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OBJECTIVE: This study aimed to investigate the effects of six weeks of continuous training and Nutrition Bio-shield (NBS) Superfood Supplementation on the state of oxidative stress by the expression of Nrf2, NOX4, superoxide dismutase, and malondialdehyde genes in the lungs of rats after methamphetamine withdrawal. METHODS: Forty male Wistar rats were randomly divided into five groups (nâ=â8, per group), undergoing methamphetamine administration (six weeks, 5âmg/kg ip, and once per day) followed by a 21-day withdrawal period. The rats were supplemented NBS superfood at a dosage of 25âg/kg per day for six weeks. The training protocol was 30 minutes of daily continuous training (treadmill running), five days a week for six weeks. The regimen escalated from a pace of 3âm/min for the initial 5 minutes, to 5âm/min for the following 5 minutes, culminating at 8âm/min for the remainder of the session, all at a 0° incline. A one-way analysis of variance was performed to analyze the gene expression of Nrf2, NOX4, MDA, and SOD in the lungs tissue of rats. RESULTS: The results indicated that, in the experimental groups which underwent continuous training and NBS Superfood supplementation, the expression of the Nrf2 gene exhibited a significant elevation compared to the control group (Pâ<â0.05), while the NOX4, MDA, and SOD genes expression exhibited a significant decline in comparison to the control group (Pâ<â0.05). CONCLUSION: In general, both exercise interventions and NBS superfood supplementation, when employed separately or in combination after methamphetamine withdrawal, can enhance the state of oxidative stress in the lung.
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BACKGROUND: "Slow flow" is one very important concept in modern fundamental and clinical biomedicine. Slow coronary flow is indicative of delayed filling of the terminal coronary artery vessels, occurring in the absence of significant coronary stenosis. This group patient of patients exhibits a high incidence of disability and represents a significant financial and material burden for the state and the healthcare system in general. OBJECTIVE: The primary objective of our study was to examine patients with slow coronary flow. METHODS: We studied the standard parameters recommended by the international health care system (electrocardiography (by Medica QRS-12, Germany), through the electrical activity of a patient's heart by the electrical impulses (beating) of the heart; HC1(Germany); coagulogramma by Coatron M1 (Germany), troponin by AQT 90 (Germany); general blood test we used automatic human counting device HC1(Germany). Also, we investigate the original parameters (non-standard parameters, which we use in this pilot study) that we were first studied for this diagnosis and non-standard parameters. RESULTS: A general blood test showed that patients with slow flow had a higher blood leukocyte count than the control group, but the amount of hemoglobin was normal, the hematocrit was much higher than in the control group, and the platelet count was close to the lower limit of clinical standards.We obtained details of blood flow by coagulation situation, such as prothrombin time, prothrombin index, international normalized ratio, activated partial thromboplastin time, thrombin time, fibrinogen, and rheological properties such as index of erythrocyte aggregability, index of erythrocyte deformability, plasma viscosity, in silico blood rheological index. CONCLUSSION: Blood flow can be considered as a superposition of vortices with similar frequencies and wave vectors that change after bifurcations or other obstacles in the vascular network. These factors together determine the conditions for structuring the flow of moving blood. Disruption or alteration of these factors results in slow flow. It has been found that the speed of blood flow in the coronary arteries depends on changes in the number and function of red blood cells. Slow flow is directly influenced by the aggregation and deformation of red blood cells, their number, and plasma viscosity. Consequently, the rheological status plays a crucial role in determining blood flow and its velocity.
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Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxylic acid cycle and the subsequent reduction of iron-sulfur cluster protein levels. Ferredoxin1 facilitates the lipoacylation of dihydrolipoyl transacetylase, which in turn degrades iron-sulfur cluster proteins by reducing Cu2+ to Cu+, thereby inducing cell death. Furthermore, copper homeostasis is regulated by the copper transporter, and disturbances in this homeostasis result in cuproptosis. Current evidence suggests that cuproptosis plays an important role in the onset and development of several cardiovascular diseases. Copper-chelating agents, including ammonium tetrathiomolybdate (VI) and DL-penicillamine, have been shown to facilitate the alleviation of cardiovascular disease by inhibiting cuproptosis. It is hypothesized that oxidative phosphorylation inhibitors such as physical training may inhibit cuproptosis by inhibiting the protein stress response. In conclusion, the implementation of physical training may be a viable strategy to reducte the incidence of cuproptosis.
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Over the last few years, there has been an increasing focus on integrating artificial intelligence (AI) into existing imaging systems. This also applies to ultrasound. There are already applications for thyroid and breast lesions that enable AI-assisted sonography directly on the device. However, this is not yet the case for lymph nodes.The aim was to test whether already established programs for AI-assisted sonography of breast lesions and thyroid nodules are also suitable for identifying and measuring superficial lymph nodes. For this purpose, the two programs were used as a supplement to routine ultrasound examinations of superficial lymph nodes. The accuracy of detection by AI was then evaluated using a previously defined score. If available, a comparison was made with cross-sectional imaging.The programs that were used are able to adequately detect lymph nodes in the majority of cases (78.6%). Problems were caused in particular by a high proportion of echo-rich fat, blurred differentiation from the surrounding tissues and the occurrence of lymph node conglomerates. The available cross-sectional images did not contradict the classification of the lesion as a lymph node in any case.In the majority of cases, the tested programs are already able to detect and measure superficial lymph nodes. Further improvement can be expected through specific training of the software. Further developments and studies are required to assess risk of malignancy. · The inclusion of AI in imaging is increasingly becoming a scientific focus.. · The detection of lymph nodes is already possible using device-integrated AI software.. · Malignancy assessment of the detected lymph nodes is not yet possible.. · Rink M, Künzel J, Stroszczynski C et al. Smart scanning: automatic detection of superficially located lymph nodes using ultrasound - initial results. Fortschr Röntgenstr 2024; DOI 10.1055/a-2331-0951.
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OBJECTIVES: The purpose of this study was to investigate the effects of 6 weeks of resistance training (RT) combined with aerobic training (AT) and Tirzepatide supplementation on lipid profiles, insulin resistance, anthropometric characteristics and physical fitness in prediabetic obese soldiers. METHODS: 61 obese men were randomly divided into six groups: Placebo; Tirzepatide 5âmg (T5); Tirzepatide 2.5âmg (T2.5); Hypertrophy, Strength, Power-Circuit Training+Placebo (Ex+P); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 5âmg (Ex+T5); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 2.5âmg (Ex+T2.5). All training groups performed aerobic training (AT) after resistance training. Subjects trained for six weeks, three sessions per week. Before and after the intervention period, the participants were evaluated for anthropometric measures, body composition [body weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM)], cardiorespiratory fitness (VO2max), and muscle strength (chest press 1RM and leg press 1RM). Blood biochemistry evaluations included triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), insulin level and insulin resistance (HOMA-IR). To evaluate the differences between the groups, ANCOVA statistical method was used along with Bonferroni's post hoc test, and the significance level was Pâ<â0.05. RESULTS: Body weight, BMI, WC, FM, FBG, LDL-C, TC, TG and HOMA-IR were significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. WHR significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo group. HDL-C, chest press and leg press significantly increased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. VO2max significantly increased and insulin significantly decreased in Ex+P group compared to Placebo, T5 and T2.5 groups. FM, FBG and TG were significantly decreased in both the T2.5 and T5 groups compared to Placebo group. HOMA-IR, LDL-C and TC significantly decreased in the T5 group compared to Placebo group. Also, leg press significantly increased in Ex+P group compared to all other groups. CONCLUSIONS: Performing six weeks of combined resistance and aerobic training in the form of RT+AT alone is more effective than the simultaneous use of Tirzepatide on cardiorespiratory fitness, strength, and modulating insulin levels. Taking Tirzepatide in doses of 5âmg and 2.5âmg in combination with exercise training did not have a significant advantage over exercise training alone. Finally, taking Tirzepatide in doses of 5âmg or 2.5âmg in combination with exercise training is not significantly superior to each other.
Subject(s)
Obesity , Humans , Obesity/therapy , Obesity/blood , Obesity/physiopathology , Male , Adult , Insulin Resistance , Resistance Training/methods , Exercise/physiology , Body Mass IndexABSTRACT
In severe cases, SARS-CoV-2 infection leads to severe respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, SARS-CoV-2 can interact with red blood cells (RBCs) via several receptors or auxiliary membrane proteins. Recent data show that viral infection causes significant damage to the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation, as has been described to occur in COVID-19 patients. In addition, many patients also develop systemic endotheliitis associated with generalized coagulopathy. This manifests itself clinically as obstructive microthrombi in the area of the medium and smallest vessels, which can affect all internal organs. It is thought that such changes in the RBCs may contribute to the microangiopathy/microthrombosis associated with COVID-19 and may result in impaired capillary blood flow and tissue oxygenation.
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BACKGROUND: The continuous development of ultrasound techniques increasingly enables better description and visualization of unclear lesions. New ultrasound systems must be evaluated with regard to all these diagnostic possibilities. METHODS: A multifrequency C1-7 convex probe (SC7-1M) with the new high-end system Resona A20 Series was used. Modern technologies, including HiFR CEUS, SR CEUS and multimodal tissue imaging with shear wave elastography (SWE), fat evaluation and viscosity measurements (M-Ref) were applied. RESULTS: Of nâ=â70 (mean value 48,3 years±20,3 years, range 18-84 years) cases examined, a definitive diagnosis could be made in nâ=â67 cases, confirmed by reference imaging and/or follow-up. Of these, nâ=â22 cases were malignant changes (HCC (hepatocellular carcinoma) nâ=â9, CCC (cholangiocellular carcinoma) nâ=â3, metastases of colorectal carcinomas or recurrences of HCC nâ=â10). In all 12 cases of HCC or CCC, the elastography measurements using the shear wave technique (with values >2âm/s to 3.7âm/s) showed mean values of 2.3±0.31âm/s and a degree of fibrosis of F2 to F4. In nâ=â14 cases, changes in the fat measurement (range 0.51 to 0.72âdB/cm/MHz, mean values 0.58±0.12âdB/cm/MHz) in the sense of proportional fatty changes in the liver were detected. In the 4 cases of localized fat distribution disorders, the values were >0.7âdB/cm/MHz in the sense of significant fatty deposits in the remaining liver tissue. Relevant changes in the viscosity measurements with values >1.8âkPa were found in nâ=â31 cases, in nâ=â5 cases of cystic lesions with partially sclerosing cholangitis, in nâ=â13 cases of malignant lesions and in nâ=â9 cases post-interventionally, but also in nâ=â4 cases of benign foci with additional systemic inflammation. CONCLUSIONS: The results are promising and show a new quality of ultrasound-based liver diagnostics. However, there is a need for further investigations with regard to the individual aspects, preferably on a multi-center basis.
Subject(s)
Carcinoma, Hepatocellular , Elasticity Imaging Techniques , Liver Neoplasms , Humans , Elasticity Imaging Techniques/methods , Contrast Media , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Viscosity , Liver/diagnostic imaging , Liver/pathology , Ultrasonography/methodsABSTRACT
Ferroptosis is a form of programmed cell death that plays a significant role in causing several diseases such as heart attack and heart failure, through alterations in fat, amino acid, and iron metabolism. Comprehending the regulatory mechanisms of ferroptosis signaling is critical because it has a considerable effect on the elderly's mortality. Conversely, age-related changes in substrate metabolism and metabolite levels are recognized to give rise to obesity. Furthermore, research has proposed that aging and obesity-related changes in substrate metabolism may aggravate ferroptosis. The suppression of ferroptosis holds potential as a successful therapeutic approach for managing different diseases, including sarcopenia, cardiovascular diseases, and central nervous system diseases. However, the pathologic and biological mechanisms behind the function of ferroptosis are not fully comprehended yet. Physical activity could affect lipid, amino acid, and iron metabolism to modulate ferroptosis. The aim of this study is to showcase the current understanding of the molecular mechanisms leading to ferroptosis and discuss the role of aging and physical activity in this phenomenon.
Subject(s)
Aging , Exercise , Ferroptosis , Humans , Ferroptosis/physiology , Aging/physiology , Exercise/physiology , Iron/metabolismABSTRACT
BACKGROUND: Liver biotransformation is the major route for drug metabolism in humans, often catalysed by cytochrome P450 (CYP) enzymes. This first-pass effect can lead to hepatotoxicity and influences the bioavailability of drugs. OBJECTIVE: We aimed to establish in vitro culture systems simulating the liver first-pass to study effects of the proteasome inhibitor MG-132 simultaneously on hepatocytes and cancer cells. METHODS: The first-pass effect was simulated by conditioned medium transfer (CMT) from pre-treated HepG2 CYP3A4-overexpressing cells to either pancreatic cancer cell line PANC-1 or primary colon cancer cells, and by indirect co-culture (CC) of liver and cancer cells in a shared medium compartment. Experimental proteasome inhibitor MG-132 was used as test substance as it is detoxified by CYP3A4. RESULTS: Cancer cells showed higher viabilities in the first-pass simulation by CMT and CC formats when compared to monocultures indicating effective detoxification of MG-132 by HepG2 CYP3A4-overexpressing cells. HepG2-CYP3A4 cells showed reduced viabilites after treatment with MG-132. CONCLUSIONS: We successfully established two different culture systems to simulate the liver first-pass effect in vitro. Such systems easily allow to study drug effects simultaneously on liver and on target cancer cells. They are of great value in pre-clinical cancer research, pharmaceutical research and drug development.
Subject(s)
Cytochrome P-450 CYP3A , Leupeptins , Neoplasms , Humans , Hep G2 Cells , Proteasome Inhibitors/pharmacology , Liver , Cytochrome P-450 Enzyme System/metabolism , BiotransformationABSTRACT
OBJECTIVE: To test and initially describe a new handheld wireless ultrasound technique (TE Air) for clinical use. METHODS: In this pilot study, the new ultrasound device TE Air from Mindray was used to examine the hepatic and renal vessels of healthy volunteers for first impressions. The probe has a sector transducer with a frequency range of 1.8-4.5 MHz. The B-mode and color-coded doppler sonography (CCDS) scanning methods were used. A high-end device from the same company (Resona 9, Mindray) was used as a reference. The results were evaluated using an image rating scale ranging from 0 to 5, with 0 indicating not assessable and 5 indicating without limitations. RESULTS: Altogether, 61 participants (nâ=â34 female [55.7%], nâ=â27 male [44.3%]), age range 18-83 years, mean age 37.9±16.5 years) could be adequately studied using TE AIR and the high-end device. With one exception, the image quality score for TE Air never fell below 3 and had a mean/median scored of 4.97/5.00 for the B-mode, 4.92/5.00 for the color flow (CF) mode, and 4.89/5.00 for the pulse wave (PW) mode of the hepatic vein, 4.90/5.00 for the portal vein, 4.11/4.00 for the hepatic artery, and 4.57/5.00 for the renal segmental artery. A significant difference in the assessment of flow measurement of the hepatic artery and renal segmental arteries was found between TE AIR and the high-end device. CONCLUSIONS: TE Air represents a new dimension in point-of-care ultrasound via wireless handheld devices. Especially, its flow measurement ability offers a relevant advantage over other available handheld models. TE Air provides a formally sufficient image quality in terms of diagnostic significance.
Subject(s)
Portal Vein , Ultrasonography, Doppler, Color , Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Pilot Projects , Ultrasonography , Portal Vein/diagnostic imaging , LiverABSTRACT
AIMS: To assess the value of using integrated parametric ultrasound software for contrast-enhanced ultrasonography (CEUS) of liver tumors. METHODS: 107 patients with liver tumors were studied. CEUS were performed to detect focal lesions. Parametric images were based on continuous CINE LOOPs, from the early-arterial phase (15 s) to the portal-venous phase (1 min) generated by perfusion software. The evaluations of the parametric images and their dignity for liver lesions were performed independently by an experienced and a less-experienced investigator. Computed tomography, magnetic resonance imaging scans or histological analysis were used as references. RESULTS: High parametric image quality were obtained in all patients. Among the patients, 44% lesions were benign, 56% were malignant. The experienced investigator correctly classified 46 of 47 (98%) as benign, and 60 of 60 (100%) as malignant tumors based on the parametric images. The less-experienced investigator correctly classified 39 of 47 (83%) as benign, and 49 of 60 (82%) malignant tumors, acheaving a high statistical accuracy of 98% with this type of diagnostic. CONCLUSION: Parametric imaging for grading the malignant degree of tumor may be a good complement to existing ultrasound techniques and was particularly helpful for improving the assessments of the less-experienced examiner.
Subject(s)
Image Interpretation, Computer-Assisted , Liver Neoplasms , Ultrasonography , Humans , Contrast Media , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Perfusion/methods , Sensitivity and Specificity , Ultrasonography/methods , SoftwareABSTRACT
In the liver, phase-1 biotransformation of drugs and other xenobiotics is largely facilitated by enzyme complexes consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs). Generated from human liver-derived cell lines, recombinant in vitro cell systems with overexpression of defined phase-1 enzymes are widely used for pharmacological and toxicological drug assessment and laboratory-scale production of drug-specific reference metabolites. Most, if not all, of these cell lines, however, display some background activity of several CYPs, making it difficult to attribute effects to defined CYPs. The aim of this study was to generate cell lines with stable overexpression of human phase-1 enzymes based on Chinese hamster ovary (CHO) suspension cells. Cells were sequentially modified with cDNAs for human CPR in combination with CYP1A2, CYP2B6, or CYP3A4, using lentiviral gene transfer. In parallel, CYP-overexpressing cell lines without recombinant CPR were generated. Successful recombinant expression was demonstrated by mRNA and protein analyses. Using prototypical CYP-substrates, generated cell lines proved to display specific enzyme activities of each overexpressed CYP while we did not find any endogenous activity of those CYPs in parental CHO cells. Interestingly, cell lines revealed some evidence that the dependence of CYP activity on CPR could vary between CYPs. This needs to be confirmed in further studies. Recombinant expression of CPR was also shown to enhance CYP3A4-independent metabolisation of testosterone to androstenedione in CHO cells. We propose the novel serum-free CHO suspension cell lines with enhanced CPR and/or defined CYP activity as a promising "humanised" in vitro model to study the specific effects of those human CYPs. This could be relevant for toxicology and/or pharmacology studies in the pharmaceutical industry or medicine.
Subject(s)
Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System , Animals , Cricetinae , Humans , CHO Cells , Cricetulus , Cytochrome P-450 CYP3A/genetics , BiotransformationABSTRACT
Cancer patients are at a very high risk of serious thrombotic events, often fatal. The causes discussed include the detachment of thrombogenic particles from tumor cells or the adverse effects of chemotherapeutic agents. Cytostatic agents can either act directly on their targets or, in the case of a prodrug approach, require metabolization for their action. Cyclophosphamide (CPA) is a widely used cytostatic drug that requires prodrug activation by cytochrome P450 enzymes (CYP) in the liver. We hypothesize that CPA could induce thrombosis in one of the following ways: (1) damage to endothelial cells (EC) after intra-endothelial metabolization; or (2) direct damage to EC without prior metabolization. In order to investigate this hypothesis, endothelial cells (HUVEC) were treated with CPA in clinically relevant concentrations for up to 8 days. HUVECs were chosen as a model representing the first place of action after intravenous CPA administration. No expression of CYP2B6, CYP3A4, CYP2C9 and CYP2C19 was found in HUVEC, but a weak expression of CYP2C18 was observed. CPA treatment of HUVEC induced DNA damage and a reduced formation of an EC monolayer and caused an increased release of prostacyclin (PGI2) and thromboxane (TXA) associated with a shift of the PGI2/TXA balance to a prothrombotic state. In an in vivo scenario, such processes would promote the risk of thrombus formation.
Subject(s)
Neoplasms , Prodrugs , Thrombosis , Humans , Prodrugs/pharmacology , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Endothelial Cells/metabolism , Cyclophosphamide/therapeutic use , Cytochrome P-450 Enzyme System/metabolism , Neoplasms/drug therapy , Thrombosis/drug therapyABSTRACT
BACKGROUND: Physical training in patients with heart failure can affect hemodynamic, cardiac and angiogenesis parameters. OBJECTIVE: The aim of the present study was to investigate the effects of traditional moderate-intensity rehabilitation training and interval training on some angiogenesis factors in coronary artery bypass graft (CABG) patients. METHODS: Thirty CABG patients (mean age±SD, 55±3 years) were randomly assigned to one of three groups: high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) or the control group. After the initial assessments, eligible patients in the experimental groups (HIIT and MICT) performed exercise training for 8 weeks, while the control group did not. Angiogenesis and angiostatic indices, including pro-adrenomedullin (pro-ADM), basic fibroblast growth factor (bFGF), and endostatin, were then measured. RESULTS: The results showed no significant difference between pro-ADM in the HIIT and MICT groups (Pâ=â0.99), but a significant difference was found between MICT and the control group and between HIIT and the control group (Pâ=â0.001). There is also no significant difference between the bFGF levels in the HIIT and MICT training groups (Pâ=â1.00), but the changes in this factor between the training groups and the control group were significant (Pâ=â0.001). There was a significant difference between the levels of endostatin in all three groups. CONCLUSIONS: Two methods of cardiac rehabilitation (HIIT and MICT) may be useful for the recovery of patients with coronary artery bypass grafting. This improvement manifested itself in changes in angiogenesis and angiostatic indices in this study. However, more extensive studies are needed to investigate the effects of these two types of rehabilitation programs on other indicators of angiogenesis and angiostatic.
Subject(s)
Cardiac Rehabilitation , Coronary Artery Bypass , Exercise , High-Intensity Interval Training , Humans , Middle Aged , Cardiac Rehabilitation/methods , Endostatins , High-Intensity Interval Training/methodsABSTRACT
AIM: To examine to what extent the high frame rate contrast-enhanced ultrasound (HiFR) diagnostic enables the conclusive diagnosis of liver changes with suspected malignancy. MATERIAL/METHODS: Ultrasound examinations were performed by an experienced examiner using a multifrequency probe (SC6-1) on a high-end ultrasound system (Resona 7, Mindray) to clarify liver changes that were unclear on the B-scan. A bolus of 1-2.4âml of the Sulphur hexafluoride ultrasound microbubbles contrast agent SonoVue™ (Bracco SpA, Italy) was administered with DICOM storage of CEUS examinations from the early arterial phase (5-15âs) to the late phase (5-6 min). Based on the image files stored in the PACS, an independent reading was performed regarding image quality and finding-related diagnostic significance (0 not informative/non-diagnostic to 5 excellent image quality/confident diagnosis possible). References were clinical follow-up, if possible, comparison to promptly performed computed tomography or magnetic resonance imaging, in some cases also to histopathology. RESULTS: We examined 100 patients (42 women, 58 men, from 18 years to 90 years, mean 63±13 years) with different entities of focal and diffuse liver parenchymal changes, which could be detected in all cases with sufficient image quality with CEUS and with high image quality with HiFR-CEUS. Proportionally septate cysts were found in nâ=â19 cases, scars after hemihepatectomy with local reduced fat in nâ=â5 cases, scars after microwave ablation in nâ=â19 cases, hemangiomas in nâ=â9 cases, focal nodular hyperplasia in nâ=â8 cases, colorectal metastases in nâ=â15 cases, hepatocellular carcinoma (HCC) in nâ=â11 cases, Osler disease in nâ=â8 cases. The size of lesions ranged from 5âmm to 200âmm with a mean value of 33.1±27.8âmm. Conclusive diagnoses could be made by the experienced investigator in 97/100 cases with CEUS, confirmed by reference imaging, in parts by histopathology or follow-up. The image quality for HiFR CEUS was rated with a score of 3 to 5; 62 cases were assessed with an average of good (4 points), 27 cases with very good (5 points), and in 11 cases (3 points) still satisfactory despite aggravated acoustic conditions. The specificity of HIFR-CEUS was 97%, the sensitivity 97%, the positive predictive value 94%, the negative predictive value 99% and the accuracy 97%. CONCLUSION: HIFR-CEUS has demonstrated has demonstrated an improved image quality resulting in a high diagnostic accuracy. In the hands of an experienced investigator, HiFR-CEUS allows the assessment of focal and diffuse unclear liver parenchymal changes on B-scan and dynamic assessment of microcirculation in solid and vascular changes.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Male , Humans , Female , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Cicatrix/pathology , Contrast Media , Ultrasonography/methods , Magnetic Resonance ImagingABSTRACT
The cyanobacterium Arthrospira platensis (Spirulina platensis) is a natural source of considerable amounts of ingredients that are relevant for nutra- and pharmaceutical uses. Different hydrophilic and hydrophobic substances can be obtained by extraction from the biomass. The respective extraction techniques determine the composition of substances in the extract and thus its biological activity. In this short review, we provide an overview of the hydrophilic compounds (phenols, phycobiliproteins, polysaccharides, and vitamins) and lipophilic ingredients (chlorophylls, vitamins, fatty acids, and glycolipids) of Arthrospira platensis. The principal influences of these substances on blood and tissue cells are briefly summarized.
ABSTRACT
The characterization of novel radiotracers toward their metabolic stability is an essential part of their development. While in vitro methods such as liver microsome assays or ex vivo blood or tissue samples provide information on overall stability, little or no information is obtained on cytochrome P450 (CYP) enzyme and isoform-specific contribution to the metabolic fate of individual radiotracers. Herein, we investigated recently established CYP-overexpressing hepatoblastoma cell lines (HepG2) for their suitability to study the metabolic stability of radiotracers in general and to gain insight into CYP isoform specificity. Wildtype HepG2 and CYP1A2-, CYP2C19-, and CYP3A4-overexpressing HepG2 cells were incubated with radiotracers, and metabolic turnover was analyzed. The optimized protocol, covering cell seeding in 96-well plates and analysis of supernatant by radio thin-layer-chromatography for higher throughput, was transferred to the evaluation of three 18F-labeled celecoxib-derived cyclooxygenase-2 inhibitors (coxibs). These investigations revealed time-dependent degradation of the intact radiotracers, as well as CYP isoform- and substrate-specific differences in their metabolic profiles. HepG2 CYP2C19 proved to be the cell line showing the highest metabolic turnover for each radiotracer studied here. Comparison with human and murine liver microsome assays showed good agreement with the human metabolite profile obtained by the HepG2 cell lines. Therefore, CYP-overexpressing HepG2 cells provide a good complement for assessing the metabolic stability of radiotracers and allow the analysis of the CYP isoform-specific contribution to the overall radiotracer metabolism.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Cell Line , Cytochrome P-450 CYP2C19 , Cytochrome P-450 Enzyme System/metabolism , Humans , Mice , Protein IsoformsABSTRACT
BACKGROUND: Ultrasound follow-up of transjugular intrahepatic portosystemic shunt (TIPS) is challenging due to the bent course of the stent-graft. OBJECTIVE: Aim of this retrospective study was to assess to which extent the combination of HR flow with Glazing Flow improves hemodynamic assessment in the ultrasound follow-up of TIPS. METHODS: Comparative studies with CCDS and High Resolution (HR)-Flow with Glazing Flow were evaluated regarding image quality and artifacts on a 5-point scale (0â=âcannot be assessed up to 5â=âmaximum image quality without artifacts). In all cases, an experienced examiner performed the examinations with a 1-6âMHz probe (Resona 7, Mindray). RESULTS: 61 ultrasound examinations in 48 patients were performed; the mean patient age was 54±14.2 years. The use of HR-Flow with Glazing Flow resulted in an improved flow display in 55/61 cases (90.2%). Both methods correlated well (râ=â0.71), but HR flow with Glazing flow values were in general higher than CCDS values. The reading resulted in an average value of 2.52±0.54 for CCDS and 3.52±0.57 for HR flow with Glazing flow (pâ=â0.013). CONCLUSION: The combination of HR-Flow and Glazing Flow results in improved flow representation and reduction of artifacts in the ultrasound follow-up of TIPS.
Subject(s)
Hemodynamics , Portal Vein , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Blood Flow Velocity , Stents , Treatment OutcomeABSTRACT
Light-emitting diodes (LED) can be utilized as tailorable artificial light sources for the cultivation of cyanobacteria such as Arthrospira platensis (AP). To study the influence of different LED light colors on phototrophic growth and biomass composition, AP was cultured in closed bioreactors and exposed to red, green, blue, or white LED lights. The illumination with red LED light resulted in the highest cell growth and highest cell densities compared to all other light sources (order of cell densities: red > white > green > blue LED light). In contrast, the highest phycocyanin concentrations were found when AP was cultured under blue LED light (e.g., order of concentrations: blue > white > red > green LED light). LED-blue light stimulated the accumulation of nitrogen compounds in the form of phycobiliproteins at the expense of cell growth. The results of the study revealed that exposure to different LED light colors can improve the quality and quantity of the biomass gained in AP cultures.