Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats.

Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

Relationship between regulatory and type 1 T cells in dogs with oral malignant melanoma.

Recent data suggest a decreased prevalence of IFN-gamma-producing T lymphocytes (Type 1 T cells) in tumor-bearing hosts. Moreover, it has been reported that Treg have a strong impact on the activation and proliferation of CD4 (+) and CD8 (+) lymphocytes; however, no previous reports have described the relationship between Treg and the progression of tumor, or Type 1 T cell populations in dogs with malignant tumor. In this study, the percentage of Treg, Th1, and Tc1 in the peripheral blood of dogs with oral malignant melanoma and healthy dogs was measured and compared. Although the percentages of Th1 and Tc1 in dogs with oral malignant melanoma were less than those in healthy dogs (Th1: P < 0.01, Tc1: P < 0.05), the percentage of Treg was increased (P < 0.01). A significant inverse correlation between the percentage of Tc1 and the clinical tumor stage (P < 0.01), and a significant correlation between that of Treg and the clinical tumor stage (P < 0.001) was found. Moreover, there was a significant inverse correlation between the percentages of Treg and Th1 (P < 0.05) or Tc1 (P < 0.001). In conclusion, the percentage of Treg increases with the tumor stage in the peripheral blood of dogs with oral malignant melanoma. In dogs, Treg appears to suppress Type 1 immunity, which may be responsible for anti-tumor responses.

Increase of regulatory T cells in the peripheral blood of dogs with metastatic tumors.

It is well known that lymphocytes from patients with advanced-stage cancer have impaired immune responsiveness and that type1 T lymphocyte subsets in tumor bearing hosts are suppressed. Treg have been reported to comprise a subgroup which inhibits T cell mediated immune responses. In the present study, the percentage of Treg, Th1 and Tc1 in the peripheral blood of tumor bearing dogs with or without metastases was evaluated. The percentages of Th1 and Tc1 in dogs with metastatic tumor were significantly less, and that of Treg was significantly greater, than those of dogs without metastatic tumor. The percentage of Treg showed an inverse correlation with that of Th1 and Tc1 in tumor bearing dogs. It was concluded that an increase in Treg in the peripheral blood of dogs with metastatic tumor may induce suppression of tumor surveillance by the Type1 immune response and lead to metastasis of tumor[0][0].[0].

Evaluation of immunological status in tumor-bearing dogs.

The purpose of this study was to evaluate immunological status in dogs with cancers at different stages, in comparison with normal dogs. The population of canine peripheral blood lymphocytes (cPBL), lymphocyte phenotypes, interleukin (IL)-6 activity and alpha 1-acid glycoprotein (alpha(1)-AG) level were analyzed. The tumor-bearing dogs had higher numbers of leukocytes than normal dogs, the count being higher in dogs with more advanced tumors. In the tumor-bearing dogs, differential leukocyte counts revealed higher percentages of inflammatory cells such as neutrophils, acidophils and monocytes, and lower numbers of CD4(+)T cells, than in normal dogs, the lymphocyte counts becoming much lower with tumor progression. In the tumor-bearing dogs, the CD8(+)T cell count at the early tumor stage was similar to that in normal dogs, but decreased with tumor progression, possibly reflecting the development of humoral immunity (Th2). Plasma IL-6 and TGF-beta activities were high in the tumor-bearing dogs. The plasma alpha(1)-AG concentration was also significantly high in the tumor-bearing dogs. Our findings suggest that assay of IL-6, TGF-beta and alpha(1)-AG may be very useful for prognostication in dogs with cancer, and that anti-tumor immunity is potently suppressed in such dogs.

T-helper (Th)1/Th2 imbalance in the peripheral blood of dogs with malignant tumor.

T helper type 1 cell (Th1)/Th2 imbalance has been observed in a variety of pathological conditions, including malignant diseases. We evaluated the Th1/Th2 in peripheral blood Th cells by means of intracytoplasmic cytokine analysis in 11 dogs with advanced malignant tumor; four of them showed metastatic tumor. The percentage of Th1 was significantly lower and the percentage of Th2 was significantly higher in diseased dogs compared to healthy dogs. The percentage of Th1 in three patients with metastatic tumor was significantly lower than that in the patients with non-metastatic tumor. We conclude that the Th1/Th2 balance was polarized to Th2 in dogs with cancer.

Th1/Th2 balance in canine peripheral blood lymphocytes--a flow cytometric study.

The canine immune system undergoes continuous remodeling with advancing age. We measured the Th1/Th2 balance in peripheral blood lymphocytes (PBLs) obtained from 23 Beagles ranging in age from 0.5 to 11.8 years by flow cytometric analysis using intracellular cytokine staining. The percentage of CD4 cells producing interferon-gamma (Th1) increased with age. The percentage of CD4 cells producing interleukin-4 (Th2) increased but much less so. In conclusion, we demonstrated that the Th1/Th2 balance in canine peripheral blood could be measured by this flow cytometry technique and the Th1/Th2 balance inclined to dominance of the Th1 subpopulation in PBLs as the dog matured.

Immunological effects of recombinant feline interferon-omega (KT-80) administration in the dog.

The immunological effects of recombinant feline interferon-omega (rFeIFN-omega ; KT-80, Toray) were examined on administration to healthy dogs. The activities of whole blood cells, macrophages, and natural killer cells were enhanced. Moreover, the whole blood activity was examined when KT-80 was administered to dogs which had been diagnosed as having natural canine parvovirus (CPV) infection. Only some cases in which the activity increased until 3 hr post-administration survived. These results suggest that rFeIFN-omega (KT-80) treatment enhanced the cellular immunity of normal dogs, and could exert significant therapeutic effects on only natural CPV infected dogs with induced continuous immunoenhancement.

A case of anaplastic meningioma in a dog.

A tumor sized in 2.0x2.0x2.5 cm developed in the cerebellum of a female Beagle was pathologically investigated. Histopathologically, the tumor grew by compression and partially by infiltration into the adjacent cerebellar parenchyma. There were a large number of necrotic lesions and proliferation of collagen fibers. The tumor cells had oval nucleus showing cellular atypia and a high mitotic index. The tumor cells were reacted with vimentin antibody on immunostain. Electron microscopic examination revealed the tumor cells interdigitated with cytoplasmic processus where the desmosomes developed on cell junction. This tumor was diagnosed as anaplastic meningioma, which is rarely observed in dogs.

Scanning electron microscopy of root resorption of feline teeth.

Scanning electron microscopy was carried out on 10 feline extracted permanent teeth from 3 cases with root resorption. Various-sized resorption lacunae were well defined, showing an etched pattern and configuration as shown in human deciduous teeth. In cats, regardless of the shape and depth of lacunae, the resorption lacunae showed opening dentinal tubules in the wall with or without cement matrix apperring only in the deep and round lacunae of human cases. Some specific process of mineralization for repairing dental root resorption was suggested in cats.

Successful treatment by percutaneous transvenous coil embolization in a small-breed dog with intrahepatic portosystemic shunt.

A Miniature Dachshund, 3-month-old, 3.1 kg, was diagnosed as an intrahepatic portosystemic shunt (PSS) with the shunting vessel in 6-mm diameter. Percutaneous transvenous coil embolization (PTCE) was performed with a stainless steel coil in 8-mm diameter. Intraoperative portal pressure elevated about 2.5 times after one-stage coil occlusion. Two weeks after the PTCE, serum bile acid levels reduced within the normal range. The portogram showed complete occlusion of the shunting vessel 4 months after the PTCE. Approximately 3 years after the PTCE, the patient has shown no clinical signs. PTCE could be performed more easily and less invasively in a small-breed dog. It is therefore suggested that PTCE is a promising therapeutic technique in canine intrahepatic PSS.

Potential application of high-resolution microfocus X-ray techniques for observation of bone structure and bone-implant interface.

PURPOSE: The aim of the present study was to evaluate the potential application of 2 types of microfocus x-ray units to study the bone structure around dental implants and at the bone-implant interface. MATERIALS AND METHODS: IMZ titanium implants were placed in the maxilla and mandible of a beagle dog. After implantation periods of 1, 2, and 3 months, the bone-implant interface was evaluated with microfocus x-ray computed tomography (CT) and microfocus x-ray fluoroscopy. RESULTS: Microfocus x-ray CT images of the bone-implant specimen at 3 months after implant placement revealed a clear distinction between the implant and the bone. The implant surface was partially covered with bone, and direct contact between the implant and bone could be clearly seen. Differences in degrees of calcification were identified by the differences in relative black and white intensity. Microfocus x-ray fluoroscopy also showed clear features of the bone and titanium implant The original drill hole and new bone formation could be recognized. These findings corresponded with traditional histologic observations by light microscopy. DISCUSSION AND CONCLUSION: Microfocus x-ray techniques are non-destructive and require a very short examination time. They are considered useful to observe details of the bone structure and bone-implant interface. Microfocus x-ray fluoroscope and microfocus x-ray CT techniques can provide a clear and distinguishable image of the bone-implant interface because of their high spatial resolution.

Effect of germanium, poly-trans-[2-carboxyethyl] germasesquioxane on natural killer (NK) activity in dogs.

In an attempt to study the immunological effects on normal and adenocarcinoma (AC) dogs, the natural killer (NK) activity was determined. Augmentation of NK cell activities in responsive normal and AC dogs that indicatedanergy in the phaseolus vulgaris agglutinin (PHA) skin-test was manifested when the animals were accordingly treated with germanium (GN).