Sulfonated phthalimidomethyl aluminum phthalocyanine : the effect of hydrophobic substituents on the in vitro phototoxicity of phthalocyanines

The photocytotoxicity of sulfonated phthalimidomethyl aluminum phthalocyanine, a more hydrophobic photosensitizer as compared to phthalocyanine substituted with sulfonate groups only, was investigated. Inclusion of 1-2 phthalimidomethyl groups into disulfonated aluminum phthalocyanine, resulted in increased partition coefficients between n-octanol and water, and a six-fold increase in both cellular uptake and photocytotoxicity towards Chinese hamster lung fibroblast cells (line V-79). Reducing the number of phthalimidomethyl groups, or increasing the degree of sulfonation, lead to a decrease in the partition coefficient, cellular uptake, and phototoxicity. The quantum yield of singlet oxygen was comparable for all dyes tested in this series, indicating that no significant change in this photophysical parameter resulted from phthalimidomethylation. These results suggest that the addition of 1-2 phthalimidomethyl groups to disulfonated aluminum phthalocyanine improves cellular uptake, but, as the relative efficiency of cell killing was not effected, the intracellular distribution on photosensitive molecules may not be modified

Biological activities of phthalocyanines-X. Syntheses and analyses of sulfonated phthalocyanines

Synthetic methods to obtain selectively sulfonated metallo phthalocyanines are compared. Both condensation and direct sulfonation procedures lead to mixtures of mono- to tetrasulfonated products which are resolved by reverse phase liquid chromatography in buffered aqueous-methanol. The proportion of sulfonated derivatives is examined as a function of the starting reagents in the case of the condensation method. and as a function of the temperature and reaction time in the case of the direct sulfonation procedure. The number of sulfonate groups per phthalocyanine molecule is determined by oxidative degradation of the phthalocyanine ring followed by quantitative chromatographic analysis of the sulfophthalamide and phthalamide fragments

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Development of a novel benchmark method to identify and characterize best practices in home care across six European countries: design, baseline, and rationale of the IBenC project.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBACKGROUND: Europe's ageing society leads to an increased demand for long-term care, thereby putting a strain on the sustainability of health care systems. The 'Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of Community Care' (IBenC) project aims to develop a new benchmark methodology based on quality of care and cost of care utilization to identify best practices in home care. The study's baseline data, methodology, and rationale are reported. METHODS: Home care organizations in Belgium, Finland, Germany, Iceland, Italy, and the Netherlands, home care clients of 65 years and over receiving home care, and professionals working in these organizations were included. Client data were collected according to a prospective longitudinal design with the interRAI Home Care instrument. Assessments were performed at baseline, after six and 12 months by trained (research) nurses. Characteristics of home care organizations and professionals were collected cross-sectionally with online surveys. RESULTS: Thirty-eight home care organizations, 2884 home care clients, and 1067 professionals were enrolled. Home care clients were mainly female (66.9%), on average 82.9 years (± 7.3). Extensive support in activities of daily living was needed for 41.6% of the sample, and 17.6% suffered cognitive decline. Care professionals were mainly female (93.4%), and over 45 years (52.8%). Considerable country differences were found. CONCLUSION: A unique, international, comprehensive database is established, containing in-depth information on home care organizations, their clients and staff members. The variety of data enables the development of a novel cost-quality benchmark method, based on interRAI-HC data. This benchmark can be used to explore relevant links between organizational efficiency and organizational and staff characteristics.7th Framework Programme of the European Commissio

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Biological activities of phthalocyanines-XI. Phototoxicity of sulfonated aluminum naphthalocyanines towards V-79 chinese hamster cells

The phototoxicity of sulfonated aluminum naphthalocyanines towards V-79 Chinese hamster cells is investigated. The disulfonated naphthalocyanine exhibits similar photostability, but better cell penetrating properties than the tetrasulfonated dyes. The capacity of the naphthalocyanines to generate singlet oxygen is comparable to that of the corresponding phthalocyanines. However, in contrast to the phthalocyanine dyes, the sulfonated aluminum naphthalocyanines show very little phototoxicity towards the V-79 cells, suggesting close association with non-vital cell constituents or extensive formation of photoinactive adducts and aggregates

Biological activities of phthalocyanines-VIII. Cellular distribution in V-79 Chinese hamster cells and phototoxicity of selectively sulfonated aluminum phthalocyanines

Water soluble chloro aluminum phthalocyanines sulfonated to different degrees are studied for phototoxicity and cellular distribution in V-79 Chinese hamster cells. The more hydrophobic disulfonated dyes, with sulfonate substituents on adjacent benzyl groups of the phthalocyanine ring structure, exhibited the best cell penetrating properties and the highest phototoxicity. Fluorescence microscopy revealed that the dye was uniformly distributed in the cytoplasm but absent in the nucleus. The greater cell membrane penetrating properties of the lower as compared to the higher sulfonated dyes are attributed to the amphiphilic nature of the former

Biological activities of phthalocyanines-XI. Phototoxicity of sulfonated aluminum naphthalocyanines towards V-79 chinese hamster cells

The phototoxicity of sulfonated aluminum naphthalocyanines towards V-79 Chinese hamster cells is investigated. The disulfonated naphthalocyanine exhibits similar photostability, but better cell penetrating properties than the tetrasulfonated dyes. The capacity of the naphthalocyanines to generate singlet oxygen is comparable to that of the corresponding phthalocyanines. However, in contrast to the phthalocyanine dyes, the sulfonated aluminum naphthalocyanines show very little phototoxicity towards the V-79 cells, suggesting close association with non-vital cell constituents or extensive formation of photoinactive adducts and aggregates

Biological activities of phthalocyanines-VIII. Cellular distribution in V-79 Chinese hamster cells and phototoxicity of selectively sulfonated aluminum phthalocyanines

Water soluble chloro aluminum phthalocyanines sulfonated to different degrees are studied for phototoxicity and cellular distribution in V-79 Chinese hamster cells. The more hydrophobic disulfonated dyes, with sulfonate substituents on adjacent benzyl groups of the phthalocyanine ring structure, exhibited the best cell penetrating properties and the highest phototoxicity. Fluorescence microscopy revealed that the dye was uniformly distributed in the cytoplasm but absent in the nucleus. The greater cell membrane penetrating properties of the lower as compared to the higher sulfonated dyes are attributed to the amphiphilic nature of the former

3D Imaging of vascular networks for biophysical modeling of perfusion distribution within the heart

One of the main determinants of perfusion distribution within an organ is the structure of its vascular network. Past studies were based on angiography or corrosion casting and lacked quantitative three dimensional, 3D, representation. Based on branching rules and other properties derived from such imaging, 3D vascular tree models were generated which were rather useful for generating and testing hypotheses on perfusion distribution in organs. Progress in advanced computational models for prediction of perfusion distribution has raised the need for more realistic representations of vascular trees with higher resolution. This paper presents an overview of the different methods developed over time for imaging and modeling the structure of vascular networks and perfusion distribution, with a focus on the heart. The strengths and limitations of these different techniques are discussed. Episcopic fluorescent imaging using a cryomicrotome is presently being developed in different laboratories. This technique is discussed in more detail, since it provides high-resolution 3D structural information that is important for the development and validation of biophysical models but also for studying the adaptations of vascular networks to diseases. An added advantage of this method being is the ability to measure local tissue perfusion. Clinically, indices for patient-specific coronary stenosis evaluation derived from vascular networks have been proposed and high-resolution noninvasive methods for perfusion distribution are in development. All these techniques depend on a proper representation of the relevant vascular network structure