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1.
PLoS One ; 19(3): e0299567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38457412

RESUMO

Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a progressive loss of motor neurons resulting in paralysis and muscle atrophy. One of the most prospective hypothesis on the ALS pathogenesis suggests that excessive inflammation and advanced glycation end-products (AGEs) accumulation play a crucial role in the development of ALS in patients and SOD1 G93A mice. Hence, we may speculate that RAGE, receptor for advanced glycation end-products and its proinflammatory ligands such as: HMGB1, S100B and CML contribute to ALS pathogenesis. The aim of our studies was to decipher the role of RAGE as well as provide insight into RAGE signaling pathways during the progression of ALS in SOD1 G93A and RAGE-deficient SOD1 G93A mice. In our study, we observed alternations in molecular pattern of proinflammatory RAGE ligands during progression of disease in RAGE KO SOD1 G93A mice compared to SOD1 G93A mice. Moreover, we observed that the amount of beta actin (ACTB) as well as Glial fibrillary acidic protein (GFAP) was elevated in SOD1 G93A mice when compared to mice with deletion of RAGE. These data contributes to our understanding of implications of RAGE and its ligands in pathogenesis of ALS and highlight potential targeted therapeutic interventions at the early stage of this devastating disease. Moreover, inhibition of the molecular cross-talk between RAGE and its proinflammatory ligands may abolish neuroinflammation, gliosis and motor neuron damage in SOD1 G93A mice. Hence, we hypothesize that attenuated interaction of RAGE with its proinflammatory ligands may improve well-being and health status during ALS in SOD1 G93A mice. Therefore, we emphasize that the inhibition of RAGE signaling pathway may be a therapeutic target for neurodegenerative diseases.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Superóxido Dismutase-1 , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Modelos Animais de Doenças , Progressão da Doença , Camundongos Transgênicos , Estudos Prospectivos , Receptor para Produtos Finais de Glicação Avançada/genética , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
2.
Polim Med ; 53(2): 105-110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38112253

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis. OBJECTIVES: Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients. MATERIAL AND METHODS: Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test. RESULTS: Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease. CONCLUSIONS: The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.


Assuntos
Produtos da Oxidação Avançada de Proteínas , Esclerose Lateral Amiotrófica , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Produtos da Oxidação Avançada de Proteínas/metabolismo , Estudos Longitudinais , Estresse Oxidativo
3.
Biomolecules ; 13(10)2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37892232

RESUMO

Myo-inositol belongs to one of the sugar alcohol groups known as cyclitols. Phosphatidylinositols are one of the derivatives of Myo-inositol, and constitute important mediators in many intracellular processes such as cell growth, cell differentiation, receptor recycling, cytoskeletal organization, and membrane fusion. They also have even more functions that are essential for cell survival. Mutations in genes encoding phosphatidylinositols and their derivatives can lead to many disorders. This review aims to perform an in-depth analysis of these connections. Many authors emphasize the significant influence of phosphatidylinositols and phosphatidylinositols' phosphates in the pathogenesis of myotubular myopathies, neurodegenerative disorders, carcinogenesis, and other less frequently observed diseases. In our review, we have focused on three of the most often mentioned groups of disorders. Inositols are the topic of many studies, and yet, there are no clear results of successful clinical trials. Analysis of the available literature gives promising results and shows that further research is still needed.


Assuntos
Miopatias Congênitas Estruturais , Doenças Neurodegenerativas , Humanos , Fosfatidilinositóis/metabolismo , Inositol/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Carcinogênese/genética , Patrimônio Genético , Redes e Vias Metabólicas , Doenças Neurodegenerativas/genética
4.
Toxics ; 11(9)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37755779

RESUMO

Lead is known to be highly toxic to humans, causing various disorders infetal development. An experiment was conducted to examine the effects of lead acetate on the structural organization of female rat ovaries. The study involved 40 non-linear female rats divided into four groups: a control group, a low-dose group, a moderate-dose group, and a high-dose group. The rats were given lead acetate solutions in varying doses for 30 days, and their ovarian tissue was examined using light microscopy.The results showed that increasing doses of lead acetate led to morphological changes in the cortex and medulla of the rat ovaries. The changes were characterized by a decrease in ovarian mass, alterations in the thickness of the tunica albuginea (protein envelope), and a reduction in the number of follicles. Light microscopy revealed that exposure to lead acetate resulted in a significant decrease in the number of follicles in all experimental groups, with the high-dose group experiencing the most significant decrease.These findings suggest that lead acetate has a dose-dependent negative impact on the morphology and function of female rat ovaries. Further studies are needed to investigate the potential impact of lead on human ovarian tissue.

5.
Life (Basel) ; 13(7)2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37511845

RESUMO

The effects of severe burn injuries on the cardiovascular system, specifically the atria and auricles of the heart, were investigated. The potential benefits of using lyophilized xenodermotransplants as a treatment option were also evaluated. The experiments were conducted on adult guinea pigs divided into three groups: intact animals, animals with burns, and animals with burns who underwent early necrectomy followed by wound closure with lyophilized xenodermotransplants. Third-degree burns caused significant ultrastructural changes in atrial cardiomyocytes, leading to long-term destructive changes in the structural components of the atria. However, the use of lyophilized xenodermotransplants had a positive effect on the atrial ultrastructure over time. This study highlights the complex and varied effects of burn injuries on the body and the potential benefits of lyophilized xenodermotransplants in treating severe burn injuries. By preventing destructive changes in the heart and activating regenerative processes, lyophilized xenodermotransplants can improve the condition of the heart after thermal injury. Further research and development in this area are necessary for understanding the potential of lyophilized xenodermotransplants in tissue repair and regeneration.

6.
Nutrients ; 15(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37432155

RESUMO

One of the most common cyclitols found in eukaryotic cells-Myo-inositol (MI) and its derivatives play a key role in many cellular processes such as ion channel physiology, signal transduction, phosphate storage, cell wall formation, membrane biogenesis and osmoregulation. The aim of this paper is to characterize the possibility of neurodegenerative disorders treatment using MI and the research of other therapeutic methods linked to MI's derivatives. Based on the reviewed literature the researchers focus on the most common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Spinocerebellar ataxias, but there are also works describing other seldom encountered diseases. The use of MI, d-pinitol and other methods altering MI's metabolism, although research on this topic has been conducted for years, still needs much closer examination. The dietary supplementation of MI shows a promising effect on the treatment of neurodegenerative disorders and can be of great help in alleviating the accompanying depressive symptoms.


Assuntos
Doença de Alzheimer , Ciclitóis , Doença de Huntington , Humanos , Doença de Alzheimer/tratamento farmacológico , Células Eucarióticas , Osmorregulação
7.
J Mol Med (Berl) ; 101(8): 1015-1028, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37462767

RESUMO

Multiple molecular pathways including the receptor for advanced glycation end-products-diaphanous related formin 1 (RAGE-Diaph1) signaling are known to play a role in diabetic peripheral neuropathy (DPN). Evidence suggests that neuropathological alterations in type 1 diabetic spinal cord may occur at the same time as or following peripheral nerve abnormalities. We demonstrated that DPN was associated with perturbations of RAGE-Diaph1 signaling pathway in peripheral nerve accompanied by widespread spinal cord molecular changes. More than 500 differentially expressed genes (DEGs) belonging to multiple functional pathways were identified in diabetic spinal cord and of those the most enriched was RAGE-Diaph1 related PI3K-Akt pathway. Only seven of spinal cord DEGs overlapped with DEGs from type 1 diabetic sciatic nerve and only a single gene cathepsin E (CTSE) was common for both type 1 and type 2 diabetic mice. In silico analysis suggests that molecular changes in spinal cord may act synergistically with RAGE-Diaph1 signaling axis in the peripheral nerve. KEY MESSAGES: Molecular perturbations in spinal cord may be involved in the progression of diabetic peripheral neuropathy. Diabetic peripheral neuropathy was associated with perturbations of RAGE-Diaph1 signaling pathway in peripheral nerve accompanied by widespread spinal cord molecular changes. In silico analysis revealed that PI3K-Akt signaling axis related to RAGE-Diaph1 was the most enriched biological pathway in diabetic spinal cord. Cathepsin E may be the target molecular hub for intervention against diabetic peripheral neuropathy.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Neuropatias Diabéticas , Hiperglicemia , Animais , Camundongos , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/complicações , Catepsina E , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Nervo Isquiático/patologia , Hiperglicemia/genética , Hiperglicemia/patologia
8.
Int J Mol Sci ; 24(10)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37240271

RESUMO

Articular cartilage has very low metabolic activity. While minor injuries may be spontaneously repaired within the joint by chondrocytes, there is very little chance of a severely impaired joint regenerating itself when damaged. Therefore, any significant joint injury has little chance of spontaneously healing without some type of therapy. This article is a review that will examine the causes of osteoarthritis, both acute and chronic, and how it may be treated using traditional methods as well as with the latest stem cell technology. The latest regenerative therapy is discussed, including the use and potential risks of mesenchymal stem cells for tissue regeneration and implantation. Applications are then discussed for the treatment of OA in humans after using canine animal models. Since the most successful research models of OA were dogs, the first applications for treatment were veterinary. However, the treatment options have now advanced to the point where patients suffering from osteoarthritis may be treated with this technology. A survey of the literature was performed in order to determine the current state of stem cell technology being used in the treatment of osteoarthritis. Then, the stem cell technology was compared with traditional treatment options.


Assuntos
Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite , Humanos , Animais , Cães , Células-Tronco , Condrócitos , Osteoartrite/terapia
9.
Eur J Neurosci ; 57(10): 1642-1656, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37070486

RESUMO

This review focuses on receptor for advanced glycation endproducts/diaphonous related formin 1 (RAGE/Diaph1) interaction as a modulator of actin cytoskeleton dynamics in peripheral nervous system (PNS) in diabetes. Deciphering the complex molecular interactions between RAGE and Diaph1 is crucial in expanding our understanding of diabetic length dependent neuropathy (DLDN). DLDN is a common neurological disorder in patients with diabetes. It is well known that actin cytoskeletal homeostasis is disturbed during DLDN. Thus, we review the current status of knowledge about RAGE/Diaph1 impact on actin cytoskeletal malfunctions in PNS and DLDN progression in diabetes. We also survey studies about small molecules that may block RAGE/Diaph1 axis and thus inhibit the progression of DLDN. Finally, we explore examples of cytoskeletal long-non coding RNAs (lncRNAs) currently unrelated to DLDN, to discuss their potential role in this disease. Most recent studies indicated that lncRNAs have a great potential in many research areas, including RAGE/Diaph1 axis as well as DLDN. Altogether, this review is aimed at giving us an insight into the involvement of cytoskeletal lncRNAs in DLDN.


Assuntos
Hiperglicemia , RNA Longo não Codificante , Humanos , Transdução de Sinais , Actinas , Receptor para Produtos Finais de Glicação Avançada , Citoesqueleto de Actina/metabolismo , Sistema Nervoso Periférico/metabolismo , Forminas/metabolismo
10.
Int J Mol Sci ; 24(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37108760

RESUMO

Epilepsy, with about 70 million affected people worldwide, is one of the biggest challenges of medicine today. It is estimated that about one-third of epileptic patients receive inadequate treatment. Inositols have proved effective in many disorders; hence, in the current study, we tested potential antiepileptic properties of scyllo-inositol (SCI)-one of the most common commercially available inositols-in zebrafish larvae with pentylenetetrazol-induced seizures. First, we studied the general effect of SCI on zebrafish motility, and then we tested SCI antiepileptic properties over short (1 h) and long (120 h) exposure protocols. Our results demonstrated that SCI alone does not reduce zebrafish motility regardless of the dose. We also observed that short-term exposure to SCI groups reduced PTZ-treated larva motility compared to controls (p < 0.05). In contrast, prolonged exposure did not produce similar results, likely due to the insufficient concentration of SCI given. Our results highlight the potential of SCI use in epilepsy treatment and warrant further clinical studies with inositols as potential seizure-reducing drugs.


Assuntos
Anticonvulsivantes , Epilepsia , Animais , Anticonvulsivantes/efeitos adversos , Pentilenotetrazol/farmacologia , Peixe-Zebra , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Larva
11.
Int J Mol Sci ; 23(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36232547

RESUMO

Myo-inositol is the most popular inositol in living organisms, where it is present as a sugar alcohol, in a free form, and can also be described as a lipid. The aim of this study was to check the concentration change of a myo-inositol solution from the time of oral administration and over a 48 h period in Wistar-type rats. All rats received 2 g/kg of inositol as a solution in distilled water by oral gavage. Estimated parameters were based on the serum concentration of myo-inositol observed in nine individual rats with regard to time. Observations were described as a one-compartment pharmacokinetic model with first-order absorption and zero-order endogenous input of checked inositol. The highest myo-inositol concentration was observed in the first hour after oral administration in the serum of all tested rats. Then, the concentration began decreasing immediately after the maximal peak. The inositol concentration continued to decrease, but after 24 h its level was still higher than before the administration. The plasma profile of the myo-inositol concentration showed a rapid decline over time, possibly due to the metabolism of this compound.


Assuntos
Inositol , Lipídeos , Animais , Modelos Animais de Doenças , Inositol/metabolismo , Ratos , Ratos Wistar , Água
12.
Med Sci Monit ; 28: e936738, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35923084

RESUMO

BACKGROUND Bisphenol A (BPA) and its analogue bisphenol S (BPS), widely utilized in numerous fields of industry, may seep into the environment and into human organisms. Hitherto, BPA was regarded as the bisphenol to which people were exposed to the greatest extent. As endocrine disruptors, bisphenols have negative effects on human health. Therefore, defining the levels of human exposure to these compounds is a key issue in toxicology. Hair analysis has been increasingly used for biomonitoring of bisphenols in humans, but information about the coexistence of BPA and BPS in human hair is extremely scarce. The present study aimed to analyze hair samples from 25 individuals from Olsztyn, northeastern Poland, to evaluate the levels of these 2 industrial pollutants. MATERIAL AND METHODS The method used in the research was liquid chromatography with a mass spectrometry technique. RESULTS BPA was found in 72% of samples analyzed and its concentration levels fluctuated from 3.6 to 52.9 ng/g (median 17.7 ng/g). The BPS concentration levels were higher - from 13.4 to 1054.9 ng/g (median 98.7 ng/g). We also found that gender, age, and the presence of artificial hair color (hair dye) did not affect the BPA and BPS levels in the hair. CONCLUSIONS This study has shown that hair samples may be used to measure the levels of bisphenols, and that exposure to BPS may be greater than that to BPA in this area. The investigation also revealed that hair analysis is a useful approach for the biomonitoring of BPA and BPS levels in human organisms.


Assuntos
Compostos Benzidrílicos , Análise do Cabelo , Cabelo/química , Humanos , Fenóis , Projetos Piloto , Polônia
13.
Artigo em Inglês | MEDLINE | ID: mdl-35954685

RESUMO

INTRODUCTION: The response to the COVID-19 pandemic by anesthesiologists has been simply heroic. Unfortunately, there are very few evidence-based studies in the literature that focus on anesthesiologists' burnout during that time. The purpose of our study was to examine the psychological distress, after the COVID-19 pandemic, among anesthesiologists in Poland. METHODS: We conducted an anonymous internet survey among a group of anesthesiologists in Poland. It contained a questionnaire, entitled "Oldenburg Burnout Inventory (OLBI)", with demographic questions about sex, age, and family, as well as questions related to working conditions during the COVID-19 pandemic. We received data from 158 people, including 109 women and 49 men. RESULTS: Results from the analysis showed that 73% (115/158) of the participants suffered from burnout. Moreover, 95.6% of the participants thought that the COVID-19 pandemic had had an influence on their level of burnout, and 97.3% found that it had had a negative impact. CONCLUSIONS: There is no doubt that healthcare workers, despite the difficulties associated with their daily work, have not faced challenges on such a scale in a very long time. Support for their mental health should be an essential component of the modern public healthcare system.


Assuntos
Esgotamento Profissional , COVID-19 , Angústia Psicológica , Anestesiologistas , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pandemias , Polônia/epidemiologia
14.
J Clin Med ; 11(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35807006

RESUMO

Current data indicate that heart failure (HF) is associated with inflammation and microvascular dysfunction and remodeling. These mechanisms could be involved in HF development and progression, especially in HF with preserved ejection fraction (HFpEF). We aimed to compare structural changes in retinal arterioles and carotid arteries between HF patients and patients without heart failure. This preliminary, retrospective, case-control study included 28 participants (14 patients with HFpEF and 14 age- and sex-matched healthy controls). Carotid intima-media thickness to lumen ratio (cIMTLR) was assessed using B-mode ultrasonography. Retinal arterioles wall- to-lumen ratio (rWLR) was assessed by adaptive optics camera rtx1. The HF patients had higher IMTLR (Δmedian [HFpEF-control group] 0.07, p = 0.01) and eWLR (Δmedian 0.03, p = 0.001) in comparison to patients without HF. In the whole study group, rWLR correlated significantly with IMTLR (r = 0.739, p = 0.001). Prevalence of arterial hypertension was similar in both groups, however, patients with HF had a significantly lower office, central and 24-h ambulatory blood pressure (systolic Δmedian -21 to -18 mmHg; diastolic Δmedian -23 to -10 mmHg). Our data suggests gradual and simultaneous progression of vascular remodeling in both retinal arterioles and carotid arteries in HFpEF patients. This process could be a marker of HF development. Significantly lower blood pressure values in HF group may indicate that vascular remodeling could be independent of BP control. Nevertheless, further and larger prospective studies allowing to reduce the impact of confounding and address temporality are warranted.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35409481

RESUMO

Triclosan (TCS) is an organic substance showing antibacterial action, which is commonly used in many branches of industry, including, among others, cosmetics, pharmaceuticals and the food industry. TCS may penetrate into living organisms and negatively affect the health of humans and animals. The majority of previous investigations on TCS biomonitoring in humans have been performed on urine, but currently, studies on hair samples are becoming increasingly important. The aim of this study was to evaluate TCS concentration levels in residents of Olsztyn, a city in northeastern Poland, using a liquid chromatography-mass spectrometry technique. The presence of TCS was observed in 96.7% of samples tested, with concentration levels from 37.9 pg/mg to 3386.5 pg/mg. The mean concentration level of TCS in the present study was 402.6 (±803.6) pg/mg, and the median value was 103.3 pg/mg. Although there were some differences in TCS concentration levels between males and females, humans of various ages and humans with colored and natural hair had no statistically significant differences in TCS concentration levels. The obtained results have clearly indicated that people living in northeastern Poland are exposed to TCS to a large degree, and hair analysis, despite some limitations, is a suitable method for TCS biomonitoring in humans.


Assuntos
Triclosan , Animais , Feminino , Cabelo/química , Análise do Cabelo , Humanos , Masculino , Projetos Piloto , Polônia , Triclosan/análise
16.
Int J Mol Sci ; 23(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35216298

RESUMO

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive degeneration of upper and lower motor neurons that causes paralysis and muscle atrophy. The pathogenesis of the disease is still not elucidated. Receptor for Advanced Glycation End Product (RAGE) is a major component of the innate immune system and has implications in ALS pathogenesis. Multiple studies suggest the role of RAGE and its ligands in ALS. RAGE and its ligands are overexpressed in human and murine ALS motor neurons, astrocytes, and microglia. Here, we demonstrated the expression of RAGE and its ligands during the progression of the disease in the transgenic SOD1 G93A mouse lumbar spinal cord. We observed the highest expression of HMGB1 and S100b proteins at ALS onset. Our results highlight the potential role of RAGE and its ligands in ALS pathogenesis and suggest that some of the RAGE ligands might be used as biomarkers in early ALS diagnosis and potentially be useful in targeted therapeutic interventions at the early stage of this devastating disease.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Receptor para Produtos Finais de Glicação Avançada , Esclerose Lateral Amiotrófica/metabolismo , Animais , Modelos Animais de Doenças , Progressão da Doença , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doenças Neurodegenerativas/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Medula Espinal/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
17.
Sci Rep ; 11(1): 23673, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880378

RESUMO

Parabens (PBs) are a group of substances commonly used in industry. They also pollute the environment, penetrate into living organisms and adversely affect various internal organs. During this study, the degree of exposure of people living in Olsztyn, a city in north eastern Poland, to selected parabens most often used in industry was studied. The chemicals under investigation included: methyl paraben-MePB, ethyl paraben-EtPB, propyl paraben-PrPB, benzyl paraben BePB and butyl paraben -BuPB. To this aim, hair samples collected from the scalps of 30 volunteers were analyzed using a liquid chromatography-mass spectrometry technique. All PBs studied were present in a high percentage of analyzed samples (from 76.7% in the case of BePB to 100% in the case of MePB and PrPB). The mean concentration levels were 4425.3 pg/mg for MeBP, 704.0 pg/mg for EtPB, 825.7 pg/mg for PrPB, 135.2 pg/mg for BePB and 154.5 pg/mg for BuPB. Significant differences in PB concentration levels between particular persons were visible. On the other hand, gender, age and artificial hair coloring did not cause statistically significant differences in PB levels. Obtained results have clearly indicated that people living in north eastern Poland are exposed to various PBs, and therefore these substances may affect their health status. However, the evaluation of PBs influence on human health requires further research.


Assuntos
Exposição Ambiental/efeitos adversos , Análise do Cabelo , Avaliação do Impacto na Saúde/métodos , Avaliação do Impacto na Saúde/estatística & dados numéricos , Parabenos/efeitos adversos , Parabenos/análise , Idoso , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/análise , Feminino , Análise do Cabelo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Polônia/epidemiologia , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade
18.
Life (Basel) ; 11(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34833143

RESUMO

The objective of the study was to compare the effects of experimentally induced type 1 or type 2 diabetes (T1D or T2D) on the functional, structural and biochemical properties of mouse peripheral nerves. Eight-week-old C57BL/6 mice were randomly assigned into three groups, including the control (CTRL, chow-fed), STZ (streptozotocin (STZ)-injected), and HFD (high-fat diet (HFD)-fed) group. After 18-weeks of experimental treatment, HFD mice had higher body weights and elevated levels of plasma lipids, while STZ mice developed hyperglycemia. STZ-treated mice, after an extended period of untreated diabetes, developed motor and sensory nerve conduction-velocity deficits. Moreover, relative to control fibers, pre- and diabetic axons were lower in number and irregular in shape. Animals from both treatment groups manifested a pronounced overexpression of nNOS and a reduced expression of SOD1 proteins in the sciatic nerve, indicating oxidative-nitrosative stress and ineffective antioxidant protection in the peripheral nervous system of these mice. Collectively, STZ- and HFD-treated mice revealed similar characteristics of peripheral nerve damage, including a number of morphological and electrophysiological pathologies in the sciatic nerve. While hyperglycemia is a large component of diabetic neuropathy pathogenesis, the non-hyperglycemic effects of diabetes, including dyslipidemia, may also be of importance in the development of this condition.

19.
Medicine (Baltimore) ; 100(39): e26585, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596107

RESUMO

ABSTRACT: The use of local antibiogram in guiding clinical decisions is an integral part of the antimicrobial stewardship program. Conventional antibiograms are not disease-specific, ignore the distribution of microorganisms, obscure the in-vitro efficacy interrelationships, and have limited use in polymicrobial infections.We aimed to develop an in-house empiric, disease-specific, antimicrobial prescription auxiliary for the treatment of hospitalized pediatric pneumonia patients and to present the methods which help to choose the first and the second line antimicrobial therapy, while accounting for cost and safety aspects.A retrospective single center observational study was conducted on bronchoscopy obtained sputum culture. Analysis of probabilities, variance minimization, Boolean network modeling, and dominance analysis were applied to analyze antibiogram data. The Kirby-Bauer disk diffusion method was used to test the susceptibility of all isolates. Final optimization analysis included local drug acquisition cost (standardized to price per DDD) and safety profile.Data of 145 pediatric patients hospitalized with pneumonia with 218 isolates over 5 years was collected. A combination of statistical methods such as probabilities of drug efficacy, variance minimization, Boolean network modeling, and dominance analysis can help to choose the optimal first-line and the second-line antimicrobial treatment and optimize patient care. This research reveals that ampicillin is the optimal choice as the first-line drug and piperacillin-tazobactam is the second-line antimicrobial drug if the first one is not effective, while accounting for cost and safety aspects.The paper proposes a new methodology to adapt empiric antimicrobial therapy recommendations based on real world data and accout for costs and risk of adverse events.


Assuntos
Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Infecções Respiratórias/tratamento farmacológico , Criança , Humanos , Pulmão , Estudos Retrospectivos , Traqueia
20.
Nutrients ; 13(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34684347

RESUMO

Inositol is a natural substance found widely in plants. It is used in therapies for many medical cases. The aim of this study was to determine the toxicity of myo-inositol (MI) and to investigate its potential hepatoprotective character. In the first part of the study, zebrafish embryos were incubated with 5, 10, 20, 40, 60, 80, and 100 mg/mL MI. Endpoints such as survivability, hatching rate, malformation, and mobility were evaluated. Our results demonstrated that the high doses of MI lead to increased mortality and malformations and reduce the hatching rate in comparison to the control group. Moreover, low doses of this compound do not produce a negative effect on zebrafish and even have the ability to increase the hatching rate and mobility. In the second part of the study, the hepatoprotective effect of MI was tested. Zebrafish larvae from the line Tg (fabp10a:DsRed) were incubated for 24 h with 1% and 2% ethanol (EtOH), 5 mg/mL of MI with 1% EtOH, and 5 mg/mL of MI with 2% EtOH. No significant differences between the groups with EtOH and the group treated with EtOH with MI were observed. Our results suggest that MI has no positive benefits on hepatocytes of zebrafish larvae.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Inositol/farmacologia , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/efeitos dos fármacos , Etanol , Fluorescência , Inositol/química , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Fígado/patologia , Modelos Animais , Análise de Sobrevida , Testes de Toxicidade
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