Search Results (15)

Pituitary cells are specialized cells located within the pituitary gland, a small, pea-sized gland situated at the base of the brain. Through the use of cellular electrophysiological techniques, the electrical properties of these cells have been revealed. This review paper aims to introduce the ion currents that are known to be functionally expressed in pituitary cells. These currents include a voltage-gated Na⁺ current (I_Na), erg-mediated K⁺ current (I_K(erg)), M-type K⁺ current (I_K(M)), hyperpolarization-activated cation current (I_h), and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel. The biophysical characteristics of the respective ion current were described. Additionally, we also provide explanations for the effect of various drugs or compounds on each of these currents. GH₃-cell exposure to GV-58 can increase the magnitude of I_Na with a concurrent rise in the inactivation time constant of the current. The presence of esaxerenone, an antagonist of the aldosterone receptor, directly suppresses the magnitude of peak and late I_Na. Risperidone, an atypical antipsychotic agent, is effective at suppressing the I_K(erg) amplitude directly, and di(2-ethylhexyl)-phthalate suppressed I_K(erg). Solifenacin and kynurenic acid can interact with the K_M channel to stimulate I_K(M), while carisbamate and cannabidiol inhibit the I_h amplitude activated by sustained hyperpolarization. Moreover, the presence of either rufinamide or QO-40 can enhance the activity of single BK_Ca channels. To summarize, alterations in ion currents within native pituitary cells or pituitary tumor cells can influence their functional activity, particularly in processes like stimulus–secretion coupling. The effects of small-molecule modulators, as demonstrated here, bear significance in clinical, therapeutic, and toxicological contexts. Full article

The core subunits of the K_V7.2, K_V7.3, and K_V7.5 channels, encoded by the KCNQ2, KCNQ3, and KCNQ5 genes, are expressed across various cell types and play a key role in generating the M-type K⁺ current (I_K(M)). This current is characterized by an activation threshold at low voltages and displays slow activation and deactivation kinetics. Variations in the amplitude and gating kinetics of I_K(M) can significantly influence membrane excitability. Notably, I_K(M) demonstrates distinct voltage-dependent hysteresis when subjected to prolonged isosceles-triangular ramp pulses. In this review, we explore various small-molecule modulators that can either inhibit or enhance the amplitude of I_K(M), along with their perturbations on its gating kinetics and voltage-dependent hysteresis. The inhibitors of I_K(M) highlighted here include bisoprolol, brivaracetam, cannabidiol, nalbuphine, phenobarbital, and remdesivir. Conversely, compounds such as flupirtine, kynurenic acid, naringenin, QO-58, and solifenacin have been shown to enhance I_K(M). These modulators show potential as pharmacological or therapeutic strategies for treating certain disorders linked to gain-of-function or loss-of-function mutations in M-type K⁺ (K_V7x or KCNQx) channels. Full article

As the need for effective antiviral treatment intensifies, such as with the coronavirus disease 19 (COVID-19) infection, it is crucial to understand that while the mechanisms of action of these drugs or compounds seem apparent, they might also interact with unexplored targets, such as cell membrane ion channels in diverse cell types. In this review paper, we demonstrate that many different drugs or compounds, in addition to their known interference with viral infections, may also directly influence various types of ionic currents on the surface membrane of the host cell. These agents include artemisinin, cannabidiol, memantine, mitoxantrone, molnupiravir, remdesivir, SM-102, and sorafenib. If achievable at low concentrations, these regulatory effects on ion channels are highly likely to synergize with the identified initial mechanisms of viral replication interference. Additionally, the immediate regulatory impact of these agents on the ion-channel function may potentially result in unintended adverse effects, including changes in cardiac electrical activity and the prolongation of the QTc interval. Therefore, it is essential for patients receiving these related agents to exercise additional caution to prevent unnecessary complications. Full article

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: Our aim was to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. Methods: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. The obtained data were analysed using the program “IBM SPSS Statistics 29.0”. Haplotype analysis was performed using the online program “SNPStats”. Results: The TERC rs12696304 G allele of this SNP is associated with 1.4-fold lower odds of developing MS (p = 0.035). TERC rs35073794 is associated with approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G—rs1713418-A haplotype is statistically significantly associated with 1.75-fold increased odds of developing MS (p = 0.006). The rs12696304-C–rs35073794-A haplotype is statistically significantly associated with twofold decreased odds of developing MS (p = 0.008). In addition, the rs12696304-G—rs35073794-A haplotype was found to be statistically significantly associated with 5.3-fold decreased odds of developing MS (p < 0.001). Conclusion: The current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect. Full article

Background and Objectives: Periodontitis is a multifactorial inflammatory disease associated with biofilm dysbiosis and is defined by progressive periodontium destruction. Genes largely regulate this entire process. SIRTs are a group of histone deacetylases (HDACs) intimately involved in cell metabolism and are responsible for altering and regulating numerous cell functions. Understanding SIRTs and their functions in periodontitis may be useful for therapeutic treatment strategies in the future. The aim of our study was to investigate the associations amid SIRT1 single-gene nucleotide polymorphisms (rs3818292, rs3758391, and rs7895833) and SIRT1 serum levels for patients affected by periodontitis in the Caucasian population. Materials and Methods: The study included 201 patients affected by periodontitis and 500 healthy controls. DNA extraction from peripheral leukocytes was carried out using commercial kits. The real-time PCR method was selected for the determination of the genotype of the periodontitis patients and the control group. The ELISA method was used to measure the SIRT1 concentration. A statistical data analysis was performed using “BM SPSS Statistics 27.0” software. Results: The SIRT1 rs3818292 AG genotype was associated with a 2-fold and 1.9-fold increase in the development of periodontitis under the codominant and overdominant models (OR = 1.959; CI = 1.239–3.098; p = 0.004; and OR = 1.944; CI = 1.230–3.073; p = 0.004, respectively). The serum SIRT1 levels were not statistically significantly different between subjects in the periodontitis and control groups (0.984 (5.159) ng/mL vs. 0.514 (7.705) ng/mL, p = 0.792). Conclusions: in our study, the genotypes and alleles of SIRT1 rs3818292, rs3758391, and rs7895833 statistically significantly differed between the periodontitis and control groups, exclusively in the male population and subjects older than 60 years. Full article

Background and objective: Optic neuritis (ON) is characterized by painful, usually monocular vision loss with decreased visual acuity and defects of the visual field and color vision. The etiology and pathophysiology of ON is not completely clear. It is thought that a matrix metalloproteinase 2 (MMP-2) gene plays an essential role in this autoimmune inflammatory disease. The aim of this study was to determine the relationship between the MMP-2 (-1306 C/T) rs243865 gene polymorphism and ON, and that of ON with multiple sclerosis. Materials and methods: Patients with ON/ON and multiple sclerosis and a control group of healthy individuals were enrolled in this study. The genotyping test of the MMP-2 (-1306 C/T) was carried out using a real-time polymerase chain reaction (PCR) method. Results: Analysis revealed that T allele at the MMP-2 (-1306 C/T) was less frequent in the ON group compared to the control group (14.5% vs. 23.3%, p = 0.031), and was associated with decreased likelihood of ON development (OR = 0.566; 95% CI: 0.333-0.962; p = 0.036). No significant associations were revealed while comparing the subgroups of ON patients with and without multiple sclerosis. Conclusion: The MMP-2 (-1306 C/T) gene polymorphism was found to be associated with ON development. Full article

Age-related macular degeneration (AMD) affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people aged more than 60 years. This disease affects 2.5 million individuals in Europe. AMD is caused by both environmental and genetic factors. Numerous risk factors have been reported, but the pathogenesis of AMD is complex and fairly understood. Age, female gender, obesity, race, education status, family history, hyperopia, iris color, cigarette smoking, previ- ous cataract surgery, history of cardiovascular and cerebrovascular disease, diabetes, sunlight exposure and many other factors have been shown to be associated with AMD development. Scientific evidence shows that genes may play a role in the development of nearly 3 out of 4 cases of this devastating eye disease. The genes that have been shown to be associated with AMD are genes encoding complement system components such as CFH, C2, C3, CFB, and other. Full article

Background and objective: To determine the association between age-related macular degeneration (AMD) and color perception established by the Farnsworth–Munsell 100 hue (F–M 100) and maximum color contrast sensitivity (MCCS) tests.
Materials and methods: We performed a case–control study, which comprised of 100 patients with AMD and 100 healthy controls. To test visual acuity (VA), a typical Snellen chart was used. The computerized F–M 100 and MCCS programs were used for color discrimination.
Results: The results of VA, and the F–M 100 and MCCS tests in the healthy controls were statistically significantly better than in the patients with AMD (1.0 vs. 0.82 ± 0.16, P = 0.005; 87.39 ± 24.11 vs. 185.39 ± 74.43, P = 0.005; 1.33 ± 1.17 vs. 1.96 ± 0.46, P = 0.005, respectively). When VA was 1.0 in patients with AMD, the total error scores of the F–M 100 test and MCCS test compared with healthy persons were even worse (166.09 ± 66.57 vs. 87.39 ± 24.11, P = 0.002; 1.67 ± 0.92 vs. 1.33 ± 1.17, P = 0.001, respectively). Analysis of the results of patients with AMD compared to healthy controls showed the highest error score in the blue color range.
Conclusions: The results of the color contrast sensitivity test decreased by half in patients with AMD compared with ophthalmologically healthy patients when they performed the F–M 100 test and by one and half when they performed a MCCS test in the blue color range. Full article

Objective. The aim of this study was to assess age-related visual functions (visual acuity and contrast sensitivity) and compare the results by different age groups.
Material and Methods. A total of 231 patients were examined. The patients were divided into 5 age groups: 10 patients in group 1, 30–39 years; 40 patients in the group 2, 40–49 years; 77 patients in the group 3, 50–59 years; 71 patients in the group 4, 60–70 years; and 33 patients in the group 5, 71–85 years. A typical Snellen’s chart (the direction of the gap in Landolt C) was used for noncorrected and best-corrected visual acuity testing. Contrast sensitivity was evaluated by employing a Ginsburg Box, VSCR-CST-6500.
Results. Noncorrected visual acuity was significantly better in the group 2 than the group 3 (0.86 [0.28] vs. 0.69 [0.33], P=0.018). Moreover, noncorrected and best-corrected visual acuity was significantly better in the group 4 than the group 5 (0.52 [0.35] vs. 0.35 [0.28], P<0.001; and 0.9 [0.21] vs. 0.69 [0.27], P<0.005, respectively). Contrast sensitivity at the nighttime without glare was significantly worse in the group 2 than the group 1 at the spatial frequencies of 3, 12, and 18 cycles per degree (P=0.001, P=0.05, and P=0.01, respectively). The patients in the group 2 had significantly worse contrast sensitivity at the nighttime and daytime with glare at the spatial frequencies of 1.5, 12, and 18 cycles per degree (P=0.054, P=0.04, and P=0.01 and P=0.011, P=0.031, and P=0.011, respectively). The greatest differences in contrast sensitivity were observed between the groups 4 and 5, and it was 2 to 4 times better in the group 4. Comparing these groups, all the differences at the nighttime and daytime with and without glare were significant.
Conclusions. Contrast sensitivity was worst among the oldest persons (71–85 years), and it began to worsen already in the persons aged 40–49 years. Contrast sensitivity was very similar in the age groups of 40–49 and 50–59 years. Full article

Background and Objective. The aim of this study was to evaluate associations between visual functions (visual acuity, perimetry, optic nerve disc condition, and color contrast sensitivity) and pituitary adenoma (PA) diameter.
Material and Methods. In the study, 20 patients with PA, which was confirmed by computed tomography or magnetic resonance imaging scans, were examined. The patients were divided into 2 groups: those with a PA diameter of ≤1 cm (14 eyes) and with a PA diameter of >1 cm (26 eyes). The control group comprised 40 healthy age- and gender-matched persons (80 eyes). The diameter of PA, visual acuity, and perimetry were analyzed; the F-M 100 hue test for color discrimination was used in patients with PA.
Results. Visual acuity was better in the control group as compared with both groups of patients (1.0 vs. 0.90 [SD, 0.50] and 0.64 [SD, 0.21]; P=0.01; respectively). The results of the Farnsworth- Munsell 100 hue test were also better in the control group compared with the patients with PA of ≤1 cm and >1 cm (error score of 80.1 [SD, 53.0] vs. 131.8 [SD, 30.6] and 244.68 [SD, 51. 6], respectively; P=0.011). There was a very strong positive correlation between the error score of the F-M 100 hue test and PA diameter (r=0.905), but the correlation between the error score and visual acuity (r=–0.32), perimetry (r=0.21), and eye fundus changes (r=0.36) and PA diameter was weak.
Conclusions. Our results showed that PA can cause the impairments of visual acuity, perimetry, and color contrast sensitivity. The computerized F-M 100 hue test can be one of the methods for an early diagnosis of chiasm damage in patients with PA. Full article

The inherited macular dystrophies are characterized by different grade central visual loss and different character macula atrophy, because of retinal pigment epithelium lesion. The cause of photoreceptors degeneration is still not known. In this article, we review subjective and objective ophthalmological examines essential to diagnosis and differential diagnosis of inherited autosomal dominant and autosomal recessive macular dystrophies. It is known seven gene mutations (ABCA4, ELOVL4, PROML1, VMD2, Peripherin/RDS, TIMP3, XLRS), which may cause inherited macular dystrophies development. Inheritance type of inherited macular dystrophies, prevalence, beginning of disease, spread of the disease between female and male, clinic, electroretinography, electrooculography, differential diagnosis, genetic research and prognosis are also reviewed. Full article

Objective. The aim of our study was to determine if the genotype of the matrix metalloproteinase- 3 (MMP-3) gene might carry the risk of age-related macular degeneration (ARMD) in patients with myocardial infarction.
Material and Methods. A total of 499 patients with an acute myocardial infarction or with a history of myocardial infarction were enrolled into the study. They were subdivided into 2 groups: 273 patients with ARMD and 226 patients without ARMD. The control group comprised 560 persons from a random sample of the Lithuanian population. DNA was analyzed using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position –1171 of the MMP-3 gene promoter.
Results. Of the 499 patients with myocardial infarction, 47% had early-stage ARMD. The patients with ARMD were older than the patients in the group without ARMD (62.1±10.8 vs. 59.6±11.1, P<0.01). The analysis of MMP-3 gene polymorphism did not reveal any differences in the distribution of 5A/5A, 5A/6A, and 6A/6A genotypes between the ARMD group, non-ARMD group, and the control group (24.2%, 52.5%, and 23.3% in the ARMD group; 28.7%, 51.9%, and 19.4% in non-ARMD group; and 25.7%, 49.3% and 25.0%, in the control group, respectively). Conclusions. MMP-3 gene polymorphism had no predominant effect on the development of ARMD in patients with myocardial infarction. Full article

Coats’ disease is an idiopathic disorder defined by an abnormal development of retinal vessels with a progressive deposition of intraretinal or subretinal exudates, leading to exudative retinal detachment. The most difficult task is to differentiate Coats’ disease from retinoblastoma. We present a rare case of Coats’ disease diagnosed in a 3-year-old girl. From the age of 6 months, the girl was followed up 2 times a year at the Department of Ophthalmology, Hospital of Lithuanian University of Health Sciences, due to congenital convergent strabismus and refractive errors. At the age of 3.6 years, a routine examination of the fundus of the right eye revealed hard exudates, telangiectasia and tortuosity, gray color lesion below the optic nerve disc, submacular exudation in the inferior nasal part of the retina, and exudative retinal detachment, which extended from the 7-o’clock position to the 4-o’clock position. Before this examination, no abnormalities were found in the fundus of her both eyes. The girl was not treated with laser photocoagulation, cryocoagulation, or intravitreal injections, as the diagnosis of retinoblastoma could not be excluded; therefore, only eye drops were prescribed. In order to exclude the diagnosis of retinoblastoma, ultrasonography, magnetic resonance imaging, and computed tomography were carried out, and an appointment to see an ophthalmic oncologist was scheduled. Due to early and appropriate treatment, the progression of Coats’ disease in patients could be arrested. However, in some cases, when the diagnosis is ambiguous, it is better to follow up the patient and to treat only with eye drops. Full article

Tyrimo tikslas. Nustatyti ribinio spalvinio kontrastinio jautrumo ir Munsell-Farnsworth 100 atspalvių atrinkimo tyrimų rodmenų ir regėjimo aštrumo sąsajas, esant regos nervo disko drūzų.
Tyrimo medžiaga ir metodai. Atliktas 137 pacientų atvejo–kontrolės tyrimas. Ištirti 37 pacientai (67 akys), kuriems diagnozuotos regos nervo disko drūzos ir 100 sveikų žmonių (200 akių) kontrolinė grupė. Nekoreguotas ir geriausias koreguotas regėjimo aštrumas vertintas naudojant Landolto žiedus (C optotipais), pagal Sneleno principą. Spalvinio kontrastinio jautrumo tyrimui naudoti kompiuteriniai Farnsworth-Munsell 100 atspalvių ir ribinio spalvinio kontrastinio jautrumo tyrimai.
Rezultatai. Kontrolinės grupės tiriamųjų, ribinis spalvinis kontrastinis jautrumas ir Farnsworth- Munsell 100 atspalvių atrinkimo tyrimo rezultatai buvo geresni nei pacientų (1,94±0,66 palyginti su 2,2±0,85, p=0,02; 94,1±53,9 palyginti su 120,6±61, p=0,003, atitinkamai). Išvada. Tyrimo duomenimis, regos nervo disko drūzos susijusios su spalvų juslės sumažėjimu. Full article

Age-related macular degeneration affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people older than 60 years. The pathogenesis of age-related macular degeneration is complex and not completely understood. It is thought that age-related macular degeneration has a multifactorial etiology, the development of which may be caused by interrelation of environmental and genetic factors and body characteristics. In this article, risk factors such as age, gender, cigarette smoking, color of the iris, nutrition, body mass index, oxidative stress, and genetic factors (complement factor H gene, Apo E gene, and others) are reviewed. Here, choroidal neovascularization process, in which hypoxia, inflammatory process, and proteolytic enzymes play a determinant role, is discussed. Considerable attention is paid to genetic polymorphism of matrix metalloproteinases, especially to matrix metalloproteinases 2 and 9, respectively gelatinases A and B, also to matrix metalloproteinase 9. Full article