Probenecid: its chromatographic determination, plasma protein binding, and in vivo pharmacokinetics in dogs

Pharmacokinetics (PK) of probenecid including plasma probenecid concentrations, in vitro plasma protein binding properties, and in vivo PK parameters were determined in dogs. Probenecid concentrations were best determined by HPLC, which showed good linearity and good recovery with simple plasma preparation. The quantification limit of probenecid was approximately 50 ng/ml at S/N ratio = 3, by simple procedure with HCl and methanol treatment. Probenecid showed two types of binding characteristics, i.e., high-affinity with low-capacity and low-affinity with high-capacity binding. This result indicated 80-88% of probenecid was bound to plasma protein(s) at observed concentrations (< 80 microg/ml) in vivo at an intravenous dose of 20 mg/kg. Plasma probenecid concentration-time profile following i.v. administration in dogs showed biphasic decline and well fitted a two-compartment open model. The total body clearance was 0.34 +/- 0.04 ml/min/kg, volume of distribution at steady-state was 0.46 +/- 0.07 l/kg, elimination half-life was 18 +/- 6 hr, and mean residence time (MRT) was 23 +/- 6 hr. Since probenecid has been known as a potent inhibitor of renal tubular excretion of acidic drugs and highly binds to plasma proteins, our observation in relation to plasma protein binding and PK parameters will serve as the basic information concerning drug-drug interactions in dogs and in other mammalian species.     

Corneal squamous cell carcinoma in two dogs

Purpose To report two cases of corneal squamous cell carcinoma (SCC) in dogs. Methods Corneal tumors were resected by superficial keratectomy in two cases. Immunohistochemistry of the corneal tissues was performed using anti‐p53 antibody. Results The prominent features of the cases were a clinical history of pigmentary keratitis and chronic keratitis. In each case, a corneal mass was surgically removed with a superficial keratectomy and histologically diagnosed as corneal SCC. Both masses were negative for p53. To reduce chronic corneal irritation, 0.1% hyaluronate sodium ophthalmic solution was applied. After more than 15 months of postsurgical follow‐up there has been no recurrence of either neoplasm. Conclusion and discussion Chronic corneal irritation was suspected as the primary etiology for the corneal SCC. Appropriate surgical removal of the mass and subsequent conservative treatment for keratitis provided effective therapy in these two cases.     

Effects of epidermal growth factor on placental amino acids uptake in pregnant rats

To evaluate the effects of epidermal growth factor (EGF) on placental amino acids uptake, transport activities for L-proline, L-leucine, and L-alanine were kinetically examined in placental microvillous vesicles(PMV) obtained from pregnant rats administered with EGF(100 and 200 microg/kg/day) from day 18 to 21 of pregnancy. The Vmax of Na(+)-dependent proline uptake remarkably increased with a dose-dependent manner of EGF, while Km did not change. In contrast, Vmax and Km values of Na(+)-dependent and -independent alanine, and Na(+)-independent leucine uptake were not affected. These results suggested that EGF enhanced proline transport activity in placental microvillous membranes, resulting in an increase of proline concentration in the fetal blood. The selective up-regulation of proline uptake was considered to contribute to fetal growth by EGF.     

Malignant Mesothelioma in the Thoracic Cavity of a Crj:CD(SD) Rat Characterized by Round Hyalinous Stroma

Spontaneous malignant mesothelioma was found in a 104-week-old male Crj:CD(SD) rat. The tumor was scattered on the surface of the lung, heart, mediastinal pleura and thoracic wall and metastasized to the alveolar septa. Histopathologically, small flattened or cuboidal tumor cells proliferated with stroma, formed almost normal papillary structures and reacted positively to colloidal iron stain and immunohistochemical staining for mesothelin. Round hyalinous stromata were pronounced, which is a characteristic feature, and the possible reason for this is as follows; at first, a small amount of collagen fibers was formed in the center of the clusters of several tumor cells, and then the cell clusters expanded like balloons with an increase in the collagen fibers.     

Emergence and frequency of highly benzimidazole-resistant Colletotrichum gloeosporioides, pathogen of Japanese pear anthracnose, after discontinued use of benzimidazole

From July to October 1999, two Japanese pear varieties, Housui and Niitaka, were unexpectedly infected with Colletotrichum gloeosporioides causing anthracnose in Saga Prefecture of Japan. More than 90?% of the anthracnose fungus strains collected in 1999 were highly benzimidazole-resistant and distributed at high frequencies across pear-producing areas. The control of anthracnose by benzimidazole fungicides could not be confirmed in orchards where the isolation frequency of resistant strains was high. The frequency of resistant strains did not significantly decline, even 2?C5?years after the last use of benzimidazole fungicides.     

Identification of potato scab-causing Streptomyces sp. occurring in strongly acidic soils in Saga Prefecture in Japan

Acid scab of potatoes occurs frequently in strongly acidic soils at pH 3.9–5.2. On the basis of the phylogenetic relationships derived from 16S rDNA sequences and physiological characteristics, we identified the organism causing this disease in potatoes grown in the Uwaba district of Saga Prefecture, Kyushu Island, southwest Japan, as Streptomyces acidiscabies. Another pathogen that occurred more frequently in weakly acidic to neutral soils, rather than strongly acidic soils, was identified as S. scabiei. Streptomyces acidiscabies tended to produce superficial lesions, while S. scabiei mostly produced raised and/or erumpent lesions.     

L-leucine: a neuroactive substance in insects

A compound was isolated from the blood of silkworm larvae, Bombyx mori, which had been prostrated with DDT; this compound increased the spontaneous discharge in the isolated abdominal nerve cord of the American cockroach, Periplaneta americana. The compound was identified as L-leucine.     

Estimation of mean tree height using small-footprint airborne LiDAR without a digital terrain model

In order to estimate mean tree height using small-footprint airborne light detection and ranging (LiDAR) data, a digital terrain model (DTM), which is a continuous elevation model of the ground surface, is usually required. However, generating accurate DTMs in mountainous forests using only the LiDAR data is laborious and time consuming, because it requires human-assisted methods, especially in the forests with poor laser penetration rates. Based on our previous finding that a hypothetical continuous surface model passing through the predominant tree tops (hereafter, called the “top surface model” or TSM) might be nearly parallel to a DTM, we assumed that the vertical difference between the TSM and the ground return was the mean tree height. According to this assumption, we propose a new methodology that does not require a DTM to estimate mean tree height. This method completely, automatically, and directly estimates mean tree height (MTH _E) from the LiDAR data without requiring a regression analysis using reference data. From the relationships between the MTH _E and the observed mean tree height (MTH _O) in different hinoki cypress forests, we demonstrate that this method effectively estimates the mean tree height with nearly 1-m accuracy.     

Aboveground productivity of an unsuccessful 140-year-old <Emphasis Type="Italic">Cryptomeria japonica</Emphasis> plantation in northern Kyushu,Japan

We measured the aboveground biomass, biomass increment and litterfall production of a 140-year-old, abandoned Cryptomeria japonica plantation in order to infer the effects of topography on biomass production. The plantation was unsuccessful and the naturally regenerated broad-leaved trees contributed 93.4% (374.2 Mg ha⁻¹) of the total aboveground biomass (400.2 Mg ha⁻¹). Comparing between different slope positions, aboveground biomass decreased downslope corresponding to the decrease in broad-leaved tree biomass. The biomass of C. japonica did not vary with slope position. Biomass increment and litterfall production of the broad-leaved trees also decreased downslope. However, litterfall production per unit biomass and aboveground net primary production per unit biomass increased downslope. Results of a path analysis showed that biomass increment of C. japonica decreased with increasing topographical convexity, whereas biomass and litterfall production of broad-leaved tree increased. Litterfall production of broad-leaved tree decreased with increasing biomass of C. japonica, suggesting that, despite their small biomass, the presence of residual C. japonica may have negative effects on the distribution and productivity of the broad-leaved trees. Our results indicated that total aboveground biomass of the study site was comparable to that of old-growth C. japonica plantations. We inferred that the variation in aboveground biomass of the broad-leaved trees was largely determined by the topography, while their productivity was affected by interactions with planted C. japonica.