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Article ; Online: Effect of Calcitriol and Vitamin D Receptor Modulator 2 on Recovery of Injured Skeletal Muscle in Wistar Rats

Ioannis Stratos / Svenja Schleese / Ingmar Rinas / Brigitte Vollmar / Thomas Mittlmeier

Biomedicines, Vol 11, Iss 2477, p

2023 Volume 2477

Abstract: Muscle injuries often result in functional limitations due to insufficient healing. This study assessed the influence of calcitriol and vitamin D Receptor Modulator 2 (VDRM2) on muscle regeneration in male Wistar rats following open blunt muscle injury. ... ...

Abstract	Muscle injuries often result in functional limitations due to insufficient healing. This study assessed the influence of calcitriol and vitamin D Receptor Modulator 2 (VDRM2) on muscle regeneration in male Wistar rats following open blunt muscle injury. The injured left soleus muscle of the rats was treated for the first four days after trauma with local injections of either calcitriol, VDRM2, or a 10% ethanol solution (control). Although muscle strength significantly decreased post-injury, all groups showed gradual improvement but did not achieve full recovery. By the 14th day, calcitriol-treated rats significantly outperformed the control group in the incomplete tetanic force, with VDRM2-treated rats showing muscle strength values that fell between the control and calcitriol groups. Similar trends were observed in complete tetanic contractions and were confirmed histologically via muscle cell width quantification. Additionally, histological analysis showed increased cellular turnover on the fourth postoperative day in the calcitriol group, as indicated by elevated cell proliferation rates and fewer apoptotic cells. VDRM2-treated animals showed only an increased proliferative activity on day 4 after injury. No noticeable differences between the groups for CAE-positive cells or visible muscle tissue area were found. In conclusion, predominantly calcitriol positively influenced post-trauma muscle recovery, where VDRM2 had substantially lower biological activity.
Keywords	muscle injury ; calcitriol ; vitamin D receptor modulator 2 (VDRM2) ; healing ; cellular turnover ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ALM Therapy Promotes Functional and Histologic Regeneration of Traumatized Peripheral Skeletal Muscle

Nina Sarah Hoeger / Thomas Mittlmeier / Brigitte Vollmar / Ioannis Stratos / Geoffrey P. Dobson / Robert Rotter

Biology, Vol 12, Iss 870, p

2023 Volume 870

Abstract: Skeletal muscle trauma is a common injury with a range of severity. Adenosine, lidocaine and Mg 2+ (ALM) is a protective solution and improves tissue perfusion and coagulopathy. Male Wistar rats were anesthetized and subjected to standardized skeletal ... ...

Abstract	Skeletal muscle trauma is a common injury with a range of severity. Adenosine, lidocaine and Mg 2+ (ALM) is a protective solution and improves tissue perfusion and coagulopathy. Male Wistar rats were anesthetized and subjected to standardized skeletal muscle trauma of the left soleus muscle with the protection of the neurovascular structures. Seventy animals were randomly assigned to saline control or ALM. Immediately after trauma, a bolus of ALM solution was applied intravenously, followed by a one-hour infusion. After 1, 4, 7, 14 and 42 days, the biomechanical regenerative capacity was examined using incomplete tetanic force and tetany, and immunohistochemistry was used to examine for proliferation and apoptosis characteristics. Biomechanical force development showed a significant increase following ALM therapy for incomplete tetanic force and tetany on days 4 and 7. In addition, the histological evaluation showed a significant increase in proliferative BrdU-positive cells with ALM therapy on days 1 and 14. Ki67 histology also detected significantly more proliferative cells on days 1, 4, 7, 14 and 42 in ALM-treated animals. Furthermore, a simultaneous decrease in the number of apoptotic cells was observed using the TUNEL method. ALM solution showed significant superiority in biomechanical force development and also a significant positive effect on cell proliferation in traumatized skeletal muscle tissue and reduced apoptosis.
Keywords	muscle regeneration ; apoptosis ; ALM solution ; muscle crush injury ; muscle contraction force ; proliferation ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inhibition of TNF-α Restores Muscle Force, Inhibits Inflammation, and Reduces Apoptosis of Traumatized Skeletal Muscles

Ioannis Stratos / Ann-Kathrin Behrendt / Christian Anselm / Aldebarani Gonzalez / Thomas Mittlmeier / Brigitte Vollmar

Cells, Vol 11, Iss 2397, p

2022 Volume 2397

Abstract: Background: Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In ... ...

Abstract	Background: Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In this study we assumed that TNF-α inhibition could reduce the TNF-α-associated tissue degradation after muscle injury. Materials and methods: Therefore, the left soleus muscle of 42 male Wistar rats was injured using a standardized open muscle injury model. All rats were treated immediately after injury either with infliximab (single i.p. injection; 10 mg/kg b.w.) or saline solution i.p. Final measurements were conducted at day one, four, and 14 post injury. The muscle force, the muscle cell proliferation, the muscle cell coverage as well as the myofiber diameter served as read out parameters of our experiment. Results: Systemic application of infliximab could significantly reduce the TNF-α levels in the injured muscle at day four upon trauma compared to saline treated animals. The ratio of muscle weight to body weight was increased and the twitch muscle force showed a significant rise 14 days after trauma and TNF-α inhibition. Quantification of myofiber diameter in the penumbra zone showed a significant difference between both groups at day one and four after injury, indicated by muscle hypertrophy in the infliximab group. Planimetric analysis of the injured muscle at day 14 revealed increased muscle tissue fraction in the infliximab group compared to the control animals. Muscle cell proliferation did not differ between both groups. Conclusions: These data provide evidence that the TNF-α blockade positively regulates the restauration of skeletal muscles upon injury.
Keywords	muscle injury ; regeneration ; infliximab ; tumor necrosis factor alpha ; Biology (General) ; QH301-705.5
Subject code	610 ; 796
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sarcomeric network analysis of ex vivo cultivated human atrial appendage tissue using super-resolution microscopy

Oleksandra Chabanovska / Heiko Lemcke / Hermann Lang / Brigitte Vollmar / Pascal M. Dohmen / Robert David / Christian Etz / Catharina Neßelmann

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 13

Abstract: Abstract Investigating native human cardiac tissue with preserved 3D macro- and microarchitecture is fundamental for clinical and basic research. Unfortunately, the low accessibility of the human myocardium continues to limit scientific progress. To ... ...

Abstract	Abstract Investigating native human cardiac tissue with preserved 3D macro- and microarchitecture is fundamental for clinical and basic research. Unfortunately, the low accessibility of the human myocardium continues to limit scientific progress. To overcome this issue, utilizing atrial appendages of the human heart may become highly beneficial. Atrial appendages are often removed during open-heart surgery and can be preserved ex vivo as living tissue with varying durability depending on the culture method. In this study, we prepared living thin myocardial slices from left atrial appendages that were cultured using an air-liquid interface system for overall 10 days. Metabolic activity of the cultured slices was assessed using a conventional methyl thiazolyl tetrazolium (MTT) assay. To monitor the structural integrity of cardiomyocytes within the tissue, we implemented our recently described super-resolution microscopy approach that allows both qualitative and quantitative in-depth evaluation of sarcomere network based on parameters such as overall sarcomere content, filament size and orientation. Additionally, expression of mRNAs coding for key structural and functional proteins was analyzed by real-time reverse transcription polymerase chain reaction (qRT-PCR). Our findings demonstrate highly significant disassembly of contractile apparatus represented by degradation of $$\alpha $$ α -actinin filaments detected after three days in culture, while metabolic activity was constantly rising and remained high for up to seven days. However, gene expression of crucial cardiac markers strongly decreased after the first day in culture indicating an early destructive response to ex vivo conditions. Therefore, we suggest static cultivation of living myocardial slices derived from left atrial appendage and prepared according to our protocol only for short-termed experiments (e.g. medicinal drug testing), while introduction of electro-mechanical stimulation protocols may offer the possibility for long-term integrity of such ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diagnostic Ability of Methods Depicting Distress of Tumor-Bearing Mice

Wentao Xie / Marcel Kordt / Rupert Palme / Eberhard Grambow / Brigitte Vollmar / Dietmar Zechner

Animals, Vol 11, Iss 2155, p

2021 Volume 2155

Abstract: Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized. For this purpose, one ...

Abstract	Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized. For this purpose, one must assess the diagnostic ability of readout parameters to evaluate distress. In this study, we evaluated different noninvasive readout parameters such as body weight change, adjusted body weight change, faecal corticosterone metabolites concentration, burrowing activity and a distress score by utilising receiver operating characteristic curves. Eighteen immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used for this study; half were subcutaneously injected with A-375 cells (human malignant melanoma cells) that resulted in large tumors. The remaining mice were inoculated with SCL-2 cells (cutaneous squamous cell carcinoma cells), which resulted in small tumors. The adjusted body weight and faecal corticosterone metabolites concentration had a high diagnostic ability in distinguishing between mice before cancer cell injection and mice bearing large tumors. All other readout parameters had a low diagnostic ability. These results suggest that adjusted body weight and faecal corticosterone metabolites are useful to depict the distress of mice bearing large subcutaneous tumors.
Keywords	animal model ; animal welfare ; xenograft models ; in vivo ; 3Rs ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	630
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distress Analysis of Mice with Cervical Arteriovenous Fistulas

Wentao Xie / Rupert Palme / Clemens Schafmayer / Dietmar Zechner / Brigitte Vollmar / Eberhard Grambow

Animals, Vol 11, Iss 11, p

2021 Volume 3051

Abstract: The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently, a new cervical ... ...

Abstract	The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently, a new cervical arteriovenous model was created in mice to understand the pathophysiology of arteriovenous fistula, which is the most commonly used access for hemodialysis. This study evaluates the distress caused by this new animal model. Ten male C57B6/J mice with cervical arteriovenous fistula were observed for 21 days. Non-invasive parameters, such as body weight, faecal corticosterone metabolites, burrowing activity, nesting activity and distress scores were evaluated at each time point. Six out of ten created arteriovenous fistula matured within the observation time as defined by an increased diameter. The body weight of all animals was reduced after surgery but recovered within five days. In addition, the distress score was significantly increased during the early time point but not at the late time point after arteriovenous fistula creation. Neither burrowing activity nor nesting behaviour were significantly reduced after surgical intervention. Moreover, faecal corticosterone metabolite concentrations did not significantly increase. Therefore, the cervical murine arteriovenous fistula model induced moderate distress in mice and revealed an appropriate maturation rate of the fistulas.
Keywords	hemodialysis access ; animal model ; distress ; animal welfare ; 3R rule ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	630
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Ambivalent Function of YAP in Apoptosis and Cancer

Xianbin Zhang / Ahmed Abdelrahman / Brigitte Vollmar / Dietmar Zechner

International Journal of Molecular Sciences, Vol 19, Iss 12, p

2018 Volume 3770

Abstract: Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and ... ...

Abstract	Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and more evidence demonstrates that this protein is also an essential contributor of p73-mediated apoptosis. This questions the concept that yes-associated protein is always a good target for developing novel anti-cancer drugs. Thus, the aim of this review was to evaluate the clinical relevance of yes-associated protein for cancer pathophysiology. This review also summarized the molecules, processes and drugs, which regulate Hippo-YAP signaling and discusses their effect on apoptosis. In addition, issues are defined, which should be addressed in the future in order to provide a solid basis for targeting the Hippo-YAP signaling pathway in clinical trials.
Keywords	Hippo ; YAP ; signaling pathway ; cell death ; autophagy ; p73 ; cancer ; therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Generalizability, Robustness and Replicability When Evaluating Wellbeing of Laboratory Mice with Various Methods

Dietmar Zechner / Benjamin Schulz / Guanglin Tang / Ahmed Abdelrahman / Simone Kumstel / Nico Seume / Rupert Palme / Brigitte Vollmar

Animals, Vol 12, Iss 2927, p

2022 Volume 2927

Abstract: An essential basis for objectively improving the status of animals during in vivo research is the ability to measure the wellbeing of animals in a reliable and scientific manner. Several non-invasive methods such as assessing body weight, burrowing ... ...

Abstract	An essential basis for objectively improving the status of animals during in vivo research is the ability to measure the wellbeing of animals in a reliable and scientific manner. Several non-invasive methods such as assessing body weight, burrowing activity, nesting behavior, a distress score and fecal corticosterone metabolites were evaluated in healthy mice and after three surgical interventions or during the progression of four gastrointestinal diseases. The performance of each method in differentiating between healthy and diseased animals was assessed using receiver operating characteristic curves. The ability to differentiate between these two states differed between distinct surgical interventions and distinct gastrointestinal diseases. Thus, the generalizability of these methods for assessing animal wellbeing was low. However, the robustness of these methods when assessing wellbeing in one gastrointestinal disease was high since the same methods were often capable of differentiating between healthy and diseased animals independent of applied drugs. Moreover, the replicability when assessing two distinct cohorts with an identical surgical intervention was also high. These data suggest that scientists can reach valid conclusions about animal wellbeing when using these methods within one specific animal model. This might be important when optimizing methodological aspects for improving animal wellbeing. The lack of generalizability, however, suggests that comparing animal models by using single methods might lead to incorrect conclusions. Thus, these data support the concept of using a combination of several methods when assessing animal welfare.
Keywords	distress of animals ; suffering ; severity assessment ; 3Rs ; animal welfare science ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	630
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of Animal Well-Being When Supplementing Drinking Water with Tramadol or Metamizole during Chronic Pancreatitis

Guanglin Tang / Wiebke-Felicitas Nierath / Rupert Palme / Brigitte Vollmar / Dietmar Zechner

Animals, Vol 10, Iss 2306, p

2020 Volume 2306

Abstract: Pain management during in vivo experiments is an animal welfare concern and is in many countries also legally required. In this study, we evaluated C57Bl/6J mice when 3 g/L metamizole or 1 g/L tramadol was provided via drinking water, before and during ... ...

Abstract	Pain management during in vivo experiments is an animal welfare concern and is in many countries also legally required. In this study, we evaluated C57Bl/6J mice when 3 g/L metamizole or 1 g/L tramadol was provided via drinking water, before and during cerulein-induced chronic pancreatitis. Supplementation of drinking water with metamizole or tramadol did not significantly reduce the amount of consumed water. In order to evaluate the wellbeing of mice, a distress score, burrowing activity, nesting behavior, and body weight was assessed. Before induction of pancreatitis, neither tramadol nor metamizole influenced these readout parameters. Chronic pancreatitis caused a significantly increased distress score, decreased burrowing activity and a reduction in body weight. Mice drinking tramadol-supplemented water experienced less loss in body weight and consumed more water than mice drinking metamizole, at a few time-points during chronic pancreatitis. Pancreatic atrophy, a characteristic feature of chronic pancreatitis was not differentially influenced by either analgesic. In conclusion, both analgesics can be used during 33 days of chronic pancreatitis, but tramadol seems to be moderately advantageous when compared to metamizole.
Keywords	wellbeing ; analgesia ; rodents ; sweetened water ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Effect of Early Application of Synthetic Peptides 19-2.5 and 19-4LF to Improve Survival and Neurological Outcome in a Mouse Model of Cardiac Arrest and Resuscitation

Rika Bajorat / Lena Danckert / Florian Ebert / Theresa Bancken / Stefan Bergt / Felix Klawitter / Brigitte Vollmar / Daniel A. Reuter / Tobias Schürholz / Johannes Ehler

Biomedicines, Vol 11, Iss 855, p

2023 Volume 855

Abstract: The synthetic antimicrobial peptides (sAMPs) Pep19-2.5 and Pep19-4LF have been shown in vitro and in vivo to reduce the release of pro-inflammatory cytokines, leading to the suppression of inflammation and immunomodulation. We hypothesized that ... ...

Abstract	The synthetic antimicrobial peptides (sAMPs) Pep19-2.5 and Pep19-4LF have been shown in vitro and in vivo to reduce the release of pro-inflammatory cytokines, leading to the suppression of inflammation and immunomodulation. We hypothesized that intervention with Pep19-2.5 and Pep19-4LF immediately after cardiac arrest and resuscitation (CA-CPR) might attenuate immediate systemic inflammation, survival, and long-term outcomes in a standardized mouse model of CA-CPR. Long-term outcomes up to 28 days were assessed between a control group (saline) and two peptide intervention groups. Primarily, survival as well as neurological and cognitive parameters were assessed. In addition, systemic inflammatory molecules and specific biomarkers were analyzed in plasma as well as in brain tissue. Treatment with sAMPs did not provide any short- or long-term benefits for either survival or neurological outcomes, and no significant benefit on inflammation in the CA-CPR animal model. While no difference was found in the plasma analysis of early cytokines between the intervention groups four hours after resuscitation, a significant increase in UCH-L1, a biomarker of neuronal damage and blood–brain barrier rupture, was measured in the Pep19-4LF-treated group. The theoretical benefit of both sAMPs tested here for the treatment of post-cardiac arrest syndrome could not be proven.
Keywords	cardiac arrest ; cardiopulmonary resuscitation ; antimicrobial peptide ; Pep19-2.5 ; Pep19-4LF ; neurological outcome ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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