Lipid metabolism during exercise I: Physiological and biochemical characterization of normal healthy male subjects in relation to their physical fitness

Summary On the basis of maximal oxygen uptake ( O₂ max) 18 normal, healthy men were divided into two groups of equal size: moderately trained subjects (MTR) each having O₂ max below 65.0 ml·min^–1·kg^–1 body weight (54.0±8.3) and well trained subjects (WTR), whose O₂ max exceeded 65.0 ml·min^–1·kg^–1 body weight (69.2±4.1). The WTR group had slightly (non significant, n.s.) higher percentage of slow twitch, oxidative (SO) fibers in M. vastus lateralis and higher (n.s.) activities of cytochrome c oxidase (CytOx), succinate dehydrogenase (SDH), 3-hydroxyacyl-CoA-dehydrogenase (HADH), and citrate synthase (CS), while lactate dehydrogenase (LDH) activity was lower (n.s.). In the MTR group only, the SO-%, and the activities of CytOx, SDH and HADH correlated positively with O₂ max, and LDH negatively with O₂ max. These correlations were not significant in the WTR group possibly because of the adaptations produced by training in this group. Multiple regression analysis was used to elucidate the best combination of variables to explain the variance in O₂ max. The best model consisted of the sum of relative activities of oxidative muscle enzymes (CytOx, SDH, HADH, CS), muscle LDH activity, body fat content (% F) and lean body mass. This model explained 69% of the variance in O₂ max; and of the individual variables % F was of utmost importance.     

Different effects of depolarization and muscarinic stimulation on the Ca2+/force relationship during the contraction-relaxation cycle in the guinea pig ileum

The effects of K⁺ depolarization and of the muscarinic agonist carbachol on [Ca²⁺]_i and force were investigated in smooth muscle sheets of the longitudinal layer of the ileum loaded with Fura-2. K⁺ -rich solutions increased [Ca²⁺]_i and force to an initial peak value, which was determined by the concentration of [K⁺]_o. Thereafter, [Ca²⁺]_i and force declined to a lower maintained level. The Ca²⁺/force relationship observed during this contraction-relaxation cycle is represented by a clockwise hysteresis loop. At 140 mM [K⁺]_o, this loop consisted of three components while at lower [K⁺]_o a two-component loop was observed. The stimulation with 0.1 mM carbachol resulted in a transient increase of [Ca²⁺]_i and force followed by a continuous decline of these parameters despite the presence of the drug. Its EC₅₀ of relaxation was around 270 nM [Ca²⁺]_i. The Ca²⁺/force relationship proceeded along a counterclockwise hysteresis loop during the contraction-relaxation cycle. The extent of this loop decreased but remained unaltered in its direction during repeated stimulation with carbachol. These results suggest that (a) both agonists increase force and [Ca²⁺]_i during stimulation; (b) during depolarization with K⁺, desensitization to Ca²⁺ occurs resulting in a clockwise hysteresis loop; (c) during carbachol stimulation, a counterclockwise hysteresis is observed. This could be due to an increased sensitivity to Ca²⁺ mainly in tonic smooth muscle. These observations might be explained by a modulation of the Ca²⁺ sensitivity by sensitizing and desensitizing mechanisms. These modulations during different stimuli could be due to different myosin light-chain kinase/myosin light-chain phosphatase ratios.     

Failure to demonstrate early metabolic changes in weanling growth-retarded hypophagic rats with lesions in the dorsomedial hypothalamic nuclei

Experiment 1: Weanling male rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated animals served as controls. Rats were killed four hours and three and seven days postoperatively (post-op). Plasma was obtained and epididymal fat pads, diaphragm and liver aliquots were harvested and the in vitro incorporation of U-14C-glucose into CO2, glycogen, lipid and saponifiable fatty acids (FAs) were measured. Body weight, carcass lipid and food intake were significantly lower in DMNL rats than in controls. The only significant lesion-induced metabolic changes were hypoglycemia and greater tracer incorporation into epididymal fat pad lipid and diaphragm glycogen. Both DMNL rats and controls showed similar time courses of tracer incorporation into epididymal CO2 and FAs, diaphragm lipid and liver CO2, glycogen, lipid and FAs. Lesioned rats also showed more pronounced decreases of tracer incorporation from day 0 to day 3 in epididymal glycogen and lipid and diaphragm CO2 and glycogen. These data make it appear unlikely that very early deficits in glucose metabolism are the cause of the growth retardation seen in long-term studies with DMNL rats. The data also demonstrate considerable locus specificity, since weanling rats with ventromedial hypothalamic lesions (VMNL rats) in similar short-term studies have shown dramatic alterations in the above parameters. Experiment 2: Weanling DMNL rats and sham-operated rats were injected via tail vein with tritiated water one hour post-op. One hour after the injection they were decapitated. There were no significant differences between DMNL rats and controls in mumoles tritiated water incorporated into total liver, grams liver tissue, mg liver glycogen and ml or mg plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠三叉神经脊束间质核内接受内脏伤害性信息的含CB神经元向孤束核的投射

目的 探讨大鼠三叉神经脊束间质核(INV)内接受内脏伤害性信息的含calbindin D-28K(CB)神经元与孤束核(NTS)的投射联系。方法 用福尔马林刺激上消化道，应用荧光金(FG)逆行束路追踪结合Fos和CB的免疫荧光组织化学三重标记法。结果 INV的背侧边缘旁核(PaMd)和三叉旁核(PaV)内可见到大量FG逆标细胞，以注射FG的同侧为主。大部分FG逆标细胞(约71.2％)为CB免疫反应阳性。部分FG和CB双标记神经元(约31．5％)同时呈Fos免疫反应阳性的三重标记。结论 INV内部分接受内脏伤害性刺激的CB神经元可直接投射至NTS，含CB的神经元在内脏伤害性信息经INV向NTS的传导通路中，可能发挥重要作用.     

Cold-sensitive mechanoreceptors with afferent C-fibres in the sheep duodenum

The effect of changes of temperature on the impulse activity of duodenal mechanoreceptors with afferent C-fibres was studied in acute electrophysiological experiments in chloralose-anaesthetised sheep. The impulse activity of 4 tension receptor units increased when the duodenal mucosa was cooled over the range 0–39° C. The impulse activity of 10 tension receptors was reduced when the mucosa was cooled. Temperature changes between 39° C and 52° C did not alter the discharge pattern of either type of tension receptor response. An additional unit, which may have been associated with pyloric circular muscle, was excited by cooling over the temperature range 0–39° C. This unit was insensitive to compression and was excited by close-intra-arterial injections of pentagastrin, nor-adrenaline, prostaglandin F₂ and prostaglandin E₂. The cold-sensitivity of mechanoreceptors in the duodenal muscularis externa may play a role in the reflexes regulating gastric emptying in experimental situations when duodenal chyme is cold.     

Improved detection of amyloid in fat pad aspiration: an evaluation of Congo red stain by fluorescent microscopy

Amyloid fat pad aspiration specimens for cases with a clinical suspicion of amyloid typically are stained with Congo red and examined by brightfield microscopy. Congophilia with apple-green birefringence by polarization microscopy (PM) is considered diagnostic for amyloid. Examination of Congo red-stained slides by fluorescent microscopy (FM) is considered by some to be a more sensitive detection method. In this study, we assessed the utility of this technique in cytopathology archival slides from abdominal fat pad aspirations previously stained with Congo red dye. Seventy-eight cases of abdominal fat pad aspirations collected during the last 5 yr and stained with the Congo red procedure were obtained from archival files. Additionally, 20 adipose tissue material slides prepared from the surgical pathology specimens were examined as controls. One representative smear was examined in each case using FM equipped with rhodamine excitation/absorption (540/570 nm) filters. Relevant clinical information was obtained in all cases. Twelve cases (15.4%) of the 78 fat pad aspiration cases were reported originally as positive by Congo red stain using polarization and apple-green birefringence as diagnostic criteria. On review, four cases were deemed unsatisfactory. By FM examination 29 of the 74 (39.2%) cases were reclassified as positive for amyloid. The results were confirmed by immunohistochemical stain for amyloid P protein and electron microscopy. A number of similar distinct fluorescence and immunohistochemical patterns were recognized in the positive cases. Minimally weak fluorescence in the adipose tissue was observed in the control cases. The use of FM in Congo red-stained fat pad smears can improve the detection of amyloid in cytology preparations.     

Differences in diazepam pharmacokinetics in Chinese and white Caucasians – Relation to body lipid stores

Summary We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0–3 h samples) and HPLC (3–72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase <6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to Ideal body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p<0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p=0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50–0.75, p<0.05). Obesity indices contributed most to the overall regressions (R² up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (C_max) was similar in both ethnic groups. Time to C_max (t_max) was more often prolonged in the Chinese (X ² test, p=0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.     

Guanine nucleotide and cation regulation of radioligand binding to R i adenosine receptors of rat fat cells

Summary The modulation of radioligand binding at R _i adenosine receptors of rat fat cells by guanine nucleotides and cations was investigated. Guanine nucleotides (in the order of potency: GTP=GDP>Gpp(NH)p>5-GMP) decreased the binding of the R _i receptor agonist (–)N⁶-phenylisopropyl[³H]adenosine ([³H]PIA), but did not affect binding of the antagonist 1,3-diethyl-8[³H]phenylxanthine ([³H]DPX). Saturation of [³H]PIA binding revealed that GTP (100 mol/l) converts the high affinity form of the R _i receptor into a low affinity form. This effect was confirmed in kinetic experiments. GTP decreased the potency of agonists in competing for [³H]DPX binding, as shown by a 50-fold shift of the K _i-value for (–)PIA, whereas antagonist-induced inhibition of binding remained unchanged. The divalent cations Mg²⁺ and Ca²⁺ produced a slight increase in [³H]PIA binding but did not affect [³H]DPX binding. Mn²⁺ markedly decreased both agonist and antagonist binding at R _i adenosine receptors. Divalent cations reversed the guanine nucleotide-induced decrease of affinity of the R _i receptor. Na⁺ did not significantly affect agonist or antagonist binding but abolished the stimulatory effect of Mg²⁺ on agonist binding in the presence of GTP. Our data indicate that guanine nucleotides convert the R _i adenosine receptor of rat fat cells from a high to a low agonist affinity state and that the modulation of radioligand binding by mono-and divalent cations differs from that of R _i receptors of other tissues.     

Effects of several 5′-carboxamide derivatives of adenosine on adenosine receptors of human platelets and rat fat cells

Summary The effects of several 5-carboxamide derivatives of adenosine on stimulatory (R _a) adenosine receptors of human platelets and inhibitory (R _i) adenosine receptors of rat fat cells have been compared. 5-N-Cyclopropylcarboxamidoadenosine (CPCA) and 5-N-ethylcarboxamidoadenosine (NECA) most potently inhibited ADP-induced aggregation of human platelets as shown by IC₅₀-values of 0.24 and 0.34 mol/l. 5-N-Methylcarboxamidoadenosine (MECA; IC₅₀ 0.81 mol/l) and 5-N-carboxamidoadenosine (NCA; IC₅₀ 2.1 mol/l) were less potent, whereas adenosine, 2-chloroadenosine and (-)N⁶-phenylisopropyladenosine [(-)PIA] exhibit IC₅₀-values of about 1.5 mol/l. Nearly the same rank order of potency was obtained for stimulation of adenylate cyclase activity of platelet membranes and for inhibition of [³H]NECA binding to human platelets. In order to examine the effects of the carboxamide analogues on R _i adenosine receptors of rat fat cells inhibition of lipolysis and adenylate cyclase were studied. (-)PIA was the most potent inhibitor of lipolysis as shown by an IC₅₀ of 0.5 nmol/l, followed by CPCA (IC₅₀ 1.1 nmol/l) and NECA (IC₅₀ 1.3 nmol/l), whereas MECA (IC₅₀ 17.9 nmol/l) and NCA (IC₅₀ 20.1 nmol/l) were much less potent than NECA in inhibiting lipolysis. Similar results were obtained for inhibition of adenylate cyclase activity of fat cell membranes and for competition with [³H]PIA binding to fat cell membranes. The relative potencies of the adenosine analogues at both receptor subclasses were calculated from the ratio of the IC₅₀-values for inhibition of platelet aggregation and of lipolysis. (-)PIA showed the highest selectivity for R _i receptors as indicated by a 2,900-fold lower IC₅₀ for the antilipolytic than for the antiaggregatory effect. The R _a/R _i activity ratio for NECA was about 260, for CPCA 220, for NCA 105 and for MECA 45. These results indicate that all 5-carboxamide adenosine derivatives are more potent agonists at R _i receptors than at R _a receptors. Since MECA has a higher selectivity for R _a receptors than NECA, it may be useful for the characterization of stimulatory adenosine receptors in different tissues.     

华中地区省会城市青春期青少年体脂率状况及其与血压的关联

目的 了解华中地区青春期青少年体脂率状况以及与血压之间存在的关联关系,为该地区青少年心血管疾病的早期预防提供参考和借鉴。方法 2 019年4—6月在河南、湖南、湖北三省省会城市的15所中学对4 846名初中学生进行生物电阻抗（BIA）的身体脂肪测试和问卷调查及血压测试,通过t检验、χ2检验和logistic回归分析等方法分析体脂肪率与血压偏高之间存在的关联关系。结果 华中地区省会城市青春期青少年血压偏高检出率为10.96%。男生血压偏高检出率为8.96%,女生为13.12%,差异有统计学意义（χ2 = 21.48,P＜0.01）。不同城乡、年龄、BMI和是否遗精/月经青少年血压偏高检出率存在显著差异（χ2 = 7.28、86.98、178.68、45.76,P＜0.01）。青春期青少年体脂率平均为（23.14±9.26）,其中男生为（21.02±10.86）,女生为（25.25±8.13）,差异存在统计学意义（t值 = - 15.248,P＜0.01）。Logistic回归分析显示,与男生体脂率＜P 25者相比较,P25～＜P50、P50～＜P75、P75～＜P90、≥P90者患血压偏高的比例是其3.14（OR值95%CI = 1.76～5.52）、4.05（OR值95%CI = 2.31～7.01）、6.33（OR值95%CI = 3.55～11.17）、12.44（OR值95%CI = 6.97～22.13）倍（P＜0.01）;与女生体脂率＜P 25者相比较,P50～＜P75、P75～＜P90、≥P90者患血压偏高的比例是其2.25（OR值95%CI = 1.45～3.45）、3.29（OR值95%CI = 2.09～5.12）、6.14（OR值95%CI = 3.88～9.64）倍（P＜0.01）。结论 华中地区省会城市青春期青少年体脂率与血压偏高之间存在显著正相关关系,男生关联关系大于女生,今后应保持合理的体脂率,以预防血压偏高的发生。