Mechanisms of Organ Damage and Novel Treatment Targets in AL Amyloidosis

The deposition of amyloid light chains (LCs) in target sites translates into tissue damage and organ dysfunction. Clinical and experimental advances have cast new light on the pathophysiology of damage in AL amyloidosis. The currently accepted view is that, besides the alterations caused by fibrillar deposits in the extracellular space, direct proteotoxicity exerted by prefibrillar LC species is an important pathogenic factor. As our knowledge on the pathological species and altered cellular pathways grows, novel potential therapeutic strategies to prevent or reduce damage can be rationally explored. Complementing chemotherapy with approaches aimed at disrupting the deposited fibrils and stabilizing prefibrillar amyloidogenic LC may allow halting or even reverting damage in target sites. This review recapitulates the current knowledge and the most recent acquisitions regarding the mechanisms of organ damage in AL amyloidosis, with special emphasis on the heart, and will provide a critical discussion on possible novel treatment targets.

Impact of Neurofascin on Chronic Inflammatory Demyelinating Polyneuropathy via Changing the Node of Ranvier Function: A Review

The effective conduction of action potential in the peripheral nervous system depends on the structural and functional integrity of the node of Ranvier and paranode. Neurofascin (NF) plays an important role in the conduction of action potential in a saltatory manner. Two subtypes of NF, NF186, and NF155, are involved in the structure of the node of Ranvier. In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), anti-NF antibodies are produced when immunomodulatory dysfunction occurs, which interferes with the conduction of action potential and is considered the main pathogenic factor of CIDP. In this study, we describe the assembling mechanism and anatomical structure of the node of Ranvier and the necessary cell adhesion molecules for its physiological function. The main points of this study are that we summarized the recent studies on the role of anti-NF antibodies in the changes in the node of Ranvier function and its impact on clinical manifestations and analyzed the possible mechanisms underlying the pathogenesis of CIDP.

Histidine-rich protein 2: a new pathogenic factor of Plasmodium falciparum malaria

Plasmodium falciparum causes serious malaria symptoms; when this protozoan parasite infects human erythrocytes, it produces and secretes large amounts of histidine–rich protein 2 (PfHRP2) into human blood. Thus, PfHRP2 is a well–known diagnostic marker for malaria infection. Here, however, we also identified PfHRP2 as a pathogenic factor produced by P. falciparum. PfHRP2 showed cell penetration and cytotoxicity against various human cells. In particular, PfHRP2 showed significant cytotoxicity over 5 days at the same concentration as in P. falciparum–infected patients′ blood (90–100 nM). This result is consistent with the mortality rate of P. falciparum malaria, which increases rapidly in untreated cases for 3–7 days. In addition, the cell penetration and cytotoxicity of PfHRP2 increased 2.5– and 2.6–fold, respectively, in the absence of serum, which suggests that low serum protein concentrations (occurring during malnutrition, for example) increase the risk of adverse effects from PfHRP2 (consistent with malnutrition increasing the lethality of malaria infection). We also showed that PfHRP2 bound to Ca2+ ions, localized to intracellular lysosomes, increased lysosomal Ca2+ levels, and inhibited the basal level of autophagy by inhibiting autolysosome formation. Furthermore, the Ca2+–dependent cytotoxicity of PfHRP2 was suppressed by the metal ion chelator ethylenediaminetetraacetic acid (EDTA). In summary, our findings suggest that PfHRP2 acts as a pathogenic factor in P. falciparum–infected patients and is associated with the exacerbation of malaria. Furthermore, EDTA is a promising candidate as a therapeutic agent for the suppression of PfHRP2 pathogenicity. Overall, this study provides new insights into P. falciparum malaria pathogenesis and treatment.

Public awareness of contagious diseases

Introduction: Restrictions against the COVID-19 pandemic have resulted in a decrease in other contagious diseases. However, their prevention and treatment are still a topical issue. Purpose: To present the public awareness on infectious diseases taking into account the knowledge of people with medical education. Material and method: The study was conducted by means of the author's questionnaire. 158 questionnaires were collected and analysed. Results: Men and women of different age took part in the survey. Half of the respondents had medical education. The analysis showed that as many as 89.2% of the respondents were aware of the pathogenic factor of influenza, which is the virus. Only a small percentage of respondents had information regarding the number of influenza infections in Poland (10.8%) and worldwide (21.5%). Medics were aware of this in 10.0% and 28.8% respectively. Influenza was admitted by 81.0% of the respondents, while for other infectious disease (except COVID-19) the result was 75.3%. The respondents indicated as the most common route of transmission of infectious diseases the droplet route (66.5%), while fever was the typical symptom (81.0%). Washing hands turned out to be the most important prophylactic behaviour of respondents (50.6%) and especially of students (93.7%). Conclusions: Awareness of infectious diseases among Poles is not at the highest level. Those with medical education have slightly higher knowledge, but it is necessary to introduce educational programmes and update knowledge.

Prevalence of Epstain–Bar Virus among Patients with Periodontitis in Al–Najaf Al–Ashraf / Iraq

Periodontitis, a complex chronic inflammatory disease caused by subgingival infection, is among the most prevalent microbial diseases in humans which characterized by periodontal damage, alveolar bone resorption, pain, and eventual tooth loss. Epstein–Barr Virus (EBV) has widely infected >90% adults in the world and is associated with many human diseases, so that this study aimed to investigate the association between EBV and periodontitis. Patients and samples: Subgingival paper point samples were collected from 100 patients with periodontitis and 30 healthy people. All samples undergo direct DNA extraction to amplified EBVs DNA using PCR technique. The results indicated a high percentage of EBV infections (18%) in patient suffering from periodontitis while there was no EBV infection were detected in healthy persons. A high percentage of EBV was detected in female (56%) in comparison with male (44%). The results improved the association between EBV and periodontitis suggesting that EBV may serve as a pathogenic factor leading to periodontitis among patients.

EVALUATION OF INFLUENCE OF THE UNITED COMPLEX AND SURGICAL TREATMENT ON SOME INDEXES OF CARBOHYDRATE EXCHANGE FOR PATIENTS ON GENERALIZED PERIODONTITIS І-ІІ DEGREE OF DEVELOPMENT

The dynamics of the inflammatory process in the periodontium, its generalization and chronization are determined not only by the composition of the microflora, but also by the state of the protective reactions of the organism (the pro-atherogenic spectrum of lipids and the disturbance of the carbohydrate metabolism) and the reactivity of the immune system in response to the pathogenic factor. Purpose of the study. The study of changes in the parameters of carbohydrate metabolism in the oral fluid of patients with generalized periodontitis (GP), before and during the different terms after the complex and surgical treatment, was determined the relevance of the direction which was chosen by us. Materials and methods. Somatically healthy people were examined and treated: 30 patients with chronic generalized periodontitis – group І, 32 patients – with exacerbation of chronic generalized periodontitis – group II and 30 persons with a healthy parodontium. Indicators of carbohydrate metabolism were determined in the oral liquid: content of glucose, pyruvate (pyruvic acid) and lactate (lactic acid) and lactate dehydrogenase (LDG) activity before, immediately and after 6 and 12 months after the treatment. A significant increase of all studied by us carbohydrate metabolism parameters (p<0.001) was found, which confirms its imbalance. In order to regulate the revealed violations, initial periodontal therapy was prescribed; oral dishes with the solution of St. John’s wort, gum applications and application of the gel were developed by us on the basis of medicinal herbs (extract of Echinacea purpureum, tincture of Eleutherococcus and St. John’s wort) and sorbent, and inside – the herbal syrup “Immuno-tone” and surgical treatment. Conclusions. The regulation of the parameters of carbohydrate metabolism in the oral liquid of patients of groups I and II with the achievement of these standards, especially after 6 and 12 months after the treatment, showed the effectiveness of the developed by us therapeutic complex and surgical treatment allowed us to recommend it for the widespread introduction into practice.

Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive.