Lymphatic Microcirculation Research Articles

Harnessing the lymphatic system.

Heart failure (HF) is a growing concern, with significant implications for mortality, morbidity, and economic sustainability. Traditionally viewed primarily as a hemodynamic disorder, recent insights have redefined HF as a complex systemic syndrome, emphasizing the importance of understanding its multifaceted pathophysiology. Fluid overload and congestion are central features of HF, often leading to clinical deterioration and hospital admissions, with the role of the lymphatic system previously largely overlooked, partly due to diagnostic challenges and visualization difficulties. With the advancement of those techniques, pathophysiological changes occurring in the lymphatic system during HF, such as enlargement of the thoracic duct and the increased lymphatic flow, are now becoming apparent. This emerging research has begun to uncover the interplay between lymphatic dysfunction and HF, suggesting novel therapeutic targets. Advances in molecular biology, such as targeting vascular endothelial growth factor and promoting lymphangiogenesis, hold promise for improving lymphatic function and mitigating HF complications. This article provides a comprehensive overview of the evolving landscape of lymphatic system-targeted therapies for HF. It explores various intervention levels, from mechanical lymphatic decongestion to pharmaceutical interactions and lymphatic micro-circulation, offering insights into future directions and potential clinical implications for HF management.

EXERCISE PRECONDITIONING IMPROVES MESENTERIC LYMPHATIC CONTRACTILITY THROUGH MAM IN RATS FOLLOWING HEMORRHAGIC SHOCK.

Restoration of mesenteric lymphatic microcirculation is crucial for alleviating severe hemorrhagic shock-induced death. Exercise preconditioning (EP) enhances adaptability and resistance to injury and disease. The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the energy and information exchange between the two organelles. Therefore, we hypothesized that EP ameliorates mesenteric lymphatic contractility through MAM in rats following hemorrhagic shock, aiming to confirm that EP enhances resistance to hemorrhagic shock and further popularizes the idea that exercise is beneficial for health. To test this hypothesis, we observed the effects of EP for 4 weeks on survival time and mesenteric lymphatic contractility in conscious rats following hemorrhagic shock and further explored the effects of MAM agonists and inhibitors. The results showed that EP prolonged the survival time and improved the mesenteric lymphatic contractility and reactivity in vivo and in vitro in rats underwent hemorrhagic shock, ameliorated the MAM ultrastructure in lymphatic smooth muscle cells (LSMCs) and reduced the voltage-dependent anion channel 1 (VDAC1, a vital protein of MAM) and IP3R1 expressions in mesenteric lymphatic tissue. Importantly, treatment with 2-APB (IP3R1 inhibitor) or VBIT-12 (VDAC1 inhibitor) prolonged the survival time, improved mesenteric lymphatic contractility in vivo , ameliorated the MAM ultrastructure injury, and decreased the IP3R1 or VDAC1 expressions in LSMCs in rats following hemorrhagic shock. In contrast, the administration of drinking water containing CdCl 2 (IP3R1 activator) abolished the beneficial effect of EP on hemorrhagic shock. Taken together, the protective effect of EP on lymphatic contractility following hemorrhagic shock was achieved by improving MAM in LSMCs.

Effect of Infrared Radiation on the Regulation of Oxidative Netabolism in C57BL/KsJYLepr<sup>db/+</sup> Mice

We studied the effect of infrared radiation (IR) course exposure on pathological changes in the tissues of C57BL/KsJYLeprdb/+ (db/db) mutant mice with type 2 diabetes mellitus using a LASMA ST device. This apparatus allows simultaneous non-invasive monitoring of blood and lymph microcirculation, as well as determining the activity of mitochondrial oxidative coenzymes in tissues before and after IR therapy. IR waves (690 nm) were found to have a positive therapeutic effect on the functional state of db/db mice. This included a rapid healing of skin wounds caused by maceration and prolonged normalization of oxidative metabolism parameters (NADH, FAD, POM) in body tissues. IR therapy has a cumulative effect, leading to a 2.3–2.5-fold increase in life expectancy and life quality, compared to the control group.

Changes in Microcirculation in the Brain, Heart, and Liver in Female Rats with Translational Model of Alcoholic Cardiomyopathy.

We studied some features of blood and lymph microcirculation in the brain, heart, and liver of female rats with developed alcoholic cardiomyopathy. In female rats after 24-week forced consumption of 10% ethanol solution, the size and inotropic function of the heart were measured by echocardiography. Microcirculation in the brain, myocardium, and liver was assessed by laser Doppler flowmetry using LAKK-OP2 and LAZMA-D computerized laser analyzers. Using spectral wavelet analysis, we determined the absolute and normalized to total perfusion amplitudes of microcirculation oscillations reflecting various regulatory mechanisms. Intact animals served as controls. In rats of the experimental group, alcoholic cardiomyopathy completely developed. Under these conditions, the index of microcirculation in the brain, myocardium, and liver significantly decreased. At the same time, there was a redistribution in the brain between shunting and nutritive blood flow in favor of the latter. In the myocardium and liver, this ratio did not change.

The effects of Kinesio tapes on facial swelling following bimaxillary orthognathic surgery in the supraclavicular region

BackgroundSeveral osteotomies are required for orthognathic surgery to reposition the jaws correctly. This study aimed to evaluate whether Kinesiotaping can reduce swelling, pain, and trismus following orthognathic surgery of the facial skull.Materials and methodsThe present study consists of two phases. In the split-mouth phase, 16 skeletal class III patients underwent Bimax Orthognathic surgery, and Kinesiological tape (KT) was applied on one half of the face. In the prospective case–control phase, 30 patients were divided into two groups. Kinesio tape was applied on both sides of the face of the Kinesio group, and pressure dressing and ice therapy were used for the second group. The tape was parallel to the lower border of the mandible along its entire length, tangent to the labial commissure area on the studied side. The tape was placed in place for 5 days. Edema was evaluated by measuring the distance from the menton to the lower edge of the tragus. The maximum mouth-opening trismus was evaluated, and the VAS index was used to evaluate pain.ResultsThere was evidence of swelling reduction after KT; within the same study, differences between the left and right sides as well as for the same side were statistically significant (p < 0.001). As a result of tapping lymphatic Kinesio tape on the affected area, tension was reduced, and lymphatic circulation was restored. Blood and lymph microcirculation was improved, enabling the body to heal itself.ConclusionKinesio tape reduced swelling after orthognathic surgery in a positive way. As a simple, non-traumatic, economical method, Kinesio taping seems promising.

Lymphatic microcirculation profile in the progression of hypertension in spontaneously hypertensive rats.

The contractile behavior of collecting lymphatic vessels occurs in essential hypertension in response to homeostasis, suggesting a possible role for microcirculation. We aimed to clarify the nature of the lymphatic microcirculation profile in spontaneously hypertensive rats (SHRs) and normotensive controls. The vasomotion of collecting lymphatic vessels in eight- and thirteen-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs, n=4 per group) was visualized by intravital video and VasTrack. The lymphatic vasomotion profile (frequency and amplitude) and contractile parameters (contraction fraction and total contractility activity index) were compared. Plasma nitrite/nitrate levels were assessed by the Griess reaction, and plasma endothelin-1 was measured by enzyme-linked immunosorbent assay. WKYs and SHRs differed in the vasomotion of collecting lymphatic vessels. Both eight- and thirteen-week-old WKYs revealed a high-amplitude pumping pattern, whereas a low-amplitude pattern was observed in SHRs. Moreover, compared with age-matched WKYs, SHRs exhibited deteriorated output and reflux capability and lost the ability to regulate collecting lymphatic vasomotion. Additionally, the chemistry complements the microcirculatory lymphatic profile as demonstrated by an increase in plasma nitrite, nitrate, and endothelin-1 in SHRs. ET-1 inhibitor meliorated the lymphatic contractile capability in SHRs partially through regulating frequency of lymphatic vasomotion. We used an intravital lymphatic imaging system to observe that SHRs exhibit an impaired collecting lymphatic vasomotion profile and deteriorated contractility and reflux.

Effect of Treatment with Silver Sulfate on the Physiological Effects of Natural Mineral Water

The treatment of mineral water with silver allows to significantly extend its shelf life without deteriorating its organoleptic properties, which makes it possible to use mineral water away from the natural deposit and is critical for business and the end consumer. However, possible changes in the physiological properties of mineral waters when treated with silver have not been studied until now. We have carried out a preclinical double-blind randomized placebo-controlled, experimental study, during which the effect of treatment with silver sulfate at a dose of 0.02 mg / liter (according to the EAEU tR 044–2017 regulation) of natural mineral water of sulphate-hydrocarbonate calcium-sodium (Russia, Stavropol territory, deposit “Slavyanovskaya”, well No. 69 bis) for cellular metabolism, microcirculation and micro-lymphocyte when applied externally to the area of the inner surface of the forearm. A comparison of the effect on cell metabolism and microcirculation has been made for applications with native mineral water “Slavyanovskaya”, “Slavyanovskaya, enriched with silver sulfate” and placebo (tap water) after 30 minutes and after 24 hours. Number of patients: 15. Number of studies by location: 45. the results were monitored using the LAZMA St device. the study carried out simultaneous registration of diagnostic parameters of blood microcirculation, lymph microcirculation, as well as fluorescence amplitudes of coenzymes participating in oxidative metabolism - reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD). It was revealed that the mineral water “Slavyanovskaya enriched with silver” differs in its physiological effect on cellular metabolism, microcirculation and micro-lymph flow from the physiological effect of the mineral water “Slavyanovskaya”, namely that, compared to “Slavyanovskaya”, the mineral water “Slavyanovskaya enriched with silver” has a more pronounced positive effect on cellular metabolism, metabolic reserves of the cell, promotes the activation of microcirculation and micro-lymphatic flow. Mineral water “Slavyanovskaya, enriched with silver” has a longer effect on cellular metabolism, microcirculation and micro-lymphatic flow than mineral water “Slavyanovskaya”. A statistically significant positive effect of cell metabolism activation was detected both 30 minutes and 24 hours after exposure. Thus, this method of processing mineral water with silver sulfate not only does not decrease its positive physiological effect, but also improves it, prolonging its action, which makes further use of silver preparations in the processing of mineral water justified.

Lipedema—Pathogenesis, Diagnosis, and Treatment Options

Lipedema is often unrecognized or misdiagnosed; despite an estimated prevalence of 10% in the overall female population, its cause is still unknown. There is increasing awareness of this condition, but its differential diagnosis can still be challenging. In this article, we summarize current hypotheses on its pathogenesis and the recommendations of current guidelines for its diagnosis and treatment. This review is based on publications about lipedema that were retrieved by a selective search in the MEDLINE, Web of Science, and Cochrane Library databases. The pathophysiology of lipedema remains unclear. The putative causes that have been proposed include altered adipogenesis, microangiopathy, and disturbed lymphatic microcirculation. No specific biomarker has yet been found, and the diagnosis is currently made on clinical grounds alone. Ancillary tests are used only to rule out competing diagnoses. The state of the evidence on treatment is poor. Treatment generally consists of complex decongestive therapy. In observational studies, liposuction for the permanent reduction of adipose tissue has been found to relieve symptoms to a significant extent, with only rare complications. The statutory healthinsurance carriers in Germany do not yet regularly cover the cost of the procedure; studies of high methodological quality will be needed before this is the case. The diagnosis of lipedema remains a challenge because of the hetero - geneous presentation of the condition and the current lack of objective measuring instruments to characterize it. This review provides a guide to its diagnosis and treatment in an interdisciplinary setting. Research in this area should focus on the elucidation of the pathophysiology of lipedema and the development of a specific biomarker for it.

Systemic Sclerosis Serum Significantly Impairs the Multi-Step Lymphangiogenic Process: in Vitro Evidence.

In systemic sclerosis (SSc), the possible involvement of lymphatic microcirculation and lymphangiogenesis has traditionally been overshadowed by the greater emphasis placed on dysfunctional blood vascular system and angiogenesis. In the present in vitro study, we explore for the first time whether the SSc microenvironment may interfere with lymphangiogenesis, a complex, multi-step process in which lymphatic microvascular endothelial cells (LMVECs) sprout, migrate, and proliferate to generate new lymphatic capillaries. Normal human adult dermal LMVECs from three donors were treated with serum from SSc patients (n = 8), serum from healthy individuals (n = 8), or recombinant human vascular endothelial growth factor (VEGF)-C as a positive control for lymphangiogenesis. Cell proliferation, Boyden chamber Matrigel chemoinvasion, wound healing capacity, and lymphatic capillary morphogenesis on Geltrex were assayed. VEGF-C serum levels were measured by enzyme-linked immunosorbent assay. Gene and protein expression levels of the lymphangiogenic orchestrators VEGF receptor-3 (VEGFR-3)/Flt-4 and neuropilin-2 (NRP-2) were determined by real-time PCR and Western blotting, respectively. Conditioning with SSc serum significantly inhibited LMVEC proliferation, Matrigel invasion, and wound healing capacity with respect to healthy serum. The ability of LMVECs to form lymphatic tubes on Geltrex was also severely compromised in the presence of SSc serum. VEGF-C levels were comparable in SSc and healthy sera. Treatment with SSc serum resulted in a significant downregulation of both VEGFR-3/Flt-4 and NRP-2 mRNA and protein levels. In SSc, the pathologic environment severely hampers every lymphangiogenesis step, likely through the reduction of pro-lymphangiogenic VEGFR-3/NRP-2 co-receptor signaling. The impairment of the lymphangiogenic process opens a new scenario underlying SSc vascular pathophysiology, which is worth investigating further.

Gut Lymphangiopathy: Adding Fuel to the Fire in Chronic Liver Disease

The splanchnic inflammation inchronic liver disease increases intestinal angiogenesis. In the current study our aim was demonstrating that the small bowel lymphangiogenesis is associated with angiogenesis in chronic cholestasis in the rat. A stereological study of the lymphatic microcirculation in the small intestine was performed in cholestatic rats. Portal enteropathy in cholestasis increases lymphatic microvessels in the mucosa and submucosa layers. Thus, the lymphatic microvessel volume fraction was superior (p -2; p -2; p -2). These alterations predominate in the duodenum (volume fraction: 0.10 ± 0.01 and length density: 33.55 ± 5.98 mm-2) and ileum (volume fraction: 0.16 ± 0.01 and length density: 38.62 ± 6.07 mm-2). This study demonstrates the predominance of an increased lymphangiogenic response in both end sides of the small bowel associated with chronic liver disease. Since the porto-systemic venous collateral circulation in the chronic liver insufficiency is developed in the ends of the gastrointestinal tract, the excessive duodeno-ileal lymphangiogenesis could suggest the development of amesenteric-systemic lymphatic bypass in the chronic portal hypertension.

Экспериментальное обоснование применения синтетического пептида в комплексном хирургическом лечении острой кишечной непроходимости

Высокая смертность при хирургическом лечении острой кишечной непроходимости (ОКН) определила поиск новых методов сопутствующей терапии. Обнаруженная ранее высокая эффективность опиоидных пептидов в стимулировании лимфотока в микрососудах брыжейки тонкой кишки у крыс, восстановлении нарушенной микроциркуляцию и снижении смертности при ряде заболеваний, определила цель данного исследования: изучить роль фармакологической стимуляции лимфотока в динамике ОКН. В работе использовали методы: биомикроскопия, лазерная допплеровская флоуметрия брыжейки и стенки тонкой кишки крысы, регистрация сократительной активности лимфатических микрососудов ЛМ методом фотометрии, морфометрия микрососудов, видео- и фотосъемка. Полученные результаты предполагают наличие адаптационной роли у активатора микролимфоциркуляции (опиоидного пептида-171 прямого действия) в комплексном хирургическом лечении ОКН. Однократное орошение пептидом межкишечного анастомоза (после удаления) и поврежденного лигатурой фрагмента кишки (перед зашиванием операционной раны) увеличивало выживаемость животных с ОКН на 23%. У всех выживших животных отмечено восстановление: проходимости кишки, микроциркуляции в кровеносных и лимфатических микрососудах, а также структуры стенки кишки. High mortality in the surgical treatment of acute intestinal obstruction (AIO) has warranted the search for new methods of concomitant therapy. Opioid peptides have proved highly effective in stimulating the lymphatic flow in rat small intestinal mesenteric microvessels, restoring the impaired microcirculation, and reducing mortality in many diseases. This had determined this study objective: to investigate the role of lymphatic stimulation in the dynamics of AIO. The study used methods of biomicroscopy, laser Doppler flowmetry, and histological examination of the mesentery and the small intestinal wall in rats; recording the contractile activity of lymphatic microvessels using photometry; microvessel morphometry; video and photography. The study results suggested an adaptive role of the lymphatic microcirculation activator (direct-action opioid-171) in the complex surgical treatment of AIO. A one-time peptide irrigation of the intestinal anastomosis (after removal) and the intestinal injuried by the ligature (before the surgical wound was sutured) increased the survival of animals with AIO by 23%. In all surviving animals, recovery of the intestinal patency, blood and lymphatic microcirculation, and the intestinal wall structure was observed.

Histological and histochemical changes in the dogs liver at poisoning isoniazid

The article presents the results of macroscopic, histological and histochemical studies of dogs liver for isoniazid poisoning. The pathoanatomical section of 18 corpses of dogs of all ages and breeds has been carried out, fragments of different parts of the liver have been selected. Liver samples were fixed in a 10% aqueous solution of neutral formalin, Carnoua and Buena liquids. The dewatering in ethanol of increasing concentration was conducted, sealed in paraffin. The sections were made on a microtome MC-2 in the thickness of 7 microns, stained with hematoxylin and eosin, according to the technique of McManus, Pearles. The produced histoplasts were examined under a light microscope Leica DM 2500 (Switzerland), photocycled by the Leica DFC450C camera using the Leica Application Suite Version 4.4 software. Macroscopically, the liver in all studied corpses of dogs is enlarged, the edges are rounded, inhomogeneously colored (from dark cherry to light brown), loose consistency, a light bloody fluid is secreted on the cut, the structure of the organ is smoothed out. Optically light in the liver of most dogs for isoniazid poisoning noted profound violations of all structures of angioarhitectonics, stroma and parenchyma of the organ. Prevalent non-fibrotic changes in the endothelium, dilatation and deformation of central veins and sinusoidal mesh with the formation of cells filled with blood plasma. The expressed dystrophy and necrobiosis of hepatocytes and Kupferov cells were combined with erythrocyte hemolysis, which was reflected by the deposition of hemosiderin in the cytoplasm of macrophages and bilirubin in hepatocytes. In rare cases, in the liver of poisoned dogs, acute congestive hyperemia, diapedeous hemorrhages in peripartal regions and non-fibrotic changes in hepatocytes were observed. On the basis of conducted morphological studies, it can be argued that derivatives of isoniazid compounds in the dog's organism have a pronounced hepatotoxic effect characterized by a severe violation of blood and lymph microcirculation and all metabolic processes in liver cells, manifested by dystrophic-non-fibrotic processes in the body.

Lagopsis supina exerts its diuretic effect via inhibition of aquaporin-1, 2 and 3 expression in a rat model of traumatic blood stasis

Ethnopharmacological relevanceLagopsis supina has been used as a traditional medicinal herb for centuries in China. In folk medicine, it is used for promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuretic activities. Modern pharmacological investigation have shown that L. supina have an improvement in blood and lymphatic microcirculation, myocardioprotective, and antioxidative activities. Although the pharmacological research of L. supina was more, there was no report on the diuretic activity. Aim of the studyThis study was to evaluate the diuretic activity and the underlying mechanism of an ethanol extract of L. supina (LS) in a rat model of traumatic blood stasis (TBS). Materials and methodsThere were 30 male Sprague-Dawley rats that were randomly assigned to the control group, TBS group, and LS group (10 animals in each group). LS was administered orally (460 mg/kg) once daily for 7 successive days. The control group and TBS group were given an equal amount of 0.3% sodium carboxymethyl cellulose (CMC-Na). For the efficacy evaluation, the urine output volume, the urinary electrolyte concentrations (Na+, K+, Cl- and Ca2+) and pH value, the levels of angiotensin II (Ang II), atriopeptin (ANP), anti-diuretic hormone (ADH) and aldosterone (ALD), as well as aquaporin (AQP)-1, 2 and 3 protein expressions were detected in a rat model of TBS. The protein expressions of AQP-1, 2 and 3 were detected by quantitative immunohistochemistry (IHC) and Western blot analysis. ResultsIn the efficacy evaluation, rat models treated with LS showed a significant increase in the total urine output (p < 0.01). The urinary electrolyte and the acid-base disturbances, including the decrease of Na+ and Ca2+ levels and the Na+/K+ value together with the increase in the Cl- level and the pH value, in the urine of the LS group were compared with the TBS group. Moreover, the levels of Ang II, ADH and ALD of rat model were decreased after being treated with LS (p < 0.05 or p < 0.01), while the ANP level was increased (p < 0.05). In addition, the results of the quantitative IHC and the Western blot analysis showed that the expression levels of AQP-1, 2 and 3 proteins decreased significantly compared with those of the TBS group. ConclusionsThis is the first reported notable diuretic effect by LS, which probably was through the suppression of the renin-angiotensin-aldosterone system (RAAS) and the regulation of the signaling pathways of AQP-1, 2 and 3 protein expressions. Based on our results, we conclude that L. supina carries out its diuretic effect mainly by down-regulating the levels of AQP-1, 2 and 3 expressions in TBS rat model. These data also embody the traditional Chinese medicine (TCM) application principle of Huo xue li shui. These findings suggest that LS may warrant further evaluation as a possible agent for the diuretic drug in clinical applications. Further research is underway to elucidate the active compounds responsible for the diuretic activity of LS.

The Impact of the Use of Kinesio Taping Method on the Reduction of Swelling in Patients After Orthognathic Surgery: A Pilot Study.

BackgroundOrthognathic surgery (OGS) is associated with extensive surgical intervention within the soft and hard tissues of the facial region of the skull leading to inflammatory reactions. The presence of postoperative swelling indicates the accumulation of exudate or transudate; both these fluids occur in surgery. Massive swelling is a significant problem, because the tension of tissues intensifies pain sensations. The aim of the study was to evaluate the effectiveness of the kinesio taping method (KT) in patients after orthognathic surgery in the area of the facial skull in terms of eliminating postoperative swelling.Material/methodsThe study of the impact of kinesiology tape applied after orthognathic surgery to the craniofacial area on the elimination of swelling was performed in sixteen patients who suffered from this complication after bilateral sagittal split osteotomy.ResultsThe swelling was shown to be reduced after KT; within the same study the differences were statistically significant between the left and right sides and for the same side (p<0.05). The application of the lymphatic kinesio taping method led to the reduction of tension in the affected area and restoration of proper lymphatic circulation in the region covered by swelling. This allows for the improvement of the blood and lymph microcirculation and activation of self-healing processes.ConclusionsThe analysis of the impact of the practical use of the lymphatic KT on complications after orthognathic surgery revealed that it had a beneficial effect on the reduction of swelling. The use of the KT method seems promising because it is simple to carry out, not traumatic, economical and rarely causes undesirable allergies.

Effect of Bone Marrow Multipotent Mesenchymal Stromal Cells on Blood and Lymphatic Vasculature in Uterine Wall of Wistar Rats during Experimental Chronic Metroendometritis.

The study examined the effect of bone marrow multipotent mesenchymal stromal cells and their products secreted into the conditioned medium on uterine microcirculatory bed in Wistar rats during chronic inflammation. The parameters of blood and lymphatic microcirculation in the uterus changed in various directions in relation to the administration routes of biomedical cell product, which is important when the cell therapy is employed in the treatment of inflammatory-degenerative alterations in the lesser pelvis organs.

The capabilities of laser Doppler flowmetry in assessment of lymph and blood microcirculation

The aim of the work was to explore the capabilities of LDF method in studying the human skin blood and lymph microcirculation. Materials and methods. It was assumed that analyzing LDF signals in different frequency ranges of the Doppler shift allows the evaluation of the motion of various scattering particles. Results and discussion. When conducting functional tests, the reverse reaction of the microcirculation index in the low frequency ranges was observed in comparison with the high-frequency ones. Additional differences were obtained in the wavelet analysis of LDF signals. Conclusions. The proposed approach with division into frequency ranges proved useful in the joint study of microhemo- and lymphocirculation.

Protective effects of marrubiin improve endometriosis through suppression of the expression of RANTES.

Marrubiin can improve blood and lymph microcirculation disturbance, and has pharmacological effects in myocardial protection, anti‑inflammation and anti‑oxidation. The aim of the present study was to evaluate the protective effects of marrubiin on endometriosis through suppression of the expression of regulated on activation, normal T cell expressed and secreted (RANTES). Endometriotic cells were implanted into the peritoneal cavity of mice, and these mice were injected estradiol benzoate (30µg/kg) once each day for 14days. The mice with endometriosis were then treated with 12, 25 or 50mg/kg marrubiin. Reverse transcription‑quantitative polymerase chain reaction was used to assess the mRNA expression of RANTES, and western blot analysis was used to analyze the protein expression of RANTES, TNF‑α and PGE2. Inflammation factors were measured by ELISA. Treatment with marrubiin effectively improved lesion regression and inhibited toxicity in the mouse model of endometriosis. Marrubiin significantly inhibited endometrial lesions and monocyte chemotaxis in the mice with endometriosis, and reduced U937 cell migration. Calcium mobilization, levels of tumor necrosis factor‑α and the secretion of RANTES were effectively suppressed by marrubiin treatment. The calcium levels were effectively induced, whereas the protein expression of prostaglandin E2 (PGE2) and formation of thromboxane B2 (TXB2) were effectively inhibited by marrubiin treatment. These findings indicated that the protective effect of marrubiin improved endometriosis in the mice through the suppression of inflammation and downregulation of the expression of RANTES, followed by mediation of the levels of calcium, PGE2 and TXB2.

Microcirculatory blood and lymph flow examination in eyelid skin by laser Doppler flowmetry

to study normal blood and lymph microcirculation of the upper and lower eyelids in different age groups. The study included 108 volunteers (216 eyes) aged from 20 to 80 years with no signs of changes in anterior segment structures, who were grouped by age ranges (20-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and 71-80 years) into 6 groups equal in gender and quantitative composition. In all volunteers, microcirculation of the upper and lower eyelids was examined by laser Doppler flowmetry (LDF) ('LASMA MC-1' peripheral blood and lymph flow analyzer and 'LASMA MC' laser diagnostic complex, LASMA LLC). The average perfusion changes in blood and lymph flow as well as blood and lymph flow oscillations were analyzed. Blood and lymph flow in the microvasculature of the upper and lower eyelids is variable and depends on neither the age, nor gender of the test subject. On LDF-gram, every increase in amplitude of blood flow corresponds to a decrease in that of lymph flow. The non-invasive method of LDF expands our diagnostic capabilities as it enables assessment of not only blood, but also lymph flow. The data obtained can serve as a starting point for exploring microcirculation in different age groups in the presence of different pathological processes.

Physiology and pathophysiology of the lymphatic system. Research results and further prospects

The review summarizes own research and literature on the role of the lymphatic system in a number of physiological and pathological conditions. The typical reaction of lymph circulation seen in shock, acute diffuse peritonitis, in postoperative period is the lymph flow volumetric rate increase. Mobilization of the lymphatic system, extravascular fluid and proteins in well-studied emergencies is explained considering the role of the lymphatic system as a natural source of circulating blood volume regulation and serum proteins replacement («autotransfusion»). These pathological processes are associated with progression of lymphatic failure on the late terms. The principle of lymph circulation targeted stimulation as a way to detoxify the body using hormones and procaine (Novocain) blockade of splanchnic nerves and the borderline sympathetic trunks was proposed based on modeled acute peritonitis. Increased microcirculation and central lymph flow, alterations in resorption, transport and filtration barrier function of the lymphatic system, as well as morphologic and functional reorganization of the lymph nodes were revealed in fever of different duration. Of particular interest are studies on the role of the lymphatic system in the immediate and long-term body adaptation to physical stress. Activation of central lymph circulation in adequate dynamic loads correlated with changes in the system lymph microcirculation (acceleration of lymph flow, increased peristalsis of the lymph microvessels walls and contractile activity of their valves). Extreme physical exhaustion was accompanied by expressed lymphovascular, extravascular and intravascular changes in the microvasculature. Lymphatic failure, as well as structural microcirculation impairments in a trained body occur only in extreme physical stress. Thus, the lymphatic system is involved in many physiological and pathological processes; its functional condition affects the course and outcome of the disease. Therefore, the treatment of the diseases requires, among other measures, correction of lymph formation and circulation (stimulation or inhibition, endolymphatic treatment, thoracic duct drainage, lymphosorption, blockade of nodal pathways and other methods - depending on the specific disease).

Quantitative immunohistochemical assessment of blood and lymphatic microcirculation in cutaneous lichen planus lesions.

Latest advances have brought to light the hypothesis that angiogenesis and lymphangiogenesis are tightly connected to some chronic inflammatory diseases. The present study focuses on immunohistochemical assessment of the quantitative changes in the blood and lymphatic microcirculatory bed in common chronic dermatosis - cutaneous lichen planus. Double immunohistochemistry with CD34 and podoplanin antibodies was used to detect blood and lymphatic endothelium, while anti-human VEGF was used for the observation of a key angiogenesis and lymphangiogenesis inducer. Morphometric analysis was performed with QuickPhoto Micro image analysis software. Results confirmed statistically significant enlargement of both the blood and lymphatic microcirculatory beds. Compared to healthy skin, cutaneous lichen planus lesions revealed 1.6 times enlarged blood microcirculatory bed and 1.8 times enlarged lymphatic microcirculatory bed. Vascular endothelial growth factor (VEGF) expression in lesional skin was significantly higher in the epidermis (19.1 times increase) than in the dermis (10.3 times increase). These findings indicate a tight association of angiogenesis and lymphangiogenesis with the pathogenesis of cutaneous lichen planus.