Carbon monoxide: mechanism of toxic action, pathogenesis and clinical manifestations of acute intoxication

Regulatory Effects ◽

Mitochondrial Cytochrome Oxidase

Introduction. Carbon monoxide (CO) remains one of the most common causes of acute poisoning and death, both in everyday life and in emergency situations, especially in fires.Material and methods. The paper summarizes information about the regulatory effects, mechanisms of toxic action, pathogenesis and clinical picture of intoxication, as well as predictors of the severity of CO poisoning.Results. The main mechanism of the toxic effect of CO is due to its ability to bind to the protohemal iron of hemoglobin (Hb) to form carboxyhemoglobin (HbCO). The toxicity of CO may also be enhanced by impaired functions of the myoglobin of the myocardium and skeletal muscles, mitochondrial cytochrome oxidase, and iron-containing enzymes of the antioxidant system. The leading link in the pathogenesis of acute CO intoxication is a violation of the oxygen transport function of hemoglobin and the associated development of hemic and tissue hypoxia. CO-induced cell and tissue damage due to the induction of mitochondrial dysfunction, oxidative stress, free radical hyperproduction, lipid peroxidation, inflammation, and apoptosis also play a role in the pathogenesis of intoxication.Conclusion. The mechanism of toxic action of CO, associated primarily with the formation of carboxyhemoglobin and the development of hypoxia, determines the clinical manifestations of acute intoxication, which depend on the concentration of CO and the duration of exposure, but are almost always associated with the central nervous system and cardiovascular system.

Postoperative cognitive dysfunction: progress mechanisms and clinical characteristics

Medical alphabet ◽

10.33667/2078-5631-2019-2-19(394)-29-33 ◽

2019 ◽

Vol 2 (19) ◽

pp. 29-33

Author(s):

K. B. Manysheva ◽

M. A. Akhmedov ◽

A. A. Rakhmanova ◽

S. M. Khutalieva

Keyword(s):

Cognitive Dysfunction ◽

Clinical Characteristics ◽

Cognitive Deficit ◽

Neuropsychological Testing ◽

Postoperative Cognitive Dysfunction ◽

Clinical Manifestations ◽

Postoperative Recovery ◽

Neuropsychological Rehabilitation ◽

Brain Barrier Permeability ◽

The article is devoted to the study of postoperative cognitive dysfunction — a syndrome that is often found in the postoperative period and does not depend on the volume of surgeon. Based on the analysis of the results of modern studies, the authors cite the most likely etiological causes of the syndrome, grouped according to different categories of risk factors. The pathogenetic algorithm for cognitive dysfunction includes the appearance of systemic inflammation, improving blood-brain barrier permeability with the endothelial dysfunction, the migration of inflammatory agents into the central nervous system, and the formation of oxidative stress. The clinical manifestations of cognitive deficit in the outcome of surgeon performed under general anesthesia, the authors illustrate with their own observations of patients with a neurosurgical profile with spinal pathology operated on with the use of propofol anesthesia, comparing the results of neuropsychological testing with an assessment of the level of anxiety. In conclusion, the authors outline a strategy for the prevention of postoperative cognitive dysfunction and recommend conducting neuropsychological rehabilitation as an important component of postoperative recovery for all patients with a diagnosed cognitive deficit that occurred after surgery.

Mild Clinical Presentation of Joubert Syndrome in a Male Adult Carrying Biallelic MKS1 Truncating Variants

Diagnostics ◽

10.3390/diagnostics11071218 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1218

Author(s):

Raffaella Brunetti-Pierri ◽

Marianthi Karali ◽

Francesco Testa ◽

Gerarda Cappuccio ◽

Maria Elena Onore ◽

...

Keyword(s):

Wide Spectrum ◽

Clinical Manifestations ◽

Brain Magnetic Resonance Imaging ◽

Joubert Syndrome ◽

Male Adult ◽

Full Field ◽

Pathogenic Variants ◽

Disease Spectrum ◽

Male Individual ◽

Pathogenic variants in the MKS1 gene are responsible for a ciliopathy with a wide spectrum of clinical manifestations ranging from Meckel and Joubert syndrome (JBTS) to Bardet-Biedl syndrome, and involving the central nervous system, liver, kidney, skeleton, and retina. We report a 39-year-old male individual presenting with isolated Retinitis Pigmentosa (RP), as assessed by full ophthalmological evaluation including Best-Corrected Visual Acuity measurements, fundus examination, Goldmann Visual Field test, and full-field Electroretinography. A clinical exome identified biallelic nonsense variants in MKS1 that prompted post-genotyping investigations for systemic abnormalities of ciliopathy. Brain magnetic resonance imaging revealed malformations of the posterior cranial fossa with the ‘molar tooth sign’ and cerebellar folia dysplasia, which are both distinctive features of JBTS. No other organ or skeletal abnormalities were detected. This case illustrates the power of clinical exome for the identification of the mildest forms of a disease spectrum, such as a mild JBTS with RP in the presented case of an individual carrying biallelic truncating variants in MKS1.

β-Elemene Suppresses Obesity-Induced Imbalance in the Microbiota-Gut-Brain Axis

Biomedicines ◽

10.3390/biomedicines9070704 ◽

2021 ◽

Vol 9 (7) ◽

pp. 704

Author(s):

Yingyu Zhou ◽

Wanyi Qiu ◽

Yimei Wang ◽

Rong Wang ◽

Tomohiro Takano ◽

...

Keyword(s):

Intestinal Microbiota ◽

High Fat Diet ◽

Brain Regions ◽

Cerebral Metabolites ◽

Cerebral Inflammation ◽

Regulatory Effects ◽

Induced Changes ◽

Pearson Correlations ◽

Glucose Cycle

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria. Furthermore, we evaluated the interaction between cerebral metabolites and intestinal microbiota via Pearson correlations. The prediction results suggested that Firmicutes were possibly controlled by neuron integrity, cerebral inflammation, and neurotransmitters, and Bacteroidetes in mouse intestines might be related to cerebral aerobic respiration and the glucose cycle. Such results also implied that Actinobacteria probably affected cerebral energy metabolism. These findings suggested that β-elemene has regulatory effects on the imbalanced microbiota-gut-brain axis caused by obesity and, therefore, would contribute to the future study in on the interplay between cerebral metabolites from different brain regions and the intestinal microbiota of mice.

Tropheryma whipplei, Immunosuppression and Whipple's Disease: From a Low-Pathogenic, Environmental Infectious Organism to a Rare, Multifaceted Inflammatory Complex

Digestive Diseases ◽

10.1159/000369538 ◽

2015 ◽

Vol 33 (2) ◽

pp. 190-199 ◽

Cited By ~ 10

Author(s):

Thomas Marth

Keyword(s):

Heart Valves ◽

Clinical Manifestations ◽

Systemic Infection ◽

Tropheryma Whipplei ◽

Molecular Techniques ◽

Whipple’S Disease ◽

Whipple's Disease ◽

New Findings ◽

Body Compartments

Background: The actinobacterium Tropheryma whipplei was detected 20 years ago by molecular techniques, and following its culture has been characterized as the cause of a systemic infection known as Whipple's disease (WD). T. whipplei occurs in the environment, is prevalent only in humans, is believed to be transmitted via oral routes and to be host dependent. Key Messages: The classical form of T. whipplei infection, i.e. classical WD (CWD), is rare. It is well defined as slowly progressing chronic infection with arthralgia, diarrhea and weight loss, mostly in middle-aged men. However, current research revealed a much broader spectrum of clinical features associated with T. whipplei infection. Thus, T. whipplei may cause acute and transient infections (observed primarily in children) and the bacterium, which is found in soil and water, occurs in asymptomatic carriers as well as in CWD patients in clinical remission. In addition, T. whipplei affects isolated and localized body compartments such as heart valves or the central nervous system. Subtle immune defects and HLA associations have been described. New findings indicate that the progression of asymptomatic T. whipplei infection to clinical WD may be associated with medical immunosuppression and with immunomodulatory conditions. This explains that there is a discrepancy between the widespread occurrence of T. whipplei and the rareness of WD, and that T. whipplei infection triggered by immunosuppression presents with protean clinical manifestations. Conclusions: This review highlights recent findings and the clinical spectrum of infection with T. whipplei and WD, focusing specifically on the role of host immunity and immunosuppression. Current concepts of the pathogenesis, diagnosis and therapy are discussed.

Multi-organ coordination of lipoprotein secretion by hormones, nutrients and neural networks

Endocrine Reviews ◽

10.1210/endrev/bnab008 ◽

2021 ◽

Author(s):

Priska Stahel ◽

Changing Xiao ◽

Avital Nahmias ◽

Lili Tian ◽

Gary Franklin Lewis

Keyword(s):

Neural Networks ◽

Adipose Tissue ◽

Peptide Yy ◽

Atherosclerotic Cardiovascular Disease ◽

Neural Signals ◽

Nutritional Factors ◽

Lipoprotein Secretion ◽

Regulatory Effects ◽

The Brain

Abstract Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease (ASCVD). Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs, and provide our perspective on the relative importance of these factors. Hormones and peptides originating from the pancreas (insulin, glucagon), gut (GLP-1, GLP-2, ghrelin, CCK, peptide YY), adipose tissue (leptin, adiponectin) and brain (GLP-1) modulate TRL secretion by receptor-mediated responses and indirectly via neural networks. In addition, the gut microbiome and bile acids influence lipoprotein secretion in humans and animal models. Several nutritional factors modulate hepatic lipoprotein secretion through effects on the central nervous system. Vagal afferent signalling from the gut to the brain and efferent signals from the brain to the liver and gut are modulated by hormonal and nutritional factors to influence TRL secretion. Some of these factors have been extensively studied and shown to have robust regulatory effects whereas others are ‘emerging’ regulators, whose significance remains to be determined. The quantitative importance of these factors relative to one another and relative to the key regulatory role of lipid availability remains largely unknown. Our understanding of the complex interorgan regulation of TRL secretion is rapidly evolving to appreciate the extensive hormonal, nutritional and neural signals emanating not only from gut and liver but also from the brain, pancreas, and adipose tissue.

A foodborne norovirus outbreak among the film crew in the Autonomous Province of Vojvodina, Serbia

Medicinski pregled ◽

10.2298/mpns1908235s ◽

2019 ◽

Vol 72 (7-8) ◽

pp. 235-241

Author(s):

Mirjana Strbac ◽

Mioljub Ristic

Keyword(s):

Cohort Study ◽

Retrospective Cohort ◽

Clinical Manifestations ◽

Food Poisoning ◽

Medical Attention ◽

Microbiological Analysis ◽

Environmental Investigation ◽

Common Causes ◽

The World ◽

Autonomous Province

Introduction. Norovirus is one of the most common causes of acute gastroenteritis in the world. The aim of this study was to describe characteristics of an outbreak of norovirus infection and present all the steps of an outbreak investigation. Material and Methods. A retrospective cohort study was conducted among all individuals who ate food from the same restaurant. All the exposed persons filled out an adapted questionnaire that is routinely used in patients with food poisoning. Results. This paper presents a norovirus outbreak among film crew members and measures taken to control the epidemic. Gastroenteritis was diagnosed in 20 exposed persons. In most patients, symptoms lasted 1 - 3 days, and every third patient sought medical attention. The predominant clinical manifestations were vomiting and diarrhea. The food that probably caused the infection were sandwiches with ham, cheese and lettuce and microbiological analysis confirmed that the outbreak was caused by norovirus. Conclusion. Although the source of this outbreak remains unclear, the results of environmental investigation of the restaurant showed several irregularities in the kitchen that may have caused norovirus transmission.

Postoperative agitation syndrome in young children with perinatal damage to the central nervous system

CHILD`S HEALTH ◽

10.22141/2224-0551.16.5.2021.239715 ◽

2021 ◽

Vol 16 (5) ◽

pp. 355-360

Author(s):

V.I. Snisar ◽

O.S. Pavlysh

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Young Children ◽

Postoperative Period ◽

Anesthetic Management ◽

Clinical Manifestations ◽

Postoperative Recovery ◽

Inhalation Anesthesia ◽

Ventriculoperitoneal Shunting ◽

One of the complications of the postoperative period in children is postanesthetic agitation, a significant emotional and uncontrollable worry, clouding of consciousness, feeling of anxiety and fear, inappropriate behavior, irritability, inconsolable crying, aggressive and negative attitude towards parents and medical staff. Postoperative agitation is very important for clinicians and hospitals, it has a risk of harming a patient, staying longer in the ward after anesthesia, and increasing the period of postoperative recovery. The frequency of postoperative agitation depends on age group. Most often agitation occurs in young children. There is evidence that agitation can also be due to the immature nervous system and a consequence of pathological conditions of the central nervous system (asthenoneurotic syndrome, encephalopathy, hyperactivity syndrome, perinatal posthypoxic and organic brain lesions, history of prematurity, epilepsy, psychophysical and speech delay, etc.). That is why the goal of our research was to study the patterns of clinical manifestations of postoperative agitation syndrome in children with prenatal damage to the central nervous system. The work was performed based on the analysis of the postoperative period in 109 young children: 59 patients with acquired hydrocephalus, who underwent ventriculoperitoneal shunting, and 50 children without neurological disorders in whom reconstructive surgeries were carried out. Depending on the type anesthetic management, each group was divided into two subgroups: children, who received inhalation anesthesia with sevoflurane, and those, who received total intravenous anesthesia using propofol. In the postoperative period, the behavior of children was assessed on a Pediatric Anesthesia Emergence Delirium scale 30 minutes after anesthesia was completed. Criterion for the development of agitation was the presence of excitement in a child with a score of ≥ 10 points. Study showed that young children with perinatal damage to the central nervous system and children whose anesthetic provision is carried out using sevoflurane are the most vulnerable to the development of agitation syndrome. Agitation in such children is more pronounced and longer. These cases require prediction, detection and active surveillance.

Autoantibodies Against Ubiquitous and Confined Antigens in Patients With Ocular, Neuro-Ophthalmic and Congenital Cerebral Toxoplasmosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.606963 ◽

2021 ◽

Vol 12 ◽

Author(s):

Monica Goldberg-Murow ◽

Carlos Cedillo-Peláez ◽

Luz Elena Concha-del-Río ◽

Rashel Cheja-Kalb ◽

María José Salgar-Henao ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Molecular Mimicry ◽

Clinical Manifestations ◽

Protective Role ◽

Cross Reactivity ◽

Ocular Toxoplasmosis ◽

Cerebral Toxoplasmosis ◽

Blood Retinal Barrier ◽

Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).

Japanese encephalitis

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.8.2.2016.12697 ◽

2016 ◽

Vol 8 (2) ◽

Author(s):

Novie H. Rampengan

Keyword(s):

Japanese Encephalitis ◽

Virus Isolation ◽

Clinical Manifestations ◽

Elisa Test ◽

Culex Mosquito ◽

Capture Elisa ◽

Infective Disease ◽

Pig Farm ◽

Intra Cranial Pressure

Abstract: Japanese encephalitis (JE) is an acute infective disease in the central nervous system. Pigs and birds are the main reservoirs of JE viruses, albeit, there is no transmission from human to human with mosquito bites. Clinical manifestations of JE in human vary from mild symptoms like rhinitis until severe symptoms, and even death. Incubation period of JE varies from 4 until 14 days. Development of JE symptoms are divided into 4 stadiums, as follows: prodormal, acute, sub-acute, and convalescent. Diagnosis is based on anamnesis about fever and the presence of pig farm around the house, and physical examination consisted of increased intra-cranial pressure and decreased consciousness, meanwhile, the definite diagnosis is confirmed with virus isolation either IgM capture ELISA test from serum or cerebrospinal fluid; both have sensitivity almost 100%. Treatment of JE is only symptomatic and supportive. Prevention and erradication of JE virus are aimed to human, mosquito Culex as vector and its larvae, and pig as the reservoir. Japanese encephalitis can be prevented with immunization. In severe cases, sequelae are found around 40%-75%.Keywords: Japanese encephalitis, culex mosquito, pig farm, vaccinationAbstrak: Japanese encephalitis (JE) merupakan penyakit infeksi akut pada SSP. Babi dan unggas merupakan reservoir virus ini, namun tidak terjadi penularan dari manusia ke manusia lain melalui gigitan nyamuk. Manifestasi klinis penyakit JE pada manusia bervariasi, mulai dari gejala ringan seperti demam flu biasa sampai berat bahkan kematian. Masa inkubasi JE bervariasi antara 4 sampai 14 hari. Perkembangan gejala JE terbagi atas 4 stadium yaitu stadium prodormal, akut, sub-akut, dan konvalesen. Diagnosis pasti dengan anamnesis adanya perternakan babi disekitar rumah dan demam, pemeriksaan fisik terdapat peningkatan tekanan intra kranial serta penurunan kesadaran, dan diagnosis pasti dengan isolasi virus maupun pemeriksaan IgM capture ELISA dari serum atau CSS dengan sensitivitas hampir 100%. Terapi JE hanya bersifat simtomatis dan suportif. Pencegahan dan pemberantasan JE virus ditujukan pada manusia, vektor nyamuk Culex beserta larvanya, dan reservoir babi. Penyakit JE dapat dicegah dengan imunisasi. Pada kasus berat, ditemukan gejala sisa sekitar 40%-75%.Kata kunci: Japanese encephalitis, nyamuk Culex, peternakan babi, imunisasi

Neurobrucellosis mimicking primary vasculitis of the central nervous system: we should perform a metagenomic analysis of the cerebrospinal fluid prior to brain biopsy

10.5327/1516-3180.422 ◽

2021 ◽

Author(s):

Marina Barrionuevo Mathias ◽

Fernando Gatti ◽

Gustavo Bruniera ◽

Vitor Paes ◽

Gisele Sampaio Silva ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Psychiatric Symptoms ◽

Brain Mri ◽

Genetic Material ◽

Clinical Manifestations ◽

Brain Biopsy ◽

Metagenomic Analysis ◽

Normal Brain ◽

Context Primary angiitis of the central nervous system (PACNS) is characterized by the inflammation of small and medium CNS arteries; the clinical manifestations include headache, cognitive impairment and focal neurological deficits. The gold standard test for diagnosis is brain biopsy. Neurobrucellosis is an infection associated with cattle farming, which leads to neurological and psychiatric symptoms. We report a case of neurobrucellosis mimicking PACNS. Case report Male, 32 years old, with fever, headache, dizziness and cognitive impairments for 30 days. History of stroke 2 years before, with mild sequelae right hemiparesis; investigation showed suspected intracranial dissection. On physical examination, he had apathy, preserved strength, reduced reflexes with plantar flexor responses. General laboratory tests, autoantibodies and serology were normal. Brain MRI showed deep left nucleocapsular gliosis and cerebral angiography revealed stenosis of the ICA and MCA. CSF showed 42 cells/ mm³, glucose 46 mg/dL, protein 82 mg/dL. Blood PCR was negative for Brucella. Immunophenotyping of the CSF and PET-CT excluded neoplasia. Brain biopsy was inconclusive for vasculitis. Metagenomic analysis of the CSF detected 78% of Brucella genetic material. Serum agglutination test was 1:40 for brucella. Conclusions PACNS is diagnosed by exclusion. The patient filled criteria for possible PACNS, image compatible with vascular stenosis, but inconclusive brain biopsy. Brucellosis is an endemic disease in underdeveloped countries that can present as CNS vasculitis. Metagenomic analysis allows the detection of different pathogens using a single method. The case illustrates the use of metagenomics in rare diseases characterized by vasculitis, with change in clinical outcomes and conduct.