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International Journal of Clinical... Jun 2024There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney...
OBJECTIVE
There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney dysfunction. The aim was to determine favipiravir pharmacokinetics (oral, 1,600 mg, q12h on day 1, then 600 mg, q12h for 4 days) in critically ill COVID-19 patients with kidney dysfunction and to compare those with observations reported in healthy adults.
MATERIALS AND METHODS
In a descriptive study, blood samples taken from patients meeting the relevant criteria (estimated glomerular filtration rate < 60 mL/min) were collected and analyzed. Analysis of blood samples was done by high performance liquid chromatography (HPLC), and the maximal concentration (C), the time of maximal concentration (t), half-life (T) and area under the curve (AUC) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration.
RESULTS
Based on analysis of samples collected in 7 patients, the C (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T (5.8 vs. 4.8 hours) longer, t delayed, while total exposure was lower (AUC: 192.53 vs. 446.09 μg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5.
CONCLUSION
In patients with kidney dysfunction related to COVID-19, favipiravir did not reach the expected exposure. This may be due to poorer and delayed absorption, and subsequent altered disposition. Population pharmacokinetic and mechanistic studies are needed to better explore the relevant covariates and to determine the optimal dose in these patients, as this drug is likely of relevance for other indications.
PubMed: 38920081
DOI: 10.5414/CP204496 -
Combinatorial Chemistry & High... Jun 2024The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are...
BACKGROUND
The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore,this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY.
OBJECTIVE
The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS.
METHODS
In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB).
RESULTS
The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses.
CONCLUSION
In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.
PubMed: 38920065
DOI: 10.2174/0113862073294620240527102409 -
Journal of Mother and Child Feb 2024Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an...
BACKGROUND
Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an autosomal dominant inheritance with variable expressivity.
METHODS
The study group consisted of 24 consecutive patients (13 males and 11 females) with VWS operated on at a single center between 2009 and 2022. They suffered from: bilateral cleft lip and palate - 6 patients; unilateral cleft lip and palate - 9 patients; cleft lip - 1 patient; and isolated cleft palate - 8 patients.
RESULTS
In 16 (66%) cases pits of lower lip occurred on both side of midline, while in 8 (34%) the pits were detected unilaterally. The primary cleft repairs were performed according to one-stage principle at the mean age of 8.6 months (SD 1.4, range 6-12). In all patients lower lip pits repairs were performed after the primary cleft repairs as a separate procedure at the mean age of 37 months (SD 11.3 range 14-85). The mean number of all primary repairs of the syndrome-both cleft defect and lower lip pits repairs-was 2.46. Nine patients (37.5%) required additional secondary corrections of the lower lip due to the poor aesthetic post-operative outcome.
CONCLUSIONS
The frequent need for secondary corrections of residual lower lip deformities indicates the considerable difficulties in obtaining a satisfactory outcome of the repairs to lip pits caused by VWS. The average number of the primary surgical interventions in evaluated material remained low.
Topics: Humans; Cleft Lip; Female; Cleft Palate; Male; Retrospective Studies; Lip; Abnormalities, Multiple; Child, Preschool; Infant; Child; Treatment Outcome; Plastic Surgery Procedures; Cysts
PubMed: 38920016
DOI: 10.34763/jmotherandchild.20242801.d-24-00020 -
Food & Function Jun 2024The increasing prevalence of obesity and type 2 diabetes (T2D) signifies the failure of conventional treatments for these diseases. The gut microbiota has been proposed...
The increasing prevalence of obesity and type 2 diabetes (T2D) signifies the failure of conventional treatments for these diseases. The gut microbiota has been proposed as a key player in the pathophysiology of diet-induced T2D. Urolithin B (Uro B), a gut microbiota-derived polyphenol metabolite, exerts several beneficial health effects. In this study, we investigated the metabolic effects of Uro B on high-fat/high-sucrose (HFHS)-fed mice and determined whether its antidiabetic effects are related to the modulation of the gut microbiota. C57BL/6J mice were fed either a chow or HFHS diet. HFHS-fed mice were administered daily with either a vehicle (water) or different doses of Uro B (100 or 200 mg kg) for eight weeks. The composition of the gut microbiota was assessed by 16S rRNA sequencing. The results showed that Uro B treatment reduced HFHS-induced weight gain and visceral obesity and decreased liver weight and triglyceride accumulation associated with blunted hepatic oxidative stress and inflammation. Furthermore, Uro B administration improved insulin sensitivity as revealed by improved insulin tolerance, a lower homeostasis model assessment of insulin resistance, and decreased glucose-induced hyperinsulinemia during the oral glucose tolerance test. Uro B treatment was found to lower the intestinal triglyceride content and alleviate intestinal inflammation and oxidative stress. Remarkably, Uro B treatment markedly increased the proportion of the mucin-degrading bacterium in metagenomic samples. In conclusion, Uro B exerts beneficial metabolic effects by alleviating HFHS diet-induced features of metabolic syndrome, which is associated with a proportional increase in the population of spp.
PubMed: 38920000
DOI: 10.1039/d4fo02545h -
Journal of Medicinal Food Jun 2024Probiotics are well-known to be directly or indirectly involved in the host immune system. In this study, we analyzed the immune-boosting effects of lactic acid...
Probiotics are well-known to be directly or indirectly involved in the host immune system. In this study, we analyzed the immune-boosting effects of lactic acid bacteria, including and , in immunocompetent C57BL/6J mice. Three different lactic acid bacteria strains were orally administered to C57BL/6J mice for 8 weeks. Then, liver, spleen, and whole blood were harvested after sacrificing the animals. There were no significant changes in whole-body weight, weight of organs, or complete blood cell count by oral administration of lactic acid bacteria. The frequencies of CD3, CD4, and CD8 T cells were significantly increased in the MG5462 group compared to control. The frequency of NK1.1 cells was significantly increased in the MG5474 group compared to control. On the other hand, splenocyte proliferations and natural killer cytotoxicity did not differ between groups. In addition, the MG5462 group had a significant increase in the production of TNF-α compared to the control, which is consistent with the upregulation of T cells in the MG5462 group. Therefore, could be a functional food additive to boost immunity by positively affecting T cell populations.
PubMed: 38919987
DOI: 10.1089/jmf.2024.k.0085 -
Case Reports in Dentistry 2024Managing dental care in children with special health care needs poses distinct challenges. This case report explores these challenges within the context of a 9-year-old...
BACKGROUND
Managing dental care in children with special health care needs poses distinct challenges. This case report explores these challenges within the context of a 9-year-old boy with Down syndrome (DS) facing dental treatment refusal. Over ten months and 13 visits, a tailored approach was devised for the patient who presented with multiple cavities and retained primary teeth. Key strategies included gradually introducing dental procedures, including tooth brushing, intraoral examination, tooth preparation, extraction, and myofunctional therapy. Behaviour guidance techniques include tell-show-do, desensitization, positive reinforcement, and close collaboration between dental professionals and the patient's mother. This methodical approach helped overcome the child's initial refusal without sedation or general anaesthesia, facilitating successful dental care.
CONCLUSION
This case emphasizes the effectiveness of patient-centred strategies and detailed communication in pediatric dentistry for children with DS, providing valuable insights for managing similar challenges in dental care.
PubMed: 38919976
DOI: 10.1155/2024/2966972 -
Heliyon Jun 2024Periodontal disease is highly prevalent in both humans and dogs. Although there have been reports of cross-infection of periodontopathic bacteria, methods for assessing...
Periodontal disease is highly prevalent in both humans and dogs. Although there have been reports of cross-infection of periodontopathic bacteria, methods for assessing it have yet to be established. The actual status of cross-infection remains to be seen. The purpose of this study was to evaluate the utility of bacterial DNA and serum immunoglobulin G (IgG) antibody titer assays to assess infection of human-pathogenic and dog-pathogenic species in dogs. Four experimental beagles were used for establishing methods. Sixty-six companion dogs at veterinary clinics visiting for treatment and prophylaxis of periodontal disease were used and divided into healthy, gingivitis, and periodontitis groups. Periodontal pathogens such as and were investigated as target bacteria. DNA levels of both bacteria were measured using species-specific primers designed for real-time polymerase chain reaction (PCR). Serum IgG titers of both bacteria were measured by enzyme-linked immunosorbent assay (ELISA). PCR primers were confirmed to have high sensitivity and specificity. However, there was no relationship between the amount of bacterial DNA and the severity of the periodontal disease. In addition, dogs with periodontitis had higher IgG titers against both bacteria compared to dogs in the healthy and gingivitis groups; there was cross-reactivity between the two bacteria. Receiver operating characteristic (ROC) analysis of IgG titers against both bacteria showed high sensitivity (>90 %) and specificity (>75 %). Since both bacteria were distinguished by DNA assays, the combination of these assays may be useful in the evaluation of cross-infection.
PubMed: 38919974
DOI: 10.1016/j.heliyon.2024.e31872 -
HemaSphere Jun 2024Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red...
Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted < 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight-week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted < 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.
PubMed: 38919958
DOI: 10.1002/hem3.109 -
Frontiers in Genetics 2024Periodontitis, a common chronic inflammatory disease, significantly impacted oral health. To provide novel biological indicators for the diagnosis and treatment of...
INTRODUCTION
Periodontitis, a common chronic inflammatory disease, significantly impacted oral health. To provide novel biological indicators for the diagnosis and treatment of periodontitis, we analyzed public microarray datasets to identify biomarkers associated with periodontitis.
METHOD
The Gene Expression Omnibus (GEO) datasets GSE16134 and GSE106090 were downloaded. We performed differential analysis and robust rank aggregation (RRA) to obtain a list of differential genes. To obtain the core modules and core genes related to periodontitis, we evaluated differential genes through enrichment analysis, correlation analysis, protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network analysis. Potential biomarkers for periodontitis were identified through comparative analysis of dual networks (PPI network and ceRNA network). PPI network analysis was performed in STRING. The ceRNA network consisted of RRA differentially expressed messenger RNAs (RRA_DEmRNAs) and RRA differentially expressed long non-coding RNAs (RRA_DElncRNAs), which regulated each other's expression by sharing microRNA (miRNA) target sites.
RESULTS
RRA_DEmRNAs were significantly enriched in inflammation-related biological processes, osteoblast differentiation, inflammatory response pathways and immunomodulatory pathways. Comparing the core ceRNA module and the core PPI module, C1QA, CENPK, CENPU and BST2 were found to be the common genes of the two core modules, and C1QA was highly correlated with inflammatory functionality. C1QA and BST2 were significantly enriched in immune-regulatory pathways. Meanwhile, LINC01133 played a significant role in regulating the expression of the core genes during the pathogenesis of periodontitis.
CONCLUSION
The identified biomarkers C1QA, CENPK, CENPU, BST2 and LINC01133 provided valuable insight into periodontitis pathology.
PubMed: 38919957
DOI: 10.3389/fgene.2024.1398582 -
Frontiers in Medicine 2024Systemic administration of corticosteroids is used in the treatment of chronic eosinophilic pneumonia (CEP). However, in patients with CEP as well as other...
Systemic administration of corticosteroids is used in the treatment of chronic eosinophilic pneumonia (CEP). However, in patients with CEP as well as other comorbidities, the adverse effects of corticosteroids should be minimized as much as possible. A 71-year-old woman was presented with aggravating asthma with CEP and sinusitis, and she had uncompensated liver cirrhosis (LC) with a Child-Pugh score of 7. Initial treatment with a low dose of oral corticosteroids (OCSs) in combination with tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody, resulted in rapid improvement of asthma and CEP without deteriorating LC. Sinusitis also improved after ceasing OCS. This case suggested that tezepelumab may be useful as a treatment option for patients with CEP, especially those with liver dysfunction.
PubMed: 38919941
DOI: 10.3389/fmed.2024.1381261