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The Veterinary Quarterly Dec 2024Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in...
Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in veterinary medicine, there are no specific therapeutic approaches for managing this hypercoagulability. This study aimed to determine the preventive effect of clopidogrel on post-operative hypercoagulability during the first 2 weeks post-splenectomy in dogs with splenic masses. This study included 12 dogs that had splenectomy. Seven dogs received no treatment (group A), and five were treated with clopidogrel (group B). Clopidogrel was loaded at 10 mg/kg on day 2 and continued at 2 mg/kg until day 14. Blood samples were collected on the day of surgery and 2, 7, and 14 days after splenectomy in both groups. In group B, thromboelastography (TEG) was performed on the same days. In group A, there was significant elevation of platelet counts on days 7 ( = 0.007) and 14 ( = 0.001) compared to day 0. In group B, the platelet counts were significantly elevated on day 7 ( = 0.032) but no significant difference was found on day 14 compared to day 0. Platelet counts on day 14 were significantly higher in group A than in group B ( = 0.03). The lower platelet counts were correlated with alterations in TEG parameters, and no significant differences were found in the K and α-angle values at all postoperative assessment points compared to day 0. Our study suggests that clopidogrel may reduce post-operative thrombocytosis and hypercoagulability in dogs that undergo splenectomy for splenic masses.
Topics: Animals; Dogs; Splenectomy; Clopidogrel; Dog Diseases; Platelet Count; Female; Male; Thrombophilia; Platelet Aggregation Inhibitors; Thrombelastography; Postoperative Complications; Splenic Neoplasms; Splenic Diseases; Thrombocytosis
PubMed: 38823415
DOI: 10.1080/01652176.2024.2347926 -
Scientific Reports May 2024Aspirin is widely used for both primary and secondary prevention of panvascular diseases, such as stroke and coronary heart disease (CHD). The optimal balance between...
Aspirin is widely used for both primary and secondary prevention of panvascular diseases, such as stroke and coronary heart disease (CHD). The optimal balance between reducing panvascular disease events and the potential increase in bleeding risk remains unclear. This study aimed to develop a predictive model specifically designed to assess bleeding risk in individuals using aspirin. A total of 58,415 individuals treated with aspirin were included in this study. Detailed data regarding patient demographics, clinical characteristics, comorbidities, medical history, and laboratory test results were collected from the Affiliated Dongyang Hospital of Wenzhou Medical University. The patients were randomly divided into two groups at a ratio of 7:3. The larger group was used for model development, while the smaller group was used for internal validation. To develop the prediction model, we employed least absolute shrinkage and selection operator (LASSO) regression followed by multivariate logistic regression. The performance of the model was assessed through metrics such as the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). The LASSO-derived model employed in this study incorporated six variables, namely, sex, operation, previous bleeding, hemoglobin, platelet count, and cerebral infarction. It demonstrated excellent performance at predicting bleeding risk among aspirin users, with a high AUC of 0.866 (95% CI 0.857-0.874) in the training dataset and 0.861 (95% CI 0.848-0.875) in the test dataset. At a cutoff value of 0.047, the model achieved moderate sensitivity (83.0%) and specificity (73.9%). The calibration curve analysis revealed that the nomogram closely approximated the ideal curve, indicating good calibration. The DCA curve demonstrated a favorable clinical net benefit associated with the nomogram model. Our developed LASSO-derived predictive model has potential as an alternative tool for predicting bleeding in clinical settings.
Topics: Humans; Aspirin; Male; Female; Hemorrhage; Middle Aged; Aged; ROC Curve; Risk Assessment; Risk Factors; Logistic Models; Platelet Aggregation Inhibitors
PubMed: 38822153
DOI: 10.1038/s41598-024-63437-6 -
Scientific Reports May 2024Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1)...
Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic β cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.
Topics: Tuberous Sclerosis Complex 2 Protein; Animals; Acetylation; Lysosomes; Mice; Mitochondria; Mechanistic Target of Rapamycin Complex 1; Sirtuin 1; Autophagy; Protein Transport; Resveratrol; Signal Transduction; Fibroblasts; Insulin-Secreting Cells; Cell Line, Tumor
PubMed: 38822085
DOI: 10.1038/s41598-024-63525-7 -
Brain Stimulation 2024Dopaminergic neurons in the ventral tegmental area (VTA) are crucially involved in regulating arousal, making them a potential target for reversing general anesthesia....
BACKGROUND
Dopaminergic neurons in the ventral tegmental area (VTA) are crucially involved in regulating arousal, making them a potential target for reversing general anesthesia. Electrical deep brain stimulation (DBS) of the VTA restores consciousness in animals anesthetized with drugs that primarily enhance GABA receptors. However, it is unknown if VTA DBS restores consciousness in animals anesthetized with drugs that target other receptors.
OBJECTIVE
To evaluate the efficacy of VTA DBS in restoring consciousness after exposure to four anesthetics with distinct receptor targets.
METHODS
Sixteen adult Sprague-Dawley rats (8 female, 8 male) with bipolar electrodes implanted in the VTA were exposed to dexmedetomidine, fentanyl, ketamine, or sevoflurane to produce loss of righting, a proxy for unconsciousness. After receiving the dopamine D1 receptor antagonist, SCH-23390, or saline (vehicle), DBS was initiated at 30 μA and increased by 10 μA until reaching a maximum of 100 μA. The current that evoked behavioral arousal and restored righting was recorded for each anesthetic and compared across drug (saline/SCH-23390) condition. Electroencephalogram, heart rate and pulse oximetry were recorded continuously.
RESULTS
VTA DBS restored righting after sevoflurane, dexmedetomidine, and fentanyl-induced unconsciousness, but not ketamine-induced unconsciousness. D1 receptor antagonism diminished the efficacy of VTA stimulation following sevoflurane and fentanyl, but not dexmedetomidine.
CONCLUSIONS
Electrical DBS of the VTA restores consciousness in animals anesthetized with mechanistically distinct drugs, excluding ketamine. The involvement of the D1 receptor in mediating this effect is anesthetic-specific.
Topics: Animals; Ventral Tegmental Area; Sevoflurane; Rats, Sprague-Dawley; Dexmedetomidine; Male; Fentanyl; Rats; Female; Unconsciousness; Deep Brain Stimulation; Consciousness; Ketamine; Anesthetics, Inhalation
PubMed: 38821397
DOI: 10.1016/j.brs.2024.05.012 -
Biomedicine & Pharmacotherapy =... Jul 2024Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a...
Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT, 5-HT, 5-HT and 5-HT receptor agonists, respectively). Blocking 5-HT receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT and 5-HT activation.
Topics: Animals; Succinates; Male; Diabetes Mellitus, Experimental; Rats, Wistar; Kidney; Sympathetic Nervous System; Rats; Serotonin 5-HT2 Receptor Antagonists; Serotonin; Diabetic Nephropathies; Vasoconstriction
PubMed: 38820974
DOI: 10.1016/j.biopha.2024.116814 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
Turkish Journal of Medical Sciences 2023To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
BACKGROUND/AIM
To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
MATERIALS AND METHODS
Herein, 6 equal groups of rats were formed (n: 48): control group, sham group, torsion/detorsion (T/D)-1 h group, T/D-1 h + ASA group, T/D-8 h group, and T/D-8 h + ASA group. Testicular torsion was created by rotating the left testis 720° clockwise. At 30 min before torsion, 100 mg/kg of ASA was injected intraperitoneally. Elastography was performed at 8 and 24 h. After orchiectomy, specimens were collected for histopathological evaluation.
RESULTS
When comparing the left testicular volume (LV) parameters obtained from the elastography applied at 8 h, significant differences were observed between the following group pairs: the sham and T/D-8 h groups, T/D-1 h and T/D-8 h groups, and T/D-1 h + ASA and T/D-8 h groups (p = 0.004, p = 0.023, and p = 0.026, respectively). The mean LVS (velocity) (stiffness assessment) of the groups was similar at 8 h. When comparing the LV parameters at 24 h, significant differences were found between the T/D-1 h and T/D-8 h groups and between the T/D-8 h and T/D-8 h + ASA groups (p = 0.008 and p = 0.004, respectively). For the LVS mean values at 24 h, significant differences were found between the control and sham groups, sham and T/D-1 h groups, sham and T/D-8 h groups, and sham and T/D-8 h + ASA groups (p = 0.009, p = 0.021, p = 0.027, and p = 0.009, respectively).Histopathological evaluation showed a decrease in the morphological grades and an increase in the mean testicular injury scores in the T/D-1 h + ASA group compared to the T/D-1 h group. The T/D-8 h + ASA group had a higher morphological grade than the T/D-8 h group, whereas their mean testicular injury scores were similar.
CONCLUSION
ASA treatment for testicular torsion was shown to be ineffective. Elastography can be a complementary method to Doppler ultrasonography in the diagnosis of testicular torsion and can guide surgeons in their approach to surgery.
Topics: Male; Spermatic Cord Torsion; Animals; Aspirin; Elasticity Imaging Techniques; Rats; Testis; Disease Models, Animal; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38813515
DOI: 10.55730/1300-0144.5729 -
Frontiers in Endocrinology 2024Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases...
INTRODUCTION
Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases of absolute asthenozoospermia has been demonstrated for ICSI, data related to babies born from the PF-ICSI are still severely lacking. Concerns have been raised regarding the potential embryotoxicity of PF due to the controversial results obtained from the analysis of this compound on animal embryo development. This study aimed to determine whether the application of PF to trigger frozen-thawed TESA (testicular sperm aspiration) spermatozoa increases the risk of adverse obstetric and neonatal outcomes compared with non-PF frozen-thawed TESA ICSI and conventional ICSI using fresh ejaculation.
MATERIALS AND METHODS
A total of 5438 patients were analyzed in this study, including 240 patients underwent PF-TESA ICSI (ICSI using PF triggered frozen-thawed testicular spermatozoa), 101 patients underwent non-PF TESA ICSI (ICSI using frozen-thawed testicular spermatozoa) and 5097 patients underwent conventional ICSI using fresh ejaculation. Propensity score matching was executed to control the various characteristics of patients.
RESULTS
No significant differences in pregnancy outcomes were observed among the three groups (PF-TESA ICSI, non-PF TESA ICSI and conventional ICSI), including biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live birth, following propensity score matching. Additionally, neonatal outcomes were found to be similar among the three groups, with no statistical differences observed in the birth defect, birth weight, gestational age, preterm birth, and early-neonatal death.
DISCUSSION AND CONCLUSION
PF-ICSI may be an alternative treatment in patients using frozen-thawed testicular spermatozoa, resulting in comparable pregnancy and neonatal outcomes.
Topics: Humans; Pentoxifylline; Pregnancy; Female; Male; Sperm Injections, Intracytoplasmic; Adult; Pregnancy Outcome; Spermatozoa; Cryopreservation; Infant, Newborn; Pregnancy Rate; Sperm Retrieval; Retrospective Studies; Semen Preservation
PubMed: 38812814
DOI: 10.3389/fendo.2024.1364285 -
BMC Cardiovascular Disorders May 2024Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane...
BACKGROUND
Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.
METHODS
The H9C2 cardiomyocytes were cultured to establish the hypoxia-reoxygenation (H/R) model and randomly divided into 4 groups: Control group, H/R group, sevoflurane postconditioning (H/R + SpostC) group and PI3K/AKT blocker (H/R + SpostC + LY) group. Cell survival rate was determined by CCK-8; Apoptosis rate was determined by flow cytometry; mitochondrial membrane potential was evaluated by Mito Tracker™ Red; mRNA expression levels of AKT, HIF-1α, Opa1and Drp1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR); Western Blot assay was used to detect the protein expression levels of AKT, phosphorylated AKT (p-AKT), HIF-1α, Opa1 and Drp1.
RESULTS
Compared with the H/R group, the survival rate of cardiomyocytes in the H/R + SpostC group increased, the apoptosis rate decreased and the mitochondrial membrane potential increased. qRT-PCR showed that the mRNA expression of HIF-1α and Opa1 were higher in the H/R + SpostC group compared with the H/R group, whereas the transcription level of Drp1 was lower in the H/R + SpostC group. In the H/R + SpostC + LY group, the mRNA expression of HIF-1α was lower than the H/R + SpostC group. There was no difference in the expression of Opa1 mRNA between the H/R group and the H/R + SpostC + LY group. WB assay results showed that compared with the H/R group, the protein expression levels of HIF-1α, Opa1, P-AKT were increased and Drp1 protein expression levels were decreased in the H/R + SpostC group. HIF-1α, P-AKT protein expression levels were decreased in the H/R + SpostC + LY group compared to the H/R + SpostC group.
CONCLUSION
SpostC mediates HIF-1α-regulated mitochondrial fission and fusion-related protein expression to maintain mitochondrial dynamic balance by activating the PI3K/AKT pathway and increasing AKT phosphorylation, thereby attenuating myocardial I/R injury.
Topics: Hypoxia-Inducible Factor 1, alpha Subunit; Proto-Oncogene Proteins c-akt; Animals; Myocytes, Cardiac; Sevoflurane; Signal Transduction; Myocardial Reperfusion Injury; Mitochondrial Dynamics; Cell Line; Rats; Apoptosis; Phosphatidylinositol 3-Kinase; Mitochondria, Heart; Membrane Potential, Mitochondrial; Cell Hypoxia; Dynamins; GTP Phosphohydrolases; Phosphoinositide-3 Kinase Inhibitors; Cytoprotection; Ischemic Postconditioning; Phosphorylation
PubMed: 38811893
DOI: 10.1186/s12872-024-03868-1 -
BMC Cardiovascular Disorders May 2024Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic... (Review)
Review
BACKGROUND
Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired).
CASE PRESENTATION
We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward.
CONCLUSIONS
Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.
Topics: Humans; Male; Middle Aged; Acute Coronary Syndrome; Treatment Outcome; Aortic Diseases; Recurrence; Thrombosis; Anticoagulants; Computed Tomography Angiography; Coronary Angiography; Platelet Aggregation Inhibitors; Non-ST Elevated Myocardial Infarction; Aortography
PubMed: 38811879
DOI: 10.1186/s12872-024-03956-2