Oral high dose 1,25(OH)2D3 pulse therapy

To 13 uremic patients with secondary hyperparathyroidism, 4 micrograms of 1,25(OH)2D3 were given orally twice a week for 4 weeks. Intact PTH values fell from 488.3 +/- 84.2 to 235.2 +/- 59.6 pg/ml (Mean +/- SE, p less than 0.01), while serum total and ionized calcium elevated from 10.3 +/- 0.2 to 11.8 +/- 0.6 mg/dl (p less than 0.01), from 1.43 +/- 0.03 to 1.64 +/- 0.06 mmol/l (p less than 0.05), respectively, in 9 patients whose initial intact PTH level had been below 1000 pg/ml. The other 4 patients, of whom intact PTH level had been above 1000 pg/ml, did not show significant change in intact PTH values, though serum ionized calcium elevated slightly after this treatment. The correlation curve, determined by ionized calcium and intact PTH values in each period, was found to shift in only 2 out of 5. During the 4 weeks of high dose oral 1,25(OH)2D3 therapy, mean blood pressure elevated from 92.4 +/- 3.3 to 103.5 +/- 3.5 mmHg (p less than 0.01) in general, and 7 patients out of 13 complained of mental irritability. These data suggest that oral administration of high dose 1,25(OH)2D3 suppresses PTH secretion of uremic patients directly, however, reliability of this effect is still controversial. Indication of this therapy and adverse effects caused by rapid increase in serum calcium should be studied in more detail.     

Plasma monoaminergic metabolites and catecholamines in subarachnoid hemorrhage. Clinical implications

We examined plasma catecholamines and monoaminergic metabolites (3-methoxy-4-hydroxyphenylethyleneglycol [MHPG], homovanillic acid [HVA], and 5-hydroxyindoleacetic acid) in patients with stroke successively up to three weeks after the initiation of symptoms. Plasma levels of free catecholamines were significantly elevated in patients with subarachnoid hemorrhage (SAH). However, no significant differences in plasma catecholamines were found when the patients with SAH were subdivided into noncomatose and comatose groups. In contrast, plasma HVA, MHPG, and 5-hydroxyindoleacetic acid levels in comatose patients with SAH significantly increased as compared not only with normal controls but also with noncomatose patients with SAH, and the peak levels of HVA and MHPG occurred within seven days poststroke. Such trends as observed in SAH were not observed in patients with cerebral hemorrhage. Our results suggest the usefulness of plasma monitoring of possibly centrally originating monoaminergic metabolites for predicting the degree of cerebral dysfunction in patients with SAH.     

Molecular epidemiology of Sporothrix schenckii]

Restriction fragment length polymorphism (RFLP) in mitochondrial DNA (mtDNA) of clinical and environmental isolates of Sporothrix schenckii was investigated. Among mtDNA RFLP patterns with Hae III, of 14 environmental isolates morphologically identified as S. schenckii, only 2 isolates were confirmed as S. schenckii, while of more than 500 clinical isolates, all were confirmed to have this condition. Therefore, RFLP analysis of mtDNA is essential for the identification of environmental, but not clinical, isolates of S. schenckii. Isolates of Sporothrix schenckii were classified into 23 mtDNA types (Types l-23) based on mtDNA RFLP patterns with HaeIII and clustered into two major groups by phylogeny, Group A (Types 1-3, 11, 14-19, 22 and 23) and Group B (Types 4-10, 12, 13, 20 and 21). Group A isolates are predominant in South Africa, North America, Central America and South America, while Group B isolates are predominant in Australia and Japan. In Japan, the relative distribution of the mtDNA types varied with geographic region: Types 4, 6 are comparatively abundant in West Japan (Kansai and Kyushu districts), Type 5 is comparatively abundant in East Japan (Tokai, Kanto and Tohoku districts) and Type 2 is abundant in the Hokuriku district. Type 1 is found only in the Hokuriku district.     

A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition.

Our previous study showed that several drugs inhibited quinine 3-hydroxylation, a cytochrome P450 (CYP) 3A4-mediated reaction, in vitro. In this extended study, 13 drugs were selected and tested by human liver microsomes in order to further determine their respective inhibition constant (Ki) and type of inhibition. According to the apparent Ki values, the inhibitory rank order of these tested drugs was as follows: ketoconazole > doxycycline > omeprazole > tetracycline > troleandomycin (with pre-incubation) > primaquine > troleandomycin (without pre-incubation) > nifedipine > erythromycin > verapamil > oleandomycin > diltiazem > cimetidine > hydralazine. Among these drugs, doxycycline, tetracycline, ketoconazole, nifedipine and hydralazine were judged as mixed inhibitors; whereas, the remaining other drugs tested were judged as competitive inhibitors. When the plasma/serum concentrations possibly attained after their usual therapeutic doses were taken into account, tetracycline, doxycycline, omeprazole, ketoconazole, nifedipine, troleandomycin and erythromycin are likely to be inhibitors of quinine metabolism in patients when these drugs are co-administrated with quinine.     

Effect of beta-adrenoceptor blockade on exercise-induced plasma catecholamine concentrations and their dissipation profile.

The time-course of plasma noradrenaline (NA) and adrenaline (A) concentrations and their dissipation profiles were examined concomitantly with heart rate changes after strenuous exercise in eight normal subjects receiving either placebo or carteolol, a beta-adrenoceptor blocker. Post-exercise NA concentrations declined with time in a biexponential manner, while A disappearance curves were apparently monophasic. Plasma NA concentrations and their peak value attained within 3 min after exercise were higher in the carteolol than in the placebo phase, whereas there were no significant differences in the first and second disappearance t1/2 between the two trials. The monoexponential t1/2 of A in the carteolol trial was significantly longer than in the placebo trial. Our results suggest that the dissipation profiles of catecholamines released by exercise appear to be affected by beta-adrenoceptor blockade.     

Arachidonic acid metabolism in cultured astrocytes from rat embryo and in C6 glioma cells

Arachidonic acid metabolism in primary cultures of astroglial cells prepared from cerebra of rat embryos was examined. Arachidonic acid was mainly metabolized through the lipoxygenase pathway and the major metabolites formed were 12-hydroxyeicosatetraenoic acid (12-HETE), 11-HETE and 15-HETE. By contrast, in C6 cells, which are considered to be of astroglial origin, arachidonic acid was mainly metabolized through the cyclooxygenase pathway and the major metabolites formed were prostaglandin (PG)E2, PGF2 alpha and thromboxane B2.     

Serum levels of bone Gla-protein in inhabitants exposed to environmental cadmium

Serum levels of bone Gla-protein (BGP)--the vitamin K-dependent CA2(+)-binding protein--were evaluated in 76 cadmium (Cd)-exposed subjects with renal tubular dysfunction (32 men, 44 women) and 133 nonexposed subjects (53 men, 80 women). Serum BGP levels were higher in the Cd-exposed subjects than in nonexposed subjects. Significant correlations between BGP and each index measured by bone microdensitometry (MD), serum alkaline phosphatase activity, and Cd in blood and urine were found. For all of the Cd-exposed and nonexposed men and women, BGP showed a significant standard partial regression coefficient (multiple regression analysis) with the metacarpal index (MCI), which was one of the MD indicators. Bone Gla-protein also correlated significantly with urinary beta 2-microglobulin in the men and with serum creatinine in the women. Serum BGP values strongly reflect the degree of bone damage and also reflect, although less strongly, the degree of renal damage induced by exposure to Cd.     

A calculation of percutaneous drug absorption--II. Computation results

The numerical computation data of percutaneous drug absorption are reported in this article. When the concentration of a drug in the uppermost epidermis can be considered unchanged, more than 50, 75, 90, 95 and 99% of the amount saturated at quasi-steady-state are accumulated after the respective time intervals of 0.5, 1, 2, 3 and 4 times the lag-time. After the ointment removal, the drug flux from the skin becomes linear on a semilogarithmic scale and the elimination rate constant is not dependent on the initial condition.     

Quantitative evaluation of right ventricular overload in cor pulmonale using 201T1 myocardial SPECT

In patients with right ventricular overload, the free wall of the right ventricle is often visualized by 201T1 myocardial scintigraphy. To determine quantitatively the discriminant and characteristics of cor pulmonale, 201T1 myocardial perfusion single photon emission computed tomography (SPECT) was performed in 16 patients with chronic obstructive pulmonary disease (COPD) and seven with restrictive pulmonary disease (RPD). We selected one section of the short-axis image of SPECT in which the right ventricle was most clearly visualized, and defined the T1-score as the ratio of the sum of counts in the region of interest (ROI) at the anterior, mid and posterior regions of the right ventricular free wall to the sum of counts in the ROI at the posterior, lateral, anterior walls of the left ventricle, and the anterior and posterior regions of the interventricular septum. Correlation of the T1-score with mean pulmonary arterial pressure (mPAP), systolic pulmonary arterial pressure (sPAP), and total pulmonary vascular resistance (TPR), as obtained by right cardiac catheterization, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were evaluated. The results were as follows: 1. In the patients with COPD, the T1-score correlated positively with mPAP (r = 0.71, p less than 0.005), TPR ( r = 0.69, p less than 0.005), and PaCO2 (r = 0.63, p less than 0.01), and it correlated inversely with PaO2 (r = -0.58, p less than 0.05). However, there was no significant correlation between the T1-score and mPAP, TPR, PaCO2, and PaO2 in the patients with RPD.(ABSTRACT TRUNCATED AT 250 WORDS)