Therapeutic possibilities of Bothrops jararaca in high dilution

Introduction: The knowledge and use of the venom of Bothrops jararaca in high dilutions is still quite limited. One of the important properties is the use of one of its components, bradykinin, for the development of antihypertensive medication known as captopril. Other situations, such as clinical, local and systemic should receive more depth to the composition of Materia Medica related to various medical actions on the man and mammals in general. The systemic action of the bite of this snake, includes hemostasis disorders, culminating as bleeding gums, in addition to sweating, hypertension, and hypothermia. The action includes local pain and swelling with bruising, bleeding and often blistering and tissue necrosis. The action on the immune system, through action on the complement C3 and other complement components may show its possible use in cases of bacterial infections, including mycobacteria, as presented in the study of 1970 Vanessa Birdsey, "Interactions of poisons toxic with the addition, "the journal of Immunology 1971. Today, this poison has a toxicology published by Anibal Melgarejo, "Venomous Animals of Brazil", 2003, which subsidizes the development of study for its use in high dilutions, and a comprehensive study of the biology of the animal itself. Published studies on biomolecular analysis add more details about the relations of the poison and mammals. All these characteristics suggest the use of poison as a homeopathic remedy. Objective: To investigate the therapeutic possibilities in high dilutions of the venom of the snake Bothrops jararaca, expanding its clinical use. Methodology: Methodological description of this poison in contemporary bases including: Origin, physical description chemistry, toxicology, pharmacology and medicine in preparation of high dilution, general action, specific actions on systems or organs, sensations, modalities, concomitants, etiological indications relations main clinics. Results: Defining the therapeutic indications such as modulation of the complement system, action on the cardiovascular system, among other uses, by Bothrops jararaca in high dilution. Conclusion: This evaluation can be used for different sources of products and allows the rational use of Bothrops jararaca in high dilution. The results can and should be complemented by clinical studies and pathogenetic. Bacterial infectious diseases such as tuberculosis and leprosy, and autoimmune disease LES and may receive treatment studies with the drug based on Bothrops jararaca snake venom because they are indirectly associated with them via similarity of the failure of complement, an important marker for bacterial the defense of mammals. Action on clinical aspects like hypertension, sweating, hypothermia and necrosis shall be seen. Perhaps the search for the stimulation of complement show a new pathway for the harmonization, long-predicted by Hahnemann, Hering and searched for among the many that followed the creator of this therapy.

Neuronal Loss after Stroke Due to Microglial Phagocytosis of Stressed Neurons

After stroke, there is a rapid necrosis of all cells in the infarct, followed by a delayed loss of neurons both in brain areas surrounding the infarct, known as ‘selective neuronal loss’, and in brain areas remote from, but connected to, the infarct, known as ‘secondary neurodegeneration’. Here we review evidence indicating that this delayed loss of neurons after stroke is mediated by the microglial phagocytosis of stressed neurons. After a stroke, neurons are stressed by ongoing ischemia, excitotoxicity and/or inflammation and are known to: (i) release “find-me” signals such as ATP, (ii) expose “eat-me” signals such as phosphatidylserine, and (iii) bind to opsonins, such as complement components C1q and C3b, inducing microglia to phagocytose such neurons. Blocking these factors on neurons, or their phagocytic receptors on microglia, can prevent delayed neuronal loss and behavioral deficits in rodent models of ischemic stroke. Phagocytic receptors on microglia may be attractive treatment targets to prevent delayed neuronal loss after stroke due to the microglial phagocytosis of stressed neurons.

Risk surveillance and mitigation: autoantibodies as triggers and inhibitors of severe reactions to SARS-CoV-2 infection

COVID-19 clinical presentation differs considerably between individuals, ranging from asymptomatic, mild/moderate and severe disease which in some cases are fatal or result in long-term effects. Identifying immune mechanisms behind severe disease development informs screening strategies to predict who are at greater risk of developing life-threatening complications. However, to date clear prognostic indicators of individual risk of severe or long COVID remain elusive. Autoantibodies recognize a range of self-antigens and upon antigen recognition and binding, important processes involved in inflammation, pathogen defence and coagulation are modified. Recent studies report a significantly higher prevalence of autoantibodies that target immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins in COVID-19 patients experiencing severe disease compared to those who experience mild or asymptomatic infections. Here we discuss the diverse impacts of autoantibodies on immune processes and associations with severe COVID-19 disease.

Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections

Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 ± 39.0 ng/mL) and TCC (11.03 ± 8.52 µg/mL) in patients compared to healthy controls (p < 0.01 and p < 0.0001, respectively). Furthermore, systemic NETosis was significantly augmented in patients (5.87 (±3.71) × 106 neutrophils/mL) compared to healthy controls (0.82 (±0.74) × 106 neutrophils/mL) (p < 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections.

Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review

BackgroundTrypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant Neglected Tropical Diseases (NTD) according to World Health Organization (WHO). During the infectious process, immune system is immediately activated, and parasites can invade nucleated cells through a broad diversity of receptors. The complement system − through classical, alternative and lectin pathways − plays a role in the first line of defense against these pathogens, acting in opsonization, phagocytosis and lysis of parasites. Genetic modifications in complement genes, such as Single Nucleotide Polymorphisms (SNPs), can influence host susceptibility to these parasites and modulate protein expression.MethodsIn March and April 2021, a literature search was conducted at the PubMed and Google Scholar databases and the reference lists obtained were verified. After applying the inclusion and exclusion criteria, the selected studies were evaluated and scored according to eleven established criteria regarding their thematic approach and design, aiming at the good quality of publications.ResultsTwelve papers were included in this systematic review: seven investigating CD and five focusing on Leishmaniasis. Most articles presented gene and protein approaches, careful determination of experimental groups, and adequate choice of experimental techniques, although several of them were not up-to-date. Ten studies explored the association of polymorphisms and haplotypes with disease progression, with emphasis on lectin complement pathway genes. Decreased and increased patient serum protein levels were associated with susceptibility to CD and Visceral Leishmaniasis, respectively.ConclusionThis systematic review shows the influence of genetic alterations in complement genes on the progression of several infectious diseases, with a focus on conditions caused by trypanosomatids, and contributes suggestions and evidence to improve experimental design in future research proposals.

Serum levels of immunoglobulin and complement in UTI of patients caused by Proteus mirabilis and using AgNPs as antiswarming

The use of plant extracts represents a promising approach for the synthesis of silver nanoparticles (AgNPs). This study reports the low-cost, green synthesis of AgNPs using the extract of clove and black seeds. The biosynthesized AgNPs were confirmed and characterized by analysis of the spectroscopy profile of the UV-visible spectrophotometer. The purpose of the present study is to evaluate the inhibitory effect concentration (MIC) of AgNPs, clove, and black cumin seed extracts on the growth and swarming of P. mirabilis. Clinical isolates of P. mirabilis were isolated from patients suffering from urinary tract infections. Thirteen types of antibiotics were used in the present study to detect their ability to inhibit P. mirabilis's resistance. Immunological findings included the determination of serum levels of IgG, IgM, IgA and complement protein C3 and C4. Results showed that IgG and IgA concentrations significantly increased (1311.13 ± 72.54 and 279 ± 21.31) respectively in UTI patients in comparison to the healthy control group which was 1089.88 ± 37.33 and 117.611 ± 4.19 respectively, While IgM concentrations were increased non significantly in UTI patients (153.331 ± 6.45) in comparison to healthy control (145.2 ± 13.49). Complement components C3 showed a significant increase in UTI patients with mean values of 125.95 ± 6.22 compared to the control group with mean values of 55.191 ± 9.64, while C4 showed statically non-significant among UTI patients in comparison with the control group (35.195 ± 2.34 and 34.371 ± 1.22) respectively.

In vitro, classical complement activation differs by disease severity and between SARS-CoV-2 antigens

Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of anti-SARS-CoV-2 antibodies from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the antigen and subjects studied. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending on the specific antigen targeted and the disease status of the subject.

Profile of several autoantibodies, complement and vitamin D levels in Brazilian patients with Chikungunya infection

Introduction. Chikungunya virus infection (CKV) may lead to chronic arthritis in up to 40% of the patients. There are previous data regarding positive auto antibodies in CKV. Objective is to systematically evaluate the prevalence of auto antibodies in CKV patients. Methods. All study participants had clinical manifestations being CKV positive at least serologally or by RT-PCR data. The following autoantibodies were assessed: antinuclear antibodies (ANA), anti-dsDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-U1RNP, IgG and IgM anticardiolipin, anticyclic citrullinated peptide (antiCCP), rheumatoid factor (RF), antiribosomal P protein, lupus anticoagulant, anti-Jo-1 and anti-Scl-70. CH100, C3 and C4 complement components, serum levels of immunoglobulins, C-reactive protein, erythrocyte sedimentation rate, alpha1-acid glycoprotein, antithyroglobulin, antithyroperoxidase, TRAb, 25 hydroxyvitamin D (25OHD), dengue and zika IgG and IgM antibodies were also measured. Results. 30 CKV patients were included. Mean age was 59.1±15.7 years, 85% females and 77% Caucasian subjects. Disease duration comprised 4.9±4.0 months. Oligoarthritis was observed in 93% cases. Mean C-reactive protein levels were 10.1±6.8 ng/dL, erythrocyte sedimentation rate — 34.2±19.9 mm/1st hour and alpha1-acid glycoprotein 115.5±52.6 mg/dL. Intramuscular betamethasone depot single dose injection was administered in 54%, prednisone — in 15% and methotrexate — in 23% cases. Importantly, 1/30 (3.3%) cases was positive for ANA, 4/30 (13.3%) — for RF and none was positive for anti-CCP or any other autoantibodies. Complement and immunoglobulin levels were all within the normal range. Low levels of 25OHD were observed in 88% cases.

Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients

ALS remains a fatal, neurodegenerative motor neuron disease. Numerous studies seem to confirm that innate immune system is involved in the pathophysiology of ALS. Hence, the assessment of the complement system and attempts to modify its activity remain the target of medical intervention in ALS. In the present study, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin–) cells were performed every 6 weeks in 20 sporadic ALS patients. The concentrations of various complement components in the cerebrospinal fluid and plasma at different time points after cell injection were quantified using a Luminex multiplex. The results of the complement system were correlated with the level of leukocytes, neutrophils, lymphocytes, fibrinogen and CRP in the peripheral blood and the functional status of ALS patients using Norris and ALS-FRSr scales. The study showed a statistically significant decrease in plasma C3b concentration in all 7th days after cell application. In parallel, a peak decrease in neutrophil count and CRP level was observed on days 5–7, with a simultaneous maximum clinical improvement on days 7–28 of each Lin– cell administration. Adjuvant Lin– cell therapy appears to have the silencing potential on the complement-mediated immune system and thus suppress pro-inflammatory reactions responsible for neurodegeneration. However, further in-depth studies are necessary to address this issue.