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Metabolic enzymes can adapt during energy stress, but the consequences of these adaptations remain understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, forms rings around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and mitochondrial dynamics protein (MiD51). HK1-rings prevent mitochondrial fission by displacing the dynamin-related protein 1 (Drp1) from mitochondrial fission factor (Mff) and mitochondrial fission 1 protein (Fis1). The disassembly of HK1-rings during energy restoration correlated with mitochondrial fission. Mechanistically, we identified that the lack of ATP and glucose-6-phosphate (G6P) promotes the formation of HK1-rings. Mutations that affect the formation of HK1-rings showed that HK1-rings rewire cellular metabolism toward increased TCA cycle activity. Our findings highlight that HK1 is an energy stress sensor that regulates the shape, connectivity, and metabolic activity of mitochondria. Thus, the formation of HK1-rings may affect mitochondrial function in energy-stress-related pathologies.
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Dinaminas , Metabolismo Energético , Hexoquinase , Mitocôndrias , Dinâmica Mitocondrial , Proteínas Mitocondriais , Hexoquinase/metabolismo , Hexoquinase/genética , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/genética , Mitocôndrias/enzimologia , Dinaminas/metabolismo , Dinaminas/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Animais , Trifosfato de Adenosina/metabolismo , Estresse Fisiológico , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Ciclo do Ácido Cítrico , Glucose-6-Fosfato/metabolismo , Camundongos , Células HeLa , Células HEK293 , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , MutaçãoRESUMO
OBJECTIVE: To investigate the relationship between intraprostatic 68Ga-prostate-specific membrane antigen (PSMA) uptake values and volumetric parameters derived from early pelvic and standard-time whole-body 68Ga-PSMA PET/computed tomography (CT) images in untreated prostate cancer (PCa) patients, and to assess the predictive significance of these data in relation to disease prognosis, comparing them with the Gleason score, clinical risk classification and the presence of metastatic disease detected in 68Ga-PSMA PET/CT imaging. METHODS: Eighty-one newly diagnosed PCa patients underwent early phase pelvic imaging at the 5th minute and standard time whole-body imaging at the 60th minute. Various threshold values were used in intraprostatic delineations to compute maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), intraprostatic PSMA tumor volume and intraprostatic total lesion PSMA uptake. Correlations between early and standard time measurements, as well as changes in SUV parameters over time, were examined. The association of these values with Gleason score, clinical risk status (National Comprehensive Cancer Network), and metastatic disease was explored. RESULTS: SUVmax measurements from both early and standard time images distinguished all three groups (clinical risk scores, Gleason score and metastatic group), with standard imaging demonstrating statistical superiority in receiver operating characteristic analyses. Strong correlations were observed between early and standard-time PET parameters. Changes in intraprostatic SUVmax and SUVmean values over time did not exhibit predictive value. CONCLUSION: Although intraprostatic PSMA PET parameters generally aligned at both early and standard times, parameters obtained from standard time images showed more robust correlations with clinical risk scores, Gleason score and metastasis status in newly diagnosed, untreated PCa patients.
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Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Idoso , Pessoa de Meia-Idade , Ácido Edético/análogos & derivados , Carga Tumoral , Fatores de Tempo , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Although rhinoplastic surgery has progressed considerably in recent years, nasal dorsal irregularities still cause postoperative distress for both surgeons and patients. PURPOSE: The aim of this study was to measure the association between two biologic graft adjuncts, platelet-rich plasma (PRP) and concentrated growth factor (CGF), and ultra-diced cartilage viability in an animal model. STUDY DESIGN, SETTING, AND SAMPLE: This study was designed as a randomized in-vivo study using a rabbit model. Fourteen rabbits were utilized in this investigation. The ultra-diced cartilage was obtained from auricular cartilage. PREDICTOR VARIABLE: The graft biologic adjunct is the predictor variable. There were three treatment groups: graft mixed with PRP or CGF or untreated (control). The grafts were placed in three separate pockets opened on the same rabbit. Grafts were harvested 3 months after insertion for analysis. MAIN OUTCOME VARIABLE(S): The primary outcome variable was histopathological and regenerative scores obtained from multiple histopathological parameters indicating the viability of the cartilage. Histopathological score parameters were chondrocyte loss, inflammation, fibrosis, cartilage fragmentation, and calcified area formations in the lacunae. Regenerative score parameters were peripheral cell proliferation in the cartilage tissue, vascularization in the connective tissue, proteoglycan increase in the matrix, and the amount of connective tissue. COVARIATES: The variables were age, sex, and weight. ANALYSES: Statistical analysis employed the analysis of variance test, with a significance level of P < .05. RESULTS: The sample was composed of 14 rabbits and 42 samples. The histopathologic scores were 11.93 (±2.49), 8.78 (±2.19), and 6.85 (±1.46) for the control, PRP, and CGF groups, respectively. A statistically significant difference was found in the PRP (P < .0275) and CGF (P < .0001) groups compared to the control group. The regenerative scores were 6.21 (±0.97), 8.85 (±1.70), and 12.07 (±1.26) for the control, PRP and CGF groups, respectively. A statistically significant difference was found in the PRP (P < .0159) and CGF (P < .0001) groups compared to the control group. CONCLUSION AND RELEVANCE: This is the first study investigating the ultra-diced cartilage graft in an experimental animal model. Histopathological examination has shown that mixing ultra-diced cartilage with CGF or PRP increases viability by reducing the histopathological score and increasing the regenerative score.
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BACKGROUND: The metabolic impacts of including soya meal, wheat gluten and corn gluten in the diet of male lambs could influence their reproductive performance. OBJECTIVES: An experiment was carried out to assess the effects of corn gluten, wheat gluten and soya meal on the reproductive system of male lambs. METHODS: Twenty-four male Morkaraman lambs, aged 9 months, were utilized in this study and were fed experimental diets for 56 days. The lambs were divided into a control group (soybean meal + safflower meal), a corn group (corn gluten) and a wheat group (wheat gluten). RESULTS: The serum follicle-stimulating hormone level of the control group was significantly higher and tumour necrosis factor-alpha (TNF-α) level was lower than the wheat and corn gluten groups (p < 0.05). The lowest malondialdehyde level in testicular tissue was observed in the control group, whereas the highest was in the wheat gluten group (p < 0.05). The glutathione level in the control group was significantly higher than in the other groups (p < 0.05). The corn gluten group showed the highest CHOP and IRE1 levels; the lowest Bcl-2 levels and the highest IL-1B and P2 × 7R levels were found in the wheat group; and the lowest TNF-α levels were in the control group (p < 0.05). Additionally, the study revealed that diet had a significant impact on spermatological parameters of the testis such as diameter, volume and weight (p < 0.05). CONCLUSIONS: These results concluded that the inclusion of different protein sources in the diet of reproductive male lambs affects the metabolism of testicular tissue.
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Ração Animal , Dieta , Estresse do Retículo Endoplasmático , Espermatozoides , Testículo , Animais , Masculino , Dieta/veterinária , Ração Animal/análise , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Espermatozoides/fisiologia , Espermatozoides/efeitos dos fármacos , Análise do Sêmen/veterinária , Carneiro Doméstico/fisiologia , Ovinos/fisiologia , Triticum/química , Fenômenos Fisiológicos da Nutrição Animal , Zea mays/química , Glycine max/químicaRESUMO
AIM: To evaluate certain factors that may affect the decision-making process for the rational management approach in cases presenting with bilateral ureteral stones. METHODS: A total of 153 patients presenting with bilateral ureteral stones from 6 centers were evaluated and divided in three groups. Group 1 (n:21) Patients undergoing DJ stent insertion in one ureter and ureterorenoscopic (URS) lithotripsy for the contralateral ureteral stone. Group 2 (n:91), URS lithotripsy for both ureteral stones and Group 3 (n:41) patients undergoing bilateral DJ stent insertion. The outcomes of the procedures and the relevant patient as well as stone related factors have been comparatively evaluated in three groups. RESULTS: While associated UTI rates and serum creatinine levels were significantly higher in bilateral DJ group, previous URS history was found to be significantly higher in cases undergoing bilateral URS than those undergoing bilateral DJ stenting. URS was performed significantly more often in cases with lower ureteral stones and DJ stenting seems to be more rational approach in upper ureteral stones. In patients with lower ureteral stones, larger and harder stones, endourologists tended to perform URS as the first option. CONCLUSIONS: Decision making for a rational approach in cases with bilateral ureteral stones my be challenging. Our findings demonstated that serum creatinine levels, associated UTI, location and the hardness of the stone and previous ureteroscopy anamnesis could be important factors in making a decision between JJ stenting and ureteroscopic stone extraction in emergency conditions.
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Tomada de Decisão Clínica , Litotripsia , Stents , Cálculos Ureterais , Ureteroscopia , Humanos , Cálculos Ureterais/cirurgia , Cálculos Ureterais/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Litotripsia/métodos , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Creatinina/sangue , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologiaRESUMO
Introduction: Juvenile idiopathic arthritis ( JIA) is a persistent autoimmune-inflammatory disease that affects children younger than 16. Aggressive synovitis of the hip may cause joint destruction, hip protrusion, erosion, pseudosubluxation, dysplasia, and osteoarthritis. Subluxation of the hip had been reported previously. However, dislocation of the hip in JIA is an extremely rare situation, and only two cases have been reported up to date. Reduction of the dislocated hip has to be performed in any way. However, there is no algorithm to be followed for the treatment of hip dislocations caused by JIA. Case Presentation: In this study, we presented two cases of hip dislocation caused by JIA.Case 1: An 11-year-old boy had JIA and chronic recurrent multifocal osteomyelitis (CRMO). X-rays and computed tomography (CT) revealed a posterior dislocation of the left hip. An urgent operation was planned for the reduction of the hip. Avascular necrosis, dysplasia, or erosions were not evident at the last follow-up.Case 2: An 11-year-old girl was referred to the hospital with excessive left hip pain starting 24 h ago. A limited synovectomy with joint irrigation was performed. However, pathological examination of the synovium showed chronic inflammation consistent with JIA. On the post-operative 10th day, the patient was consulted for an increase in hip pain and deformity of the left hip. X-rays and MRI revealed posterior dislocation of the left hip with synovial hypertrophy. An urgent operation was planned. The hip could be reduced under anesthesia with mild traction, and a pelvipedal cast was applied only for 3 weeks. Avascular necrosis, dysplasia, destruction, or erosions were not evident at the last follow-up. Conclusion: For early diagnosed patient reduction under anesthesia and medial soft-tissue contracture release; for late diagnosed patient medial soft-tissue contracture release, capsulotomy and synovectomy were effective to prevent destruction and early degenerative changes of the hip joint for treatment of dislocation caused by JIA.
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Diffuse axonal injury (DAI), one of the most common and devastating type of traumatic brain injury, is the result of the shear force on axons due to severe rotational acceleration and deceleration. Neurogranin (NRGN) is a postsynaptic protein secreted by excitatory neurons, and synaptic dysfunction can alter extracellular NRGN levels. In this study, we examined NRGN levels in serum and cerebrospinal fluid (CSF) after experimental DAI in terms of their diagnostic value. Experimental DAI was induced using the Marmarou technique in male Wistar albino rats. Serum and CSF NRGN levels of the sham group, onehour, sixhour, 24hour, and 72hour postDAI groups were measured by ELISA method. DAI was verified by staining with hematoxylineosin and ßamyloid precursor protein in the rat brain samples. While no histopathological and immunohistochemical changes were observed in the early hours of the postDAI groups, the staining of the ßAPP visibly increased over time, with positivity being most frequent and intense in the 72hour group. It was found that serum NRGN levels were significantly lower in the 6hour group than in the sham group. The serum NRGN levels in the 24hour group were significantly higher than those in the sham group. This study showed a dichotomy of postDAI serum NRGN levels in consecutive time periods. NRGN levels in CSF were higher in the onehour group than in the sham group and returned to baseline by 72 hours, although not significantly. Our study provides an impression of serum and CSF NRGN levels in a rat DAI model in consecutive time periods. Further studies are needed to understand the diagnostic value of NRGN.
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Lesão Axonal Difusa , Neurogranina , Ratos , Masculino , Animais , Neurogranina/metabolismo , Ratos Wistar , Lesão Axonal Difusa/metabolismo , Lesão Axonal Difusa/patologia , Neurônios/metabolismo , Axônios/metabolismoRESUMO
PURPOSE: Body donors continue to have an important role in anatomy education in medical schools. Furthermore, the demand for organ transplantation is increasing as life expectancy increases. In Turkey, there are efforts to enable both donations to be made through a single system. These issues were addressed together, and it was aimed to evaluate the level of knowledge and attitudes of medical and law students regarding tissue-organ and body donation. METHODS: A questionnaire consisting of 29 questions was administered to 693 individuals to measure these aspects. Data were analyzed using a one-way analysis of variance with Bonferroni correction. Categorical data collected during the study were summarized in terms of frequency and percentage. RESULTS: When asked about their willingness to donate their bodies, 39.4% answered no, 29.5% responded yes, and 31.1% were undecided. Regarding organ donation, 61.8% of the participants expressed willingness, 22.8% were undecided, and 15.4% declined. Notably, there was a significant difference between those who had prior knowledge of organ tissue and body donation and those who did not (p < 0.001). CONCLUSION: The findings of our research indicate that knowledge about organ tissue and body donation, as well as the inclination to donate, increased as medical education progressed into clinical practice. Additionally, the level of knowledge among university students on this subject was found to be correlated with whether they had received prior training on the topic. It was observed that there is a need to provide more education for students to understand the importance of organ and body donation.
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Conhecimentos, Atitudes e Prática em Saúde , Obtenção de Tecidos e Órgãos , Humanos , Feminino , Masculino , Estudos Transversais , Inquéritos e Questionários , Adulto Jovem , Turquia , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Adulto , Anatomia/educação , Universidades , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Adolescente , Doadores de Tecidos/psicologiaRESUMO
Tissue-like constructs, intended for application in tissue engineering and regenerative medicine, can be produced by three-dimensional (3D) bioprinting of cells in hydrogels. It is essential that the viability and proliferation of the encapsulated cells can be reliably determined. Methods currently used to evaluate cell proliferation, such as quantification of DNA and measurement of metabolic activity, have been developed for application in 2D cultures and might not be suitable for bioinks. In this study, human fibroblasts were either cast or printed in gelatin methacryloyl (GelMA) or sodium alginate hydrogels and cell proliferation was assessed by AlamarBlue, PicoGreen and visual cell counts. Comparison of data extrapolated from standard curves generated from 2D cultures and 3D hydrogels showed potential inaccuracies. Moreover, there were pronounced discrepancies in cell numbers obtained from these assays; the different bioinks strongly influenced the outcomes. Overall, the results indicate that more than one method should be applied for better assessment of cell proliferation in bioinks.
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Bioimpressão , Humanos , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Hidrogéis , Gelatina , Proliferação de Células , Alicerces TeciduaisRESUMO
Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of central or peripheral nervous system tumors. The most common form, known as NF1 or Von Recklinghausen's disease, presents with distinct clinical features, including cutaneous and ocular manifestations, along with various other organ and systemic symptoms. While the lung findings associated with neurofibromatosis lack specificity, they can include parenchymal cysts and bullae formation, primarily in the upper-apical regions. Additionally, progressive fibrotic changes, such as ground-glass areas, consolidations, and paving stone patterns, may manifest in the basal parts of the lungs. In this case report, a case of NF1 diagnosed in adulthood and accompanying pneumoconiosis was discussed as a coincidence.
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Neurofibromatose 1 , Pneumoconiose , Humanos , Neurofibromatose 1/complicações , Masculino , Pneumoconiose/etiologia , Adulto , Pessoa de Meia-IdadeRESUMO
Objective: Currently, electrocautery devices have frequently been used in penile surgical procedures. We hypothesized that electrocautery using during penile surgical procedures may harm the taste rosea and the dorsal nerve of the penis or clitoris. Methods: Eighteen young age male New Zealand rabbits were studied: five in the control (Group I, n=5), five in the penile surgery without using electrocautery (sham group, Group II, n=5), eight in the monopolar cautery (study group, Group III, n=8) groups under general anesthesia. The animals were followed for 3 weeks and sacrificed. Penile tissue-pudendal nerve root complexes and dorsal root ganglion of sacral 3 level were examined using stereological methods. The results were compared statistically. Results: The live and degenerated taste bud-like structures and degenerated neuron densities of pudendal ganglia (mean±standard deviation, n/mm3) were estimated as 198±24/mm3, 4±1/mm3, and 5±1/mm3 in Group I; 8±3/mm3, 174±21/mm3, and 24±7/mm3 in Group II; and 21±5/mm3, 137±14/mm3, and 95±12/mm3 in Group III, respectively. Neurodegeneration of taste buds and pudendal ganglia was significantly different between groups. Conclusion: Intact spinal cord and normal parasympathetic and thoracolumbar sympathetic networks are crucial for human sexual function. The present study indicates that the glans penis injury by using electrocautery may lead to pudendal ganglia degeneration. Iatrogenic damage to taste rosea and retrograde degeneration of the pudendal nerve may be the cause of sexual dysfunction responsible mechanism.
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BACKGROUND: Cerebral vasospasm, a serious complication of subarachnoid hemorrhage (SAH), has been extensively studied for its neurochemical and pathophysiologic mechanisms. However, the contribution of inner elastic membrane dissection and subintimal hemorrhage to basilar artery occlusion remains underexplored. This study investigates inner elastic membrane-related changes in the basilar artery after SAH. METHODS: Twenty-four hybrid rabbits were divided into control, sham, and SAH groups, with SAH induced by autologous blood injection. After 2 weeks, basilar artery changes, vasospasm indexes (VSIs), and dissections were evaluated. RESULTS: The SAH group showed significantly higher VSI, with vascular wall thickening, luminal narrowing, convoluted smooth muscle cells, intimal elastic membrane disruption, endothelial cell desquamation, and apoptosis. Some SAH animals exhibited subintimal hemorrhage, inner elastic membrane dissection, and ruptures. Basilar arteries with subintimal hemorrhage had notably higher VSI. CONCLUSIONS: These findings highlight the role of subintimal hemorrhage and inner elastic membrane dissection in basilar artery occlusion post-SAH, offering valuable insights into vasospasm pathophysiology.
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Spinal cord injuries are very common worldwide, leading to permanent nerve function loss with devastating effects in the affected patients. The challenges and inadequate results in the current clinical treatments are leading scientists to innovative neural regenerative research. Advances in nanoscience and neural tissue engineering have opened new avenues for spinal cord injury (SCI) treatment. In order for designed nerve guidance conduit (NGC) to be functionally useful, it must have ideal scaffold properties and topographic features that promote the linear orientation of damaged axons. In this study, it is aimed to develop channeled polycaprolactone (PCL)/Poly-D,L-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, modify their surfaces by IKVAV pentapeptide/gold nanoparticles (AuNPs) or polypyrrole (PPy) and investigate the behavior of motor neurons on the designed scaffold surfaces in vitro under static/bioreactor conditions. Their potential to promote neural regeneration after implantation into the rat SCI by shaping the film scaffolds modified with neural factors into a tubular form is also examined. It is shown that channeled groups decorated with AuNPs highly promote neurite orientation under bioreactor conditions and also the developed optimal NGC (PCL/PLGA G1-IKVAV/BDNF/NGF-AuNP50) highly regenerates SCI. The results indicate that the designed scaffold can be an ideal candidate for spinal cord regeneration.
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Fator Neurotrófico Derivado do Encéfalo , Ouro , Nanopartículas Metálicas , Fator de Crescimento Neural , Traumatismos da Medula Espinal , Alicerces Teciduais , Animais , Ratos , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Oligopeptídeos/farmacologia , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Alicerces Teciduais/químicaRESUMO
BACKGROUND: The nucleosome assembly protein 1-like 1 (NAP1L1) is suggested to have an oncogenic role in several tumors based on its overexpression. However, its diagnostic and prognostic role in gastric cancer remains unclarified. This study aimed to evaluate the diagnostic and prognostic utility of NAP1L1 in gastric cancer patients. METHODS: A total of 85 patients [mean (SD) age: 60.9 (1.6) years, 49.4% were males] with newly-diagnosed gastric cancer and 40 healthy individuals [mean (SD) age: 60.7 (1.7) years, 52.5% were males] were included. Data on patient demographics (age, gender), TNM stages and tumor size, and the serum NAP1L1 levels were recorded. RESULTS: Serum NAP1L1 levels were significantly higher in gastric cancer patients than in control subjects [12 (9.5-13.8) vs. 1.8 (1.5-2.4) ng/mL, p < 0.001]. Also, certain tumor characteristics such as tumor size of >4 vs. <4 cm (p < 0.001), M1 vs. M0 stage (p < 0.001), N2 vs. N0 and N1 stage (p < 0.001), and T4 vs. lower T stage (p < 0.001) were associated with significantly higher serum NAP1L1 levels in gastric cancer patients. CONCLUSIONS: Our findings revealed for the first time that serum levels for NAP1L1 were overexpressed in the gastric cancer, as also correlated with the disease progression. NAP1L1 seems to be a potential biomarker for gastric cancer, providing clinically important information on early diagnosis and risk stratification.
This study aimed to investigate serum levels for nucleosome assembly protein 1-like 1 (NAP1L1) in patients with gastric cancer in relation to healthy controls and tumor pathology.It was demonstrated for the first time that serum levels for NAP1L1 were overexpressed in the gastric cancer, as also correlated with the disease progression.These findings seem to implicate the potential role of serum NAP1L1 as a distinct diagnostic and prognostic factor in patients with gastric cancer, offering clinically important information on early diagnosis and risk stratification.
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Proteína 1 de Modelagem do Nucleossomo , Neoplasias Gástricas , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Proteína 1 de Modelagem do Nucleossomo/metabolismo , Prognóstico , Neoplasias Gástricas/diagnóstico , BiomarcadoresRESUMO
When a cell sustains damage, it liberates cytosolic ATP, which can serve as an injury signal, affecting neighboring cells. This study presents a methodological approach that employs in vitro axotomy and in vivo laser ablation to simulate cellular injury. Specially tailored biosensors are employed to monitor ATP dynamics and calcium transients in injured cells and their surroundings. To simultaneously visualize extracellular and cytosolic ATP, we developed bicistronic constructs featuring GRABATP1.0 and MaLionR biosensors alongside the calcium sensor RCaMP, enabling multiparametric imaging. In addition to transducing primary neuron cultures, we developed another method where we cocultured dorsal root ganglion neurons together with specialized "sniffer" cell lines expressing the bicistronic biosensors. Exploiting these approaches, we successfully demonstrated the release of ATP from the injured neurons and its extracellular diffusion in response to cellular injury in vitro and in vivo. Axotomy triggered intracellular calcium mobilization not only in the injured neuron but also in the intact neighboring cells, providing new insights into ATP's role as an injury signal. The tools developed in this study have demonstrated remarkable efficiency in unraveling the intricacies of ATP-mediated injury signaling.
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Técnicas Biossensoriais , Cálcio , Ratos , Animais , Cálcio/metabolismo , Ratos Sprague-Dawley , Neurônios/metabolismo , Trifosfato de AdenosinaRESUMO
BACKGROUND: Increased intraocular pressure (IOP) likely secondary to an activated oculo-trigeminal reflex network is an important issue following subarachnoid hemorrhage (SAH). The relationship between the IOP and trigeminal ganglion (TGG) following experimental SAH was investigated in this study. METHODS: Twenty-three rabbits were used in this study. Five rabbits (n = 5) were used as the control group, another 5 as the sham group (n = 5), and the remaining 13 (n = 13) as the study group. The study group was further divided into two groups of animals with mild (n = 6) and severe (n = 7) TGG degeneration. The IOP values were recorded. After 2 weeks, the animals were decapitated. The mean degenerated neuron density of TGGs was estimated by stereological methods and analyzed statistically. RESULTS: The average IOP values were 11.85, 14.12, and 21.45 mm Hg in the control (n = 5), sham (n = 5), and study (n = 13) groups, respectively. The mean degenerated neuron density was 34, 237, and 3,165 mm3 in the control, sham, and study groups, respectively. CONCLUSION: According to the findings of this study, the experimental SAH leads to changes in IOP by affecting the TGG. By predicting and preventing IOP elevation in the setting of SAH, our findings will shed light on secondary sequelae such as glaucoma and irreversible blindness.
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Pressão Intraocular , Hemorragia Subaracnóidea , Animais , Coelhos , Modelos Animais de Doenças , Hemorragia Subaracnóidea/complicações , Gânglio Trigeminal , Degeneração NeuralRESUMO
OBJECTIVE: Although the effect of oculomotor and cervical sympathetic networks on pupil diameter is well known; the effect of the trigeminal nerve on pupil diameter has not been investigated yet. This subject was investigated. MATERIALS AND METHODS: Five of 23 rabbits were used as a control group (GI; n = 5); 0.5 ccs saline solution into cisterna magna injected animals used as SHAM (GII; n = 5); autologous blood injected to produce SAH used as the study group (GIII; n = 13) and followed up three weeks. Light-stimulated pupil diameters were measured with an ocular tomography device before, middle, and at the end of the experiment. Considering the sclera area/pupil area ratio index (PRI) as the pupillary reaction area, we used this equation for the pupil's rush to light. Degenerated neuron densities of trigeminal ganglia and pupil diameters compared with the Mann-Whitney U test. RESULTS: The PRI, degenerated neuron density of trigeminal ganglia (n/mm3) were: (2.034 ± 0.301)/(13 ± 3) in GI; (1.678 ± 0.211)/(46 ± 9) in GII; and (0.941 ± 0.136)/(112 ± 21) in GIII. P-values between groups as: p < 0.005 in GI/GII; p < 0.0001 in GII/GIII and p < 0.00001 in GI/GIII. CONCLUSION: Light stimulates the cornea which is innervated by the trigeminal nerves. This experimental study indicates that the pupil remains mydriatic as the cornea is damaged by trigeminal ischemia following SAH and blocks the light flow.
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Hemorragia Subaracnóidea , Gânglio Trigeminal , Animais , Coelhos , Hemorragia Subaracnóidea/complicações , Isquemia/complicações , Neurônios , Reflexo , Reflexo PupilarRESUMO
SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Longitudinais , Estudos Retrospectivos , Rim , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Creatinina , Fatores de Risco , Fibrose , AtrofiaRESUMO
BACKGROUND: Neurogenic pulmonary edema (NPE) following subarachnoid hemorrhage (SAH) is still one of the most catastrophic complications with high morbidity and mortality rates. Systemic sympathetic hyperactivity has been considered in the pathogenesis, but it has not been clarified. In this study, we investigate the relationship between the degeneration of the T3 dorsal root ganglion (DRG) and the development of NPE following spinal SAH. METHODS: The study was conducted on 23 rabbits. Five rabbits were used as the control group, 5 as the sham group (n = 5), and 13 as the study group. The correlation between the degenerated neuronal densities of the T3 nerve axons and neurons in the DRG and NPE scores was analyzed statistically. RESULTS: A correlation between the neuronal degeneration of the T3 nerve, its DRG, and high NPE scores was found in the study group and the sham group. Massive NPE was detected in the study group along with neural degeneration of T3 axons and ganglia. CONCLUSION: The present study indicates that NPE and pulmonary artery vasospasm can be prevented by reducing T3 DRG degeneration.