Purpose: The aim of this study was to use non-invasive impedance cardiography (ICG) to determine the hemodynamic status of patients with grade 1 and grade 2 hypertension in relation to gender and ...age. Patients and Methods: We analyse prospectively collected data of 158 patients with grade 1 or grade 2 arterial hypertension. Patients were grouped according to age: 1) <50 years and 2) greater than or equal to50 years. Hemodynamic status of patients was assessed by using noninvasive ICG. For the purpose of this study two hemodynamic parameters were used: a) systemic vascular resistance index (SVRI) and b) left cardiac work index (LCWI). The primary endpoint was the hemodynamic status of patients. The secondary endpoint was hypertension-mediated organ damage. Results: Increased SVRI was assessed in 80% of patients, more common in the greater than or equal to50 years group than in the <50 years group (88.5% vs 64.8%; p < 0.01). The occurrence of increased systemic vascular resistance correlates hierarchically with increasing age. Elevated LCWI (hypervolemia and/or hyperinotropy) was present in 63% of patients, more often in males than females (70.3% vs 57.1%; p < 0.05) as well in those <50 years than in older patients (70.4% vs 59.6%; p < 0.05). Patients with diabetes were less likely to have hypervolemia/hyperinotropy than those without diabetes (46.7% vs 67.2%; p < 0.01). Hypervolemia/hyperinotropy (46.7%) and hypovolemia/hypoinotropy (43.3%) were present in a similar percentage of diabetic patients. Left ventricular hypertrophy was found in 30 patients (19%). Patients with left ventricular hypertrophy were more commonly male (66.7% vs 42.2%; p = 0.016) and had increased systemic vascular resistance (96.7% vs 77.3%; p = 0.015) compared to the patients without left ventricular hypertrophy. Hypertensive retinopathy grade III was found in 14 patients (8.9%). Elevated daytime systolic pressure, diabetes and increased age are independent predictors of grade III hypertensive retinopathy. Patients with reduced renal function had higher mean systolic blood pressure (p < 0.05), were more commonly male (p < 0.01) and older (p < 0.01) than those without reduced renal function. Conclusion: Although there are certain correlations between hemodynamic disorders and age and gender, specific hemodynamic status of an individual patient with hypertension cannot reliably be predicted on the basis of age and gender. The measurement of hemodynamic parameters by ICG can guide the clinician to select appropriate antihypertensive therapy to the patients' hemodynamic pathophysiologic condition. Keywords: hypertension, hemodynamics, impedance cardiography
Oilseed crops are widely cultivated and are related to nutrition and human health as valuable nutraceutical sources with valuable biological properties. The growing demand for oil plants used in ...human and animal nutrition or for the processing industry has contributed to the diversification and development of a new variety of oil crops. Increased oil crop diversity, besides ensuring reduced sensitivity to pests and climate conditions, has also led to improved nutritional values. In order to enable oil crop cultivation to become commercially sustainable, a comprehensive characterization of newly created varieties of oilseeds, including their nutritional and chemical composition, is required. In this study, two varieties of safflower and white and black mustard were investigated as alternative oil species for nutritional parameters, mainly protein, fat, carbohydrate, moisture, ash, polyphenols, flavonoids, chlorophylls contents, acids and mineral composition, and compared with those of two different genotypes of rapeseeds as a traditional oil crop plant. The proximate analysis found that the highest oil content was found in the oil rape NS Svetlana genotype (33.23%), while the lowest was in black mustard (25.37%). The protein content varies from around 26% in safflower samples to 34.63%, determined in white mustard. High content of unsaturated fatty acids and low content of saturated fatty acid was observed in the analyzed samples. In mineral analysis, the dominant elements were phosphorus, potassium, calcium and magnesium, in descending order. The observed oil crops are also good sources of microelements, including iron, copper, manganese and zinc, accompanied by high antioxidant activity due to the presence of significant amounts of polyphenolic and flavonoid compounds.
Summary
Background
GSK2894512 is a topically delivered investigational drug being developed for treatment of atopic dermatitis and psoriasis.
Objectives
To investigate, in a phase I clinical trial, ...the spatial biodistribution and residency of GSK2894512 within the epidermis and dermis of healthy human participants noninvasively using fluorescence lifetime imaging microscopy (FLIM).
Methods
Two topical drug formulations containing GSK2894512 1% were applied to the right and left forearms of six participants for seven consecutive days, followed by seven days of observation for residency. FLIM images were obtained daily throughout the study, approximately every 24 h. During the treatment phase of the study, images were collected from each participant pretreatment, reflecting the residual dose from the previous day. Three punch biopsies from each participant of one formulation was obtained from the treated region during the post‐treatment follow‐up period between days 8 and 14 for comparison with FLIM results.
Results
Cellular and subcellular features associated with different epidermal and dermal layers were visualized noninvasively, down to a depth of 200 μm. Results yielded three‐dimensional maps of GSK2894512 spatial distribution and residency over time. This fluorescence data provided a marker that was used as a monitor for day‐to‐day variance of drug presence and residency postapplication.
Conclusions
The results suggest FLIM could be a viable alternative to skin biopsies without the usual patient discomfort and limitations, thereby enabling the direct measurement of skin distribution through longitudinal monitoring. These results are the first step in establishing the unique capabilities that multiphoton imaging could provide to patients through noninvasive drug detection.
What's already known about this topic?
Fluorescence lifetime imaging (FLIM) has been used to image noninvasively cellular features in humans.
FLIM has demonstrated the potential to monitor morphological and metabolic changes at the subcellular level that occur in patients with skin cancer and atopic dermatitis.
Its potential for wider utilization in dermal drug discovery or dermatological disease monitoring has seen limited development.
What does this study add?
This is a first‐of‐its‐kind clinical study in which FLIM was used to monitor drug distribution and residency.
It is a first step in establishing the unique capabilities multiphoton imaging could provide to patients via noninvasive drug detection.
More information was generated per patient while reducing patient burden and population size using FLIM.
Imaging end points can be utilized to improve patient outcomes through improved monitoring capabilities.
What is the translational message?
Optical imaging can assess the heterogeneity of pharmacokinetic responses to topical drugs with optical signatures.
Advanced nonlinear optical imaging techniques can provide label‐free contrast in skin, which allows investigation of the efficacy of a topical treatment by monitoring structural/functional changes in skin.
Personalized therapeutic approaches may be possible by visualizing the distribution, residency and clearance of anti‐inflammatory drugs.
Commercial imaging systems facilitate the translation of nonlinear optical imaging techniques into clinical applications.
Linked Comment: Jeong and Evans. Br J Dermatol 2018; 179:1245–1246.
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Toll-like receptor 3 (TLR3) is a member of Toll-like receptors who recognize structurally conserved molecules derived from pathogens and trigger the immune response. To clarify if TLR3, is expressed ...in certain tumour cell lines and whether it is functional and what is the response of these cell lines to different concentrations of poly I:C treatment, we have screened SW480, SW620, FaDu and Detroit 562 cell lines using real-time PCR, flow cytometry and ELISA. We have shown that all these cell lines express TLR3 on mRNA and protein level but it is only functional in Detroit 562 cell line since only in these cells poly I:C treatment triggered the IL-6 secretion. In addition, poly I:C treatment inhibited cell growth and triggered up-regulation of IL-12p40, IL-8 and Il-1α in Detroit 562 cell line. By using annexin-V apoptosis detection kit, we have found that poly I:C triggers apoptosis in Detroit 562 cell line. We have found here that based on the results of TLR3 functionality there is a huge difference between FaDu and Detroit 562 cell lines which are of the same origin (pharynx) but FaDu is primary and Detroit 562 metastatic carcinoma. Our study also shows that Detroit 562 cell line could be a good model for cancer therapy research and development as it is responsive to TLR3 agonists which consequently drives it to apoptosis.
Camelina, a traditional oil-producing plant, has gained global interest due to the high-quality oil found in its seeds. It has numerous applications, including human dietary consumption, aviation ...biofuel, and biodiesel production. Seed quality testing is crucial for identifying suitable seed batches for market sale. Currently, vigor tests have been established for a limited selection of commercially cultivated plant species, including camelina. This study aims to assess seed vigor and contribute to the development and validation of methods/tests for reliable vigor assessment. The experiment used two camelina genotypes developed at the Institute of Field and Vegetables Crops in Novi Sad, Serbia. The findings revealed a noteworthy reduction in germination percentages for both genotypes across all the conducted tests, as compared to the conventional laboratory germination. Simultaneously, there was a notable increase in abnormal seedlings. However, no statistically significant differences in the values of growth parameters were observed among the applied tests. In summary, the reduced seed vigor values indicate potential issues with this trait, despite generally sound germination. Additionally, the preliminary findings and methodology developed for testing the camelina seed vigor highlighted the need for optimization when applying these tests to other species to ensure their reliability and applicability.
Objectives: Visceral fat is more harmful than subcutaneous fat. Women with high amounts of visceral fat have an increased risk of metabolic syndrome (MetS), insulin resistance and low level of serum ...vitamin D.
Methods: This was a prospective, randomized and controlled study. Postmenopausal women (n = 101) aged 45-70 years were included. The assessed parameters were: body mass index (BMI), waist circumference (WC), 25-hydroxyvitamin D (25-OHD) status, serum insulin and HOMA-IR, bone mineral density, total fat mass, fat mass index (FMI) measured by DXA, and muscle strength.
Results: Significantly lower values of 25-OHD (35.26 ± 1.61 nmol/l) were found in women with MetS compared to those without MetS (47.52 ± 3.47nmol/l) (t = 3.699; p < 0.000). A significant negative correlation was observed between 25-OHD levels and: WC (rho
WC
= −0.94; p < 0.004), BMI (rho
BMI
= −0.80; p < 0.002), FMI (rho
FMI
= −0.31; p < 0.002) and impaired fasting glucose (IFG) (rho
IFG
= −0.23
;
p < 0.001). The percentage of body fat was statistically significantly higher in the group with insufficient 25-OHD (39.6%) and in the group with a deficit of 25-OHD (48.2%), compared with the maximum permitted percentage body fat of 35% for a female (t = −22.63; p < 0.002). The average hand grip strength of these moderately obese participants was 27.4 ± 4.7 kg. It was significantly lower than the normative grip strength for referent range groups (t = −21.65; p < 0.001).
Conclusion: A low 25-OHD level in postmenopausal women is associated with high body fat, metabolic syndrome, low muscular strength and osteopenia.
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