Methylglyoxal impairs GLUT4 trafficking and leads to increased glucose uptake in L6 myoblasts.

Methylglyoxal (MG) is a highly reactive dicarbonyl compound derived mainly from glucose degradation pathways, but also from protein and fatty acid metabolism. MG modifies structure and function of different biomolecules and thus plays an important role in the pathogenesis of diabetic complications. Hyperglycemia-associated accumulation of MG might be associated with generation of oxidative stress and subsequently insulin resistance. Therefore, the effects of MG on insulin signaling and on translocation of glucose transporter 4 (GLUT4) were investigated in the rat skeletal muscle cell line L6-GLUT4myc stably expressing myc-tagged GLUT4. Twenty four-hour MG treatment resulted in elevated GLUT4 presentation on the surface of L6 myoblasts and in an increased uptake of glucose even without insulin stimulation. Exogenously added MG neither effected IRS-1 expression nor IRS-1 phosphorylation. A decreased expression of Akt1 but not Akt2 and concomitantly increased apoptosis were detected following MG treatment. To exclude that oxidative stress caused by MG treatment leads to increased GLUT4 translocation, effects of pretreatment with 2 antioxidants were investigated. The antioxidant and MG scavenger NAC prevented the MG-induced GLUT4 translocation. In contrast, tiron, a well-known antioxidant that does not exert MG-scavenger function, had no impact on MG-induced GLUT4 translocation supporting the hypothesis of a direct effect of MG on GLUT4 trafficking. In conclusion, prolonged treatment with MG augments GLUT4 level on the surface of L6 myoblasts, at least in part through a higher translocation of GLUT4 from the intracellular compartment as well as a reduction of GLUT4 internalization, resulting in increased glucose uptake.

Heat shock protein 27 modification is increased in the human diabetic failing heart.

Chronic conditions like diabetes mellitus (DM) leading to altered metabolism might cause cardiac dysfunction. Hyperglycemia plays an important role in the pathogenesis of diabetic complications including accumulation of methylglyoxal (MG), a highly reactive alpha-dicarbonyl metabolite of glucose degradation pathways and increased generation of advanced glycation endproducts (AGEs). The aim of this investigation was to study the extent of the MG-modification argpyrimidine in human diabetic heart and in rat cardiomyoblasts grown under hyperglycemic conditions. Left ventricular myocardial samples from explanted hearts of patients with cardiomyopathy with (n=8) or without DM (n=8) as well as nonfailing donor organs (n=6), and rat cardiac myoblasts H9c2 treated with glucose were screened for the MG-modification argpyrimidine. The small heat shock protein 27 (Hsp27) revealed to be the major argpyrimidine containing protein in cardiac tissue. Additionally, the modification of arginine leading to argpyrimidine and the phosphorylation of Hsp27 are increased in the myocardium of patients with DM. In H9c2 cells hyperglycemia leads to a decrease of the Hsp27-expression and an increase in argpyrimidine content and phosphorylation of Hsp27, which was accompanied by the induction of oxidative stress and apoptosis. This study shows an association between diabetes and increased argpyrimidine-modification of myocardial Hsp27, a protein which is involved in apoptosis, oxidative stress, and cytoskeleton stabilization.

Comparative contraceptive experience with three-month and six-month medroxyprogesterone acetate regimens.

Three-month (150 mg) and six-month (450 mg) contraceptive regimens of medroxyprogesterone acetate (DMPA) as an intramuscular depot injection are compared in this paper. A total of 19,875 women participated in the study, accounting for 220,530 woman-months of use. A Pearl index of 0.1069 for the three-month regimen was significantly lower than for the six-month group, where the index was 0.4943 (p less than 0.01). Side effects were limited insofar as personal reasons and loss to follow-up were the most important single category for discontinuation of this contraceptive method. No thrombotic incidents occurred. It is concluded that both contraceptive regimens of DMPA appear to be acceptable with regard to use-effectiveness, patient acceptance and prevalence of side effects.

[Perinatal deaths in the rural areas of the Cape Province, January--December 1985]. / Kaaplandse plattelandse perinatale sterftes, Januarie--Desember 1985.

In this study 18 rural hospitals in the Cape Province were prospectively surveyed in respect of the number of deliveries, perinatal deaths, low-birth-weight babies, and the hospital facilities available for routine antenatal, intrapartum and neonatal care. During the study period (1 January - 31 December 1985) there were a total of 19,274 deliveries (birth weight greater than or equal to 1,000 g). The mean perinatal mortality rate was 27,3/1,000 deliveries (range 15.3-45.3). The prevalence of low-birth-weight babies ranged from 13.3% to 34.4% with a mean of 17.7%. By plotting the perinatal mortality rate against the prevalence of low-birth-weight babies a perinatal care index was established. A low perinatal mortality coupled with a high prevalence of low-birth-weight infants, for example, signifies proper care. The perinatal index was then used to compare the neonatal outcome of different hospitals. Outcome varied considerably, as did facilities and care. Serological tests for syphilis and blood groups were not known in the majority of patients at 4 hospitals involving 2,387 deliveries. No cervical cytology was done at 6 hospitals involving 5,462 deliveries. One hospital had no neonatal resuscitation equipment. There were no facilities for serum bilirubin measurements at 10 hospitals involving 8,867 deliveries. However, most problems identified are easily and cheaply rectifiable.

[Interval Falope ring sterilization in the Cape Province: experience with 9175 cases over 4 years]. / Interval-Falope-ring-sterilisasies in die Kaapprovinsie. Ondervinding met 9175 gevalle oor 4 jaar.

During a 4-year period 9175 women were sterilized under local anaesthesia by the laparoscopic Falope ring method. These procedures were performed in smaller towns in the Cape Province. The method used, its cost-effectiveness, and its acceptability to patients are described in detail. This venture proves convincingly that a highly sophisticated medical service can be made available to rural areas, ensuring greater support for a high-priority primary health care service.

Complications in 8509 laparoscopic Falope ring sterilizations performed under local anaesthesia.

During the 3-year period 1 January 1980-31 December 1982, 8509 laparoscopic Falope ring sterilizations were performed under local anaesthesia in rural areas of the Cape Province by the Sterilization Service of Tygerberg Hospital. Despite the fact that 476 of the patients had undergone previous lower abdominal surgery, major complications (anaphylactic shock after injection of lignocaine and inadvertent perforation of the bladder by the trocar) occurred in only 2 cases. It was not possible to complete the sterilization under local anaesthesia in 98 cases, resulting in a technical failure rate of 1.15%. A prospective study of the minor complications encountered among the 193 patients sterilized during November 1982 showed that torn tubes occurred in 3.1% and uterine perforation in 2.1%. This can be partially explained by the fact that evidence of previous pelvic infection was seen during laparoscopy in 9.3% of cases. The pregnancy rate after sterilization was 0.28% for the group as a whole.