Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such transrepression are not fully understood. In this study, the dynamics of coregulator recruitment to BSEP promoter after FXR activation and E2 treatment were established with quantitative chromatin immunoprecipitation assays. Coactivator peroxisome proliferator-activated receptor-γ coactivator-1 was predominantly recruited to the BSEP promoter upon FXR activation, and its recruitment was decreased by E2 treatment. Meanwhile, recruitment of nuclear receptor corepressor was markedly increased upon E2 treatment. Functional evaluation of ERα and ERβ chimeras revealed that domains AC of ERα are the determinants for ERα-specific transrepression on BSEP. Further studies with various truncated ERα proteins identified the domains in ERα responsible for ligand-dependent and ligand-independent transrepression. Truncated ERα-AD exhibited potent ligand-independent transrepressive activity, whereas ERα-CF was fully capable of transrepressing BSEP ligand dependently in vitro in Huh 7 cells and in vivo in mice. Both ERα-AD and ERα-CF proteins were associated with FXR in the coimmunoprecipitation assays. In conclusion, E2 repressed BSEP expression through diminishing peroxisome proliferator-activated receptor-γ coactivator-1 recruitment with a concurrent increase in nuclear receptor corepressor recruitment to the BSEP promoter. Domains AD and CF in ERα mediated ligand-independent and ligand-dependent transrepression on BSEP, respectively, through interacting with FXR.
Recently, a large amount of evidence has been obtained on the possible involvement of inflammatory processes in epileptogenesis. Thus, in a number of studies, an increase in the synthesis of specific inflammatory mediators in the brain of patients and, accordingly, the activation of some pro-inflammatory pathways in the foci of seizures, as well as the participation of oxidative stress, was found. There was also information that some chronic infections, such as neurocistercosis, HIV and herpes, without causing acute cerebral pathology, can provoke epileptic seizures and even the formation of refractory epilepsy in the future. This review summarizes the experimental and clinical data from studies on the relationship between epilepsy and chronic infectious diseases and neuroinflammation.
Objective. Clinical-neurophysiological and neuropsychological examination of patients with bruxism was conducted to determine the functional condition of the peripheral and central trigeminal nerve and to justify the combined therapy.Materials and methods. 26 patients (14 women and 12 men) aged 20 to 50 years with complaints and typical neurological symptoms of bruxism were examined. The control group consisted of 30 volunteers in the age from 24 to 35 years, who underwent a comprehensive examination as part of a medical check-up, who did not have severe somatic, neurological or mental diseases and did not have complaints of impaired function of the masticatory muscles. Clinical and neurological, electrophysiological and neuropsychological diagnostic methods were used in the trial. Quantitative sensory testing was performed using TSA II device (Medoc, Israel), and temperature sensitivity thresholds were determined using the Marstok method on symmetrical facial areas according to the Zelder zones. Diagnostics of the functional condition of the masticatory muscles was carried out using a computer neuroelectromyograph M-Test ‘DX-Systems’ and a computer system for analyzingelectromyographic records. Electroencephalography (EEG) was performed using 16-channel computer electroencephalography system. C. D. Spielberger scale adapted by Yu. L. Khanin (C. D. Spielberger, 2010) was used to determine the level of anxiety. The results were processed using Statistica and Microsoft Excel 2015 programs.Results. Patients with bruxism had a high level of personal anxiety, which was found in 73 % of the participants. Determination of the thresholds of cold sensitivity on the faces of patients with bruxism showed a lower threshold of cold sensitivity in the lateral parts and a higher threshold in the oral parts. Electromyography of masticatory muscles showed an increase in the duration of mastication period, a decrease in the masticatory rhythm, a decrease in masticatory efficiency, and irrational functioning of the masticatory muscles of varying severity in the patients of the examined group. Assessment of brain biopotentials showed an increase in the ascending activating effects of nonspecific median brain structures (72 %). The data obtained helped to obtain a comprehensive assessment of functional condition of the trigeminal nerve in patients with bruxism and to justify pharmaceutical therapy aimed at both the muscular apparatus (muscle relaxants) and the peripheral and central parts of the trigeminal nerve (antiepileptic drugs) in combination with a medicine that has a stabilizing effect on the functional condition of neurons and normalization of bioelectric processes in the central nervous system (correctors of metabolism).
This literature review is devoted to the problem of epilepsy caused by pituitary neuroendocrine tumors: their detailed classification with the latest recommendations of the World Health Organization 2022, clinical picture of each variant of pituitary neuroendocrine tumor in a complex multidisciplinary approach are considered. The main feature of the review is a detailed consideration of the epilepsy associated with this condition, which is considered to be a rather rare manifestation of the disease (incidence in patients is 0.5 %), due to which very few cases of epilepsy in patients with pituitary adenoma have been described in the literature. Our work has analyzed the fundamental works of domestic scientists in this field, as well as current information from foreign sources and most of the available clinical cases of epilepsy in this group of patients, revealing in detail the pathogenesis of epilepsy at all levels, including molecular changes. Modern techniques for the treatment approach in this group of patients are also described, the effectiveness of drug and surgical therapy is analyzed according to the criteria of the frequency of long-term persistent remission and recurrence, side effects of drugs and complications of transsphenoidal tumor resection are reviewed, including in terms of possible epilepsy; conclusions about the most rational and effective approach to treatment of various types of hypophysial neuroendocrine tumors are drawn.
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