Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?

2021 ◽  
Vol 23 ◽  
Author(s):  
Concetta Cafiero ◽  
Alessandra Micera ◽  
Agnese Re ◽  
Loredana Postiglione ◽  
Andrea Cacciamani ◽  
...  

: SARS-CoV-2 pathogenesis has been recently extended to human central nervous system (CNS), in addition to nasopharyngeal truck, eye, lung and gut. The recent literature highlights that some SARS-CoV-2 spike glycoprotein regions homologous to neurotoxin-like peptides might bind to human nicotinic Acetyl-Choline Receptors (nAChRs). Spike-nAChR interaction can probably cause dysregulation of CNS and cholinergic anti-inflammatory pathways and uncontrolled immune-response, both associated to a severe COVID-19 pathophysiology. Herein, we hypothesize that inside the Open Reading Frame (ORF) region of spike glycoprotein, the RNA polymerase can translate small neurotoxic peptides by means of a “jumping mechanism” already demonstrated in other coronaviruses. These small peptides can bind the snAChRs instead of Spike glycoproteins. A striking homology occurred between these small peptides observed by sequence retrieval and proteins alignment. Acting as nAChRs antagonists, these small peptides (conotoxins) could be the explanation for the extrapulmonary clinical manifestations (neurological, hemorrhagic and thrombotic expressions, the prolonged apnea, the cardiocirculatory collapse, the heart arrhythmias, the ventricular tachycardia, the body temperature alteration, the electrolyte K+ imbalance and finally the significant reduction of butyryl cholinesterase (BuChE) plasma levels, as observed in COVID-19 patients. Several factors might induce the expression of these small peptides, including microbiota. The main hypothesis regarding the presence of these small peptides opens a new scenario on the etiology of COVID-19 clinical symptoms observed so far, including the neurological manifestations.

2005 ◽  
Vol 58 (5-6) ◽  
pp. 236-239 ◽  
Author(s):  
Julijana Dragojlovic ◽  
Branko Milosevic ◽  
Neda Sasic ◽  
Miomir Pelemis ◽  
Milan Sasic

Introduction Streptococcus suis is a bacterium causing a disease in pigs and rarely in humans. This zoonosis is mostly found as a sporadic disease in individuals that were in contact with the affected or infected pigs: farmers, veterinarians and workers engaged in fresh pork processing. It is assumed that the bacterium enters the body through a cut abrasion in the skin. Initially, the condition resembles a flu, followed by signs of bacteriemia and sepsis. The most frequent clinical manifestation of Streptococcus suis infection is meningitis, leading to hearing loss in over 75% of patients, and subsequent arthritis, endophtalmitis, endocarditis and pneumonia. Toxic shock syndrome with hemorhagic manifestations rarely develops. Material and methods This study included five male patients aged 22 to 63 years treated in the Intensive Care Unit of the Institute of Infectious and Tropical Diseases in Belgrade, due to Streptococcus suis infection. The aim of this study was to point to the existence of this bacteria in our environment, to describe clinical manifestations of the disease and to point out the importance of its prevention. Results All patients had epidemiological evidence of being in contact with pork meat. There were no data about diseased pigs. The estimated incubation period was 4 to 8 days. All patients had meningeal signs. Clinical symptoms included shivering, fever, vomiting, headache, malaise, vertigo and tinitus. Three patients presented with alerterd level of awareness. Four patients developed very severe bilateral hearing impairemnt, whereas one endophtalmtis and one developed endocarditis. The cerebrospinal fluid (CSF) was opalescent in four patients, and only one patient presented with clear CSF. CSF examination showed typical changes characeteristic for bacterial meningitis. Streptoccocus suis was isolated in CSF in all patients, and in one patient the bacteria was isolated in blood as well. All patients underwent treatment with II and III generation cephalosporins and one with one aminoglycosides. All patients were cured, but 4 of them developed sequelae like permanent sensorineural deafness and mild ataxia. Conclusions Streptococcus suis infection is present as a zoonosis in pigs, while humans are contracted occasionally, most frequently related to occupational risk. In cases with bacterial meningitis with sepsis and hearing loss, Streptococcus suis infections must be suspected. Effective prevention requires collaboration between epidemiologists, veterinarians and human medicine physicians. .


2018 ◽  
Vol 128 (3) ◽  
pp. 107-110
Author(s):  
Anna Maria Dąbrowska ◽  
Agnieszka Zwolak

Abstract Introduction. Neurofibromatosis type 1 (NF1), caused by mutation of the tumour-suppressor gene encoding neurofibromin, is an autosomal dominant disorder affecting various organs. Aim. The aim of the study was to discuss the clinical symptoms of NF1 based on seven cases of the disease with regard to the literature. Material and methods. We analyzed retrospectively patients with NF1 (4 females and 3 males) aged 19-52 who were treated at Endocrinology Department between 2003 and 2017. The diagnosis was made in childhood (4 patients) or in adolescence (3 cases), based on clinical symptoms and genetic tests. Results. Five patients had a positive family history of NF1, two cases represented spontaneous mutation. All of analyzed subjects presented café-au-lait spots and neurofibromas on the body. We observed neurological disorders such as: epilepsy (2 patients), Arnold-Chiari malformation (1 man), benign brain neoplasms (2 persons). Optic gliomas appeared in two cases. Tumours were also found in other organs, including the uterus (2 women), the lung, the adrenals, the pituitary and the parathyroid gland (with signs of primary hyperparathyroidism) – each tumour in another patient. Four subjects suffered from cognitive impairment. Skeletal manifestations of neurofibromatosis type 1 such as scoliosis (1 man) and short stature (6 patients) have been noted as well. Five patients presented thyroid disorders – hypothyroidism due to Hashimoto’s disease (4 patients), toxic nodular goiter (1 woman). Other clinical symptoms e.g. vitiligo, alopecia areata and coarctation of aorta have also been found. Conclusions. Variety of clinical symptoms causes that NF1 still remains a diagnostic and management challenge for many physicians. Therefore, multidisciplinary approach is needed to optimize patients’ treatment.


2019 ◽  
Vol 190 (11) ◽  
pp. 66-70
Author(s):  
А. КРАСНОПЕРОВ ◽  
A. KRASNOPEROV ◽  
С. Малков ◽  
S. Malkov ◽  
Наталья Верещак ◽  
...  

Abstract. Purpose – study the effect of enterosorbent on the immunological parameters of blood and the productivity of young cattle. Methods. The object of the study was newborn calves from 2 to 6 days of age (n = 54). Studies on the enterosorbent based on colloidal silicon dioxide (CSD) for calves with alimentary dyspepsia have been carried out. During the experiment, the clinical condition of the animals, the increase in live body weight were evaluated, blood samples were taken for immunohematological studies. Results. In calves at 2–6 days of age, alimentary dyspepsia is accompanied by the development of endogenous intoxication of the body. Animals show leukocytosis – 16.60 ± 5.11×109/l; leukocyte shift to the left with an increase in the number of adolescent and stab neutrophils – 1.41 ± 0.23×109/l; monocytes up to 1.21 ± 0.13x×109/l; circulating immune complexes (CIC) level in blood serum up to 202.4 ± 8.5 cu Under conditions of endogenous intoxication, the immunological protection of the organism was characterized by an increase in the number of phagocytic cells to 71 % of the total number of granulocytes. Clinical symptoms of endogenous intoxication in 86 % of cases disappeared by the 5th day of the use of enterosorbent CSD in the treatment regimen of calves with alimentary dyspepsia. This is associated with blocking and weakening the inflammatory response in the gastrointestinal tract. The effect of enterosorbent CSD on the immunological parameters was expressed in a balanced stabilization of the processes of phagocytosis and immunogenesis. The trend towards normalization of immunological parameters was registered: the level of the CIC was significantly reduced to 97.5 ± 5.48 cu; the phagocytic activity (PA) of the neutrophilic cells was 50.1 ± 2.4 %. Treatment of animals according to the basic scheme approved by the farm turned out to be less effective. In calves that did not receive enterosorbent CSD, in 11 % of cases, clinical manifestations of endogenous intoxication were recorded up to and including 14 days. In these animals, the level of the CIC remained high – 143.6 ± 8.57 cu, the voltage of phagocytic function was noted – 64.3 ± 7.6 % and the imbalance in the ratio of T/B-lymphocytes – 1.13 (normal 1.5–2.0). The effect of the CSD enterosorbent on the calves productivity was reflected in the fact that the rate of weight gain during the experiment was higher in the experimental group. At 4 months, their weight was 149.17 ± 13.57 kg, while in the control group and the comparison group – 135.00 ± 5.00 and 130.00 ± 22.73 kg, respectively. Scientific novelty. Alimentary dyspepsia causes the development of endogenous intoxication in the body of newborn calves. The lack of therapeutic measures leads to a long recovery period and a decrease in productivity.


2007 ◽  
Vol 60 (9-10) ◽  
pp. 493-496
Author(s):  
Zeljko Mijailovic ◽  
Predrag Canovic ◽  
Olgica Gajovic

Introduction. Leptospirosis is an acute zoonotic infection, caused by spirochetes of the genus Leptospira. It is characterized by extensive vasculitis. It is usually transmitted indirectly, per contaminated water, rarely directly, through contact with infected animals. Leptospira bacteria commonly enter the body through damaged skin or mucous membranes. The clinical syndromes may vary from a subclinical infection and mild febrile condition to severe clinical symptoms with jaundice and renal failure. Case report. This is a case report of a patient with leptospirosis (Weil's disease) whose clinical manifestations included: icterus, renal failure, hemorrhagic syndrome and disturbances of consciousness. After the use of antibiotics, symptomatic and substitution therapy, all symptoms resolved completely. However, in our patient, hemodialysis was necessary due to renal failure, as a palliative measure. Discussion. Weil?s syndrome is a severe form of leptospirosis, which can be fatal. Early clinical diagnosis of the disease, as well as serologic verification of infection, are very important prerequisites, followed by antibiotic and other symptomatic therapy, as soon as possible. Conclusion. This is a case report of a patient with rare clinical manifestations of leptosirosis. Although presenting with severe symptoms, thanks to palliative therapeutic measures, complete and fast recovery was achieved. We especially point out the role of hemodialysis in the treatment of this patient. .


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 550
Author(s):  
Carlo Brogna ◽  
Simone Cristoni ◽  
Mauro Petrillo ◽  
Maddalena Querci ◽  
Ornella Piazza ◽  
...  

Background: SARS-CoV-2 that causes COVID-19 disease and led to the pandemic currently affecting the world has been broadly investigated. Different studies have been performed to understand the infection mechanism, and the involved human genes, transcripts and proteins. In parallel, numerous clinical extra-pulmonary manifestations co-occurring with COVID-19 disease have been reported and evidence of their severity and persistence is increasing. Whether these manifestations are linked to other disorders co-occurring with SARS-CoV-2 infection, is under discussion. In this work, we report the identification of toxin-like peptides in COVID-19 patients by application of the Liquid Chromatography Surface-Activated Chemical Ionization – Cloud Ion Mobility Mass Spectrometry.   Methods: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study peptidomic toxins’ profiles. Protein precipitation preparation procedure was used for plasma, to remove high molecular weight proteins and efficiently solubilize the peptide fraction; in the case of faeces and urine, direct peptide solubilization was employed.   Results: Toxin-like peptides, almost identical to toxic components of venoms from animals, like conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in samples from COVID-19 patients, but not in control samples.  Conclusions: The presence of toxin-like peptides could potentially be connected to SARS-CoV-2 infection. Their presence suggests a possible association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. Their involvement in a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like neurological ones, cannot be excluded. Although the presence of each individual symptom is not selective of the disease, their combination might be related to COVID-19 by the coexistence of the panel of the here detected toxin-like peptides. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.


2021 ◽  
Vol 48 (1) ◽  
Author(s):  
I. M. Fushtey ◽  
A. M. Pidlubna

Abstract One of the diseases that is quite common in modern rheumatology and leads to dysfunction of the musculoskeletal system and creates a major medical and social problem, is gonarthrosis. The incidence of degenerative-dystrophic diseases in HA in women is two to four times higher than in men. In order to establish the patterns of clinical manifestations of GA in women with hypertension (GC) and overweight (HB) of the body, on the basis of the rheumatology department of the city KNP «City Hospital №10» ZMR (Zaporozhye), with informed consent, was prospectively examined 198 women for the period 2018–2020. According to the results of the study, a significant (p <0.05) deterioration of clinical symptoms in women with a combined course of HA with GC and HB, relative to the isolated course of HA, on the indicators: pain during active and passive movements and palpation, stiffness, crepitation and swelling of the joints. The correlations between clinical manifestations of HA, arthrosonographic data and BMI have been established. The characteristics of the pain syndrome associated with exercise, impaired mobility and functionality of the joints significantly increased with increasing stage of GA, joining comorbid pathology and increased BMI.  Keywords: gonarthrosціis, comorbidity, hypertension, overweight.


2018 ◽  
Vol 55 (4) ◽  
pp. 609-612
Author(s):  
Gheorghe Raftu ◽  
Geta Mitrea ◽  
Luana Andreea Macovei ◽  
Aurel Nechita

Many of the chemical additives in the plastic products, besides the possible safety problems that may arise during the production process, have negative effecty, too, on the environment and human health. Plastic is a synthetic polymer. The polymers include starch, latex and cellulose, combined with different substances and chemicals, used in various formulas, the polymer is included in the naylon. At high temperatures such as microwave oven temperature, polymers can migrate from the packaging plastic in food. In most cases, establishing the diagnosis of allergic disease is a complex and difficult operation. This difficulty is primarily related to the polymorphism of the clinical manifestations accompanying allergic reactions, the existence during the evolution of these conditions, of long clinical asymptomatic latencies, as well as due to numerous subjective and objective symptoms that overlap with those caused by the allergen, complicating and altering the clinical picture. Allergies are an abnormal reaction of the body to allergens and develop in two stages. After the first contact with the allergen, the IgE antibodies are produced, and the second contact produces the allergic reaction. The produced antibodies will release the chemical mediators (histamine, prostaglandine, etc.) which cause an inflammatory response, vascular changes and irritation of the tissues, with the appearance of symptoms specific to allergy: redness, rash, itching, edema, etc.The so complex symptom of allergic diseases comprises several systems and organs at the same time, and the existence of over-additive phenomena makes it impossible to have characteristic clinical symptoms of allergic diseases that allow their identification only by clinical examination. However, this does not mean that the clinical exam and the analysis of the various objective and subjective symptoms presented by the patient is of no importance in establishing the diagnosis and recognizing the allergic character of the disease.The study includes a number of patients studied at the Galati Allergy Clinic. Specific immunotherapy known as desensitization or anti-allergic vaccination, is designed to fight the causes of allergies that occur when the immune system misinterprets harmless substances. Clinical examination results are complemented by allergen and specific antibody research; skin tests are the most common method for allergen detection.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 550
Author(s):  
Carlo Brogna ◽  
Simone Cristoni ◽  
Mauro Petrillo ◽  
Maddalena Querci ◽  
Ornella Piazza ◽  
...  

Background: SARS-CoV-2 that causes COVID-19 disease and led to the pandemic currently affecting the world has been broadly investigated. Different studies have been performed to understand the infection mechanism, and the involved human genes, transcripts and proteins. In parallel, numerous clinical extra-pulmonary manifestations co-occurring with COVID-19 disease have been reported and evidence of their severity and persistence is increasing. Whether these manifestations are linked to other disorders co-occurring with SARS-CoV-2 infection, is under discussion. In this work, we report the identification of toxin-like peptides in COVID-19 patients by application of the Liquid Chromatography Surface-Activated Chemical Ionization – Cloud Ion Mobility Mass Spectrometry.   Methods: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study peptidomic toxins’ profiles. Protein precipitation preparation procedure was used for plasma, to remove high molecular weight proteins and efficiently solubilize the peptide fraction; in the case of faeces and urine, direct peptide solubilization was employed.   Results: Toxin-like peptides, almost identical to toxic components of venoms from animals, like conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in samples from COVID-19 patients, but not in control samples.  Conclusions: The presence of toxin-like peptides could potentially be connected to SARS-CoV-2 infection. Their presence suggests a possible association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. Their involvement in a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like neurological ones, cannot be excluded. Although the presence of each individual symptom is not selective of the disease, their combination might be related to COVID-19 by the coexistence of the panel of the here detected toxin-like peptides. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.


2020 ◽  
pp. 14-17
Author(s):  
Irina A. Shkuratova ◽  
◽  
Lyudmila I. Drozdova ◽  
Aleksander I. Belousov ◽  

Mycotoxicological monitoring of forages shows that the problem of mycotoxicosis has been relevant for several decades. Minimal doses of mycotoxins in feed lead to a decrease in milk productivity, increased sensitivity to infectious and non-infectious diseases. When several mycotoxins enter the body simultaneously, a synergistic effect develops, causing a significant increase in toxicity. Feed contaminated with several types of fungi and their toxins is dangerous for dairy cattle. It was found that the feed mixture contained the types of associations of Aspergillus spp. fungi + Fusarium; Aspergillus spp. + Penicillium spp. + Mucor spp; Fusarium + Penicillium; Mucor spp. + Fusarium + Ustilaginales. Pathogenetic features of metabolic and morphological changes in highly productive cows with polymycotoxicosis were studied. Feeding food contaminated with various metabolites of mold fungi leads to the development of signs of chronic toxemia in animals. Clinical manifestations are the development of diarrhea and dehydration, with a decrease in milk productivity. Metabolic disorders feature the development of an inflammatory process, metabolic acidosis, hyperfermentonemia, with an increase in the amount of creatinine and urea in the blood serum. Metabolic signs indicate the development of hepatorenal syndrome due to structural disorders of the liver and kidneys. Histological signs of polymicotoxicosis are intracapillary and hemorrhagic glomerulonephritis, hepatocyte micronecrosis, and proliferation of connective tissue stroma cells, which leads to the development of atrophic cirrhosis in the interstitial and circular phases.


Author(s):  
E.P. Dolgov ◽  
◽  
A.A. Abramov ◽  
E.V. Kuzminova ◽  
E.V. Rogaleva ◽  
...  

The article presents the data on the study of the influence of mycotoxins combination (T-2 toxin at the concentration of 0.095 mg/kg and aflatoxin B1 in the concentration of 0.019 mg/kg) on the body of quails and the results of pharmacocorrection of toxicosis with a complex consisting of beet pulp and lecithin. Structural changes in the intestines of quais at fodder mycotoxicosis are described. The use of antitoxic feed additives in poultry led to a weakening of the action of xenobiotics, which was confirmed by an increase in the safety of poultry and increase in body weight of quails, a decrease in the clinical manifestations of intoxication, as well as in positive changes in the structure of the intestine of the poultry during histological examination.


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