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RESEARCH QUESTION: Are there any differences in viability, spindle abnormalities and mitochondrial and other organelle structures amongst embryos biopsied on day 3 versus day 5 before and after vitrification? DESIGN: A total of 240 day 3 biopsied embryos that developed to blastocysts but were rejected for transfer following preimplantation genetic testing for monogenic/single gene defects (PGT-M) (nâ¯=â¯115) or for aneuploidies (PGT-A) (nâ¯=â¯125) were divided into two groups: (i) 120 blastocysts treated for viability, spindle/chromosome configuration (SCC) analysis and transmission electron microscopy (TEM) analysis (fresh nâ¯=â¯20, nâ¯=â¯20, nâ¯=â¯20 and following vitrification/warming nâ¯=â¯20, nâ¯=â¯20, nâ¯=â¯20); (ii) 120 embryos were re-biopsied at the blastocyst stage and treated for viability, SCC and TEM analysis (fresh nâ¯=â¯20, nâ¯=â¯20, nâ¯=â¯20 and following vitrification/warming nâ¯=â¯20, nâ¯=â¯20, nâ¯=â¯20). Also, 60 vitrified blastocysts biopsied only on day 5 that were rejected for transfer following PGT-M (nâ¯=â¯6) or PGT-A (nâ¯=â¯54) were treated following warming for viability (nâ¯=â¯20), SCC (nâ¯=â¯20) and TEM analysis (nâ¯=â¯20). RESULTS: No differences were observed in SCC and ultrastructure between embryos biopsied on day 5 and day 3 but following vitrification higher numbers of abnormal spindles, distension of mitochondria, multivesicular bodies, lipofuscin droplets, altered cell junctions and occasionally excessive accumulation of glycogen granules were evident. The fresh day 3 biopsied group also had a lower incidence of damaged (propidium iodide-stained) cells compared with the fresh day 3+5 (Pâ¯=â¯0.02) and the vitrified day 5 (Pâ¯=â¯0.001) biopsied groups. CONCLUSIONS: Biopsies on day 5 and day 3 do not adversely affect embryo viability, SCC or ultrastructure, although following vitrification minimal embryo quality-dependent increases in spindle abnormalities and cell damage are observed.
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Blastocisto , Vitrificação , Biópsia , Cromossomos , Criopreservação , Embrião de Mamíferos , HumanosRESUMO
BACKGROUND: The aim of this study was to investigate bacterial translocation and its possible role in the development of post-resuscitation inflammatory response following Cardio-Pulmonary Resuscitation (CPR) after cardiac arrest. METHODS: Munich female swine were employed for a model of cardiac arrest via application of electrical current. After 7 min, CPR was initiated, and animals were either successfully return to spontaneous circulation (ROSC) within 40 min or not (no-ROSC). At the end of experimental period and prior to sacrifice, samples from the intestine, mesenteric lymph nodes (MLN), liver and portal vein blood were obtained. Evaluation of inflammation and gut permeability was performed; MLN, liver and portal vein samples were analyzed for 16 s rRNA detection and cytokine mRNA expression. RESULTS: A decreased expression of the tight junction protein Occludin, with higher levels of inflammation, greater epithelial disintegration, ulceration, loss of crypts and villi height were found in the intestines of the ROSC swine in comparison to no-ROSC. The macrophage surface antigen CD-14 staining was relatively more intense in the ROSC than in no-ROSC. Higher levels of TNF-α mRNA expression were present in the liver of the ROSC group. Finally, despite the inflammatory response and the gut mucosal alterations in ROSC group, no bacterial translocation was detected in liver, MLN and portal vein. CONCLUSIONS: We show that resuscitation from cardiac arrest induces inflammatory response and intestinal permeability in swine 4h after resuscitation, but not a bacterial translocation. Bacterial translocation is not an early phase phenomenon but probably part of the pathophysiologic sequelae.
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Reanimação Cardiopulmonar , Parada Cardíaca , Síndrome Pós-Parada Cardíaca , Animais , Translocação Bacteriana , Feminino , Parada Cardíaca/complicações , Parada Cardíaca/terapia , Inflamação , RNA Mensageiro , SuínosRESUMO
BACKGROUND: This study aims to investigate the probable lesions and injuries induced in the renal tissue after a cardiac arrest. The renal ischemia-reperfusion model in cardiac arrest describes the effects of ischemia in the kidneys, alongside a whole-body ischemia-reperfusion injury. This protocol excludes ischemic conditions caused by surgical vascular manipulation, venous injury or venous congestion. METHODS: For the experimental study, 24 swine were subjected to cardiac arrest. Seven minutes later, the cardiopulmonary resuscitation technique was performed for 5 min. Afterwards, advanced life support was provided. The resuscitated swine consisted one group and the non-resuscitated the other. Tissue samples were obtained from both groups for light and electron microscopy evaluation. RESULTS: Tissue lesions were observed in the tubules, parallel to destruction of the microvilli, reduction in the basal membrane invaginations, enlarged mitochondria, cellular vacuolization, cellular apoptosis and disorganization. In addition, fusion of the podocytes, destruction of the Bowman's capsule parietal epithelium and abnormal peripheral urinary space was observed. The damage appeared more extensive in the non-resuscitated swine group. CONCLUSIONS: Acute kidney injury is not the leading cause of death after cardiac arrest. However, evidence suggests that the kidney damage after a cardiac arrest should be highly considered in the prognosis of the patients' health outcome.
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Injúria Renal Aguda , Reanimação Cardiopulmonar , Parada Cardíaca , Traumatismo por Reperfusão , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Reanimação Cardiopulmonar/métodos , Humanos , Rim/patologia , Traumatismo por Reperfusão/patologia , SuínosRESUMO
BACKGROUND: Fungal infections can pose great threat to sight. Immediate treatment is usually required; antifungal agents are widely accepted and are effective in most cases. The present experimental study aims to investigate the probable effects of intravitreal injection of antifungal agents on the structure and mechanical properties of the surface of peripheral blood erythrocytes. METHODS: Nine albino New Zealand white rabbits, aged five months old, were chosen for the experiment. Solutions of micafungin, voriconazole, or balanced salt solution (BSS) were injected into the midvitreous. Animals were divided into two experimental groups and one control group. Blood sampling from an intravenous (IV) line was performed after 10 days from the last IV injection. An atomic force microscope (AFM) was used to study the structural and mechanical properties of cell surfaces. RESULTS: The analysis results showed that the parameters of the cytoskeleton's spatial organization changed insignificantly with the antifungal drug treatment. CONCLUSIONS: Our findings suggest that locally administered antifungal drugs can cause significant changes to the structure and frictional properties of the erythrocyte surface. These effects occur in the long-term period after administration of the drugs and represent a potential possibility for violation of blood supply to tissues, and the further development of negative side effects.
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Antifúngicos , Micoses , Animais , Antifúngicos/uso terapêutico , Eritrócitos , Micafungina/uso terapêutico , Micoses/tratamento farmacológico , Coelhos , Voriconazol/farmacologiaRESUMO
Background and objectives: Preimplantation genetic testing (PGT) offers patients the possibility of having a healthy baby free of chromosomal or genetic disorders. The present study focuses on the application of PGT for patients located in Northern Greece, investigating their clinical outcomes, their motives, and their overall physical and emotional experience during the treatment, in association with their socioeconomic background. Materials and Methods: Couples who underwent PGT for a monogenic condition (PGT-M, n = 19 cycles) or aneuploidy (PGT-A, n = 22 cycles) participated in the study. Fertilization, implantation, and pregnancy rates were recorded for all cycles. The couples were asked to fill in a questionnaire about the consultation they had received prior to treatment, their sociodemographic information, and the psychological impact PGT had on both the female and male partner. Results: The fertilization, implantation, and ongoing pregnancy rates for the PGT-M and PGT-A cycles were 81.3%, 70.6%, and 52.9%, and 78.2%, 64.3%, and 57.1%, respectively. Females experienced more intense physical pain than their male partners while psychological pain was encountered by both partners and occasionally in higher instances in males. No typical socioeconomic background of the patients referred for PGT in Northern Greece was noticed. Conclusion: PGT is an attractive alternative to prenatal diagnosis (PND), aiming to establisha healthy pregnancy by identifying and avoiding the transfer of chromosomally or genetically abnormal embryos to the uterus. Although the benefits of PGT were well-received by all patients undergoing the procedure, psychological pain was evident and especially prominent in patients with a previous affected child or no normal embryos for transfer. Holistic counseling is of utmost importance in order to make patients' experience during their journey to have a healthy baby less emotionally demanding and help them make the right choices for the future.
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Diagnóstico Pré-Implantação , Feminino , Humanos , Masculino , Gravidez , Fertilização in vitro/métodos , Testes Genéticos/métodos , Dor , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Classe SocialRESUMO
Background and Objectives: Ankylosing spondylitis (AS) is a condition that affects 0.1% to 0.5% of the adult population. The aim of this case report was to investigate the possible effects of the drugs taken for treatment of AS as well as mRNA vaccination for COVID-19 on semen quality by performing a highly detailed analysis. Materials and Methods: Sperm characteristics were examined by light microscopy, DNA fragmentation (DFI) was analysed by flow cytometry and morphology was evaluated by transmission electron microscopy (TEM). Results: Semen analysis under therapy with (1) celecoxib and sulphasalazine showed: concentration 47 million/mL, 53% progressive motility, 7% normal morphology and 9.6% DFI, (2) Golimumab and before mRNA Vaccination showed: concentration 108 million/mL, 82% progressive motility, 1% normal morphology and 7.6% DFI, and (3) Golimumab and after 3 doses of mRNA Vaccination showed: concentration 142 million/mL, 85% progressive motility, 1% normal morphology and 6.8% DFI. TEM revealed head, neck and tail abnormalities, as well as the presence of cells with incomplete spermiogenesis white cells and phagocytes in the sample under therapy with celecoxib and sulphasalazine. Golimumab treatment lead to an increased incidence of elongated heads but in general reduced inflammation as no white cells were evident in TEM. Conclusion: The anti-inflamatory drugs celecoxib and sulphasalazine had no adverse effect on sperm quality as all parameters were within normal limits and the patient achieved under that treatment 2 pregnancies following natural conception that lead to the birth of a healthy boy and girl respectively. Anti-TNFa treatment with Golimumab exerted a negative effect on morphology but not on concentration, motility and DFI. After 3 doses of mRNA Vaccination, sperm concentration increased while motility, morphology and DFI remained similar to the values before vaccination suggesting no negative effect of the mRNA vaccine for COVID-19 on sperm quality.
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COVID-19 , Infertilidade Masculina , Espondilite Anquilosante , Vacinas contra COVID-19 , Feminino , Humanos , Infertilidade Masculina/genética , Masculino , Gravidez , RNA Mensageiro , SARS-CoV-2 , Sêmen , Análise do Sêmen , Espondilite Anquilosante/tratamento farmacológico , Vacinação , Vacinas Sintéticas , Vacinas de mRNARESUMO
RESEARCH QUESTION: Are there any differences in viability and ultrastructure amongst embryos biopsied on Day 5 versus Day 3 following vitrification in open and closed systems and compared to fresh embryos? DESIGN: One hundred human embryos (40 blastocysts biopsied on Day 5 and subsequently vitrified in open or closed systems and 60 Day 3 biopsied embryos that developed to blastocysts but were rejected for transfer following preimplantation genetic testing for monogenic/single gene defects and for aneuploidies were either treated fresh [nâ¯=â¯20] or vitrified [nâ¯=â¯40] in open or closed systems) and following warming and culture for 4 h were subjected to viability staining with carboxyfluorescein-diacetate succinimidylester/propidium iodide or processed for transmission electron microscopy. RESULTS: No statistically significant differences were observed in the viability of human biopsied embryos following vitrification in open and closed systems. Compared to fresh embryos, vitrified ones had a higher incidence of damage (propidium iodide-stained cells) irrespective of the vitrification method (Pâ¯=â¯0.005). These damaged cells were more prominent in Day 5 biopsied blastocysts and mainly located at the position of cutting. Characteristic lipofuscin droplets (representative of apoptosis) and a higher number of vacuoles and distension of mitochondria were also more evident in vitrified embryos, although this was not statistically assessed. CONCLUSIONS: Vitrification in open and closed systems does not adversely affect the viability and ultrastructure of Day 5 and Day 3 biopsied embryos as revealed by the minimal yet statistically significant cell damage observed. This damage may be compensated by the embryos, which in their attempt to fully recover following vitrification, potentially enable 'rescue' processes to eliminate it.
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Biópsia , Sobrevivência Celular/fisiologia , Criopreservação/métodos , Embrião de Mamíferos/fisiologia , Embrião de Mamíferos/ultraestrutura , Corantes Fluorescentes , Blastocisto/ultraestrutura , Técnicas de Cultura Embrionária , Fluoresceínas , Humanos , Microscopia Eletrônica de Transmissão , Propídio , SuccinimidasRESUMO
Background and objectives: Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. Materials and Methods: In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY) - High-Motility Group (HMG) - box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Results: Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker's expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. Conclusions: The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function.
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Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Nervo Femoral/metabolismo , Administração Oral , Alendronato/efeitos adversos , Alendronato/uso terapêutico , Animais , Antígenos Nucleares/efeitos dos fármacos , Antígenos Nucleares/metabolismo , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Casos e Controles , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Feminino , Nervo Femoral/efeitos dos fármacos , Nervo Femoral/fisiopatologia , Nervo Femoral/ultraestrutura , Humanos , Imuno-Histoquímica/métodos , Modelos Animais , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/ultraestrutura , Proteínas do Tecido Nervoso/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Ratos Wistar , Fatores de Transcrição SOXE/efeitos dos fármacos , Fatores de Transcrição SOXE/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Bisphosphonates (BPs) are selective inhibitors of osteoclasts, used for the treatment of bone disorders. The objective of this study is to investigate the possible effects of BPs on the tongue's mucosa. MATERIALS AND METHODS: Specimens of the tongue of 20 female 12-month old Wistar rats were taken. Ten were used as control group, while in the remaining alendronate (Fosamax, Merck) was administered per os from 13 weeks. Observation of the harvested samples was made by Transmission Electron Microscopy (TEM). RESULTS: In the experimental group, focal alterations were observed to various extent in all specimens. The basement membrane was intact. Furthermore, an increase at the intercellular space was observed, predominantly at the middle layer, and the desmosomes were disorganized. In the lamina propria focal edema was observed. CONCLUSIONS: Investigation on the effect of BPs on the tongue's mucosa through TEM hasn't been documented in the past. According to our results, BPs seem to cause mild mucosal lesions on the tongue.
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Difosfonatos/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Feminino , Microscopia Eletrônica/métodos , Mucosa Bucal/patologia , Mucosa Bucal/fisiopatologia , Osteoporose/prevenção & controle , Ratos , Ratos Wistar , Língua/efeitos dos fármacos , Língua/patologia , Língua/fisiopatologiaRESUMO
Crocus sativus L., a dietary herb, has been used for various diseases including cancer. This is an in vitro study investigating the antineoplastic effect of the extract of the plant against C6 glioma rat cell line. The mechanism of cellular death and the synergistic effect of the extract with the alkylating agent temozolomide (TMZ) were investigated. Cellular viability was examined in various concentrations of the extract alone or in combination with TMZ. Apoptosis was determined with flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and autophagy by western blotting of the light chain 3 (LC3)-II. Cellular viability was reduced after exposure to the extract with half maximal inhibition concentration at 3 mg/ml. Flow cytometry and TUNEL assay suggested that the extract does not induce apoptosis. Moreover, their combination increased the ratio dead/apoptotic cells 10-fold (P < 0.001). LC3-II protein levels reduced after Crocus extract while this effect was reversed when the calpain inhibitor MDL28170 was added, suggesting a calpain-dependent death possibly through autophagy. We concluded that the extract of Crocus increases dead cell number after 48 h of exposure. Our results suggest that the cell undergoes calpain-dependent programmed cell death while co-exposure to Crocus extract and TMZ enhances the antineoplastic effect of the latter.
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Calpaína/fisiologia , Morte Celular/efeitos dos fármacos , Crocus/química , Glioma/patologia , Extratos Vegetais/farmacologia , Temozolomida/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Calpaína/antagonistas & inibidores , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Sinergismo Farmacológico , Glioma/tratamento farmacológico , Marcação In Situ das Extremidades Cortadas , RatosRESUMO
Vitrification is widely used to cryopreserve supernumerary embryos following in vitro fertilization (IVF). The mouse model was used to investigate the effects of vitrification on blastomere viability, using viability markers, and on the cytoskeleton, by analysing spindle/chromosome configurations, using confocal scanning microscopy. Ninety cleavage and morula stage dimethyl sulphoxide (DMSO)/EG vitrified mouse embryos were either processed immediately following warming for viability assessment by labelling with the fluorescent markers carboxyfluorescein-diacetate succinimidylester (CFSE) and propidium iodide (PI) or were cultured to the blastocyst stage and immunostained with α-tubulin antibody to visualize microtubules and DAPI or PI to visualize DNA. Sixty-five fresh embryos were also used as the control. Vitrified embryos showed high survival rates following warming, but they had a higher incidence of damaged blastomeres compared with fresh embryos. Most mitotic spindles examined in all groups were normal, but multivariable analysis revealed that the proportion of abnormal spindles was significantly higher in vitrified/warmed embryos (P < 0.05). This study is the first to examine the immediate effects of vitrification on blastomere viability, using fluorescent markers and shows that although vitrification results in a higher incidence of damaged blastomeres, vitrified embryos may compensate for this limited number of damaged/abnormal cells, as development to the blastocyst stage was not compromised.
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Blastômeros/citologia , Blastômeros/fisiologia , Embrião de Mamíferos/citologia , Vitrificação , Animais , Blastocisto/patologia , Criopreservação/métodos , Citoesqueleto , Dimetil Sulfóxido , Embrião de Mamíferos/fisiologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Mórula , Fuso Acromático , Tubulina (Proteína)/metabolismoRESUMO
Interleukins are potential therapeutic targets that can alter the prognosis and progression of inflammatory bowel disease (IBD). The roles of IL-6, IL-10, IL-17, and IL-23 have been extensively studied, setting the stage for the development of novel treatments for patients with IBD. Other cytokines have been less extensively studied. Members of the IL-20 family, mainly IL-19 and IL-24, are involved in the pathogenesis of IBD, but their exact role remains unclear. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of colonic Tregs in animal models of colitis and patients with IBD. IL-21 is involved in the Th1, Th2, and Th17 responses. Data support a promising future use of these interleukins as biomarkers of severe diseases and as potential therapeutic targets for novel monoclonal antibodies. This review aims to summarize the existing studies involving animal models of colitis and patients with IBD to clarify their role in the intestinal mucosa.
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Background IL-19 and IL-24 induce proinflammatory cytokine production through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. The primary objective of this study was to investigate any changes in IL-19 and IL-24 expression between inflammatory bowel disease (IBD) patients and healthy controls, as well as before and after the initiation of biologics. The secondary objective was to investigate any relation between their expression and disease phenotype and activity. Methods IL-19 and IL-24 expression was measured in intestinal tissue samples from 121 patients with moderate to severe IBD versus healthy controls using immunohistochemistry. Their expression was then measured 12 months after treatment on the patient group treated with biologics. The disease activity was measured before and after treatment using the Harvey Bradshaw Index (HBI) for Crohn's disease (CD) patients and the Mayo Score (MS) for ulcerative colitis (UC) patients. Data were analyzed using SPSS (IBM Inc., Armonk, New York). Results IL-19 expression was raised in the IBD group versus healthy controls. In the CD group, the IL-19 expression was related with the disease activity score post-biologic treatment. IL-24 was also highly expressed in patients with active UC and CD and was increased post-treatment. Its expression in UC was statistically related with the MS. Conclusions IL-24 and IL-19 are key factors in IBD-related intestinal inflammation and this is one of the few human studies to suggest that. An immunosuppressive role of IL-24 was demonstrated in the UC group. A future use as biomarkers of disease activity and response to treatment might be feasible.
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Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.
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PURPOSE: Pancreatic cancer (PC) is a fatal malignancy with an aggressive course derived from the cells of pancreatic tissue. Gestational diabetes mellitus (GDM) is a state of spontaneous hyperglycemia occurring during gestation and has been suggested as a risk factor PC. Women with a history of GDM revealed a risk rate of 7.1% for the development of PC. The current systematic review aims to investigate the correlation between GDM and the degree to the prevalence of PC. METHODOLOGY: For this systematic review, the PICO model was prepared to construct and outline the exact questions of the study, a PRISMA flow diagram was prepared and quality assessment was conducted using the Newcastle Ottawa Scale (NOS) for Cohort Studies, the NIH Quality Assessment Tool-Criteria for Case Reports and the Cochrane quality assessment tool for Systematic Reviews and Meta-analysis studies. RESULT: A total of eight articles were retrieved from the main databases, and a table was created to summarize the information found. Even though the data found were limited, the quality assessment performed revealed that the articles were of high validity. CONCLUSIONS: It can be concluded that GDM has an association with the development of PC and can be considered as a risk factor.
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CD24 and CD171 are cell adhesion proteins, which have been shown to be overexpressed in several carcinomas and to be associated with a poor clinical outcome. Our aim was to determine the expression of these two adhesion molecules in ovarian borderline neoplasms. We investigated 50 ovarian borderline tumors (serous, mucinous and endometrioid) as well as 29 benign cystadenomas and 25 carcinomas, which were used as controls. Paraffin sections were stained immunohistochemically for CD24 and CD171, and their expression was recorded in a semi-quantitative manner. In normal epithelium and benign ovarian cystadenomas both the CD24 and CD171 expression was negative to low, while their expression was significantly increased in borderline and malignant ovarian tumors. High-grade carcinomas, and carcinomas with metastases to the omentum presented considerably higher CD24 expression than low-grade carcinomas, and carcinomas without metastases. In addition, a few borderline and many malignant tumors presented cytoplasmic CD24 immunoreactivity, whereas all benign and most borderline tumors showed apical localization of this molecule. In conclusion, borderline tumors and carcinomas of the ovary present increased expression of CD24 and CD171 in relation to their benign counterparts, as is the case in malignant tumors of other organs. Change of staining pattern of CD24 (apical to cytoplasmic) apparently relates to a more aggressive phenotype.
Assuntos
Biomarcadores Tumorais/análise , Antígeno CD24/biossíntese , Molécula L1 de Adesão de Célula Nervosa/biossíntese , Neoplasias Ovarianas/metabolismo , Adulto , Antígeno CD24/análise , Feminino , Humanos , Imuno-Histoquímica , Molécula L1 de Adesão de Célula Nervosa/análise , Neoplasias Ovarianas/patologiaRESUMO
Interleukins are considered to be potential therapeutic targets that can alter the prognosis and disease progression of IBD. IL-21 has proven to be involved in effector Th1, Th2 and Th17 responses. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of the colonic Tregs in animal models of colitis and patients with IBD. In this retrospective study, we have studied the expression of these interleukins, using immunohistochemistry, in 121 patients with moderate to severe IBD before and after treatment with biologics. The results were statistically processed using SPSSTM. Increased IL-21 expression was found in the UC and CD groups versus the controls. The IL-33 expression was found to be increased in the post-treatment UC and CD groups, suggesting a protective role of this interleukin against bowel inflammation. The IL-33 expression post-treatment was reversely correlated with the activity index score in CD patients, suggesting a better response to treatment in patients with higher IL-33 mucosa levels. This is the first immunohistochemical study of the expression of those interleukins in bowel mucosa before and after treatment with biologics. These data support a possibly promising future use of these interleukins as biomarkers of severe disease and response to treatment and as potential therapeutic targets for novel monoclonal antibodies.
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PURPOSE: Tinnitus, the generation of phantom sounds, can be the result of noise exposure, however, understanding of its underlying mechanisms is limited. Purpose of the study was is to determine whether different concentrations of salicylate can cause tinnitus of different intensity. METHODS: For the purposes of this study 50 male Wistar rats were used. The animals were divided into 5 groups (10 rats in each group). The animals that did not receive any substance were allocated to the control group (Group A). The second group (Group B) of rats received salicylate (Sigma Aldrich) intraperitoneally for 7 days (300 mg/Kg/day). The 3rd group (Group C) received salicylate intraperitoneally for 7 days, but at twice the concentration of the animals in the second group (600 mg/kg/d). The 4th group (Group D) simultaneously received salicylate (300 mg/Kg/day) and pure Memantine (Sigma Aldrich, 10 mg/kg/d) intraperitoneally for 7 days. The 5th group (Group E) did not receive any substance but was exposed for 168 consecutive hours (7 days) to sound to induce tinnitus. Cochlear activity was evaluated with the use of Distortion Product Otoacoustic Emissions (DPOAEs). At the end of the experimental period, the animals were sacrificed, and the right cochlea was removed and prepared for further histological and immunohistochemical studies. RESULTS: The DPOAEs of animals treated either with salicylate as monotherapy or salicylate combined with memantine were indistinguishable from the noise floor, did not differ significantly compared to the animals of the control group or those expose to constant noise. The cochlear structures of Group E remained anatomically and functionally unaffected from the exposure to constant noise. Memantine does not seem to offer substantial protection to the cochlear structures, according to histological examination and hearing tests, however, the rats receiving it exhibited better results in behavioral tests. CONCLUSIONS: The administration of memantine does not contribute significantly to the reduction of tinnitus.
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Harlequin ichthyosis (HI) is a life-threatening genetic disorder that largely affects the skin of infants. HI is the most severe form of the autosomal recessive disorder known as ichthyosis. It is caused by mutations in the A12 cassette (lipid-transporter adenosine triphosphate-binding cassette A12). Neonates affected by this disease are born with specific morphological characteristics, the most prominent of which is the appearance of platelet keratotic scales separated by erythematous fissures. The facial features include eclabium, ectropion, a distinct flattened nose, and dysplastic ears. A common finding among those with HI is impaired skin barrier function. The purpose of the present narrative review is to assess the most recent literature regarding the management of HI. Emphasis is given to surgical management and consultation, to the indications for timing and surgical intervention, to the risks that are presented with surgery, and to the details of the surgical procedure itself. Management of HI requires a multidisciplinary team of experts, and specific guidelines are needed in order for the risks to be minimized and viability to be increased.
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Hidrocystomas are benign lesions with frequent localization on the eyelids and common appearance as isolated translucent cystic lesions. The multiple and bilateral localization has been associated with systemic diseases or epidermodysplasia. The histological and ultrastructural study contributes to the distinction in eccrine or apocrine. In this clinical case, multiple bilateral skin lesions of the eyelids were removed surgically from a 55-year-old male patient with free medical history. The lesions were fully removed surgically without rupture of the cysts. The obtained tissues were fixed and prepared for an anatomical pathology study as well as observation under the electron microscope. The histological study revealed cystic lesions with low cuboid epithelium and presence of cells and collagen fibrils, while the ultrastructural study also revealed the presence of apoptotic and secretory cells as well as vacuolization of the cytoplasm. No relapse of the lesions was obtained. In conclusion, the histological and ultrastructural study of multiple hidrocystomas can highlight special features that help to better classify and diagnose eccrine or apocrine hidrocystomas, while surgical removal without rupture of the cyst can prevent reappearance.