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Plastic and Reconstructive Surgery.... Sep 2023Hematoma-induced vasospasm is a significant factor that can compromise the success of flap reconstructive surgery. Despite advances in microsurgical techniques and...
Hematoma-induced vasospasm is a significant factor that can compromise the success of flap reconstructive surgery. Despite advances in microsurgical techniques and knowledge, vasospasm remains a direct cause of flap loss. Hematoma-induced vasospasm occurs due to the presence of blood breakdown products, which can lead to arterial constriction and reduced blood flow to the transplanted tissue. A 77-year-old man with a history of coronary angina developed soft tissue sarcoma on the right groin. Postoperative hematoma-induced vasospasm occurred subsequent to the reconstruction using a pedicled anterolateral thigh flap for the defect after wide resection. The hematoma was evacuated, and blood flow to the flap was restored with topical application of warm saline and vasodilators. Postoperative administration of intravenous alprostadil was used to counteract the vasospasm, and the flap completely survived without any problems with blood flow. It is important to recognize the triggers of vasospasm, such as hematomas, which may occur intra- or postoperatively, and to take appropriate measures to prevent or treat them. Treatment of vasospasm includes the intraoperative topical application of warm saline or vasodilators and the administration of intravenous alprostadil or 4% lidocaine postoperatively. Nevertheless, in the case of hematoma-induced vasospasm, it is important to remove the hematoma.
PubMed: 37711725
DOI: 10.1097/GOX.0000000000005271 -
Journal of Biotechnology Jan 2024We evaluated the suitability of Komagataeibacter europaeus, a vinegar production organism adept at synthetic media growth, as a host for heterologous gene expression....
We evaluated the suitability of Komagataeibacter europaeus, a vinegar production organism adept at synthetic media growth, as a host for heterologous gene expression. Cryptic plasmids (pGE1 and pGE2 derivatives) from K. europaeus strain KGMA0119 were employed as vectors for heterologous gene expression. The focus was placed on the groES promoter as a potential inducible switch. The groES promoter was fused with the EGFP gene and introduced into a pGE1 derivative to assess its suitability. Ethanol, acetic acid, and heat stresses were examined under various conditions for induction. EGFP transcription surged 600-fold when late logarithmic phase K. europaeus cells, cultured at 30 °C, endured heat stress at 40 °C, coupled with 20% acetic acid and 30% ethanol stress after an additional 6-hour cultivation. This robust induction system was then applied to express two proteins, Tth pol from the thermophilic bacterium Thermus thermophilus strain M1 and UPV230, a restriction enzyme from the acid-tolerant microorganism Ureaplasma parvum, known to cause vaginal infections and miscarriages. Both Tth pol and UPV230 were successfully expressed in K. europaeus cells and purified. The recovery of Tth pol from K. europaeus cells (480 µg protein per liter culture) was approximately half that from E. coli (960 µg protein per liter culture). In contrast, UPV230 recovery from K. europaeus cells (640 µg protein per liter culture) was nearly 10 times higher than that from Escherichia coli (66 µg protein per liter). The data highlights the potential of acetic acid bacteria as a host for producing acidophilic proteins. The shift in recognition from a 6-base sequence to a 4-base sequence of UPV230 was observed, accompanied by a change in structure as the pH transitioned from acidic pH to near-neutral pH.
Topics: Acetic Acid; Escherichia coli; Alprostadil; Recombinant Proteins; Ethanol
PubMed: 38135188
DOI: 10.1016/j.jbiotec.2023.12.009 -
Journal of Molecular Endocrinology Jul 2024The prostanoid G protein-coupled receptor (GPCR) EP2 is widely expressed and implicated in endometriosis, osteoporosis, obesity, pre-term labour and cancer....
The prostanoid G protein-coupled receptor (GPCR) EP2 is widely expressed and implicated in endometriosis, osteoporosis, obesity, pre-term labour and cancer. Internalisation and intracellular trafficking are critical for shaping GPCR activity, yet little is known regarding the spatial programming of EP2 signalling and whether this can be exploited pharmacologically. Using three EP2-selective ligands that favour activation of different EP2 pathways, we show that EP2 undergoes limited agonist-driven internalisation but is constitutively internalised via dynamin-dependent, β-arrestin-independent pathways. EP2 was constitutively trafficked to early and very early endosomes (VEE), which was not altered by ligand activation. APPL1, a key adaptor and regulatory protein of the VEE, did not impact EP2 agonist-mediated cAMP. Internalisation was required for ~70% of the acute butaprost- and AH13205-mediated cAMP signalling, yet PGN9856i, a Gαs-biased agonist, was less dependent on receptor internalisation for its cAMP signalling, particularly in human term pregnant myometrial cells that endogenously express EP2. Inhibition of EP2 internalisation partially reduced calcium signalling activated by butaprost or AH13205 and had no effect on PGE2 secretion. This indicates an agonist-dependent differential spatial requirement for Gαs and Gαq/11 signalling and a role for plasma membrane-initiated Gαq/11-Ca2+-mediated PGE2 secretion. These findings reveal a key role for EP2 constitutive internalisation in its signalling and potential spatial bias in mediating its downstream functions. This, in turn, could highlight important considerations for future selective targeting of EP2 signalling pathways.
Topics: Humans; Receptors, Prostaglandin E, EP2 Subtype; Signal Transduction; Female; Pregnancy; Cyclic AMP; GTP-Binding Proteins; Endosomes; Protein Transport; Myometrium; Alprostadil; HEK293 Cells; Animals
PubMed: 38639976
DOI: 10.1530/JME-23-0153 -
Annals of Vascular Surgery Jun 2024This study was carried out to assess the effectiveness of alprostadil (prostaglandin E1) when used as an adjuvant therapy with indirect revascularization in patients...
Outcomes of Alprostadil As an Adjuvant Therapy with Indirect Angiosomal Revascularization in Patients with Critical Limb Ischemia after Failure of Direct Revascularization.
BACKGROUND
This study was carried out to assess the effectiveness of alprostadil (prostaglandin E1) when used as an adjuvant therapy with indirect revascularization in patients with critical limb ischemia (CLI) after the failure of direct revascularization (DR).
METHODS
At our centers, 120 patients suffering from infrainguinal peripheral arterial disease with CLI underwent a failed trial of DR procedure, all revascularization procedures were endovascular. Median follow-up was 2 years and 2.5 years for patients with and without diabetes mellitus (DM). In the alprostadil group, the mean age was 63.41 ± 12.52; 36 (60%) for males and 24 (40%) for females. Post-endovascular intervention alprostadil was administrated immediately postoperatively by intravenous infusion of 40 μg alprostadil diluted in 100 ml of normal saline, over 2 hr every 12 hr for 6 days.
RESULTS
In the alprostadil group, the mean ± standard deviation (SD) of the baseline ankle-brachial index (ABI) was 0.45 ± 0.175, while the mean ± SD of ABI at the end of our study was 0.65 ± 0.216 with a difference from the baseline of 0.2 ± 0.041 (P value = 0.08, <0.05 meaning that it is significant). Our 1-month primary patency rate was 93.3%, while our 3- and 6-month patency rate was 92.9%. In the control group, the mean ± SD of the baseline ABI was 0.68 ± 0.22, while the mean ± SD of ABI at the end of our study was 0.69 ± 0.23 with a difference from the baseline of 0.01 ± 0.01 (P value >0.05 meaning that it is nonsignificant) 1-month patency rate was 89%, while 3- and 6-month patency rate was 75%. When we compared the patient's leg vessels before and after our intervention, we found that the percentage of the no-runoff-vessels group decreased from 10 (16.7%) to 4 (6.67%). One-runoff-vessel group percentage dropped from 40 (66.7%) to 36 (60%), whereas, in the two-runoff-vessel group, the percentage increased from 10 (16.7%) to 20 (33.3%). We evaluate leg arteries; we do no pedal arch intervention in the alpostradil group. Out of the total of 60 patients, limb salvage occurred in 58 (96.7%) patients, and 2 (3.3%) patients underwent below-the-knee amputation before the study ended.
CONCLUSIONS
Our results show the efficacy and safety of alprostadil as an adjuvant therapy with indirect angiosomal revascularization in patients with tissue loss due to CLI.
Topics: Humans; Alprostadil; Male; Female; Aged; Middle Aged; Time Factors; Peripheral Arterial Disease; Ischemia; Critical Illness; Ankle Brachial Index; Vascular Patency; Limb Salvage; Treatment Failure; Endovascular Procedures; Infusions, Intravenous; Vasodilator Agents; Lower Extremity; Amputation, Surgical; Treatment Outcome; Risk Factors; Retrospective Studies
PubMed: 38431199
DOI: 10.1016/j.avsg.2023.12.078 -
Medicine Oct 2023It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous...
BACKGROUND
It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis.
METHODS
We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency.
RESULTS
After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered.
CONCLUSION
For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.
Topics: Male; Humans; Child; Adolescent; Femoral Vein; Anticoagulants; Thrombosis; Blood Coagulation Disorders; Leukemia, Myeloid, Acute; Vitamin K Deficiency; Arteries
PubMed: 37832057
DOI: 10.1097/MD.0000000000035121 -
International Journal of Biological... May 2024The survival rate of flap is a crucial factor for determining the success of tissue repair and reconstruction. Flap transplantation surgery often leads to ischemic and...
The survival rate of flap is a crucial factor for determining the success of tissue repair and reconstruction. Flap transplantation surgery often leads to ischemic and reperfusion injury, causing apoptosis and tissue necrosis, which significantly reduces the survival rate of flap. To address this issue, we developed a porcine skin decellularized matrix gel nanocomplex loaded with alprostadil (Alp) in Prussian blue nanoparticles (PB NPs) called Alp@PB-Gel. This gel not only maintained the cell affinity of the extracellular scaffold but also exhibited a high degree of plasticity. In vitro assays demonstrated that Alp@PB-Gel possessed antioxidant activity, scavenging ROS ability, and effectively promoted the angiogenesis and migration of human vascular endothelial cells (HUVECs) by stimulating the proliferation of vascular epithelial cells and fibroblasts. In vivo assays further confirmed that Alp@PB-Gel could effectively alleviate necrosis in the early and late stages after surgery, downregulate the levels of NLRP3 and CD68 to inhibit apoptosis and attenuate inflammation, while upregulate the levels of VEGF and CD31 to promote vascular tissue regeneration. Moreover, Alp@PB-Gel exhibited excellent cell affinity and biocompatibility, highlighting its potential for clinical application.
Topics: Animals; Ferrocyanides; Nanoparticles; Humans; Gelatin; Swine; Ischemia; Extracellular Matrix; Surgical Flaps; Skin; Human Umbilical Vein Endothelial Cells; Neovascularization, Physiologic; Mice
PubMed: 38574902
DOI: 10.1016/j.ijbiomac.2024.131361 -
Cardiology in the Young Feb 2024The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The...
The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.
Topics: Infant, Newborn; Humans; Alprostadil; Ductus Arteriosus; Ductus Arteriosus, Patent; Heart Defects, Congenital; Spasm
PubMed: 37403735
DOI: 10.1017/S1047951123001403 -
Journal of Cardiovascular Pharmacology Feb 2024As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events....
Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification.
As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second -1 , respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A 150s ), and mean fluorescence intensity (F 150s ) were used as quantitative indicators. Aspirin (80 μM) prolonged Ti and reduced F 150s . Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A 150s and F 150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second -1 . Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.
Topics: Humans; Platelet Aggregation Inhibitors; Ticagrelor; Microfluidics; Alprostadil; von Willebrand Factor; Blood Platelets; Platelet Aggregation; Aspirin; Platelet Glycoprotein GPIb-IX Complex
PubMed: 38032897
DOI: 10.1097/FJC.0000000000001514 -
Academic Radiology Mar 2024To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic...
RATIONALE AND OBJECTIVES
To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is feasible for staging Crohn's disease (CD) activity.
MATERIALS AND METHODS
A total of 65 CD patients were enrolled and analyzed in this retrospective study. The simplified endoscopic score for Crohn's disease (SES-CD) and magnetic resonance index of activity (MaRIA) were used as the reference. The MUSE-IVIM and DCE-MRI data were acquired at 3.0-T MRI scanner and processed by two radiologists. Three MUSE-IVIM parameters: fast apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (ADC), and the fractional perfusion (Fraction of ADC), as well as four DCE-MRI parameters: volume transfer constant (K), rate constant (K), extravascular extracellular volume fraction (V), and plasma volume fraction (V) were generated. Intraclass correlation coefficient (ICC), non-parametric test (Kruskal-Wallis H and Mann-Whitney U), logistic regression, receiver operating characteristic analysis, Delong test, and Spearman's correlation test were performed.
RESULTS
According to SES-CD, 116 ileocolonic segments with CD lesions were identified as: inactive, mild, and moderate to severe. With multivariable logistic regression analysis, ADC (p < 0.001), Fraction of ADC (p = 0.005), K (p < 0.001) and K (p = 0.003) were identified as significant factors for differentiating among the three groups. Binary logistic analyses identified ADC (p = 0.001), K (p = 0.014), and K (p = 0.029) as independent predictors for the active status. The combination of ADC, K, and K performed better than MaRIA score (p = 0.028), for differentiating inactive and active status. MaRIA score was positively correlated with ADC (p < 0.001), K (p < 0.001), K (p < 0.001), and V (p = 0.001), however, negatively correlated with Fraction of ADC (p < 0.001).
CONCLUSION
The combination of MUSE-IVIM and DCE-MRI has been demonstrated to accurately stage inflammatory activity in CD.
Topics: Humans; Alprostadil; Multiparametric Magnetic Resonance Imaging; Crohn Disease; Retrospective Studies; Contrast Media; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 37730492
DOI: 10.1016/j.acra.2023.08.028 -
Urologiia (Moscow, Russia : 1999) Jul 2023Blood flow parameters in cavernous arteries during full-erection phase on Doppler ultrasonography are associated with intracavernosal pressure and, consequently, with...
INTRODUCTION
Blood flow parameters in cavernous arteries during full-erection phase on Doppler ultrasonography are associated with intracavernosal pressure and, consequently, with penile rigidity.
AIM
To examine the relationship between blood flow parameters in cavernous arteries and the penile rigidity.
MATERIALS AND METHODS
A total of 54 healthy men and patients with erectile dysfunction of various degrees of severity, with mean age of 43,0 +/- 2,2 years ranging from 18 to 74 years, were included in the study. Erectile function was examined and 81 Doppler ultrasonography were performed after intracavernosal injection of alprostadil (10 mcg). In full-erection phase, peak systolic velocity (PSV) and systolic acceleration (SA) were measured, as well as resistive index (RI). Mean values were calculated for both cavernous arteries. Penile rigidity was assessed in three ways: clinical evaluation according to I. Goldstein, measurement of surface rigidity and evaluation of longitudinal rigidity.
RESULTS
During Doppler ultrasonography a strong correlation of penile rigidity with RI (0,71-0,85) and SA (0,63-0,69) was found. Indirect assessment of penile rigidity using PSV values was less precise. With RI values close to 1,0, SA is a more reliable method for indirect rigidity assessment.
CONCLUSION
Penile blood flow parameters, RI and SA, allow to evaluate a degree of rigidity and to eliminate subjectivity of the specialist performing the examination, as well as to obtain a range of penile rigidity values.
Topics: Male; Humans; Infant, Newborn; Penis; Penile Erection; Erectile Dysfunction; Hemodynamics; Ultrasonography, Doppler, Color
PubMed: 37417415
DOI: No ID Found