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Transient receptor potential canonical channel 6 (TRPC6) is a non-selective cation channel that is activated by diacylglycerol. It belongs to the TRP superfamily, is expressed in numerous tissues and has been shown to be associated with diseases, such as focal segmental glomerulosclerosis, idiopathic pulmonary arterial hypertension and cardiac hypertrophy. The investigation of the channel in human lymphoid tissues has thus far been limited to mRNA analysis or the western blotting of isolated lymphoid cell lines. The present study aimed to detect the channel in human lymphoid tissue using immunohistochemistry. For this purpose, lymphatic tissues were obtained from body donors. The lymphatic organs analyzed included the lymph nodes, spleen, palatine tonsil, gut-associated lymphoid tissues (ileum and vermiform appendix) and thymus. A total of 102 samples were obtained and processed for hematoxylin and eosin (H&E) staining. The H&E staining method was employed to identify five samples with good morphology. In total, three samples of the palatine tonsil of patients were included. Immunostaining was carried out using a knockout-validated anti-TRPC6 antibody. As shown by the results, using immunohistochemical staining, the presence of TRPC6 was confirmed in all the analyzed lymphatic tissue samples. Lymphocytes in lymph nodes, spleen, palatine tonsil, thymus, and gut-associated lymphatic tissues in ileum and vermiform appendix exhibited a positive staining signal. The follicle-associated epithelium of the palatine tonsil, ileum and appendix also demonstrated staining. Vessels of the lymphatic organs, particularly the trabecular arteries of the spleen, the submucosal vessels of the appendix and ileum, as well as the high endothelial venules in the palatine tonsils and lymphatic vessels of the lymph nodes expressed TRPC6 protein. TRPC6 in follicles may be involved in the immune response. TRPC6 in high endothelial venules suggests a role in leukocyte migration. The role of TRPC6 and other channels of the TRP family in lymphatic organs warrant further investigations to elucidate whether TRP channels are a pharmacological target.
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BACKGROUND: Canonical transient receptor potential channels play a crucial role in cancer cell proliferation. While TRPC6 subtype detection in submandibular glands and the relevance of some TRPC channels in this gland have been shown in animal models, its histological detection in human lacrimal and submandibular glands, as well as related tumors, lacks systematic study. Studying TRPC6 in humans could lead to new therapeutic options. This research aimed to immunohistochemically detect TRPC6 in human samples of physiological lacrimal and submandibular glands and of adenoid cystic carcinoma and mucoepidermoid carcinoma. METHODS: Seven fixed body donors and samples of six cancer patients were examined. The ten tissue samples collected from the submandibular and lacrimal glands were then processed into histological slides and stained with hematoxylin-eosin. Tumor samples were provided as sections. TRPC6 presence was determined by immunohistochemistry, which was performed by indirect detection with a primary TRPC6 antibody, a secondary HRP-conjugated antibody and the chromogen diaminobenzidine. RESULTS: Results confirm TRPC6 expression in all ten physiological gland samples: all samples showed a immunohistochemical signal with varying intensity. No significant gender-specific differences could be observed. TRPC6 was detected in four of six submandibular adenoid cystic carcinoma and the mucoepidermoid carcinoma samples, especially in tumor cells' cytoplasma and nuclei. Excretory ducts consistently showed TRPC6. Mucous tubules, their nuclei and the nuclei of adipocytes generally showed no signal while serous acini and their nuclei showed a weak TRPC6 signal. CONCLUSION: The discovery of TRPC6 in glandular tissue indicates a role in salivary gland function and calcium homeostasis is a basis for further research into its significance for tumor development in adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands. TRPC6 could be used as a target for treatment of these tumors. However, the correlation between TRPC6 and submandibular and lacrimal gland diseases requires further exploration.
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Carcinoma Adenoide Quístico , Inmunohistoquímica , Aparato Lagrimal , Neoplasias de las Glándulas Salivales , Glándula Submandibular , Canal Catiónico TRPC6 , Humanos , Femenino , Masculino , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/metabolismo , Persona de Mediana Edad , Aparato Lagrimal/patología , Aparato Lagrimal/metabolismo , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/metabolismo , Canal Catiónico TRPC6/metabolismo , Glándula Submandibular/patología , Glándula Submandibular/metabolismo , Anciano , Adulto , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisisRESUMEN
Transient receptor potential channel canonical 5 (TRPC5) is a non-selective ion channel; ion influx through TRPC5 causes activation of downstream signaling pathways. In addition, TRPC5 has been identified as having a potential role in pathological processes, particularly in diseases caused by cellular cation homeostasis dysregulation, such as bronchial asthma or pulmonary hypertension. However, the expression and distribution of TRPC5 in the human lung remain unclear. To date, TRPC5 has only been detected in a few cell types in the human lung, such as airway, pulmonary venous and arterial smooth muscle cells. The present study therefore aimed to investigate the protein expression of TRPC5 in the human lung and to evaluate its histological distribution. Human lung samples were obtained from six preserved body donors. After processing, both hematoxylin & eosin staining, as well as immunohistochemistry were performed. Microscopic analysis revealed medium to strong immunostaining signals in all lung structures examined, including the pleura, pulmonary arteries and veins, bronchioles, alveolar septa, type 1 and 2 pneumocytes, as well as alveolar macrophages. Current research suggests that TRPC5 may be involved in various pathological processes in the human lung and some pharmacological compounds have already been identified that affect the function of TRPC5. Therefore, TRPC5 may present a novel drug target for therapeutic intervention in various lung diseases. The results of the present study indicate that the TRPC5 protein is expressed in all examined histological structures of the human lung. These findings suggest that TRPC5 may be more important for physiological cell function and pathophysiological cell dysfunction in the lung than is currently known. Further research is needed to explore the role and therapeutic target potential of TRPC5 in the human lung.
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BACKGROUND: Expression and function of TRPC3 and TRPC6 in the pancreas is a controversial topic. Investigation in human tissue is seldom. We aimed to provide here a detailed description of the distribution of TRPC3 and TRPC6 in the human exocrine and endocrine pancreas. METHODS: We collected healthy samples from cadavers (n = 4) and visceral surgery (n = 4) to investigate the respective expression profiles using immunohistochemical tracing with knockout-validated antibodies. RESULTS: TRPC3- and TRPC6-proteins were detected in different pancreatic structures including acinar cells, as well as epithelial ductal cells from intercalate, intralobular, and interlobular ducts. Respective connective tissue layers appeared unstained. Endocrine islets of Langerhans were clearly and homogenously immunolabeled by the anti-TRPC3 and anti-TRPC6 antibodies. Insular α, ß, γ, and δ cells were conclusively stained, although no secure differentiation of cell types was performed. CONCLUSIONS: Due to aforementioned antibody specificity verification, protein expression in the immunolabeled localizations can be accepted. Our study in human tissue supports previous investigations especially with respect to acinar and insular α and ß cells, while other localizations are here reported for the first time to express TRPC3 and TRPC6, ultimately warranting further research.
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Páncreas Exocrino , Canales Catiónicos TRPC , Canal Catiónico TRPC6 , Humanos , Canales Catiónicos TRPC/metabolismo , Canal Catiónico TRPC6/metabolismo , Páncreas Exocrino/metabolismo , Islotes Pancreáticos/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , InmunohistoquímicaRESUMEN
During routine dissections of cadavers as part of the medical curriculum, we identified a rare unilateral variation in the brachial plexus on the right side of a female body donor. This variation consisted of four unusual changes to the regular pattering of nerve bundles and the dorsal scapular artery permeating the complex neural network. The variation included contributions of root C4 to the plexus by a root C4/C5 anastomosis, a rare fusion of the superior and middle trunks to a 'superomiddle' trunk, a preliminary, proximal branching of the suprascapular nerve off the C5 root. We further observed an accessory 'medial anterior division' branching off the fused upper and middle trunks merging with the anterior division of the inferior trunk forming the medial cord. The latter event potentially introduced nerve fibers from C5 to C7, which are absent in common patterns. We aim to relate these observations to previous categorizations and quantifications of brachial plexus patterns. We believe that the combination of different variations in this case resulted in a unique pattern. Since this observation was made in the dissection class, we further aim to raise awareness among medical students and anatomical instructors for the likelihood of variations to textbook patterns. This will hopefully foster an appreciation of uniqueness and individuality in the interaction with future patients demonstrating that proper preparation prior to surgical interventions is always a necessary prerequisite.
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Posterior fixation of the subaxial cervical spine (SCS) commonly relies on the application of lateral mass screws (LMS), with pedicle screws being a less prevalent alternative. The present study provides another option: A recently introduced novel approach, the Attallah screw, intended to ensure a safety profile comparable to that of LMS, combined with a strength profile similar to that of pedicle screws. The focus of the present study is the comparative analysis of peak insertion torques for these three screw types. Employing standard surgical techniques and instruments, Attallah screws were scheduled for insertion on the right side of the SCS in 15 cadavers, pedicle screws on the left side in 8 cadavers, and LMS on the left side in the remaining 7 cadavers. The peak insertion torque was recorded using an electronic torque screwdriver. The results revealed that the peak insertion torques were similar in the pedicle and the Attallah screw at C3, C4 and C7, but differed at C5 (mean ± SD; pedicle, 79.5±19.6 cNm; Attallah, 56.7±18.5 cNm; P=0.029) and C6 (pedicle, 85.4±28.7 cNm; Attallah, 49.8±17.9 cNm; P=0.004) in favor of the superior pedicle screw measurements. The peak insertion torques of the pedicle screw were superior to the corresponding data from the LMS from C4 to C7. By contrast, the peak insertion torques of the Attallah screw were only superior to those of the LMS at C7 (Attallah, 69.5±24.5 cNm; lateral mass, 40.5±21.4 cNm; P=0.030), although similar trends were observed at the other cervical levels. On the whole, the findings presented herein indicate the level-dependent superior robustness of the Attallah screw as a posterior cervical fixation method compared to the LMS. However, from a biomechanical perspective, the pedicle screw remains the preeminent choice for fixation within the C5-C6 range.
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Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.
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Regulación hacia Abajo , Hiperparatiroidismo Primario , Glándulas Paratiroides , Canales Catiónicos TRPC , Canal Catiónico TRPC6 , Humanos , Canales Catiónicos TRPC/metabolismo , Canales Catiónicos TRPC/genética , Hiperparatiroidismo Primario/metabolismo , Hiperparatiroidismo Primario/genética , Hiperparatiroidismo Primario/patología , Glándulas Paratiroides/metabolismo , Glándulas Paratiroides/patología , Femenino , Masculino , Canal Catiónico TRPC6/metabolismo , Canal Catiónico TRPC6/genética , Persona de Mediana Edad , Anciano , Adulto , Inmunohistoquímica , Hormona Paratiroidea/metabolismoRESUMEN
Micro- and nanoplastics (MNPs) are ubiquitous in the environment, resulting in the uptake of MNPs by a variety of organisms, including humans, leading to particle-cell interaction. Human macrophages derived from THP-1 cell lines take up Polystyrene (PS), a widespread plastic. The question therefore arises whether primary human macrophages also take up PS micro- and nanobeads (MNBs) and how they react to this stimulation. Major aim of this study is to visualize this uptake and to validate the isolation of macrophages from peripheral blood mononuclear cells (PBMCs) to assess the impact of MNPs on human macrophages. Uptake of macrophages from THP-1 cell lines and PBMCs was examined by transmission electron microscopy (TEM), scanning electron microscopy and live cell imaging. In addition, the reaction of the macrophages was analyzed in terms of metabolic activity, cytotoxicity, production of reactive oxygen species (ROS) and macrophage polarization. This study is the first to visualize PS MNBs in primary human cells using TEM and live cell imaging. Metabolic activity was size- and concentration-dependent, necrosis and ROS were increased. The methods demonstrated in this study outline an approach to assess the influence of MNP exposure on human macrophages and help investigating the consequences of worldwide plastic pollution.
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Macrófagos , Microplásticos , Poliestirenos , Especies Reactivas de Oxígeno , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Poliestirenos/química , Poliestirenos/toxicidad , Células THP-1 , Microplásticos/toxicidad , Leucocitos Mononucleares/efectos de los fármacos , Nanopartículas/toxicidad , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Microscopía Electrónica de Transmisión , Tamaño de la PartículaRESUMEN
BACKGROUND: A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the chemical excitability of the iris can be used to further narrow intervals estimated by temperature-based methods. Postmortem iris excitability was mostly assessed by parasympatholytic or parasympathomimetic substances. Little is known regarding sympathomimetic agents. The present study aims to describe the postmortem iris excitability using the sympathomimetic drug phenylephrine. METHODS: Cadavers were included after body donors gave written informed consent during lifetime. Exclusion criteria were known eye disease, or a postmortem interval exceeding 26â¯hours. A pupillometer with a minimum measurement range of 0.5â¯mm was used to determine the horizontal pupil diameter before and 20â¯minutes after the application of phenylephrine. Increase in pupil diameter was labeled as positive reaction, unchanged pupil diameter was labeled as negative reaction, and decrease in pupil diameter was labeled as paradox reaction. RESULTS: 30 eyes from 16 cadavers (median age = 80.0; 9 males, 7 females) were examined. Initial pupil size was in median 3.5â¯mm (interquartile range [IQR]: 3.0-4.5â¯mm) and progressed to 4.0â¯mm (IQR: 3.5-5.0â¯mm) 20â¯minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5â¯mm (IQR: 0.0-1.0â¯mm). A positive reaction was observed in 21 cases. Negative reactions were observed in 5 cases and paradox reactions in 4 cases. Overall, there was a statistically significant difference in diameter between the initial and the reactive pupil (P = 0.0002). CONCLUSION: Although relatively rarely used, sympathomimetic drugs seem to be eligible for chemical postmortem iris excitability. Currently, assessment of postmortem iris excitability usually only involves parasympatholytic and parasympathomimetic agents. The findings of the present study give a hint that the application of a third agent with a sympathomimetic mechanism of action could provide additional information. Further studies assessing such a triple approach in the compound method in comparison with the current gold standard for estimation of time since death are mandatory to ensure reliable results.
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Cadáver , Iris , Fenilefrina , Cambios Post Mortem , Pupila , Simpatomiméticos , Humanos , Masculino , Femenino , Iris/efectos de los fármacos , Iris/anatomía & histología , Iris/fisiología , Fenilefrina/farmacología , Pupila/efectos de los fármacos , Pupila/fisiología , Anciano de 80 o más Años , Anciano , Simpatomiméticos/farmacologíaRESUMEN
Introduction: The management of fractured bones is a key domain within orthopedic trauma surgery, with the prevention of delayed healing and non-unions forming a core challenge. This study evaluates the efficacy of the AO Fracture Monitor in conjunction with biomechanical simulations to better understand the local mechanics of fracture gaps, which is crucial for comprehending mechanotransduction, a key factor in bone healing. Through a series of experiments and corresponding simulations, the study tests four hypotheses to determine the relationship between physical measurements and the predictive power of biomechanical models. Methods: Employing the AO Fracture Monitor and Digital Image Correlation techniques, the study demonstrates a significant correlation between the surface strain of implants and interfragmentary movements. This provides a foundation for utilizing one-dimensional AO Fracture Monitor measurements to predict three-dimensional fracture behavior, thereby linking mechanical loading with fracture gap dynamics. Moreover, the research establishes that finite element simulations of bone-implant systems can be effectively validated using experimental data, underpinning the accuracy of simulations in replicating physical behaviors. Results and Discussion: The findings endorse the combined use of monitoring technologies and simulations to infer the local mechanical conditions at the fracture site, offering a potential leap in personalized therapy for bone healing. Clinically, this approach can enhance treatment outcomes by refining the assessment precision in trauma trials, fostering the early detection of healing disturbances, and guiding improvements in future implant design. Ultimately, this study paves the way for more sophisticated patient monitoring and tailored interventions, promising to elevate the standard of care in orthopedic trauma surgery.
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Several reports previously investigated the Transient Receptor Potential Canonical subfamily channel 3 (TRPC3) in the kidney. However, most of the conclusions are based on animal samples or cell cultures leaving the door open for human tissue investigations. Moreover, results often disagreed among investigators. Histological description is lacking since most of these studies focused on functional aspects. Nevertheless, the same reports highlighted the potential key-role of TRPC3 in renal disorders. Hence, our interest to investigate the localization of TRPC3 in human kidneys. For this purpose, both healthy mouse and human kidney samples that were originated from tumor nephrectomies have been prepared for immunohistochemical staining using a knockout-validated antibody. A blocking peptide was used to confirm antibody specificity. A normalized weighted diaminobenzidine (DAB) area score between 0 and 3 comparable to a pixelwise H-score was established and employed for semiquantitative analysis. Altogether, our results suggest that glomeruli only express little TRPC3 compared to several segments of the tubular system. Cortical and medullary proximal tubules are stained, although intracortical differences in staining exist in mice. Intermediate tubules, however, are only weakly stained. The distal tubule was studied in three localizations and staining was marked although slightly varying throughout the different subsegments. Finally, the collecting duct was also immunolabeled in both human and mouse tissue. We therefore provide evidence that TRPC3 is expressed in various localizations of both human and mouse samples. We verify results of previous studies and propose until now undescribed localizations of TRPC3 in the mouse but especially and of greater interest in the human kidney. We thereby not only support the translational concept of the TRPC3 channel as key-player in physiology and pathophysiology of the human kidney but also present new potential targets to functional analysis.
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Técnicas de Cultivo de Célula , Riñón , Animales , HumanosRESUMEN
BACKGROUND: Airway tuft cells, formerly called brush cells have long been described only morphologically in human airways. More recent RNAseq studies described a chemosensory cell population, which includes tuft cells, by a distinct gene transcription signature. Yet, until which level in the tracheobronchial tree in native human airway epithelium tuft cells occur and if they function as regulators of innate immunity, e.g., by regulating mucociliary clearance, remained largely elusive. METHODS: We performed immunohistochemistry, RT-PCR and immunoblotting analyses for various tuft cell markers to confirm the presence of this cell type in human tracheal samples. Immunohistochemistry was conducted to study the distribution of tuft cells along the intrapulmonary airways in humans. We assessed the influence of bitter substances and the taste transduction pathway on mucociliary clearance in mouse and human tracheal samples by measuring particle transport speed. RESULTS: Tuft cells identified by the expression of their well-established marker POU class 2 homeobox 3 (POU2F3) were present from the trachea to the bronchioles. We identified choline acetyltransferase in POU2F3 expressing cells as well as the transient receptor potential melastatin 5 (TRPM5) channel in a small population of tracheal epithelial cells with morphological appearance of tuft cells. Application of bitter substances, such as denatonium, led to an increase in mucociliary clearance in human tracheal preparations. This was dependent on activation of the TRPM5 channel and involved cholinergic and nitric oxide signalling, indicating a functional role for human tuft cells in the regulation of mucociliary clearance. CONCLUSIONS: We were able to detect tuft cells in the tracheobronchial tree down to the level of the bronchioles. Moreover, taste transduction and cholinergic signalling occur in the same cells and regulate mucociliary clearance. Thus, tuft cells are potentially involved in the regulation of innate immunity in human airways.
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Depuración Mucociliar , Tráquea , Humanos , Ratones , Animales , Tráquea/fisiología , Transducción de Señal , Gusto , Colinérgicos/metabolismoRESUMEN
Background: Revision hip arthroplasty presents a surgical challenge, necessitating meticulous preoperative planning to avert complications like periprosthetic fractures and aseptic loosening. Historically, assessment of the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has focused exclusively on primary hip arthroplasty. Materials and Methods: In this retrospective study, we examined the accuracy of 3D templating for acetabular revision cups in 30 patients who underwent revision hip arthroplasty. Utilizing computed tomography scans of the patients' pelvis and 3D templates of the implants (Aesculap Plasmafit, B. Braun; Aesculap Plasmafit Revision, B. Braun; Avantage Acetabular System, Zimmerbiomet, EcoFit 2M, Implantcast; Tritanium Revision, Stryker), we performed 3D templating and positioned the acetabular cup implants accordingly. To evaluate accuracy, we compared the planned sizes of the acetabular cups in 2D and 3D with the sizes implanted during surgery. Results: An analysis was performed to examine potential influences on templating accuracy, specifically considering factors such as gender and body mass index (BMI). Significant statistical differences (p < 0.001) in the accuracy of size prediction were observed between 3D and 2D templating. Personalized 3D templating exhibited an accuracy rate of 66.7% for the correct prediction of the size of the acetabular cup, while 2D templating achieved an exact size prediction in only 26.7% of cases. There were no statistically significant differences between the 2D and 3D templating methods regarding gender or BMI. Conclusion: This study demonstrates that 3D templating improves the accuracy of predicting acetabular cup sizes in revision arthroplasty when compared to 2D templating. However, it should be noted that the predicted implant size generated through 3D templating tended to overestimate the implanted implant size by an average of 1.3 sizes.
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Artroplastia de Reemplazo de Cadera , Humanos , Estudios Retrospectivos , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Índice de Masa Corporal , PelvisRESUMEN
Since the discovery of TRP proteins in 1969, during studies of the fruit fly Drosophila melanogaster, interest around them and the subfamily of TRPC channels has remained high. TRPC3 was able to be detected in a number of organs in rodents, such as rats and mice, and also in various human tissues. For the most part, these investigations were carried out using gene expression of TRPC3. Further work has already confirmed the relevance of TRPC3 in the context of neurodegenerative diseases, such as spinocerebellar ataxia, and carcinogenic entities, such as ovarian carcinoma. An association with TRPC3 has also been demonstrated for diseases that affect the liver. In order to confirm the expression of TRPC3 in the human liver, this study uses samples taken from eight (n = 8) fixated human body donors and analyzed with immunohistochemistry. In accordance with the macroscopic anatomy of the organs, six samples (n = 6) of liver tissue and three (n = 3) of gallbladder tissue were obtained. TRPC3 was clearly detected in all liver and gallbladder samples examined. Thus, it is not unlikely that TRPC3 plays a role in the extensive metabolic processes of the liver and could also serve as a target for pharmacological interventions in an imbalance of calcium homeostasis.
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Vesícula Biliar , Canales Catiónicos TRPC , Humanos , Ratas , Ratones , Animales , Canales Catiónicos TRPC/genética , Canales Catiónicos TRPC/metabolismo , Vesícula Biliar/metabolismo , Drosophila melanogaster/metabolismo , Hígado , Calcio/metabolismoRESUMEN
BACKGROUND: Renal denervation is optimised when guided by knowledge of nerve distribution. AIMS: We aimed to assess sympathetic nerve distribution along the renal arteries, especially in post-bifurcation vessel segments. METHODS: Renal arteries and surrounding tissue from 10 body donors were collected and examined histologically. Immunohistochemical staining was used to analyse nerve distribution and to identify afferent and efferent sympathetic nerves. RESULTS: A total of 6,781 nerves surrounding 18 renal arteries were evaluated. The mean lumen-nerve distance of the left renal artery (2.32±1.95 mm) was slightly greater than the right (2.29±2.03 mm; p=0.161); this varied across the arteries' courses: 3.7±2.3 mm in proximal segments, 2.5±2.0 mm in middle segments, 1.9±1.6 mm in distal prebifurcation segments and 1.3±1.0 mm in post-bifurcation segments (p<0.001). The number of nerves per quadrant was highest in the proximal segments (13.7±18.6), followed by the middle (9.7±7.9), distal prebifurcation (8.0±7.6), and distal post-bifurcation (4.3±4.0) segments (p<0.001). Circumferentially, the number of nerves was highest in the superior (7.8±9.4) and the ventral (7.6±13.1) quadrants (p=0.638). The mean tyrosine hydroxylase (TH) to calcitonin gene-related peptide (CGRP) ratio increased from proximal (37.5±33.5) to distal (72.0±7.2 in the post-bifurcation segments; p<0.001). Thirty-eight neuroganglia were identified along 14 (78%) renal arteries. CONCLUSIONS: Nerves converge to the renal arteries' lumen in the distal segments and along branches, resulting in the lowest number of nerves per quadrant and the shortest lumen-nerve distance in the distal post-bifurcation segments. Efferent nerves occur predominantly, and the ratio of efferent to afferent nerves continues to increase in the vessels' course.
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Simpatectomía , Sistema Nervioso Simpático , Humanos , Simpatectomía/métodos , Riñón , Arteria Renal/inervaciónRESUMEN
Introduction: In human and experimentally induced asthma, a dysfunction of the intra-alveolar-surface active agent (surfactant) has been demonstrated. Type II alveolar epithelial cells (AEII) synthesize, secrete and recycle surfactant. Prior to secretion, intracellular surfactant is stored in specific secretory organelles of AEII. The lamellar bodies (Lb) represent its ultrastructural correlate. The aim of this study was to investigate whether disturbances of the intra-alveolar surfactant are accompanied by alterations in the intracellular surfactant.Material and Methods: Brown-Norway rats were sensitized twice with ovalbumin (OVA) and heat killed Bordetella pertussis bacilli. During airway challenge, an aerosol of 5% ovalbumin/saline solution (0.25 l/min) was nebulized. 24 h after airway challenge, lungs were fixed by vascular perfusion. AEII and their Lb were characterized stereologically by light and electron microscopy.Results: In both groups, AEII were structurally intact. The number of AEII per lung and their number-weighted mean volume did not differ (controls: 49 × 106, 393 µm3; asthmatics: 44 × 106, 390 µm3). A mean of 90 Lb in AEII of asthmatics and of 93 Lb in AEII of controls were evaluated. The Lb mean total volume was 59 µm in asthmatics and 68 µm in controls. Values of both parameters did not reach significance. Also, the size distribution and mean volume of Lb was not influenced by asthma induction, because the volume weighted mean volume of Lb (2.18 µm in asthmatics compared to 1.87 µm in controls) and the numerical weighted mean volume (0.96 µm in asthmatics and 0.75 µm in controls) were comparable in both groups.Conclusion: The obtained results suggest that asthma-induced surfactant dysfunction is not related to disturbances in the intracellular surfactant´s ultrastructural correlates.
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Asma , Surfactantes Pulmonares , Humanos , Animales , Ratas , Tensoactivos/farmacología , Ovalbúmina , Células Epiteliales Alveolares , Asma/inducido químicamenteRESUMEN
TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, and the inner ear was first assessed based on computed tomography scans. Decalcification was then performed using 20% EDTA solutions. Immunohistochemistry with knockout-tested antibodies followed. The organ of Corti, the stria vascularis, the spiral lamina, spiral ganglion neurons and cochlear nerves were specifically stained. This unique report of TRPC channels in the human cochlea supports the hypothesis of the potentially critical role of TRPC channels in human cochlear health and disease which has been suggested in previous rodent experiments.
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Cóclea , Oído Interno , Animales , Humanos , Inmunohistoquímica , Cóclea/metabolismo , Oído Interno/metabolismo , Estría Vascular/metabolismo , AudiciónRESUMEN
BACKGROUND: Flexor hallucis longus (FHL) transfer is a well-established method for treating chronic Achilles tendon ruptures and tendinopathy. Harvesting of the FHL tendon in zone 2 results in greater length but is also associated with an increased risk of injury to the medial plantar nerve and requires an additional plantar incision. Because of the anatomic proximity of the FHL tendon to the tibial neurovascular bundle in zone 2, the purpose of this study was to investigate the risk of vascular or nerve injury with arthroscopic assisted percutaneous tenotomy in zone 2 of the FHL tendon. METHODS: Endoscopically assisted percutaneous FHL transfer was performed on 10 right lower extremities from 10 cadaveric human specimens. The FHL tendon lengths and the relationship between FHL tendon and the tibial neurovascular bundle at zone 2 was analyzed. RESULTS: We observed a complete transection of the medial plantar nerve in 1 case (10%). The mean length of the FHL tendon was 54.7 ± 9.5 mm and the mean distance from the distal stump of the FHL tendon to local neurovascular structures was 1.3 ± 0.7 mm. CONCLUSION: There is a risk of neurovascular injury after endoscopic FHL tenotomy in zone 2. The tenotomy site is within 2 mm of the local neurovascular structures in the majority of cases. The additional length gained from this technique is unlikely to be required for the majority of FHL tendon transfer procedures. If additional length is needed, we would recommend the use of intraoperative ultrasonography or a mini-open approach to minimize injury risk. LEVEL OF EVIDENCE: Level V, expert opinion.