Introduction: Febrile seizures (FS) are the most common neurological disease in childhood. The etiology of FS is the subject of numerous studies including studies regarding genetic predisposition. ...Aim: The aim of the study was to analyze the association of TRPV1 rs222747 and KCC2 rs2297201 gene polymorphisms with the occurrence of FS. Materials and Methods: The study included 112 patients diagnosed with FS classified as simple febrile seizures (SFS) or complex febrile seizures (CFS). We analyzed selected polymorphisms of KCC2 and TRPV1 genes using the Real-time PCR method. Results: The CT and TT genotypes of the rs2297201 polymorphism of the KCC2 gene are significantly more common in the group of children with FS than the control group (p = .002) as well as the allele T of this polymorphism (p = .045). Additionally, genotypes CT and TT of the rs2297201 polymorphism of the KCC2 gene were more frequent in the group of children with CFS compared to the control group (p < .001). Different genotypes and alleles of the rs222747 TRPV1 gene polymorphism were not associated with the occurrence of febrile seizures or epilepsy, nor were associated with the occurrence of a particular type of febrile seizure (p = .252). Conclusion: These results indicate that the CT and TT genotypes, as well as the T allele of rs2297201 polymorphism of the KCC2 gene, could be a predisposing factor for the FS, as well as the occurrence of CFS.
Fruticin (amorphin) is a constituent of the fruit of the false indigo-bush (Amorpha fruticosa L.), which belongs to the class of rotenoid glycosides, and shows several interesting pharmacological ...activities. The aim of this study was to isolate and chemically characterize this natural product, as well as to determine the optimal period of the year for A. fruticosa fruits collection. Fruticin was obtained by re-crystallization of the precipitate that formed after partial evaporation of the extract, prepared by 3fold extraction of powdered plant material by chloroform - ethanol (1:1, v/v). The structure of the final product was determined by various techniques of instrumental analysis (NMR, UV and MS), and confirmed by comparing the obtained spectra with corresponding data in available literature. The content of fruticin in A. fruticosa fruit was determined by LC-DAD-MS, using the external standard method based on the constructed calibration curve. Limits of detection (LOD) and quantification (LOQ) were also determined. A substantial increase in fruticin content was observed during the ripening period (>50 %). It has also been established that the optimal time for fruit collection is mid-December. Obtained results indicate that the content of fruticin in the A. fruticosa fruit is highly dependable on the time of collection. Since the biosynthesis of secondary plant metabolites is influenced not only by the time of collection, but by numerous other factors as well, additional studies are needed to define, with greater certainty, the conditions that are necessary for design of prospective efficient and sustainable production process.
Cadmium (Cd) has been listed as one of the most toxic substances affecting numerous tissues/organs, including the immune system. Due to variations in studies examining Cd effects on the immune system ...(exposure regime, experimental systems, immune endpoint measured), data on Cd immunotoxicity in humans and experimental animals are inconsistent. However, it is clear that Cd can affect cells of the immune system and can modulate some immune responses. Due to the complex nature of the immune system and its activities which are determined by multiple interactions, the underlying mechanisms involved in the immunotoxicity of this metal are still vague. Here, the current knowledge regarding the interaction of Cd with cells of the immune system, which may affect immune responses as well as potential mechanisms of consequent biological effects of such activities, is reviewed. Tissue injury caused by Cd-induced effects on innate cell activities depicts components of the immune system as mediators/effectors of Cd tissue toxicity. Cd-induced immune alterations, which may compromise host defense against pathogenic microorganisms and homeostatic reparative activities, stress this metal as an important health hazard.
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•The complex structure of the immune system makes it a sensitive cadmium (Cd) target.•Cd-induced neutrophil inflammatory activities are responsible for tissue injury.•Cd can exert both stimulation and inhibition of mononuclear phagocytes.•Cd alters lymphocyte development.•Cd-induced alteration of cellular immune reactions increases susceptibility to pathogens.
To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd).
The effect of Cd on AhR activation (CYP1A1 and CYP1B1 mRNA expression) was examined ...in lung leukocytes of Cd-exposed rats (5 and 50 mg/L, 30 d orally) and by in vitro leukocyte exposure. The involvement of AhR signaling in the effects of Cd on the interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) lung leukocyte response was investigated in vitro using the receptor antagonist CH-223191.
Cd increased CYP1B1 (in vivo and in vitro) and CYP1A1 (in vitro) mRNA, indicating AhR involvement in the action of Cd. In response to Cd, lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels, but decreased IL-1β production due to reduced NLRP3. The AhR antagonist CH-223191 abrogated the observed effects of Cd on the cytokine response. The absence of AhR reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high AhR repressor mRNA level.
AhR signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd. The relevance of the AhR to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.
ObjectiveThe effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including the skin, in which it ...disturbs homeostasis, thus resulting in inflammation and injury. MethodsMale rats were evoked with experimental contact hypersensitivity reaction (CHS) to hapten dinitrochlorobenzene (DNCB), after prolonged (30 day) oral exposure to an environmentally relevant Cd dose (5 ppm). The ear cell population was analyzed with flow cytometry. Cytokine production by ear skin cells and the activity of skin-draining lymph node (DLN) cells were measured using enzyme-linked immunosorbent assay (ELISA). ResultsOrally acquired Cd (5 ppm) increased CHS intensity only in Dark Agouti (DA) rats by affecting inflammatory responses in both the sensitization (an increase of IFN-γ and IL-17 cytokine production) and challenge (an increase of CD8 + and CD4 + cell number and TNF, IFN-γ and IL-17 cytokine production) phases. An increased CHS reaction was seen in Albino Oxford (AO) rats only at a high Cd dose (50 ppm), during the challenge phase (an increase of CD8 + and CD4 + cell number and TNF, IFN-γ and IL-17 cytokine production). ConclusionThese novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.
•Cd accumulation in organs could cause inflammatory / autoimmune reactions.•Cd-induced responses contribute to tissue/organ injury and dysfunction.•Such reactions might be relevant for disease ...promotion and/or exacerbation.
Cadmium (Cd) represents a unique hazard because of the long biological half-life in humans (20–30 years). This metal accumulates in organs causing a continuum of responses, with organ disease/failure as extreme outcome. Some of the cellular and molecular alterations in target tissues can be related to immune-modulating potential of Cd. This metal may cause adverse responses in which components of the immune system function as both mediators and effectors of Cd tissue toxicity, which, in combination with Cd-induced alterations in homeostatic reparative activities may contribute to tissue dysfunction. In this work, current knowledge concerning inflammatory/autoimmune disease manifestations found to be related with cadmium exposure are summarized. Along with epidemiological evidence, animal and in vitro data are presented, with focus on cellular and molecular immune mechanisms potentially relevant for the disease susceptibility, disease promotion, or facilitating development of pre-existing pathologies.
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The use of anticoagulant rodenticides (ARs) is one of the most commonly employed management methods for pest rodents. ARs compete with vitamin K (VK) required for the synthesis of blood clotting ...factors in the liver, resulting in inhibition of blood coagulation and often animal death due to hemorrhage. Besides rodents (target species), ARs may affect non-target animal species and humans. Out of hemostasis disturbance, the effects of ARs may be related to the inhibition of proteins that require VK for their synthesis but are not involved in the coagulation process, to their direct cytotoxicity, and their pro-oxidant/proinflammatory activity. A survey of the cellular and molecular mechanisms of these sublethal/asymptomatic AR effects is given in this review. Data from field, clinical, and experimental studies are presented. Knowledge of these mechanisms might improve hazard characterization and identification of potential ecotoxicological risks associated with ARs, contributing to a safer use of these chemicals.
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•Anticoagulant rodenticides (ARs) affect blood coagulation causing hemorrhage•Basic effect is on the synthesis of vitamin-K (VK)- dependent coagulation proteins•ARs also affect other biological processes resulting in tissue injury/dysfunction•Effect on VK-dependent proteins not involved in hemostasis affect some tissues•Tissue toxicity may be caused by direct and/or pro-inflammatory ARs effects
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Cadmium (Cd) is a toxic heavy metal that when absorbed into the body causes nephrotoxicity and effects in other tissues.Anatomical barrier tissues are tissues that prevent the entry ...of pathogens and include skin, mucus membranes and the immune system. The adverse effects of Cd-induced immune cell’s activity are the most extensively studied in the kidneys and the liver. There are though fewer data relating the effect of this metal on the other tissues, particularly in those in which cells of the immune system form local circuits of tissue defense, maintaining immune-mediated homeostasis. In this work, data on the direct and indirect effects of Cd on anatomical barrier tissue of inner and outer body surfaces (the lungs, gut, reproductive organs, and skin) were summarized.
Since the realization that the lungs are not sterile but are normally inhabited by various bacterial species, studies have been conducted to define healthy lung microbiota and to investigate whether ...it changes during lung diseases, infections, and inflammation. Using next-generation sequencing, we investigated bacterial microbiota from whole lungs in two rat strains (previously shown to differ in gut microbiota composition) in a healthy state and during pulmonary infection caused by the opportunistic fungus Aspergillus fumigatus. No differences in alpha diversity indices and microbial composition between DA and AO rats before infection were noted. Fungal infection caused dysbiosis in both rat strains, characterized by increased alpha diversity indices and unchanged beta diversity. The relative abundance of genera and species was increased in DA but decreased in AO rats during infection. Changes in lung microbiota coincided with inflammation (in both rat strains) and oxidative stress (in DA rats). Disparate response of lung microbiota in DA and AO rats to pulmonary fungal infection might render these two rat strains differentially susceptible to a subsequent inflammatory insult.
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