41 research outputs found
Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons
No full textAsthma is a prevalent chronic non-communicable disease, affecting approximately 300 million people worldwide. It is characterized by significant airway inflammation, hyperresponsiveness, obstruction, and remodeling. Eosinophilic asthma, a subtype of asthma, involves the accumulation of eosinophils in the airways. These eosinophils release mediators and cytokines, contributing to severe airway inflammation and tissue damage. Emerging evidence suggests that targeting eosinophils could reduce airway remodeling and slow the progression of asthma. To achieve this, it is essential to understand the immunopathology of asthma, identify specific eosinophil-associated biomarkers, and categorize patients more accurately based on the clinical characteristics (phenotypes) and underlying pathobiological mechanisms (endotypes). This review delves into the role of eosinophils in exacerbating severe asthma, exploring various phenotypes and endotypes, as well as biomarkers. It also examines the current and emerging biological agents that target eosinophils in eosinophilic asthma. By focusing on these aspects, both researchers and clinicians can advance the development of targeted therapies to combat eosinophilic pathology in severe asthma
Gut modulator effect of methanolic extract of Solanum surattense explains its traditional use in constipation and diarrhea
No full textPapar has been withdrawn by the edito
Folkloric uses of Jatropha gossypifolia in emesis and gut motility disorders: Pharmacological validation
No full textJatropha gossypifolia is used in folkloric system to manage emesis and gastrointestinal motility disorders such as constipation and diarrhea. The present study was undertaken to provide pharmacological evidences for these folkloric uses by in vivo and in vitro experimental setting. Ethanolic extract of J. gossypifolia showed the significant antiemetic potential (p<0.05) against different emetogenic stimuli, when compared with chlorpromazine. The extract (0.01-1.0 mg/mL) on application to isolated rabbit jejunum preparation exerted spasmogenic effect, followed by the spasmolytic effect (3-10 mg/mL). In the presence of atropine, spasmogenic effect was blocked while spasmolytic effect was emerged, suggesting the involvement of muscarinic receptor activation. J. gossypifolia caused relaxation of high K+ (80 mM)-induced contraction and shifted the Ca2+ concentration-response curve to the right in a manner similar to verapamil, thus conforming its Ca2+-channel blocking activity. These findings provide pharmacological validation for the presence of antiemetic and gut modulator (spasmogenic and spasmolytic) activates, validating its folkloric uses
Pharmacological evaluation and validation for the folkloric use of Oligochaeta ramose in constipation and diarrhea
Get PDFCrude extract of Oligochaeta ramose and its fractions were studied to rationalize its traditional use in GIT disturbance. In spontaneous contracting jejunum preparation, O. ramose (0.01-1.0 mg/mL) caused a transient spasmogenic effect followed by the spasmolytic effect at higher doses (3.0-10.0 mg/mL). In atropinized jejunum preparation, O. ramose inhibit the spontaneous and K+ (80 mM)-induced contraction at the similar doses (0.01-1.0 mg/mL), suggesting calcium channel blocking effect. The calcium channel blocking effect was confirmed when pretreatment of tissue with O. ramose produced a dose-dependent shift in Ca+2 dose- response curve to the right, similar to that produced by the verapamil. Activity-directed fractionation revealed that the spasmolytic effect is concentrated in the dichloromethane fraction while, aqueous fraction contains both spasmogenic and spasmolytic constituents. This study validate the presence of both spasmogenic and spasmolytic components mediated through muscarinic receptor activation and calcium channel blockade respectively, which may explain its traditional uses in constipation and diarrhea
Probabilistic modeling and simulation of microstructural evolution in zr based bulk metallic glass matrix composites during solidification
No full text© The Minerals, Metals & Materials Society 2018. Bulk metallic glass and their composites are unique new materials which have superior mechanical and structural properties as compared to existing conventional materials. However, their mechanical behavior is dubious, unpredictable and requires extensive experimentation to draw conclusive results. In present study, which is continuation of previous work of author, a non-linear one-dimensional iterative deterministic model is combined with two-dimensional probabilistic cellular automaton method to describe nucleation and growth of primary ductile phase from melt in glassy matrix during solidification. Preliminary methodology ad philosophy of model making is described with an aim to explain the grounds on which this approach is adopted. MATLAB® is chosen as programing platform. Results indicate that the effect of incorporating all heat transfer, mass transfer and diffusion coefficients with appropriate interpolation play a vital role in refining the model and bringing it closer to actual experimental observations. Two types of hypo and hyper eutectic systems were studied with different inoculants
Cardioprotective Effect of Rumex vesicarius Linn. Leaf Extract against Catecholamine-Induced Cardiotoxicity
No full textRumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius’s therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005–0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases
Development and evaluation of ivabradine microspheres for controlled release
No full text The objective of this study was to formulate and evaluate controlled release formulations of ivabradine hydrochloride (HCl)-loaded microspheres consisting of Kollicoat MAE 100 P and ethyl cellulose prepared by the oil-in-oil solvent evaporation method. The drug was encapsulated into microspheres by an in situ method by varying the polymer contents. The resultant microspheres were characterized with respect to drug loading, flow properties, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffractometry (XRD), thermal analysis and release behavior. Chemically stable loaded microspheres were confirmed by FTIR, differential scanning calorimetry (DSC), thermogravimetric analysis and XRD. SEM images showed that the microspheres were spherical with smooth surfaces. FTIR spectra confirmed the presence of the drug in pure form and revealed no interaction between the drug and polymers. XRD and DSC were conducted to determine the nature of the drug in drug-loaded microspheres, and the results revealed that the drug was present in amorphous form. The maximum percentage entrapment efficiency was found to be 82 ± 2·11%, and the percentage yield was 89 ± 3·31%. The maximum in vitro drug release was more than 90% for pH 7·4, which demonstrated that drug-loaded formulations had a pH-dependent drug release. Cumulative drug release data were analyzed by using different kinetic models. The Korsmeyer–Peppas equation was used to determine the value of n which follows non-Fickian diffusion. </jats:p
Knowledge, attitude, preventive practices and perceived barriers to screening about colorectal cancer among university students of newly merged district, Kpk, Pakistan – A cross-sectional study
No full textExploration of the anti-inflammatory potential of Polygonum bistorta L.: protection against LPS-induced acute lung injury in rats via NF-ĸβ pathway inhibition
Get PDFTraditional medicine uses the roots and rhizomes of Polygonum bistorta L. (Polygonaceae) to treat cough, bronchitis, and other respiratory infections. Our goal was to gain insights into the lung protective effects of the roots of P. bistorta L. against lipopolysaccharide-induced acute lung injury in rats, along with the possible mechanism(s). The outcomes revealed deliberate quantities of the total phenolic and flavonoid contents of 156.2 ± 5.13 GAE/g and 179.45 ± 2.08 mg QE/g, respectively. Crude extract possesses a maximum inhibitory potential of 81.77% ± 0.62% for acetylcholinesterase against eserine. Acute oral toxicity study revealed LD50 beyond 7 g/kg. Plant extract markedly restored LPS-induced hypoxemia, pulmonary edema, histopathological alterations, and leukocyte infiltration in the lung. ELISA testing on BALF found that the plant extract efficiently reinstated superoxide dismutase, total anti-oxidant capacity, malondialdehyde, and total oxidative stress. qRT-PCR indicated a decline in the endotoxin-induced overproduction of pro-inflammatory markers, oxidative stress, transcription factor, and downregulated antioxidant potential in extract-treated groups. Furthermore, 24 metabolites were identified and quantified via GC-MS. A molecular docking procedure was implemented on the bioactive metabolites that were identified to evaluate their potential for inhibiting AChE. In conclusion, P. bistorta roots mitigate inflammation and oxidative stress by improving redox signaling and NF-ĸβ (p65) pathways and can thus play a role in strategies for overcoming therapeutic challenges
Pharmacological Validation for the Folklore Use of Ipomoea nil against Asthma: In Vivo and In Vitro Evaluation
No full textOxidative stress is the key factor that strengthens free radical generation which stimulates lung inflammation. The aim was to explore antioxidant, bronchodilatory along with anti-asthmatic potential of folkloric plants and the aqueous methanolic crude extract of Ipomoea nil (In.Cr) seeds which may demonstrate as more potent, economically affordable, having an improved antioxidant profile and providing evidence as exclusive therapeutic agents in respiratory pharmacology. In vitro antioxidant temperament was executed by DPPH, TFC, TPC and HPLC in addition to enzyme inhibition (cholinesterase) analysis; a bronchodilator assay on rabbit’s trachea as well as in vivo OVA-induced allergic asthmatic activity was performed on mice. In vitro analysis of 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) expressed as % inhibition 86.28 ± 0.25 with IC(50) 17.22 ± 0.56 mol/L, TPC 115.5 ± 1.02 mg GAE/g of dry sample, TFC 50.44 ± 1.06 mg QE/g dry weight of sample, inhibition in cholinesterase levels for acetyl and butyryl with IC(50) (0.60 ± 0.67 and 1.5 ± 0.04 mol/L) in comparison with standard 0.06 ± 0.002 and 0.30 ± 0.003, respectively, while HPLC characterization of In.Cr confirmed the existence with identification as well as quantification of various polyphenolics and flavonoids i.e., gallic acid, vanillic acid, chlorogenic acid, quercetin, kaempferol and others. However, oral gavage of In.Cr at different doses in rabbits showed a better brochodilation profile as compared to carbachol and K(+)-induced bronchospasm. More significant (p < 0.01) reduction in OVA-induced allergic hyper-responses i.e., inflammatory cells grade, antibody IgE as well as altered IFN-α in airways were observed at three different doses of In.Cr. It can be concluded that sound mechanistic basis i.e., the existence of antioxidants: various phenolic and flavonoids, calcium antagonist(s) as well as enzymes’ inhibition profile, validates folkloric consumptions of this traditionally used plant to treat ailments of respiration
