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Transplantation Direct Jul 2024Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living...
BACKGROUND
Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function.
METHODS
In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay.
RESULTS
There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ± 20.2 versus 71 ± 39.5 mg, < 0.01). Postoperative pain scores were significantly lower ( < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter ( = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ± 907 versus 2168 ± 1347 mL, = 0.049). Time to tolerating regular diet was shorter by 2 h ( < 0.008), and length of hospital stay was decreased by 10.1 h.
CONCLUSIONS
The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.
PubMed: 38953038
DOI: 10.1097/TXD.0000000000001663 -
The Canadian Veterinary Journal = La... Jul 2024A 21-year-old retired polo Argentinian thoroughbred horse from a teaching herd was presented for a routine bronchoalveolar lavage demonstration, during which an...
A 21-year-old retired polo Argentinian thoroughbred horse from a teaching herd was presented for a routine bronchoalveolar lavage demonstration, during which an incidental finding of a granulomatous mass on the dorsal aspect of the epiglottis was made. was suspected from a histological section obtained from an initial biopsy, and the mass was removed laser surgery for cytology and PCR. Sequencing of the PCR amplicons confirmed the diagnosis of A treatment protocol of nebulized voriconazole for 10 d postoperatively was used. Long-term follow-up required 2 more laser surgeries plus oral fluconazole to resolve the remaining fungal spores. However, 2.5 y later, there was no evidence of remaining fungal spores. Key clinical message: Horses from endemic regions can potentially be exposed to Based on its travel history, this horse may have contracted the infection in South America, California, or Alberta. Treatments administered, including diode laser resection, voriconazole antifungal nebulization, and oral fluconazole administration, were successful but required repeated interventions.
Topics: Animals; Horses; Horse Diseases; Voriconazole; Antifungal Agents; Male; Rhinosporidiosis; Nebulizers and Vaporizers; Laser Therapy; Polymerase Chain Reaction; Laryngeal Diseases
PubMed: 38952752
DOI: No ID Found -
Pakistan Journal of Medical Sciences Jul 2024This case report is of herpes zoster which is caused by Varicella zoster virus (VZV). The patient was presented with acute renal failure associated with intravenous...
This case report is of herpes zoster which is caused by Varicella zoster virus (VZV). The patient was presented with acute renal failure associated with intravenous acyclovir administration for its management. A 50 years old man visited the hospital with rashes on his back. The serum sample was positive for anti-VZV IgM via Enzyme Linked Immunosorbent Assay (ELISA), and vesicular swab for VZV via polymerase chain reaction (PCR). Phylogenetic analysis identified it as M2-genotype. Patient was treated with intravenous acyclovir administration, which led to acute renal failure. Later with shift to oral acyclovir, renal functions were restored. Elderly patients with reactivation of VZV in Pakistan are at risk to contract herpes zoster. Acyclovir is drug of choice via intravenous route was found to be nephrotoxic, however oral acyclovir was safe and effective. This is first report on pathogenic VZV genotype from Pakistan and is presented to highlight that the herpes zoster cases of elderly patients' treatment option need to be revisited.
PubMed: 38952536
DOI: 10.12669/pjms.40.6.8764 -
Drug Design, Development and Therapy 2024The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications... (Review)
Review
PURPOSE
The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use.
METHODOLOGY
The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (C), time to C, half-life (t), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies.
RESULTS
Semaglutide has a predictable pharmacokinetic profile with a long t that allows for once-weekly subcutaneous administration. The AUC and C of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this.
CONCLUSION
This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.
Topics: Glucagon-Like Peptides; Humans; Administration, Oral; Injections, Subcutaneous; Hypoglycemic Agents; Drug Interactions
PubMed: 38952487
DOI: 10.2147/DDDT.S470826 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jun 2024To investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of , so as to provide insights into for...
OBJECTIVE
To investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of , so as to provide insights into for toxoplasmosis prevention and control.
METHODS
ICR mice at ages of 6 to 8 weeks, each weighing 20 to 25 g, were intraperitoneally injected with tachyzoites of the PRU strain at a dose of 1 × 10 tachyzoites per mouse, orally administered with cysts at a dose of 20 oocysts per mouse or oocysts at a dose of 200 oocysts per mouse for modeling chronic infection in mice, and the clinical symptoms and survival of mice were observed post-infection. Mice were orally infected with cysts at doses of 10 (low-dose group), 20 (medium-dose group), 40 cysts per mouse (high-dose group), and the effect of different doses of infections on the number of cysts was examined in the mouse brain. Mice were orally administered with cysts at a dose of 20 cysts per mouse, and grouped according to gender (female and male) and time points of infections (20, 30, 60, 90, 120, 150, 180 days post-infection), and the effects of gender and time points of infections on the number of cysts was examined in the mouse brain. In addition, mice were divided into the tachyzoite group (Group T), the first-generation cyst group (Group C1), the second-generation cyst group (Group C2), the third-generation cyst (Group C3) and the fourth-generation cyst group (Group C4). Mice in the Group T were intraperitoneally injected with tachyzoites at a dose of 1 × 10 tachyzoites per mouse, and the cysts were collected from the mouse brain tissues 30 days post-infection, while mice in the Group C1 were orally infected with the collected cysts at a dose of 30 cysts per mouse. Continuous passage was performed by oral administration with cysts produced by the previous generation in mice, and the effect of continuous passage on the number of cysts was examined in the mouse brain.
RESULTS
Following infection with tachyzoites, cysts and oocysts in mice, obvious clinical symptoms were observed on days 6 to 13 and mice frequently died on days 7 to 12. The survival rates of mice were 67.0%, 87.0% and 53.0%, and the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0) and (581.0 ± 183.1) in the mouse brain ( = 11.94, < 0.01) on day 30 post-infection with tachyzoites, cysts and oocysts, respectively, and the numbers of cysts in the brain tissues were significantly lower in mice infected with tachyzoites and oocysts than in those infected with cysts (all values < 0.01). The survival rates of mice were 87.0%, 87.0% and 60.0%, and the mean numbers of cysts were (953.0 ± 355.5), (1 084.0 ± 474.3) and (1 113.0 ± 546.0) in the mouse brain in the low-, medium- and high-dose groups on day 30 post-infection, respectively ( = 0.42, > 0.05). The survival rates of male and female mice were 73.0% and 80.0%, and the mean numbers of cysts were (946.4 ± 411.4) and (932.1 ± 322.4) in the brain tissues of male and female mice, respectively ( = 1.63, > 0.05). Following continuous passage, the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0), (896.8 ± 332.3), (782.5 ± 423.9) and (829.2 ± 306.0) in the brain tissues of mice in the T, C1, C2, C3 and C4 groups, respectively ( = 4.82, < 0.01), and the number of cysts was higher in the mouse brain in Group 1 than in Group T ( < 0.01). Following oral administration of 20 cysts in mice, cysts were found in the moues brain for the first time on day 20 post-infection, and the number of cysts gradually increased over time, peaked on days 30 and 90 post-infection and then gradually decreased; however, the cysts were still found in the mouse brain on day 180 post-infection.
CONCLUSIONS
There is a higher possibility of developing chronic infection in mice following infection with cysts than with oocysts or tachyzoites and the most severe chronic infection is seen following infection with cysts. The number of cysts does not correlate with the severity of chronic infection, and the number of cysts peaks in the mouse brain on days 30 and 90 post-infection.
Topics: Animals; Mice; Female; Male; Mice, Inbred ICR; Brain; Chronic Disease; Toxoplasmosis, Animal; Toxoplasma; Toxoplasmosis; Disease Models, Animal
PubMed: 38952318
DOI: 10.16250/j.32.1374.2024044 -
Veterinary Medicine and Science Jul 2024Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of...
BACKGROUND
Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties.
OBJECTIVES
The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C.
METHODS
The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis.
RESULTS
The elimination half-life (t) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent.
CONCLUSIONS
While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
Topics: Animals; Oncorhynchus mykiss; ortho-Aminobenzoates; Biological Availability; Anti-Inflammatory Agents, Non-Steroidal; Administration, Oral; Blood Proteins; Injections, Intramuscular; Protein Binding; Injections, Intravenous; Half-Life
PubMed: 38952278
DOI: 10.1002/vms3.1533 -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal...
[Vitamin D3 alleviates the gastritis that associated with Helicobacter pylori infection in mice with hypercholesterolemia by enhancing the activity of vitamin D receptors in the liver tissue and blocking the signaling pathway of JAK/STAT3].
Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Methods High-cholesterol mouse model and Hp infected mouse model were established. Each was treated with VD3 via oral administration for 8 weeks. Real-time quantitative PCR was used to detect the expression of vitamin D receptor (VDR), insulin-induced gene 2 (Insig-2), and gastrin mRNA. Western blot analysis was used to examine the expression of JAK, STAT3, and cyclooxygenase-2 (COX2) proteins in gastric tissues. Biochemical analyses were performed to measure serum cholesterol levels, and ELISA was utilized to evaluate serum gastrin, interleukin 6 (IL-6), and IL-8 levels, along with histopathological examination of liver and gastric tissues using HE staining. Results After oral administration of VD3, the levels of VDR and Insig-2 in mouse liver tissue significantly increased in the high cholesterol group and the high cholesterol combined with Hp infection group. And the expression of serum gastrin decreased. The expression of JAK, STAT3 in gastric tissues reduced, as did the expression of COX2. Serum cholesterol levels decreased, with no significant changes in IL-6 levels, but a reduction in IL-8 levels. Compared to the control group, the high cholesterol combined with Hp infection group showed reduced hepatic ballooning degeneration and alleviated gastric tissue inflammation. In addition, inflammation in gastric tissue was also reduced in the cholesterol group and the Hp infection group. Conclusion VD3 alleviates gastritis by enhancing the activity of VDR in liver tissues, blocking the JAK/STAT3 signaling pathway, and inhibiting the expression of inflammatory factors.
Topics: Animals; Helicobacter Infections; STAT3 Transcription Factor; Cholecalciferol; Receptors, Calcitriol; Signal Transduction; Liver; Mice; Janus Kinases; Gastritis; Male; Helicobacter pylori; Hypercholesterolemia
PubMed: 38952091
DOI: No ID Found -
Journal of Nanobiotechnology Jul 2024Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the...
Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.
Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.
Topics: Animals; MicroRNAs; Myocardial Reperfusion Injury; Exosomes; NF-kappa B; Signal Transduction; Rats; Rats, Sprague-Dawley; Male; Milk; Myocardium; Cardiotonic Agents; Myocytes, Cardiac
PubMed: 38951872
DOI: 10.1186/s12951-024-02631-0 -
Nature Aging Jul 2024Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a...
Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16 reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.
PubMed: 38951692
DOI: 10.1038/s43587-024-00663-7 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2024This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it...
[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation].
This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% 2.2-4.3 months, =0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; =0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.
Topics: Humans; fms-Like Tyrosine Kinase 3; Leukemia, Myeloid, Acute; Male; Female; Adult; Hematopoietic Stem Cell Transplantation; Middle Aged; Retrospective Studies; Mutation; Pyrazines; Adolescent; Aniline Compounds; Aged; Young Adult; Transplantation, Homologous; Remission Induction; Disease-Free Survival
PubMed: 38951063
DOI: 10.3760/cma.j.cn121090-20231207-00297