The rate of gluconeogenesis from lactate increased in perfused livers after exposure of rats to cold for 5 days, and it returned to the control rate after 20 days [M. Shiota, T. Tanaka, and T. Sugano. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E281-E286, 1985.]. The relationship between the increased gluconeogenic activity and its zonal distribution in liver lobules was studied in cold-exposed rats that had been starved for 24 h by examination of preparations enriched for periportal hepatocytes (PP-H) and for perivenous hepatocytes (PV-H), which had been isolated by the digitonin-collagenase perfusion technique. In the control group, the rate of gluconeogenesis from lactate or alanine was three times higher in PP-H than in PV-H. The rate of gluconeogenesis from these substrates in PP-H was not changed by exposure of rats to cold. The rates of PV-H increased to the level in PP-H after 5 days of exposure of rats to cold and then returned to the control rates after 20 days. The rate of gluconeogenesis from fructose was not altered in either preparation of cells by cold treatment of rats. The change in gluconeogenic capacity in PV-H caused by exposure of rats to cold was unrelated to changes in the activity of the malate-aspartate shuttle and of pyruvate kinase. The increased capacity in mitochondrial respiration was observed in both preparations of cells by cold treatment of rats for 5 days. The activity of phosphoenolpyruvate carboxykinase was higher in PP-H than in PV-H in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
This report summarizes our experience with the combination of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for patients with gynecological sarcomas. We reviewed the records of all patients who had received the MAID regimen for a gynecological sarcoma between 1993 and 2000. The MAID regimen was administered intravenously every 4 weeks in the hospital as follows: (1) mesna 1500 mg/m2/day x 4 days; (2) doxorubicin 15 mg/m2/day x 3 days; (3) ifosfamide 1500 mg/m2/day x 3 days; (4) dacarbazine 250 mg/m2/day x 3 days. The results of treatment with MAID were disappointing. Overall, the response rate was 9% with one complete response and one partial response (both in patients with uterine leiomyosarcoma). We did not observe any responses among the patients with carcinosarcomas of either ovarian or uterine origin. The median progression-free interval and survival were 11 months and 29 months, respectively. This regimen was associated with substantial toxicity (including a death from neutropenic sepsis) as well as high cost and inconvenience due to the requirement for inpatient administration. Although our study contains a limited number of patients with a variety of gynecological sarcomas, our review has led us to discontinue using MAID. It remains to be established if any combination chemotherapy regimen is better than single agent treatment.
The relationship between the enhanced responses of gluconeogenesis to norepinephrine (NE) and glucagon and its zonal distribution was studied in liver lobules of cold-exposed rats by examination of preparations enriched for periportal hepatocytes (PP-H) and for perivenous hepatocytes (PV-H) by the digitonin-collagenase perfusion technique. In the control group, gluconeogenesis from lactate (10 mM) plus pyruvate (1 mM) was higher in PP-H than in PV-H. NE (100 nM) and glucagon (100 nM) increased the rate of gluconeogenesis by 80 and 70%, respectively, in both PP-H and PV-H. Gluconeogenesis in PP-H was unchanged by cold exposure. The rate in PV-H increased to the rate in PP-H at 5 days after cold exposure, and then the rate returned to the control value at 20 days. The gluconeogenic response to the alpha-adrenergic action of NE in both PP-H and PV-H doubled after 5 days. The response to glucagon tripled in PP-H and was cut in half in PV-H after 20 days. Phorbol 12-myristate 13-acetate (PMA; 1 microM), A-23187 (100 nM), and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 1 mM) increased the rate of gluconeogenesis by 200, 100, and 80%, respectively, in both PP-H and PV-H from the control group. The responses to PMA and A-23187 were unchanged by exposure to cold. The response to DBcAMP was doubled in PP-H and was cut in half in PV-H after 20 days of cold exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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