Double voice on the admissibility of scientific research using human biological material : legal issues and ethical perspective

Przedstawiony w pierwszej części dwugłosu stan polskich regulacji prawnych dotyczących prowadzenia badań z wykorzystaniem ludzkiego materiału biologicznego, skłania do rozważań nad pożądanym, z etycznego punktu widzenia, doprecyzowaniem zidentyfikowanych niejasności. Druga część dwugłosu została więc poświęcona roli świadomej zgody dawcy (donatora) na wykorzystanie w badaniach pobranych od niego próbek biologicznych, a przede wszystkim na użycie w celach naukowych zwłok. W rozważaniach dotyczących badań z użyciem zwłok na pierwszy plan wysuwa się pytanie o powody, dla których w ogóle należy uwzględniać przedśmiertną wolę zmarłych i czy chodzi o wolę domniemaną, czy też faktycznie wyrażoną; natomiast w dyskusji dotyczącej wykorzystywania próbek biologicznych zasadnicze znaczenie będzie miało pytanie o formę jaką powinna przybrać rzeczywista - nie domniemana - zgoda dawcy.The text is devoted to consideration on the morally desirable way of clarifying the ambiguities identified in a previous part of the double voice. So it contains deliberations on meaning and authority of biological material donor informed consent. Considering research on human corpses the author focus on two questions: why deceased patient’s premortem preferences should be taken into account at all and whether "an advance research directives" of that kind should take a form opt-in or opt-out arrangements? Whereas when it comes to research on biological samples the most important question is what type of actual - not presumed - consent meet ethical standards

Intracranial Rosai-Dorfman Disease: pathophysiology, diagnosis and treatment

Introduction and purpose: ​Rosai-Dorfman Disease (RDD), known also as sinus histiocytosis with massive lymphadenopathy(SHML) is a benign histiocytic proliferative syndrome. The etiology and pathogenesis of RDD remains unclear. Central nervous system involvement is a rare event and concerns approximately 7.8% of RDD cases, whereas intracranial lesions constitute almost 90% of CNS-RDD cases. The aim of this literature review was to summarize current knowledge about the diagnosis and treatment of intracranial manifestation of RDD. We also described possible hypotheses regarding the pathophysiology of this disorder. State of knowledge: ​Even though Rosai-Dorfman disease was thought to be a reactive process, recent evidencedemonstrate the presence of clonality, which means that in this histiocytosis the process that underlies the pathology is neoplastic. Intracranial lesions caused by RDD can be easily misdiagnosed with many diseases such as meningiomas, malignant gliomas or metastatic tumors. The final diagnosis of Rosai-Dorfman disease should be made based on histologic and immunohistochemical examinations. Current therapeutic options for this condition include surgery, radiotherapy, chemotherapy, corticosteroids and immunotherapy. Surgical treatment often constitutes the first-line treatment for intracranial RDD and is the most beneficial treatment option. However, the implementation of adjuvant therapies is very important to avoid the recurrence of lesions, which appear in approximately 14% of subjects after about 10 years from surgery. Conclusion: ​This literature review presents current data about pathophysiology, diagnosis and treatment of intracranial involvement of Rosai-Dorfman disease. Further studies on this topic should focus on exploring etiologic mechanisms underlying on this pathology and comparing available treatment methods

Alveolar osteitis: the current state of knowledge

Introduction and purpose: Alveolar osteitis, also known as dry socket is a common complication after tooth extraction, especially third molar extraction. Taking into consideration only third molar extractions, the prevalence of dry socket reaches even 45%. The aim of this literature review was to describe current knowledge about etiology, risk factors, treatment, and prevention of dry socket. State of knowledge: The symptoms of alveolar osteitis most frequently are reported between the first and third post-extraction days and they include discomfort, lancing, and intense pain which radiates to the neck and ear. The etiopathogenesis of dry socket remains unclear. However, the currently accepted hypothesis describes a loss of formed after an extraction blood clot from the alveolar socket as the main cause of this pathology. Several factors may increase the risk of dry socket and include smoking, oral hygiene, female gender, oral contraceptive drugs, and anesthesia. In the treatment of alveolar osteitis, irrigation of the socket with chlorhexidine gluconate, iodopovidone, or physiological saline followed by filling the socket with intra-alveolar dressing constitute a current fundamental procedure. Plenty of substances are currently used as an intra-alveolar dressing. Part of them exhibits only pain-decreasing features, whereas some drugs can also stimulate the regeneration of treated tissue. In the prevention, the use of alveolar osteitis warm saline, antibiotics, chlorhexidine, ozone gas, or autologous platelet therapy may be useful maneuvers. Conclusion: This literature review summarizes the current state of knowledge about causes, risk factors, and therapeutic and preventive methods with regard to alveolar osteitis

Diverse structural approaches to haem appropriation by pathogenic bacteria

The critical need for iron presents a challenge for pathogenic bacteria that must survive in an environment bereft of accessible iron due to a natural low bioavailability and their host's nutritional immunity. Appropriating haem, either direct from host haemoproteins or by secreting haem-scavenging haemophores, is one way pathogenic bacteria can overcome this challenge. After capturing their target, haem appropriation systems must remove haem from a high-affinity binding site (on the host haemoprotein or bacterial haemophore) and transfer it to a binding site of lower affinity on a bacterial receptor. Structural information is now available to show how, using a combination of induced structural changes and steric clashes, bacteria are able to extract haem from haemophores, haemopexin and haemoglobin. This review focuses on structural descriptions of these bacterial haem acquisition systems, summarising how they bind haem and their target haemoproteins with particularly emphasis on the mechanism of haem extraction

Sequestration and Scavenging of Iron in Infection

The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen

Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 310-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 310-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with upstream ligands

Staphylococcus aureus infection dynamics

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed