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1.
Int J Mol Sci ; 24(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38139396

RESUMO

Experimental studies reveal that caffeine (trimethylxanthine) at subconvulsive doses, distinctly reduced the anticonvulsant activity of numerous antiseizure medications (ASMs) in rodents, oxcarbazepine, tiagabine and lamotrigine being the exceptions. Clinical data based on low numbers of patients support the experimental results by showing that caffeine (ingested in high quantities) may sharply increase seizure frequency, considerably reducing the quality of patients' lives. In contrast, this obviously negative activity of caffeine was not found in clinical studies involving much higher numbers of patients. ASMs vulnerable to caffeine in experimental models of seizures encompass carbamazepine, phenobarbital, phenytoin, valproate, gabapentin, levetiracetam, pregabalin and topiramate. An inhibition of R-calcium channels by lamotrigine and oxcarbazepine may account for their resistance to the trimethylxanthine. This assumption, however, is complicated by the fact that topiramate also seems to be a blocker of R-calcium channels. A question arises why large clinical studies failed to confirm the results of experimental and case-report studies. A possibility exists that the proportion of patients taking ASMs resistant to caffeine may be significant and such patients may be sufficiently protected against the negative activity of caffeine.


Assuntos
Anticonvulsivantes , Cafeína , Humanos , Lamotrigina/farmacologia , Lamotrigina/uso terapêutico , Oxcarbazepina/uso terapêutico , Cafeína/farmacologia , Cafeína/uso terapêutico , Topiramato/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Canais de Cálcio
2.
Orphanet J Rare Dis ; 18(1): 257, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37653408

RESUMO

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disorder of PANK2, which enables mitochondrial synthesis of coenzyme A. Its loss causes neurodegeneration with iron accumulation primarily in motor-related brain areas. Symptoms include dystonia, parkinsonism, and other disabilities. PKAN has been categorized as classic PKAN, with an age of onset ≤ 10 years, rapid progression, and early disability or death; and atypical PKAN, with later onset, slower progression, generally milder, and more diverse symptom manifestations. Available treatments are mostly palliative. Information on the lived experience of patients with PKAN and their caregivers or on community-level disease burden is limited. It is necessary to engage patients as partners to expand our understanding and improve clinical outcomes. This patient-oriented research study used multiple-choice and free-form question surveys distributed by patient organizations to collect information on the manifestations and disease burden of PKAN. It also assessed respondents' experiences and preferences with clinical research to inform future clinical trials. RESULTS: The analysis included 166 surveys. Most respondents (87%) were parents of a patient with PKAN and 7% were patients, with 80% from Europe and North America. The study cohort included 85 patients with classic PKAN (mean ± SD age of onset 4.4 ± 2.79 years), 65 with atypical PKAN (13.8 ± 4.79 years), and 16 identified as "not sure". Respondents reported gait disturbances and dystonia most often in both groups, with 44% unable to walk. The classic PKAN group reported more speech, swallowing, and visual difficulties and more severe motor problems than the atypical PKAN group. Dystonia and speech/swallowing difficulties were reported as the most challenging symptoms. Most respondents reported using multiple medications, primarily anticonvulsants and antiparkinsonian drugs, and about half had participated in a clinical research study. Study participants reported the most difficulties with the physical exertion associated with imaging assessments and travel to assessment sites. CONCLUSIONS: The survey results support the dichotomy between classic and atypical PKAN that extends beyond the age of onset. Inclusion of patients as clinical research partners shows promise as a pathway to improving clinical trials and providing more efficacious PKAN therapies.


Assuntos
Distonia , Neurodegeneração Associada a Pantotenato-Quinase , Humanos , Criança , Lactente , Pré-Escolar , Cuidadores , Anticonvulsivantes , Encéfalo
3.
J Clin Med ; 12(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37373708

RESUMO

The aim of this study was to investigate the association between PMS (premenstrual syndrome)-related pain among young women following a particular type of diet during the COVID-19 pandemic. This was compared to the period before the pandemic. Furthermore, we aimed to determine whether the increase in the intensification of pain was correlated to their age, body weight, height and BMI, and whether there are differences in PMS-related pain between women who differ in their diet. A total of 181 young female Caucasian patients who met the criteria for PMS were involved in the study. Patients were divided according to the kind of diet they had followed during the last 12 months before the first medical evaluation. The rise in pain score was evaluated according to the Visual Analog Scale before and during the pandemic. Women following a non-vegetarian ("basic") diet had a significantly higher body weight in comparison to those on a vegetarian diet. Furthermore, a significant difference was noted between the level of intensification of pain before and during the pandemic in women applying a basic diet, a vegetarian and an elimination diet. Before the pandemic, women from all groups felt weaker pain than during the pandemic. No significant difference in the intensification of pain during the pandemic was shown between women with various diets, nor was there a correlation between intensification of pain and the girl's age, BMI, their body weight and also height for any of the diets applied.

4.
Neurol Neurochir Pol ; 57(2): 183-188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36537370

RESUMO

INTRODUCTION: Patients with cerebral palsy (CP) present mobility limitations altering their activity and participation in social life. The aim of this study was to assess changes in Gross Motor Function Classification System (GMFCS) and Functional Mobility Scale (FMS) in children with CP who received repeated BoNT-A injections within a rehabilitation treatment over a five-year follow-up period. MATERIAL AND METHODS: This retrospective, observational study included 200 consecutive children with bilateral CP (GMFCS I-IV). Annual assessments of the five-year follow-up period were analysed. RESULTS: The mean age of the patients at the beginning was 32.23 months (± 6.96). The GMFCS level improved in 67 (33.5%) (p < 0.001) and worsened in four (2%) children. In children with GMFCS III and IV levels, improvement was observed in 50% and 40%, respectively. FMS 5 and 50 metres improved in 54% and 52.5% of children respectively. CONCLUSIONS: Our study showed a significant, positive effect of integrated treatment on functional mobility in patients with CP.


Assuntos
Toxinas Botulínicas Tipo A , Paralisia Cerebral , Humanos , Criança , Pré-Escolar , Paralisia Cerebral/tratamento farmacológico , Estudos Retrospectivos , Toxinas Botulínicas Tipo A/uso terapêutico
5.
Healthcare (Basel) ; 10(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36553909

RESUMO

Human Papillomavirus (HPV) is the main cause of cervical cancer and genital warts and constitutes one of the most common sexually transmitted infections. Cervical cancer is the only reproductive cancer that has a primary prevention programme through the introduction of HPV vaccinations. Even though the majority of European countries have nationally funded HPV vaccination programmes, in Poland these are exclusively local and scarcely funded. Moreover, the majority of local programmes are directed to females only. Meanwhile, Poland has one of the highest cervical cancer incidence rates among high income countries. The aim of this study was to measure HPV vaccination levels among final-year students in Poland and to establish the association between vaccination status and gender, region and level of sexual education received. This study is a part of the POLKA 18 Study, which used original self-reported paper-based questionnaires distributed in schools in six Polish regions. The study was conducted between April and December 2019. The obtained data were analysed in STATA 17. In total, 2701 fully completed questionnaires were collected. Over half of the respondents (58.2%) did not know their HPV vaccination status. Only 16.0% of the respondents replied that they have been vaccinated against HPV (18.2% of females and 14.5% of males). There was no direct association between vaccination status and access to 'family life education' classes. The vaccination level significantly differed among the different regions of Poland (p < 0.0001), with the Slaskie and Wielkopolskie regions achieving the highest rates. At least a quarter of adolescents after their sexual debut have not been vaccinated against HPV. Regions with immunization programmes introduced to their provincial capitals had higher vaccination rates. Our findings indicate the need for the introduction of state-funded vaccination programmes at the national level for the vaccination rate to increase, which will have the potential to decrease cervical cancer incidence in the country.

6.
J Clin Med ; 11(19)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36233690

RESUMO

Patients with endometriosis had limited possibilities for contemporary diagnosis and treatment during the SARS-CoV-2 (COVID-19) pandemic. Surgeries that may have eliminated pain or restored fertility were postponed. Endometriosis may affect the vagina, peritoneum, bladder, or other organs outside the pelvis and impact women's sexual health, especially during pandemics. Holistic care of patients is crucial to improving their lives and sexual health. A scoping review was conducted to analyze the relevant literature in light of our experience in gynecology and physiotherapy during the COVID-19 pandemic.

7.
Healthcare (Basel) ; 10(10)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36292396

RESUMO

HIV data for 2020 show a decline in the number and rate of new HIV cases diagnosed in the EU during the last decade. The COVID-19 pandemic has paralyzed the functioning of healthcare facilities in Poland and worldwide, also impacting the detection of HIV infection. Early diagnosis of HIV and implementation of antiretroviral treatment limit HIV transmission. A woman with HIV diagnosed during pregnancy should be under the care of a specialist in infectious diseases experienced in antiretroviral treatment. In this way, she will be properly protected during the delivery, and relevant medications can be implemented for the newborn baby. Taking these aspects into account, the medical team should consist of: A specialist in infectious diseases, an obstetrician, a neonatologist and pediatrician, a midwife, and a dermato-venereologist. Every effort should be made to increase the scope and quality of monitoring of the spread of the epidemic in Poland, with special emphasis on diagnostics based on specific tests among populations particularly exposed to HIV infections cooperating with non-governmental organizations.

8.
Vaccines (Basel) ; 10(10)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36298441

RESUMO

One of the groups most vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is healthcare workers (HCWs) who have direct contact with suspected and confirmed coronavirus diseases 2019 (COVID-19) patients. Therefore, this study aimed to (i) conduct a longitudinal analysis of the seroprevalence of SARS-CoV-2 infection among HCWs working in two healthcare units (HCUs) in Poland and (ii) identify anti-SARS-CoV-2 IgG antibody (Ab) response factors following infection and anti-COVID-19 vaccination. The overall seroprevalence increased from 0% at baseline in September 2020 to 37.8% in December 2020. It reached 100% in February 2021 after BNT126b2 (Pfizer New York, NY, USA/BioNTech Mainz, Germany) full vaccination and declined to 94.3% in September 2021. We observed significant differences in seroprevalence between the tested high- and low-risk infection HCUs, with the highest seropositivity among the midwives and nurses at the Gynecology and Obstetrics Ward, who usually have contact with non-infectious patients and may not have the proper training, practice and personal protective equipment to deal with pandemic infections, such as SARS-CoV-2. We also found that anti-SARS-CoV-2 Ab levels after coronavirus infection were correlated with disease outcomes. The lowest Ab levels were found among HCWs with asymptomatic coronavirus infections, and the highest were found among HCWs with severe COVID-19. Similarly, antibody response after vaccination depended on previous SARS-CoV-2 infection and its course: the highest anti-SARS-CoV-2 Ab levels were found in vaccinated HCWs after severe COVID-19. Finally, we observed an approximately 90-95% decrease in anti-SARS-CoV-2 Ab levels within seven months after vaccination. Our findings show that HCWs have the highest risk of SARS-CoV-2 infection, and due to antibody depletion, extra protective measures should be undertaken. In addition, in the context of the emergence of new pathogens with pandemic potential, our results highlight the necessity for better infectious disease training and regular updates for the low infection risk HCUs, where the HCWs have only occasional contact with infectious patients.

9.
Front Physiol ; 13: 911636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111161

RESUMO

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.

10.
Antioxidants (Basel) ; 11(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36009196

RESUMO

Oxidative stress has been implicated in many diseases, including reproductive and pregnancy disorders, from subfertility to maternal vascular disease or preterm labour. There is, however, discrepancy within the standardized markers of oxidative stress in obstetrics and gynaecology in clinical studies. This review aims to present the scope of markers used between 2012 and 2022 to describe oxidative stress with regard to reproduction, pregnancy, and pregnancy-related issues. Despite the abundance of evidence, there is no consensus on the set of standardised markers of oxidative stress which poses a challenge to achieve universal consensus in order to appropriately triangulate the results.

11.
Antioxidants (Basel) ; 11(6)2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35740015

RESUMO

Movement is a physiological phenomenon and a fundamental aspect of the living human body in a global context (e.g., musculoskeletal system function) and local one (e.g., visceral system function). The local activity of the body is expressed in the rhythm of pulsations, peristalsis and vibrations. Visceral therapy supports movement, articulation and tissue rhythm. The use of visceral treatment for pain is complementary and is relevant for pregnant women. Maintaining the mobility and motility of internal organs by means of visceral techniques can regulate anatomical relations and physiological processes within the urogenital diaphragm. The role of physical activity is also important. A scoping review was conducted to analyze the relevant literature on pain in pregnant women, the role of visceral therapy in pregnant women and oxidative stress. Eligible articles presented aspects of the occurrence of pain in locomotive organs in pregnant women, the use of visceral therapy in pain management, and the reduction of oxidative stress. The use of visceral therapy and physical activity in the treatment of pain is complementary and also important for pregnant women, and so may have an effect on reducing oxidative stress in pregnant women.

12.
Ginekol Pol ; 93(12): 1018-1027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36602196

RESUMO

Proper diet and physical activity are a form of prevention of female genital prolapse disorders. The causal substrate of pelvic floor dysfunction is multifactorial. Fifty percent of women over the age of 50 have pelvic organ prolapse, often accompanied by urinary incontinence. It is a complicated social and medical (urogynecological and sexological) problem. The authors conducted a literature review on the role of visceral therapy, Kegel and core stability exercises and diet in pelvic support disorders and urinary incontinence. The eligible articles provided insights into sexological factors, as well as the role of osteopathy and physiotherapy. These results provide new insights into the relevance of clinical practice. In addition to standard treatment methods used in gynaecology, sexology, physiotherapy and osteopathy (e.g., visceral therapy), Kegel muscle and core stability exercises are becoming increasingly important. The aim of visceral therapy is to restore the mobility of the organs while reducing increased tension and improving blood and lymph circulation. This has the effect of reducing pain sensations, thereby influencing the function of the uterus and ovaries.


Assuntos
Estabilidade Central , Incontinência Urinária , Feminino , Humanos , Incontinência Urinária/terapia , Modalidades de Fisioterapia , Dieta , Músculos
13.
Front Bioeng Biotechnol ; 9: 773123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917599

RESUMO

Processing of MSCs to obtain a therapeutic product consists of two main steps: 1) the in vitro expansion of the cells until an appropriate number of them is obtained, and 2) freezing and storage of the expanded cells. The last step is critical and must be optimized so that after thawing the cells retain all their physiological properties including the secretory function. In this paper, we evaluated physiological parameters of AT-MSC's after a full cycle of their processing, particularly freezing and storing at the liquid nitrogen vapor temperature. Based on the recovered proliferative and secretory capacities of the thawed cells, we have designed the optimal technique for processing of MSCs for clinical applications. In our work, we tried to select the best DMSO-based cryoprotectant mixture on the base of post thawing fully retain their properties. We have demonstrated the effectiveness of the use of DMSO in various configurations of the constituent cryoprotective fluids. We have also shown that AT-MSCs that show control levels in most standard tests (viability, shape, culture behaviour, and proliferative properties) after thawing, may show transient variations in some important physiological properties, such as the level of secreted growth factors. Obtained results let us to indicate how to optimize the AT-MSC preparation process for clinical applications. We suggest that before their clinical application the cells should be cultured for at least one passage to recover their physiological stability and thus assure their optimal therapeutic potential.

14.
Int J Mol Sci ; 22(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34575901

RESUMO

The term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifying the progress of epileptogenesis. Most antiepileptic drugs possess only a weak or no antiepileptogenic potential at all, but a few of them appear promising in this regard; these include, for example, eslicarbazepine (a sodium and T-type channel blocker), lamotrigine (a sodium channel blocker and glutamate antagonist) or levetiracetam (a ligand of synaptic vehicle protein SV2A). Among the approved non-antiepileptic drugs, antiepileptogenic potential seems to reside in losartan (a blocker of angiotensin II type 1 receptors), biperiden (an antiparkinsonian drug), nonsteroidal anti-inflammatory drugs, antioxidative drugs and minocycline (a second-generation tetracycline with anti-inflammatory and antioxidant properties). Among other possible antiepileptogenic compounds, antisense nucleotides have been considered, among these an antagomir targeting microRNA-134. The drugs and agents mentioned above have been evaluated in post-status epilepticus models of epileptogenesis, so their preventive efficacy must be verified. Limited clinical data indicate that biperiden in patients with brain injuries is well-tolerated and seems to reduce the incidence of post-traumatic epilepsy. Exceptionally, in this regard, our own original data presented here point to c-Fos as an early seizure duration, but not seizure intensity-related, marker of early epileptogenesis. Further research of reliable markers of early epileptogenesis is definitely needed to improve the process of designing adequate antiepileptogenic therapies.


Assuntos
Anticonvulsivantes/farmacologia , Biomarcadores , Suscetibilidade a Doenças , Descoberta de Drogas , Epilepsia/etiologia , Epilepsia/metabolismo , Animais , Anticonvulsivantes/química , Antioxidantes/administração & dosagem , Terapia Combinada , Suplementos Nutricionais , Descoberta de Drogas/métodos , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Humanos , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-fos/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-fos/metabolismo
15.
Ann Agric Environ Med ; 28(3): 502-508, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34558276

RESUMO

INTRODUCTION: Premature birth is connected with the risk of incidence of numerous health complications, the consequences of which are observed in the long-term. Decreased physical and cardiorespiratory fitness can also be associated with preterm birth. OBJECTIVE: The aim of the study is evaluation of the development level of physical and cardiorespiratory fitness in 7-year-old prematurely born children. MATERIAL AND METHODS: The following 7-year-old children were qualified for participation in the research: 30 children born on time and 30 children born prematurely. Physical fitness was evaluated with the International Physical Fitness Test (IPFT), whereas cardiorespiratory fitness was assessed on the basis of the Kasch Pulse Recovery Test. RESULTS: The results obtained demonstrate a lower level of physical and cardiorespiratory fitness in the studied group. Statistically significant differences are noticeable with respect to all IPFT components, except for long jump. The studied group display statistically significant higher values of pulse rate after exercise than the control group. On the other hand, there is no statistically significant correlation between a child's gestational age week of birth and the parameters evaluated. CONCLUSIONS: 7-year-old prematurely born children present lower physical and cardiorespiratory fitness than children born on time. The research results show a need for long-term monitoring of prematurely born children's development, as well as overall body efficiency. Further studies and observation of a higher number of patients are planned in order to confirm the findings.


Assuntos
Aptidão Cardiorrespiratória , Aptidão Física , Nascimento Prematuro/fisiopatologia , Criança , Exercício Físico , Feminino , Humanos , Masculino
16.
J Clin Med ; 10(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34501366

RESUMO

Patients with end-stage renal disease have higher cardiovascular morbidity and mortality compared with the general population. Preemptive kidney transplant (KTx) has been shown to be associated with improved survival, better quality of life, lower healthcare burden, and reduced cardiovascular risk. In this case-control study, we investigated the cardiovascular benefits of two approaches to KTx: with and without previous chronic hemodialysis. We enrolled 21 patients who underwent preemptive KTx and 21 matched controls who received chronic hemodialysis before KTx. Cardiac morphological and functional parameters were assessed by echocardiography. Overall, patients undergoing preemptive KTx showed less extensive cardiac damage compared with controls, as evidenced by higher global longitudinal strain, peak atrial and contractile strain, and early diastolic mitral annular velocity as well as a lower left ventricular mass, left atrial volume index, and the ratio of mitral inflow early diastolic velocity to the mitral annular early diastolic velocity. In the multivariable analysis, the presence of chronic hemodialysis prior to KTx was an independent determinant of post-transplant cardiac functional and structural remodeling. These findings may have important clinical implications, supporting the use of preemptive KTx as a preferred treatment strategy in patients with end-stage renal disease.

17.
Exp Mol Pathol ; 123: 104679, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34481839

RESUMO

Gaucher disease (GD) caused by mutation in the GBA gene has a wide spectrum of phenotypes. Besides the storage disorder, secondary alteration of various pathways occurs with modification of the expression of many genes. In our work we analysed the expression profile of genes in adult patients with type 1 GD. METHODS: This study was an observational, cross-sectional analysis of a group of twenty patients with type 1 GD and ten healthy volunteers as a control group. First, on the group of ten persons, microarray gene analysis was performed. Afterwards, significantly regulated genes were selected, and the microarray results were confirmed by real-time PCR on the whole study group. RESULTS: Based on the microarray results in the pathway analysis, we focused on genes related to chemokines, inflammatory processes, endocytosis, autophagy, and apoptosis. Patients with GD demonstrated up-regulation of genes related to NFkB pathway (NFkB, NKkBR SQSTM1), inflammation (IL-1b), endocytosis and autophagy (BCN1, SMAD), genes coding proteins involved in apoptosis (CASP, NFkB, BCL2) as well as genes related to proteasome degradation (PSMD2, PSMB9) and SNARE complex (SNAP, STX). Simultaneously, we showed down-regulation of genes coding proteins of chemokines and their receptors (GNB4, CCL5). The qRT-PCR results confirmed changes in expression of selected genes. Parallel microarray results showed inhibition of genes related to neurones development and survival (NTRK1) and stimulation of gene expression related to neurodegeneration and apoptosis (BCN1, IL1B). CONCLUSIONS: The work revealed different pathway activation, especially inflammatory processes followed by autophagy and apoptosis. Our results also pay attention to new pathways leading to disorders of the functioning of the nervous tissue in patients with type 1 GD, which may lead to the development of polyneuropathy and chronic pain. These are clinical symptoms that severely decrease the quality of life in GD patients.


Assuntos
Apoptose/genética , Autofagia/genética , Endocitose/genética , Doença de Gaucher/genética , Inflamação/genética , Adulto , Idoso , Feminino , Doença de Gaucher/patologia , Regulação da Expressão Gênica/genética , Glucosilceramidase/genética , Humanos , Inflamação/patologia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Transdução de Sinais/genética , Adulto Jovem
18.
Molecules ; 26(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074008

RESUMO

C-11 is a hybrid compound derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide, with a wide spectrum of anticonvulsant activity and low neurotoxicity. The aim of this study was to determine the effects of C-11 on the protective action of various antiepileptic drugs (i.e., carbamazepine CBZ, lacosamide LCM, lamotrigine LTG, and valproate VPA) against maximal electroshock-induced seizures (MES) in mice, as well as its neuroprotective and physicochemical/pharmacokinetic properties. Results indicate that C-11 (30 mg/kg, i.p.) significantly enhanced the anticonvulsant action of LCM (p < 0.001) and VPA (p < 0.05) but not that of CBZ and LTG in the MES test. Neither C-11 (30 mg/kg) alone nor its combination with other anticonvulsant drugs (at their ED50 values from the MES test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength and passive avoidance tests, respectively. Pharmacokinetic characterization revealed that C-11 had no impact on total brain concentrations of LCM or VPA in mice. Qualitative analysis of neuroprotective properties of C-11, after a single administration of pilocarpine, revealed no protective effect of this substance in the tested animals. Determination of physicochemical descriptors showed that C-11 meets the drug-likeness requirements resulting from Lipinski and Veber's rules and prediction of gastrointestinal absorption and brain penetration, which is extremely important for the CNS-active compounds.


Assuntos
Anticonvulsivantes/farmacologia , Eletrochoque , Animais , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Camundongos , Força Muscular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pilocarpina/toxicidade , Desempenho Psicomotor/efeitos dos fármacos
19.
Stem Cell Rev Rep ; 17(5): 1780-1795, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33860454

RESUMO

Mesenchymal stromal/stem cells (MSCs) are a unique population of cells that play an important role in the regeneration potential of the body. MSCs exhibit a characteristic phenotype and are capable of modulating the immune response. MSCs can be isolated from various tissues such as: bone marrow, adipose tissue, placenta, umbilical cord and others. The umbilical cord as a source of MSCs, has strong advantages, such as no-risk procedure of tissue retrieval after birth and easiness of the MSCs isolation. As the umbilical cord (UC) is a complex organ and we decided to evaluate, whether the cells derived from different regions of umbilical cord show similar or distinct properties. In this study we characterized and compared MSCs from three regions of the umbilical cord: Wharton's Jelly (WJ), the perivascular space (PRV) and the umbilical membrane (UCM). The analysis was carried out in terms of morphology, phenotype, immunomodulation potential and secretome. Based on the obtained results, we were able to conclude, that MSCs derived from distinct UC regions differ in their properties. According to our result WJ-MSCs have high and stabile proliferation potential and phenotype, when compare with other MSCs and can be treated as a preferable source of cells for medical application.


Assuntos
Células-Tronco Mesenquimais , Cordão Umbilical , Proliferação de Células , Feminino , Humanos , Imunomodulação , Células-Tronco Mesenquimais/citologia , Gravidez , Cordão Umbilical/citologia , Geleia de Wharton/citologia
20.
Ann Agric Environ Med ; 28(1): 183-188, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33775086

RESUMO

INTRODUCTION: Premature babies are a special group at risk of persistent brain damage caused by diseases, the most serious of which are cerebral palsy(CP), autism spectrum disorders (ASD) and mental retardation, among others. These conditions may occur concurrently, but appear more often as separate disease syndromes in the same group of at-risk children. Long-term observation of psychomotor development by an interdisciplinary medical team closely cooperating with parents is necessary. It is important to detect the risk of developing these diseases as soon as possible in all development spheres. MATERIAL AND METHODS: The research was conducted to demonstrate the prognostic value of 'red flags' of developmental milestones and the ability to detect early signs of risk of developing CP and ASD in extremely premature babies. In this preliminary study, 42 preterm babies, born after less than 32 weeks pregnancy participated. RESULTS: The occurrence of 'red flags'in the spheres: gross motor, fine motor and cognitive at 9 months was strongly associated with their presence at 24 months. The sensitivity and specificity were: gross motor - 0.91 (95% CI: 0.59, 1.00) and 0.94 (95% CI: 0.79, 0.99); fine motor - 0.83 (95% CI 0.36-1.00) and 1.00 (95% CI: 0.90-1.00); cognitive - 1.00 (0.40, 1.00) and 0.97 (0.86, 1.00). Other spheres had lower sensitivity but high specificity. CONCLUSIONS: The conclusion is that the 'red flags'at the 9 months milestones already predict the normal or developmental delay of premature babies, and predict the risk of CP and ASD. Due to the availability and lack of the need for specialized and costly training, it is worth considering their use in everyday life medical practice.


Assuntos
Doenças do Prematuro/diagnóstico , Transtornos Psicomotores/diagnóstico , Desenvolvimento Infantil , Cognição , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido Prematuro/psicologia , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/psicologia , Masculino , Atividade Motora , Transtornos Psicomotores/fisiopatologia , Transtornos Psicomotores/psicologia
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