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1.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612610

RESUMO

This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type C, chitosan unmodified injections, and polypropylene mesh. Ovine models were chosen due to their morphological resemblance to human reproductive organs. Animals were sacrificed after 90 days for macroscopic, pathomorphological, and immunohistochemical analysis. In the chitosan type B group, IL-6 and IL-10 levels decreased after 28 days, while chitosan type C and injection groups exhibited higher IL-6 than IL-10 levels. The polypropylene group displayed the highest IL-6 and lowest IL-10 levels. Histological examination of the polypropylene group revealed no degenerative changes or inflammation, whereas chitosan injection induced local inflammation. Other groups exhibited no degenerative changes. Ewes implanted with chitosan displayed reduced inflammation compared to polypropylene-implanted ewes. Chitosan implantation facilitated vaginal tissue healing, in contrast to polypropylene mesh, which led to extrusion. While chitosan holds promise as an alternative to polypropylene mesh, further research is imperative for comprehensive evaluation. This study suggests the potential of a chitosan biomaterial in pelvic organ prolapse treatment, warranting additional investigation.


Assuntos
Quitosana , Hemostáticos , Prolapso de Órgão Pélvico , Ovinos , Animais , Feminino , Humanos , Interleucina-10 , Interleucina-6 , Polipropilenos , Estudos Prospectivos , Prolapso de Órgão Pélvico/cirurgia , Materiais Biocompatíveis/farmacologia , Inflamação , Vagina
2.
Cells ; 11(20)2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36291101

RESUMO

The hippocampus is one of the few privileged regions (neural stem cell niche) of the brain, where neural stem cells differentiate into new neurons throughout adulthood. However, dysregulation of hippocampal neurogenesis with aging, injury, depression and neurodegenerative disease leads to debilitating cognitive impacts. These debilitating symptoms deteriorate the quality of life in the afflicted individuals. Impaired hippocampal neurogenesis is especially difficult to rescue with increasing age and neurodegeneration. However, the potential to boost endogenous Wnt signaling by influencing pathway modulators such as receptors, agonists, and antagonists through drug and cell therapy-based interventions offers hope. Restoration and augmentation of hampered Wnt signaling to facilitate increased hippocampal neurogenesis would serve as an endogenous repair mechanism and contribute to hippocampal structural and functional plasticity. This review focuses on the possible interaction between neurogenesis and Wnt signaling under the control of antidepressants and mesenchymal stem cells (MSCs) to overcome debilitating symptoms caused by age, diseases, or environmental factors such as stress. It will also address some current limitations hindering the direct extrapolation of research from animal models to human application, and the technical challenges associated with the MSCs and their cellular products as potential therapeutic solutions.


Assuntos
Células-Tronco Mesenquimais , Doenças Neurodegenerativas , Animais , Adulto , Humanos , Doenças Neurodegenerativas/metabolismo , Qualidade de Vida , Neurogênese/fisiologia , Hipocampo/metabolismo , Células-Tronco Mesenquimais/metabolismo , Antidepressivos/farmacologia
3.
J Cell Mol Med ; 26(5): 1501-1514, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35076984

RESUMO

The importance of the biophysical characterization of mesenchymal stem cells (MSCs) was recently pointed out for supporting the development of MSC-based therapies. Among others, tracking MSCs in vivo and a quantitative characterization of their regenerative impact by nuclear magnetic resonance (NMR) demands a full description of MSCs' MR properties. In the work, Wharton Jelly MSCs are characterized in a low magnetic field (LF) in vitro by using different approaches. They encompass various settings: MSCs cultured in a Petri dish and cell suspensions; experiments- 1D-T 1 , 1D-T 2 , 1D diffusion, 2D T 1 -T 2 and D-T 2 ; devices- with a bore aperture and single-sided one. Complex NMR analysis with the aid of random walk simulations allows the determination of MSCs T 1 and T 2 relaxation times, cells and nuclei sizes, self-diffusion coefficients of the nucleus and cytoplasm. In addition, the influence of a single layer of cells on the effective diffusion coefficient of water is detected with the application of a single-sided NMR device. It also enables the identification of apoptotic and necrotic cell death and changed diffusional properties of cells suspension caused by compressing forces induced by the subsequent cell layers. The study delivers MSCs-specific MR parameters that may help tracking MSCs in vivo.


Assuntos
Células-Tronco Mesenquimais , Geleia de Wharton , Diferenciação Celular , Proliferação de Células/fisiologia , Células Cultivadas , Espectroscopia de Ressonância Magnética , Células-Tronco Mesenquimais/metabolismo , Geleia de Wharton/metabolismo
4.
Cells ; 10(8)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34440639

RESUMO

Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the development of RMS are still poorly understood. Therefore, by analysis of two RMS RH30 cell line subclones, one subclone PAX7 negative, while the second one PAX7 positive, and comparison with other RMS cell lines we aimed at identifying new mechanisms crucial for RMS progression. RH30 subclones were characterized by the same STR profile, but different morphology, rate of proliferation, migration activity and chemotactic abilities in vitro, as well as differences in tumor morphology and growth in vivo. Our analysis indicated a different level of expression of adhesion molecules (e.g., from VLA and ICAM families), myogenic microRNAs, such as miR-206 and transcription factors, such as MYOD, MYOG, SIX1, and ID. Silencing of PAX7 transcription factor with siRNA confirmed the crucial role of PAX7 transcription factor in proliferation, differentiation and migration of RMS cells. To conclude, our results suggest that tumor cell lines with the same STR profile can produce subclones that differ in many features and indicate crucial roles of PAX7 and ID proteins in the development of RMS.


Assuntos
Diferenciação Celular , Fator de Transcrição PAX7/metabolismo , Rabdomiossarcoma Alveolar/metabolismo , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica , Fator de Transcrição PAX7/genética , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/patologia , Transdução de Sinais , Carga Tumoral
5.
Cells ; 10(7)2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34359837

RESUMO

Induced pluripotent stem (iPS) cells constitute a perfect tool to study human embryo development processes such as myogenesis, thanks to their ability to differentiate into three germ layers. Currently, many protocols to obtain myogenic cells have been described in the literature. They differ in many aspects, such as media components, including signaling modulators, feeder layer constituents, and duration of culture. In our study, we compared three different myogenic differentiation protocols to verify, side by side, their efficiency. Protocol I was based on embryonic bodies differentiation induction, ITS addition, and selection with adhesion to collagen I type. Protocol II was based on strong myogenic induction at the embryonic bodies step with BIO, forskolin, and bFGF, whereas cells in Protocol III were cultured in monolayers in three special media, leading to WNT activation and TGF-ß and BMP signaling inhibition. Myogenic induction was confirmed by the hierarchical expression of myogenic regulatory factors MYF5, MYOD, MYF6 and MYOG, as well as the expression of myotubes markers MYH3 and MYH2, in each protocol. Our results revealed that Protocol III is the most efficient in obtaining myogenic cells. Furthermore, our results indicated that CD56 is not a specific marker for the evaluation of myogenic differentiation.


Assuntos
Técnicas de Cultura de Células , Meios de Cultura/farmacologia , Corpos Embrioides/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Colforsina/farmacologia , Colágeno Tipo I/farmacologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Indóis/farmacologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Insulina/farmacologia , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Proteína MyoD/genética , Proteína MyoD/metabolismo , Fator Regulador Miogênico 5/genética , Fator Regulador Miogênico 5/metabolismo , Fatores de Regulação Miogênica/genética , Fatores de Regulação Miogênica/metabolismo , Miogenina/genética , Miogenina/metabolismo , Oximas/farmacologia , Selênio/farmacologia , Transferrina/farmacologia
6.
Cells ; 10(4)2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804895

RESUMO

The aim of our work was to develop a protocol enabling a derivation of mesenchymal stem/stromal cell (MSC) subpopulation with increased expression of pluripotent and neural genes. For this purpose we used a 3D spheroid culture system optimal for neural stem cells propagation. Although 2D culture conditions are typical and characteristic for MSC, under special treatment these cells can be cultured for a short time in 3D conditions. We examined the effects of prolonged 3D spheroid culture on MSC in hope to select cells with primitive features. Wharton Jelly derived MSC (WJ-MSC) were cultured in 3D neurosphere induction medium for about 20 days in vitro. Then, cells were transported to 2D conditions and confront to the initial population and population constantly cultured in 2D. 3D spheroids culture of WJ-MSC resulted in increased senescence, decreased stemness and proliferation. However long-termed 3D spheroid culture allowed for selection of cells exhibiting increased expression of early neural and SSEA4 markers what might indicate the survival of cell subpopulation with unique features.


Assuntos
Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Esferoides Celulares/citologia , Geleia de Wharton/citologia , Biomarcadores/metabolismo , Forma Celular , Sobrevivência Celular , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Neurônios/metabolismo , Fenótipo , Células-Tronco Pluripotentes/metabolismo
7.
Cancers (Basel) ; 12(7)2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32664538

RESUMO

Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, we demonstrate for the first time that the SNAIL transcription factor regulates the metastatic behavior of RMS both in vitro and in vivo. SNAIL upregulates the protein expression of EZRIN and AKT, known to promote metastatic behavior, by direct interaction with their promoters. Our data suggest that SNAIL promotes RMS cell motility, invasion and chemotaxis towards the prometastatic factors: HGF and SDF-1 by regulating RHO, AKT and GSK3b activity. In addition, miRNA transcriptome analysis revealed that SNAIL-miRNA axis regulates processes associated with actin cytoskeleton reorganization. Our data show a novel role of SNAIL in regulating RMS cell metastasis that may also be important in other mesenchymal tumor types and clearly suggests SNAIL as a promising new target for future RMS therapies.

8.
Pharmacol Rep ; 72(5): 1407-1417, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32715434

RESUMO

BACKGROUND: Multiple myeloma (MM) is defined as plasma cells malignancy, developing in the bone marrow. At the beginning of the disease, the malignant plasma cells are dependent on bone marrow microenvironment, providing growth and survival factors. Importantly, the recent studies pointed hypoxia as an important factor promoting progression of MM. In particular, hypoxia-triggered HIF-1 signaling was shown to promote chemoresistance, angiogenesis, invasiveness and induction of immature phenotype, suggesting that strategies targeting HIF-1 may contribute to improvement of anti-myeloma therapies. METHODS: The Western Blot and RT-PCR techniques were applied to analyze the influence of metformin on HIF-1 pathway in MM cells. To evaluate the effect of metformin on the growth of MM cell lines in normoxic and hypoxic conditions the MTT assay was used. The apoptosis induction in metformin treated hypoxic and normoxic cells was verified by Annexin V/PI staining followed by FACS analysis. RESULTS: Our results showed, for the first time, that metformin inhibits HIF-1 signaling in MM cells. Moreover, we demonstrated the effect of metformin to be mainly oxygen dependent, since the HIF-1 pathway was not significantly affected by metformin in anoxic conditions as well as after application of hypoxic mimicking compound, CoCl2. Our data also revealed that metformin triggers the growth arrest without inducing apoptosis in either normoxic or hypoxic conditions. CONCLUSIONS: Taken together, our study indicates metformin as a promising candidate for developing new treatment strategies exploiting HIF-1 signaling inhibition to enhance the overall anti-MM effect of currently used therapies, that may considerably benefit MM patients.


Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Metformina/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Microambiente Tumoral/efeitos dos fármacos
9.
Acta Biochim Pol ; 66(4): 499-507, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883363

RESUMO

The MSCs are immature cells that can be found in numerous different tissue types. In recent years, they have gained considerable attention, particularly with regard to their regenerative properties. Due to their paracrine activity, ability to migrate, adhesion and homing, MSCs currently appear to be the most relevant for therapeutic use. Numerous bioactive molecules secreted by MSCs exert paracrine effects and modulate many physiological processes, such as angiogenesis, immunomodulation and neuroprotection. Cell-cell communication may be also mediated by extracellular vesicles released from the cells. Due to these properties, MSCs have been widely studied for evaluation of their therapeutic benefits expected in the clinical applications. For effective tissue regeneration, transplanted MSCs have to exit the circulation and locate at the site of damage, which is possible because of their ability to migrate, adhere and engraft at the target site. Accumulating evidence suggests that MSCs recruitment from remote sites is similar to leukocytes' migration. All of these biological features make MSCs highly investigated stem cells and the most commonly used cells in regenerative medicine. Since environmental factors affect the MSCs behavior, we discuss importance of oxygen concentration as a one of the key factors affecting MSCs properties.


Assuntos
Adesão Celular/genética , Transplante de Células-Tronco Mesenquimais , Neovascularização Patológica/terapia , Medicina Regenerativa , Comunicação Celular/genética , Movimento Celular/genética , Humanos , Leucócitos/citologia , Células-Tronco Mesenquimais/citologia
10.
Int J Mol Sci ; 20(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766164

RESUMO

The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide "off-the-shelf" cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient's immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an "off-the-shelf" medical product.


Assuntos
Antígenos HLA/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Animais , Ensaios Clínicos como Assunto , Humanos , Imunomodulação , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Transplante Homólogo/métodos
11.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491893

RESUMO

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are multipotent stem cells that can be used in regenerative medicine. However, to reach the high therapeutic efficacy of WJ-MSCs, it is necessary to obtain a large amount of MSCs, which requires their extensive in vitro culturing. Numerous studies have shown that in vitro expansion of MSCs can lead to changes in cell behavior; cells lose their ability to proliferate, differentiate and migrate. One of the important measures of cells' migration potential is their elasticity, determined by atomic force microscopy (AFM) and quantified by Young's modulus. This work describes the elasticity of WJ-MSCs during in vitro cultivation. To identify the properties that enable transmigration, the deformability of WJ-MSCs that were able to migrate across the endothelial monolayer or Matrigel was analyzed by AFM. We showed that WJ-MSCs displayed differences in deformability during in vitro cultivation. This phenomenon seems to be strongly correlated with the organization of F-actin and reflects the changes characteristic for stem cell maturation. Furthermore, the results confirm the relationship between the deformability of WJ-MSCs and their migration potential and suggest the use of Young's modulus as one of the measures of competency of MSCs with respect to their possible use in therapy.


Assuntos
Células-Tronco Mesenquimais/citologia , Microscopia de Força Atômica , Geleia de Wharton/citologia , Actinas/metabolismo , Biomarcadores , Diferenciação Celular , Movimento Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , Microscopia de Força Atômica/métodos
12.
Int J Mol Sci ; 20(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540534

RESUMO

In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality in regenerative medicine. They hold great promise for treating civilization-wide diseases, including cardiovascular diseases, such as acute myocardial infarction and critical limb ischemia. MSCs isolated from Wharton's jelly (WJ-MSCs) may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits for patients. The efficacy of WJ-MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Ischemic limb disease is caused by insufficient nutrient and oxygen supplies resulting from damaged peripheral arteries. The lack of nutrients and oxygen causes severe tissue damage in the limb, thereby resulting in severe morbidities and mortality. The therapeutic effects of the conventional treatments are still not sufficient. Cell transplantations in small animal model (mice) are vital for deciphering the mechanisms of MSCs' action in muscle regeneration. The stimulation of angiogenesis is a promising strategy for the treatment of ischemic limbs, restoring blood supply for the ischemic region. In the present study, we focus on the therapeutic properties of the human WJ-MSCs derived product, Cardio. We investigated the role of CardioCell in promoting angiogenesis and relieving hindlimb ischemia. Our results confirm the healing effect of CardioCell and strongly support the use of the WJ-MSCs in regenerative medicine.


Assuntos
Membro Posterior/irrigação sanguínea , Isquemia/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Geleia de Wharton/citologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos SCID , Neovascularização Fisiológica , Regeneração
13.
Cell Transplant ; 28(7): 801-812, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31018669

RESUMO

The need to search for new, alternative treatments for various diseases has prompted scientists and physicians to focus their attention on regenerative medicine and broadly understood cell therapies. Currently, stem cells are being investigated for their potentially widespread use in therapies for many untreatable diseases. Nowadays modern treatment strategies willingly use mesenchymal stem cells (MSCs) derived from different sources. Researchers are increasingly aware of the nature of MSCs and new possibilities for their use. Due to their properties, especially their ability to self-regenerate, differentiate into several cell lineages and participate in immunomodulation, MSCs have become a promising tool in developing modern and efficient future treatment strategies. The great potential and availability of MSCs allow for their various clinical applications in the treatment of many incurable diseases. In addition to their many advantages and benefits, there are still questions about the use of MSCs. What are the mechanisms of action of MSCs? How do they reach their destination? Is the clinical use of MSCs safe? These are the main questions that arise regarding MSCs when they are considered as therapeutic tools. The diversity of MSCs, their different clinical applications, and their many traits that have not yet been thoroughly investigated are sources of discussions and controversial opinions about these cells. Here, we reviewed the current knowledge about MSCs in terms of their therapeutic potential, clinical effects and safety in clinical applications.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Medicina Regenerativa/métodos
14.
Int J Mol Sci ; 20(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013696

RESUMO

The properties of mesenchymal stem cells (MSCs), especially their self-renewal and ability to differentiate into different cell lines, are widely discussed. Considering the fact that MSCs isolated from perinatal tissues reveal higher differentiation capacity than most adult MSCs, we examined mesenchymal stem cells isolated from Wharton's jelly of umbilical cord (WJ-MSCs) in terms of pluripotency markers expression. Our studies showed that WJ-MSCs express some pluripotency markers-such as NANOG, OCT-4, and SSEA-4-but in comparison to iPS cells expression level is significantly lower. The level of expression can be raised under hypoxic conditions. Despite their high proliferation potential and ability to differentiate into different cells type, WJ-MSCs do not form tumors in vivo, the major caveat of iPS cells. Owing to their biological properties, high plasticity, proliferation capacity, and ease of isolation and culture, WJ-MSCs are turning out to be a promising tool of modern regenerative medicine.


Assuntos
Diferenciação Celular , Autorrenovação Celular , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Geleia de Wharton/citologia , Animais , Biomarcadores , Linhagem Celular , Transformação Celular Neoplásica , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Camundongos , Gravidez , Transcriptoma , Cordão Umbilical
15.
Pol Przegl Chir ; 92(5): 1-5, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-32945264

RESUMO

INTRODUCTION: Fournier gangrene (FG) is life - threatening condition, defined as the necrotizing fascitis of perineum and can spread to the adjacent areas. It is rare disease and infection is caused by mixed bacterial flora, seldom by fungal infection. Risk factors are: male sex, diabetes, hypertension, malignant neoplasms, alcoholism, immunospression. MATERIAL AND METHODS: The analysis of four group patients treateted for Fournier gangrene was made about diagnostic and therapeutic process, assessment of prognosis based on Fournier's Gangrene Severity Index). RESULTS: All patients were males. Average age at the moment of diagnosis was 60 years. All of them had comorbidities resulting with the higher risk of susceptibility to FG. Morbitity was 50%, despite of all of patients had less than 9 points in FGSI. DISCUSSION: The FG, despite of better diagnostic tools and technological progres remaines the significant clinical issue because of the mortality - 80%. "The golden standard" is surgical excision of necrotic tissues, antibiotics support, equation of fluid, electrolytes and base - acid balance, level of glycemia is very important. The treating results were assessed on the base of FGSI. The significance has the moment of performing the surgical intervention - it is proven, that should be carried out during 24 hours. The hyperbaric oxygen therapy is controversial. Seem to be appropriate if the infection is caused by anaerobic bacteria. CONCLUSIONS: Fournier syndrome is significant clinical issue. Its treatment requires early surgical approach with exicision of necrotic tissues, antibiotics support and treatment of hyperbaric oxygen in some cases.


Assuntos
Gangrena de Fournier/cirurgia , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/cirurgia , Índice de Gravidade de Doença , Antibacterianos/uso terapêutico , Desbridamento/métodos , Gangrena de Fournier/diagnóstico , Humanos , Oxigenoterapia Hiperbárica/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Pol Przegl Chir ; 93(1): 55-60, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33729173

RESUMO

INTRODUCTION: Fournier gangrene (FG) is life - threatening condition, defined as the necrotizing fascitis of perineum and can spread to the adjacent areas. It is rare disease and infection is caused by mixed bacterial flora, seldom by fungal infection. Risk factors are: male sex, diabetes, hypertension, malignant neoplasms, alcoholism, immunospression. MATERIAL AND METHODS: The analysis of four group patients treateted for Fournier gangrene was made about diagnostic and therapeutic process, assessment of prognosis based on Fournier's Gangrene Severity Index). RESULTS: All patients were males. Average age at the moment of diagnosis was 60 years. All of them had comorbidities resulting with the higher risk of susceptibility to FG. Morbitity was 50%, despite of all of patients had less than 9 points in FGSI. DISCUSSION: The FG, despite of better diagnostic tools and technological progres remaines the significant clinical issue because of the mortality - 80%. "The golden standard" is surgical excision of necrotic tissues, antibiotics support, equation of fluid, electrolytes and base - acid balance, level of glycemia is very important. The treating results were assessed on the base of FGSI. The significance has the moment of performing the surgical intervention - it is proven, that should be carried out during 24 hours. The hyperbaric oxygen therapy is controversial. Seem to be appropriate if the infection is caused by anaerobic bacteria. CONCLUSIONS: Fournier syndrome is significant clinical issue. Its treatment requires early surgical approach with exicision of necrotic tissues, antibiotics support and treatment of hyperbaric oxygen in some cases.


Assuntos
Antibacterianos/uso terapêutico , Desbridamento/métodos , Gangrena de Fournier/terapia , Oxigenoterapia Hiperbárica/métodos , Idoso , Gangrena de Fournier/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Food Chem Toxicol ; 116(Pt B): 369-378, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29698782

RESUMO

The aim of this study is to assess a potential mechanism by which the serotonergic system can control the expression and activity of cytochrome (CYP) 2C11 and CYP3A isoforms during liver insufficiency. A rat model of diethylnitrosamine (DEN)-induced liver insufficiency was developed by administering 50 mg/kg of DEN twice a week for 7 weeks. Dysfunction of the serotonergic system was evoked by feeding the rats with a tryptophan-free diet for three weeks. Dysfunction of the serotonergic system during liver insufficiency decreased the level of proinflammatory cytokines (TGF-ß and IL-1ß) and increased the level of an anti-inflammatory cytokine (IL-4). Simultaneously, activation of the repressive mechanism IL-4/JAK1/STAT6/SOCS1 of the JAK2/STAT5b-mediated signal transduction pathway and the pERK1/2/GR/STAT6 signal transduction pathway resulted in the suppression of the CYP2C11 and CYP3A isoforms. Moreover, dysfunction of the serotonergic system during liver insufficiency equalized the level of testosterone to the basal level, did not change the steady state of the corticosterone level and significantly enhanced the reduced level of growth hormone. An altered cytokine profile under control of the serotonergic system determines the regulation of CYP2C11 and CYP3A isoforms during liver insufficiency through mechanisms based on posttranscriptional and posttranslational processes.


Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP3A/metabolismo , Família 2 do Citocromo P450/metabolismo , Citocinas/sangue , Insuficiência Hepática/enzimologia , Serotonina/fisiologia , Esteroide 16-alfa-Hidroxilase/metabolismo , Animais , Biomarcadores/metabolismo , Peso Corporal , Dietilnitrosamina/toxicidade , Modelos Animais de Doenças , Insuficiência Hepática/induzido quimicamente , Insuficiência Hepática/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Tamanho do Órgão , Processamento de Proteína Pós-Traducional , Processamento Pós-Transcricional do RNA , Ratos Wistar , Transdução de Sinais , Testosterona/metabolismo , Fator de Crescimento Transformador beta/metabolismo
18.
Food Chem Toxicol ; 97: 70-81, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27565560

RESUMO

This study aimed to evaluate the impact of serotonergic system dysfunction on the regulation of cytochrome P4501A (CYP1A) during liver insufficiency. A rat model of liver insufficiency with a dysfunctional serotonergic system was developed. To induce liver insufficiency, animals were treated with nitrosodiethylamine (DEN) at 50 mg/kg of body weight twice a week for 7 weeks. To induce serotonergic system dysfunction, the animals were fed a tryptophan-free diet for 3 days. Serotonergic system dysfunction during liver insufficiency generated the aryl hydrocarbon receptor (AhR) activation and the "superinduction" of the AhR target genes: CYP1A1, CYP1B1 and UGT1A, with a concomitant increase in CYP1A1 protein and activity. CYP1A2 gene expression was simultaneously down-regulated, with a concomitant decrease in CYP1A2 protein and activity. A significant reduction in TRß receptor levels, together with a simultaneous increase of TRα receptor gene and protein level (mainly TRα2 isoform) after serotonergic system dysfunction, suggests that the serotoninergic system is involved in the regulation of CYP1A isoforms without influence from thyroid hormones during liver insufficiency. The interplay between the serotonergic system and the regulation of CYP1A isoforms, which are downstream targets of AhR activation, is dependent on hepatic function and can be observed without influence from thyroid hormones.


Assuntos
Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Regulação Enzimológica da Expressão Gênica , Insuficiência Hepática/metabolismo , Hormônios Tireóideos/metabolismo , Alquilantes/toxicidade , Animais , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Dietilnitrosamina/toxicidade , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Insuficiência Hepática/induzido quimicamente , Homeostase , Ratos , Receptores alfa dos Hormônios Tireóideos/genética , Receptores alfa dos Hormônios Tireóideos/metabolismo , Receptores beta dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/metabolismo
19.
Arthropod Struct Dev ; 45(4): 389-98, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27140505

RESUMO

The development and organization of the ovaries of ten species from four Psylloidea families (Psyllidae, Triozidae, Aphalaridae and Liviidae) have been investigated. The ovaries of the last larval stage (i.e. fifth instar) of all examined species are filled with numerous clusters of cystocytes which undergo synchronous incomplete mitotic division. Cystocytes of the given cluster are arranged into a rosette with polyfusome in the centre. These clusters are associated with single somatic cells. At the end of the fifth instar, the clusters begin to separate from each other, forming spherical ovarioles which are surrounded by a single layer of somatic cells. In the ovarioles of very young females all cystocytes enter the prophase of meiosis and differentiate shortly thereafter into oocytes and trophocytes (nurse cells). Meanwhile, somatic cells differentiate into cells of the inner epithelial sheath surrounding the trophocytes and into the prefollicular cells that encompass the oocytes. During this final differentiation, the trophocytes lose their cell membranes and become syncytial. Oocytes remain cellular and most of them (termed arrested oocytes) do not grow. In the ovarioles of older females, one oocyte encompassed by its follicle cells starts growing, still connected to the syncytial tropharium by a nutritive cord. After the short phase of previtellogenesis alone, the oocyte enters its vitellogenic the growth phase in the vitellarium. At that time, the second oocyte may enter the vitellarium and start its previtellogenic growth. In the light of the obtained results, the phylogeny of psyllids, as well as phylogenetic relationships between taxa of Hemiptera: Sternorrhyncha are discussed.


Assuntos
Hemípteros/crescimento & desenvolvimento , Animais , Feminino , Hemípteros/classificação , Hemípteros/citologia , Hemípteros/ultraestrutura , Larva/citologia , Larva/crescimento & desenvolvimento , Larva/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Ninfa/citologia , Ninfa/crescimento & desenvolvimento , Ninfa/ultraestrutura , Oócitos/citologia , Oócitos/crescimento & desenvolvimento , Oócitos/ultraestrutura , Ovário/citologia , Ovário/ultraestrutura , Filogenia
20.
Wideochir Inne Tech Maloinwazyjne ; 10(2): 320-3, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26240636

RESUMO

Cholecystectomy is a common procedure for the treatment of symptomatic cholecystitis. A rare complication is the occurrence of subcapsular haematoma of the liver. In the literature, there are only a few case reports of this type. A 25-year-old woman was admitted to the Surgical Department for surgical treatment of cholecystitis. No complications were observed intra-operatively. On the first day after surgery, the patient manifested symptoms of hypovolaemic shock. The patient was qualified for surgical treatment in the mode of emergency surgery - a giant subcapsular haematoma was found. She was referred to the Clinic of General, Transplant and Liver Surgery of the Medical University of Warsaw for further treatment. This case shows the importance of monitoring the life parameters of patients who have undergone laparoscopic surgery due to symptomatic cholecystitis during the first day after surgery.

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