Effect of age and caloric restriction on insulin receptor binding and glucose transporter levels in aging rats

We report on the effect of age and chronic caloric restriction (CR) on insulin binding and glucose transporter content in both diaphragm and heart muscle membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR animals were allowed 60% of ad libitum food. The CR regimen was initiated at four months of age and the animals were maintained on their respective diets until necropsy. There was no effect of age on insulin binding for either ad libitum or CR animals at each age evaluated. Caloric restriction significantly lowered insulin levels at each age studied when compared to the ad libitum-fed rats. However, CR animals were noted to have increased insulin binding (p < 0.001) compared to ad libitum-fed animals at each age for diaphragm muscle. For the heart, there appeared to be a decreased binding, particularly at higher insulin concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4 levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane between ad libitum or CR animals. This data indicates that caloric restriction may have tissue-specific effects for insulin receptor binding, and that the improved insulin sensitivity in CR states is not a result of altered glucose transporter protein content.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

L—门冬酰胺酶前体脂质体对小鼠毒性及对实验性肿瘤作用

目的：研究L－门冬酰胺酶（L－Asparaginase,L-A)前体脂质体（Proliposome,PL)[L-APL]iv对小鼠的毒性及对荷瘤小鼠的抗肿瘤活性。方法：以小鼠的急性毒性和外周血中白细胞数及血小板数为指标观察药物对小鼠的毒性及以荷瘤小鼠的瘤重和生命延和工率观察药物的抗肿瘤活性;结果：L－APL iV对小鼠的急性毒性与L－A相比明显降低,L－APL对正常小鼠外周血中白细胞数,血小板数无明显影响,而相同剂量L－A对小鼠外周血中白细胞数,血小板数明显降低。与对照组相比,L－APL和L－Aip可明显延长腹水型小鼠移瘤L1210,P388的存活天数,与同剂量L－A相比,L－APL高剂量有明显延长腹水型小鼠移植瘤的存活天数作用。L－APL及L－A ip对小鼠移植瘤Heps,EC实体型的肿瘤生长具有明显的抑制作用,两者抑瘤作用相近。结论：L－APL对小鼠的毒性明显小于相同剂量的L－A,L－APL不仅保持了L－A的抗肿瘤活性,而且有明显的增效作用。     

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months’duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71 % and 79%, respectively.     

Kinetics of lactate transport into rat liver in vivo

Lactate clearance by liver plays an important role in lactate homeostasis and in the development of lactic acidosis. The role of lactate delivery to liver as a limiting factor in hepatic uptake of lactate is unclear. Lactate delivery of mechanisms could be important if rates of lactate transport approximate rates of lactate metabolism by liver. The rates of lactate transport into liver have been determined in vitro with isolated liver cells and the results have been conflicting. Therefore, the present studies measure the rate of transport of [14C]-L-lactate, and its poorly metabolizeable stereoisomer, [14C]-D-lactate, into rat liver in vivo using a portal vein injection technique. The transport of [3H]-water and of [14C]-sucrose, an extracellular reference compound, were also studied. Portal blood flow was determined from the kinetics of [3H]-water efflux in liver and was 1.93 +/- 0.22 mL/min/g. The volumes of distribution of [14C]-L-lactate, and [14C]-sucrose were 1.31 +/- 0.22, 0.71 +/- 0.07, and 0.22 +/- 0.07 mL/g, respectively. The extraction of unidirectional influx of [14C]-L-lactate and [14C]-D-lactate by rat liver was 93% +/- 10% and 91% +/- 9%, respectively. The rate of lactate transport into rat liver in vivo, 1.8 mumols.min-1.g-1, is approximately twofold greater than the rate of lactate metabolism by rat liver reported in the literature. Therefore, lactate uptake by liver may not be limited by transport under normal conditions. However, conditions such as decreased portal blood flow, which slow lactate delivery to liver by 50% or more, could cause lactate uptake by liver to be limited by transport of circulating lactate.