Recently, influence of bacteria colonization on development and maturation of gut wall is getting more into the focus of gastrointestinal research. For years, the main interest and research were ...aimed to the development and maturation of gut wall and its functional properties in normal conditions, less attention has been paid on the germ-free animals. Germ-free (GF) piglets have clear microbiological background and are reared in sterile environment. GF piglets are regarded as clinically relevant models for studying of human diseases, as these piglets’ manifest similar clinical symptoms to humans. In this study we briefly summarised the main characteristics in the distribution of goblet cells in the wall of jejunum and colon of GF piglets as healthy control (HC) group and piglets, which were experimentally infected by E. coli O149:K88 as ECK group. Neutral mucins were stained with periodic acid-Shiff (PAS) whereas acidic mucins are stained with Alcian blue. Numbers of goblet cells containing total acidic mucins in both, the jejunum and colon, differed significantly between HC and ECK piglets and in the colon, a similar trend was also observed. In the ECK piglets, jejunal goblet cells exhibited decrease in neutral mucins. This change in mucin profile in response to bacterial colonization suggests a potential role as a protective mechanism against pathogenic invasion of the intestinal mucosa during of gut mucosa development in piglets.
•A variety of pyrethroids and their metabolites have the potential to affect the reproductive system.•Dose-dependent effects on reproduction are associated with exposure across pyrethroid types.•Some ...pyrethroids cause morphometric and structural changes in the female genital organs.•The potential hormonal activity of pyrethroids showed that certain pyrethroids and their metabolites have multiple effects on the endocrine system.
Pyrethroids have been associated with a range of toxicological effects on various organs in animals.Recent animal studies suggest that neurodevelopmental, reproductive, and immunological effects may result following exposure to some pyrethroids at levels below those that induce overt signs of neurotoxicity. A variety of pyrethroids and their metabolites have the potential to affect the reproductive system. Dose-dependent effects on reproduction are associated with exposure across pyrethroid types. In mammals, permethrin and tetramethrin and cypermethrin have been found to be associated with adverse effects at high doses. Fenvalerate, deltamethrin, cypermethrin, caused morphometric and structural changes in the female genital organs. These pyrethroids affect ovulation, cause atresia of follicles, decrease the number of follicular cells, oocytes and corpora lutea and induce vesicular atrophy of the endometrial glands. The potential hormonal activity of pyrethroids showed that certain pyrethroids and their metabolites have multiple effects on the endocrine system. The level of steroid hormones, such as progesterone and estradiol, was inhibited. The pyrethorids may have the potential to mimic estrogens or to inhibit estrogen action. Some metabolites of pyrethroids, in particular permethrin and cypermethrin, are more likely to interact with the cellular estrogen receptors than the parent pyrethroids. Though several pyrethroids posses low toxicity, some pyrethroids, such as deltamethrin, cypermethrin, fenvalerate and bifenthrin have showed considerable toxicity.
Conazoles are azole antifungals used in agricultural and pharmaceutical products. Exposure to conazole fungicides leads to several toxic endpoints, including reproductive and endocrine. The results ...of animal experiments have shown that various conazole fungicides at high doses affect the structure and functions of reproductive organs. In males, adverse effects of conazole fungicides are manifested in the testes, prostate, sperm viability, fertility and sexual behaviour. Reduced testis weight, testis atrophy and reduced or absent sperm production were frequently observed. In female genitalia, structural changes in the ovaries and uterus have been observed. The extent of the changes depends on the dose and duration of treatment. Triazoles affected the expression of multiple genes involved in steroid hormone metabolism and modulate enzyme activity of multiple cytochrome P450 (CYP) and other metabolic enzymes in mammalian liver and other tissues. Conazole fungicides act as endocrine disruptors. Conazoles have been reported to reduce oestradiol and testosterone production and to increase progesterone concentration, indicating the inhibition of enzymes involved in the conversion of progesterone to testosterone. The reproductive effects are consistent with impairment of testosterone homeostasis. The disruption in steroid homeostasis is a common mode of action, leading to abnormal reproductive development and diminished reproductive function. At high doses, azole fungicides affect reproductive organs and fertility in several species.
We focused on investigating the influence of Escherichia coli (E. coli) on the intestinal barrier.
We studied changes in the distribution and secretory activities of goblet cells and enteroendocrine ...cells (EECs), as well as changes in the population of mast cells (MCs) in the jejunal and colonic mucosa of germ-free (GF) piglets as a healthy control group and GF piglets whose intestines were colonised with E. coli bacteria on day 5.
The results suggest that the colon of GF piglets is more resistant and less prone to coliform bacterial infection compared to the jejunum. This can be confirmed by a lower degree of histopathological injury index as well as an improvement of the morphometric parameters of the colonic mucosa, together with a significantly increased (p < 0.05) expression of MUC1/EMA, and ZO-3. We also observed a significant decrease in the population of activated MCs (p < 0.001) and EECs (p < 0.001). These findings may indicate a rapid response and better preparation of the intestinal barrier for possible pathological attacks and the subsequent development of mucosal lesions during the development and progression of the intestinal diseases.
To date, gut-targeted therapeutic approaches that can modulate bacterial translocation and chronic inflammation are still in their infancy but represent one of the most promising areas of research for the development of new effective treatments or clinical strategies in the future. Therefore, a better understanding of these processes can significantly contribute to the development of these targeted strategies for disease prevention and treatment.
•We studied goblet cells and enteroendocrine cells in jejunal and colonic epithelium of germ-free piglets (HC group) and GF piglets infected by E. coli (ECK group).•We investigated changes in intestinal mucosal mast cells and evaluated the intestinal mucosal barrier and its changes after E. coli infection.•We also briefly summarised the differences in the histopathological index of injury of the jejunum and colon wall in HC piglets and ECK piglets.•Results indirectly confirm higher resistance of colon to E. coli, probably due to more effective immune and neuroendocrine cells cooperation.
Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), known as Hashimoto's encephalopathy (HE), represents a heterogeneous group of neurological and neuropsychiatric ...symptoms associated with a presence of antithyroid antibodies in case of other causes of encephalopathy were excluded. Clinical symptoms most commonly includes acute onset of encephalopathy, behaviour changes and cognitive dysfunction, epileptic seizures as well as cerebellar and extrapyramidal symptoms. Corticoids provides rapid and sustained therapeutic benefit in most patients and only a few patients require other immunosuppressive therapy such as plasmapheresis, intravenous immunoglobulins, or others. We present the cases of two patients with acute onset of encephalopathy, status epilepticus based on SREAT, with rapid improvement after steroid treatment.
Idiopathic REM-sleep behavior disorder (iRBD) is considered the most specific prodromal marker of Parkinson's disease (PD). With the need to improve early detection of prodromal α-synucleinopathies, ...several methods to identify peripheral α-synuclein (α-syn) pathology have been exploited in manifest and prodromal PD with varying diagnostic accuracy. Recently, a disease specific 5G4 antibody has been evaluated in skin biopsies of manifest PD patients. The aim of our study was to analyze the 5G4 α-syn immunoreactivity in skin biopsies of deeply phenotyped subjects with iRBD and controls.
The study cohort consisted of 28 patients with PD, 24 subjects with iRBD and 27 healthy controls, recruited from the CEGEMOD, PDBIOM and PARCAS cohorts. All subjects were deeply phenotyped and assessed for prodromal PD (pPD) probability based on MDS research criteria. Abdominal skin punch biopsies were processed and stained using a conformation specific 5G4 α-syn antibody as well as axonal markers SMI-31 and S100.
5G4-positivity was identified in 23/28 PD patients, 20/24 iRBD subjects and 8/27 healthy controls. Compared to healthy controls, sensitivity and specificity reached 83.33 % and 70.37 % for iRBD; and 82.14 % and 70.37 % for PD, respectively. 5G4-positivity rate in our study was irrespective of the calculated pPD probability of iRBD subjects.
This work establishes the diagnostic yield of conformation specific 5G4 α-syn antibody testing in skin biopsies of subjects with pPD, specifically iRBD. The diagnostic accuracy for this method seems to be similar for both manifest and prodromal PD and is not dependent on the pPD probability ratios.
•5G4 synuclein antibody identifies PD and iRBD subjects in skin biopsies.•5G4-positivity in iRBD was irrespective of the calculated prodromal PD probability.•Higher overall load of 5G4-positive structures was detected in iRBD compared to PD.•Distribution of 5G4-positive structures in dermis of patients with PD and iRBD showed the same percentage trend.
Intestinal ischemic-reperfusion (IR) injury has detrimental effects on both local and distant organs in the body. Betanin is known for its antioxidant properties, and it is found mostly in ...vegetables. Therefore, the aim of the present study was to test the hypothesis that betanin administration prior intestinal IR, may be beneficial in protecting jejunal mucosa and lung parenchyma against IR damage. Male specific pathogen-free Charles River Wistar rats were used (n = 42). Betanin (50 mg/kg) was administered intraperitoneally 30 min before ischemia of the superior mesenteric artery lasting 1 h, followed by 1, 4 and 24 h of reperfusion. Immunohistochemical as well as histomorphometrical analysis indicated a protective effect of betanin pretreatment on jejunal tissue. Regarding morphometrical analysis betanin significantly (p < 0.01) augments intestinal villus height after 24 of reperfusion comparing to early stages. Betanin application reduced number of mast cells population in early reperfusion periods (p < 0.05). The protective effect of betanin on lung parenchyma, was detected in late reperfusion period (24 h) with improvement of histopathological injury index and morphometric analysis (p < 0.001 for both). The improvement of histopathological injury index (p < 0.001) and morphometric analysis (p < 0.001) during the late reperfusion period, suggests a protective effect of betanin on lung parenchyma. Moreover, suppression of the inflammatory response was mirrored by the reduction of myeloperoxidase (MPO) positive cells within lung parenchyma after 1 and 4 h of reperfusion (p < 0.001). Especially, during the first 4 h of reperfusion after betanin administration, a reduction of 74% of the polymorphonuclear neutrophils infiltration (MPO positive cell population) and of a nearly 46% of active MCs was observed. Upon morphometric examination, the lung histological architecture after 24 h of reperfusion appeared to be almost 100% better following betanin treatment, with 25% thinner interalveolar septa and 20% larger alveolar surface for respiratory gas exchange. The results suggest that betanin pretreatment protects the jejunal mucosa and the lung parenchyma, as well as reduces the inflammatory cell density after intestinal IR injury.
The enteric nervous system (ENS), considered as separate branch of the autonomic nervous system, is located throughout the length of the gastrointestinal tract as a series of interconnected ...ganglionic plexuses. Recently, the ENS is getting more in the focus of gastrointestinal research. For years, the main interest and research was aimed to the enteric neurons and their functional properties in normal conditions, less attention has been paid to the germ-free animals. Germ-free (GF) piglets have clear microbiological background and are reared in sterile environment. GF piglets are regarded as clinically relevant models for studying of human diseases, as these piglets’ manifest similar clinical symptoms to humans. In this study we briefly summarised the main characteristics in immunohistochemical distribution of ENS elements in the wall of jejunum and colon of germ-free piglets.