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  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 12 ( 2023-06-09), p. 9963-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-09), p. 9963-
    Abstract: It is unclear to what extent systemic arterial blood pressure influences portal pressure. This relationship is clinically important as drugs, which are conventionally used for therapy of portal hypertension, may also influence systemic arterial blood pressure. This study investigated the potential correlation between mean arterial (MAP) and portal venous pressure (PVP) in rats with healthy livers. In a rat model with healthy livers, we investigated the effect of manipulation of MAP on PVP. Interventions consisted of 0.9% NaCl (group 1), 0.1 mg/kg body weight (bw) Sildenafil (low dose), an inhibitor of phosphodiesterase-5 (group 2), and 1.0 mg/kg bw Sildenafil (high dose, group 3) in 600 µL saline injected intravenously. Norepinephrine was used to increase MAP in animals with circulatory failure while PVP was monitored. Injection of the fluids induced a transient drop in MAP and PVP, probably due to a reversible cardiac decompensation. The drop in MAP and drop in PVP are significantly correlated. The time lag between change in MAP and change in PVP by 24 s in all groups suggests a cause-and-effect relationship. Ten minutes after the injection of the fluid, cardiac function was normalized. Thereafter, MAP gradually decreased. In the NaCl group, PVP decreases by 0.485% for a 1% drop of MAP, by 0.550% in the low-dose sildenafil group, and by 0.651% in the high-dose sildenafil group (p 〈 0.05 for difference group two vs. group one, group three vs. group one, and group three vs. group two). These data suggest that Sildenafil has an inherent effect on portal pressure that exceeds the effect of MAP. Injection of norepinephrine led to a sudden increase in MAP followed by an increase in PVP after a time lag. These data show a close relationship between portal venous pressure and systemic arterial pressure in this animal model with healthy livers. A change in MAP is consequently followed by a change in PVP after a distinct time lag. This study, furthermore, suggests that Sildenafil influences portal pressure. Further studies should be performed in a model with cirrhotic livers, as these may be important in the evaluation of vasoactive drugs (e.g., PDE-5-inhibitors) for therapy of portal hypertension.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    In: Nutrients, MDPI AG, Vol. 12, No. 1 ( 2020-01-17), p. 244-
    Abstract: The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess the impact of a 6-week non-energy-restricted KD on the abdominal fat distribution and the hepatic fat composition in healthy adults. Body fat distribution and composition were measured by comparing magnetic resonance imaging (MRI) and spectroscopy (MRS) results with air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) measurements. A total of 12 subjects from the KetoPerformance study were recruited for this ancillary study. Body mass index (BMI), total mass, total fat mass, total subcutaneous mass, and subcutaneous fat mass decreased significantly. None of the MRS parameters showed a significant change during the study. Even though the average change in body weight was 〉 2kg, no significant changes in intrahepatic lipid (IHL) content could be observed. Total fat mass and total fat-free mass derived from MRI has a strong correlation with the corresponding values derived from BIA and ADP data. BMI and the absolute fat parameter of all three modalities decreased, but there were no or only minor changes regarding the fat-free parameter. Magnetic resonance imaging provides body composition information on abdominal fat distribution changes during a ketogenic diet. This information is complementary to anthropomorphic and laboratory measures and is more detailed than the information provided by ADP and BIA measures. It was shown that there was no significant change in internal fat distribution, but there was a decrease in subcutaneous fat.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 3
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 10 ( 2023-10-09), p. 1478-
    Abstract: Background: The COVID-19 pandemic resulted in unprecedented restrictions on public and private life. The aim of the study was to investigate the impact of the COVID-19 pandemic on the physical and mental health of employees in the public sector, especially patient-related professions. Methods: For the data collection in summer 2021, an online questionnaire was used. Compared to a pre-pandemic point of time, the prevalence, frequency, and intensity of musculoskeletal pain, mental well-being, health status, and quality of life were recorded. Results: The questionnaire was completed by 1678 employees (f: 1045, m: 617). A total of 1504 employees (89.6%) were affected by complaints. Compared to before the pandemic, the prevalence and intensity of musculoskeletal complaints and psychological distress increased significantly. Patient-related professions (n = 204) showed significantly higher levels of stress and discomfort in several aspects (p 〈 0.05). Conclusions: Due to the COVID-19 pandemic, there was an increase in musculoskeletal complaints and a decrease in psychological well-being. Preventive factors related to mental health were identified as male gender, a middle- to older-age group, employees with children, and working from home. Attention should be drawn to these findings and prevention strategies should be brought into focus to strengthen the employees’ health. Special focus should be drawn to patient-related professions who are particularly confronted with pandemic-associated challenges.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 19 ( 2021-09-26), p. 10372-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 19 ( 2021-09-26), p. 10372-
    Abstract: The NO-cGMP signal transduction pathway plays a crucial role in tone regulation in hepatic sinusoids and peripheral blood vessels. In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). This results in constriction of hepatic sinusoids, contributing about 30% of portal pressure. In contrast, in peripheral arteries, dilation prevails with excess cGMP due to low PDE-5. Both effects eventually lead to circulatory dysfunction in progressed liver cirrhosis. The conventional view of portal hypertension (PH) pathophysiology has been described using the “NO-paradox”, referring to reduced NO availability inside the liver and elevated NO production in the peripheral systemic circulation. However, recent data suggest that an altered availability of cGMP could better elucidate the contrasting findings of intrahepatic vasoconstriction and peripheral systemic vasodilation than mere focus on NO availability. Preclinical and clinical data have demonstrated that targeting the NO-cGMP pathway in liver cirrhosis using PDE-5 inhibitors or sGC stimulators/activators decreases intrahepatic resistance through dilation of sinusoids, lowering portal pressure, and increasing portal venous blood flow. These results suggest further clinical applications in liver cirrhosis. Targeting the NO-cGMP system plays a role in possible reversal of liver fibrosis or cirrhosis. PDE-5 inhibitors may have therapeutic potential for hepatic encephalopathy. Serum/plasma levels of cGMP can be used as a non-invasive marker of clinically significant portal hypertension. This manuscript reviews new data about the role of the NO-cGMP signal transduction system in pathophysiology of cirrhotic portal hypertension and provides perspective for further studies.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 17 ( 2020-08-28), p. 6223-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 17 ( 2020-08-28), p. 6223-
    Abstract: Liver cirrhosis is a frequent condition with high impact on patients’ life expectancy and health care systems. Cirrhotic portal hypertension (PH) gradually develops with deteriorating liver function and can lead to life-threatening complications. Other than an increase in intrahepatic flow resistance due to morphological remodeling of the organ, a functional dysregulation of the sinusoids, the smallest functional units of liver vasculature, plays a pivotal role. Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Recent data showed characteristic alterations in the expression of these regulatory enzymes or metabolite levels in liver cirrhosis. Additionally, a disturbed zonation of the components of this pathway along the sinusoids was detected. This review describes current knowledge of the pathophysiology of PH with focus on the enzymes regulating cGMP availability, i.e., sGC and PDE-5. The results have primarily been obtained in animal models of liver cirrhosis. However, clinical and histochemical data suggest that the new biochemical model we propose can be applied to human liver cirrhosis. The role of PDE-5 as potential target for medical therapy of PH is discussed.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    In: Nutrients, MDPI AG, Vol. 7, No. 12 ( 2015-12-01), p. 9825-9833
    Abstract: The aim of the present study was to investigate the effect of a meal-replacement regimen vs. comprehensive lifestyle changes in overweight or obese subjects on intra-abdominal fat stores (Magnetic Resonance Imaging (MRI) measurements) and cardiometabolic risk factors. Forty-two obese men (n = 18) and women (n = 24) (age 49 ± 8 years; weight 96.3 ± 12.1 kg; BMI 32.7 ± 2.3 kg/m2) were selected for this randomized parallel-group design investigation. Subjects in the lifestyle group (LS-G; n = 22) received dietary counselling sessions and instructions how to increase physical activity. In the meal replacement group (MR-G; n = 20) meals were replaced by a low-calorie drink high in soy protein. After six months, subjects in the LS-G lost 8.88 ± 6.24 kg and subjects in the MR-G lost 7.1 ± 2.33 kg; p 〈 0.01 for changes within groups; no significant differences were found between the groups. Lean body mass remained constant in both intervention groups. MRI analyses showed that internal fat was significantly reduced in both groups to a comparable amount; the higher fat loss in the LS-G in the abdominal area was due to a higher reduction in subcutaneous fat. Both interventions significantly reduced components of the cardiometabolic risk profile and leptin levels. The decrease in the adipokines fetuin A and resistin was more pronounced in the MR-G. In conclusion, both interventions significantly reduced body weight, total fat mass and internal abdominal fat while preserving lean body mass. The reduction in the adipokines fetuin A and resistin was more pronounced in the meal replacement group suggesting an additional effect of soy protein components.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2015
    detail.hit.zdb_id: 2518386-2
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