Blood Vessel Area Research Articles

Cadmium reduces growth of male fetuses by impairing development of the placental vasculature and reducing expression of nutrient transporters

In utero exposure to the toxic metal cadmium (Cd) alters fetoplacental growth in rodents and has been inversely associated with birth weight and infant size in some birth cohorts. Moreover, studies suggest that Cd may have differential effects on growth and development according to offspring sex. The purpose of the current study was to evaluate changes in male and female fetoplacental development following a single injection of saline (5 ml/kg ip) or cadmium chloride (CdCl2, 2.5, 5 mg/kg, ip) on gestational day (GD) 9. By GD18, no changes in fetal or placental weights were observed after treatment with 2.5 mg/kg CdCl2. By comparison, the weight and length of male fetuses and their placentas were reduced following treatment with 5 mg/kg CdCl2 whereas no change was observed in females. In addition, the area of maternal and fetal blood vessels as well as the expression of the glucose transporters, Glut1 and Glut3, and the endothelial marker, CD34, were reduced in the placentas of CdCl2-treated male offspring compared to females. Interestingly, the placentas of females accumulated 80% more Cd than males after CdCl2 (5 mg/kg) administration. Female placentas also had higher concentrations of zinc and the zinc transporter Znt1 compared to males which may explain the limited changes in fetal growth observed following CdCl2 treatment. Taken together, disruption of vasculature development and reduced expression of glucose transporters in the placenta provide potential mechanisms underlying reduced fetal growth in male offspring despite the greater accumulation of Cd in female placentas.

HISTOMORPHOMETRIC ASSESSMENT OF ARCHITECTONICS AND VASCULARIZATION IN MAXILLARY ALVEOLAR PROCESS BONE TISSUE

The expansion of the most relevant priority fields in fundamental and applied medicine, along with the progress in modern dentistry and reconstructive maxillofacial surgery, requires in-depth understanding of the morphological and functional status of the maxillary alveolar process bone tissue and knowledge of the mandibular alveolar part, thus allowing selecting a reasonable treatment tactics for maxillofacial pathologies. Qualitative features of maxillary alveolar process microarchitectonics, angioarchitectonics, as well as the periodontal ligament arrangement at various levels of the teeth roots, histological and morphometric studies of bone tissue in the frontal and distal sections, as well as the maxillary segments of the maxillary medial incisors and the first molars were studied in 5 certified male cadavers with preserved dentition. The histological findings show, that the microarchitectonics of the maxillary alveolar process features a lamellar bone consists of plates that are adjacent tightly to each other. The bone plates orientation in the frontal section is longitudinal, while in the distal part it is along concentric circles located around the Haversian canals. The angioarchitectonics of the maxillary alveolar process features tubular structures, which run mainly perpendicular to the bone surface, with numerous anastomoses. As the morphometric analysis of the maxillary alveolar process vascular system shows, in the frontal section the number of vessels per 1 mm2 is 22.41± 1.76 - 22.87± 2.08; in the distal section − 23.94± 1.88 - 25.02±2.69 (p≤0.01); the average diameter of vessels in the frontal section is 25.34±2.45 microns – 26.06 ±3.17 microns, in the distal section − 25.72±2.31 microns – 26.14± 2.93 microns (p≤0.05); the average wall thickness in the frontal section is 1.43± 0.09 microns - 1.48± 0.12 microns, in the distal section − 1.50± 0.11 microns – 1.54± 0.14 microns (p≤ 0.01). The vestibular surface of the maxillary medial incisors at the level of the root gingival part, as well as the oral surface at the root apical level have been found to be zones of periodontal ligament compression, while the oral surface at the root gingival level and the vestibular surface at the root apical level – zones of the periodontal ligament stretching. At the root gingival level of the first maxillary molars, the medial and vestibular surfaces are zones of the periodontal ligament compression, whereas the oral and the distal surfaces stand as the zones of the periodontal ligament stretching. As a quantitative assessment showed, the structural elements of the medial incisors periodontal ligament, and the first maxillary molars had loose connective tissue – taken by its specific area – prevailing in the periodontal ligament compression zone; the specific area of dense connective tissue, though, was found to be prevailing at the periodontal ligament stretching zone under chewing stress. The data obtained through a quantitative analysis of the periodontal ligament microvascular bed of the medial incisors, and the first maxillary molars, reveal that the area with blood vessels in the compression zones by far exceeds the area of blood vessels in the stretching zones. It appears rather reasonable that in case of a biomechanical stress experienced by the incisor-maxillary and molar-maxillary segments of the upper jaw, the periodontal ligament morphology will change throughout the root, depending on the compression and stretching zone localization.

Topical brimonidine for the management of facial erythema in rosacea: a histological, histometric, and immunohistochemical study.

Facial erythema in rosacea is a troublesome embarrassing presentation with limited options of treatment. Daily brimonidine gel was shown to be an effective modality of treatment. Being unavailable in Egypt and the scarcity of objective evaluation of its therapeutic effect motivated the search for other alternatives. To evaluate the use and effectiveness of topical brimonidine eye drops for the management of facial erythema in rosacea with the aid of objective assessment. The study was conducted on 10 rosacea patients presented with facial erythema. Brimonidine tartrate eye drops 0.2% were applied twice daily for 3 months on areas of red facial skin. Punch biopsies were obtained before and after 3 months of treatment. Routine hematoxylin and eosin (H&E) staining as well as CD34 immunohistochemical staining were performed for all biopsies. Sections were examined to detect the changes in the count and the surface area of blood vessels. Evaluation of clinical results showed good improvement of facial redness at the end of treatment (55-75%). Only 10% of subjects expressed rebound erythema. H&E and CD34 stained sections showed an increased count of dilated dermal blood vessels, which decreased significantly after treatment in count and surface area (P = 0.005, and P = 0.004, respectively). Topical brimonidine eye drops proved to be effective in managing facial erythema in rosacea, providing an available and cheaper alternative to brimonidine gel. The study improved the subjective evaluation in the context of objective assessment of treatment efficacy.

Inhibition of vascular endothelial growth factor-A downregulates angiogenesis in psoriasis: A pilot study.

Vascular Endothelial Growth Factor (VEGF)-A-mediated angiogenesis participates in the pathogenesis of psoriasis, thus inviting the hypothesis that anti-VEGF-A therapy could be beneficial in psoriasis. While anti-angiogenic agents are used in oncology and ophthalmology, these therapeutic strategies remain unexplored for the management of psoriasis. Our objective was to investigate ex vivo how VEGF-A blockade impacts blood vessels, epidermis and immune cells in organ-cultured plaque and non-lesional skin from patients with psoriasis. Skin biopsies from patients with psoriasis (n=6; plaque and non-lesional skin) and healthy controls (n=6) were incubated with anti-VEGF-A monoclonal antibody (bevacizumab, Avastin®) or a human IgG1 isotype control for 72-h in serum-free organ culture. CD31/LYVE-1, Ki-67, and mast cell tryptase expression were assessed by quantitative immunohistomorphometry. VEGF-A levels in plasma, PBMCs and skin culture supernatants were measured. Inhibition of VEGF-A blocked all free VEGF-A ex vivo, reduced blood vessel area and the number of blood vessel endothelial cells in plaques of psoriasis (*p<0.05). The treatment effect correlated significantly with levels of VEGF-A in organ culture supernatants (r=0.94; *p<0.05) from plaque skin and with plasma levels of VEGF-A from patients with psoriasis (r=0.943; *p=0.017). These ex vivo data are the first studies to objectively investigate the potential of VEGF-A inhibition as a novel adjuvant treatment strategy for psoriasis. Taken together, our data encourage further investigation by clinical trial to explore whether downregulating pathological angiogenesis has clinical utility, especially in patients with severe psoriasis or those with elevated levels of VEGF-A in plasma and/or skin.

CT quantitative analysis of pulmonary changes in rheumatoid arthritis.

To explore the application of quantitative computed tomography (CT) in analyses of lung changes in patients with rheumatoid arthritis (RA). A total of 150 clinically diagnosed RA patients underwent chest CT and 150 matched non-smokers subjects with normal chest CT are enrolled. A CT software is applied to analyze CT obtained from both groups. The quantitative indices of emphysema are expressed as the percentage of lung area with attenuation < -950HU to the total lung volume (LAA-950%), and pulmonary fibrosis was expressed as the percentage of lung area with a attenuation of -200 to -700HU to the total lung volume (LAA-200--700%), quantitative indicators of pulmonary vascular include aortic diameter (AD), pulmonary artery diameter (PAD), the ratio of PAD to AD (PAD/AD ratio), the number of blood vessels (TNV), and the cross area of blood vessels (TAV). The receiver operating characteristic (ROC) curve is used to evaluate the ability of these indexes in identifying the changes in the lung in RA patients. Compared to the control group, the RA group has significantly lower TLV, larger AD, and smaller TNV and TAV (3921±1101 vs. 4490±1046, 33.26±4.20 vs. 32.95±3.76, 13.14±4.93 vs. 17.53±3.34, and 96.89±40.62 vs. 163.32±34.97, respectively, with all p < 0.001). Peripheral vascular indicator TAV has the better ability to identify lung changes in RA patients (area under ROC curve AUC = 0.894) than TNV (AUC = 0.780) or LAA-200&sim-700% (AUC = 0.705). Quantitative CT can detect changes in lung density distribution and peripheral vascular injury in patients with RA and assess the severity.

Effect of Intracoronal Sealing Biomaterials on the Histological Outcome of Endodontic Revitalisation in Immature Sheep Teeth—A Pilot Study

The influence of intracoronal sealing biomaterials on the newly formed regenerative tissue after endodontic revitalisation therapy remains unexplored. The objective of this study was to compare the gene expression profiles of two different tricalcium silicate-based biomaterials alongside the histological outcomes of endodontic revitalisation therapy in immature sheep teeth. The messenger RNA expression of TGF-β, BMP2, BGLAP, VEGFA, WNT5A, MMP1, TNF-α and SMAD6 was evaluated after 1 day with qRT-PCR. For evaluation of histological outcomes, revitalisation therapy was performed using Biodentine (n = 4) or ProRoot white mineral trioxide aggregate (WMTA) (n = 4) in immature sheep according to the European Society of Endodontology position statement. After 6 months' follow-up, one tooth in the Biodentine group was lost to avulsion. Histologically, extent of inflammation, presence or absence of tissue with cellularity and vascularity inside the pulp space, area of tissue with cellularity and vascularity, length of odontoblast lining attached to the dentinal wall, number and area of blood vessels and area of empty root canal space were measured by two independent investigators. All continuous data were subjected to statistical analysis using Wilcoxon matched-pairs signed rank test at a significance level of p < 0.05. Biodentine and ProRoot WMTA upregulated the genes responsible for odontoblast differentiation, mineralisation and angiogenesis. Biodentine induced the formation of a significantly larger area of neoformed tissue with cellularity, vascularity and increased length of odontoblast lining attached to the dentinal walls compared to ProRoot WMTA (p < 0.05), but future studies with larger sample size and adequate power as estimated by the results of this pilot study would confirm the effect of intracoronal sealing biomaterials on the histological outcome of endodontic revitalisation.

Abstract 6592: An AI platform for vascular and fibrosis analysis of pathology images

Abstract Introduction: Changes in the number of blood vessels and the proportion of fibrosis regions in xenograft tumors are key indicators for efficacy of oncology drugs, which currently are assessed mainly by human visual examination that is time-consuming, inaccurate and biased because only part of a pathology image is checked. We developed an online AI platform that integrates machine learning algorithms in Computer Vision to quickly and automatically obtain accurate and comprehensive information on blood vessels and fibrosis regions from a whole pathology image. Methods: In a stained pathology image, blood vessels are stained with a different color than other components (e. g. connective tissues, tumor cells, background), so we can directly locate pixels representing them. They also have different topological structures, so we can outline and count the contours of vessels. To count the number of vessels more precisely and reduce the interference of noise, we keep a contour only if it intersects with some located pixels and the number of pixels in the intersection exceeds an adjustable threshold. The fibrosis regions are identified by color contrast since they are stained with a distinct and easily recognizable color. The algorithms were implemented using the OpenCV package. Results: Our AI platform automatically annotates blood vessels and fibrosis regions in pathology images, and generates reports in excel format to report the number and total area of blood vessels, the area and ratio of fibrosis regions, and execution time. It demonstrates superior performance to standard pathology software. Citation Format: Yawen Zheng, Likun Zhang, Dawei Wang, Sheng Gao. An AI platform for vascular and fibrosis analysis of pathology images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6592.

Physiological Functions of the Platelets and the Importance of the Correction of Their Disorders in Acute Coronary Syndrome

Abstract—Platelets play a key role in the development of thrombosis and inflammation. These cells are the key participants in pathological thrombosis due to their ability to attach to damaged areas of blood vessels and further accumulation at the sites of damage. Although platelet activation and adhesion should be considered as a physiological response to a sudden rupture of an atherosclerotic plaque, which frequently contributes to its repair, the uncontrolled progression of such a process in the coronary arteries may result in the formation of a thrombus occluding the lumen of the vessel, that cause the development of myocardial infarction. This review is mainly devoted to the consideration of the correction of platelet function using antiplatelet drugs, which have led to significant positive changes in the fight against acute coronary syndrome and myocardial infarction.

Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone.

Peripheral nerve injuries result in impaired neuromuscular interactions, leading to morphological and functional alterations. Adjuvant suture repair methods have been used to improve nerve regeneration and modulate the immune response. Heterologous fibrin biopolymer (HFB), a scaffold with adhesive properties, plays a critical role in tissue repair. The aim of this study is to evaluate neuroregeneration and immune response focusing on neuromuscular recovery, using suture-associated HFB for sciatic nerve repair. Forty adult male Wistar rats were distributed into four groups (n=10): C (control), only sciatic nerve location; D (denervated), neurotmesis and 6-mm gap removal and fixation stumps in subcutaneous tissue; S (suture), neurotmesis followed by suture; and SB (suture + HFB), neurotmesis followed by suture and HFB. Analysis of M2 macrophages (CD206+ ), as well as the morphology and morphometry of nerves, soleus muscle, and neuromuscular junctions (NMJs), were performed at 7 and 30 days after surgery. The SB group had the highest M2 macrophage area in both periods. After 7 days, SB was the only group similar to the C group regarding the number of axons; furthermore, after 30 days, the SB group was closer to the C group concerning blood vessel and central myonuclear numbers, NMJ angle, and connective tissue volume. After 7 days, increases in nerve area, as well as the number and area of blood vessels, were also observed in SB. HFB potentiates the immune response, increases axonal regeneration, induces angiogenesis, prevents severe muscle degeneration, and assists in NMJ recovery. In conclusion, suture-associated HFB has major implications for improved peripheral nerve repair.

Oral formulation of Wnt inhibitor complex reduces inflammation and fibrosis in intraperitoneal implants in vivo.

The use of implantable biomaterials to replace physiological and anatomical functions has been widely investigated in the clinic. However, the selection of biomaterials is crucial for long-term function, and the implantation of certain biomaterials can cause inflammatory and fibrotic processes, triggering a foreign body reaction that leads to loss of function and consequent need for removal. Specifically, the Wnt signaling pathway controls the healing process of the human body, and its dysregulation can result in inflammation and fibrosis, such as in peritoneal fibrosis. Here, we assessed the effects of daily oral administration of a Wnt pathway inhibitor complex (CD:LGK974) to reduce the inflammatory, fibrotic, and angiogenic processes caused by intraperitoneal implants. CD:LGK974 significantly reduced the infiltration of immune cells and release of inflammatory cytokines in the implant region compared to the control groups. Furthermore, CD:LGK974 inhibited collagen deposition and reduced the expression of pro-fibrotic α-SMA and TGF-β1, confirming fibrosis reduction. Finally, the CD:LGK974 complex decreased VEGF levels and both the number and area of blood vessels formed, suggesting decreased angiogenesis. This work introduces a potential new application of the Wnt inhibitor complex to reduce peritoneal fibrosis and the rejection of implants at the intraperitoneal site, possibly allowing for longer-term functionality of existing clinical biomaterials.

Angiogenesis and activated fibroblast in a model of premature ventricular contraction-induced cardiomyopathy.

Premature ventricular contractions (PVCs) are the most common ventricular arrhythmia in the elderly, and when frequent, can result in PVC-induced cardiomyopathy (PVC-CM). PVC-CM canine model showed eccentric hypertrophy and fibrosis in the left ventricle (LV). The underlying structural and molecular mechanism behind this LV remodeling is unknown. In situ structural adaptations of the LV tissue and the activation of the VEGF/ERK1/2 signaling pathway were studied in the PVC-CM model. Pacemakers were implanted in healthy canines where PVCs were enabled only in the PVC-CM group (50% of PVC burden, 200-220-ms coupling interval) for 12 weeks. Fixed LV longitudinal- and cross-sections were stained with anti-α-SMA antibody, a marker of activated fibroblast (myofibroblasts) and smooth muscle cells (blood vessels), and WGA-AF633 (a marker of cell membranes). Confocal images were analyzed using artificial intelligence (AI)-powered autonomous software, AIVIA. Western blot (WB) analysis was used to study the pro-angiogenic signaling pathway and proteins associated with fibroblast activation. In situ analysis showed a significant increase in the total area and number of blood vessels, along with an increase in activated fibroblasts in PVC-CM LV sections. Also, the PVC group showed a 30% increase in the number of activated fibroblasts per cardiomyocyte compared with the sham group. The endothelial marker, eNOS, and IL-1β, a cytokine involved in fibroblast activation, were elevated in the PVC-CM group. Additionally, the VEGF-A, VEGF-B, and VEGF receptor 2 were upregulated in PVC-CM vs Sham; downstream ERK1/2 was hyperphosphorylated and overexpressed, and MMP9 (marker of fibroblast activation linked to this pathway) was elevated in PVC-CM vs Sham. In conclusion, activated fibroblasts and angiogenesis are a feature of the cardiac LV hypertrophic remodeling in PVC-CM.

Comparison of surgical outcomes between early and advanced class of jugular paragangliomas following application of our modified surgical techniques

To compare the safety and effectiveness of surgical treatment of jugular paragangliomas (JPs) following the application of our modified surgical techniques. Fifty-six patients with JPs were analyzed for tumor classification, surgical outcomes, and intratumor blood vessels. The gross total resection in C1–2 (100%) was significantly greater than that in C3 and D (66.7%). Good postoperative facial nerve (FN) function (House–Brackmann I–II) was achieved in 89.5% C1–2 cases, which was not significantly different from C3 and D (93.3%) (P = 0.694). Preoperative and postoperative lower cranial nerve (LCN) deficits correlated with the Fisch’s classification of tumors (P < 0.05), and intraoperative blood loss was greater in advanced tumors (P = 0.050). Further study showed that the cross-sectional area of intratumor blood vessels was positively associated with intraoperative blood loss (P < 0.001). Surgical excision of JPs is a safe and effective strategy, and early surgical treatment is a good option for patients with C1–2 tumors without surgical contraindications.

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-β). The Kruskal-Wallis/Dunn test was used for statistical analysis. PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-β immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Local Adenoviral Delivery of Vascular Endothelial Growth Factor C Induces Lymphangiogenesis in the Conjunctiva in Rabbits

Introduction: The purpose of this study was to determine if conjunctival lymphangiogenesis can be induced using adenoviral delivery of vascular endothelial growth factor C (VEGF-C). Methods: Seventeen New Zealand white rabbits received a subconjunctival injection containing 3.5 × 107 plaque-forming units of an adenoviral vector containing the gene-encoding VEGF-C (Ad-VEGF-C). The contralateral eye was used for control experiment (the same volume of either saline or an empty vector). After 2 weeks, the animals were examined with trypan blue conjunctival lymphangiography, and the eyes were harvested for histology and immunohistochemistry (podoplanin and CD31). Results: Trypan blue conjunctival lymphangiography revealed significantly more extensive conjunctival vessel network in the Ad-VEGF-C group compared with control: 1.35 ± 0.67 versus 0.28 ± 0.17 vessel length/analysed area (p = <0.0001). This finding was confirmed with immunohistochemistry, where a significant increase in the number of lymphatic vessels was found compared to control; 34 ± 9 per mm2 versus 13 ± 8 per mm2 (p = 0.0019). Furthermore, there was a significant increase in lymphatic cross-sectional area; 32,500 ± 7,900 µm2 per mm2 versus 17,600 ± 9,700 µm2 per mm2 (p = 0.0149). Quantification of blood vessels revealed no significant difference in blood vessel density between Ad-VEGF-C and control; 19 ± 9 per mm2 versus 14 ± 8 per mm2 (p = 0.1971). There was no significant difference in total blood vessel area; 13,200 ± 7,600 µm2 per mm2 versus 7,100 ± 3,000 µm2 per mm2 (p = 0.0715). Eyes treated with an adenoviral vector (VEGF-C or empty vector) responded with a reactive cellular response, predominantly lymphocytes, towards the vector. Conclusion: The study demonstrates the feasibility of inducing conjunctival lymphangiogenesis with a single subconjunctival injection of Ad-VEGF-C. Future studies will explore how this can be used with a therapeutic purpose.

Newly formated (tertiary) lymphoid structures in tumor growth

Aim to reproduce tertiary lymphoid structures and study their features in a malignant neoplasm in the experiment.&#x0D; Material and methods. Male white rats of the Wistar stress-resistant line were inoculated with the tumor strain sarcoma M1. Using the methods of microsurgical preparation, color lymphography and ultrasonic sonolipodestruction we isolated the lymph nodes without metastatic lesions (described as secondary in normal anatomy), the lymph nodes with metastases of M1 sarcoma, and the newly formed nodes (extrauterine or tertiary). Lymph nodes were examined macroscopically, micromorphometric studies were performed, histological and immunohistochemical signs of tertiary lymph nodes were determined. The obtained data were subjected to statistical analysis.&#x0D; Results. In 60% of rats, in the right axillary region, in addition to the secondary lymph nodes described in normal anatomy, the tertiary lymph nodes were found on the side of the tumor. They were located near the histologically verified metastatic lymph node. The studied parameters of the main structural and functional zones of the tertiary lymph nodes had the following features: the enlarged marginal sinuses; a fewer number of lymphoid follicles; the average total area of blood vessels increased by 92% in relation to the metastatic lymph nodes and by 78% in relation to the secondary lymph nodes. The significant differences were registered with CD3, CD4, CD20, CD30 markers.&#x0D; Conclusion. The study proved the possibility of reproducing tertiary lymphoid nodes in the experiment with malignant growth and revealed a number of their features.

The effect of spring diameter on porcine ileal distraction enterogenesis.

Spring-mediated distraction enterogenesis has proven to be successful for intestinal lengthening. We aimed to evaluate the effect of spring diameter mismatch on intestinal adaptation. Juvenile mini-Yucatan pigs underwent placement of compressed nitinol springs with diameter of 10, 11, or 12mm into the ileal lumen. Pigs were euthanized on postoperative day 7. The lengths, histology, total area of blood vessels, and enteric ganglia were evaluated. All spring groups exhibited significant ileal lengthening. Across the different diameters, spring-expanded segments were similar in terms of ileal lengthening, crypt height, muscular thickness, blood vessels, and enteric ganglia area. Spring-mediated distraction enterogenesis is successful in the porcine ileum. A smaller diameter spring is as effective as a larger diameter spring in lengthening the ileum. Springs of varying diameters result in comparable structural changes in the ileum.

The prevention of leakage of ileo-colonic anastomosis in an experimental peritonitis

Introduction. In colon surgery, intestinal anastomotic leaks are the main contributor to postoperative mortality. The incidence of this complication in the formation of small-colonic anastomoses in urgent surgery reaches 12% or more. It is required to develop simple and reliable techniques of intestinal suturing in conditions of peritonitis.The aim of the study was to investigate the morphological events occurring in the small-colonic anastomosis formed using various options under simulated peritonitis.Materials and methods. An experimental study involved 2 groups of Wistar white rats (25 animals - the control group and 25 - the main one). Peritonitis was simulated by dissecting the ileum into circles in 5-6 cm from the ileocecal angle. A day later, a relaparotomy was performed, a section of the intestine with a defect was excised, the distal loop was tied up, a small-colonic anastomosis was formed with a proximal loop: in the end-to-side study group the intervention was performed according to the author's method (RF patent No. 2709253 dated 12/17/2019), in the control group using side-to-side anastomosis. In 6 days, anastomosis was taken from the survived animals for histological examination. Histological examination was carried out at a magnification x400 and x630. Micromorphometry was performed with the count of neutrophils, fibroblasts and measurement of the relative area of ​​blood vessels in the anastomotic suture. Fisher's exact test, Mann-Whitney test were used for statistical data processing, quantitative data were described in the median and interquartile interval format.Results. An original end-to-side anastomosis resulted in a greater number of fibroblasts and blood vessels in the muscular and submucosal layers of the intestinal wall in the suture zone than in the side-to-side anastomosis. The number of anastomotic leaks in the study group was 4 times less than in the control group.Conclusion. The use of the authors end-to-side anastomosis technique improves blood supply and repair of the suture area in a small-colonic anastomosis under 1-day simulated peritonitis; this being accompanied by a decreased incidence of anastomosis failure.

Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-β1.

Hematopoietic stem cell (HSC) therapy has shown promise for tissue regeneration after ischemia. Therefore, there is a need to understand mechanisms underlying endogenous HSCs activation in response to ischemic stress and coordination of angiogenesis and repair. SHP-1 plays important roles in HSC quiescence and differentiation by regulation of TGF-β1 signaling. TGF-β1 promotes angiogenesis by stimulating stem cells to secrete growth factors to initiate the formation of blood vessels and later aid in their maturation. We propose that SHP-1 responds to ischemia stress in HSC and progenitor cells (HSPC) via regulation of TGF-β1. A mouse hind limb ischemia model was used. Local blood perfusion in the limbs was determined using laser doppler perfusion imaging. The number of positive blood vessels per square millimeter, as well as blood vessel diameter (μm) and area (μm2), were calculated. Hematopoietic cells were analyzed using flow cytometry. The bone marrow transplantation assay was performed to measure HSC reconstitution. After femoral artery ligation, TGF-β1 was initially decreased in the bone marrow by day 3 of ischemia, followed by an increase on day 7. This pattern was opposite to that in the peripheral blood, which is concordant with the response of HSC to ischemic stress. In contrast, SHP-1 deficiency in HSC is associated with irreversible activation of HSPCs in the bone marrow and increased circulating HSPCs in peripheral blood following limb ischemia. In addition, there was augmented auto-induction of TGF-β1 and sustained inactivation of SHP-1-Smad2 signaling, which impacted TGF-β1 expression in HSPCs in circulation. Importantly, restoration of normal T GF-β1 oscillations helped in the recovery of limb repair and function. HSPC-SHP-1-mediated regulation of TGF-β1 in both bone marrow and peripheral blood is required for a normal response to ischemic stress.

Cutaneous vascular structure and perfusion in patients with chronic plaque psoriasis.

Vascular dysfunction is a significant contributor to the pathophysiology of psoriasis. Some individuals have variation within the gene for vascular endothelial growth factor-A (VEGF-A), which confers an increased risk of developing psoriasis and having a severe disease phenotype, and may determine responsiveness to treatment. To determine whether patients with psoriasis have alterations in cutaneous microvascular anatomy and physiology due to expression of VEGF and whether laser Doppler imaging has utility in the assessment of this. Twelve adult volunteers with Type 1 chronic plaque psoriasis underwent laser Doppler imaging of plaque and uninvolved skin. Skin biopsies were taken from the areas imaged for immunohistochemistry, including blood and lymphatic vessel markers, and VEGF-A isotype analysis (VEGF-A121, VEGF-A165 and VEGF-D). Venous blood was collected for DNA extraction, VEGF-A genotyping and peripheral blood mononuclear cell culture. Mean blood vessel area (P < 0·01), number of blood vessels (P < 0·001), number of lymphatic vessels (P < 0·001) and blood flow (P < 0·001) was significantly increased in psoriasis plaques, as was expression of VEGF-A121 (P < 0·01), VEGF-A165 (P < 0·04) and VEGF-D (P < 0·01). Blood flow within psoriasis plaques was independent of their increased vascularity (P < 0·01) and may be associated with baseline productivity of VEGF. The number of blood vessels within uninvolved skin in patients with psoriasis was associated with the VEGF-A (rs833061) genotype (P = 0·01), in a relationship suggesting an allele dosing effect. Noninvasive imaging of blood flow may help determine the cutaneous vascular signature for individual patients. This may be a useful prognostic indicator of psoriasis susceptibility and severity, and thus support selection of treatments.

The Complex Composition of Trans-resveratrol, Quercetin, Vitamin E and Selenium Inhibits the Growth of Colorectal Carcinoma.

Numerous studies have demonstrated an anti-cancer action of plant-derived polyphenols. Their action is mainly related to antioxidant, anti-inflammatory, immunomodulatory and inhibitory properties. It is expected that proper composition of nutrition factors with anti-cancer activity may prevent from cancer incidence or inhibit cancer progression. The aim of the study was to investigate the anti-cancer properties of a standardized composition of compounds: trans-resveratrol, quercetin, vitamin E and selenium (Neoplasmoxan, Vebiot) in a mouse model of CT26 colorectal carcinoma. Colorectal carcinoma cells (CT26) were introduced subcutaneously (2×105/mouse) on the back of the mice. Neoplasmoxan suspension was administered intragastrically, daily, for 21 consecutive days. In collected tumors, the area occupied by tumor blood vessels and the number of immune cells; macrophages and CD8-positive cytotoxic T lymphocytes were evaluated. It was observed that administration of Neoplasmoxan inhibits the growth of colorectal carcinoma in mice. Tumor volume after Neoplasmoxan administration was 40% smaller than in control groups. No overall toxicity of Neoplasmoxan was observed. The area of blood vessels in tumors of mice that received Neoplasmoxan was reduced by approximately 20%. The area occupied by macrophages increased about 60% compared to the control group. However, no increased number of CD8-positive cytotoxic T lymphocytes was observed in the group that received Neoplasmoxan. A tendency of Neoplasmoxan to inhibit the growth of colorectal carcinoma was recorded. It also seems that additional combination of the tested preparation with standard chemotherapy or radiotherapy should bring a synergistic therapeutic effect.