scholarly journals Adapted Murine Sepsis Score: Improving The Research In Experimental Sepsis Mice Model

2020 ◽  
Author(s):  
Maicon Machado Sulzbacher ◽  
Lucas Machado Sulzbacher ◽  
Felipe Rafael Passos ◽  
Bruna Letícia Endl Bilibio ◽  
Kauana de Oliveira ◽  
...  

Abstract Objective The Murine Sepsis Score (MSS) is used to assess the severity of sepsis in rats and mice based on observational characteristics. The quantitative variables of blood glucose, body weight and temperature are predictors of severity in experimental models of sepsis. Therefore, our study sought to adapt the MSS with the same variables to indicate earlier the severity of the disease in murine models of the disease. Results Sepsis mice presented hypoglycemia, weight loss, and hypothermia. Therefore, these variables were included in the Adapted Murine Sepsis Score (A-MSS). The A-MASS presented 100% specificity and 87.5% sensibility been able to differentiate the early sepsis symptoms and its severity. The A-MSS allows an early and more complete diagnosis of sepsis in mice and might be considered as a procedure to improve the analysis of systemic sepsis dysfunction in murine experimental models.

2000 ◽  
Vol 278 (4) ◽  
pp. R882-R890 ◽  
Author(s):  
Claire A. Matson ◽  
Dana F. Reid ◽  
Todd A. Cannon ◽  
Robert C. Ritter

Leptin, the product of the obese gene, reduces food intake and body weight in rats and mice, whereas administration of the gut-peptide CCK reduces meal size but not body weight. In the current experiments, we report that repeated daily combination of intracerebroventricular leptin and intraperitoneal CCK results in significantly greater loss of body weight than does leptin alone. However, leptin plus CCK treatment does not synergistically reduce the size of individual 30-min sucrose meals during this period, and the effect of leptin-CCK combination on daily chow intake, while significant, is small compared with the robust effects on body weight loss. This synergistic effect on body weight loss depends on a peripheral action of CCK and a central action of leptin. These data suggest a previously unsuspected role for CCK in body weight regulation that may not depend entirely on reduction of feeding behavior and suggest a strategy for enhancing the effects of leptin in leptin-resistant obese individuals.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4557-4557
Author(s):  
Odelia Katz ◽  
Matthew Stuible ◽  
Nataliya Golishevski ◽  
Lilach Lifshitz ◽  
Michel Tremblay ◽  
...  

Abstract Abstract 4557 Erythropoietin (EPO) regulates proliferation and differentiation of erythroid precursor cells into erythrocytes. The last decade has revealed non-renal sites of EPO production and extrahematopoietic expression of the EPO-receptor (EPO-R), suggesting that EPO has pleiotropic functions. We have previously shown anti-cancer and immunomodulating effects of the hormone in humans and mice. Here we addressed the interplay among EPO, glucose metabolism, and body weight by employing a panel of relevant experimental murine models. The models focused on situations of increased EPO levels, including EPO-injected C57BL/6 and BALB/c mice, as well as transgenic mice (tg6) constitutively overexpressing human EPO and thus exposed to constantly high EPO serum levels. As experimental models for diabetes and obesity we employed protein Tyr phosphatase 1B (PTP1B) knockout mice associated with resistance to diabetes (PTP1B-/-), and ob/ob mice susceptible to diabetes and obesity. Our data demonstrated an EPO-associated decrease in blood glucose levels in all mice models tested. The tg6 mice, continuously exposed to EPO, were hypoglycemic even under non-fasting conditions. Blood glucose reduction in the experimental models tested was evident already one week following EPO administration in all models, including the PTP1B-/- and ob/ob mice. This conclusion gained further support by the glucose tolerence test (GTT). EPO overexpression or administration led to improved glucose clearance in all the tested murine models. Notably, in the ob/ob mice we observed EPO-associated attenuation of body weight gain and reduction of hemoglobin A1C. Preliminary clinical observations with several diabetic patients support these data and will be discussed further. Taken together our data bear significant clinical implications for EPO treatment in the management of a wide range of metabolic diseases and add an important novel therapeutic potential to this pleiotropic hormone. Disclosures: Mittelman: BioGAL- Start up (inactive): Equity Ownership, Patents & Royalties. Off Label Use: Non erythroid effects: immune, anti-cancer (all under investigation).


2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Mirasari Putri ◽  
Neni Anggraeni ◽  
Raden Aliya Tresna M. D. ◽  
Ghaliby Ardhia Ramli ◽  
Mia Kusmiati ◽  
...  

Sepsis causes damage for cells, behavioral phenotype regression, and will end in most patients' death. The ethanol extract of cogongrass (Imperata cylindrica L.)  acts as an antioxidant. This study aimed to observe the effect of giving ECGR to body weight (BW) and the sepsis score of the sepsis mice model by lipopolysaccharide (LPS) induction. This study was an in vivo study with a randomized post-test controlled group design at the animal laboratory of Universitas Padjadjaran, 2018. We used 4 (four) groups of male mice (Mus musculus) DDY strains. Group 1 as a control, group 2: LPS 10 μL/kgBW, group 3, and 4: LPS+ECGR (90 mg/kgBW, and a dose of 115 mg/kgBW, respectively). This treatment was performed for two weeks. Every three days, we measured their body weight. After two weeks, group 2, group 3, and 4 were injected with LPS for 8 hours to induce sepsis. Next, we measured body weight and sepsis score using murine sepsis score (MSS). Then statistical analysis was performed using ANOVA and the Kruskal-Wallis test. The results showed no differences in body weight were found in the treatment groups (3 and 4) compared with control, suggesting no effect of ECGR in decreasing mice body weight. The sepsis score was more than 21 in groups treated with LPS (2, 3, and 4), suggesting LPS can induce sepsis. There was a slight decrease in scores in-group 3 and 4 compared with group 2. This study concludes that the treatment of ECGR caused no harm to body weight and slightly decreased sepsis score in the sepsis mice model. EKSTRAK ETANOL ALANG-ALANG (IMPERATA CYLINDRICA L.) TERHADAP BERAT BADAN DAN SKOR SEPSIS MENCIT MODEL SEPSISSepsis menyebabkan kerusakan sel, regresi fenotipe perilaku, dan akan berakhir kematian pada sebagian besar pasien. Ekstrak etanol akar alang-alang (Imperata cylindrica L.) (ECGR) berperan sebagai antioksidan. Penelitian ini bertujuan mengetahui pengaruh pemberian ECGR terhadap berat badan (BB) dan skor sepsis pada mencit model sepsis yang diinduksi lipopolisakarida (LPS). Penelitian ini adalah penelitian in vivo dengan desain randomized post-test controlled group di laboratoium hewan Universitas Padjadjaran tahun 2018. Kami menggunakan 4 (empat) kelompok mencit jantan (Mus musculus) strain DDY. Kelompok 1 sebagai kontrol, kelompok 2 diinduksi LPS 10 μL/kgBB, kelompok 3 dan 4 diinduksi LPS + ECGR (dosis 90 mg/kgBB dan 115 mg/kgBB masing-masing). Perlakuan ini dilakukan selama 2 minggu. Setiap tiga hari dilakukan pengukuran berat badan mencit. Setelah dua minggu, kelompok 2, kelompok 3, dan kelompok 4 diinjeksi LPS selama 8 jam untuk menginduksi sepsis. Selanjutnya, diukur berat badan dan skor sepsis menggunakan murine sepsis score (MSS). Analisis statistik menggunakan ANOVA dan Uji Kruskal-Wallis. Hasil penelitian menunjukkan tidak terdapat perbedaan berat badan pada kelompok perlakuan (3 dan 4) dibanding dengan kelompok kontrol yang menunjukkan ECGR tidak berpengaruh dalam menurunkan berat badan mencit. Skor sepsis lebih dari 21 pada kelompok yang diinduksi LPS (2, 3, dan 4) menunjukkan LPS dapat menyebabkan sepsis. Terdapat sedikit penurunan skor pada kelompok 3 dan 4 dibanding dengan kelompok 2. Simpulan penelitian ini, pengobatan ECGR tidak membahayakan berat badan dan mengakibatkan sedikit penurunan skor sepsis pada mencit model sepsis.


Author(s):  
G. Brett Moreau ◽  
Stacey L. Burgess ◽  
Jeffrey M. Sturek ◽  
Alexandra N. Donlan ◽  
William A. Petri ◽  
...  

Abstract/SummaryMurine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19 disease. Because human ACE2 is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for five days and scored for weight loss and clinical symptoms. Infected mice did not exhibit any signs of infection until day four, when weight loss, but no other obvious clinical symptoms were observed. By day five all infected mice had lost around 10% of their original body weight, but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration and alveolar septal thickening. Overall, these results show that symptomatic SARS-CoV-2 infection can be established in the K18-hACE2 transgenic background and should be a useful mouse model for COVID-19 disease.


2006 ◽  
Vol 76 (4) ◽  
pp. 208-215 ◽  
Author(s):  
Astrup

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.


1974 ◽  
Vol 77 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Rüdiger Ghraf ◽  
Edmund Rodney Lax ◽  
Hanns-Georg Hoff ◽  
Herbert Schriefers

ABSTRACT The androgens testosterone and 5α-dihydrotestosterone, the anabolic drug 19-nortestosterone and the anti-androgen cyproterone acetate were investigated with regard to their modifying action on the sexual differentiation of the activities of rat liver enzymes involved in steroid hormone metabolism. The activities of the enzymes (Δ4-5α-hydrogenase, 20-ketoreductase, 3α-and 3β-hydroxysteroid dehydrogenase, NAD- and NADP-dependent Δ4-3β-hydroxysteroid dehydrogenase, total steroid hydroxylases, 7α- and 16α-hydroxylase) were determined in cell-free liver fractions of male animals castrated on day 25 of life and killed on day 90; and of castrated animals which, from day 75 to 89 received daily sc injections (0.3 mg/100 g body weight) of the anabolic drug or the androgen only or in combination with cyproterone acetate (3 mg/100 g body weight). With the exception of 7α-hydroxylase castration leads to a feminization of the enzyme activity pattern. However, the degree of feminization varies from enzyme to enzyme. The administration of testosterone or of 5α-dihydrotestosterone reverses the effect of castration. With 5α-dihydrotestosterone activity values were reached which in some cases were significantly higher than those obtained with testosterone. Although both androgens restored the enzyme activities to the normal male values, neither androgen was able to compensate for the weight loss of the seminal vesicles in the dose administered. The administration of 19-nortestosterone in the same dose as testosterone is only 30 % as effective in restoring the weight loss of the seminal vesicles, but leads to identical activities of Δ4-5α-hydrogenase and of hydroxysteroid dehydrogenases as are found for testosterone. 19-Nortestosterone is without influence on the activities of total steroid hydroxylases and of 16α-hydroxylase. 16α-Hydroxylase is the only enzyme in which the activity enhancing effects of testosterone or of 5α-dihydrotestosterone can be completely blocked by the simultaneous administration of the anti-androgen cyproterone acetate. In all other enzyme activities the anti-androgen does not interfere with the effect of the androgens although it blocks their action on the weight restitution of the seminal vesicles by 60–70 %. 7α-Hydroxylase does not exhibit any androgen dependency. Neither castration nor the subsequent administration of the two androgens, or of the anabolic drug leads to any alterations in activity. However, it is interesting to note that the administration of cyproterone acetate does cause an increase in activity.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1965-P
Author(s):  
TEAYOUN KIM ◽  
JESSICA P. ANTIPENKO ◽  
SHELLY NASON ◽  
NATALIE PRESEDO ◽  
WILLIAM J. VAN DER POL ◽  
...  

2018 ◽  
Vol 44 (1) ◽  
Author(s):  
Ayako Ito ◽  
Aya Nozaki ◽  
Ichiro Horie ◽  
Takao Ando ◽  
Atsushi Kawakami

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