Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.     

Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients.

1. The present study was undertaken to examine whether or not 5-HT-induced inositol monophosphate (IP-1) accumulation in human platelets is mediated by 5-HT-2 receptors and to assess 5-HT-2 receptor function as measured by 5-HT-stimulated IP-1 accumulation in platelets from normal controls and depressed patients before drug treatment. 2. In platelets prelabeled with 3H-myo-inositol, in Ca ion free HEPES buffer containing 10 mM LiCl, 5-HT caused a dose-dependent accumulation of IP-1 during 15 min incubation. A maximal increase in IP-1 formation was observed at 30 microM of 5-HT and its EC50 value was 4 microM. 3. Ketanserin, a selective 5-HT-2 antagonist, was a potent inhibitor of 5-HT-stimulated IP-1 accumulation with a Ki value of 12 nM, but (-)propranolol (10 microM), a 5-HT-1 antagonist, failed to block the 5-HT response. 4. The potencies of various compounds tested to inhibit 5-HT-stimulated IP-1 accumulation in human platelets correlated positively with the affinities to 5-HT-2 receptor as defined by radioligand binding in rat cerebral cortex. 5. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5-HT (100 microM)-induced accumulation of IP-1 (150 +/- 7% of basal for depressed patients, 132 +/- 3% for controls).     

The bronchodilating effect of pirenzepine]

The purpose of this study was to clarify the bronchodilating effect of pirenzepine (PZ) and to verify its mechanism. Ten asthmatic patients (6 men, 4 women: aged 20 to 65, 5 atopic 5 non-atopic) and ten non-asthmatic volunteers (8 men, 2 women: aged 25 to 60) were studied. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0) and peak expiratory flow rate (PEFR) were measured after intravenous administration of 20 mg PZ. PZ increased FVC, FEV1.0 and PEFR significantly by 15%, 29% and 37% respectively in asthmatic patients (p less than 0.01). We also studied the effects of PZ on the contractile responses of tracheal smooth muscle to intra-arterially administered acetylcholine (ACh) and the electrical stimulation of the vagus nerves (VNS) using isometric technique in situ in 5 mongrel dogs. PZ significantly inhibited the contractile responses elicited with ACh at doses larger than 1000 micrograms/kg (p less than 0.01). PZ also significantly inhibited the contractile responses elicited by VNS at doses larger than 100 micrograms/kg (p less than 0.01). These data demonstrate that intravenously administered PZ dilates the airway in asthmatic patients and also suggest that the bronchodilating effect of PZ related to inhibition of the M1 and M3 muscarinic receptors.     

Pulmonary kinetics of 13N-ammonia in smoking subjects--a quantitative study using dynamic PET]

To evaluate the effect of smoking on nonrespiratory function in the lung, a dynamic PET with 13NH3 in the lung was performed in 18 normal volunteers without lung disease nor congestion (9 non-smokers, 4 exsmokers, 5 smokers). After intravenous bolus injection of 13NH3, twenty serial 5.5-second scans followed by six 30-second scans were performed. Regions of interests were assigned on the ventral, lateral and dorsal part of the right lung and time-activity curves were generated through 26 images. The activity curve demonstrated a biexponential clearance from the lung with fast and slow component. The retention fraction (RF), fractional size of the slow component, was calculated, and the half-times (t 1/2) of both components were also evaluated. A significant increase of RF and prolongation of t 1/2 of slow component were observed in smokers compared to non-smokers and exsmokers. However, no significant difference of RF nor t 1/2 of both components was observed between non-smokers and exsmokers. These results suggest that long term smoking may modify the pulmonary kinetics of 13NH3, but the change is reversible after cessation of smoking for one year or longer.     

Antimuscarinic effect of tiquizium bromide in vitro and in vivo

Objective: We studied the bronchodilatory effect of tiquizium bromide [3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide; TQZ], an antimuscarinic agent, on airway smooth muscle in vitro, and also in patients with chronic obstructive pulmonary disease (COPD). Methods: In the first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ for muscarinic receptor subtypes was also examined with a radioligand binding assay. Results: The pA2 value of TQZ was 8.75. The pK _i values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot experiment, the effects of TQZ inhalation were studied in seven patients with COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁) in a dose-dependent manner. The mean maximum increases in FVC and FEV₁ caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, and they were measured 1 h after the drug had been inhaled. The FVC and FEV₁ were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were observed after inhalation of TQZ. Conclusion: These data suggest that TQZ is an effective antimuscarinic agent, and that it causes significant bronchodilation in patients with COPD. Received: 3 April 1995/Accepted in revised form: 27 November 1995     

Effect of Delayed-Type Hypersensitivity Reaction and Transferred Lymphokine on the Resistance of Mice to Salmonella typhimurium Infection

Immune mice which exhibited a delayed-type hypersensitivity reaction to bovine serum albumin after bovine serum albumin immunization and stimulation and normal mice that had been transferred with a lymphokine-rich fraction from the supernatant of concanavalin A-stimulated spleen cell cultures demonstrated resistance to Salmonella infection.     

Candidate interneurons mediating peripherally evoked disynaptic inhibition of masseter motoneurons of both sides

Location and axonal projection of interneurons presumed to mediate disynaptic inhibition evoked from the trigeminal sensory nerve in the ipsi- and contralateral masseter motoneurons were studied in pentobarbital anesthetized cats. Neurons monosynaptically excited from the periphery and antidromically activated from the contralateral trigeminal motor nucleus at low current intensity, hence probably terminating there, were found in the supratrigeminal region. Intracellular staining of such cells revealed collaterals terminating in the ipsilateral masseter motor nucleus. It is suggested that both the crossed and uncrossed disynaptic inhibition of masseter motoneurons are at least in part relayed by the same neurons in the supratrigeminal region.     

Growth retardation induced in rat fetuses by maternal fasting and massive doses of ergocalciferol

The present study was conducted in Wistar rat fetuses to investigate the growth retardation induced by maternal fasting and/or massive doses of ergocalciferol during the third trimester of pregnancy. Growth indices examined in 21-d fetuses were body weight and ossification of sacrococcygeal vertebrae, supraoccipital bone, sternebrae and proximal phalanges in the forepaw stained by alizarin red S. Growth retardation was expressed in hours by comparison with the normal standard development, or in sigma by calculating the relative difference from the control, utilizing the standard variance in normal fetuses. Degrees of growth retardation expressed in the common scales were different among the indices and between fasting and massive doses of ergocalciferol; body weight and ossification of sacrococcygeal vertebrae were most severely retarded by fasting and least by ergocalciferol. Ossification of sternebrae was moderately retarded by fasting and by ergocalciferol, and ossification of supraoccipital bone was moderately retarded by fasting but not by ergocalciferol. Ossification of proximal phalanges in the forepaw was least retarded by fasting and most severely retarded by ergocalciferol. The observed retardations were progressions relatable to the duration of fasting. Combined treatments of fasting and ergocalciferol showed more deleterious effects on growth than fasting only or ergocalciferol only and induced face anomalies, "carnival fetuses." These findings show that growth retardations induced by different nutritional disturbances may vary among indices and that comparisons of various indices are important in the analysis of teratological experiments.     

Nocturnal eating/drinking syndrome and neuroleptic-induced restless legs syndrome

Nocturnal eating/drinking syndrome secondary to neuroleptic-induced restless legs syndrome (RLS) occurred under treatment with low-dose haloperidol in a 51-year-old female schizophrenic patient. Polysomnographic investigation showed a low level of sleep efficacy, periodic leg movements, and a strict relationship between nocturnal eating episodes and non-rapid eye movement sleep. Her nocturnal eating and RLS were completely inhibited by clonazepam treatment. To our knowledge, this is the first published case of nocturnal eating/drinking syndrome secondary to neuroleptic-induced RLS.