Impaired Blood Flow Research Articles

Insights into Current Management Strategies for Dysthyroid Optic Neuropathy: A Review.

Dysthyroid optic neuropathy (DON) is a potentially sight-threatening eye disease associated with Graves’ orbitopathy (GO). DON is not common in GO patients, reportedly occurring in only about 5% of patients. The pathogenesis of severe DON is considered to involve both muscular nerve strangulation and impaired blood flow. There is some objective grading of physical examination findings and the severity of GO, including a clinical activity score (CAS) and EUropean Group On Graves’ Orbitopathy (EUGOGO), but no specialized protocol completely characterizes DON. Most clinicians have decided that the combination of clinical activity findings, including visual acuity, color vision, and central critical fusion frequency, and radiological findings, including magnetic resonance imaging (MRI), can be used to diagnose DON. MRI has the most useful findings, with T2-weighted and fat-suppressed images using short-tau inversion recovery (STIR) sequences enabling detection of extraocular changes including muscle and/orbital fat tissue swelling and inflammation and, therefore, disease activity. The first-choice treatment for DON is intravenous administration of steroids, with or without radiotherapy. Unfortunately, refractoriness to this medical treatment may indicate the need for immediate orbital decompression within 2 weeks. Especially in the acute phase of DON, thyroid function is often unstable, and the surgeon must always assume the risk of general anesthesia and intra- and post-operative management. In addition, there are currently many possible therapeutic options, including molecular-targeted drugs. The early introduction and combination of these immunomodulators, including Janus kinase inhibitors and insulin-like growth factor-1 receptor antibody (teprotumumab), may be effective for GO with DON. However, this is still under investigation, and the number of case reports is small. It is possible that these options could reduce systemic adverse events due to unfocused glucocorticoid administration. The pathophysiology of DON is not yet fully understood, and further studies of its treatment and long-term visual function prognosis are needed.

Impact of impaired cerebral blood flow autoregulation on electroencephalogram signals in adults undergoing propofol anaesthesia: a pilot study.

Cerebral autoregulation actively maintains cerebral blood flow over a range of MAPs. During general anaesthesia, this mechanism may not compensate for reductions in MAP leading to brain hypoperfusion. Cerebral autoregulation can be assessed using the mean flow index derived from Doppler measurements of average blood velocity in the middle cerebral artery, but this is impractical for routine monitoring within the operating room. Here, we investigate the possibility of using the EEG as a proxy measure for a loss of cerebral autoregulation, determined by the mean flow index. Thirty-six patients (57.5 [44.25; 66.5] yr; 38.9% women, non-emergency neuroradiology surgery) anaesthetised using propofol were prospectively studied. Continuous recordings of MAP, average blood velocity in the middle cerebral artery, EEG, and regional cerebral oxygen saturation were made. Poor cerebral autoregulation was defined as a mean flow index greater than 0.3. Eighteen patients had preserved cerebral autoregulation, and 18 had altered cerebral autoregulation. The two groups had similar ages, MAPs, and average blood velocities in the middle cerebral artery. Patients with altered cerebral autoregulation exhibited a significantly slower alpha peak frequency (9.4 [9.0, 9.9] Hz vs 10.5 [10.1, 10.9] Hz, P<0.001), which persisted after adjusting for age, norepinephrine infusion rate, and ASA class (odds ratio=0.038 [confidence interval, 0.004, 0.409]; P=0.007). In this pilot study, we found that loss of cerebral autoregulation was associated with a slower alpha peak frequency, independent of age. This work suggests that impaired cerebral autoregulation could be monitored in the operating room using the existing EEG setup. NCT03769142.

Asymptomatic forms of COVID-19 in pregnant women: long-term consequences

Purposeto establish the long-term effect of asymptomatic forms of COVID-19 on the course of pregnancy.Methods & MaterialsAn analysis of pregnancy outcomes was carried out in 40 women who had asymptomatic forms of COVID-19.ResultsThe COVID-19 pandemic in conditions of high fertility in the southern regions of Kazakhstan caused pregnant women to become ill with coronavirus infection, including asymptomatic forms. Often asymptomatic forms remain undiagnosed and unaccounted for. We have studied cases of visits to a doctor by pregnant women for various reasons: stopping fetal movement, reducing the size of the abdomen and other complications of pregnancy. When examining them by ultrasound, oligohydroamnion was detected in 85% of cases, premature aging of the placenta, placental cysts in 27.5%, and impaired blood flow in the utero-fetal-placental circulation in 12.5%. Subsequently, 51.4% of women gave birth at full term, 48.5% gave birth prematurely, that is every second woman in the study group gave birth prematurely. In a detailed retrospective laboratory examination of women with the above pathology, IgG SARS-Cov-2 was detected in 92.5% of cases, indicating an asymptomatic coronavirus infection. The development of obstetric complications required from the medical staff reinforced observation and additional assessment, more frequent reclassification of the condition of the mother and fetus, and in some cases induction of labor. This tactic was applied in 12 cases (34.2% of the total number of women who gave birth), when prolongation of pregnancy was associated with a high risk to the health of the mother and fetus.ConclusionAsymptomatic forms of COVID-19 in pregnant women have long-term consequences in the form of oligohydroamnion, premature aging of the placenta and impaired uterine blood flow. All cases of the transferred coronavirus infection in pregnant women, including asymptomatic ones, require more careful, in comparison with the generally accepted and frequent monitoring of pregnancy, in the form of control of the gravidogram, measurement of the abdominal circumference, the height of the uterine fundus, control ultrasonography of the fetus, amniotic fluid and uterine dopplerometry of fetal-placental blood flow.

Effects of Long-Term Use of Zinc and Vitamin C on Type 2 Diabetes Mellitus and Its Complications

The present study aims to use zinc and vitamin C supplements to treat diabetes mellitus disease and its complications, including diabetic foot ulcer, retinopathy, nephropathy, and neuropathy. Diabetes mellitus (DM) is recognized as the most common endocrine disease worldwide. A progressive and aggressive disease, it is characterized by both hyperglycemia and dyslipidemia. Diabetic foot ulcer is a well-known complication of the disease, and it is the most common reason for lower limb amputation. Retinopathy is another diabetic complication, which leads to blindness. Moreover, diabetic nephropathy is the main cause of chronic kidney disease. Zinc is an antioxidant element and a cofactor for more than 300 important enzymes. It is also involved in many important physiological metabolic functions. Vitamin C is a water-soluble vitamin and a powerful dietary antioxidant. It is also essential for the physiological functioning of the body. Zinc and vitamin C are closely related to DM and its complications. Fifty diabetic patients were selected to receive 100 mg zinc oxide tablets and 1000 mg vitamin C tablets every day for six months. The doses were separated and given at specified times during the day. Thirty healthy individuals comprised the control group. Wound swab cultures and antibiotic sensitivity tests were performed for the diabetic foot ulcer patients prior to the supplements being taken. A significant decrease was observed in the patients’ fasting blood glucose, glycated hemoglobin, insulin hormone, urea, creatinine levels, blood pressure, and urination, while an improvement was seen in their lipid profile. Complete healing of the foot ulcers was achieved with blood flow signs and sensation and without the use of antibiotics in most cases. Clear improvements in visual acuity were also achieved. Indeed, type 2 DM is a metabolic disease that results from zinc deficiency, impairing insulin hormone production, secretion, and function. This causes an increase in fasting blood sugar, glycated hemoglobin, blood pressure, urination, and dyslipidemia. It also leads to the inability of vitamin C to enter the cells, followed by endothelial dysfunction, impaired blood flow, and ischemia, thereby leading to diabetic complications.

Повреждения магистральных сосудов конечностей с полным нарушением кровотока у детей (результаты клинических наблюдений)

Background Trauma with associated damage to major arteries and veins typically occurs in adults; reports on such injuries in children are rare. In the organization of their treatment, difficulties are encountered such as formation of teams that must include angiosurgeons. The issues of restoring limb function after injuries with damage to muscle, nerve trunks or complete amputation of the limb remain relevant in children, despite their high abilities to recover. Each particular case in health care institutions has its own characteristics and difficulties for treatment, which was the reason for this communication. Purpose To share our clinical experience and details of providing urgent medical care to injured children with complete impairment of the main arteriovenous blood flow. Materials and methods Three cases with complete damage to major arteries and veins, including their defects, were studied. We describe the details of tactics and features of their surgical management. All patients underwent clinical and laboratory examination; emergency assistance was provided by orthopedic traumatologists and angiosurgeons. All patients were admitted in a state of hemorrhagic shock in stage 2 or 3. Surgical aid was provided in patients with a critical, almost terminal condition. Results On admission 40 minutes after the injury, one patient was diagnosed with a deep cut wound on the posterior surface of the right thigh with damage to the flexor muscles of the leg, femoral artery and vein with their defects up to 3 cm, and a cut wound on the right lower leg. Combined plasty of vascular defects with grafts from the great saphenous vein of the thigh and muscle suture were performed. An excellent result was noted after 3 months. In the second patient, there was an injury with glass in the area of the left axillary fossa with a transverse cut of all nerves, brachial artery and vein, tendons of the biceps and triceps muscles of the shoulder. An excellent result of primary reconstruction was diagnosed 1.5 years later. In the third case, the patient was admitted with a complete traumatic amputation of the right forearm in the lower third due to the use of a mechanical wood splitter; replantation began 5 hours after the cut off. Replantation was successful. It included 4 stages of treatment; the 2nd one was repeated revision and suture of the vessels 16 hours after the onset of thrombosis following the 1st operation. The next two stages included combined plastic surgery of muscles and tendons, first on the extensor and then of the flexor surface of the forearm. Movements appeared 6 months after the injury during the restoration of sensitivity. A completely satisfactory result of treatment was obtained; the patient began to use his hand in everyday life and to write after one year. Conclusion Damage to the main arteriovenous formations requires urgent surgical treatment, aimed at preserving the limb, restoring blood supply, nerve formations, and bone integrity. In complete amputation, restoration of muscle-tendon formations may be postponed for subsequent stages. In primary care, one should consider the need for subsequent, sometimes long-term rehabilitation, the result of which directly depends on the restoration of neurotrophic and sensitive functions.

Characterization of Systemic and Regional Hemodynamics and Vascular Dysfunction in Mice with Fecal Induced Peritonitis.

Sepsis is associated with circulatory dysfunction contributing to disturbed blood flow and organ injury. Decreased organ perfusion in sepsis is attributed, in part, to the loss of vasoregulatory mechanisms. Identifying which vascular beds are most susceptible to dysfunction is important for monitoring the recovery of organ function and guiding interventions. This study aimed to investigate the development of vascular dysfunction as sepsis progressed to septic shock. Anesthetized C57Bl/6 mice were instrumented with a fiberoptic pressure sensor in the carotid artery for blood pressure measurements. In subgroups of mice, regional blood flow measurements were taken by positioning a perivascular flow probe around either the left carotid, left renal, or superior mesenteric arteries. Hemodynamic parameters and their responsiveness to bolus doses of vasoactive drugs were recorded prior to and continuously after injection of fecal slurry (1.3 mg/g body weight) for 4 h. Fecal slurry-induced peritonitis reduced mean arterial pressure (62.7 ± 2.4 mmHg vs. 37.5 ± 3.2 mmHg in vehicle and septic mice, respectively), impaired cardiac function, and eventually reduced organ blood flow (71.9%, 66.8%, and 65.1% in the superior mesenteric, renal, and carotid arteries, respectively). The mesenteric vasculature exhibited dysregulation before the renal and carotid arteries, and this underlying dysfunction preceded the blood pressure decline and impaired organ blood flow.

Should mitral valve prolapse be considered as one of the risk factors for open angle glaucoma? A preliminary observation.

To assess the incidence of mitral valve prolapse in patients with newly diagnosed primary open angle glaucoma. The study included 12 patients without any other comorbidities or taking any general or local medications. Each patient underwent a full ophthalmological examination with visual field assessment and optical computed tomography of the macula and optic nerve head. Carotid Doppler ultrasound was performed to exclude impaired blood flow in this region and transthoracic echocardiography with assessment of the function and morphology of the heart valves. In the study group, mitral valve prolapse was found in seven patients (58.3%), while mitral valve regurgitation in 11 patients (91.7%). One case of normal pressure glaucoma and four cases of juvenile glaucoma were diagnosed. There were also other risk factors for glaucoma: myopia (58.3%), migraine headaches (41.7%), a positive family history of glaucoma (16.7%). Mitral valve prolapse could be indicated as a new risk factor for glaucoma. It seems reasonable to conduct screening tests for glaucoma in patients with mitral valve prolapse in the course of echocardiography.

​Circulating Cytokines in Myocardial Infarction Are Associated With Coronary Blood Flow.

BackgroundThe level of systemic inflammation correlates with the severity of the clinical course of acute myocardial infarction (AMI). It has been shown that circulating cytokines and endothelial dysfunction play an important role in the process of clot formation. The aim of our study was to assess the concentration of various circulating cytokines, endothelial function and blood clotting in AMI patients depending on the blood flow through the infarction-related artery (IRA).MethodsWe included 75 patients with AMI. 58 presented with ST-elevation myocardial infarction (STEMI) and 17 had non-ST-elevation myocardial infarction (non-STEMI). A flow-mediated dilation test (FMD test), thrombodynamics and rotational thromboelastometry as well as assessment of 14 serum cytokines using xMAP technology were performed.FindingsNon-STEMI-patients were characterized by higher levels of MDC, MIP-1β, TNF-α. Moreover, we observed that patients with impaired blood flow through the IRA (TIMI flow 0-1) had higher average and initial clot growth rates, earlier onset of spontaneous clots, C-reactive protein (CRP) and IL-10 compared to patients with preserved blood flow through the IRA (TIMI flow 2-3). Patients with TIMI 2-3 blood flow had higher level of IP-10. IL-10 correlated with CRP and pro-inflammatory cytokines levels, initial clot growth rate and clot lysis time in TIMI 0-1 patients. All these differences were statistically significant.InterpretationWe demonstrated that concentrations of the inflammatory cytokines correlate not only with the form of myocardial infarction (STEMI or non-STEMI), but also with the blood flow through the infarct-related artery. Inflammatory response, functional state of endothelium, and clot formation are closely linked with each other. A combination of these parameters affects the patency of the infarct-related artery.

Impairment of branchial and coronary blood flow reduces reproductive fitness, but not cardiac performance in paternal smallmouth bass (Micropterus dolomieu)

The capacity to extract oxygen from the water, and the ability of the heart to drive tissue oxygen transport, are fundamental determinants of important life-history performance traits in fish. Cardiac performance is in turn dependent on the heart's own oxygen supply, which in some teleost species is partly delivered via a coronary circulation originating directly from the gills that perfuses the heart, and is crucial for cardiac, metabolic and locomotory capacities. It is currently unknown, however, how a compromised branchial blood flow (e.g., by angling-induced hook damage to the gills), constraining oxygen uptake and coronary blood flow, affects the energetically demanding parental care behaviours and reproductive fitness in fish. Here, we tested the hypothesis that blocking ¼ of the branchial blood flow and abolishing coronary blood flow would negatively affect parental care behaviours, cardiac performance (heart rate metrics, via implanted Star-Oddi heart rate loggers) and reproductive fitness of paternal smallmouth bass (Micropterus dolomieu). Our findings reveal that branchial/coronary ligation compromised reproductive fitness, as reflected by a lower proportion of broods reaching free-swimming fry and a tendency for a higher nest abandonment rate relative to sham operated control fish. While this was associated with a tendency for a reduced aggression in ligated fish, parental care behaviours were largely unaffected by the ligation. Moreover, the ligation did not impair any of the heart rate performance metrics. Our findings highlight that gill damage may compromise reproductive output of smallmouth bass populations during the spawning season. Yet, the mechanism(s) behind this finding remains elusive.

Fenofibrate Nano-Eyedrops Ameliorate Retinal Blood Flow Dysregulation and Neurovascular Coupling in Type 2 Diabetic Mice.

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). The longitudinal changes in retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice treated with FenoNano (n = 6) or the vehicle (n = 6) from ages 8–14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) and the phosphorylation of peroxisome proliferator-activated receptor alpha (PPAR-α) by immunofluorescence. In db/db mice treated with FenoNano, both responses were restored from 8 to 14 weeks of age compared with the diabetic mice treated with the vehicle. At 14 weeks of age, the impaired regulation of retinal blood flow during systemic hyperoxia and flicker stimulation improved to about half of that in the db/db mice treated with FenoNano compared with the db/m control group (n = 5). FenoNano prevented the activation of VEGF and GFAP expression and increased the AQP4 expression and the phosphorylation of PPAR-α detected by immunofluorescence compared with the diabetic mice treated with the vehicle eyedrop. Our results suggested that the fenofibrate nano-eyedrops prevent retinal glial dysfunction via the phosphorylation of PPAR-α and improves the retinal blood flow dysregulation in type 2 diabetic mice.

Pericyte dysfunction and loss of interpericyte tunneling nanotubes promote neurovascular deficits in glaucoma

Reduced blood flow and impaired neurovascular coupling are recognized features of glaucoma, the leading cause of irreversible blindness worldwide, but the mechanisms underlying these defects are unknown. Retinal pericytes regulate microcirculatory blood flow and coordinate neurovascular coupling through interpericyte tunneling nanotubes (IP-TNTs). Using two-photon microscope live imaging of the mouse retina, we found reduced capillary diameter and impaired blood flow at pericyte locations in eyes with high intraocular pressure, the most important risk factor to develop glaucoma. We show that IP-TNTs are structurally and functionally damaged by ocular hypertension, a response that disrupted light-evoked neurovascular coupling. Pericyte-specific inhibition of excessive Ca2+ influx rescued hemodynamic responses, protected IP-TNTs and neurovascular coupling, and enhanced retinal neuronal function as well as survival in glaucomatous retinas. Our study identifies pericytes and IP-TNTs as potential therapeutic targets to counter ocular pressure-related microvascular deficits, and provides preclinical proof of concept that strategies aimed to restore intrapericyte calcium homeostasis rescue autoregulatory blood flow and prevent neuronal dysfunction.

Leriche syndrome diagnosed due to polytrauma: a case report

BackgroundLeriche syndrome is caused by atherosclerosis and is often characterized by symptoms such as intermittent claudication and numbness and coldness of the lower limbs. Its exact prevalence and incidence are unknown because it is a rare disease. We report a case of Leriche syndrome diagnosed incidentally on trauma pan-scan computed tomography (CT).Case presentationA 61-year-old Asian male was driving a passenger car and had a head-on collision with a dump truck that required an emergency call. The patient was transported to our hospital in a doctor’s helicopter. Physical examination revealed the following vital signs: respiratory rate, 23 breaths per min; SpO2, 98% under a 10-L administration mask; pulse rate, 133 beats per min; blood pressure, 142/128 mmHg; Focused Assessment with Sonography for Trauma, positive; Glasgow Coma Scale assessment, E3V5M6; and body temperature, 35.9 °C.Trauma pan-scan CT showed bilateral mandibular fractures, bilateral multiple rib fractures, bilateral pneumothorax, sternal fractures, hematoma around thoracic spine, small bowel perforation, mesenteric injury, right clavicle fracture, right ankle debridement injury, and thrombotic occlusion from just above the abdominal aortic bifurcation to the bilateral common iliac arteries. Although thrombotic occlusion needed to be differentiated from traumatic aortic injury, the presence of collateral blood vessels led to the diagnosis of Leriche syndrome, and conservative treatment was performed.Damage control surgery was required for the small bowel injuries. From the second day of admission, the patient was treated with continuous intravenous heparin and prostaglandin preparations. However, impaired blood flow and reperfusion injury in the right lower extremity progressed. On the fifth day of admission, right thigh amputation was performed. The patient required renal replacement therapy for 2 weeks starting from the third day of admission.ConclusionsIn this case, conservative therapy was initially chosen for Leriche syndrome. However, the complex factors in the acute phase of trauma led to development of hemorrhagic necrosis, requiring amputation of the lower extremity. Our findings indicate the need to carefully consider the unique factors affecting Leriche syndrome patients when considering treatment indications and choices for trauma.

Comparative Assessment of Retinal Blood Flow Velocity Changes Following Brimonidine and Brinzolamide Administration Using Retinal Function Imaging.

PurposeImpaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager.MethodsIn 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements.ResultsIntraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds.ConclusionsNeither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results.Translational RelevanceThe study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.

General practitioner’s tactics in the management of patients with stable angina

Ischemic heart disease (IHD) is one of the most common diseases of the cardiovascular system, which is based on a disorder of the trophism of the heart muscle against the background of pathological changes in the coronary vessels. The leading factor in changes in coronary vessels is stenosing atherosclerosis, which results in impaired blood flow. Risk factors include male gender, older age, a burdened familial history, as well as low physical activity, arterial hypertension, diabetes mellitus, and obesity. Ischemic heart disease is the leading cause of death, especially in developed countries, and the number one cause of medical visits related to heart and vascular problems. One of the most common manifestations of ischemic heart disease is angina pectoris. When pain sensations appear against the background of physical activity or emotional stress, it is called angina of effort, but if angina manifestations occur outside the period of physical and mental activity, we are speaking about resting angina pectoris. There are acute and chronic forms of ischemic heart disease, and while cardiologists and cardiac resuscitators usually deal with acute conditions, dynamic monitoring of patients after a myocardial infarction or with angina pectoris is a part of the responsibility of a general practitioner.

Ischemic heart disease (IHD) is one of the most common diseases of the cardiovascular system, which is based on a disorder of the trophism of the heart muscle against the background of pathological changes in the coronary vessels. The leading factor in changes in coronary vessels is stenosing atherosclerosis, which results in impaired blood flow. Risk factors include male gender,

In their practice, family doctors may encounter symptoms that require differential diagnosis between organic and functional disorders of the gastrointestinal tract and malignant neoplasms. The similarity of the clinical picture in some cases requires timely making the right decision about the tactics of examination, additional diagnostic measures and further referral to specialized medical institutions for treatment. One of these diseases that do not have specific clinical features at an early stage is gastric cancer, which is a malignant degeneration of the epithelium of the gastric mucosa. Symptoms of gastric cancer in its initial stages are limited to dyspeptic disorders, loss of appetite and unexpressed asthenia, which makes its manifestations similar to many diseases that affect the gastrointestinal tract — gastritis, peptic ulcer of the stomach and duodenum, adenomatous polyps of the gastric mucosa. The main diagnostic method that allows making the correct diagnosis is gastroscopy, which makes it possible not only to assess the condition of the mucosa, but also to take material for a biopsy with further histological examination of the tissue. Since the main treatment for gastric cancer is surgery, a correct and timely diagnosis plays a significant role in the further prognosis of the disease and the patient's quality of life.

Pro- and anti-apoptotic microRNAs are differentially regulated during estivation in Xenopus laevis

Xenopus laevis, the African clawed frog, undergoes seasonal estivation to survive periods of drought when its lake-bed habitats dry up. The frog can lose ∼30% of its total body water, leading to conditions of impaired blood flow and ischemia which risk cellular survival under these harsh conditions. MicroRNAs are short, noncoding, single-stranded RNAs 21–24 nt long that have been widely implicated in hypometabolic responses, and serve functions including apoptosis survival. The levels of three pro-apoptotic and four anti-apoptotic miRNAs were measured in liver and skeletal muscle of estivating X. laevis, and bioinformatic analysis was performed to verify potential mRNA targets of these miRNAs. Members of pro-apoptotic miRNAs miR-15a, miR-16, and miR-101 showed upregulation as a result of dehydration stress, while anti-apoptotic miRNAs miR-19b, miR-21, miR-92a, and miR-155 showed differential regulation between the two tissues. Together, these miRNAs act in a more diverse fashion than arbitrarily pro- or anti-apoptotic, and encompass functions ranging from the inhibition of cell proliferation through cell cycle arrest to the prevention of skeletal muscle atrophy.

Buxue Yimu Pills improve angiogenesis and blood flow in experimental zebrafish and rat models

Ethnopharmacological relevanceBuxue Yimu Pills (BYP) is a well-known traditional Chinese medicine prescription which is clinical used in gynecology and obstetrics, and is documented to exhibit therapeutic potential to defective angiogenesis and impaired blood flow. Aim of the studyThis study aimed to investigate the effects and biological mechanisms of BYP in improvement of defective angiogenesis and impaired blood flow which represent major health issues associated with various diseases including postpartum or abortion complications. Materials and methodsIn this study, VEGFR tyrosine kinase inhibitor II (VRI) was used to establish blood vessel loss model in Tg(fli-1a:EGFP) zebrafish embryos. Blood vessel loss was calculated, and quantitative real-time PCR (qRT-PCR) assay was performed to detect gene expression. Mifepristone and misoprostol were applied to construct a medical-induced incomplete abortion rats model. Whole blood viscosity indexes, hemorheology and coagulation function of the rats were investigated. Immunohistochemistry analysis was used for evaluation of the uterine tissues. ResultsBYP treatment significantly promoted angiogenesis as evidenced by the restoration of VRI-induced blood vessel loss in zebrafish embryos. BYP treatment effectively reversed VRI-induced down-regulation of the VEGFRs (Kdr, Kdrl and Flt1). Furthermore, BYP administration significantly suppressed the increase of whole blood viscosity indexes, and remarkably shortened the levels of prothrombin time and activated partial thromboplastin time in the medical-induced incomplete abortion rats, indicating the improvement of hemorheology and coagulation function. Immunohistochemistry analysis suggested that BYP administration increased the expression level of VEGFR2 in uterus tissues of the rats. ConclusionBYP exhibits therapeutic effects in promoting angiogenesis and blood circulation, and mitigating blood stasis, supporting its clinical application for postpartum or abortion complications.

Prevalence of fatty liver disease after liver transplantation and risk factors for recipients and donors

Introduction and objectivesFatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). MethodsA total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20–68] years) treated from 2011–2020 was enrolled. Three recipients died at < 3 months as a result of infection or blood flow impairment, and were excluded from the long-term FLD study. On evaluation of 88 prospective living donors, fatty liver was observed in 21. The prevalence and risk factors for FLD and survival were evaluated. ResultsAfter LT, 28 of 105 recipients (26.7%) developed FLD. FLD was more common in patients with a high body mass index (BMI) and dyslipidemia (both p < 0.01), primary nonalcoholic steatohepatitis (p = 0.02), after living-donor LT (p = 0.03) and everolimus (EVL) use (p = 0.08). Factors predictive of FLD included EVL use and a high BMI (hazard ratios = 3.00 and 1.34; p = 0.05 and p < 0.01, respectively). Sixteen donors lost 6.5 kg (range: 2.0–16.0 kg) of body weight prior to LT. However, there were no cases of primary non-function, which did not affect the FLD prevalence. Development of FLD did not have a negative impact on LT outcome; the 5-year survival rate was 92.6%. ConclusionsRecipient factors were more important than donor factors for FLD onset after LT.

Vascular Reactivity to Hypercapnia Is Impaired in the Cerebral and Retinal Vasculature in the Acute Phase After Experimental Subarachnoid Hemorrhage.

Objective: Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment.Methods: Subarachnoid hemorrhage was induced by injecting 0.5 ml of heparinized autologous blood into the cisterna magna of male Wistar rats using two anesthesia protocols [isoflurane/fentanyl n = 25 (Sham + SAH): Iso—Group, ketamine/xylazine n = 32 (Sham + SAH): K/X—Group]. CBF (laser speckle contrast analysis) and physiological parameters were measured continuously for 6 h. At six predefined time points, hypercapnia was induced by hypoventilation controlled via blood gas analysis, and retinal vessel diameter (RVD) was determined non-invasively.Results: Cerebral reactivity and retinal reactivity in Sham groups were stable with only a slight attenuation after 2 h in RVD of the K/X—Group. In the SAH Iso—Group, cerebral and retinal CO2 reactivity compared to baseline was immediately impaired starting at 30 min after SAH (CBF p = 0.0090, RVD p = 0.0135) and lasting up to 4 h (p = 0.0136, resp. p = 0.0263). Similarly, in the K/X—Group, cerebral CO2 reactivity was disturbed early after SAH (30 min, p = 0.003) albeit showing a recovery to baseline after 2 h while retinal CO2 reactivity was impaired over the whole observation period (360 min, p = 0.0001) in the K/X—Group. After normalization to baseline, both vascular beds showed a parallel behavior regarding the temporal course and extent of impairment.Conclusion: This study provides a detailed temporal analysis of impaired cerebral vascular CO2 reactivity starting immediately after SAH and lasting up to 6 h. Importantly, the retinal vessels participate in these acute changes underscoring the promising role of the retina as a potential non-invasive screening tool after SAH. Further studies will be required to determine the correlation with functional outcomes.

The role of optical coherence tomography angiography biomarkers in assessing the outcome of long-term anti-VEGF therapy of diabetic macular edema

The purpose of the study was to assess the changes of biomarkers of diabetic macular edema activity by optical coherence tomography angiography (OCTA) data and the relationship of these biomarkers with the response to anti-VEGF therapy during a two-year follow-up. Material and methods. The study included 59 patients (101) eyes, averagely aged 60.27 ± 9.50 years. The average number of intravitreal injections of aflibercept over the treatment period was 12.87 ± 3.50. The initial size of the foveolar avascular zone (FAZ) area — 0.37 ± 0.22 mm2 , and the acircularity index — 0.56 ± 0.14 remained unchanged after 5 months: 0.36 ± 0.24 mm2 and 0.56 ± 0.12, respectively, and being practically in the same level in 12 and 24 months. The large FAZ area, noted in the group where disorganization of retinal inner layers (DRIL) was observed (0.39 ± 0.21 mm2 ), correlated with a lower visual acuity (r = 0.67, p = 0.003). The acircularity index remained unchanged; no significant differences were found in the DRIL patient groups. After 5 loading injections, the average initial density of vessels in the macular region increased from 12.33 ± 3.86 mm to 12.75 ± 1.14 mm, after 1 year it was 13.48 ± 1.15 mm, after 2 years — 13.25 ± 3.39 mm. The average density of retinal perfusion increased at the 5th month from 29.81 ± 10.85 % to 31.55 ± 2.34 %, after 12 months to 32.91 ± 3.45, and by the end of the observation period to 31.41 ± 9.79 %. In the DRIL group, the baseline vascular density and mean perfusion volume were significantly lower: 11.17 ± 2.09 mm vs. 13.49 ± 1.14 mm and 28.40 ± 4.53 % vs. 31.20 ± 2.44 %). Conclusion. DRIL, a biomarker reflecting impaired capillary blood flow in the superficial capillary plexus and correlating with functional results, can be used as a predictor of antiangiogenic therapy effectiveness. After antiangiogenic therapy with DMO, the microcirculation indices (FAZ and acircularity) remained stable, and the vascular density and perfusion volume tended to increase, which testifies to the absence of ischemic damage.