesion as judged by interference reflection microscopy using up to 1% ethanol. This concentration did, however, disrupt the actin cytoskeleton of cultured cells when stained with NBD-phallacidin, but lower concentrations were ineffective. It is concluded that ethanol treatment of cultured embryos has a significant effect on the substratum relationships of some migrating mesoderm cells.