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There is no agreement as regards the nature of the acetylcholine-atropine antagonism, that is whether it is competitive or 'not competitive'. An attempt was made previously by the author (1964) to settle this issue by determining the pA and pA values but the results did not indicate unequivocally that the antagonism is competitive. In the present work, six pA values, namely, pA, pA, pA, pA, pA and pA have been determined. Two more pA values, namely, pA and pA have also been determined. The results provide an overwhelming evidence to say that the acetylcholine-atropine antagonism is competitive. Why a compound like atropine which antagonizes acetylcholine competitively even at the level of its pA-pA values does not do so at the lower level of pA-pA (or pA-pA) values still remains an unsolved problem. In the study of drug antagonism, such a large series of pA values and such high pA values for a pair of compounds have keen determined for the first time by the author. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is frequently associated with musculoskeletal complications, including sarcopenia and osteoporosis, which substantially impair patient quality of life. Despite these clinical observations, the molecular mechanisms linking AD to bone loss remain insufficiently explored. In this study, we examined the femoral bone microarchitecture and transcriptomic profiles of APP/PS1 transgenic mouse models of AD to elucidate the disease's impact on bone pathology and identify potential gene candidates associated with bone deterioration. We performed micro-computed tomography (microCT) and RNA transcriptome analysis on the femoral bone of these mice. We observed a significant reduction in bone microstructure in both male and female APP/PS1 mice compared to their wild-type counterparts. Transcriptomic analysis of femoral bone tissue revealed substantial differential gene expression between AD mice and controls. Specifically, APP/PS1 mice exhibited differential expression in 289 protein-coding genes across both sexes. Notably, in female APP/PS1 mice, 664 genes were differentially expressed, with key genes such as Shh, Efemp1, Arg1, EphA2, Irx1, and PORCN potentially implicated in bone loss. In male APP/PS1 mice, 787 genes were differentially expressed, with Sel1l, Ffar4, Hspa1a, AMH, WFS1, and CLIC1 emerging as notable candidates in the context of bone deterioration. Gene Ontology (GO) enrichment analysis further revealed distinct sex-specific gene pathways between male and female APP/PS1 mice, underscoring the differential molecular underpinnings of bone pathology in AD. This study identifies novel sex-specific genes in the APP/PS1 mouse model and proposes potential therapeutic targets to mitigate bone loss in AD patients., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that there is no other conflict of interest regarding the publication of this manuscript. F.D declares that he is an Associate Editor of Geroscience., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Joint hypermobility syndrome (JHS) and Ehlers-Danlos Syndrome (EDS) are connective tissue disorders characterized by increased joint laxity, affecting musculoskeletal health and quality of life. In this study, we explored recent trends in surgical treatment of shoulder instability among patients with these disorders., Methods: We searched the PearlDiver Mariner database, which includes deidentified US all-payer claims data from 2010 to 2020. We used procedure and diagnostic codes for EDS and JHS to select patients. The primary outcome was the yearly trend in relative utilization of the following 4 shoulder instability procedures: arthroscopic stabilization, Latarjet coracoid transfer, open capsulolabral repair, and open capsulolabral shift., Results: Among 109,274 patients with EDS and 453,885 with JHS, 3.4% and 0.8% underwent shoulder instability procedures, respectively. Arthroscopic stabilization was the predominant treatment, with a mean utilization rate of 78% for EDS and 83% for JHS. Notably, the age at surgery increased for EDS patients but decreased for JHS patients. Female patients represented large proportions of those undergoing procedures in both the EDS group (83%) and the JHS group (77%)., Conclusions: Our findings indicate a consistent preference for arthroscopic stabilization in treating shoulder instability in patients with EDS and JHS. The trends in age suggest shifts in treatment strategies, possibly influenced by advancements in nonoperative interventions or varying symptom severity. The higher proportion of female patients aligns with the known prevalence of connective tissue disorders in women. Future research should explore outcomes, complications, and specific EDS subtypes to guide optimal treatment strategies for these challenging connective tissue disorders., (© 2024 Published by Elsevier Inc. on behalf of American Shoulder and Elbow Surgeons.)

Aging is a major risk factor for multiple chronic disorders in the elderly population, including Alzheimer's disease (AD) and Osteoporosis. AD is a progressive neurodegenerative disease characterized by memory loss. In addition to dementia, several studies have shown that AD patients experience an increased rate of musculoskeletal co-morbidities, such as osteoporosis. Since tissue-specific macrophages contribute to both diseases, this study analyzed the microglia transcriptome of AD mice to determine a common gene signature involved in osteoclast biology. After comparing differentially regulated genes from GEO data sets (GSE93824 and GSE212277), there were 35 common upregulated genes and 89 common downregulated genes. Of these common genes, seven genes are known to play an important role in bone homeostasis. CSF1, SPP1, FAM20C, and Cst7 were upregulated and are associated with osteoclastogenesis and inflammation. Among the downregulated genes, LILRA6, MMP9, and COL18A1 are involved in bone formation and osteoclast regulation. We further validated some of these genes (CSF1, Cst7, and SPP1) in the cortex and the bone of AD mice models. The dysregulation of these microglial genes in AD might provide insights into the co-occurrence of AD and osteoporosis and offer potential therapeutic targets to combat disease progression., Competing Interests: Declaration of competing interest The authors also declare that there is no other conflict of interest regarding the publication of this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Sarcopenia is a medical condition that progressively develops with age and results in reduced skeletal muscle mass, alteration in muscle composition, and decreased muscle strength. Several clinical studies suggested that sarcopenia disproportionally affects males and females with age. Despite this knowledge, the molecular mechanism governing the pathophysiology is not well understood in a sex-specific manner. In this study, we utilized human gastrocnemius muscles from males and females to identify differentially regulated genes with age. We found 269 genes with at least a twofold expression difference in the aged muscle transcriptome. Among the female muscle samples, there were 239 differentially regulated genes, and the novel protein-coding genes include KIF20A, PIMREG, MTRNR2L6, TRPV6, EFNA2, RNF24, and SFN. In aged male skeletal muscle, there were 166 differentially regulated genes, and the novel-protein coding genes are CENPK, CDKN2A, BHLHA15, and EPHA. Gene Ontology (GO) enrichment revealed glucose catabolism, NAD metabolic processes, and muscle fiber transition pathways that are involved in aged female skeletal muscle, whereas replicative senescence, cytochrome C release, and muscle composition pathways are disrupted in aged male skeletal muscle. Targeting these novels, differentially regulated genes, and signaling pathways could serve as sex-specific therapeutic targets to combat the age-related onset of sarcopenia and promote healthy aging., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Traditional medicine in form of decoctions has been known for ages to possess wound healing abilities. One such traditional formulation mentioned in Indian literature Charak Samhita Chikitsa Sthanam is Kampillakadi Taila and tremendous information is available on its implication in the treatment of skin cuts and wounds, diseases, or bacterial infections. This research paper focuses on studying the wound healing property of one such herbal proprietary formulation known as a wound healing oil, derived from Kampillakadi Taila fortified with root extract of Wagatea spicata (VIKHPF)., Objective: The current research is aimed at studying chemical profiling, antioxidant activity, antimicrobial efficacy, in-vitro cell proliferating, and in-vitro wound healing activity of this VKHPF., Materials and Methods: The chemical characterization of VKHPF was done by gas chromatography- fatty acid methyl esters GC-FAME analysis for lipid analysis and gas chromatography high-resolution mass spectrometry (GC-HRMS)for revealing its chemical constituents. Proliferation and migration are two underlying mechanisms involved in the healing of wounds. Hence, in-vitro studies such as cell proliferation assay and in-vitro scratch test on NIH/3T3 mice fibroblast cell line were conducted were used to determine in-vitro wound healing capacity of VKHPF. The oil was also tested for antioxidant effect (DPPH assay) and anti-microbial potential (Time kill test)., Results: The GC-HRMS and GC-FAME analyses revealed rich medicinally important fatty acids and vitamins were present in VKHPF, such as oleic acid, hexadecanoic acid, squalene, α, γ-tocopherol, γ-sitosterol, and benzoic acid. VKHPF at 0.5 mg/ml in media without serum showed 164.00 ± 0.011% cell viability with 64.00% cell proliferation in contrast to media containing serum (100% cell viability). At the same concentration, the wound closure was 98% for VKHPF. The oil sample possessed antioxidant activity with an IC 50 value of 3.5 mg/ml and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa when tested using Time Kill Activity., Conclusion: This study is the first to report the use of Vakeri fortified Kampillakadi Taila herbal proprietary formulation (VKHPF) in in-vitro wound healing and the present data suggest that it can form a part of modern medicine., Competing Interests: Declaration of competing interest The authors declare no conflicting interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The present study was designed to evaluate the effect of sodium copper chlorophyllin (SCC) in adenine-induced chronic kidney disease (CKD). CKD was induced in male Wistar rats by feeding 0.3% w/w adenine diet for 28 days. After induction, animals were treated with sodium copper chlorophyllin at dose 2.7, 5.4, and 10.8 mg/kg for the next 28 days. The biochemical and urines parameters like creatinine, blood urea nitrogen (BUN), albumin, total protein creatinine clearance, urea clearance, and glomerular filtration rate were assessed on days 0, 14, and 28. Plasma TGF-β1, COX-2, and IL-6 levels were assessed. Various oxidative stress parameters and TGF-β1 expression were determined in the kidney. Histopathology of the kidney was studied with different stains. Sodium copper chlorophyllin-treated animals showed a significant reduction in urine output and relative kidney weight. The treatment with sodium copper chlorophyllin significantly improved kidney function by normalizing biochemical and urine parameters. Treatment with SCC significantly reduced circulatory inflammatory mediators-TGF-β1, COX-2, and IL-6. Additionally, the treatment also significantly reduced oxidative stress and TGF-β1 expression in kidney tissues. Histopathology studies showed inhibition in the kidney damage due to the treatment of SCC. The sodium copper chlorophyllin treatment attenuated adenine-induced chronic kidney disease in rats.

A simple, accurate, and precise bioanalytical method was developed and validated for the determination of pharmacokinetic parameters of sodium copper chlorophyllin, a USFDA approved food additive and colorant in rat plasma. The column used was Luna ® C 18 250×4.6 mm, 100 Å, having particle size 4.5 μm, and the mobile phase used was methanol (MeOH), and 10 mM ammonium acetate buffer in the ratio of 90 : 10, the flow rate was 1 ml/min, and the injection volume of 20 μL. The retention time of sodium copper chlorophyllin was obtained at 9 min. The method was found to be linear at the range of 0.50-8.00 μg mL -1 ., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

HEp2 cells persistently infected with measles virus were treated with trypsin to remove haemagglutinin (HA) and examined unfixed or fixed in acetone by fluorescent antibody methods, comparing those sera specific for structural antigens of the virus. Staining patterns combined with the blocking of specific immunofluorescence indicated that IgG specific for measles virus haemolysin could be recognized in multiple sclerosis (MS) sera and that in some sera from which rheumatoid factor had been removed, a residual IgM (MS-IgM) was absorbed to measles virus-infected cells and showed the same specificity in blocking tests as measles virus anti-haemolysin. MS-IgM could be removed from sera by absorption with latex particles coated with human IgG and would seem to be anti-globulin with preferential affinity for anti-haemolysin.

Four conditional-lethal temperature-sensitive mutants of RS virus were detected among the progeny of 454 plaques derived from virus grown in the presence of 10(-4)m 5-fluorouridine. These mutants were stable (reversion frequency, 10(-5.0) or less and failed to produce plaques at 38 or 39 C. Plaquing efficiency was depressed 100-fold or more at 37 C. Variable suppression of growth at the restrictive temperature of 39 C was observed, ranging from 16-fold to complete suppression. The temperature-sensitive defect of three of the mutants appeared to affect functions which were expressed late in the replicative cycle. One of the mutants produced atypical nonsyncytial plaques.