Subcutaneous Blood Vessels Research Articles

GelMA loaded with platelet lysate promotes skin regeneration and angiogenesis in pressure ulcers by activating STAT3

Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL’s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

Transformer Connections: Improving Segmentation in Blurred Near‐Infrared Blood Vessel Image in Different Depth

AbstractHigh‐fidelity segmentation of blood vessels plays a pivotal role in numerous biomedical applications, such as injection assistance, cancer detection, various surgeries, and vein authentication. Near‐infrared (NIR) transillumination imaging is an effective and safe method to visualize the subcutaneous blood vessel network. However, such images are severely blurred because of the light scattering in body tissues. Inspired by the Vision Transformer model, this paper proposes a novel deep learning network known as transformer connection (TRC)‐Unet to capture global blurred and local clear correlations while using multi‐layer attention. Our method mainly consists of two blocks, thereby aiming to remap skip connection information flow and fuse different domain features. Specifically, the TRC extracts global blurred information from multiple layers and suppresses scattering to increase the clarity of vessel features. Transformer feature fusion eliminates the domain gap between the highly semantic feature maps of the convolutional neural network backbone and the adaptive self‐attention maps of TRCs. Benefiting from the long‐range dependencies of transformers, we achieved competitive results in relation to various competing methods on different data sets, including retinal vessel segmentation, simulated blur image segmentation, and real NIR blood vessel image segmentation. Moreover, our method remarkably improved the segmentation results of simulated blur image data sets and a real NIR vessel image data set. The quantitative results of ablation studies and visualizations are also reported to demonstrate the superiority of the TRC‐Unet design. © 2024 The Author(s). IEEJ Transactions on Electrical and Electronic Engineering published by Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.

Optical diagnostic system for visualization subcutaneous blood vessels

Optical diagnostic system for visualization subcutaneous blood vessels

Optical parameters estimation in inhomogeneous turbid media using backscattered light: for transcutaneous scattering measurement of intravascular blood.

In our earlier research, a technique was developed to estimate the effective attenuation coefficient of subcutaneous blood vessels from the skin surface using the spatial distribution of backscattered near-infrared (NIR) light. The scattering effect in surrounding tissues was suppressed through the application of a differential principle, provided that the in vivo structure is known. In this study, a new method is proposed enabling the separate estimation of both scattering and absorption coefficients using NIR light of different wavelengths. The differential technique is newly innovated to make it applicable to the subcutaneous structure without requiring explicit geometrical information. Suppression of the scattering effect from surrounding tissue can be incorporated into the process of estimating the scattering and absorption coefficients. The validity of the proposed technique can be demonstrated through Monte Carlo simulations using both homogeneous and inhomogeneous tissue-simulating models. The estimated results exhibit good coherence with theoretical values (r2 = 0.988-0.999). Moreover, the vulnerability and robustness of the proposed technique against different measurement errors are verified. Optimal conditions for practical measurement are specified under various light-detection conditions. Separate estimation of scattering and absorption coefficients improves the accuracy of turbidity measurements and spectroscopy in biomedical applications considerably, particularly for noninvasive measurements and analysis of blood, lipids, and other components in subcutaneous blood vessels.

Retrospective Study of Fournier Gangrene and it’s Co-relation with FGSI Scores in its Management at a Tertiary Hospital in Mauritius

Background: Fournier’s gangrene is an acute rapidly progressive necrotizing fasciitis of infectious etiology. It usually affects scrotum, penis, perineum, perianal region and anterior abdominal wall occasionally. It is a poly-microbial infection resulting in thrombotic occlusion of small subcutaneous blood vessels leading to cutaneous gangrene. In spite of low prevalence at present FG carries considerable morbidity and mortality. It affects all age groups and both sexes. It is more prone in individuals with Diabetes Mellitus, chronic alcoholism, urogenital, anorectal diseases and immune-compromised persons. The diagnosis of FG is mostly clinical but radiological imaging was also needed to assess the extent of the disease. The management comprises of mainly aggressive surgical debridement under broad spectrum antibiotics coverage and ICU support. Material and Methods: It is a retrospective study comprising 30 number of FG cases clinically diagnosed and admitted in Dr Bruno Cheong Hospital, Flacq, Mauritius from 2019-2023. The data collected from hospital records comprising of routine and emergency cases. The preexisting co-morbidities, socio-economic status and outcome of management as per FGSI scores were assessed and recorded. Statistical Analysis: Standard statistical method, like SPSS was adopted for the analysis. Results: In the present study FGSI scores were co-related with the clinical picture and biochemical parameters of 30 no. of cases to assess severity of the disease. Moreover, FG being a serious and complicated disease, it was managed by a team comprising of surgeons and ICU team. Conclusion: FGSI scoring system is an excellent tool to assess the severity of the disease, in terms of mortality risk and outcome of management.

Visualization of Subcutaneous Blood Vessels Based on Hyperspectral Imaging and Three-Wavelength Index Images.

Blood vessel visualization technology allows nursing staff to transition from traditional palpation or touch to locate the subcutaneous blood vessels to visualized localization by providing a clear visual aid for performing various medical procedures accurately and efficiently involving blood vessels; this can further improve the first-attempt puncture success rate for nursing staff and reduce the pain of patients. We propose a novel technique for hyperspectral visualization of blood vessels in human skin. An experiment with six participants with different skin types, race, and nationality backgrounds is described. A mere separation of spectral layers for different skin types is shown to be insufficient. The use of three-wavelength indices in imaging has shown a significant improvement in the quality of results compared to using only two-wavelength indices. This improvement can be attributed to an increase in the contrast ratio, which can be as high as 25%. We propose and implement a technique for finding new index formulae based on an exhaustive search and a binary blood-vessel image obtained through an expert assessment. As a result of the search, a novel index formula was deduced, allowing high-contrast blood vessel images to be generated for any skin type.

Mechanisms of Cardiovascular Changes of Phototherapy in Newborns with Hyperbilirubinemia.

During phototherapy of jaundiced newborns, vasodilation occurs in the skin circulation compensated by vasoconstriction in the renal and mesenteric circulation. Furthermore, there is a slight decrease in cardiac systolic volume, and blood pressure, as well as an increase in heart rate and discrete changes in the heart rate variability (HRV). The primary change during phototherapy is the skin vasodilation mediated by multiple mechanisms: 1) Passive vasodilation induced by direct skin heating effect of the body surface and subcutaneous blood vessels, modified by myogenic autoregulation. 2) Active vasodilation mediated via the mechanism provided by axon reflexes through nerve C-fibers and humoral mechanism via nitric oxide (NO) and endothelin 1 (ET-1). During and after phototherapy is a rise in the NO:ET-1 ratio. 3) Regulation of the skin circulation through the sympathetic nerves is unique, but their role in skin vasodilation during phototherapy was not studied. 4) Special mechanism is a photorelaxation independent of the skin heating. Melanopsin (opsin 4) - is thought to play a major role in systemic vascular photorelaxation. Signalling cascade of the photorelaxation is specific, independent of endothelium and NO. The increased skin blood flow during phototherapy is enabled by the restriction of blood flow in the renal and mesenteric circulation. An increase in heart rate indicates activation of the sympathetic system as is seen in the measures of the HRV. High-pressure, as well as low-pressure baroreflexes, may play important role in these adaptation responses. The integrated complex and specific mechanism responsible for the hemodynamic changes during phototherapy confirm adequate and functioning regulation of the neonatal cardiovascular system, including baroreflexes.

Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study.

In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. A total of 31 individuals aged 47-87 years were randomly assigned to receive either 5g/day of fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups' blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (homeostasis model assessment ratio [HOMA-R]) than the placebo group. In addition, the percentage changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

Optical-visualized photoacoustic tomographic navigation

The current preoperative vascular imaging methods cannot achieve noninvasive high-resolution imaging of deep-localized vessels. Photoacoustic tomography (PAT) can show microvessels with centimeter depth and submillimeter diameter without the use of contrast agents. Combined with PAT and optical projection technology, the Hessian-matrix-based skin removal algorithm and the target matching method were developed to spatially align the photoacoustic data of subcutaneous blood vessels with the anatomy of real patients and to realize three-dimensional (3D) visualization of blood vessels from the body surface. The optical projection navigation system based on PAT has high spatial resolution (∼135 μm) and temporal resolution (0.1 s). In the rabbit injection experiment, 3D distributions of needle and blood vessel (>100 μm) were obtained by image segmentation, which proved that the method can guide micro plastic injection. Furthermore, healthy volunteers' forehead imaging experiments show that 3D visualization and cross-sectional images of the human forehead clearly show the vascular network and ability of the system to image submillimeter blood vessels with penetration depth (∼10.2 mm). Our work confirms that the method of integrated photoacoustic imaging and optical projection has great potential for noninvasive diagnosis and treatment of clinical blood vessels, opening a path for the application of photonics in medical esthetics.

Near-Infrared Three-Dimensional Imaging System and Recognition Algorithm for Subcutaneous Blood Vessels

Near-Infrared Three-Dimensional Imaging System and Recognition Algorithm for Subcutaneous Blood Vessels

Inflammatory Bowel Disease Presenting With Retiform Purpura.

A 7-year-old girl with sickle cell trait was admitted with inability to bear weight and a painful rash. Examination demonstrated retiform purpura (RP) of the right leg (Fig. 1A) with tenderness. The lesions had worsened despite treatment with cephalexin. Family history was unremarkable. There was no other skin involvement, history of fevers, or abnormalities on exam. Bloodwork was notable for microcytic anemia, elevated ESR, mildly elevated transaminases, and normal INR, albumin, and creatine kinase. MRI showed no muscle, bone, or joint involvement. Sequential cutaneous punch biopsies showed superficial and deep mixed perivascular and interstitial dermatitis without thromboses or leukocytoclastic vasculitis. Direct immunofluorescence findings were nonspecific. Hematologic evaluation included normal protein C and S levels, and mildly elevated d-dimer. Rheumatologic and infectious disease evaluations were also unremarkable. Over the following weeks new purpuric patches appeared, with some developing central duskiness and necrosis (Fig. 1B,C). After being noted to have mild colitic symptoms (PUCAI 25), elevated fecal calprotectin, persistently elevated transaminases, and a positive antinuclear antibody she underwent endoscopy, colonoscopy, and liver biopsy leading to the diagnoses of ulcerative colitis (Fig. 2) and autoimmune hepatitis. Treatment with systemic steroids improved her pain and transaminases, but the rash continued to evolve over the following 3 months developing a central necrotic eschar with surrounding ulceration to the subcutaneous tissue that slowly healed with supportive wound care (Fig. 1C–E).FIGURE 1.: Anterior views of the right thigh on presentation (A), 1 week later (B), 2 weeks later (C), 1 month later (D), 2 months later (E), and 3 months later (F). Purpura (A,B) were not palpable as are observed in cutaneous small-vessel vasculitis. Note the absence of marked purulence (D, E) or cribriform scarring (F) which are observed in pyoderma gangrenosum.FIGURE 2.: Colonoscopy showed gross pancolitis (A) with erythema, edema, friability and microhemorrhages. Histopathologic findings (B) included chronic active colitis with cryptitis (arrow) and abnormal crypt branching (arrowheads) but no granulomata.RP presents as branching purpuric patches and develops when dermal and subcutaneous blood vessels are compromised by vessel wall damage or lumen occlusion causing pain, necrosis, and ulceration (1). Underlying processes include those that damage the vessel wall such as small- or medium-vessel vasculitides, angioinvasive infections, and depositional diseases. RP also results from vessel lumen occlusion due to thrombosis from hypercoagulable states, platelet disorders, and red blood cell occlusion, as well as embolic processes (1,2). Clinically, it can resemble cutaneous small-vessel vasculitis (CSVV) or pyoderma gangrenosum but is differentiated by the lack of palpable purpura or marked purulence, respectively (3,4). Histologically, the vascular origin of RP is deeper than CSVV and it lacks the neutrophilic infiltrate characteristic of pyoderma gangrenosum (3–5). Treatment should address the underlying etiology and include supportive wound care (6). Here, the vaso-occlusive process RP was the presenting feature in a patient with unrecognized inflammatory bowel disease. This may reflect the incompletely understood association between coagulation and inflammation in inflammatory bowel disease that is posited to result from the interplay between a hyperactive coagulation system, decreases in natural coagulation inhibitors, abnormal fibrinolysis, endothelial dysfunction, chronically activated platelets, and systemic inflammation (2,7,8).

Near-Infrared Frequency Upconversion Luminescence Bioimaging Based on Cyanine Nanomicelles

Upconversion optical imaging has great application prospects in biomedical imaging. However, research on molecular upconversion luminescence materials is very limited. In this study, a cyanine dye modified using polyethylene glycol is reported, which has frequency upconversion luminescence (FUCL) capability and can be applied for in vivo FUCL imaging after forming nanomicelles. The optical properties of PEGylated cyanine dye show that the light absorption property of cyanine does not be influenced and can still emit near-infrared fluorescence. However, under the condition that the illumination wavelength is larger than the maximal fluorescence wavelength, the FUCL of cyanine dye is generated at the same position as the down-converted luminescence. The nanomicelles exhibit good biocompatibility. When applied to in vivo imaging, the cyanine-based nanomicelles not only qualify for high-resolution subcutaneous blood vessel imaging but also exhibit good imaging ability for various organs and tumors. These results point out that cyanine-based nanomicelles with FUCL characteristics are expected to be further applied in the field of biomedicine, providing a basis for the construction of FUCL molecules.

Shortwave infrared spatial frequency domain imaging for non-invasive measurement of tissue and blood optical properties.

.SignificanceThe shortwave infrared (SWIR) optical window (∼900 to 2000 nm) has attracted interest for deep tissue imaging due to the lower scattering of light. SWIR spatial frequency domain imaging (SWIR SFDI) provides wide-field tissue optical property measurements in this wavelength band. Key design and performance characteristics, such as portability, wavelength selection, measurement resolution, and the effect of skin have not yet been addressed for SWIR SFDI.AimTo fabricate and characterize a SWIR SFDI system for clinical use.ApproachThe optimal choice of wavelengths was identified based on optical property uncertainty estimates and imaging depth. A compact light-emitting diode-based dual wavelength SWIR SFDI system was fabricated. A two-layer inverse model was developed to account for the layered structure of skin. Performance was validated using tissue-simulating phantoms and in-vivo measurements from three healthy subjects.ResultsThe SWIR SFDI system had a resolution of at least at 880 nm and at 1100 nm. The two-layer inverse model reduced the error in deeper layer extractions by at least 24% in the phantom study. The two-layer model also increased the contrast between superficial vessels and the surrounding tissue for in-vivo measurements.ConclusionThe clinic-ready SWIR SFDI device is sensitive to small optical property alterations in diffuse media, provides enhanced accuracy in quantifying optical properties in the deeper layers in phantoms, and provided enhanced contrast of subcutaneous blood vessels.

Carbon monoxide combined with artificial blood cells acts as an antioxidant for tissues thermally-damaged by dye laser irradiation

Artificial red blood cells [i.e., hemoglobin vesicles (HbVs)] can be used as photosensitizers in pulsed-dye laser (PDL) treatment for port wine stains in animal models. Small HbVs are distributed in the vicinity of the endothelial cells of the blood vessels. In our previous in vivo experiments, both HbVs and red blood cells absorbed photons of the laser and generated heat, contributing to removal of very small blood vessels and large deeper subcutaneous blood vessels with PDL irradiation. Herein, we tested carbon monoxide-bound HbVs (CO-HbVs) that would produce heat energy while releasing CO in vessels after dye laser irradiation in a rabbit auricle model. We conducted this experiment to confirm secondary progression of thermal injury being reduced with the antioxidative property of CO. We histopathologically evaluated the damages to the large vessels and surrounding dermal tissue following PDL irradiation alone or subsequent to the intravenous injection of the qualified HbVs. The soft tissue damages were graded on a five-point scale and compared statistically. Intravenous CO-HbVs significantly reduced damage to the surrounding tissue after subsequent PDL irradiation; however, the degree of damage to the larger vessel wall resulted in a variety of changes, including a slight increase in our histopathological grades. This beneficial effect in dye laser treatment for port wine stains may be the result of the antioxidative property of CO against free radicals in the zone of stasis that may still be theoretically viable in burns. This effect of CO protecting tissues from thermal damage is consistent with previous reports of CO as a reducing agent. If the reducing agent can be delivered directly to the affected area immediately after the burn injury, even in a small amount, the complex inflammatory cascade may be reduced and unnecessary inflammation after laser treatment that lowers the patient’s quality of life can be avoided.

Applications of Multi-Contrast Optical Coherence Tomography in Assessment of Dysplastic Nevi to Malignant Melanoma

Melanoma is fatal for skin cancer. One of the essential predictive points in melanoma progression is the development of dysplastic nevi. This study observes subcutaneous blood vessels, lymphatic vessels, and skin thickness in a mouse model of dysplastic nevi in vivo through noninvasive, high-resolution, and multi-contrast optical coherence tomography (MCOCT). The subcutaneous microenvironment of the mice showed increased density of lymphatic vessels, dilated walls, and increased thickness of ears during the change of dysplastic nevi; and fragmentation of blood vessels at the later stage of the experimental period. Compared with conventional OCT only provides structure anatomy, MCOCT provides more extensive information for disease analysis and has the potential to detect progressive changes in dysplastic nevi.

Plasma-Derived Hemopexin as a Candidate Therapeutic Agent for Acute Vaso-Occlusion in Sickle Cell Disease: Preclinical Evidence.

People living with sickle cell disease (SCD) face intermittent acute pain episodes due to vaso-occlusion primarily treated palliatively with opioids. Hemolysis of sickle erythrocytes promotes release of heme, which activates inflammatory cell adhesion proteins on endothelial cells and circulating cells, promoting vaso-occlusion. In this study, plasma-derived hemopexin inhibited heme-mediated cellular externalization of P-selectin and von Willebrand factor, and expression of IL-8, VCAM-1, and heme oxygenase-1 in cultured endothelial cells in a dose-responsive manner. In the Townes SCD mouse model, intravenous injection of free hemoglobin induced vascular stasis (vaso-occlusion) in nearly 40% of subcutaneous blood vessels visualized in a dorsal skin-fold chamber. Hemopexin administered intravenously prevented or relieved stasis in a dose-dependent manner. Hemopexin showed parallel activity in relieving vascular stasis induced by hypoxia-reoxygenation. Repeated IV administration of hemopexin was well tolerated in rats and non-human primates with no adverse findings that could be attributed to human hemopexin. Hemopexin had a half-life in wild-type mice, rats, and non-human primates of 80–102 h, whereas a reduced half-life of hemopexin in Townes SCD mice was observed due to ongoing hemolysis. These data have led to a Phase 1 clinical trial of hemopexin in adults with SCD, which is currently ongoing.

Atypical longitudinal self-inflicted incised wounds as a cause of death in an ecstasy user.

A 32-year-old chronic drug abuser was found dead at the entrance to his home, covered in blood. Pools of blood, bloody footprints and bloodstains were found across the apartment. A double-edged razor was recovered from the scene. Autopsy revealed multiple incised wounds: two on the palmar aspect of both forearms (37cm and 33cm long, oriented longitudinally). The cuts extended into the subcutaneous adipose tissue, muscles and blood vessels. There was an additional 30cm cut extending across the middle of the torso anteriorly and two more cuts on the anteromedial aspect of the lower legs, set symmetrically (about 23 and 25cm long). These three cuts were more shallow than the upper extremity wounds. No hesitation wounds were identified. Toxicological analysis identified MDMA (ecstasy). The cause of death was exsanguination. The deceased has been using ecstasy for the previous five years and had a history of inpatient psychiatric treatment due to psychosis with delusions and hallucinations. These self-inflicted incised wounds had many atypical features: location (torso, legs and arms), longitudinal orientation and symmetrical distribution, absence of hesitation injuries, use of both dominant and non-dominant hand. The absence of previous suicide attempts and suicide note suggest that these self-inflicted injuries were not planned beforehand, but were abrupt. We hypothesize that this injury pattern is associated with both acute and chronic effects of MDMA.

Full-view in vivo skin and blood vessels profile segmentation in photoacoustic imaging based on deep learning

Photoacoustic (PA) microscopy allows imaging of the soft biological tissue based on optical absorption contrast and spatial ultrasound resolution. One of the major applications of PA imaging is its characterization of microvasculature. However, the strong PA signal from skin layer overshadowed the subcutaneous blood vessels leading to indirectly reconstruct the PA images in human study. Addressing the present situation, we examined a deep learning (DL) automatic algorithm to achieve high-resolution and high-contrast segmentation for widening PA imaging applications. In this research, we propose a DL model based on modified U-Net for extracting the relationship features between amplitudes of the generated PA signal from skin and underlying vessels. This study illustrates the broader potential of hybrid complex network as an automatic segmentation tool for the in vivo PA imaging. With DL-infused solution, our result outperforms the previous studies with achieved real-time semantic segmentation on large-size high-resolution PA images.

VENOUS HEMODYNAMICS IN ACUTE VARICOTHROMBOPHLEBITIS IN THE GREAT SAPHENOUS VEIN BASIN

Abstract. Objective. To evaluate the influence of venous hemodynamics in acute varicothrombophlebitis in the basin of the great saphenous vein on the spread of the thrombotic process.
 Materials and methods. The analysis of venous hemodynamic disorders in 245 patients with acute varicothrombophlebitis in the basin of the great saphenous vein was performed. The age of patients participating in the study ranged from 19 to 82 years (mean age 52±2,7 years). There were 93 men (38.0%) and 152 women (62.0%). The laboratory and instrumental methods were used for all the patients. They included doppler ultrasound and ultrasound duplex scanning. («ULTIMA PRO–30, zone Ultra», ZONARE Medical Systems Inc., USA).
 Results. When AVTF occurred in the GSV basin, all patients showed reflux in the superficial veins of the lower extremities. The ultrasound scanning was performed at the initial examination and immediately before urgent surgery for AVTF. The data of color duplex mapping allowed to reveal certain regularities of venous blood flow disturbance in AVTF and divided patients depending on the state of venous blood flow in the GSV basin into 5 groups. Each of these groups of patients, depending on the prevalence of venous reflux in the GSV pool, was divided into two subgroups: local and widespread reflux. It should be noted, that the conditions for the detection of total reflux in ATVF, with the involvement of GSV in the pathological process, were not due to thrombotic lesions of the latter. When venous reflux was detected, the elasticity and extensibility of the vein wall at the apex of thrombotic masses were evaluated. The ratio of the diameters of the GSV in these positions and the assessment of the "degree of elasticity" by Schwalb PG (2005), which indirectly characterized the state of venous tone were calculated. Venous reflux was assessed on a Valsalva test in vertical and horizontal positions. Venous reflux of blood in the femoral veins was found in 134 (54.7%) patients. At the same time, local reflux was found in 38 (15.5%), and widespread - in 96 (39.2%) patients. It should be noted that the prevalence of venous reflux was directly proportional to its power. Among all groups of patients with acute varicothrombophlebitis, 176 (71.8%) had widespread reflux in the great saphenous vein and 96 (39.2%) in the femoral vein. In 37 (15.1%) patients with acute varicothrombophlebitis revealed a combined nature of reflux, ie the spread of reflux from the superficial venous system not only to the apex of thrombotic masses, but also to the site of horizontal perforation, and reflux from the deep venous system spread through failed perineal veins in the great saphenous vein. Thus, widespread venous reflux was found in 87.3% of patients. In the absence of vertical reflux through the sapheno-femoral cochlea and the presence of an ascending process of thrombosis, it is necessary to identify another source of reflux.
 Conclusions. It is proved that the process of thrombosis in acute varicothrombophlebitis depends on the power of venous reflux, the severity of venous discharge through the communicating veins, the state of collateral venous blood flow in venous shunts and basins of large and small subcutaneous venous blood vessels. Venous reflux in the trunk of the great saphenous vein to some extent determines the embolism of the thrombus and participates in its development. Varicose veins of the great saphenous vein and the discharge of blood through incapable permeable veins reduce the power of reflux through the sapheno-femoral cochlea and reduce the rate of thrombosis in the main trunk.

Artificial red blood cells increase large vessel wall damage and decrease surrounding dermal tissue damage in a rabbit auricle model after subsequent flashlamp-pumped pulsed-dye laser treatment.

Artificial red blood cells (i.e. hemoglobin [Hb] vesicles [Hb-Vs]) function effectively as photosensitizers in flashlamp-pumped pulsed-dye laser (PDL) treatment for port-wine stains in animal models. Hb-Vs deliver more Hb to the vicinity of the endothelial cells. Both Hb-Vs and red blood cells absorb the laser energy and generate heat, supporting the removal of very small blood vessels and deeper subcutaneous blood vessels with PDL irradiation in in vivo experiments. Here, we analyzed the photosensitizing effect of Hb-Vs in PDL irradiation on large blood vessels and surrounding soft tissues. We histopathologically analyzed markers of damage to the large vessels and surrounding dermal tissue in a rabbit auricle model following PDL irradiation alone or subsequent to the addition of intravenous Hb-V injection. Markers were graded on a five-point scale and statistically compared. The changes in laser light absorption and reflection in a human skin model caused by the administration of Hb-Vs were evaluated using Monte Carlo light-scattering programs. Histological markers of damage to blood vessels were significantly greater in Hb-V-injected arteries and veins measuring 1-3mm in diameter as compared with the controls. However, Hb-V injection significantly reduced PDL-induced necrosis and hemorrhage in the surrounding tissues. During computer simulation, photon absorption increased within the vessel layer and decreased around the layer. Intravenous Hb-Vs increase the extent of damage in larger vessel walls but significantly reduce damage to the surrounding skin after subsequent PDL irradiation. These beneficial effects are the result of improving vessel selectivity by Hb-Vs in vessels. Hb-V administration prior to PDL irradiation therapy could mechanically improve the outcomes and safety profiles of port-wine stain treatment protocols.