Comparative assessment of ocular tissue distribution of drug-related radioactivity after chronic oral administration of 14C-levofloxacin and 14C-chloroquine in pigmented rats

Fluoroquinolones have been reported to have a high affinity for melanin. The ocular tissue distribution and accumulation of radioactivity was compared after repeated oral administration of 14C-levofloxacin and 14C-chloroquine at daily doses of 20 mg (0.054 mmol) kg(-1) and 28 mg (0.054 mmol) kg(-1), respectively, in pigmented rats for 84 days. The mean serum level at 24 h following each dose of 14C-levofloxacin was almost constant in the range of 0.33-0.45 nmol equiv mL(-1) after the 14th dose and thereafter. The melanin-containing ocular tissues, such as iris ciliary body and stratum pigment chorioides sclera, showed a much higher concentration of radioactivity than other non-pigmented ocular tissues. The respective concentration in iris ciliary body and stratum pigment chorioides sclera after the 1st dose was 126.47 and 74.91 nmol equiv g(-1), and gradually increased with increasing dose number, reaching 1261.81 and 447.45 nmol equiv g(-1) after the 84th dose, which was ca. 10 and 6 times higher, respectively, than after the 1st dose. The mean serum level following each dose of 14C-chloroquine was almost constant in the range 0.51-0.87 nmol equiv mL(-1) after the 7th dose and thereafter. The respective concentration in iris ciliary body and stratum pigment chorioides sclera after the 1st dose was 572.10 and 709.41 nmol equiv g(-1), and gradually increased with increasing dose number, reaching 33 317.92 and 12 322.90 nmol equiv g(-1) after the 84th dose, which was ca. 58 and 17 times higher, respectively, than after the 1st dose. The concentration in aqueous humour, cornea, lens, vitreous body and retina after the 84th dose was 1.84, 6.33, 0.48, 5.60 and 11.42 nmol equiv g(-1) for 14C-levofloxacin and 18.84, 264.99, 27.26, 158.43 and 1020.89 nmol equiv g(-1) for 14C-chloroquine (ca. 10, 42, 57, 28 and 89 times higher, respectively, than for 14C-levofloxacin). Especially, the concentration in the retina was markedly higher after 14C-chloroquine administration than after 14C-levofloxacin administration. The concentration and the extent of accumulation of radioactivity not only in melanin-containing ocular tissues but also in other non-pigmented ocular tissues, such as retina, after chronic oral administration of 14C-levofloxacin once daily for 84 days were much lower than those after multiple dosing with 14C-chloroquine under the same conditions. These results indicate that levofloxacin would have a much lower risk for ocular toxicity than chloroquine after chronic dosing.     

Tissue-specific regulation of 4E-BP1 and S6K1 phosphorylation by alpha-ketoisocaproate

The indispensable branched-chain amino acid leucine acts as a key regulator of mRNA translation by modulating the phosphorylation of proteins that represent important control points in translation initiation, including the translational repressor, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1). In the current study, we compared the effects of L- and D-enantiomers of leucine on the phosphorylation of 4E-BP1 and S6K1. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (18 h) rats were orally administered 135 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 1 h. L-Leucine administration had an obvious stimulatory effect on the phosphorylation of 4E-BP1 and S6K1 in both skeletal muscle and liver while D-leucine was much less effective, indicating that the effect of leucine is stereospecific. Oral administration of alpha-KIC mimicked the stimulatory effect of L-leucine in skeletal muscle. In contrast to skeletal muscle, provision of alpha-KIC was significantly less effective than L-leucine in the liver. The results showing that the efficacy of L-leucine and alpha-KIC in stimulating phosphorylation of S6K1 and 4E-BP1 is equivalent in skeletal muscle, may be explained by the conversion of alpha-KIC to L-leucine.     

The frequency of going outdoors, and physical, psychological and social functioning among community-dwelling older adults

PURPOSES: This cross-sectional study examined the relationship between the frequency of going outdoors and physical, psychological, and social functioning among community-dwelling older people. METHODS: Out of all residents aged 65 and over residing in Yoita town, Niigata prefecture (n = 1,673), 1,544 living at home participated in an interview survey held in November 2000. Physical, psychological, and social functioning were compared among four groups defined by the frequency of going outdoors: (1) at least once a day, (2) about once per 2-3 days, (3) about once a week, and (4) seldom. To examine the independent association between the frequency of going outdoors and potential factors, we used multiple logistic regression analysis. RESULTS: Overall distribution of the frequency of going outdoors among the subjects was 76.3% for at least once a day, 13.1% for about once per 2 or 3 days, 3.7% for about once a week, and 6.9% for seldom. The frequency of going outdoors did not differ between genders, but showed significant decrease with advancing age in both sexes. Elderly going outdoors more often were less functionally impaired, scored less for depression and were more socially active than their counterparts going outdoors less often. Multiple logistic regression analysis with the forced entry method identified walking difficulty and fear of falls as the most powerful independent factors associated with going outdoors less than or equal to once a week, while low social activity and a more depressed score were important factors associated with going outdoors about once per 2-3 days. CONCLUSIONS: The frequency of going outdoors may be regarded as a generic health indicator among community-dwelling elderly people.     

Spiral magnetic resonance coronary angiography with rapid real-time localization

A spiral high-resolution coronary artery imaging sequence (SH) interfaced with real-time localization system (RT) has been developed. A clinical study of 40 patients suspected of coronary artery disease (CAD) was conducted.Segmented k-space acquisition techniques have dominated magnetic resonance coronary angiography (MRCA) over the last decade. Although a recent multicenter trial using this technique demonstrated encouraging results, the technique was hampered by low specificity. Spiral k-space acquisition had demonstrated several advantages for MRCA. Therefore, a first clinical trial implementing spiral high-resolution coronary imaging sequence with real-time localization (SH-RT) was performed.A clinical study of 40 patients suspected of CAD undergoing X-ray angiography was conducted to analyze the clinical reliability of this novel imaging system. The SH-RT had been designed to exploit the unique capability of two imaging sequences. The RT allowed a rapid localization of the coronary arteries. Then SH achieved multislice acquisition during a short breath-hold with submillimeter resolution. The MRCA data were analyzed for scan time, anatomic coverage, image quality, and accuracy in detecting CAD.In 40 subjects, SH achieved 0.7 to 0.9 mm resolution with 14-heartbeat breath-holds. Excellent or good image quality was achieved in 78% (263/337) of the coronary segments. Blinded consensus reading among three observers generated sensitivity of 76% and specificity of 91% in the detection of CAD compared with X-ray angiography.The MRCA imaging sequence implementing a novel spiral k-space acquisition technique enabled rapid and reliable imaging of the CAD in submillimeter resolution with short breath-holds.     

In vivo test of pressure head and flow rate estimation in a continuous-flow artificial heart

To avoid using sensors with low biocompatibility and low durability in implantable total artificial heart (TAH) systems, the authors previously proposed a new method for estimating instantaneous values of flow rate and pressure head on the basis of voltage, current, and rotational speed in a motor driven centrifugal pump. The previous in vitro experiments showed that the proposed estimator could automatically compensate for the effect of the change in blood viscosity on the estimation accuracy by employing two kinds of autoregressive exogenous models. In this study, validity and reliability of this estimation method were ascertained in an acute animal experiment. In the experiment, two centrifugal blood pumps were implanted into an adult goat as a total artificial heart. Results of estimation were compared with true values when blood viscosity was changed by injecting physiological saline. The results indicated that the system could successfully estimate pressure head by compensating the change of viscosity, although the estimation accuracy of the in vivo estimation was not so high as that of the previous in vitro tests.     

Chaos attractors of ventricular elastance to evaluate cardiac performance

Quantitative evaluation of cardiac function is very important in the clinical application of a ventricular assist device. This article reports a new evaluating method of E max, which is the most reliable parameter to evaluate cardiac function. Fluctuation in the E max time series data was evaluated by the nonlinear mathematical analyzing method including chaos and fractal theory. Experimental goats were anesthetized with halothane inhalation, and left ventricular volume and pressure were measured with other hemodynamic parameters to evaluate E max during various drug administrations. E max was evaluated by two methods. One was the conventional pressure volume loop evaluation and the other was the parameter optimization method without left ventricular volume data. As a result, E max evaluated by the parameter optimization method correlated well with the E max with conventional PV curve. Furthermore, interesting results were obtained. There were rhythmical fluctuations in the E max time series data. By the methodology of Takens, E max time series data was embedded into the phase space and a strange attractor was observed. These results may be important when considering E max evaluation during left ventricular assistance.     

Epidemic nosocomial keratoconjunctivitis caused by adenovirus type 4

PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. MATERIALS AND METHODS: We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. CONCLUSIONS: The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.     

Luminance mechanisms mediate the motion of red-green isoluminant gratings: the role of "temporal chromatic aberration"

In this paper we use a dynamic noise-masking paradigm to explore the nature of the mechanisms mediating the motion perception of drifting isoluminant red-green gratings. We compare contrast thresholds for the detection and direction discrimination of drifting gratings (1.5 cpd), over a range of temporal frequencies (0.5-9 Hz) in the presence of variable luminance or chromatic noise. In the first experiment, we used dynamic luminance noise to show that direction thresholds for red-green grating motion are masked by luminance noise over the entire temporal range tested, whereas detection thresholds are unaffected. This result indicates that the motion of nominally isoluminant red-green gratings is mediated by luminance signals. We suggest that stimulus-based luminance artifacts are not responsible for this effect because there is no masking of the detection thresholds. Instead we propose that chromatic motion thresholds for red-green isoluminant gratings are mediated by dynamic luminance artifacts that have an internal, physiological origin. We have termed these "temporal chromatic aberration". In the second experiment, we used dynamic chromatic noise masking to test for a chromatic contribution to red-green grating motion. We were unable to find conclusive evidence for a contribution of chromatic mechanisms to the chromatic grating motion, although a contribution at very high chromatic contrasts cannot be ruled out. Our results add to a growing body of evidence indicating the presence of dynamic, internal luminance artifacts in the motion of chromatic stimuli and we show that these occur even at very low temporal rates. Our results are compatible with our previous work indicating the absence of a chromatic mechanism for first order (quasi-linear) apparent motion [Vision Res. 40 (2000) 1993]. We conclude that previous conclusions based on the motion of chromatic red-green gratings should be reassessed to determine the contribution of dynamic luminance artifacts.