An interesting case of reruptured endovascularly coiled aneurysm managed with clipping

Endovascular treatment has proven to be effective in the management of intracranial aneurysm, and can achieve permanent occlusion in up to 85% of cases, reducing the bleeding or rebleeding rate. A paradigm shift from microsurgical clipping to endovascular intervention has been observed since the publication of the International Subarachnoid Aneurysm Trial. Aneurysm recurrence after coil embolization remains both a major shortcoming of endovascular treatment and a daunting challenge for neurosurgeons without optimal management strategies.: We present a case report of a patient with history of previously endovascularly coiled and presenting with aneurysmal bleed. Microsurgical clipping is an effective intervention for managing reruptured previously coiled intracranial aneurysm.

Stable Gastric Pentadecapeptide BPC 157 Therapy of Rat Glaucoma

Cauterization of three episcleral veins (open-angle glaucoma model) induces venous congestion and increases intraocular pressure in rats. If not upgraded, one episcleral vein is regularly unable to acquire and take over the whole function, and glaucoma-like features persist. Recently, the rapid upgrading of the collateral pathways by a stable gastric pentadecapeptide BPC 157 has cured many severe syndromes induced by permanent occlusion of major vessels, veins and/or arteries, peripherally and centrally. In a six-week study, medication was given prophylactically (immediately before glaucoma surgery, i.e., three episcleral veins cauterization) or as curative treatment (starting at 24 h after glaucoma surgery). The daily regimen of BPC 157 (0.4 µg/eye, 0.4 ng/eye; 10 µg/kg, 10 ng/kg) was administered locally as drops in each eye, intraperitoneally (last application at 24 h before sacrifice) or per-orally in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat until the sacrifice, first application being intragastric). Consequently, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, normal retinal and choroidal blood vessel presentation and normal optic nerve presentation. As leading symptoms, increased intraocular pressure and mydriasis, as well as degeneration of retinal ganglion cells, optic nerve head excavation and reduction in optic nerve thickness, generalized severe irregularity of retinal vessels, faint presentation of choroidal vessels and severe optic nerve disc atrophy were all counteracted. In conclusion, we claim that the reversal of the episcleral veins cauterization glaucoma appeared as a consequence of the BPC 157 therapy of the vessel occlusion-induced perilous syndrome.

METHOD OF HEALTHY TEETH EXTRACTION IN ORTHODONTIC TREATMENT

In the treatment of orthodontic patients, the most difficult and controversial is the question of removing healthy teeth. The aim was to evaluate the 30-year orthodontic clinical experience of the staff of the Postgraduate Education Department of Orthodontists for the use of medical methods of removal of individual healthy teeth in the treatment of dental anomalies. The aim of our study is to evaluate 30 years of orthodontic clinical practice of the staff of the Postgradu- ate Education Department of Orthodontists for the use of medical removal of individual healthy teeth in the treatment of dental anomalies. 1340 dental outpatient cards of orthodontic patients who underwent orthodontic treatment and completed it with a positive result were reviewed at two clinical bases of the Postgraduate Education Department of Orthodontists. The analysis of selected outpatient cards was performed taking into account the age and sex of patients, as well as depending on the type of pathological occlusion (according to Angle) and the type of teeth removed. Cards of patients with Angle's class I and II pathology were selected for scientific analysis. 241 patient underwent tooth extraction at both bases in total in terms of treatment, which is 17.99%. The number of patients with removed temporary teeth was 59.39% (143/241), patients with removed permanent teeth - 40.7% (98/241). Permanent teeth were removed 1.45 times more often at the clinic "Orthodontist", which is explained by the higher frequency of requests for orthodontic care from adults and adolescents. On the basis of the Postgraduate Education Department of Orthodontists, patients with deciduous teeth predominate - 69% (51/74) against 45% (75/167) in the clinic "Orthodontist". This is due to the fact that the main contingent of patients who seek help from the department are patients in the age of variable occlusion, which means that the Hotz method and the author's method of corrective removal of temporary molars are used more often. A detailed analysis of the documentation of patients was performed at the base of the Postgraduate Edu- cation Department of Orthodontists who were treated with the use of individual teeth extraction by periods of occlusion. Children in the period of the first half of the variable occlusion accounted for 39.19% (29/74), chil- dren in the second half of the variable occlusion - 25.67% (19/74), and patients older than 13 years - 35.14% (26/74). In female patients, regardless of age, tooth extraction is performed 13% -15% of cases more often than in men, which is due to a more attentive attitude to the appearance of girls by their parents. Among patients with various types of pathological occlusions treated with the method of removal of individual healthy teeth, children, adolescents and adults with Angle class I occlusion pathology accounted for 53.94% (130/241). Assessing the frequency of application of the method of extraction of healthy teeth by age, we can say that in pathology of class II according to Angle most often the method is used in patients with permanent occlusion in 38.73% (43/111). In the treatment of pathology of class I according to Angle, the removal of healthy teeth is twice as often performed in alternating occlusion than in permanent. In the treatment of pathology of class II according to Angle, the method of removing individual teeth is more often used in patients with permanent occlusion. Research on the consequences of removing individual healthy teeth in orthodontic treatment is relevant and timely. Both in the private sector of orthodontic care and on the clinical basis of the Postgraduate Education Department of Orthodontists, about a fifth of patients of any age and any orthodontic pathology are treated orthodontically using the clinical method of removing individual healthy teeth.

Spinal Tuina Improves Cognitive Impairment in Cerebral Palsy Rats through Inhibiting Pyroptosis Induced by NLRP3 and Caspase-1

Cerebral palsy (CP) is a severe cerebral disease with high mortality and morbidity, which leads to great challenges for the suffering children and their families. Hence, the need for the efficacious and safe treatments is urgent. As a physical therapy arising from traditional Chinese medicine (TCM), Tuina has shown multiple effects on various diseases, including cerebral palsy. Nevertheless, the detailed mechanisms of Tuina on CP remain unknown, which impedes its further clinical application. Herein, we explored the effects of Tuina on CP and its potential mechanisms. Thirty Sprague Dawley (SD) male rats were randomly divided into sham, model, and Tuina groups (model + Tuina). CP rat model was established by hypoxia-ischemia via permanent occlusion of left common carotid artery and hypoxia for 2.5 hours caused by anaerobic environment, which was subsequently followed by onset of Tuina treatment from postnatal day 7 (P7) to P49. After completion of Tuina treatment, the behavioral tests showed that Tuina treatment not only improved the retarded body weight and impaired motor balance function, but also ameliorated weakened learning and memory function of CP rats. Moreover, immunohistochemistry and western blot also revealed a reduced expression of NLRP3 inflammasome and corresponding pyroptosis-related molecules induced by NLRP3 in CP rats after Tuina treatment. Therefore, our study indicated that Tuina treatment may improve impaired neurocognitive function of CP rats, which was possibly realised via inhibiting NLRP3-induced pyroptosis.

Abstract P340: Histone Methyltransferase Smyd1a Protects Heart From Ischemic Injury By Regulating Mitochondrial Respiration

SMYD1a, a myosin-specific histone lysine methyltransferase, plays a major role in regulating disease-induced remodeling in the adult heart. Previously, we demonstrated that the inducible loss of this chromatin-bound enzyme is sufficient to induce cardiac hypertrophy and failure in vivo , which is preceded by downregulation of mitochondrial proteins involved in oxidative phosphorylation (OXPHOS), and reduction of mitochondrial respiration capacity. However, our most recent data in transgenic mice (TG) displaying inducible, cardiomyocyte-specific overexpression of SMYD1a show that these mice are protected from ischemic injury after permanent occlusion (PO) of the LAD manifested by reduced infarct size and cardiac dysfunction compared to littermate controls (WT), suggesting that SMYD1 plays a protective role in the heart and mitigates disease-induced remodeling. Additionally, global proteomic evaluation of cardiac tissue from TG mice showed unique expression of metabolic enzymes, including proteins from the electron transport chain, and our high-resolution mitochondrial respirometry analysis showed that overexpression of SMYD1a leads to increased oxygen consumption rates through Complex I and II. To further asses OXPHOS efficiency in TG mice we subjected them to permanent occlusion of the LAD and evaluated ATP production rates in isolated mitochondria from TG and WT mice, by measuring the molar amount of ATP produced per mole of atomic oxygen consumed (known as ATP:O ratio). Interestingly, we observed a significant increase in ATP:O ratio in TG mice 24h after PO suggesting that they are much more efficient at producing ATP. Finally, we show that the global regulation of mitochondrial respiration in TG mice occurs through transcriptional control of Ppargc1α . Our results confirm that cardiac expression of Ppargc1α was significantly reduced in WT mice (48h after PO) but maintained at basal levels in TG mice, which also corroborated with our ChIP-qPCR data showing SMYD1a binding to the Ppargc1α promoter and regulating its expression. Overall, these results show that SMYD1a can mitigate ischemic injury and adverse remodeling in the adult myocardium, which occurs through Ppargc1α expression and regulation of cardiac energetics and metabolism.

Abstract MP263: CD8+ T-cells Regulate Macrophage Recruitment And Retention After Myocardial Infarction

Heart failure is the number one reason for admission, with myocardial infarctions (MI) as the underlying etiology in of 70% cases. Macrophages facilitate cardiac healing after the MI. Resident macrophages die due to the initial ischemic event and are replaced by monocyte-derived macrophages. The adaptive immune system, including cytotoxic CD8+ T-cells, are known regulators of inflammation and are upregulated in the circulation and in the infarct after an MI. Previously we showed mice deficient in CD8+ T-cells were protected from adverse remodeling. We hypothesized that after an MI, CD8+ T-cells regulate the recruitment and retention of monocytes. To test our hypothesis, C57Bl6J (WT; n≥3/day post-MI) and mice deficient in CD8+ T-cells (CD8-/-; n≥3/day post-MI) underwent permanent occlusion and tissue was collected at post-MI days 0 (no MI), 1, 3, 7, and 14. Mac3 staining of the infarct was performed to determine the macrophage time course. Infarct tissue was analyzed by bulk RNAseq (n=3/day/genotype) to determine possible genetic regulators at post-MI days 1, 7, and 14. Data was clustered based on the genetic markers of macrophage subtypes identified in previous single cell genomic studies. Mac3 staining of WT mice showed macrophages begin to infiltrate as early as post-MI day 1, peaking at day 7, and beginning to reach baseline levels by day 14. Interestingly, CD8-/- mice had a delay in macrophage recruitment at day 1; however, by day 3 there was almost double the amount of macrophages compared to the WT group. While no differences were observed at day 7 post-MI, CD8-/- mice had elevated macrophages at post-MI day 14 compared to the WT mice. Based on the gene clusters, the infarct tissue of CD8-/- mice had increased markers of resident-like macrophages at post-MI days 7 and 14 compared to WT mice. Resident macrophages have been shown to be cardioprotective post-MI, suggesting a possible protective mechanism in CD8-/- mice. In conclusion, our data indicates that CD8+ T-cells influence cardiac remodeling over the post-MI time course by facilitating in macrophage recruitment and retention. Furthermore, in the absence of CD8+ T-cells, there was an increase in resident-like macrophages that could prove to point to a more favorable repopulation of cells post-MI.

BPC 157 Therapy and the Permanent Occlusion of the Superior Sagittal Sinus in Rat: Vascular Recruitment

We show the complex syndrome of the occluded superior sagittal sinus, brain swelling and lesions and multiple peripheral organs lesions in rat. Recovery goes centrally and peripherally, with the stable gastric pentadecapeptide BPC 157, which alleviated peripheral vascular occlusion disturbances, rapidly activating alternative bypassing pathways. Assessments were gross recording, venography, ECG, pressure, microscopy, biochemistry. The increased pressure in the superior sagittal sinus, portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, severe brain swelling and lesions (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus), particular veins (azygos, superior mesenteric, inferior caval) dysfunction, heart dysfunction, lung congestion as acute respiratory distress syndrome, kidney disturbances, liver failure, and hemorrhagic lesions in gastrointestinal tract were all assessed. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally, intragastrically, or topically to the swollen brain at 1 min ligation-time, or at 15 min, 24 h and 48 h ligation-time. BPC 157 therapy rapidly attenuates the brain swelling, rapidly eliminates the increased pressure in the ligated superior sagittal sinus and the severe portal and caval hypertension and aortal hypotension, and rapidly recruits collateral vessels, centrally ((para)sagittal venous collateral circulation) and peripherally (left superior caval vein azygos vein-inferior caval vein). In conclusion, as shown by all assessments, BPC 157 acts against the permanent occlusion of the superior sagittal sinus and syndrome (i.e., brain, heart, lung, liver, kidney, gastrointestinal lesions, thrombosis), given at 1 min, 15 min, 24 h or 48 h ligation-time. BPC 157 therapy rapidly overwhelms the permanent occlusion of the superior sagittal sinus in rat.

Angiogenin in the Neurogenic Subventricular Zone After Stroke

Ischemic stroke is a leading cause of death and disability worldwide with effective acute thrombolytic treatments. However, brain repair mechanisms related to spontaneous or rehabilitation-induced recovery are still under investigation, and little is known about the molecules involved. The present study examines the potential role of angiogenin (ANG), a known regulator of cell function and metabolism linked to neurological disorders, focusing in the neurogenic subventricular zone (SVZ). Angiogenin expression was examined in the mouse SVZ and in SVZ-derived neural stem cells (NSCs), which were exposed to exogenous ANG treatment during neurosphere formation as well as in other neuron-like cells (SH-SY5Y). Additionally, male C57Bl/6 mice underwent a distal permanent occlusion of the middle cerebral artery to study endogenous and exercise-induced expression of SVZ-ANG and neuroblast migration. Our results show that SVZ areas are rich in ANG, primarily expressed in DCX+ neuroblasts but not in nestin+NSCs. In vitro, treatment with ANG increased the number of SVZ-derived NSCs forming neurospheres but could not modify SH-SY5Y neurite differentiation. Finally, physical exercise rapidly increased the amount of endogenous ANG in the ipsilateral SVZ niche after ischemia, where DCX-migrating cells increased as part of the post-stroke neurogenesis process. Our findings position for the first time ANG in the SVZ during post-stroke recovery, which could be linked to neurogenesis.

Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension

Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd–Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome.

Orbital metastasis from hepatocellular carcinoma revealed by sudden exophthalmos

Orbital metastases represent a rare condition and only 33 cases of metastases from hepatocellular carcinoma (HCC), usually revealed by slowly progressive exophthalmos, have been described in the literature. A 62-year-old man affected by HCC reported a sudden left exophthalmos and amaurosis. A cranial CT scan revealed pathological tissue occupying the superior portion of the orbit. During endoscopic decompression of the optic nerve, an active venous intraorbital haemorrhage was noted. Following angiography, permanent occlusion was performed on a neoforming circulus fed by ramification of the anterior deep temporal artery, anterior ramification of the superficial temporal artery and sphenoidal ramification of the medial meningeal artery. A percutaneous incisional orbital biopsy showed features of metastatic foci of HCC. This is the first description of orbital metastasis from HCC revealed by a sudden exophthalmos.