Method and means for the treatment of cachexia
A cachexia and multipurpose technology, applied in metabolic diseases, blood diseases, pharmaceutical formulations, etc., can solve problems such as skeletal muscle cachexia syndrome
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Embodiment 1
[0167] Example 1. Treatment of Cachexia Mice with α-trinositol
[0168] Material: [alpha]-trinositol (1-D-meso-inositol 1,2,6-triphosphate) was prepared according to US 4,777,134. The stock solution in glass vials was made up of 1 g of α-trinositol dissolved in saline and made up to a total of 10 ml. Store the stock solution in the refrigerator and use within 24 hours.
[0169] animal: Purebred male NMRI mice (average body weight 25g) were subcutaneously inoculated with fragments of MAC1 6 tumors in the axilla with a trocar, and the experimental animals that lost weight were selected (Bibby M C et al. Characterization of transplantable adenocarcinoma in the mouse colon producing cachexia in the recipient animals. J Natl Cancer Inst 78(1987) 539-546). Inoculated animals were fed rat and mouse growth chow (Special Diet Services, Witham, UK) and water in the laboratory. Significant weight loss was observed 10 to 12 days after tumor inoculation. 24 animals were randomize...
Embodiment 2
[0175] Example 2. Effect of Cachexia Treatment on Body Composition.
[0176] After completion of the treatment described in Example 1, the mice were sacrificed and their body composition was studied. The results are shown in Table 1. The results show that the method of the present invention not only relatively preserves the lean body mass of the animals, but it even increases it in absolute terms. Loss of lean body mass is generally present in patients with cachexia and is an important cause of morbidity. No significant change in water content was observed.
[0177] Table 1. Body composition (% body weight) of MAC1 6 mice with cachexia
[0178]
[0179] Values are mean±SD; p-values were derived from OAT.
[0180] The absolute changes relative to the control group are shown in Table 2.
[0181] Table 2. Absolute changes in body composition, fat and muscle mass in cachectic MAC16 mice
[0182]
Embodiment 3
[0183] Example 3. α-trinositol on PIF (proteolysis inducible factor) and angiotensin in vitro Inhibition of II.
[0184] To investigate the mechanism by which AT protects lean body mass in cachexia, further in vitro experiments were performed using murine myotubes as a surrogate model for skeletal muscle. Incubation with PIF or angiotensin II (Ang II) leads to protein degradation, as reported previously (Smith et al. 2004, Br. J. Cancer, and Tisdale et al. 2006, Cell. Sig), characterized by a typical bell shape Dose-response curve (bell-shaped dose-response curve), when PIF is at 4.2nM, the effect is most obvious, when Ang II is at 0.5μM, the effect is most obvious ( Figure 5 with 8 ). If adding PIF( Figure 5 ) or Ang II ( Figure 8 ) before pre-incubating myotubes with AT (100 μM) for 2 hours can fully reduce the degradation of protein to the basal level. PIF-induced protein degradation is neutralized by up-regulation of the ubiquitin-proteasome pathway (Tisdale et...
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