•Zebrafish larvae exposed to PS particles had minimal biodistribution.•Internalized particles caused an immune response by activating the complement system.•Enriched toxicity pathways for lipid ...metabolism and oxidative stress were detected.•Our results can be used to develop Adverse Outcome Pathways for microplastics.
Microplastics are a contaminant of emergent concern in the environment, however, to date there is a limited understanding on their movement within organisms and the response of organisms. In the current study zebrafish embryos at different development stages were exposed to 700nm fluorescent polystyrene (PS) particles and the response pathway after exposure was investigated using imaging and transcriptomics. Our results show limited spreading of particles within the larvae after injection during the blastula stage. This is in contrast to injection of PS particles in the yolk of 2-day old embryos, which resulted in redistribution of the PS particles throughout the bloodstream, and accumulation in the heart region. Although injection was local, the transcriptome profiling showed strong responses of zebrafish embryos exposed to PS particle, indicating a systemic response. We found several biological pathways activated which are related to an immune response in the PS exposed zebrafish larvae. Most notably the complement system was enriched as indicated by upregulation of genes in the alternative complement pathway (e.g. cfhl3, cfhl4, cfb and c9). The fact that complement pathway is activated indicates that plastic microparticles are integrated in immunological recognition processes. This was supported by fluorescence microscopy results, in which we observed co-localisation of neutrophils and macrophages around the PS particles. Identifying these key events can be a first building block to the development of an adverse outcome pathway (AOP). These data subsequently can be used within ecological and human risk assessment.
The high temperatures generated in gases by shock waves give rise to physical and chemical phenomena such as molecular vibrational excitation, dissociation, ionization, chemical reactions and ...inherently related radiation. In continuum regime, these processes start from the wave front, so that generally the gaseous media behind shock waves may be in a thermodynamic and chemical non-equilibrium state. This book presents the state of knowledge of these phenomena. Thus, the thermodynamic properties of high temperature gases, including the plasma state are described, as well as the kinetics of the various chemical phenomena cited above. Numerous results of measurement and computation of vibrational relaxation times, dissociation and reaction rate constants are given, and various ionization and radiative mechanisms and processes are presented. The coupling between these different phenomena is taken into account as well as their interaction with the flow-field. Particular points such as the case of rarefied flows and the inside of the shock wave itself are also examined. Examples of specific non-equilibrium flows are given, generally corresponding to those encountered during spatial missions or in shock tube experiments.
Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African ...Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.
Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African ...Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.
Rectal cancer is commonly treated by chemoradiation therapy, followed by the low anterior resection anal sphincter-preserving surgery, with a temporary protecting ileostomy. After reversal of the ...stoma a condition known as low anterior resection syndrome (LARS) can occur characterized by a combination of symptoms such as urgent bowel movements, lack of control over bowel movements, and difficulty fully emptying the bowels. These symptoms have a significant negative impact on the quality of life for individuals who have survived the cancer. Currently, there is limited available data regarding the presence, risk factors, and effects of treatment for these symptoms during long-term follow-up.
To evaluate long term outcomes of low anterior resection surgery and its correlation to baseline anorectal manometry (ARM) parameters and physiotherapy with anorectal biofeedback (BF) treatment.
One hundred fifteen patients (74 males, age 63 ± 11) who underwent low anterior resection surgery for rectal cancer were included in the study. Following surgery, patients were managed by surgical and oncologic team, with more symptomatic LARS patients referred for further evaluation and treatment by gastroenterologists. At follow up, patients were contacted and offered participation in a long term follow up by answering symptom severity and quality of life (QOL) questionnaires.
80 (70%) patients agreed to participate in the long term follow up study (median 4 years from stoma reversal, range 1-8). Mean time from surgery to stoma closure was 6 ± 4 months. At long term follow up, mean LARS score was 30 (SD 11), with 55 (69%) patients classified as major LARS (score > 30). Presence of major LARS was associated with longer time from surgery to stoma reversal (6.8 vs. 4.8 months; p = 0.03) and with adjuvant chemotherapy (38% vs. 8%; p = 0.01). Patients initially referred for ARM and BF were more likely to suffer from major LARS at long term follow up (64% vs. 16%, p < 0.001). In the subgroup of patients who underwent perioperative ARM (n = 36), higher maximal squeeze pressure, higher maximal incremental squeeze pressure and higher rectal pressure on push were all associated with better long-term outcomes of QOL parameters (p < 0.05 for all). 21(54%) of patients referred to ARM were treated with BF, but long term outcomes for these patients were not different from those who did not perform BF.
A significant number of patients continue to experience severe symptoms and a decline in their quality of life even 4 years after undergoing low anterior resection surgery. Prolonged time until stoma reversal and adjuvant chemotherapy emerged as the primary risk factors for a negative prognosis. It is important to note that referring patients for anorectal physiology testing alone tended to predict poorer long-term outcomes, indicating the presence of selection bias. However, certain measurable manometric parameters could potentially aid in identifying patients who are at a higher risk of experiencing unfavorable functional outcomes. There is a critical need to enhance current treatment options for this patient group.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Blood group O is known to be associated with lower levels of von Willebrand factor (VWF) and with increased bleeding complications. The influence of blood group O on postpartum blood ...loss was assessed by a few studies, however, without adjustment for important obstetric risk factors for postpartum blood loss.
Aim
Aim of this study was to investigate whether women with blood group O exhibit increased blood loss after delivery in consideration of established risk factors for postpartum bleeding.
Methods
A total of 1487 patients were prospectively included into this cohort study. Blood loss was assessed by estimated blood loss (in mL), and drop of haemoglobin (Δ haemoglobin) was calculated. Association of blood loss with risk factors (such as blood group O, cervical tears, morbidly adherent placenta, placenta praevia and uterine atony amongst others) was assessed with appropriate tests. Significant variables were entered into a stepwise multivariate regression analysis.
Results
Women with blood group O showed a significantly higher blood loss when compared to women with blood group non‐O (529.2 mL ± 380.4 mL and 490.5 mL ± 276.4 mL, respectively, P = .024)). The increased blood loss in women with blood group O remained significant after multivariate regression analysis (difference 47 mL, P = .019).
Conclusion
This is the first study reporting significantly increased blood loss following delivery in women with blood group O after adjustment for major risk factors for postpartum blood loss. Albeit having a statistically significant, but clinically minor effect on absolute blood loss, blood group O carriers may suffer from aggravated bleeding in the presence of additional obstetric bleeding pathologies.
This review discusses the challenges of chemotherapy for human African trypanosomiasis (HAT). The few drugs registered for use against the disease are unsatisfactory for a number of reasons. HAT has ...two stages. In stage 1 the parasites proliferate in the haemolymphatic system. In stage 2 they invade the central nervous system and brain provoking progressive neurological dysfunction leading to symptoms that include the disrupted sleep wake patterns that give HAT its more common name of sleeping sickness. Targeting drugs to the central nervous system offers many challenges. However, it is the cost of drug development for diseases like HAT, that afflict exclusively people of the world's poorest populations, that has been the principal barrier to new drug development and has led to them becoming neglected. Here we review drugs currently registered for HAT, and also discuss the few compounds progressing through clinical trials. Finally we report on new initiatives that might allow progress to be made in developing new and satisfactory drugs for this terrible disease.
British Journal of Pharmacology (2007) 152, 1155–1171; doi:10.1038/sj.bjp.0707354; published online 9 July 2007
Microplastics (<5 mm) are distributed ubiquitously in natural environments. The majority of microplastics in aquatic environments are shown to have rough surfaces due to various weathering processes ...(secondary microplastics; SMP), while laboratory studies predominantly utilise pristine microplastics (primary microplastics; PMP). Here we present the results from a study comparing the chronic effects of pristine PMP and artificially weathered SMP to three different Cladoceran species (Daphnia magna, Daphnia pulex, Ceriodaphnia dubia). We assessed the impact of PMP and SMP on reproductive output using various measured parameters, including time of first brood, size of first brood, size of first three broods, cumulative number of neonates, total number of broods and terminal length of test animals. Our results show that reproductive output of all species declined in a dose-dependent manner. The No Observed Effect Concentration (NOEC) was less than the lowest tested concentration (102 p/mL) for at least one measured endpoint for all species and both PMP and SMP. Further, it was inferred that species sensitivity varied inversely with body size for most endpoints, resulting in C. dubia being the most sensitive species; and D. magna being the least sensitive species under study. In addition, PMP appeared to have greater toxic potential as compared to SMP. This study is the first to directly compare the chronic toxicity of both pristine and weathered microplastic particles on three freshwater toxicological model organisms. Our results indicate that sensitivity in reproduction and growth to microplastics may differ between species and type of microplastic exposed; highlighting the importance of using multiple species and structural types of particles.
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•Sensitivity of Cladoceran species to two types of microplastics (MPs) was compared.•Both primary (PMP) and secondary (SMP) particles elicited impacts on reproduction.•For most endpoints species sensitivity decreased with body size.•PMPs caused greater impact than SMPs to all three species studied.
Capsule: Primary microplastics and artificially weathered secondary microplastics have species-specific effects on reproductive success in Cladoceran.
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