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Frontiers in Pharmacology 2024The available evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their interconversion hinder...
Unraveling the interconversion pharmacokinetics and oral bioavailability of the major ginger constituents: [6]-gingerol, [6]-shogaol, and zingerone after single-dose administration in rats.
BACKGROUND
The available evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their interconversion hinder understanding of their influence on the pharmacokinetic profiles.
PURPOSE
This study presents the first comprehensive investigation aiming to determine the interconversion pharmacokinetics in rats, and elucidate the oral bioavailability, target distribution, biotransformation, and excretion profiles of the key ginger constituents, [6]-gingerol, [6]-shogaol, and zingerone.
METHODS
The pharmacokinetics was investigated through single intravenous (3 mg/kg) or oral (30 mg/kg) administration of [6]-gingerol, [6]-shogaol, or zingerone, followed by the determination of their tissue distribution after oral dosing (30 mg/kg). Intravenous pharmacokinetics was leveraged to evaluate the interconversion, circumventing potential confounders associated with the oral route.
RESULTS
All rats tolerated these compounds throughout the pharmacokinetic study. The parent compounds exhibited rapid but partial absorption, and extensive organ distribution with substantial biotransformation, thereby limiting the oral bioavailability of each compound to below 2% when administered as pure compounds. Conversion of [6]-gingerol to [6]-shogaol after intravenous administration, demonstrated a significantly larger clearance compared to the reverse conversion ([6]-shogaol to [6]-gingerol). The irreversible metabolic clearance for both compounds was significantly greater than their reversible bioconversions. Furthermore, [6]-gingerol underwent biotransformation to zingerone. Conjugated glucuronides were eliminated partly through renal excretion, with minimal fecal excretion.
CONCLUSION
This investigation demonstrates the influence of interconversion on the disposition kinetics of [6]-gingerol, [6]-shogaol, and zingerone, as evidenced by the findings in the systemic circulation. The study further highlights the importance of considering this interconversion and tissue distribution when determining the administration dosage of ginger constituent combinations for therapeutic benefits and clinical applications.
PubMed: 38904001
DOI: 10.3389/fphar.2024.1391019 -
Frontiers in Pharmacology 2024Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of...
Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Nine Sprague Dawley rats were divided into three groups: paclitaxel ( = 3), albumin-paclitaxel nano-particles (APNs; = 3), and liposome-encapsulated APNs ( = 3). [I]Iodo-paclitaxel ([I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using -butylstannyl substituted paclitaxel as the precursor. Albumin-[I]iodo-paclitaxel nanoparticles ([I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.
PubMed: 38904000
DOI: 10.3389/fphar.2024.1381406 -
International Journal of Medical... 2024Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression.
Topics: Humans; Dexmedetomidine; Anesthesia, Spinal; Male; Female; Adult; Hypnotics and Sedatives; Middle Aged; Double-Blind Method; Infusions, Intravenous; Benzodiazepines; Anesthesia Recovery Period; Hemodynamics; Conscious Sedation
PubMed: 38903925
DOI: 10.7150/ijms.95736 -
Frontiers in Veterinary Science 2024Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic...
Updates on antifungal pharmacotherapy in elasmobranchs: pharmacokinetics of 4 mg/kg voriconazole after IM and IV administration in undulate skates () maintained under human care.
INTRODUCTION
Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic medications that can ensure both effectiveness and safety when administered to this group of animals. The empirical prescription of azole antifungal agents, particularly voriconazole, has been posited as a potentially efficacious treatment approach for addressing most common mycoses in sharks and rays. However, there are still no published pharmacokinetic studies supporting its use in elasmobranchs and there is a lack of scientific base for its utilization in elasmobranchs.
METHODS
For this study, voriconazole was administered intravenously (IV) and intramuscularly (IM), at a single dose of 4 mg/kg to six adult undulate skates (). A washout period of 8 weeks was left between each route of administration. Blood samples were collected both before and at ten predetermined intervals after each dosing (0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, and 36 h after drug administration). Plasma concentrations were quantified using a validated high-performance liquid chromatography method, and pharmacokinetic (PK) data was analyzed through non-compartmental methods.
RESULTS
The mean extrapolated concentration at 0 h (C) after IV administration was 27.19 ± 7.15 μg/mL and the mean peak plasma concentrations (C) ± SEM after IM administration resulted 2.98 ± 0.28 μg/mL at a mean time to maximum concentration (T ) of 1.33 ± 0.17 h. Terminal half-lives were calculated and resulted 11.18 ± 1.32 h for IV injections and 9.59 ± 1.38 h for IM injections. The area under the curve extrapolated to infinity was determined as 58.14 ± 2.79 h·μg/ml following IV injections and 37.60 ± 6.67 h·μg/ml following IM injections. The IM-administered voriconazole exhibited a mean absolute bioavailability of 64.67 ± 11.47%.
DISCUSSION
These discoveries provide backing for the possible application of voriconazole through the intramuscular route in undulate skates and support using lower dosage regimens compared to those required for oral administration, emphasizing the importance of conducting further pharmacokinetic studies with antifungals in elasmobranchs.
PubMed: 38903684
DOI: 10.3389/fvets.2024.1376851 -
NPJ Biofilms and Microbiomes Jun 2024Helicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori... (Review)
Review
Helicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori infection have been proven to be therapeutically insufficient, with low eradication rates and high recurrence rates. Emerging evidence suggests that antibiotic therapy for H. pylori can lead to gastrointestinal and subsequent vaginal dysbiosis, posing challenges for conventional antibiotic approaches. Thus, this article proposes a novel probiotic therapy involving simultaneous oral and intra-vaginal probiotic administration alongside antibiotics for H. pylori treatment, aiming to enhance eradication rates and mitigate dysbiosis. We begin by providing an overview of gastrointestinal and vaginal microbiota and their interconnectedness through the vagina-gut axis. We then review the efficacy of current antibiotic regimens for H. pylori and discuss how antibiotic treatment impacts the vaginal microenvironment. To explore the feasibility of this approach, we evaluate the effectiveness of oral and intra-vaginal probiotics in restoring normal microbiota in the gastrointestinal and vaginal tracts, respectively. Additionally, we analyze the direct mechanisms by which oral and intra-vaginal probiotics act on their respective tracts and discuss potential cross-tract mechanisms. Considering the potential synergistic therapeutic effects of probiotics in both the gastrointestinal and vaginal tracts, dual-channel probiotic therapy holds promise as a more effective approach for H. pylori eradication and dysbiosis mitigation, presenting a novel concept in the collaborative treatment of gastrointestinal and genital disorders.
Topics: Probiotics; Female; Humans; Dysbiosis; Anti-Bacterial Agents; Helicobacter Infections; Vagina; Helicobacter pylori; Administration, Intravaginal; Administration, Oral
PubMed: 38902244
DOI: 10.1038/s41522-024-00521-9 -
The European Respiratory Journal Jun 2024https://bit.ly/4aVFrNH
https://bit.ly/4aVFrNH
Topics: Humans; Asthma; Formoterol Fumarate; Anti-Asthmatic Agents; Ethanolamines; Adrenal Cortex Hormones; Administration, Inhalation; Evidence-Based Medicine; Bronchodilator Agents; Treatment Outcome
PubMed: 38901890
DOI: 10.1183/13993003.00523-2024 -
Translational Vision Science &... Jun 2024To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA).
PURPOSE
To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA).
METHODS
Photothrombotic BRVOs were created in both eyes of four groups of nine pigs (2, 6, 10, and 20 days). In each group, six pigs received intravitreal injections of BEV in one eye and TA in the fellow eye, with three pigs serving as untreated BRVO controls. Three untreated pigs served as healthy controls. Expression of mRNA of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), dystrophin (DMD), potassium inwardly rectifying channel subfamily J member 10 protein (Kir4.1, KCNJ10), aquaporin-4 (AQP4), stromal cell-derived factor-1α (CXCL12), interleukin-6 (IL6), interleukin-8 (IL8), monocyte chemoattractant protein-1 (CCL2), intercellular adhesion molecule 1 (ICAM1), and heat shock factor 1 (HSF1) were analyzed by quantitative reverse-transcription polymerase chain reaction. Retinal VEGF protein levels were characterized by immunohistochemistry.
RESULTS
In untreated eyes, BRVO significantly increased expression of GFAP, IL8, CCL2, ICAM1, HSF1, and AQP4. Expression of VEGF, KCNJ10, and CXCL12 was significantly reduced by 6 days post-BRVO, with expression recovering to healthy control levels by day 20. Treatment with BEV or TA significantly increased VEGF, DMD, and IL6 expression compared with untreated BRVO eyes and suppressed BRVO-induced CCL2 and AQP4 upregulation, as well as recovery of KCNJ10 expression, at 10 to 20 days post-BRVO.
CONCLUSIONS
Inflammation and cellular osmohomeostasis rather than VEGF suppression appear to play important roles in BRVO-induced retinal neurodegeneration, enhanced in both BEV- and TA-treated retinas.
TRANSLATIONAL RELEVANCE
Inner retinal neurodegeneration seen in this acute model of BRVO appears to be mediated by inflammation and alterations in osmohomeostasis rather than VEGF inhibition, which may have implications for more specific treatment modalities in the acute phase of BRVO.
Topics: Animals; Bevacizumab; Triamcinolone Acetonide; Retinal Vein Occlusion; Disease Models, Animal; Angiogenesis Inhibitors; Cytokines; Intravitreal Injections; Swine; Vascular Endothelial Growth Factor A; RNA, Messenger; Glucocorticoids; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Potassium Channels, Inwardly Rectifying
PubMed: 38899953
DOI: 10.1167/tvst.13.6.13 -
Skin Research and Technology : Official... Jun 2024Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and...
BACKGROUND
Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods.
OBJECTIVE
This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars.
METHODS
Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores.
RESULTS
Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period.
CONCLUSION
Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes.
Topics: Humans; Cicatrix; Polyesters; Female; Adult; Male; Patient Satisfaction; Asian People; Drug Delivery Systems; Administration, Cutaneous; Treatment Outcome; Atrophy; Acne Vulgaris; Young Adult
PubMed: 38899803
DOI: 10.1111/srt.13762 -
World Journal of Gastroenterology Jun 2024The combination of endoscopic ultrasound with endoscopic treatment of type 1 gastric variceal hemorrhage may improve the robustness and generalizability of the findings...
The combination of endoscopic ultrasound with endoscopic treatment of type 1 gastric variceal hemorrhage may improve the robustness and generalizability of the findings in future studies. Moreover, the esophageal varices should also be included in the evaluation of treatment efficacy in subsequent studies to reach a more convincing conclusion.
Topics: Esophageal and Gastric Varices; Humans; Ligation; Treatment Outcome; Gastrointestinal Hemorrhage; Tissue Adhesives; Endosonography; Injections; Hemostasis, Endoscopic; Endoscopy, Gastrointestinal
PubMed: 38899333
DOI: 10.3748/wjg.v30.i21.2827 -
Ciencia & Saude Coletiva Jun 2024This article aims to discuss the expectations of Homosexual Men, Bisexual Men and a Transgender Woman, who use or want to use an oral pre-exposure prophylaxis (PrEP) for...
This article aims to discuss the expectations of Homosexual Men, Bisexual Men and a Transgender Woman, who use or want to use an oral pre-exposure prophylaxis (PrEP) for the human immunodeficiency virus (HIV) about PrEP modalities. Sixteen PrEP users, who are followed up in the BCN Checkpoint, were interviewed,. The interviews were audio-recorded, subjected to thematic categorical analysis within the theoretical framework from the praxiographic perspective. They are all adapted to the use of daily oral and event-based PrEP. In relation to the new PrEP modalities (monthly pill; intramuscular injection every two months; subcutaneous injection every six months), they are all very receptive to these possibilities, but they lack information on the specificities of each and specific assessment of their needs. Comments about the use of oral PrEP are positive, and expectations regarding the new PrEP modalities are visibly high. However, the most important thing for the interviewees is the guarantee that they will have follow-up appointments to continue taking care of their affective-sexual health, which is not dependent on the type of PrEP modalities.
Topics: Humans; Pre-Exposure Prophylaxis; Male; HIV Infections; Female; Adult; Anti-HIV Agents; Sexual and Gender Minorities; Interviews as Topic; Transgender Persons; Administration, Oral; Middle Aged; Young Adult; Injections, Intramuscular
PubMed: 38896667
DOI: 10.1590/1413-81232024296.03042023