The link between Alzheimer's disease and stroke: A detrimental synergism.

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-ß plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.

Formulation and characterization of polymeric nanoparticle of Rivastigmine for effective management of Alzheimer's disease.

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer's disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (-11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

Effect of Apremilast on LPS-induced immunomodulation and inflammation via activation of Nrf2/HO-1 pathways in rat lungs.

Lipopolysaccharides (LPS), the lipid component of gram-negative bacterial cell wall, is recognized as the key factor in acute lung inflammation and is found to exhibit severe immunologic reactions. Phosphodiesterase-4 (PDE-4) inhibitor: "apremilast (AP)" is an immune suppressant and anti-inflammatory drug which introduced to treat psoriatic arthritis. The contemporary experiment designed to study the protective influences of AP against LPS induced lung injury in rodents. Twenty-four (24) male experimental Wistar rats selected, acclimatized, and administered with normal saline, LPS, or AP + LPS respectively from 1 to 4 groups. The lung tissues were evaluated for biochemical parameters (MPO), Enzyme Linked Immunosorbent Assay (ELISA), flowcytometry assay, gene expressions, proteins expression and histopathological examination. AP ameliorates the lung injuries by attenuating immunomodulation and inflammation. LPS exposure upregulated IL-6, TNF-α, and MPO while downregulating IL-4 which were restored in AP pretreated rats. The changes in immunomodulation markers by LPS were reduced by AP treatment. Furthermore, results from the qPCR analysis represented an upregulation in IL-1ß, MPO, TNF-α, and p38 whereas downregulated in IL-10 and p53 gene expressions in disease control animals while AP pretreated rats exhibited significant reversal in these expressions. Western blot analysis suggested an upregulation of MCP-1, and NOS-2, whereas HO-1, and Nrf-2 expression were suppressed in LPS exposed animals, while pretreatment with AP showed down regulation in the expression MCP-1, NOS-2, and upregulation of HO-1, and Nrf-2 expression of the mentioned intracellular proteins. Histological studies further affirmed the toxic influences of LPS on the pulmonary tissues. It is concluded that, LPS exposure causes pulmonary toxicities via up regulation of oxidative stress, inflammatory cytokines and stimulation of IL-1ß, MPO, TNF-α, p38, MCP-1, and NOS-2 while downregulation of IL-4, IL-10, p53, HO-1, and Nrf-2 at different expression level. Pretreatment with AP controlled the toxic influences of LPS by modulating these signaling pathways.

Formulation and in-vitro characterization of fast-disintegrating herbal extract sublingual immunotherapy tablet for peanut-induced allergic asthma.

Background: Allergen immunotherapy (AIT) involves the regimen of gradually incrementing doses of the allergen, thereby inducing desensitization and tolerance. Sublingual Immunotherapy tablets (SLIT-tablets) have been formulated for several allergies and had manifested efficacy for allergic rhinitis and allergic asthma. SLIT promises an alternative method to other routes of AIT enabling patients to self-administer AIT. Objective: The study aimed to formulate fast disintegrating SLIT containing crude peanut extract for peanut-induced allergic asthma. Methods: The crude peanut extract was prepared by a simple extraction method and was subjected to quantitative and qualitative analysis. The extract was also characterised for its physical properties. The preformulation study for the extract and excipients of the tablet was performed using FT-IR spectroscopy and Differential scanning calorimetry. The tablet powder blends were characterised for pre-compression properties. The SLIT tablets were developed by direct compression and the post-compression evaluation was performed. Results: The results of the quantitative and qualitative analysis of extract confirmed the presence of peanut proteins in the extract. The preformulation studies using FT-IR spectroscopy and Differential Scanning Calorimetry revealed that there is no significant interaction between the CPE and excipients. The pre-compression characterisation showed that the powder blends had good flowproperties. Three doses of SLIT tablets were formulated with each dose containing four batches and the tablet of each dose was optimized by studying the effect of varying concentrations of super disintegrants on disintegration time and dissolution rate. The post compression characterization of the tablets was performed and the optimized batch of the three doses with the concentration of 5% crospovidone and 2% croscarmellose sodium showed less wetting time and high-water absorption ratio, shorter disintegration time of 14secs and maximum drug release of >90% within 2-3 min. Conclusion: The results indicated the suitability of formulated SLIT tablets for peanut induced allergic asthma.

Topical Probiotics: More Than a Skin Deep.

Skin, an exterior interface of the human body is home to commensal microbiota and also acts a physical barrier that protects from invasion of foreign pathogenic microorganisms. In recent years, interest has significantly expanded beyond the gut microbiome to include the skin microbiome and its influence in managing several skin disorders. Probiotics play a major role in maintaining human health and disease prevention. Topical probiotics have demonstrated beneficial effects for the treatment of certain inflammatory skin diseases such as acne, rosacea, psoriasis etc., and also found to have a promising role in wound healing. In this review, we discuss recent insights into applications of topical probiotics and their influence on health and diseases of the skin. Patents, commercially available topical probiotics, and novel probiotic impregnated fabrics have been emphasized. A thorough understanding of the relationship between probiotics and the skin microbiome is important for designing novel therapeutic approaches in using topical probiotics.

Development of spray-dried amorphous solid dispersions of tadalafil using glycyrrhizin for enhanced dissolution and aphrodisiac activity in male rats.

Tadalafil (TDL) is a phosphodiesterase-5 inhibitor (PDE5I), indicated for erectile dysfunction (ED). However, TDL exhibits poor aqueous solubility and dissolution rate, which may limit its application. This study aims to prepare amorphous solid dispersion (ASD) by spray-drying, using glycyrrhizin-a natural drug carrier. Particle and physicochemical characterizations were performed by particle size, polydispersity index measurement, yield, drug content estimation, Fourier Transformed Infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and dissolution study. In order to evaluate the aphrodisiac activity of the prepared ASD, sexual behavior study was performed in male rats. It is further considered for the stability study. Our results revealed that TDL-GLZ spray-dried dispersion was a successful drug-carrier binary mixture. XRD and SEM showed that ASD of TDL with GLZ presented in the amorphous state and dented-spherical shape, unlike the drug indicating crystalline and spiked shaped. The optimized ASD3 formulation with particle size (1.92 µm), PDI (0.32), yield (97.78%) and drug content (85.00%) showed 4.07 folds' increase in dissolution rate compared to pure TDL. The results obtained from the in vivo study exhibit significantly improved aphrodisiac activity with ASD3. The stability study revealed that the prepared ASD3 did not show any remarkable changes in the dissolution and drug content for 1 month storage at room temperature.

Rutin Attenuates Carfilzomib-Induced Cardiotoxicity Through Inhibition of NF-κB, Hypertrophic Gene Expression and Oxidative Stress.

Carfilzomib is a proteasome inhibitor, commonly used in multiple myeloma, but its clinical use may be limited due to cardiotoxicity. This study was aimed to evaluate the influence of rutin in carfilzomib-induced cardiotoxicity in rats. Wistar albino male rats weighing 200-250 g (approximately 10 weeks old) were taken for this study. Animals were divided into four groups of six animals each. Group 1 served as normal control (NC), received normal saline; group 2 animals received carfilzomib (dissolved in 1 % DMSO) alone; group 3 animals received rutin (20 mg/kg) + carfilzomib; and group 4 animals received rutin (40 mg/kg) + carfilzomib. Hematological changes, biochemical changes, oxidative stress, hypertrophic gene expression, apoptotic gene expression, NFκB and IκB-α protein expression and histopathological evaluation were done to confirm the finding of carfilzomib-induced cardiotoxicity. Treatment with rutin decreased the carfilzomib-induced changes in cardiac enzymes such as lactate dehydrogenase, creatine kinase (CK) and CK-MB. For the assessment of cardiotoxicity, we further evaluated cardiac hypertrophic gene and apoptotic gene expression such as α-MHC, ß-MHC and BNP and NF-κB and p53 gene expression, respectively, using RT-PCR. Western blot analysis showed that rutin treatment prevented the activation of NF-κB by increasing the expression of IκB-α. Rutin also attenuated the effects of carfilzomib on oxidant-antioxidant including malondialdehyde and reduced glutathione. Histopathological study clearly confirmed that rutin attenuated carfilzomib-induced cardiotoxicity in rats.

A validated high-throughput UHPLC-MS/MS assay for accurate determination of rivaroxaban in plasma sample.

Rivaroxaban is a novel, selective and potent oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. Like traditional anticoagulants, routine coagulation monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In this study, a sensitive UHPLC-MS/MS assay for rapid determination of rivaroxaban in human plasma was developed and validated. Rivaroxaban and its internal standard (IS) were extracted from plasma using acetonitrile as protein precipitating agent. An isocratic mobile phase of acetonitrile: 10 mM ammonium acetate (80:20, v/v) at a flow rate of 0.3 mL/min was used for the separation of rivaroxaban and IS. Both rivaroxaban and IS was eluted within 1 min with a total run time of 1.5 min only. Electrospray ionization source in positive mode was used for the detections of rivaroxaban and IS. Precursor to product ion transition of m/z 436.00 > 144.87 for rivaroxaban and m/z 411.18 > 191.07 for IS were used in multiple reaction monitoring mode. Developed assay was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability using official guideline on bioanalytical method.