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The plant chemistry and cytotoxic activity of Colchicum baytopiorum CD Brickell (Liliaceae/Colchicaceae), an endemic species growing in Turkey, has been studied for the first time. Nine known alkaloids were isolated and their structures were identified by spectral methods (UV, IR, 1H-NMR, and ESI/MS), and the presence of three alkaloids, which could not be isolated from the plant, was also detected by LC/MS/MS spectrometry. Phenolic acids were elaborated using LC/MS and 11 phenolic acids were identified. The presence of two flavonoids appeared to be valuable for chemotaxonomic purposes. Guided by the brine shrimp lethality test (BSLT), methanol extracts were tested for cytotoxic activity by colorimetric MTT test on K562 and HL60 cells. Except the seed extract, all methanol extracts showed more cytotoxic activity on HL60 cells (IC50: 6.5– < 0.1 μg/mL) than on K562 cells (IC50: > 500–44 μg/mL). [ABSTRACT FROM AUTHOR]

Introduction: High flow nasal cannula (HFNC) reduces the need for intubation in patients with hypoxaemic acute respiratory failure (ARF), but its added value in patients with severe coronavirus disease 2019 (COVID-19) and a do-not-intubate (DNI) order is unknown. We aimed to assess (variables associated with) survival in these patients., Materials and Methods: We described a multicentre retrospective observational cohort study in five hospitals in the Netherlands and assessed the survival in COVID-19 patients with severe acute respiratory failure and a DNI order who were treated with high flow nasal cannula. We also studied variables associated with survival., Results and Discussion: One-third of patients survived after 30 days. Survival was 43.9% in the subgroup of patients with a good WHO performance status and only 16.1% in patients with a poor WHO performance status. Patients who were admitted to the hospital for a longer period prior to HFNC initiation were less likely to survive. HFNC resulted in an increase in ROX values, reflective of improved oxygenation and/or decreased respiratory rate., Conclusion: Our data suggest that a trial of HFNC could be considered to increase chances of survival in patients with ARF due to COVID-19 pneumonitis and a DNI order, especially in those with a good WHO performance status., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

To evaluate the yield of mini-bronchoalveolar lavage compared with that of directed bronchoalveolar lavage in critically ill patients with suspected coronavirus disease 2019-associated pulmonary aspergillosis., Design: A retrospective cohort study., Setting: The ICU of the Amsterdam University Medical Centers., Patients: Patients with confirmed coronavirus disease 2019 screened for coronavirus disease 2019-associated pulmonary aspergillosis., Interventions: Mini-bronchoalveolar lavage and/or directed bronchoalveolar lavage., Measurements and Main Results: In total, 76 patients were included, 20 of whom underwent bronchoalveolar lavage, 40 mini-bronchoalveolar lavage, and 16 both mini-bronchoalveolar lavage and bronchoalveolar lavage. The percentage of samples with one or more positive Aspergillus detecting test (galactomannan, culture, polymerase chain reaction) did not differ significantly between bronchoalveolar lavage and mini-bronchoalveolar lavage (16.7% vs 21.4%). However, in mini-bronchoalveolar lavage samples, this was more frequently driven by a positive polymerase chain reaction than in bronchoalveolar lavage samples (17.9% vs 2.8%; p = 0.030). In 81% of patients (13/16) with both mini-bronchoalveolar lavage and bronchoalveolar lavage, the test results were in agreement. In 11 of 12 patients (92%) with first a negative mini-bronchoalveolar lavage, the subsequent bronchoalveolar lavage sample was also negative., Conclusions: We found a similar percentage of positive test results in mini-bronchoalveolar lavage and bronchoalveolar lavage samples in patients with suspected coronavirus disease 2019-associated pulmonary aspergillosis. Our findings indicate that mini-bronchoalveolar lavage could be a useful tool for coronavirus disease 2019-associated pulmonary aspergillosis screening in ICU patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The onset of nonpulsatile cardiopulmonary bypass is known to deteriorate microcirculatory perfusion, but it has never been investigated whether this may be prevented by restoration of pulsatility during extracorporeal circulation. We therefore investigated the distinct effects of nonpulsatile and pulsatile flow on microcirculatory perfusion during on-pump cardiac surgery. Patients undergoing coronary artery bypass graft surgery were randomized into a nonpulsatile (n = 17) or pulsatile (n = 16) cardiopulmonary bypass group. Sublingual mucosal microvascular perfusion was measured at distinct perioperative time intervals using sidestream dark field imaging, and quantified as the level of perfused small vessel density and microvascular flow index (vessel diameter < 20 μm). Microcirculation measurements were paralleled by hemodynamic and free hemoglobin analyses. The pulse wave during pulsatile bypass estimated 58 ± 17% of the baseline blood pressure waveform. The observed reduction in perfused vessel density during aorta cross-clamping was only restored in the pulsatile flow group and increased from 15.5 ± 2.4 to 20.3 ± 3.7 mm/mm(2) upon intensive care admission (P < 0.01). The median postoperative microvascular flow index was higher in the pulsatile group [2.6 (2.5-2.9)] than in the nonpulsatile group [2.1 (1.7-2.5); P = 0.001]. Pulsatile flow was not associated with augmentation of free hemoglobin production and was paralleled by improved oxygen consumption from 70 ± 14 to 82 ± 16 ml·min(-1)·m(-2) (P = 0.01) at the end of aortic cross-clamping. In conclusion, pulsatile cardiopulmonary bypass preserves microcirculatory perfusion throughout the early postoperative period, irrespective of systemic hemodynamics. This observation is paralleled by an increase in oxygen consumption during pulsatile flow, which may hint toward decreased microcirculatory heterogeneity during extracorporeal circulation and preservation of microcirculatory perfusion throughout the perioperative period.

Objective: The authors hypothesized that cardiopulmonary bypass (CPB) (on-pump) is associated with more severe changes in the microcirculatory blood flow and tissue oxygenation as compared with off-pump coronary artery bypass surgery., Design: An observational study., Setting: A university hospital and teaching hospital., Participants: Patients undergoing on-pump (n = 24) or off-pump (n = 24) cardiac surgery., Interventions: Microcirculatory measurements were performed before CPB and 10 minutes after the switch to CPB or before and during cardiac luxation in off-pump patients., Measurements and Main Results: Sublingual microcirculatory perfusion was investigated using side-stream dark field imaging, and sublingual microcirculatory oxygenation was measured using reflectance spectrophotometry. Conversion to CPB resulted in an increase in cardiac output from 4.0 ± 0.2 to 4.8 ± 0.3 L/min (p < 0.01) and a 40% reduction in arterial hemoglobin concentration. Cardiopulmonary bypass was associated with an increase in venular blood velocity from 349 ± 201 μm/s to 563 ± 227 μm/s (p < 0.05), a reduction in functional capillary density of 43%, and an increase in hemoglobin oxygenation of the red blood cells in the remaining filled capillaries from 47.2% ± 6.1% to 59.7% ± 5.2% (p < 0.001). The decrease in cardiac output during cardiac luxation from 4.5 ± 1.7 to 1.8 ± 0.8 L/min (p < 0.01) without hemoglobin changes was associated with a complete halt of capillary blood flow and a reduction in maximum capillary blood velocity from 895 ± 209 to 396 ± 178 μm/s (p < 0.01). The functional capillary density remained unchanged, whereas the hemoglobin oxygenation declined from 64.2% ± 9.1% to 48.6% ± 8.7% (p < 0.01)., Conclusions: On-pump and off-pump cardiac surgery are associated with distinct alterations in sublingual microcirculatory perfusion and hemoglobin oxygenation. Although on-pump surgery results in a fall out of capillaries resulting in decreased oxygen extraction, off-pump surgery results in a cessation of flow during luxation resulting in decreased convection of oxygen transport., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The S-methyl-thiosemicarbazones of the 2-hydroxy-R-benzaldehyde (R = H, 3-OH 3-OCH(3) or 4-OCH(3)) reacted with the corresponding aldehydes in the presence of FeCl(3) and NiCl(2). New ONNO chelates of iron(III) and nickel(II) with hydroxy- or methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and (1)H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N(1)-4-methoxysalicylidene-N(4)-4-methoxysalicylidene-S-methyl-thiosemicarbazidato-iron(III) complex showed selective anti-leukemic effects in K562 cells while has no effect in ECV304 cells in the 0.53 microg/ml (IC(50)) concentrations. Also, some methoxy-substituted nickel(II) chelates exhibit high cytotoxic activity against both of these cell lines in low concentrations. Cytotoxicity data were evaluated depending on cell lines origin and position of the substituents on aromatic rings.

Background: Although it is known that cardiac resynchronization therapy (CRT) in heart failure (HF) patients improves systemic circulation, its acute effects on microcirculation are as yet unknown. Therefore we investigated the sublingual microcirculatory changes in HF patients from CRT and right ventricular (RV) pacing by use of orthogonal polarization spectral (OPS) imaging., Methods and Results: Twelve consecutive HF patients with a CRT device and 20 healthy individuals (HI) were included. Acute microcirculatory changes were assessed by functional capillary density (FCD) and capillary velocity (CV) measurement 6 months after CRT. FCD and CV were measured in HF patients sublingually after 15 minutes of programming 1 of 3 pacing modalities in random order (no pacing, RV pacing, and CRT). FCD was significantly higher in HI (11.2 +/- 2.1 cm/cm(2)) compared with HF patients with RV pacing (8.9 +/- 1.9 cm/cm(2); P = .03) and no pacing (8.3 +/- 2.4 cm/cm(2); P = .02). CRT (12.1 +/- 2.2 cm/cm(2)) significantly increased FCD in HF patients compared with RV pacing (8.9 +/- 1.9 cm/cm(2); P = .006) and no pacing (8.3 +/- 2.4 cm/cm(2); P = .008). CV was normal in all patients with or without pacing., Conclusions: CRT improves microcirculatory function as assessed by OPS imaging.

Reactions of 2-hydroxy-3-methoxy, 2-hydroxy-4-methoxy-benzaldehyde with 3- and 4-methoxy-substituted salicylaldehyde S-methyl-thiosemicarbazones in the presence of FeCl(3) and NiCl(2) resulted in the corresponding methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazone chelates. Characterisation of the compounds in the [Fe(L)Cl] and [Ni(L)] general formula was accomplished by means of elemental analysis, conductivity and magnetic measurements, (1)H NMR, UV-vis, IR and mass spectroscopy. Cytotoxicity and proliferation experiments using K562 chronic myeloid leukemia cell line and ECV 304 human endothelial cell line imply that the iron(III) chelates may have anti-leukemic effects with 3.5 microg/dl LD(50) dose.

Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage. To establish whether glycocalyx is associated with microvascular damage, we performed glycocalyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON; n = 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 +/- 0.1, 0.8 +/- 0.4, and 0.2 +/- 0.1 l, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 +/- 0.1 vs. 0.9 +/- 0.1 microm, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.

In this study, the in vitro effects of vitamin C and selenium on natural killer (NK) cell activity of ss-thalassemia major patients was investigated. At first, significant decreased NK activity was found at E:T ratios of 1:1, 5:1, and 10:1 in whole thalassemia patients. Low-dose selenium treatment enhanced NK activity in patients but there was no change in the control group. High-dose selenium decreased NK activity significantly in splenectomized patients. Different doses vitamin C enhanced NK activity significantly in both splenectomized and unsplenectomized patients. According to these results, selenium dosage should be arranged carefully in thalassemia patients, whereas vitamin C can be used confidently.

Nerium oleander (No), is a toxic plant. In recent studies, it was determined that the extracts of this plant are effective to treat some types of cancer, but these studies are limited and do not include human leukemia. In the present study, firstly we aimed to investigate in vitro the cytotoxic effects of No on the HL60 and K562 leukemia cell lines. The cells were incubated with six different concentrations of each three extracts. MTT assay was employed as a cytotoxicity test. It was observed that concentrations of 1000, 500 and 50 microg/ml from each extract possess marked antileukemic effects. No leaf and root extracts were seen to be more cytotoxic than the stem extract according to LC50. Secondly, in order to understand the role of P-gp in cytotoxicity, P-gp levels of K562 resistant and sensitive cells were measured by flow cytometry before treatment extracts, and then, the cells were incubated with No leaf, stem and root extracts in 500 microg/ml concentrations overnight. After incubation, measurements showed decreased levels of P-gp in the cells. Hence, it is possible to think contributes to their cytotoxic effects that inhibiting of the P-gp pump by No extracts on leukemia cell lines.

Background: Coronary microvascular resistance during maximal hyperemia is generally assumed to be unaffected by percutaneous coronary interventions (PCIs). We assessed a velocity-based index of hyperemic microvascular resistance (h-MR(v)) by using prototypes of a novel, dual-sensor (Doppler velocity and pressure)-equipped guidewire before and after PCI to test this hypothesis., Methods and Results: Aortic pressure, flow velocity (h-v), and pressure (h-P(d)) distal to 24 coronary lesions were measured simultaneously during maximal hyperemia induced by intracoronary adenosine. Measurements were obtained in the reference vessel before PCI and in the target vessel before and after PCI, stenting, and ultrasound-guided, upsized stenting. h-P(d) increased from 57.9+/-17.0 to 85.5+/-15.6 mm Hg, and h-MR(v) (ie, h-P(d)/h-v) decreased from 2.74+/-1.40 to 1.58+/-0.61 mm Hg x cm(-1) . s after stenting (both P<0.001). The reduction in h-MR(v) accounted for 34% of the decrease in total coronary resistance achieved by PCI. h-MR(v) of the target vessel after PCI was lower than that of the corresponding reference vessel despite a higher h-P(d) in the reference vessel (P<0.01). Post-PCI baseline MR(v) was correlated with baseline P(d) before PCI (P<0.01)., Conclusions: PCI-induced restoration of P(d) resulted in a reduction of h-MR(v) in accordance with the pressure dependence of h-MR(v). The decrease in h-MR(v) to a level below that of the corresponding reference vessel in the immediate post-PCI period and a lowered baseline MR(v) suggest microvascular remodeling induced by long-term exposure to a low-pressure environment.

Peripheral arterial disease (PAD) affects a large percentage of the elderly population. Standard invasive treatment, apart from risk factor modulation, consists of bypass surgery or percutaneous transluminal angioplasty. However, symptomatic recurrence rates are high for both procedures and a substantial part of the patient population with PAD is not a candidate for invasive revascularization due to complexity of the lesion and/or co-morbidity. Therapeutic arteriogenesis has been proposed as an alternative treatment option. The present paper describes the design of the START-trial. This trial aims to determine the potential of the pro-arteriogenic substance granulocyte/macrophage colony stimulating factor (GM-CSF) to increase maximal walking distance in patients with intermittent claudication. A double-blinded, randomized, placebo-controlled study will be performed in 40 patients with peripheral obstructive arterial disease Rutherford grade I, category 2 or 3, that are candidates for bypass surgery or percutaneous transluminal angioplasty. Based on pharmacokinetic and toxicologic studies, a dose of 10 microg/kg will be used. Patients will be treated for a period of 14 days on each consecutive day, with the last injection applied on day 12. The primary endpoint will be the change in walking distance from day 0 to day 14 as assessed by an exercise treadmill test. Secondary endpoints will be the ankle-brachial index at rest and after exercise, the pain-free walking distance and cutaneous microcirculatory alterations as assessed by laser Doppler fluxmetry. Iliac flow reserve and conductance will be measured by magnetic resonance imaging.

Background: Ultrafiltration failure (UFF) is a complication of peritoneal dialysis (PD) treatment that occurs especially in long-term patients. Etiological factors include a large effective peritoneal surface area [measured as high mass transfer area coefficient (MTAC) of creatinine], a high effective lymphatic absorption rate (ELAR), a large residual volume, or combinations., Objective: The prevalence and etiology of UFF were studied and the contribution of transcellular water transport (TCWT) was analyzed. A new definition of UFF and guidelines for the analysis of its etiology were derived from the results., Setting: Peritoneal dialysis unit in the Academic Medical Center in Amsterdam., Design: Cross-sectional study of standard peritoneal permeability analyses (4-hr dwells, dextran 70 as volume marker) with 1.36% glucose in 68 PD patients. Patients with negative net UF (change in intraperitoneal volume, dIPV < 0 mL) were analyzed further using 3.86% glucose, whenever possible., Results: Among 68 patients (duration of PD 0.3-178 months), 39 had negative net UF with 1.36% glucose. These patients had greater MTAC creatinine and glucose absorption, and higher ELAR (p < 10(-4)) than the patients with positive UF. dIPV and transcapillary UF rate (TCUFR) were lower (p < 10(-5)). Twenty of these patients could be studied using 3.86% glucose. dIPV was greater than 400 mL/4 hr in this test in 12 patients, implying that no clinically important UFF was present. Ultrafiltration failure (dIPV < 400 mL) was found in 8 patients, giving a prevalence of 23%. This last group had been treated with PD for a longer period (p = 0.03), had higher ELAR (p = 0.07), but lower residual volume (p = 0.03), and lower TCUFR (p = 0.01). Ultrafiltration failure was associated with a high MTAC creatinine in 3 patients, a high ELAR in 4 patients, and a combination of factors in one. As an additional possible cause, TCWT was studied, using the sodium gradient in the first hour of the dwell, corrected for diffusion (dNA). Five patients had dNA > 5 mmol/L, indicating normal TCWT. The 3 patients with dNA < 5 mmol/L tended to be treated longer (p = 0.19) and had lower TCUFR (p = 0.04). A smaller difference was found between dIPV 3.86% and 1.36% (p = 0.04) compared to the dNA > 5 mmol/L group, but no differences were present for MTAC creatinine, ELAR, residual volume, or glucose absorption., Conclusions: In addition to known factors, impairment of TCWT can be a cause of UFF. A standardized dwell with 1.36% glucose overestimates UFF. Therefore, 3.86% glucose should be used for identification of patients with UFF, especially because it provides additional information on TCWT. Ultrafiltration failure can be defined as net UF < 400 mL/4 hr with 3.86% glucose during a 4-hour exchange.