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BioRxiv : the Preprint Server For... Apr 2024The renin-angiotensin system involves many more enzymes, receptors and biologically active peptides than originally thought. With this study, we investigated whether...
BACKGROUND
The renin-angiotensin system involves many more enzymes, receptors and biologically active peptides than originally thought. With this study, we investigated whether angiotensin-(1-5) [Ang-(1-5)], a 5-amino acid fragment of angiotensin II, has biological activity, and through which receptor it elicits effects.
METHODS
The effect of Ang-(1-5) (1µM) on nitric oxide release was measured by DAF-FM staining in human aortic endothelial cells (HAEC), or Chinese Hamster Ovary (CHO) cells stably transfected with the angiotensin AT -receptor (AT R) or the receptor Mas. A potential vasodilatory effect of Ang-(1-5) was tested in mouse mesenteric and human renal arteries by wire myography; the effect on blood pressure was evaluated in normotensive C57BL/6 mice by Millar catheter. These experiments were performed in the presence or absence of a range of antagonists or inhibitors or in AT R-knockout mice. Binding of Ang-(1-5) to the AT R was confirmed and the preferred conformations determined by docking simulations. The signaling network of Ang-(1-5) was mapped by quantitative phosphoproteomics.
RESULTS
Key findings included: (1) Ang-(1-5) induced activation of eNOS by changes in phosphorylation at eNOS and eNOS and thereby (2) increased NO release from HAEC and AT R-transfected CHO cells, but not from Mas-transfected or non-transfected CHO cells. (3) Ang-(1-5) induced relaxation of preconstricted mouse mesenteric and human renal arteries and (4) lowered blood pressure in normotensive mice - effects which were respectively absent in arteries from AT R-KO or in PD123319-treated mice and which were more potent than effects of the established AT R-agonist C21. (5) According to modelling, Ang-(1-5) binds to the AT R in two preferred conformations, one differing substantially from where the first five amino acids within angiotensin II bind to the AT R. (6) Ang-(1-5) modifies signaling pathways in a protective RAS-typical way and with relevance for endothelial cell physiology and disease.
CONCLUSIONS
Ang-(1-5) is a potent, endogenous AT R-agonist.
PubMed: 38948791
DOI: 10.1101/2024.04.05.588367 -
Frontiers in Veterinary Science 2024This study aimed to evaluate the feasibility of establishing an arterial acute mesenteric ischemia (AMI) model in canines using transcatheter autologous thrombus...
PURPOSE
This study aimed to evaluate the feasibility of establishing an arterial acute mesenteric ischemia (AMI) model in canines using transcatheter autologous thrombus administration.
MATERIALS AND METHODS
Ten canines were divided into the experimental group (Group A, = 5) and the sham group (Group B, = 5). The canines in Group A received thrombus administration to the superior mesenteric artery (SMA) through a guiding catheter, while the canines in Group B received normal saline administration. Blood samples were collected and tested at baseline and 2 h after modelling. Canines in Group A underwent manual thromboaspiration after blood and intestine samples were collected. Ischaemic grades of intestinal mucosa were evaluated under light microscopes.
RESULTS
The AMI models were successfully conducted in all canines without procedure-related vessel injury or death. At the 2-h follow-up, the high-sensitivity C-reactive protein and D-dimer in Group A were significantly higher than in Group B (5.72 ± 1.8 mg/L vs. 2.82 ± 1.5 mg/L, = 0.024; 2.25 ± 0.8 μg/mL vs. 0.27 ± 0.10 μg/mL, = 0.005; respectively). The mean histopathologic intestinal ischaemic grade in Group A was significantly higher than in Group B (2.4 ± 0.5 vs. 0.8 ± 0.4, < 0.001). After a median of 2 times of thromboaspiration, 80% (4/5) of the canines achieved complete SMA revascularisation.
CONCLUSION
This experimental study demonstrated that establishing an arterial model in canines using endovascular approaches was feasible. The present model may play an important role in the investigation of endovascular techniques in the treatment of arterial AMI.
PubMed: 38948676
DOI: 10.3389/fvets.2024.1373914 -
Journal of Family Medicine and Primary... May 2024Corona virus disease (COVID-19) initially appeared to be an exclusively respiratory ailment. While that is true in a vast majority of the cases, its evolution and later...
Corona virus disease (COVID-19) initially appeared to be an exclusively respiratory ailment. While that is true in a vast majority of the cases, its evolution and later evidence have shown that it can afflict virtually any organ system in the human body after first gaining entry through the respiratory tract. The COVID-19 vaccines were one of the turning points in the campaign to control the COVID-19 pandemic. However, after their extensive use all over the world, it has emerged that they can cause some dangerous collateral damage. We, herein, report the case of a 58-year-old woman who presented to us with signs and symptoms of acute intestinal obstruction 4 months after receiving her first dose of Covishield vaccination for COVID-19. Her blood tests showed a high D-dimer and normal platelet count. She was previously admitted to the hospital with an acute abdomen 3 months back. A contrast-enhanced computed tomography (CECT) scan of the abdomen done then had revealed thrombi in the aorta and inferior mesenteric and splenic arteries. She was started on low-molecular-weight heparin and discharged on tablet Warfarin after clinical improvement. CECT abdomen done during her present admission revealed a proximal small bowel stricture with dilated proximal and collapsed distal loops. She underwent a laparoscopic jejuno-ileal resection anastomosis. During the post-operative period, a repeat CECT abdomen done to evaluate multiple episodes of vomiting revealed pulmonary embolism in the lower chest cuts. A venous Doppler revealed extensive deep venous thrombosis of the left lower limb. A thrombophilia profile diagnosed anti-phospholipid antibody syndrome, an exacerbation of which was likely precipitated by the COVID-19 vaccine.
PubMed: 38948557
DOI: 10.4103/jfmpc.jfmpc_1006_23 -
Clinical Case Reports Jul 2024Isolated spontaneous superior mesenteric artery (SMA) dissection is relatively rare. Often found incidentally on cross-sectional imaging, often managed non-operatively....
Isolated spontaneous superior mesenteric artery (SMA) dissection is relatively rare. Often found incidentally on cross-sectional imaging, often managed non-operatively. We present a patient who presented with chest pain and was found to have a SMA dissection.
PubMed: 38947536
DOI: 10.1002/ccr3.9121 -
Experimental & Molecular Medicine Jul 2024Angiotensin II (AngII) induces the contraction and proliferation of vascular smooth muscle cells (VSMCs). AngII activates phospholipase C-β (PLC-β), thereby inducing...
Angiotensin II (AngII) induces the contraction and proliferation of vascular smooth muscle cells (VSMCs). AngII activates phospholipase C-β (PLC-β), thereby inducing Ca mobilization as well as the production of reactive oxygen species (ROS). Since contraction is a unique property of contractile VSMCs, signaling cascades related to the proliferation of VSMCs may differ. However, the specific molecular mechanism that controls the contraction or proliferation of VSMCs remains unclear. AngII-induced ROS production, migration, and proliferation were suppressed by inhibiting PLC-β3, inositol trisphosphate (IP) receptor, and NOX or by silencing PLC-β3 or NOX1 but not by NOX4. However, pharmacological inhibition or silencing of PLC-β3 or NOX did not affect AngII-induced VSMC contraction. Furthermore, the AngII-dependent constriction of mesenteric arteries isolated from PLC-β3, NOX1, NOX4 and normal control mice was similar. AngII-induced VSMC contraction and mesenteric artery constriction were blocked by inhibiting the L-type calcium channel Rho-associated kinase 2 (ROCK2) or myosin light chain kinase (MLCK). The activation of ROCK2 and MLCK was significantly induced in PLC-β3 mice, whereas the depletion of Ca in the extracellular medium suppressed the AngII-induced activation of ROCK2, MLCK, and vasoconstriction. AngII-induced hypertension was significantly induced in NOX1 and PLC-β3 mice, whereas LCCA ligation-induced neointima formation was significantly suppressed in NOX1 and PLC-β3 mice. These results suggest that PLC-β3 is essential for vascular hyperplasia through NOX1-mediated ROS production but is nonessential for vascular constriction or blood pressure regulation.
PubMed: 38945956
DOI: 10.1038/s12276-024-01271-6 -
International Journal of Emergency... Jun 2024Mesenteric arterial thrombosis is an extremely rare thrombotic event, especially during pregnancy, that can cause rapid fatal consequences unless the patient receives...
BACKGROUND
Mesenteric arterial thrombosis is an extremely rare thrombotic event, especially during pregnancy, that can cause rapid fatal consequences unless the patient receives early definitive treatment.
CASE PRESENTATION
We report the case of a 34-year-old female presenting in her seventh week of gestation with severe abdominal pain who was promptly diagnosed with mesenteric artery occlusion amidst incipient miscarriage. The patient underwent a successful mesentery artery embolectomy, recovered and was later diagnosed with elevated factor VIII activity.
CONCLUSION
The diagnosis of mesenteric ischemia should be considered in pregnant women presenting with severe abdominal pain and any prior predisposing factors. Our case highlights the pivotal role of the emergency physician in maintaining a high index of suspicion coupled with timely and determined action. The prognosis of this high mortality condition depends on prompt diagnosis, early definite management and successful multidisciplinary cooperation.
PubMed: 38943051
DOI: 10.1186/s12245-024-00661-x -
Annals of Vascular Surgery Jun 2024During human morphogenesis, the definitive kidneys derive from the metanephros during Carnegie Stage 14 to 23. The pronephros and the mesonephros develop previously and...
OBJECTIVE
During human morphogenesis, the definitive kidneys derive from the metanephros during Carnegie Stage 14 to 23. The pronephros and the mesonephros develop previously and successively to finally lead to the formation of the urinary tract. Renal vascularization, first described in 1912 by Félix using a "ladder theory" model, is highly variable and current available morphogenesis descriptions do not explain all reported anatomical variations. The aim of this work was to study the morphogenesis of the human metanephros and its vascularization by three-dimensional reconstructions of human embryos.
METHOD
Histological sections of 23 human embryos from the Carnegie Collection and 5 human embryos from the French collection (Carnegie stages 14 to 23) were completely digitalized and reconstructed in three dimensions using specific softwares and then analyzed by descriptive method using manual annotation.
RESULTS
In all studied embryos, the mesonephric arteries did not reach the metanephros irrespective to the position of the metanephros during its cranial ascent. Before the end of the cranial metanephros migration (15 embryos), at the level of the aorto-iliac bifurcation, a "primitive" vascularization was shown in 9 of them. The renal artery originated from the primitive iliac arteries for 8 embryos and from the inferior mesenteric artery in one embryo. Further, a capillary cluster emerging from the lateral wall of the aorta and extending towards the metanephros was found in 2 embryos (Carnegie stages 21 and 22). This may correspond to a phenomenon of neo-angiogenesis responsible of the definitive renal artery.
CONCLUSION
The present study reported the morphogenesis of human renal arteries between Carnegie stages 14 and 23 using an original method of tridimensional computerized reconstructions of historical human embryos. Some original findings, in contradiction with the original Felix's description, may explain the most frequently reported anatomical variations.
PubMed: 38942378
DOI: 10.1016/j.avsg.2024.04.010 -
BMJ Case Reports Jun 2024A man in his 70s presented with a sudden onset stabbing back pain radiating to the chest and pre-syncopal symptoms. He underwent urgent investigations, including a CT...
A man in his 70s presented with a sudden onset stabbing back pain radiating to the chest and pre-syncopal symptoms. He underwent urgent investigations, including a CT angiogram aorta which did not reveal any abnormalities within the thorax, abdomen or pelvis and no cause of symptoms was identified. After being discharged, he re-presented 2 days later with syncopal episodes, abdominal pain and a significant drop in haemoglobin levels. This time, a CT mesenteric angiogram showed two hepatic artery pseudoaneurysms and a large haemoperitoneum. Following a hepatic artery embolisation, a workup showed that the likely cause of the pseudoaneurysms was a rare first presentation of polyarteritis nodosa. This case highlights the importance of considering the possibility of an aneurysmal rupture, especially when common causes of an acute abdomen have been excluded, and not relying on previous negative investigations to exclude pathology, as the outcomes can be detrimental.
Topics: Humans; Polyarteritis Nodosa; Aneurysm, False; Male; Hepatic Artery; Aged; Embolization, Therapeutic; Aneurysm, Ruptured; Computed Tomography Angiography; Rupture, Spontaneous; Hemoperitoneum; Abdominal Pain
PubMed: 38937262
DOI: 10.1136/bcr-2023-257411 -
Cancers Jun 2024The "vein definition" for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to...
The "vein definition" for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to tumor involvement or occlusion. Radical pancreatectomies with SMV resection without PV/SMV reconstruction are scarcely discussed in the literature. Retrospective analysis of 19 radical pancreatectomies for "low" LA PDAC with SMV and all its tributaries resection without PV/SMV reconstruction has shown zero mortality; overall morbidity-56%; Dindo-Clavien-3-10.5%; R0-rate-82%; mean operative procedure time-355 ± 154 min; mean blood loss-330 ± 170 mL; delayed gastric emptying-25%; and clinically relevant postoperative pancreatic fistula-8%. In three cases, surgery was associated with superior mesenteric (n2) and common hepatic artery (n1) resection. Surgery was completed without vein reconstruction (n13) and with inferior mesenteric-to-splenic anastomosis (n6). There were no cases of liver, gastric, or intestinal ischemia. A specific complication of the SMV resection without reconstruction was 2-3 days-long intestinal edema (48%). Median overall survival was 25 months, and median progression-free survival was 18 months. All the relapses, except two, were distant. The possibility of successful SMV resection without PV/SMV reconstruction can be predicted before surgery by CT-based reconstructions. The mandatory anatomical conditions for the procedure were as follows: (1) preserved SMV-SV confluence; (2) occluded SMV for any reason (tumor or thrombus); (3) well-developed inferior mesenteric vein collaterals with dilated intestinal veins; (4) no right-sided vein collaterals; and (5) no varices in the upper abdomen. Conclusion: "Low" LA PDACs involving SMV with all its tributaries can be radically and safely resected in highly and specifically selected cases without PV/SMV reconstruction with an acceptable survival rate.
PubMed: 38927939
DOI: 10.3390/cancers16122234 -
Emergency Radiology Jun 2024Intestinal obstruction is a common surgical emergency with high morbidity and mortality. Patients presenting with features of small bowel obstruction need urgent... (Review)
Review
Intestinal obstruction is a common surgical emergency with high morbidity and mortality. Patients presenting with features of small bowel obstruction need urgent evaluation to avoid complications such as bowel gangrene, perforation, or peritonitis. Imaging is necessary in most cases of suspected bowel obstruction, to take an appropriate decision, for apt patient management. Among the common causes of small bowel obstruction, adhesions, external herniae, malignancies, and Crohn's disease top the chart. Imaging helps in determining the presence of obstruction, the severity of obstruction, transition point, cause of obstruction, and associated complications such as strangulation, bowel gangrene, and peritonitis. This review is based on the cases with unusual causes of bowel obstruction encountered during our routine practice and also on the extensive literature search through the standard textbooks and electronic databases. Through this review we want our readers to have sound knowledge of the imaging characteristics of the uncommon yet important causes of bowel obstruction. We have also revisited and structured a checklist to simplify the approach while reporting a suspected case of small bowel obstruction. Imaging plays a key role in the diagnosis of small bowel obstruction and in determining the cause and associated complications. Apart from the common causes of small bowel obstruction, we should also be aware of the uncommon causes of small bowel obstruction and their imaging characteristics to make an accurate diagnosis and for apt patient management.
PubMed: 38926239
DOI: 10.1007/s10140-024-02256-8