A Smartphone App for Individual Xylazine/Ketamine Calculation Decreased Anesthesia-Related Mortality in Mice

Jara, Carlos Poblete; Carraro, Rodrigo S.; Zanesco, Ariane Maria; Andrade, Bruna Duarte Moron de; Moreira, Karina Gomes; Nogueira, Guilherme; Souza, Bruno Leandro De; Prado, Thaís Paulino do; Póvoa, Valéria; Velander, William H.; Velloso, Lı́cio A.; Araújo, Eliana P.

doi:10.3389/fvets.2021.651202

Cited by 8 publications

(6 citation statements)

References 20 publications

(28 reference statements)

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“…Mice were fasted for 4h before daily intraperitoneal injections of STZ (50 mg/kg). STZ was daily and freshly dissolved in 0.1 M sodium citrate buffer, pH 4.5, and the dose volumes for each mouse were calculated by Labinsane app (43) STZ injections were made for five consecutive days (low multiple-dose protocol) (44). HDF and Chow diet were injected sodium citrate buffer as control group.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were submitted to fasting according to previously described protocol (45). Subsequently, mice were anesthetized with lethal doses of xylocaine and ketamine calculated by Labinsane App (43). Pancreas and fragments of dorsal skin (8.0 mm punch), epididymal and white adipose tissue were extracted, weighted and prepared for molecular analysis or histological staining.…”

Section: Methodsmentioning

confidence: 99%

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A Diabetic Mice Model For Studying Skin Wound Healing

Jara

Nogueira

Morari

et al. 2022

Preprint

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Advances in wound treatment depend on the availability of animal models that reflect key aspects of human wound healing physiology. To this date, the accepted mouse models do not reflect defects in the healing process for chronic wounds that are associated with type two diabetic skin ulcers. The long term, systemic physiologic stress that occurs in middle aged or older type 2 diabetic patients is difficult to simulate in preclinical animal model. We have strived to incorporate the essential elements of this stress in a manageable mouse model: long term metabolic stress from obesity to include the effects of middle age and thereafter onset of diabetes. At six-weeks age, male C57BL/6 mice were separated into groups fed a Chow and High-Fat Diet for 0.5, 3, and 6 months. Treatment groups included long term, obesity stressed mice with induction of diabetes by streptozotocin at 5 months, and further physiologic evaluation at 8 months old. We show that this model results in a severe metabolic phenotype with insulin resistance and glucose intolerance associated with obesity and, more importantly, skin changes. The phenotype of this older age mouse model included a transcriptional signature of gene expression in skin that overlapped that observed with elderly patients who develop diabetic foot ulcers. This unique old age phenotype result contrasts with current non-obesity stressed mice models with induced diabetes at 4 months or younger which do not reflect the pathologic type 2 human phenotype.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Diabetic Mice Model For Studying Skin Wound Healing

Jara

Nogueira

Morari

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mice were fasted for 4h before daily intraperitoneal injections of STZ (50 mg/kg). STZ was daily and freshly dissolved in 0.1 M sodium citrate buffer, pH 4.5, and the dose volumes for each mouse were calculated by Labinsane app [49] STZ injections were made for five consecutive days (low multiple-dose protocol) [50]. HDF and chow diet were injected sodium citrate buffer as control group.…”

Section: Diabetes Mellitus Induction Protocolmentioning

confidence: 99%

“…Mice were submitted to fasting according to previously described protocol [51]. Subsequently, mice were anesthetized with lethal doses of xylocaine and ketamine calculated by Labinsane App [49]. Pancreas and fragments of dorsal skin (8.0 mm punch), epididymal and white adipose tissue were extracted, weighted and prepared for molecular analysis or histological staining.…”

Section: Tissue Extractionmentioning

confidence: 99%

An older diabetes-induced mice model for studying skin wound healing

et al. 2023

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Advances in wound treatment depend on the availability of animal models that reflect key aspects of human wound healing physiology. To this date, the accepted mouse models do not reflect defects in the healing process for chronic wounds that are associated with type two diabetic skin ulcers. The long term, systemic physiologic stress that occurs in middle aged or older Type 2 diabetes patients is difficult to simulate in preclinical animal model. We have strived to incorporate the essential elements of this stress in a manageable mouse model: long term metabolic stress from obesity to include the effects of middle age and thereafter onset of diabetes. At six-weeks age, male C57BL/6 mice were separated into groups fed a chow and High-Fat Diet for 0.5, 3, and 6 months. Treatment groups included long term, obesity stressed mice with induction of diabetes by streptozotocin at 5 months, and further physiologic evaluation at 8 months old. We show that this model results in a severe metabolic phenotype with insulin resistance and glucose intolerance associated with obesity and, more importantly, skin changes. The phenotype of this older age mouse model included a transcriptional signature of gene expression in skin that overlapped that observed with elderly patients who develop diabetic foot ulcers. We believe this unique old age phenotype contrasts with current mice models with induced diabetes.

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“…Both C57BL/6 and Pomc tdTomato mice were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg). To calculate the dosage of anesthesia, we used a smartphone app, Labsinsane [20]. All mice were submitted to stereotaxic surgery (Ultra Precise-model 963, Kopf).…”

Section: Stereotaxic Surgerymentioning

confidence: 99%

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2

Zanesco

Mendes

Engel

et al. 2022

Cells

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Background: The hypothalamic proopiomelanocortin (Pomc) neurons act as first-order sensors of systemic energy stores, providing signals that regulate caloric intake and energy expenditure. In experimental obesity, dietary saturated fatty acids affect Pomc endopeptidases (PCs), resulting in the abnormal production of the neurotransmitters α-melanocyte-stimulating hormone (α-MSH) and β-endorphin, thus impacting energy balance. The cAMP response element-binding protein (CREB) is one of the transcription factors that control the expression of Pomc endopeptidases; however, it was previously unknown if dietary fats could affect CREB and consequently the expression of Pomc endopeptidases. Methods: Here, we used single-cell RNA sequencing analysis, PCR, immunoblot, ELISA and immunofluorescence histological assays to determine the impact of a high-fat diet (HFD) on the expression and function of hypothalamic CREB and its impact on the melanocortinergic system. Results: The results indicate that CREB is expressed in arcuate nucleus Pomc neurons and is activated as early as nine hours after the introduction of a high-fat diet. The inhibition of hypothalamic CREB using a short-hairpin RNA lentiviral vector resulted in increased diet-induced body-mass gain and reduced energy expenditure. This was accompanied by reduced expression of the Pomc endopeptidases, protein convertase 2, which are encoded by Pcsk2, and by the loss of the high-fat-diet-induced effect to inhibit the production of α-MSH. Conclusions: This study provides the first evidence for the involvement of CREB in the abnormal regulation of the hypothalamic Pomc endopeptidase system in experimental obesity.

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A Smartphone App for Individual Xylazine/Ketamine Calculation Decreased Anesthesia-Related Mortality in Mice

Cited by 8 publications

References 20 publications

A Diabetic Mice Model For Studying Skin Wound Healing

A Diabetic Mice Model For Studying Skin Wound Healing

An older diabetes-induced mice model for studying skin wound healing

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2

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