Hyperpolarized 129Xe phase-selective imaging of mouse lung at 9.4T using a continuous-flow hyperpolarizing system

The use of hyperpolarized (HP) 129Xe magnetic resonance (MR) imaging to regionally evaluate gas diffusion and perfusion processes as well as ventilation in the lung has been expected. In this study, we used a continuous-flow hyperpolarizing (CF-HP) system to acquire gas- and dissolved-phase 129Xe images from mouse lung, employing standard gradient echo sequence equipped with chemical shift selective excitation and 90 degrees flip angle. The character of non-recoverable HP magnetization enabled the use of a phase (frequency)-selective 90 degrees pulse for direct visualization of only a given-phase 129Xe magnetization replenished into the slice during repetition time (TR). We combined gas- and dissolved-phase 129Xe images to map the ratio of dissolved- to gas-phase 129Xe replenished into the slice during TR (Mdissolved/Mgas) and found it to be approximately 0.05 to 0.08 in the peripheral regions of mouse lungs. This result suggested that replenishment of dissolved-phase 129Xe magnetization by gas diffusion and pulmonary perfusion would be faster than that of gas-phase by ventilation. The use of a CF-HP system that allows the application of relatively long TR to HP 129Xe imaging using a phase-selective 90 degrees pulse would be useful in evaluating gas transport mechanisms in the lung.     

DVC1-0101 to Treat Peripheral Arterial Disease: A Phase I/IIa Open-label Dose-escalation Clinical Trial

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.     

Relationship between abdominal fat accumulation and insulin resistance in hemodialysis patients.

It is well known that obesity and insulin resistance are closely related to the development of type 2 diabetes. However, the exact pathogenic mechanism underlying the insulin resistance in renal disease has not been clarified. The purpose of the present study was to clarify the contribution of abdominal (visceral and subcutaneous) fat accumulation to insulin resistance and various clinical parameters, including C-reactive protein (CRP), in hemodialysis (HD) patients. Visceral and subcutaneous fat areas (VFA and SFA) were evaluated at the umbilical level by CT. Insulin resistance was estimated by the homeostasis model assessment-insulin resistance index (HOMA-IR) in 80 HD patients. Insulin resistance and CRP seemed to be closely correlated with fat-related parameters such as body mass index (BMI), VFA and SFA. HOMA-IR was positively correlated with BMI, VFA, SFA, triglycerides (TG), remnant-like particle (RLP)-cholesterol and CRP in simple regression analysis. In multiple stepwise regression analysis, SFA and RLP-cholesterol were predominant determinants of HOMA-IR in HD patients. Furthermore, CRP was positively correlated with BMI, VFA, SFA, TG, high-density lipoprotein (HDL)-cholesterol, atherosclerosis index (AI), immunoreactive insulin (IRI) and HOMA-IR in simple regression analysis. In multiple stepwise regression analysis, VFA and HDL-cholesterol were predominant determinants of CRP in HD patients. In conclusion, insulin resistance and CRP were related to fat-related parameters such as BMI, VFA and SFA in HD patients. Furthermore, the contribution of SFA to insulin resistance was much higher than that of VFA, while the opposite relation was recognized for CRP.     

Usefulness of gram-stained sputum obtained just after administration of antimicrobial agents as the earliest therapeutic indicator for evaluating the effectiveness of empiric therapy in community-acquired pneumonia caused by pneumococcus or Moraxella catarrhalis

We present here three cases in which morphological changes and/or a decreased number of Streptococcus pneumoniae or Moraxella catarrhalis could be observed in gram-stained sputum obtained just after the first administration of an antimicrobial agent. Case 1 was a 53-year-old man with pneumonia caused by gram-positive diplococcus, identified as S. pneumoniae, who was administered 2 g of ampicillin over a period of 1 h. Gram-stained sputum showed smaller or gram-negative pneumococci at the completion of administration of the agent, a decreased number of cocci at 1 h after administration, and almost no cocci at 12 h after the completion of administration. Case 2 was a 72-year-old woman with pneumonia caused by diplococcus, identified as S. pneumoniae, who was administered 2 g of ampicillin over a period of 1 h. Gram-stained sputum showed weakly stained, small cocci at the completion of administration of the agent and few cocci at 1 h after the completion of administration. Case 3 was a 58-year-old woman with pneumonia caused by a gram-negative diplococcus, identified as Moraxella catarrhalis, who was administered 1 g of cefotaxime over a period of 30 min. Gram-stained sputum showed few extracellular cocci and some intracellular cocci inside neutrophils 1 h after administration and no cocci 2 h after the completion of administration. These three cases showed that gram-stained sputum obtained just after and/or 1 h after administration of the first antimicrobial agent were suitable as the quickest therapeutic indicator of the effectiveness of empiric therapy, with the effectiveness of the agent being shown much earlier than with markers such as the white blood cell count and C-reactive protein level.     

ANGIOGRAPHIC STUDY OF THE SUBDERMAL PLEXUS: A PRELIMINARY REPORT

The subdermal plexus was pictured angiographically in five fresh cadavers injected systemically with a lead oxide-gelatin mixture. Subdermal plexus was found either in the subdermal plane or in the deep part of the dermis. Diameters of vessels in the subdermal plexus are not uniform and there are differences in vascular continuity, which means that the subdermal plexus does not always have a random pattern. This observation is important when designing a thin flap.     

The inhibitory effect of KT3-671, a nonpeptide angiotensin-receptor antagonist, on rabbit and rat isolate vascular smooth muscles: a possible involvement of K(ATP) channels

The vasoinhibitory effect of KT3-671, a recently synthesized nonpeptide angiotensin II (Ang II), AT1-receptor antagonist, and the factors affecting insurmountable antagonism of Ang II were examined in rabbit and rat isolated vascular smooth muscle preparations. In rabbit and rat aortic rings, KT3-671 caused insurmountable antagonism of Ang II. In addition, KT3-671 inhibited contractile responses to angiotensin III (Ang III). In rabbit isolated smooth muscles, KT3-671 was most effective in reducing the maximal contraction induced by Ang II in the renal artery followed by the basilar artery and the aorta. In rat renal arterial rings, KT3-671 (10(-5) M) inhibited the concentration-response curves of prostaglandin F2alpha and STA2. In rabbit and rat aortic rings without endothelium, the insurmountable antagonisms of Ang II by KT3-671 and EXP 3174 were changed to surmountable antagonism by pretreatment with DuP 753 and KT3-671, respectively. In addition, KT3-671 abolished the inhibitory effect of CV- 11974 in the rat aorta but not in the rabbit aorta. Indomethacin (10(-5) M) or the removal of endothelium did not affect the inhibitory effect of Ang II by CV-11974 or EXP 3174 but enhanced the insurmountable antagonism by KT3-671. ODQ (3 x 10(-6) M), N(G)-nitro-L-arginine (3 x 10(-4) M), 4-aminopyridine (3 x 10(-3) M), tetraethylammonium (TEA; 10(-3) M), or iberiotoxin (10(-7) M) did not affect the inhibitory action of KT3-671 or CV-11974. Methylene blue (3 x 10(-6) M), KCl (10(2) M), TEA (10(-2) M), or BaC12 (10(-4) M) changed the insurmountable antagonism by KT3-671 to surmountable antagonism and abolished the inhibitory effect of CV-11974. However, glibenclamide (3 x 10(-6) M) did not affect the inhibitory action of KT3-671 but reduced the insurmountable antagonism by CV- 11974. These results indicate that KT3-671 is an insurmountable antagonist of Ang II in the rabbit and rat aorta. The results in the rat aorta also suggest that K(ATP) channels may be involved in insurmountable antagonism of Ang II by KT3-671 and CV-11974. Key Words: KT3-671-Rabbit-Rat-Vascular smooth muscle-Angiotensin II-Insurmountable antagonist-K(TP)channels.     

The effects of delayed treatment with sialyl Lewis X against lipopolysaccharide-induced acute lung injury in rabbits

The therapeutic effects of a selectin inhibitor against lipopolysaccharide-induced acute lung injury were studied in rabbits by using sialyl Lewis X-oligosaccharide. Lipopolysaccharide-induced acute lung injury, as characterized by an impairment of pulmonary gas exchange, clinically resembles that of the acute respiratory distress syndrome. Delayed treatments with sialyl Lewis X-oligosaccharide (55 mg kg(-1) i.v. bolus injection 0.5, 1 or 2 h after lipopolysaccharide administration+36 mg kg(-1) h(-1) i.v. infusion for 5.5, 5 or 4 h, respectively) prevented the lipopolysaccharide-induced impairments in pulmonary gas exchange, as well as the accumulation of polymorphonuclear leukocytes in the lung tissue. In contrast, this agent had no significant effects on lipopolysaccharide-induced systemic hypotension, the decrease in the number of circulating white blood cells and platelets or the decline in blood pH.This is the first demonstration that sialyl Lewis X-oligosaccharide is effective against the impairments in pulmonary gas exchange even if administered 0.5, 1 or 2 h following the lipopolysaccharide injection.     

Methods of sleep induction for EEG recordings: comparison between three hypnotics and natural sleep

We compared the effects of three oral hypnotics, monosodium trichloroethyl phosphate (MTP), chloral hydrate (CH), and pentobarbital calcium (PTB), to those of non-medication on wake-sleep states and sleep activation of epileptic seizure discharges. The subjects consisted of 410 epileptics and 171 non-epileptic outpatients (mean age: 12.5 years) of the Department of Pediatrics, Nagoya City University Hospital. Complete EEG records including awake and sleep states were obtained in 230/241 (95%) of patients with MTP, 20/22 (91%) of those with CH, 72/85 (85%) of those with PTB, and 225/233 (97%) of those without any hypnotics. There were no statistically significant differences in the effect of sleep induction among the four groups. Sleep activation effects were observed in 25% of patients with natural sleep and 35% of those with induced sleep. There was no statistical difference (p > 0.05). These results suggested MTP, CH, and PTB are useful hypnotics for sleep EEG recordings.