Soluble Fas Ligand: Is It a Critical Mediator of Toxic Epidermal Necrolysis and Stevens–Johnson Syndrome?

Although soluble Fas ligand (sFasL) is an important candidate in toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), Stur and colleagues report that elevated sFasL has been detected in maculopapular rashes. In addition to sFasL, other factors, including predisposing genetic factors, should also be investigated to determine their precise pathogenesis in TEN and SJS.     

Relationship between Intensity of Reflected Light and Temperature Increase: Assessment of Fundus Pigmentation for Transpupillary Thermotherapy

Purpose

To develop a new device for measuring reflected light during diode-laser irradiation in transpupillary thermotherapy (TTT) and to assess the correlation between fundus pigmentation, the measured intensity of reflected light, and the increase in fundus temperature.

Methods

We developed a device to measure reflected light by modifying a slit-lamp-mounted 810-nm diode-laser delivery system used clinically for TTT. The diode laser was used to irradiate test charts with various degrees of reflectance in in vitro experiments, and the fundus of nonpigmented or pigmented rabbits in in vivo experiments; then, the intensity of the reflected light and the temperature increase at the target were measured. The retinal sections were also examined histologically.

Results

There was a significant negative correlation between the intensity of the reflected light and the temperature increase in the target that depended on the degree of reflectance of the charts or the pigmentation of the rabbit eyes. On histopathologic examination, the extent of the changes in the irradiated retina after TTT was clearly different between pigmented and nonpigmented rabbits.

Conclusions

Correlations between fundus pigmentation, the intensity of reflected light during diode-laser irradiation, and the temperature increase in TTT were demonstrated in vitro and in vivo. Our results suggest that measurement of the intensity of reflected light should be helpful for modulating the laser power in TTT according to the degree of fundus pigmentation.?Jpn J Ophthalmol 2007;51:462–469 © Japanese Ophthalmological Society 2007     

Is cognitive impairment a risk factor for poor compliance among Japanese elderly in the community?

OBJECTIVE: The association between cognitive impairment and compliance with prescribed medications was investigated among functionally independent Japanese elderly in the community. SUBJECTS: The subjects of this study were 220 elderly persons aged 60 years and over, who lived in the community. All participants were taking a regimen of one or more prescribed drugs. We included elderly with mild to moderate cognitive impairment. Medication use was observed by pharmacist-conducted interviews during home visits. Compliance was estimated by the pill count method. The Mini-Mental State Examination (MMSE) was used to estimate cognitive function. RESULTS: The mean age (SD) of the subjects was 75.7 (6.9) years. Of the subjects, 58 (26.4%) were cognitively impaired (MMSE < or = 23), and 76 (34.6%) exhibited poor compliance (rate of compliance< 80%). Poor compliance was associated with the subjects who had a lower education level, had lower MMSE scores, had concern about taking drugs, who intentionally self-selected (intentional noncompliance) prescribed drugs, had a poor relationship with a physician, who did not have one dose package, and those who did not use a medical calendar. In multiple logistic regression analyses, intentional noncompliance (OR 19.65, 95%, CI 9.22-41.92; OR, odds ratio; CI, confidence interval), cognitive impairment (MMSE < or = 23; OR 2.94, 95%, CI 1.32-6.58), and a poor relationship with a physician (OR 6.24. 95%, CI 1.55-25.20) were independent predictors of poor compliance for elderly in the community. CONCLUSION: We found that cognitive impairment was one of the predictors for poor compliance among the elderly who are functionally independent in the community. Intentional noncompliance was the strongest predictor for poor compliance, which was influenced by the relationship between patient and physician. Physicians should establish good communication with their elderly patients and provide some support to compensate for cognitive impairment.     

Metabolism and distribution in the rat of peak E substance,a constituent inl-tryptophan product implicated in eosinophilia-myalgia syndrome

Peak E substance, 1,1-ethylidenebis[tryptophan], a contaminant found inl-tryptophan tablets, has been suggested as a causative agent for eosinophilia-myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C₈ cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5–24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 g, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro--carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than inl-tryptophantreated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than froml-tryptophan. Finally, we propose acetaldehydeinduced production of MTCA from peak E substance.     

Tissue penetration and clinical experiences of aztreonam in obstetrics and gynecology

Tissue penetration and clinical efficacy were studied on aztreonam (SQ 26,776, AZT) in obstetrics and gynecology with the following results. Number of cases was too small to sufficiently review the penetration into each uterine tissue, the ovary and the tube after the intravenous injection of AZT 1 g. Overall clinical effect for all the 6 cases reviewed was more than "good". Also, neither side effect nor abnormal laboratory findings were reported. From the above results, AZT was considered to be a highly useful antibiotic in obstetrics and gynecology.     

Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors

Lysophosphatidic acid (LPA) exerts a variety of biological responses through specific receptors: three subtypes of the EDG-family receptors, LPA1, LPA2, and LPA3 (formerly known as EDG-2, EDG-4, and EDG-7, respectively), and LPA4/GPR23, structurally distinct from the EDG-family receptors, have so far been identified. In the present study, we characterized the action mechanisms of 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425) on the EDG-family LPA receptors. Ki16425 inhibited several responses specific to LPA, depending on the cell types, without any appreciable effect on the responses to other related lipid receptor agonists, including sphingosine 1-phosphate. With the cells overexpressing LPA1, LPA2, or LPA3, we examined the selectivity and mode of inhibition by Ki16425 against the LPA-induced actions and compared them with those of dioctyl glycerol pyrophosphate (DGPP 8:0), a recently identified antagonist for LPA receptors. Ki16425 inhibited the LPA-induced response in the decreasing order of LPA1 >/= LPA3 > LPA2, whereas DGPP 8:0 preferentially inhibited the LPA3-induced actions. Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells. The difference in the inhibition profile of Ki16425 and DGPP 8:0 was exploited for the evaluation of receptor subtypes involved in responses to LPA in A431 cells. Finally, Ki16425 also inhibited LPA-induced long-term responses, including DNA synthesis and cell migration. In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions.