Effects of hyperglycemia on glucose transporters of the muscle: use of the renal glucose reabsorption inhibitor phlorizin to control glycemia.

Individuals with non-insulin dependent or insulin-dependent diabetes mellitus present insulin resistance in peripheral tissues. This is reflected in a subnormal whole body insulin-dependent glucose utilization, largely dependent on skeletal muscle. Glucose transport across the cell membrane of this tissue is rate limiting in the utilization of the hexose. Therefore, it is possible that a defect exists in insulin-dependent glucose transport in skeletal muscle in diabetic states. This review focuses on two questions: is there a defect at the level of glucose transporters in skeletal muscle of diabetic animal models, and is this a consequence of abnormal insulin or glucose levels? The latter question arises from the fact that these parameters usually vary inversely to each other. Glucose transport into skeletal muscle occurs by two membrane proteins, the GLUT1 and GLUT4 gene products. By subcellular fractionation and Western blotting with isoform-specific antibodies, it was determined that isolated plasma membranes (PM) contain GLUT4 and GLUT1 proteins at a molar ratio of 3.5:1 and that an intracellular fraction (internal membranes; IM) different from sarcoplasmic reticulum contains only GLUT4 transporters. The IM furnishes transporters to the PM in response to insulin. Both transporter isoforms bind cytochalasin B in a D-glucose-protectable fashion. In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1. In the IM, the levels of GLUT4 protein drop, as does the cellular GLUT4 mRNA. To investigate if these changes are associated with hyperglycemia, glucose levels were corrected back to normal values for a 24-h period with sc injections of phlorizin to block proximal tubule glucose reabsorption. This treatment restored cytochalasin B binding, restored GLUT4 and GLUT1 values back to normal levels in the PM, and partly restored cytochalasin B binding but not GLUT4 levels in the IM, consistent with only a partial recovery of GLUT4 mRNA. It is concluded that GLUT4 protein in the PM correlates inversely whereas GLUT1 protein correlates directly with glycemia. It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prognostic significance of cytochemical analysis of leukemic M2 blasts

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR),i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.     

Absence of a relationship between umbilical cord thickness and coiling patterns.

OBJECTIVE: The purpose of this study was to evaluate a relationship between the umbilical cord thickness and cord coiling patterns during the fetal sonographic anatomic survey in the second trimester of pregnancy. METHODS: This was a prospective study of 470 patients with singleton pregnancies who had a fetal anatomic survey with recorded umbilical coiling patterns between 18 and 23 weeks' gestation. The umbilical cord thickness was assessed as an umbilical diameter at the level of the fetal abdominal cord insertion and compared with the antenatal umbilical coiling index (aUCI), calculated as a reciprocal value of the distance between a pair of umbilical cord coils. RESULTS: Three hundred twenty-one patients had adequate sonographic umbilical cord images and maternal demographic, antenatal, and labor data to meet inclusion criteria. The mean aUCI was 0.41 with 10th and 90th percentiles of 0.21 and 0.60, respectively. A total of 10.6% (34/321) and 9.3% (30/321) of patients were categorized as having hypocoiled and hypercoiled umbilical cords, respectively. The mean cord diameter +/- SD was 9.48 +/- 0.97 mm (range 7.0-12.5 mm). There was no statistically significant correlation between aUCI and umbilical cord thickness (P = .1164). CONCLUSIONS: An aUCI, or umbilical coiling pattern, does not correlate with umbilical cord thickness. It appears that a lesser amount of the umbilical supportive tissue, mainly Wharton jelly, is not related to an increased umbilical cord coiling pattern.     

Neglected rupture of the Achilles tendon treated with peroneus brevis transfer: A functional assessment of 5 cases

The purpose of this study was to review the clinical results of 5 patients who underwent repair of a chronic Achilles tendon rupture using a combination of peroneus brevis transfer and plantaris tendon augmentation. The technique belongs to the group of local tendon transfer procedures making use of the transferred peroneus brevis tendon as strengthening material together with the plantaris tendon as suturing material. There were 4 males and 1 female with an average age of 49.4 years and an average time to presentation postinjury of 19.8 weeks (range 5-40 wk). All patients underwent Cybex strength testing before and approximately 1 year after surgery. This testing demonstrated a postoperative improvement in peak plantarflexion torque (Newton-meters/body weight) in all cases. The peak torque of plantar flexion increased in all patients (range, 21%-410%). Four patients were found to have an increase of the dorsal flexors peak torque (range, 31%-290%), whereas one patient showed a decrease (-37%). No patient experienced wound closure complications, postoperative pain, or functional limitations. In spite the possibility of residual lateral ankle instability, we found this modification to be a valuable innovation that offers a very good functional result, low morbidity, technical advantages to the surgeon and, most important, a durable and satisfactory result for the patients.     

Multiple genetic alterations in malignant metastatic insulinomas

Proto-oncogenes, growth factors/receptors, and tumour suppressor genes were analysed in malignant metastatic insulinomas. Normal pancreas showed only a moderate immunoreaction for c-myc proto-oncogene and a strong reaction for insulin. Benign insulinomas were slightly or moderately positive for transforming growth factor a (TGFα), weakly positive for epidermal growth factor receptor (EGF-R), and strongly positive for c-myc and insulin. In malignant insulinomas, besides a strong immunoreaction for c-myc and TGFα, activation of c-K-ras and overexpression of p53 protein were found. Insulin reaction was moderate or strong. Three out of six malignant insulinomas displayed a c-K-ras point mutation at codon 12. All mutations were guanine to cytosine transversion, resulting in amino acid substitution, glycine to arginine. Mutations were present in metastatic insulinomas only. Patients with mutated c-K-ras oncogene had overexpression of p53 protein as well as c-myc and TGFα overexpression. Our results support the view that malignant progression is a consequence of more than one genetic lesion and suggest that activation of myc, TGFα, and ras genesα plays a role in a multistep process of tumour progression, perhaps serving as an initiating event.     

Biochemical changes in the sublingual and submandibular glands after interruption of chorda tympani

The left chorda tympani nerve was interrupted through meatus acusticus externus in ten dogs. In total, 40 dog salivary glands (20 submandibular and 20 sublingual) innervated via chorda tympani were examined. Twenty glands (10 submandibular and 10 sublingual) on the left side were deprived of parasympathetic innervation by chordectomy, whereas contraleteral glands, on the right side, served as controls. Biochemical analysis showed that the interruption of chorda tympani did not cause any significant changes in the concentrations of eight enzymes investigated, i.e. lactate dehydrogenase, alkaline phosphatase, acid phosphatase, amylase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and creatine kinase. There were no significant changes in the concentrations of most important extracellular ions (sodium, potassium, chloride and phosphorus) in the right glands, but the loss of parasympathetic innervation in the left glands was found to cause a statistically significant decrease in the concentration of potassium as intracellular cation and of phosphorus as extracellular anion.     

Cystoid macular edema in anterior chamber lens implantation following posterior capsule rupture

By comparing the incidence of cystoid macular edema (CME) in three groups of patients having different surgical procedures, we attempted to assess the role of vitreous loss as a risk factor for CME development. In the first group (n = 470), the surgical procedure was extracapsular cataract extraction followed by implantation of posterior chamber lens (EC-CE + PC-IOL). The second group (n = 42) had extracapsular cataract extraction which was complicated by posterior capsule rupture, and therefore anterior vitrectomy followed by implantation of anterior chamber lens had to be performed (ECCE + anterior vitrectomy + AC-IOL). In the third group (n = 22) the surgery was intracapsular cataract extraction followed by anterior chamber lens implantation (ICCE + AC-IOL). The third group was included in this follow up study to assess the role of AC-IOL as a possible causative factor for development of CME in uncomplicated cases of ICCE and AC-IOL. The difference of incidences of CME in the second and third group would therefore depend mostly on the vitreous loss. The incidence of CME diagnosed by fluorescein angiography in the first, second and third group was 1.5% (7/470), 35.7% (15/42) and 9.0% (2/22), respectively. All patients who developed CME were treated with combination of corticosteroid-antibiotic drops, dexamethasone retrobulbarly (40 mg/day) and peroral indomethacine (25 mg/day/6 weeks). This therapeutic regime resulted in only moderate improvement of visual acuity.Abbreviations AC-IOL anterior chamber intraocular lens - CME cystoid macular edema - ECCE extracapsular cataract extraction - ICCE intracapsular cataract extraction - IOL intraocular lens - PC-IOL posterior chamber intraocular lens