Angiopoietin-like protein 2 sensitively responds to weight reduction induced by lifestyle intervention on overweight Japanese men.

OBJECTIVE: Overexpression of Angiopoietin-like protein 2 (Angptl2) in obese adipose tissues promotes adipose tissue inflammation and its-related metabolic abnormalities. In a comparative study with adiponectin, we investigated whether alterations in serum Angptl2 concentrations reflect the effect of lifestyle intervention on weight loss and improved metabolic parameters in overweight subjects. METHODS: A total of 154 Japanese men (age, 40.9±5.1 years; body mass index, 26.9±3.6 kg m(-2); abdominal circumference, 94.1±8.9 cm) underwent a 3-month lifestyle intervention and underwent follow-up for 3 months thereafter. RESULTS: Decreased serum Angptl2 levels, but not increased serum adiponectin levels, were immediately apparent at the end of 3-month lifestyle intervention. Angptl2 levels continued to decrease for 3 months in parallel with body weight loss and improvement in metabolic indicators. In subjects showing 6% weight reduction, markedly reduced Angptl2 levels were detected at the end of 3-month intervention, whereas increased adiponectin levels were detected 3 months after the end of intervention. Multivariate analysis revealed changes in serum Angptl2 levels associated with changes in triglycerides (TGs), aspartate aminotransferase and alanine aminotransferase. In contrast, changes in serum adiponectin levels were associated with altered high-density lipoprotein cholesterol (HDL-C) and fasting plasma glucose levels. CONCLUSION: A 3-month lifestyle intervention promoted weight reduction and improved glucose and lipid metabolism, an effect maintained 3 months later. Notably, our findings indicate that decreased Angptl2 levels are a good indicator of reduced visceral fat and metabolic improvement at early stages of lifestyle intervention. Thus, Angptl2 reflects adiposity and might be a key protein to regulate inflammation and TG metabolism, whereas adiponectin levels could reflect improved glucose and HDL-C metabolism.

Spontaneous firing in the isolated anucleate axonal segment of an identified crayfish motoneuron.

The aim of this study was to present evidence for prolonged spontaneous firing in an anucleate axonal segment of an identifiable crayfish anal motoneuron L (AML) and to determine the initiation site of this firing. AML has its soma in the 6th abdominal ganglion (A6). By separating a nerve with the AML axon from A6 and the target muscle, various lengths of an anucleate AML axonal segment were procured. Then, AML activity was recorded extracellularly for 14-26 hr from the distal end of this axonal segment. This segment (n=19) exhibited spontaneous firing, which occurred without any stimulation 0.03-5.13 hr after the A6-cut and persisted tonically for 0.20-19.98 hr. During firing, the frequency augmented gradually, whereas the amplitude decreased gradually. There was no significant correlation between latency and duration of the firings. No correlation was noted between latency and length of the axonal segment or its size, or between duration and length or size. These results revealed that the anucleate AML axon itself can inherently generate prolonged firing. The delay in the appearance of AML impulses between the proximal and distal regions at the same axonal segment proved that the firing occurred proximally. There was no significant difference in delays between firing following the A6-cut and the spontaneous firing observed after the A6-cut. This suggests that the initiation site of the spontaneous firing is at the proximal end of the AML axonal segment, since the AML firing following the A6-cut occurs at its cut end.

Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue.

A 20-year-old Japanese female needed frequent hospitalization due to premenstrual exacerbation of hereditary coproporphyria (HCP). Intranasal buserelin acetate, a gonadotropin-releasing hormone analogue, was given to suppress her menstrual cycles. Her porphyric symptoms subsided dramatically as she became amenorrhoeic. Urinary excretion of porphyrin derivatives fell significantly. She has been free from recurrent attacks, but suffers a minor porphyric attack once in 5 years. However, borderline osteopenia secondary to hypoestrogenism has been noted. Although these analogues are potent in suppressing estrogen-induced porphyric symptoms, due precautions should be taken to avoid bone demineralization in the long-term use.

Ionic dependence of the axotomy-induced long-lasting firing in an identified crayfish motoneuron.

I have reported previously that axotomy of an identifiable anal motoneuron of crayfish Procambarus clarkii induces a long-lasting firing and that a prolonged depolarizing pulse to its cut end can induce a similar response. In this study, I confirmed that this stimulus is comparable to axotomy; the frequency of stimulus-induced firing increases linearly with the stimulus intensity and its firing pattern is the same as that following axotomy. Then, when the cut end was bathed for more than 1 hr in test solutions, it was examined whether the stimulus to the cut end induces or blocks the response. Na(+)-free saline (Tris(+) replaced Na(+)) or TTX (3 x 10(-7) M) reversibly blocked the response within 30 min. By contrast, Mn(2+) saline (40 mM Mn(2+) replaced Ca(2+)) or Ca(2+)-free salines (Mg(2+) or 1 mM EDTA replaced Ca(2+)) cannot block the response, but instead increased the firing frequency. These results obtained with stimulus were confirmed also by those with axotomy. I concluded that axotomy-induced firing, which occurs locally at its cut region, is primarily responsible for voltage-dependent Na(+) conductances, but not for Ca(2+) ones.

Nifedipine dilates the pulmonary vasculature without producing symptomatic systemic hypotension in upright resting and exercising patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Vasodilator therapy may lower pulmonary vascular resistance in patients with chronic air-flow limitation. However, the effects of these agents on left ventricular afterload, cardiac output, and bronchial smooth muscle could lower the calculated pulmonary vascular resistance without specifically affecting pulmonary vascular tone. In addition, systemic hypotension in the upright position and worsening ventilation/perfusion heterogeneity could limit their use. We determined the pulmonary driving pressure (pulmonary arterial-pulmonary arterial wedge pressure) to flow relationship, as well as the transmural pulmonary arterial pressure in 9 patients with severe chronic air-flow limitation with pulmonary hypertension while in a clinically stable condition. Measurements were made at rest and during 3 stages of progressively increasing upright exercise on a bicycle before and after a single 20-mg dose of nifedipine. Nifedipine displaced both the driving pressure to flow and the pulmonary arterial transmural pressure to flow relationships towards higher flows in every subject, suggesting an active vasodilation. In the upright position, PaO2 did not change, and the systemic arterial pressure was only mildly reduced. In patients with pulmonary hypertension from chronic air-flow limitation, acute administration of nifedipine to upright patients causes pulmonary, as well as systemic vasodilation without causing symptomatic hypotension or reducing arterial oxygenation.

Increases in intrathoracic pressure do not explain the rise in left ventricular end-diastolic pressure that occurs during exercise in patients with chronic obstructive pulmonary disease.

During exercise, patients with chronic obstructive pulmonary disease (COPD) increase their pulmonary arterial wedge (Ppaw) and left ventricular (LV) end-diastolic pressures more than normal control subjects. The increase in pressure is commonly attributed to an increase in intrathoracic pressure (Pit). However, mean esophageal pressure (Pes) does not increase with supine exercise in patients with COPD. Because changes in Pes may not represent changes in Pit when recorded in the supine position, we measured Ppaw and Pes during upright exercise in 8 patients with severe air-flow limitation (mean +/- SD) FEV1, 0.88 +/- 0.27 L secondary to COPD and no history or electrocardiographic abnormalities suggesting a previous myocardial infarct, history of angina, evidence of systemic hypertension, or use of cardiac medications. In addition, all patients completed a progressive exercise test to exhaustion without angina or ST segment changes, and all had normal LV function at rest assessed by equilibrium radionuclide ventriculography. The Ppaw increased a mean of 7.2 +/- 4.3 mmHg, whereas Pes increased a mean of only 1.3 +/- 1.6 mmHg. By multiple linear regression analysis, Ppaw was significantly associated with the work level performed (p less than 0.01), but had no significant association with Pes (p greater than 0.1). The change in Ppaw could not be attributed to changes in Pes. If changes in Pes during upright exercise are representative of changes in Pit or juxtacardiac pressure, a rise in Pit does not explain the exercise-induced increase in Ppaw and LV end-diastolic pressure that occurs in patients with COPD.

An approach to clinical magnetocardiology.

Magnetocardiograms (MCGs) of normal human subjects and patients with various heart diseases and of fetuses (fetal magnetocardiogram, FMCG) were recorded using a SQUID magnetometer with a built-in second derivative gradiometer in a magnetically unshielded environment. MCGs and ECGs in this study were taken simultaneously at the same precordial chest positions (V1 approximately V6). The following results were obtained: (1) The waves of MCG showed a variety of changes which can never be detected in ECGs. (2) Clear FMCGs could be recorded without being overlapped by MCG of the mother. (3) In MCGs from a patient with complete A-V block, there was a secondary pacemaker spike which was presumably related to ventricular depolarization. (4) There were two kinds of characteristic changes with time in MCGs after onset of anterior myocardial infarction, which could be confirmed in experiments with dogs. Thus, the results obtained so far indicate a bright future of magnetocardiology in clinical medicine.