Microcirculatory Changes Research Articles

Low-intensity pulsed ultrasound reduces lymphedema by regulating macrophage polarization and enhancing microcirculation.

Background: Conventional therapies reduce lymphedema but do not cure it because they cannot modulate the pathophysiology of secondary lymphedema. Lymphedema is characterized by inflammation. We hypothesized that low-intensity pulsed ultrasound (LIPUS) treatment could reduce lymphedema by enhancing anti-inflammatory macrophage polarization and microcirculation. Methods: The rat tail secondary lymphedema model was established through the surgical ligation of lymphatic vessels. The rats were randomly divided into the normal, lymphedema, and LIPUS treatment groups. The LIPUS treatment (3min daily) was applied 3days after establishing the model. The total treatment period was 28days. Swelling, fibro adipose deposition, and inflammation of the rat tail were evaluated by HE staining and Masson's staining. The photoacoustic imaging system and laser Doppler flowmetry were used to monitor microcirculation changes in rat tails after LIPUS treatment. The cell inflammation model was activated with lipopolysaccharides. Flow cytometry and fluorescence staining were used to observe the dynamic process of macrophage polarization. Results: After 28days of treatment, compared with the lymphedema group, the tail circumference and subcutaneous tissue thickness of rats in the LIPUS group were decreased by 30%, the proportion of collagen fibers and the lymphatic vessel cross-sectional area was decreased, and tail blood flow was increased significantly. Cellular experiments revealed a decrease in CD86+ macrophages (M1) after LIPUS treatment. Conclusion: The transition of M1 macrophage and the promotion of microcirculation could be responsible for the beneficial effect of LIPUS on lymphedema.

The acute adaptation of skin microcirculatory perfusion in vivo does not involve a local response but rather a centrally mediated adaptive reflex.

Introduction: Cardiovascular homeostasis involves the interaction of multiple players to ensure a permanent adaptation to each organ's needs. Our previous research suggested that changes in skin microcirculation-even if slight and distal-always evoke an immediate global rather than "local" response affecting hemodynamic homeostasis. These observations question our understanding of known reflexes used to explore vascular physiology, such as reactive hyperemia and the venoarteriolar reflex (VAR). Thus, our study was designed to further explore these responses in older healthy adults of both sexes and to potentially provide objective evidence of a centrally mediated mechanism governing each of these adaptive processes. Methods: Participants (n = 22, 52.5 ± 6.2 years old) of both sexes were previously selected. Perfusion was recorded in both feet by laser Doppler flowmetry (LDF) and photoplethysmography (PPG). Two different maneuvers with opposite impacts on perfusion were applied as challengers to single limb reactive hyperemia evoked by massage and a single leg pending to generate a VAR. Measurements were taken at baseline (Phase I), during challenge (Phase II), and recovery (Phase III). A 95% confidence level was adopted. As proof of concept, six additional young healthy women were selected to provide video imaging by using optoacoustic tomography (OAT) of suprasystolic post-occlusive reactive hyperemia (PORH) in the upper limb. Results: Modified perfusion was detected by LDF and PPG in both limbs with both hyperemia and VAR, with clear systemic hemodynamic changes in all participants. Comparison with data obtained under the same conditions in a younger cohort, previously published by our group, revealed that results were not statistically different between the groups. Discussion: The OAT documentary and analysis showed that the suprasystolic pressure in the arm changed vasomotion in the forearm, displacing blood from the superficial to the deeper plexus vessels. Deflation allowed the blood to return and to be distributed in both plexuses. These responses were present in all individuals independent of their age. They appeared to be determined by the need to re-establish hemodynamics acutely modified by the challenger, which means that they were centrally mediated. Therefore, a new mechanistic interpretation of these exploratory maneuvers is required to better characterize in vivo cardiovascular physiology in humans.

Clinical profile and dynamic magnetic resonance imaging in Hirayama disease: a single-centered cross-sectional study in Nepal.

Eighteen patients were assessed for clinical and radiological Hirayama disease. Clinical criteria included insidious onset nonprogressive chronic upper limb weakness and atrophy in teens or early twenties without sensory deficits and coarse tremors. MRI was done in a neutral position followed by neck flexion to evaluate cord atrophy and flattening, abnormal cervical curvature, loss of attachment between the posterior dural sac and subjacent lamina, anterior shifting of the posterior wall of the cervical dural canal, posterior epidural flow voids, and an enhancing epidural component with its dorsal extension. The mean age was 20.33 years, and the majority, 17 (94.4%), were male. Neutral-position MRI revealed loss of cervical lordosis in 5 (27.8%) patients, cord flattening in all patients with asymmetry in 10 (55.5%), and cord atrophy was observed in 13 (72.2%) patients with localized cervical cord atrophy in only 2 (11.1%) and extension of atrophy to dorsal cord in 11 (61.1%) patients. Intramedullary cord signal change was seen in 7 (38.9%) patients. Loss of attachment of posterior dura and subjacent lamina and anterior displacement of dorsal dura was seen in all patients. A crescent-shaped epidural intense enhancement was noted along the posterior aspect of the distal cervical canal in all patients, with dorsal level extension in 16 (88.89%) patients. The mean thickness of this epidural space was 4.38±2.26 (mean±2SD), and the mean extension was 5.5±4.6 vertebral levels (mean±2SD). The high degree of clinical suspicion can guide additional contrast studies in flexion as a set MRI protocol for early detection and avoiding false negative diagnoses of HD.

A lumbar disc degeneration model established through an external compressive device for the study of microcirculation changes in bony endplates

ObjectiveTo establish a new animal model of intervertebral disc degeneration (IDD) by axial compression on lumbar spine of rabbits and to investigate the changes of microcirculation in bony endplates during the progress of IDD. Methods32 New Zealand white rabbits were equally divided into 4 groups as follows: Control group with no operation and compression, Sham operation group with apparatus placement only, 2-week compression group and 4-week compression group with the devices installed and compressed for their preset duration. All groups of rabbits underwent MRI, histological evaluation, disc height index measurement and Microfil contrast agent perfusions to examine the ratio of endplate microvascular channels. ResultsThe new animal model of IDD was successfully established after axial compression for 4 weeks. The MRI grades for the 4-week compression group was 4.63 ± 0.52 and significantly different to the sham operation group (P < 0.05). Histologically, decrease of normal NP cells and extracellular matrix and disorganization of the architecture of the annulus fibrosus apparently occurred in 4-week compression group, which was different to the sham operation group (P < 0.05). There was no statistically difference between the 2-week compression and sham operation group no matter in the histology and MRI assessment. The disc height index slowly decreased as the compression duration rose. The ratio of microvascular channel volume within the bony endplate in 2-week and 4-week compression group were both reduced whereas the 4-week compression group obtained significantly less vascularization volume (6.34 ± 1.52 vs. 19.52 ± 4.63, P < 0.05). ConclusionA new model of lumbar IDD was successfully established by axial compression and the volume of microvascular channels in the bony endplate gradually decreased as the grade of IDD increased. This model provides a new choice for etiological studies on IDD and investigation of nutrient supply disturbance.

Structural and functional characteristics of the pulmonary hemomicrocirculatory bed in induced systemic sclerosis: an experimental study.

The objective of this study was to investigate the effects of prolonged exposure to the oxidative agent NaClO on histopathological changes in the lung tissues of laboratory animals. Specifically, the study aimed to examine morphological changes in the pulmonary microcirculation and the level of vascular cell adhesion molecule-1 (VCAM-1) as a functional activity indicator of endothelial cells in animals with induced systemic sclerosis (SSc). A laboratory animal model was used to assess the impact of long-term exposure to NaClO on lung tissues. The animals were divided into three groups: the experimental group (25 rats) was exposed to NaClO, while the control group (20 rats) received an isotonic solution, and the intact group (15 animals) was without any exposure. The concentration of VCAM-1 in the serum of the animals was measured using an enzyme-linked immunosorbent assay. Histopathological analysis of lung tissue specimens was performed using both light and electron microscopy. The concentration of VCAM-1 in the serum of the animals in the experimental group was significantly higher than that of the control group (91.25 [85.63-143.75] vs 19.50 [13.53-22.20], p < 0.05). The histopathological analysis revealed significant abnormalities in the lung tissue specimens from the experimental group, including disruption in the structure of the hemocapillaries of the lungs, narrowing of the microvessel lumen, and perivascular infiltration by polymorphonuclear cells. The electron microscopic analysis showed several ultrastructural changes in the endotheliocytes of the hemocapillaries, including uneven expansion of the perinuclear space, swollen mitochondria, and fragmentation of the membranes of the granular endoplasmic reticulum. Additionally, the basement membrane of hemocapillaries showed uneven thickening with indistinct contours, and the peripheral parts of endotheliocytes were marked by numerous micropinocytotic vesicles and vacuoles. Erythrocyte aggregates and leukocyte adhesion were identified in the lumen of many hemocapillaries, while adhesion and aggregation of platelets were also observed in several hemocapillaries. Long-term exposure to NaClO can cause significant histopathological changes in lung tissues, including damage to the hemocapillaries and disruption in the structure of endotheliocytes.

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders.

Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric-hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric-hypoxic conditions should be considered when planning training and physical activity at altitude.

MICROSTRUCTURAL ORGANIZATION OF THE SUBMANDULAR GLAND UNDER CONDITIONS OF 5-WEEK OPIOID INFLUENCE

The use of opioids is an effective method of treatment for severe and acute pain; however, when they used inappropriately, in addition to their powerful pain-relieving properties, opioids cause significant side effects. The initial changes in the human body caused by the use of narcotic substances (opiates) are detected in the oral cavity, in particular, in the salivary glands. The earliest manifestations of pathological changes in the oral cavity are caries, stomatitis, gingivitis, periodontitis and xerostomia. Based on the results of our research and the study of the effect of opioids on other organs, we can conclude that long-term use of opioids has a significant negative effect on the structure of the submandibular gland and homeostasis of the oral cavity as a whole. The presence of a number of unsolved questions regarding the problems of structural reconstruction of the salivary glands during the use of narcotic agents, as well as the possibility of selecting the most effective methods of treatment and prevention of salivary gland diseases determined the choice of this research topic.&#x0D; Materials and methods. The research was performed on 15 mature, white, male rats with body weight 200–220 g, aged 4.5–6 months, which were kept under standard conditions at the vivarium of the Danylo Halytsky Lviv National Medical University. Animals were divided into two groups: experimental and control. In the experimental group, animals (10 rats) were daily administered an opioid analgesic (nalbuphine) intramuscularly according to the following schedule: 1st week – 8 mg/kg, 2nd week – 15 mg/kg, 3rd week – 20 mg/kg, 4th week – 25 mg/kg, V week – 30 mg/kg. Controls were 5 rats that were injected with 0.9% sodium chloride solution in a volume of 1 ml for 5 weeks. We used the histological method to conduct the research.&#x0D; Results. Damage to the organs of the oral cavity and the submandibular gland, in particular, is an element of comorbid pathology caused by long-term use of opioids. During the 5-week administration of the opioid, we observed irreversible destructive changes in the structural organization of the submandibular gland, which was characterized by the dilation of the vessels of the microcirculation, dystrophic and necrotic changes of the final serous and mucous secretory acini, necrosis of serocytes. Such pathological processes in the structural organization of the submandibular gland can cause an imbalance in the quantitative and qualitative composition of saliva and, as a result, a violation of the homeostasis of the oral cavity and the upper parts of the gastrointestinal tract.&#x0D; Conclusions. The results of the research demonstrate the negative impact of long-term opioid exposure on the structural organization of the submandibular gland and are similar to changes in other organs and body systems during long-term opioid exposure. The damage to microcirculation vessels is the starting and primary mechanisms in this process with the subsequent increase of irreversible destructive changes of the submandibular gland. The data of the scientific work have a wide practical and theoretical significance for morphologists, pathomorphologists and dentists in the aspect of developing new methods of diagnosis, prevention and treatment of salivary gland pathology in patients with opiomania and make it possible to establish safe terms of use of «nalbuphine».

Dynamic myocardial perfusion computed tomography with mental stress test to detect changes in myocardial microcirculation in patients with anxiety and no obstructive coronary artery disease.

Mental stress can induce myocardial ischemia in patients with anxiety and other psychological disorders. Computed tomography myocardial perfusion imaging (CT-MPI) has the potential to quantitatively diagnose myocardial ischemia. The aim of this study was to measure changes in myocardial microcirculation perfusion (MMP) in patients with anxiety who have angina symptoms/ischemia but no obstructive coronary artery disease (INOCA) using dynamic CT-MPI in combination with a mental stress test. Patients with INOCA were divided into five subgroups (none, minimal, mild, moderate, and severe) according to the generalized anxiety disorder scale. Patients underwent dynamic CT-MPI with mental stress testing using a series of the standardized color word/arithmetic stressors. Myocardial blood flow (MBF) during resting and stress phases of CT-MPI was recorded. Fifty-eight patients with 986 segments were included for final analysis. Compared to patients with none, minimal, mild, and moderate anxiety, those with severe anxiety had the largest rate of MBF decrease and the largest MBF decrease value. At the same time, those with no anxiety had the largest rate of MBF increase, the largest MBF increase value (all p< 0.05). As anxiety intensified, the rate of MBF increased and the MBF value increased (r= -0.24, r= -0.27, p< 0.05). Concomitantly, the rate of MBF decreased and the MBF value decreased (r= 0.63, r= 0.43, p< 0.05). Dynamic CT-MPI with a mental stress test can be used to evaluate MMP in patients with anxiety and INOCA. Mental stress resulted in significant differences in changes in the rate and value of MBF among patients with different anxiety degrees. • Dynamic CT-MPI with mental stress test worked well to quantitatively evaluate myocardial microcirculation perfusion in patients with anxiety and INOCA. • The rates of MBF decrease and MBF decrease value were positively correlated with anxiety degree of anxiety patients with INOCA. • MBF change derived from CT-MPI with mental stress test had a good performance to predicting anxiety degree of patients with anxiety and INOCA.

Artificial intelligence in radiodiagnosis assessment of circulatory disorders in cases of community-acquired pneumonia before and in the COVID-19 pandemic

Introduction. The COVID-19 pandemic not only caused a surge of viral pneumonia patients, but also opened up new opportunities in the field of radiology. One of the conditional «pluses» was the quantitative damage assessment of the lung parenchyma and microcirculation in COVID-19 using an artificial intelligence program. Objective. To evaluate the AI capabilities to detect the severity of anatomical and microcirculatory post-inflammatory disorders by CT and SPECT of pneumonic patients data. Materials and Methods. We analyzed prospective and retrospective data obtained by radiological studies of 187 patients with community-acquired pneumonia from 2006 to 2022 in the clinics of the St. Petersburg State Medical University named after acad. I.P. Pavlov. The follow-up period varied from 3 months to 8 years. The mean age of the patients was 34.3±9.2 years (w/m – 107/80). All patients underwent CT scan, a comprehensive functional examination of external respiration (KFIVD), SPECT. Results. The community-acquired pneumonia before the COVID-19 pandemic was generally characterized by signs of exudative bronchiolitis/bronchopneumonia, infectious viral alveolitis and pleuropneumonia. The first two forms in contrast to pleuropneumonia were associated with microcirculation disturbances. Signs of lung damage in COVID-19 had staging pattern based on morphological changes: edema, reticulation (increased severity of edema, cellular infiltration, intraalveolar fibrin), organization=consolidation (cellular infiltration, intraalveolar fibrin, fibroblast proliferation). Residual anatomical changes were accompanied by clinical symptoms (shortness of breath of varying severity, dry cough, weakness, intoxication). Conclusions. Using the artificial intelligence for post-processor CT and SPECT image processing seems to be relevant to assess the postinflammatory anatomical and microcirculatory disorders severity. Experience accumulation in combined AI and radiological study of patients with community-acquired pneumonia is capable to quantify residual anatomical and microcirculatory changes and useful for treatment tactics.

Microcirculatory Changes as a Hallmark of Aging in the Heart and Kidney

Microcirculatory Changes as a Hallmark of Aging in the Heart and Kidney

The Effect of Photobiostimulation by Light Waves in the Blue Range of the Spectrum on Microcirculation Parameters and the Activity of Oxidative Homeostasis Enzymes in the Skin

The study employs laser doppler flowmetry and laser fluorescence spectroscopy to reveal the changes in microcirculation and activity of coenzymes of oxidative metabolism in the finger skin under the influence of photobiostimulation by monochrome incoherent low-intensity electromagnetic radiation with a wavelength of 470 nm. Photobiostimulation with light waves in the blue range has contributed to an increase in hemomicrocirculation during and 15 min after the termination of exposure, while the indicator lymph outflow, on the contrary, decreased during the irradiation period and recovered after its termination. The dynamics of changes within the parameters of blood microcirculation, the lymph flow in microvessels and the indicators of oxidative metabolism showed that the skin microcirculation system is an important acceptor of the photobiostimulating effect of light in the blue range of the spectrum. Photobiostimulation triggers the mechanism of activation of hemomicrocirculation by reducing myogenic vasomotion, thereby increasing the conductivity of cardiogenic biorhythm in the vessels of the microcirculatory bed. With an increase in the level of hemomicrocirculation, photobiostimulation is directly associated with the activation of tissue oxidative metabolism.

Influence of high-energy laser therapy to the patellar tendon on its ligamentous microcirculation: An experimental intervention study.

Laser therapeutic applications, such as the use of high energy lasers (HILT), are widely used in physical therapy, but basic studies on the mechanisms of action of HILT on tendinous/ligamentous tissue are largely lacking. The aim of this study was to investigate microcirculatory changes of the patellar tendon by HILT. 21 healthy volunteers were included in the present investigation. Before and after HILT, as well as 10 minutes later, the microcirculation was measured by noninvasive laser Doppler and white light spectroscopy (O2C device). Tissue temperature was recorded at the measurement time points using thermography. Blood flow increased significantly by 86.38 arbitrary units (AU; p < 0.001) after the intervention and by 25.76 AU (p < 0.001) at follow-up. Oxygen saturation increased by 20.14% (p < 0.001) and 13.48%, respectively (p < 0.001), whereas relative hemoglobin decreased by 6.67 AU and 7.90 AU, respectively. Tendon temperature increased by 9.45° and 1.94° Celsius, respectively. Acceleration of blood flow by improving the flow properties of erythrocytes and platelets may have caused the results. HILT could be a therapeutic perspective for tendon pathologies with impaired microcirculation, although further studies are needed to validate the experimental results.

The main causes of death in patients with COVID-19.

By March 21, 2022, 6.1 million deaths from COVID-19 were reported, most of them in the United States, Brazil, and India. Between January 1, 2020, and December 31, 2021, the global estimated mortality due to the COVID-19 pandemic was 120.3 deaths (113.1-129.3) per 100,000 of the population for all ages. So far, many of the potentially fatal mechanisms of COVID-19 have been reported. In this manuscript, we analyzed the available data on the causes of deaths from COVID-19. This analysis suggests that the primary attributable cause of death from COVID-19 is multiple organ failure resulting from numerous pathological mechanisms, including genetic predisposition to the severe inflammatory response. Increased inflammatory response affects the lungs locally as well as systemic thrombotic microangiopathy. It seems that many comorbidities associated with an increased mortality rate among patients with COVID-19 per se predispose them to an increased risk of thrombotic changes. Furthermore, the role of inflammation in the lungs and the changes that lead to hypoxia cannot be overlooked. However, the thrombotic changes in microcirculation seem to be the most dominant.

Assessment of Blood Microcirculation Changes after COVID-19 Using Wearable Laser Doppler Flowmetry.

The present work is focused on the study of changes in microcirculation parameters in patients who have undergone COVID-19 by means of wearable laser Doppler flowmetry (LDF) devices. The microcirculatory system is known to play a key role in the pathogenesis of COVID-19, and its disorders manifest themselves long after the patient has recovered. In the present work, microcirculatory changes were studied in dynamics on one patient for 10 days before his disease and 26 days after his recovery, and data from the group of patients undergoing rehabilitation after COVID-19 were compared with the data from a control group. A system consisting of several wearable laser Doppler flowmetry analysers was used for the studies. The patients were found to have reduced cutaneous perfusion and changes in the amplitude-frequency pattern of the LDF signal. The obtained data confirm that microcirculatory bed dysfunction is present in patients for a long period after the recovery from COVID-19.

Differences in the Basal Flow and Occlusion-induced Reactive Hyperemia of the Apical and Non-apical Cutaneous Microcirculation. Effect of Botulinum Toxin

Introduction: In general, two types of skin are distinguished: apical (glabrous, A) and non-apical (hairy, NA), but less is known regarding the differences in their microcirculation. Thus we aimed to measure changes in subcutaneous microcirculation in these two skin types and its modulation by botulinum toxin (BT). Materials and Methods: Perimed 5000 Laser Doppler flowmetry was used to measure the perfusion (perfusion unit, PU) of skin in the temporal (A) and lower arm (NA) regions. The temporal artery or the upper arm was occluded for 2 min, then released, which was followed by reactive hyperemia. Also the effects of 25 IU BT injected under the forehead skin on PU were observed. Results: In the skin of temporal region PU changed from control PU: 73,01±15,4 to occlusion: 51,64±7,16, then after release to 110,76±22,56. In the skin of upper arm, PU changed from control PU: 10,4±1,2, to occlusion: 1.9±05, then after release to 48,8±25,5. In the forehead skin BT elicited a biphasic response then PU returned close to control, whereas BT inhibited reactive hyperemia; PU changed from 70,63 ±16,08 to occlusion 55,73 ± 6,75 and after release to 71,37±29,22. Conclusion: Thus there is 1) a higher level of microcirculation in the temporal region of the forehead skin than that of the forearm, 2) ischemia/reperfusion elicited greater reactive hyperemia (RH) in the forearm skin then in the temporal skin 3) BT interferes with the mechanisms eliciting reactive hyperemia.

Low FODMAP Diet Relieves Visceral Hypersensitivity and Is Associated with Changes in Colonic Microcirculation in Water Avoidance Mice Model.

(1) Background: Irritable bowel syndrome (IBS) is a global public health problem, the pathogenesis of which has not been fully explored. Limiting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can relieve symptoms in some patients with IBS. Studies have shown that normal microcirculation perfusion is necessary to maintain the primary function of the gastrointestinal system. Here, we hypothesized that IBS pathogenesis might be related to abnormalities in colonic microcirculation. A low-FODMAP diet could alleviate visceral hypersensitivity (VH) by improving colonic microcirculation; (2) Methods: C57BL/6 mice were raised to establish an IBS-like rodent model using water avoidance (WA) stress or SHAM-WA as a control, one hour per day for ten days. The mice in the WA group were administered different levels of the FODMAP diet: 2.1% regular FODMAP (WA-RF), 10% high FODMAP diet (WA-HF), 5% medium FODMAP diet (WA-MF), and 0% low FODMAP diet (WA-LF) for the following 14 days. The body weight and food consumption of the mice were recorded. Visceral sensitivity was measured as colorectal distention (CRD) using the abdominal withdrawal reflex (AWR) score. Colonic microcirculation was assessed using laser speckle contrast imaging (LCSI). Vascular endothelial-derived growth factor (VEGF) was detected using immunofluorescence staining; (3) Results: The threshold values of CRD pressure in the WA-RF, WA-HF, and WA-MF groups were significantly lower than those in the SHAM-WA group. Moreover, we observed that colonic microcirculation perfusion decreased, and the expression of VEGF protein increased in these three groups of mice. Interestingly, a low-FODMAP dietary intervention could reverse this situation. Specifically, a low-FODMAP diet increased colonic microcirculation perfusion, reduced VEGF protein expression in mice, and increased the threshold of VH. There was a significant positive correlation between colonic microcirculation and threshold for VH; (4) Conclusions: These results demonstrate that a low-FODMAP diet can alter VH by affecting colonic microcirculation. Changes in intestinal microcirculation may be related to VEGF expression.

КЛИНИКО-РЕНТГЕНОЛОГИЧЕСКИЙ АНАЛИЗ СТРУКТУР ПАРОДОНТА ПРИ АНАТОМО-ФУНКЦИОНАЛЬНЫХ НАРУШЕНИЯХ МУКОГИНГИВАЛЬНОГО КОМПЛЕКСА

Subject. Anatomical and functional disorders of the mucogingival complex.&#x0D; Objectives. To evaluate microcirculatory, clinical and radiological changes in periodontal tissues in various variants of mucogingival complex disorders.&#x0D; Methodology. The study was conducted at the Department of Therapeutic Dentistry of ASMU. In the course of the study, 80 patients (49 women, 31 men) aged 18 to 35 years were examined with a ratio of dentition close to orthognathic bite in the presence of maximum occlusion. Three groups were formed depending on the anatomical and functional state of the mucogingival complex. In the clinical part of the study, an objective assessment of the condition of periodontal tissues was carried out on the basis of a dental examination with a comprehensive analysis of the periodontal status. The X-ray examination included the analysis and description of cone-beam computed tomograms for patients of clinical groups. To assess microcirculation in periodontal tissues, the method of ultrasonic Dopplerography with functional probe breakdown was used.&#x0D; Results. In the studied groups, the level of oral hygiene was characterized as good, and the indicators of hygiene indices did not differ significantly, periodontal indices indicated the absence or minimal degree of inflammation in periodontal tissues. Carrying out a functional tension test made it possible to divide patients into subgroups according to the type of reaction: normal, compensated, subcompensated, decompensated. According to the results of the study of CBCT in the comparison group, pathological changes in the bone tissue of the alveolar process of the studied areas were not recorded, in patients of the first clinical group, in most cases (80.2%), pathological changes in the bone tissue of the alveolar process were not observed, in the rest (19.8%), a low level of alveolar bone was noted. In patients of the second clinical group, the phenomena of osteoporosis and an increase in the distance from the dental enamel-cement border to the edge of the outer cortical plate were recorded.&#x0D; Conclusions. X-ray changes in bone tissue most often corresponded to the already existing clinical symptoms of periodontal tissue damage against the background of mucogingival pathology. The predictors of prenosological diagnosis in anatomical and functional disorders of the mucogingival complex were changes in microcirculation indicators.

Camptothecin improves sorafenib sensitivity by inhibiting Nrf2‑ARE pathway in hepatocellular carcinoma.

Sorafenib is a targeted drug for hepatocellular carcinoma (HCC), however, its efficacy is limited. Nuclear factor erythroid 2‑related factor 2 (Nrf2) contributes to sorafenib resistance. The present study investigated camptothecin (CPT) as a Nrf2 inhibitor to sensitize HCC to sorafenib. The effect of CPT on sorafenib sensitivity in HCC was assessed invivo using H22 mice model (n=32) and VX2 rabbit models (n=32), which were sorted into four treatment groups. The expression levels of Nrf2, its downstream genes, including heme oxygenases‑1 (HO‑1) and NAD(P)H quinone oxidoreductase 1 (NQO1), and the epithelial‑mesenchymal transition markers Snail and N‑cadherin in tumors were determined using immunohistochemical staining and western blotting. Magnetic resonance imaging was used to monitor changes in tumor microcirculation and activity before and after treatment. Mouse body weights, liver and kidney function were monitored to evaluate the safety of combined therapy. The results revealed that the mean tumor size of the combined group was significantly smaller than that of sorafenib group for both models. The expression levels of Nrf2, heme oxygenase‑1, NAD(P)H quinone oxidoreductase 1, Snail, and N‑cadherin in the sorafenib group were significantly higher than control group (P<0.05). However, the expression levels of these genes were decreased in the combined group (P<0.05). Microcirculation perfusion and tumor activity in the combined group were also lower than sorafenib group. There were no significant differences in mouse body weight or liver and kidney function among the four groups. In summary, CPT is a Nrf2 inhibitor that could enhance the efficacy of sorafenib against HCC.

The use of radiofrequency and vacuum-mechanical massage in cellulite reduction. A case report

Cellulite is one of the most common skin defects in women, of multifactorial etiology. The dominant hypotheses that aim to explain the pathophysiology of cellulite indicate an excessive accumulation of water in the intercellular matrix, negative changes in tissue microcirculation, differentiated anatomical structure of tissues depending on sex, race, biological type, hormonal changes in the body, lifestyle together with diet and physical activity. Predispositions to the development of lipodystrophy are genetically and hormonally conditioned, however, environmental factors are also important. The study aimed to assess the effectiveness of combined therapy with the use of radio waves and vacuum-mechanical massage in a 27-year-old woman.

Platelets mediate acute hepatic microcirculatory injury in a protease-activated-receptor-4-dependent manner after extended liver resection

BackgroundSmall-for-size syndrome (SFSS) is a major complication following extended liver resection. The role of platelets in the early development of SFSS remains to be cleared. We aimed to investigate the impact of platelets and PAR-4, a receptor for platelet activation, on the acute phase microcirculatory injury after liver resection by in vivo microscopy analyzing the changes in leukocyte recruitment, platelet-neutrophil interaction, and microthrombosis-induced perfusion failure. MethodsSixty-percent partial hepatectomy (PH) models using C57BL/6 mice receiving platelet depletion with anti-GPIbα, PAR-4 blockade with tcY-NH2, or vehicle treatment with saline were used. Sham-operated animals served as controls. Epifluorescence microscopic analysis was performed 2 h after PH to quantify the leukocyte recruitment and microcirculatory changes. Sinusoidal neutrophil recruitment, platelet-neutrophil interaction, and microthrombosis were evaluated using two-photon microscopy. ICAM-1 expression and liver liver injury were assessed in tissue/blood samples. ResultsThe increments of leukocyte recruitment in post-sinusoidal venules and sinusoidal perfusion failure, the upregulation of ICAM-1 expression, and the deterioration of liver function 2 h after 60% PH were alleviated in the absence of platelets or by PAR-4 blockade. Intensified platelet-neutrophil interaction and microthrombosis in sinusoids were observed 2 h after 60% PH, which significantly attenuated after PAR-4 blockade. ConclusionPlatelets play a critical role in acute liver injury after extended liver resection within 2 h. The deactivation of platelets via PAR-4 blockade ameliorated liver function deterioration by suppressing early leukocyte recruitment, platelet-neutrophil interaction, and microthrombosis in hepatic sinusoids.