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Article ; Online: Postmortem sympathomimetic iris excitability.

Englisch, Colya N / Alrefai, Reem / Lesan, Cristina Martin / Seitz, Berthold / Tschernig, Thomas

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft

2024 Volume 254, Page(s) 152240

Abstract: 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 ... ...

Abstract	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 26 hours. A pupillometer with a minimum measurement range of 0.5 mm was used to determine the horizontal pupil diameter before and 20 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 3.5 mm (interquartile range [IQR]: 3.0-4.5 mm) and progressed to 4.0 mm (IQR: 3.5-5.0 mm) 20 minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5 mm (IQR: 0.0-1.0 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.
Language	English
Publishing date	2024-03-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1106738-x
ISSN	1618-0402 ; 0940-9602
ISSN (online)	1618-0402
ISSN	0940-9602
DOI	10.1016/j.aanat.2024.152240
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Article ; Online: TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System

Colya N. Englisch / Friedrich Paulsen / Thomas Tschernig

International Journal of Molecular Sciences, Vol 24, Iss 1, p

What Do We Know?

2022 Volume 181

Abstract: The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating ... ...

Abstract	The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca 2+ homeostasis and is involved in transcellular Ca 2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.
Keywords	TRPC3 ; TRPC6 ; kidney ; renal tubular system ; transient receptor potential ; renal carcinoma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: TRPC3 Is Downregulated in Primary Hyperparathyroidism.

Kirstein, Emilie / Schaudien, Dirk / Wagner, Mathias / Diebolt, Coline M / Bozzato, Alessandro / Tschernig, Thomas / Englisch, Colya N

International journal of molecular sciences

2024 Volume 25, Issue 8

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Humans ; TRPC Cation Channels/metabolism ; TRPC Cation Channels/genetics ; Hyperparathyroidism, Primary/metabolism ; Hyperparathyroidism, Primary/genetics ; Hyperparathyroidism, Primary/pathology ; Parathyroid Glands/metabolism ; Parathyroid Glands/pathology ; Female ; Male ; TRPC6 Cation Channel/metabolism ; TRPC6 Cation Channel/genetics ; Down-Regulation ; Middle Aged ; Aged ; Adult ; Immunohistochemistry ; Parathyroid Hormone/metabolism
Chemical Substances	TRPC Cation Channels ; TRPC3 cation channel ; TRPC6 Cation Channel ; TRPC6 protein, human ; Parathyroid Hormone
Language	English
Publishing date	2024-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25084392
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Article ; Online: New insights in the renal distribution profile of TRPC3 - Of mice and men.

Diebolt, Coline M / Schaudien, Dirk / Junker, Kerstin / Krasteva-Christ, Gabriela / Tschernig, Thomas / Englisch, Colya N

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft

2023 Volume 252, Page(s) 152192

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Humans ; Cell Culture Techniques ; Kidney
Chemical Substances	TRPC3 cation channel
Language	English
Publishing date	2023-11-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1106738-x
ISSN	1618-0402 ; 0940-9602
ISSN (online)	1618-0402
ISSN	0940-9602
DOI	10.1016/j.aanat.2023.152192
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Article ; Online: New insights in the renal distribution profile of TRPC3 - Of mice and men

Diebolt, Coline M. / Schaudien, Dirk / Junker, Kerstin / Krasteva-Christ, Gabriela / Tschernig, Thomas / Englisch, Colya N.

2024

Abstract	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. 252
Subject code	616
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunohistochemistry Reveals TRPC Channels in the Human Hearing Organ-A Novel CT-Guided Approach to the Cochlea.

Englisch, Colya N / Steinhäuser, Jakob / Wemmert, Silke / Jung, Martin / Gawlitza, Joshua / Wenzel, Gentiana / Schick, Bernhard / Tschernig, Thomas

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Humans ; Immunohistochemistry ; Cochlea/metabolism ; Ear, Inner/metabolism ; Stria Vascularis/metabolism ; Hearing
Language	English
Publishing date	2023-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24119290
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Article ; Online: Establishing an experimental Pseudomonas aeruginosa keratitis model in mice - Challenges and solutions.

Englisch, Colya N / Wadood, Noran Abdel / Pätzold, Linda / Gallagher, Andrew / Krasteva-Christ, Gabriela / Becker, Sören L / Bischoff, Markus

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft

2023 Volume 249, Page(s) 152099

Abstract: ... Results: We found that older C57BL/6 N mice (8-11 months) are more susceptible to develop a keratitis ... experimental P. aeruginosa keratitis in C57BL/6 N mice that is sustained or aggravated over the observation ...

Abstract	Background: With the ongoing increase in antimicrobial resistances seen in bacterial isolates causing a keratitis in humans, animal models have become an important tool to study new antimicrobial therapies. Nevertheless, the establishment of experimental keratitis is difficult. Here, we discuss the impact of different arrangements, including animal age, bacterial strain and dose as well as epithelium removal on the outcome of experimental keratitis. We therefore present the methods and results of our establishing experiments. Methods: Bacterial load determination and flow cytometry were performed using eye homogenate gained from a 72 h lasting murine Pseudomonas aeruginosa keratitis model. Additionally, the intensity of the infection was scored from 0 to 5, the mice weighed, and blood immune cells counted. Results: We found that older C57BL/6 N mice (8-11 months) are more susceptible to develop a keratitis than younger mice (5-6 weeks). Epithelium removal has no major impact on infectivity and disease progression in aged mice. P. aeruginosa exoU Conclusions: We present a replicable method to achieve a successful experimental P. aeruginosa keratitis in C57BL/6 N mice that is sustained or aggravated over the observation period of 3 days in 80 % of all animals tested. Our work is of particular interest to all researchers planning the establishment of such experimental models. We show some key aspects that can simplify and quicken the procedure, ultimately saving costs and animal life.
MeSH term(s)	Humans ; Animals ; Mice ; Pseudomonas aeruginosa ; Eye Infections, Bacterial/microbiology ; Mice, Inbred C57BL ; Pseudomonas Infections/microbiology ; Keratitis/microbiology ; Disease Models, Animal
Language	English
Publishing date	2023-04-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1106738-x
ISSN	1618-0402 ; 0940-9602
ISSN (online)	1618-0402
ISSN	0940-9602
DOI	10.1016/j.aanat.2023.152099
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Article ; Online: Immunohistochemistry Reveals TRPC Channels in the Human Hearing Organ—A Novel CT-Guided Approach to the Cochlea

Colya N. Englisch / Jakob Steinhäuser / Silke Wemmert / Martin Jung / Joshua Gawlitza / Gentiana Wenzel / Bernhard Schick / Thomas Tschernig

International Journal of Molecular Sciences, Vol 24, Iss 9290, p

2023 Volume 9290

Abstract	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.
Keywords	TRPC6 ; TRPC5 ; TRPC3 ; human cochlea ; organ of Corti ; temporal bone ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-Term Astigmatism after Intraocular Pressure Sensor Implantation and Nonpenetrating Glaucoma Surgery - EYEMATE-SC Trial.

Englisch, Colya N / Boden, Karl T / Szurman, Peter / Mansouri, Kaweh / Dick, H Burkhard / Hoffmann, Esther M / Mackert, Marc J / Schütte, Paul / Langenbucher, Achim / Messias, André / Wakili, Philip

Journal of cataract and refractive surgery

2024

Abstract: ... the observation period in both the EYEMATE-SC (n = 24) and the canaloplasty (n = 24) group (P > 0.05 or ...

Abstract	Purpose: To investigate the long-term astigmatism after combined non-penetrating glaucoma surgery (NPGS) and implantation of the first miniaturized suprachoroidal intraocular pressure (IOP) sensor EYEMATE-SC. Setting: The study was conducted in five medical centers in two different countries. Design: Retrospective multicenter clinical study. Methods: Astigmatism of patients instrumented with the EYEMATE-SC IOP sensor was assessed over a follow-up period of three years. Refraction and corrected distance visual acuity (CDVA) were obtained preoperatively, after 6 months, 1, 2, and 3 years. A canaloplasty-operated patient cohort served as control. Astigmatism was evaluated using 3-dimensional power vector analysis involving the spherical equivalent M, and the Jackson crossed cylinder projections J0 and J45. Exclusion criteria included neovascular and angle-closure glaucoma, myopia, axial length outside 22 to 26 mm, other ocular diseases, prior glaucoma surgery, other ocular surgery within 6 months (cataract surgery within 3 months) prior to NPGS, serious generalized conditions, and other active medical head/neck implants. Results: Multivariate analysis indicated no changes in astigmatism along the observation period in both the EYEMATE-SC (n = 24) and the canaloplasty (n = 24) group (P > 0.05 or nonsignificant after Bonferroni correction). Astigmatism was unchanged between the EYEMATE-SC and the canaloplasty group at all time points (P > 0.05). CDVA didn't change along the observation period of three years in each of both groups (P > 0.05). Conclusions: Despite its suprachoroidal localization, the present study indicates that the miniaturized EYEMATE-SC IOP sensor doesn't negatively affect the long-term astigmatism after combined implantation with NPGS.
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	632744-8
ISSN	1873-4502 ; 0886-3350
ISSN (online)	1873-4502
ISSN	0886-3350
DOI	10.1097/j.jcrs.0000000000001470
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Article ; Online: TRPC6 Is Found in Distinct Compartments of the Human Kidney

Colya N. Englisch / Daniel Röhricht / Mariesa Walz / Kerstin Junker / Anja Beckmann / Carola Meier / Friedrich Paulsen / Martin Jung / Thomas Tschernig

International Journal of Translational Medicine, Vol 2, Iss 13, Pp 156-

2022 Volume 163

Abstract: In the context of renal proteinuric diseases, TRPC6 has been shown to play an important role in ultrafiltration associated with the slit diaphragm through the control of the intracellular Ca 2+ concentration in the podocytes of glomeruli. However, to ... ...

Abstract	In the context of renal proteinuric diseases, TRPC6 has been shown to play an important role in ultrafiltration associated with the slit diaphragm through the control of the intracellular Ca 2+ concentration in the podocytes of glomeruli. However, to date, the properties of TRPC6 have been studied mainly in cell lines or in animal models. Therefore, the aim of the study presented here was to investigate the presence and distribution of TRPC6 in human kidneys in order to possibly verify the applicability of the results previously obtained in nonhuman experiments. For this purpose, kidneys from nine cadavers were prepared for immunohistochemical staining and were supplemented with a fresh human kidney obtained by nephrectomy. TRPC6 was detected in glomeruli and in the parietal epithelial cells of Bowman’s capsule. Larger amounts were detected in the tubular system and collecting ducts. In contrast to the peritubular capillary bed, which showed no immune reaction, the cortical resistance vessels showed mild TRPC6 staining. In conclusion, our studies on the expression of TRPC6 in human kidney tissue support the translational concept of the involvement of TRPC6 in various renal diseases and reveal new aspects of the distribution of TRPC6 in the human kidney.
Keywords	TRPC6 ; human kidney ; glomeruli ; tubular system ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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