-
Archives of Razi Institute Jun 2023Validation is a Good Manufacturing Practice principle that proves any procedure, process, method, equipment, material, activity, or system actually leads to the expected...
Validation is a Good Manufacturing Practice principle that proves any procedure, process, method, equipment, material, activity, or system actually leads to the expected results. This study validates the method for the determination of free formaldehyde in biological products (including the diphtheria-tetanus vaccine and tetanus toxoid antigen). The operating procedure of this method is based on pharmacopoeial monographs. It also does not require full validation, although its suitability under the actual condition of use should be verified. Performance characterizations, such as accuracy, intra-precision (repeatability), intermediate precision (inter-precision), linearity, range, and the limit of quantitation, were investigated and calculated. Accuracy and precision were studied at different concentration levels by spiking known amounts of formaldehyde in real samples. The accuracy and precision results were expressed as the recovery and the relative standard deviation (RSD), respectively. Precision was expressed as intra-precision (repeatability) and inter-precision. Intra-precision or repeatability was performed by one operator in one day by adding three levels of concentration to the products. The inter-precision was conducted by one operator in three individual days within the same laboratory at three concentration levels. Range and linearity were assessed by investigating the correlation coefficient of the regression line between different concentrations of formaldehyde and their response. The acceptance criteria and limits were defined for these validation parameters in these biological products. The RSD for intra-day and inter-day precision studies was less than 5% in a medium concentration of linear range. At this concentration level, accuracy was 90%-110%. The method's linearity ranged between 0.0000039%-0.01% w/v of formaldehyde with a correlation coefficient of 0.9999. The results exhibited sufficient linearity, accuracy, precision, and range. Therefore, this method can be used successfully to determine free formaldehyde for biological products.
Topics: Animals; Diphtheria-Tetanus Vaccine; Tetanus Toxoid; Formaldehyde
PubMed: 38028856
DOI: 10.22092/ARI.2023.358602.2484 -
Social Science & Medicine (1982) Sep 2023This paper explores the relations between light and dark/white and black disclosed in a study of Gartnavel Royal Hospital in Glasgow, Scotland, where an old Victorian...
This paper explores the relations between light and dark/white and black disclosed in a study of Gartnavel Royal Hospital in Glasgow, Scotland, where an old Victorian lunatic asylum remains, if becoming ruined, on the same site as a modern mental healthcare campus. In-depth interview work recovering the 'spatial stories' of patients and staff, past and present, reveals a complex mixture of positive and negative memories and interpretations prompted by both the 'darkened spaces' of Old Gartnavel and the liveliness associated with both sets of spaces. These findings are framed by (a) a reading of Badiou's short monograph on Black (Badiou, 2017) and (b) an engagement with light and dark studies, both of which suggest a rebalancing of the normal valuations whereby dark/black is cast as the realm of death, everything that deadens and threatens life, whereas light/white is cast as that of life, liveliness and vitality. The scholarship here speaks to work on vitalist health geographies, agreeing that vital health-worlds can surface almost anywhere, but reminding that the fragility of such worlds can always be threatened by too much over-ordering.
Topics: Humans; Health Facilities; Hospitals, Psychiatric; Geography; Light; Mental Health Services
PubMed: 37634427
DOI: 10.1016/j.socscimed.2023.116137 -
International Journal of Pharmaceutics:... Dec 2023Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and... (Review)
Review
Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler.
PubMed: 37953972
DOI: 10.1016/j.ijpx.2023.100216 -
The Canadian Journal of Hospital... 2023Biological sex-related factors influence pharmacokinetic, pharmacodynamic, and disease processes that may affect the predictability of drug dosing and adverse effects,... (Review)
Review
BACKGROUND
Biological sex-related factors influence pharmacokinetic, pharmacodynamic, and disease processes that may affect the predictability of drug dosing and adverse effects, which may in turn have clinical consequences for patients' lives. Nonetheless, sex-related factors are not always taken into account in clinical trial design or clinical decision-making, for multiple reasons, including a paucity of studies that clearly and objectively study and measure sex-disaggregated and sex-related outcomes, as well as gaps in regulatory and policy structures for integrating these considerations.
OBJECTIVES
To complete a narrative review and use a case study to understand available evidence, inform future research, and provide policy considerations that incorporate information on sex- and gender-related factors into clinician-facing resources.
METHODS
A comprehensive review of available literature was conducted using a sex- and gender-based analysis plus (SGBA Plus) approach to identify sex- and/or gender-disaggregated information for gilteritinib, a chemotherapeutic agent. Systematic searches were performed in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus, and ClinicalTrials.gov, from inception to March 18, 2021. The information was then summarized and compared with the Canadian product monograph for this drug.
RESULTS
Of 311 records screened, 3 provided SGBA Plus information as a component of outcomes, rather than just as categories or demographic characteristics. Of these, 2 were case studies, and 1 was a clinical trial. No studies from the ClinicalTrials.gov database that were in progress at the time of this review provided details about sex-disaggregated outcomes. The Canadian product monograph did not include sex-disaggregated outcome data.
CONCLUSIONS
The available evidence from clinical trials, other published literature, and guidance documents does not provide details about sex-disaggregated outcomes for gilteritinib. This paucity of available evidence may create a challenge for clinicians who are making decisions about the efficacy and safety of prescribed therapies in sex-specific populations that have not been well studied.
PubMed: 37409151
DOI: 10.4212/cjhp.3299 -
Gualou-Xiebai-Banxia-Tang regulates liver-gut axis to ameliorate Metabolic Syndrome in HFD-fed mice.Phytomedicine : International Journal... Jan 2024Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases....
BACKGROUND
Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases. Gualou-Xiebai-Banxia-Tang decoction (GT) was first described in the Synopsis of the Golden Chamber, the earliest traditional Chinese medicine (TCM) monograph on diagnosis and treatment of miscellaneous diseases in China. According to TCM precepts, based on its ability to activate yang to release stagnation, activate qi to reduce depression, remove phlegm, and broaden the chest, GT has been used for more than 2,000 years to treat cardiovascular ailments. However, the molecular bases of its therapeutic mechanisms remain unclear.
PURPOSE
The aim of this study was to identify lipid- and glucose-related hepatic genes differentially regulated by GT, and to assess GT impact on gut microbiota composition, in mice with high-fat diet (HFD)-induced MetS.
STUDY DESIGN AND METHODS
ApoE/ mice were fed with an HFD for 24 weeks, with or without concurrent GT supplementation, to induce MetS. At the study's end, body weight, visceral fat weight, blood lipid levels, and insulin sensitivity were measured, and histopathological staining was used to evaluate hepatosteatosis and intestinal barrier integrity. Liver transcriptomics was used for analysis of differentially expressed genes in liver and prediction of relevant regulatory pathways. Hepatic lipid/glucose metabolism-related genes and proteins were detected by RT-qPCR and western blotting. Gut microbial composition was determined by 16S rRNA gene sequencing.
RESULTS
GT administration reduced MetS-related liver steatosis and weight gain, promoted insulin sensitivity and lipid metabolism, and beneficially modulated gut microbiota composition by decreasing the relative abundance of g_Lachnospiraceae_NK4A136_group and increasing the relative abundance of g_Alistipes. Liver transcriptomics revealed that GT regulated the expression of genes related to lipid and glucose metabolism (Pparγ, Igf1, Gpnmb, and Trem2) and of genes encoding chemokines/chemokine receptors (e.g. Cxcl9 and Cx3cr1). Significant, positive correlations were found for Ccr2, Ccl4, Ccr1, and Cx3cr1 and the g_Lachnospiraceae_NK4A136_group, and between Cxcl9, Ccr2, Ccl4, and Cx3cr1 and g_Desulfovibrio. GT treatment downregulated the protein expressions of SCD1 and CX3CR1 and upregulated the expression of PCK1 protein.
CONCLUSION
GT supplementation alleviates HFD-induced MetS in mice by improving hepatic lipid and glucose metabolism. The anti-metabolic syndrome effects of GT may be related to the regulation of the gut-liver axis.
PubMed: 38901285
DOI: 10.1016/j.phymed.2023.155320 -
JAMA Network Open Aug 2023Central nervous system (CNS)-penetrant systemic therapies have significantly advanced care for patients with melanoma brain metastases. However, improved understanding...
IMPORTANCE
Central nervous system (CNS)-penetrant systemic therapies have significantly advanced care for patients with melanoma brain metastases. However, improved understanding of the molecular landscape and microenvironment of these lesions is needed to both optimize patient selection and advance treatment approaches.
OBJECTIVE
To evaluate how bulk and single-cell genomic features of melanoma brain metastases are associated with clinical outcome and treatment response.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study analyzed bulk DNA sequencing and single nuclear RNA-sequencing data from resected melanoma brain metastases and included 94 consecutive patients with a histopathologically confirmed diagnosis of melanoma brain metastasis who underwent surgical resection at a single National Comprehensive Cancer Network cancer center in San Francisco, California, from January 1, 2009, to December 31, 2022.
EXPOSURE
A Clinical Laboratory Improvement Amendments-certified targeted sequencing assay was used to analyze tumor resection specimens, with a focus on BRAF V600E alteration. For frozen pathologic specimens from CNS treatment-naive patients undergoing surgical resection, commercial single nuclear RNA sequencing approaches were used.
MAIN OUTCOMES AND MEASURES
The primary outcome was overall survival (OS). Secondary outcomes included CNS progression-free survival (PFS), microenvironmental composition with decreased T-cell and macrophage populations, and responses to immunotherapy.
RESULTS
To correlate molecular status with clinical outcome, Kaplan-Meier survival analysis of 94 consecutive patients (median age, 64 years [range, 24-82 years]; 70 men [74%]) with targeted BRAF alteration testing showed worse median intracranial PFS (BRAF variant: 3.6 months [IQR, 0.1-30.6 months]; BRAF wildtype: 11.0 months [IQR, 0.8-81.5 months]; P < .001) and OS (BRAF variant: 9.8 months [IQR, 2.5-69.4 months]; BRAF wildtype: 23.2 months [IQR, 1.1-102.5 months]; P = .005; log-rank test) in BRAF V600E variant tumors. Multivariable Cox proportional hazards regression analysis revealed that BRAF V600E status was an independent variable significantly associated with both PFS (hazard ratio [HR], 2.65; 95% CI, 1.54-4.57; P < .001) and OS (HR, 1.96; 95% CI, 1.08-3.55; P = .03). For the 45 patients with resected melanoma brain metastases undergoing targeted DNA sequencing, molecular classification recapitulated The Cancer Genome Atlas groups (NRAS variant, BRAF variant, NF1 variant, and triple wildtype) with no subtype enrichment within the brain metastasis cohort. On a molecular level, BRAF V600E variant lesions were found to have a significantly decreased tumor mutation burden. Moreover, single nuclear RNA sequencing of treatment-naive BRAF V600E variant (n = 3) brain metastases compared with BRAF wildtype (n = 3) brain metastases revealed increased immune cell populations in BRAF wildtype tumors (mean [SD], 11% [4.1%] vs 3% [1.6%] CD45-positive cells; P = .04). Survival analysis of postoperative immunotherapy responses by BRAF status revealed that BRAF wildtype lesions were associated with a response to checkpoint inhibition (median OS: with immunotherapy, undefined; without immunotherapy, 13.0 months [range, 1.1-61.7 months]; P = .001; log-rank test) while BRAF variant lesions (median OS: with immunotherapy, 9.8 months [range, 2.9-39.8 months]; without immunotherapy, 9.5 months [range, 2.5-67.2 months]; P = .81; log-rank test) were not.
CONCLUSIONS AND RELEVANCE
This molecular analysis of patients with resected melanoma brain metastases found that BRAF V600E alteration is an important translational biomarker associated with worse clinical outcomes, differential microenvironmental composition, and benefit from immunotherapy. Patients with BRAF V600E variant melanoma brain metastases may thus benefit from alternative CNS-penetrant systemic regimens.
Topics: Male; Humans; Middle Aged; Cohort Studies; Proto-Oncogene Proteins B-raf; Brain Neoplasms; Immunotherapy; Melanoma; Tumor Microenvironment
PubMed: 37589977
DOI: 10.1001/jamanetworkopen.2023.29186 -
Frontiers in Nutrition 2024The French maritime pine bark extract Pycnogenol is a proprietary product from Aiton. It complies with the quality specifications in the monograph "Pine extract" in... (Review)
Review
The French maritime pine bark extract Pycnogenol is a proprietary product from Aiton. It complies with the quality specifications in the monograph "Pine extract" in the section of dietary supplements. Pycnogenol is standardized to contain 65-75% procyanidins which are a variety of biopolymers consisting of catechin and epicatechin monomeric units. The effects of Pycnogenol have been researched in a multitude of human studies. The basis for any activity is the bioavailability of constituents and metabolites of the extract. General principles of compound absorption, distribution, metabolism and elimination as well as specific data from studies with Pycnogenol are summarized and discussed in this review. Based on plasma concentration profiles it can be concluded that low molecular weight constituents of the extract, such as catechin, caffeic and ferulic acid, taxifolin are readily absorbed from the small intestine into systemic circulation. Procyanidin oligomers and polymers are subjected to gut microbial degradation in the large intestine yielding small bioavailable metabolites such as 5-(3',4'-dihydroxyphenyl)-γ-valerolactone. After intake of Pycnogenol, constituents and metabolites have been also detected in blood cells, synovial fluid and saliva indicating a substantial distribution in compartments other than serum. In studies simultaneously investigating concentrations in different specimen, a preferential distribution of individual compounds has been observed, e.g., of ferulic acid and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone into synovial fluid compared to serum. The main route of elimination of constituents and metabolites of the French pine bark extract is the renal excretion. The broad knowledge accumulated regarding the pharmacokinetics of compounds and metabolites of Pycnogenol constitute a rational basis for effects characterized on a cellular level and observed in human clinical studies.
PubMed: 38757126
DOI: 10.3389/fnut.2024.1389422 -
World Neurosurgery Jun 2024Sir William Macewen, a Scottish surgeon, made significant contributions to neurosurgery, beginning with his successful brain tumour resection in 1879. Born in 1848,... (Review)
Review
Sir William Macewen, a Scottish surgeon, made significant contributions to neurosurgery, beginning with his successful brain tumour resection in 1879. Born in 1848, Macewen's upbringing in a maritime family fostered a practical approach to learning. Macewen's pivotal brain tumour surgery demonstrated his adherence to antiseptic practices and precise localisation techniques. Controversy arose regarding his precedence in neurosurgery, which he addressed through meticulous documentation and public presentations. His diagnostic prowess extended to cases of cerebral abscesses and intracranial conditions, relying on clinical observations rather than imaging technology. His 1893 monograph on brain infections remains influential in neurosurgery. Beyond neurosurgery, Macewen innovated in asepsis, hernia repair, and bone surgery. His legacy as a clinical educator and advocate for surgical advancements earned him widespread recognition. This historical review aims to explore and evaluate the published literature regarding Macewen's early brain tumour surgeries, seeking to establish his precedence over later surgeons like Godlee and Bennett.
PubMed: 38852713
DOI: 10.1016/j.wneu.2024.06.006 -
Saudi Pharmaceutical Journal : SPJ :... Dec 2023India has a sparkling pharmaceutical sector that holds a distinguished place by producing and supplying high-quality and affordable medicines across the globe. Ensuring... (Review)
Review
India has a sparkling pharmaceutical sector that holds a distinguished place by producing and supplying high-quality and affordable medicines across the globe. Ensuring the quality and safety of the marketed medicinal products is one of the most important components of the drug regulatory framework and assessment of the quality of medicines is usually achieved by referring to the public standards of the official Pharmacopoeia. In India, the Indian Pharmacopoeia (IP) is published at regular intervals to fulfill the requirements of the Drugs and Cosmetics Act, 1940 to ensure the quality of medicines being manufactured and/or marketed in India. The present article aims to provide an overview of the history of the IP, its standards-setting process, and the current status of monographs in the 9th edition of the IP 2022. Special focus is placed on the newly added and upgraded general chapters and monographs within the IP 2022. There are a total of 223 general chapters and 3152 drug monographs available under various categories in the IP 2022. This study also highlights a total of 92 new drug monograph additions and 412 monograph revisions in the IP 2022. It is anticipated that the standards laid down in the IP 2022 will play an imperative role in delivering quality medicines to patients within and outside India.
PubMed: 37965488
DOI: 10.1016/j.jsps.2023.101825 -
Journal of Medical Biography Oct 2023Dr Graham Steell, MB CM MD FRCP (1851-1942), an Edinburgh graduate, was a physician at the Manchester Royal Infirmary (1878-1911) and professor of medicine at the...
Dr Graham Steell, MB CM MD FRCP (1851-1942), an Edinburgh graduate, was a physician at the Manchester Royal Infirmary (1878-1911) and professor of medicine at the Victoria Manchester University (1907-1911). He is mainly remembered for describing the 'Graham Steel murmur', however his name is also associated with the 'Graham Steell monaural stethoscope', which he designed. His clinical examination of the cardiovascular system at the bedside was meticulous, using only his stethoscope, percussion hammer, and a sphygmograph to record the radial pulse. His work is described in his monograph, (1906) and other numerous papers. The University of Manchester Museum of Medicine and Health has a collection of monaural stethoscopes, percussors and sphygmographs. This article explores Dr Steell's clinical techniques and contribution to cardiology in an era before chest X-rays and electrocardiography, and also discusses the use of monaural stethoscopes and percussion hammers by the wider medical profession during the Victorian and Edwardian period.
PubMed: 37797176
DOI: 10.1177/09677720231203384