Spontaneous granulocytic leukemia in a NOD/Shi-scid IL-2Rγnull mouse.

Here, we report a case of spontaneous granulocytic leukemia in a 51-week-old male NOD/Shi-scid IL-2Rγ null (NOG) mouse. The mouse showed progressive anemia and rough respiratory movement. Macroscopically, the spleen was discolored and enlarged. Histologically, the bone marrow of the sternum and femur was highly cellular and almost exclusively filled with neoplastic cells. The nuclei of neoplastic cells were large, oval to slightly irregular in shape, and a small number of cells had kidney- or ring-shaped nuclei. Neoplastic cells extensively infiltrated the organs, and the spleen and liver were prominently involved. Immunohistochemically, a large population of neoplastic cells in the red pulp of the spleen and sinusoid of the liver was positive for myeloperoxidase. Based on the histological features, this case was diagnosed with granulocytic leukemia. This novel information on spontaneous tumors may be helpful for the appropriate use of this mouse strain in further research.

Effectiveness of an erbium-doped: yttrium, aluminum and garnet laser for treatment of peri-implant disease: Clinical, microbiological, and biochemical marker analyses.

BACKGROUND: The effectiveness of an erbium-doped: yttrium, aluminum and garnet (Er: YAG) laser (EYL) for the treatment of peri-implant disease (PID) remains unclear. The aim of this study was to compare non-surgical EYL therapy for PID with locally delivered minocycline hydrochloride (MC) ointment therapy by evaluating clinical, microbiological, and biochemical markers. MATERIAL AND METHODS: Thirty-seven patients with PID were randomly assigned to either the EYL group (n = 18) or the MC group (n = 19). The clinical, microbiological, and biochemical markers at baseline and at 1 and 3 months after treatment were compared between the two groups. Subgingival plaque and peri-implant crevicular fluid (PICF) were collected from the diseased pockets. RESULTS: In the EYL group, probing pocket depth (PPD) was significantly decreased after treatment when compared with baseline. On the other hand, in the MC group, there was no significant decrease in PPD after treatment. Specific bacteria associated with PID were not determined. The counts of both Gram-positive and -negative species did not significantly decrease in the EYL group at 3 months after treatment. In the MC group, the counts of almost all bacterial species were significantly decreased after treatment. Biochemical marker analysis of PICF revealed significantly lower levels of metalloproteinase (MMP)-9 in the EYL group, as compared with the MC group at 3 months after treatment (p= 0.009). CONCLUSIONS: Non-surgical therapy with an EYL for PID was clinically effective, with decreased MMP-9 levels in PICF, which may lead to reduced peri-implant tissue destruction. Key words:Er: YAG laser; peri-implant disease; biomarker; peri-implant crevicular fluid.

Effects of four-week feed restriction on toxicological parameters in beagle dogs.

This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23% of control) for 4 weeks. Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs.

Usefulness of infrared thermometry in determining body temperature in mice.

The rectal temperature obtained using a standard electronic thermometer was compared with ear, back skin, tail skin, and sole skin temperatures obtained using an infrared thermometer in B6C3F1 mice. Using both methods, we investigated baseline temperatures, diurnal and 2-week variations in temperatures, and ethanol-induced hypothermia in these body locations. Ear and back temperatures were shown to be close to and consistent with rectal temperatures in various situations, and measured temperatures at these sites were almost constant, with very similar diurnal variation. Conversely, tail and sole temperatures were lower and much more variable. These results indicate that ear and back skin temperatures obtained using a convenient and non-invasive infrared thermometer are as reliable, and should be safer and less stressful to animal subjects, compared to standard rectal temperature measurements.

Myocardial necrosis related to hydrochlorothiazide-induced hypokalemia in cynomolgus monkeys.

Myocardial necrosis is a serious adverse effect that results from the administration of some medications; therefore, when it is observed during preclinical studies it becomes a major drug development concern. Although data from preclinical monkey studies are generally extrapolated to predict effects in humans, few reports have described any mechanism that might explain the occurrence of myocardial necrosis. For this reason, we examined the association between hypokalemia and myocardial necrosis in monkeys. Four female cynomolgus monkeys (Macaca fascicularis) were treated with 50 mg/kg/day hydrochlorothiazide (a thiazide diuretic used for antihypertensive therapy) for 1 or 2 weeks. Clinical, hematological, plasma biochemical, and pathological examinations were conducted. Two animals were kept in a hypokalemic state from day 3 of dosing on, and their mean plasma potassium levels were 2.52 +/- 0.24 and 2.60 +/- 0.24 mmol/l. These animals were necropsied after 1 week of dosing due to an aggravated general condition. A flattened T-wave was noted during electrocardiography. A transient increase in plasma cardiac-specific troponin-I and multifocal myocardial necrosis also occurred. The rest of the animals were occasionally hypokalemic, with mean plasma potassium levels of 3.13 +/- 0.31 or 2.96 +/- 0.30 mmol/l. These animals were necropsied after 2 weeks of dosing. One animal showed evidence of focal myocardial necrosis and a transient increase in plasma cardiac-specific troponin-I. These data suggest that the severe hypokalemia induced by hydrochlorothiazide is likely to be associated with myocardial necrosis in monkeys.