Glucose uptake in human adipose tissue

One hundred grams of glucose with 50 microCi U-14C-glucose were given orally to 17 women with widely varying amounts of body fat. Radioactivity and glucose metabolism in vitro were then measured in adipose tissue obtained by needle biopsies in the abdominal and femoral regions after four hours. Radioactivity in triglycerides was then measured in repeated biopsies 1 day, 1 week, and monthly up to 7 months after glucose administration. Glucose label in triglycerides after four hours was higher in abdominal than femoral adipocytes in obese women. It increased slightly during the following week, and then decreased exponentially with a half-life of 12 months in the abdominal region and 19 months in the femoral region. Uptake of glucose carbon in total body fat was estimated from the triglyceride label measured and determinations of body fat mass, and found to be in the order of less than 4% of given glucose. The studies in vitro suggested that much of the glucose taken up in adipose tissue is converted to lactate. If this is the case in vivo, then glucose uptake in adipose tissue might well be of significance for total body glucose homeostasis, particularly in obese subjects, amounting to maximally perhaps one third to one half of the oral glucose given. The majority of this glucose uptake would then, however, leave adipose tissue again as lactate. The shorter half-life of label in abdominal adipocytes is in agreement with findings of increased lipolysis in these adipocytes in vitro.     

PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D₁-dopamine receptor antagonists. Both compounds have been labeled with¹¹C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D₁-dopamine receptors. This striatal uptake was displaced by high doses of the selective D₁-antagonist SCH 23390 (2 mg/kg) but not by the 5HT₂-antagonist ketanserin (1.5 mg/kg) or the selective D₂-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [¹¹C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [¹¹C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [¹¹C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [¹¹C]NNC 756 the ratio was about 5. This ratio of 5 for [¹¹C]NNC 756 is the highest obtained so far for PET radioligands for the D₁-dopamine receptor.     

Factors Influencing Number of Treatments and Seizure Duration in ECT: Drug Treatment, Social Class

This investigation studies number of treatments and seizure duration during a course of unilateral electroconvulsive therapy (ECT) in 82 inpatients with major depressive disorders. Therapy with antidepressants or benzodiazepines preceding ECT was neither related to number of treatments nor to seizure duration. An average dose of methohexital higher than 1.2 mg/kg body weight was associated both with an increased number of treatments and a shorter average seizure duration. Concurrent therapy with neuroleptics was related to a reduced number of treatments. Patients in social class I, more often than others, received fewer treatments.     

The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy

Two iliac crest needle biopsies were taken from a 43-year-old lead-poisoned woman during and after completion of a Ca-EDTA treatment. By atomic absorption spectroscopy the first and second biopsy were found to contain 56, respectively 41.6 g lead/g wet tissue. In both biopsies 36% of the lead was extractable in 0.1 N HCl. Electron microbeam X-ray analysis proved to have too low sensitivity for quantitation of the lead in these biopsies. Laser microbeam mass analysis (LAMMA), performed only on the second biopsy, revealed a high and fairly constant residual lead concentration in all bone marrow cell nuclei (approximately 55 g/g) and a low lead concentration in the cytoplasm of the same cells (4–12 (g/g). The extracellular bone matrix lead was greatly concentrated in the superficial 3–6 m osteoid zone of the bony trabeculae and totally absent from deeper parts of the mineralized matrix. The LAMMA results are in good agreement with those of subcellular fractionation experiments and atomic absorption spectroscopy, provided that the relative volume fraction of nucleus and cytoplasm is accounted for. The high residual osteoid lead after completed chelation therapy indicates that lead has a stronger affinity for the organic than the mineral components of bone matrix.     

Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses

Human immunodeficiency virus type 1 (HIV-1) fusion with its target cells is initiated by sequential interactions between its envelope glycoprotein, CD4, and a co-receptor, usually CCR5 or CXCR4. Small molecules that bind to CCR5 and prevent its use by R5 HIV-1 strains are now being developed clinically as antiviral drugs. To test whether a block to CCR5 promotes the replication of viruses that enter cells via CXCR4 and are associated with accelerated disease progression, we administered a small molecule CCR5 inhibitor, CMPD 167, to three macaques dual-infected with both R5 (SIVmac251) and X4 (SHIV-89.6P) viruses. CMPD 167 caused a rapid and substantial (on average, 50-fold) suppression of R5 virus replication in each animal. In two of the animals, but not in the third, a rapid, transient, 8- to 15-fold increase in the amount of plasma X4 virus occurred. In neither animal was the increase in X4 viral load sustained throughout therapy, however. These observations may have relevance for the development of CCR5 inhibitors for treatment of HIV-1 infection of humans.     

Inclusion of a non-immunoglobulin binding protein in two-site ELISA for quantification of human serum proteins without interference by heterophilic serum antibodies

Measurement of human serum molecules with two-site ELISA can be biased by the presence of human heterophilic anti-animal immunoglobulin antibodies (HAIA) that cause false-positive signals by cross-linking the monoclonal (mAb) and/or polyclonal antibodies (pAb) used for the pre- (capture) and post-analyte steps (detection). To evaluate a novel ELISA format designed to avoid interference by HAIA, a target-specific non-immunoglobulin (Ig) affinity protein (affibody) was used to replace one of the antibodies. First, a human IgA-binding affibody (Z(IgA)) selected by phage display technology from a combinatorial library of a single Staphylococcus aureus protein A domain was used. The detection range of IgA standard using an ELISA based on Z(IgA) for capture and goat pAb against IgA (pAb(IgA)) for detection was comparable with that of using pAb(IgA) for both capture and detection. Secondly, another affibody (Z(Apo)) was combined with mAb and used to detect recombinant human apolipoprotein A-1. The affibody/antibody ELISAs were also used to quantify human serum levels of IgA and apolipoprotein A1. To verify that human serum did not cause false-positive signals in the affibody/antibody ELISA format, the ability of human serum to cross-link affibodies, mAb (mouse or rat) and/or pAb (goat) displaying non-matched specificities was assessed; affibodies and antibodies were not cross-linked whereas all combinations of mAb and/or pAb were cross-linked. The combination of affibodies and antibodies for analysis of human serum molecules represents a novel two-site ELISA format which precludes false-positive signals caused by HAIA.     

Recovery from short term intense exercise: Its relation to capillary supply and blood lactate concentration

Summary Muscle force recovery from short term intense exercise was examined in 16 physically active men. They performed 50 consecutive maximal voluntary knee extensions. Following a 40-s rest period five additional maximal contractions were executed. The decrease in torque during the 50 contractions and the peak torque during the five contractions relative to initial torque were used as indices for fatigue and recovery, respectively. Venous blood samples were collected repeatedly up to 8 min post exercise for subsequent lactate analyses. Muscle biopsies were obtained from m. vastus lateralis and analysed for fiber type composition, fiber area, and capillary density. Peak torque decreased 67 (range 47–82%) as a result of the repeated contractions. Following recovery, peak torque averaged 70 (47–86%) of the initial value. Lactate concentration after the 50 contractions was 2.9±1.3 mmol·l⁻¹ and the peak post exercise value averaged 8.7±2.1 mmol·l⁻¹. Fatigue and recovery respectively were correlated with capillary density (r=−0.71 and 0.69) but not with fiber type distribution. A relationship was demonstrated between capillary density and post exercise/peak post exercise blood lactate concentration (r=0.64). Based on the present findings it is suggested that lactate elimination from the exercising muscle is partly dependent upon the capillary supply and subsequently influences the rate of muscle force recovery. Dr. Tesch was on leave from Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden     

Contraction-specific differences in maximal muscle power during stretch-shortening cycle movements in elderly males and females

Elderly people (age 75 years; n=48 males and 34 females) were studied in order to elucidate gender differences in elderly subjects on the determinants of muscle power (force and velocity) during a stretch-shortening cycle. All subjects performed three maximal counter-movement vertical jumps using both legs, on a force platform (Kistler 9281 B). The eccentric (Ep) and concentric (Cp) phases of the jumps were analyzed. The Ep was further divided into an acceleration phase (Ep_acc: from the start of the downward movement to the maximal negative velocity) and deceleration phase (Ep_dec: from the maximal negative velocity to the end of the downward movement). Jump height for the men was higher than for the women (P < 0.001). During both Ep_acc and Ep_dec no significant differences were observed between males and females in force and power generation. However, the men had a higher peak muscle power during the Cp, which may be explained exclusively by the velocity determinant (P < 0.001). No specific gender-related strategy appeared to influence the motor pattern of the movement. The comparable eccentric force generation of the leg extensors in both genders suggests a similar ability to cope with eccentric muscle actions during everyday activities. In contrast, the marked lower capacity for concentric contractions in women may result in an impaired performance, especially in activities where intense and rapid movements are essential, for example when reversing a forward fall. This may be one reason why elderly women are more prone to falls than are elderly men. Accepted: 19 September 2000