Pharmacokinetics of oral alminoprofen (Minalfen) in elderly patients with rheumatoid arthritis and spondylosis deformans]

The pharmacokinetics of oral Alminoprofen, a nonsteroidal anti-inflammatory drug, were studied in five elderly patients with rheumatoid arthritis and spondylosis deformans after 200 mg (three times a day) repeated dose for 5 days. The pharmacokinetic parameters after oral administration of Alminoprofen were analyzed by the one-compartment open model method. The maximum plasma concentrations (Cmax) were 16.1 +/- 2.5 micrograms/ml, after dosing on day 1, 25.2 +/- 1.6 micrograms/ml on day 3 and 21.6 +/- 2.7 micrograms/ml on day 5. The maximum time (Tmax) were about 2 hours after the medication in al cases. The area under the curve in drug concentration in plasma versus time (AUC) were 58.5 +/- 6.3 micrograms hr/ml on day 1, 58.5 +/- 3.1 micrograms hr/ml on day 3 and 58.1 +/- 8.5 micrograms hr/ml on day 5. The biological half-lives (t1/2) were 2.45 +/- 0.35, 2.09 +/- 0.82 and 2.49 +/- 0.63 hours, after dosing on day 1, day 3 and day 5, respectively. The analysis of moment in pharmacokinetics revealed that the mean residence time (MRT) on day 1, day 3 and day 5 observed were 2.31 +/- 0.03, 2.15 +/- 0.09 and 2.15 +/- 0.07 hours, respectively. The variance residence times (VRT) observed were 0.95 +/- 0.05 hour2 on day 1, 0.88 +/- 0.09 hour2 on day 3 and 1.06 +/- 0.07 hour2 on day 5. The ratios of accumulation calculated were 1.16 +/- 0.05 in both the morning medication on day 3 day 5, and it therefore appears that the steady-state equilibrium is established within 3 days after commencement of dosage.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Case of Fibrous Histiocytoma Associated with Xanthogranulomatous Alteration

We report here an unusual case of fibrous histiocytoma in which an area of xanthogranuloma was observed histologically. Our case suggests that adult xanthogranuloma is a variant of fibrous histiocytoma.     

Action Spectrum for Bergamot-Oil Phototoxicity Measured by Sunburn Cell Counting

The present study investigated the phototoxic effect of bergamot oil and its photosensitive component, bergapten, on sunburn cell (SBC) production in guinea pig skin. The back skin was pretreated with bergamot oil or bergapten and exposed to monochromatic light under various conditions. After irradiation, skin specimens were excised, and histological sections were prepared. The number of sunburn cells in the interfollicular epidermis was counted. The SBC formation by bergamot oil or bergapten plus UVB radiation was the same as that without pretreatment with any photosensitizer. In contrast, a significant number of SBCs were induced by bergamot oil or bergapten plus UVA radiation, but no SBCs were found after the treatment with UVA alone. The result indicates that bergamot oil or bergapten was photosensitized by UVA irradiation. The SBCs were linearly increased in a UV-dose dependent manner. On the basis of the regression lines, an action spectrum and spectral peak for the photosensitizers plus UVA were obtained. The action spectrum for bergamot oil- and bergapten-induced SBC formation was in the ranges of 325–365 nm and 325–350 nm, and their spectral peaks were at 335–345 nm and 335–350 nm, respectively. The data are in good accordance with those estimated from skin erythema reactions. Therefore, counting SBCs is a very useful parameter for quantitative evaluation of phototoxicity.     

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 2.

A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation.     

A case of bilateral panophthalmoplegia caused by paranasal malignant lymphoma extending into the skull base]

A case of bilateral panophthalmoplegia developed after paranasal malignant lymphoma is described, and previously reported cases are reviewed. A 74-year-old female was hospitalized with the chief complaints of bilateral ptosis and bilateral deep orbital pain that had developed over a 10-day period. Neurological examination revealed bilateral dilated pupils, panophthalmoplegia, and hypalgesia in the area of the ophthalmic nerve on both sides. Laboratory studies and endocrinological examination were free from abnormal findings. Skull X-ray films showed a soft tissue lesion in the sphenoidal and ethmoidal sinus and this was associated with bony structure destruction in the surrounding area. Computed tomography demonstrated a heterogeneously enhanced mass lesion in the paranasal sinus extending into the intrasellar region and bilateral cavernous sinus. Meticulous investigation has so far revealed no distant lesions either in the thoracic or abdominal lesions. Subtotal tumor resection was undergone via the transsphenoidal route at which time tumor extension into the nasal cavity and sellar floor destruction were confirmed. Diffuse and mixed B-cell type malignant lymphoma was the pathological diagnosis. Postoperatively, improvement of abnormalities of pupils, panophthalmoplegia, and ptosis was achieved but this was only transient. Despite focal radiation therapy and repeated chemotherapy, the patient died 14-months after the diagnosis was made. On reviewing the literature, it is shown that the incidence of bilateral panophthalmoplegia among patients who develop disturbance of ocular movement is extremely low (0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hypertension on asymmetrical septal hypertrophy: an echocardiographic study

The effect of hypertension on asymmetrical septal hypertrophy was studied by echocardiography to differentiate idiopathic asymmetrical septal hypertrophy (ASH) from ASH with hypertension. One hundred eight patients with ASH proven by echocardiography were categorized in two groups; 53 patients with hypertension (greater than 160 systolic, greater than 95 diastolic) (hypertensive group: HT) and 55 patients with normal blood pressure (normotensive group: NT). Septal hypertrophy was classified as mid-portion (M-type), diffuse (D-type), and basal (B-type) hypertrophy by the long-axis view, and also diffuse (I-type), anterolateral (II-type), anteroseptal (III-type), and anterior septal (IV-type) by the short-axis view, respectively. Endomyocardial biopsy and left ventriculography were performed in 50 patients (18 hypertensives and 32 normotensives). In the hypertensive group, 45%, 30%, and 25% of cases had diffuse, basal and mid-portion hypertrophy, respectively. There was no case in the basal hypertrophy whose biopsy findings were compatible with hypertrophic cardiomyopathy. In the normotensive group, 78% and 22% of patients had midportion and diffuse hypertrophy, respectively, but none of them had the basal hypertrophy. Type IV was seen in only six patients in the normotensive group.     

Single photon emission computerized tomography in childhood hydrocephalus

Single photon emission computerized tomography (SPECT) is now widely used as one of the tools in evaluating cerebral blood flow (CBF). The authors report the CBF changes in childhood hydrocephalus. Five pediatric cases studied by ¹²³I-IM SPECT in children are presented. The authors counted radioactivities both in early and delayed images in each patient, and calculated the reabsorption ratio (RR). Two negative-RR cases and three positive-RR cases were found. All of the negative-RR patients had a poor prognosis, while all of the positive-RR patients had a favorable outcome.     

Direct effect of cadmium on citrate uptake by isolated rat renal brush border membrane vesicles

High incidence of multiple kidney stone formation has been observed among workers exposed to cadmium (Cd). Citrate is known to be a protective factor against renal stone formation. To study the direct effect of cadmium on citrate uptake by the renal brush border membrane, we exposed isolated rat renal brush border membrane vesicles (BBMV) to cadmium and determined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. Preincubation of BBMV with 2 and 10 mM CdCl₂ for 1 min significantly inhibited citrate uptake compared with that of BBMV without Cd. Analysis of the time course of citrate uptake during 30-min preincubation of BBMV with 0.5 mM Cd also revealed significant reduction of the uptake compared with that of the control BBMV without preincubation. These findings indicate that preincubation of BBMV with cadmium results in time-dependent and concentration-dependent inhibition of citrate uptake.