Effects of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine on phencyclidine-induced behavior and expression of the immediate-early genes in the discrete brain regions of rats

Because of the possible interaction between adenosine receptors and dopaminergic functions, the compound acting on the specific adenosine receptor subtype may be a candidate for novel antipsychotic drugs. To elucidate the antipsychotic potential of the selective adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA), we examined herein the effects of CPA on phencyclidine (PCP)-induced behavior and expression of the immediate-early genes (IEGs), arc, c-fos and jun B, in the discrete brain regions of rats. PCP (7.5 mg/kg, s.c.) increased locomotor activity and head weaving in rats and this effect was significantly attenuated by pretreatment with CPA (0.5 mg/kg, s.c.). PCP increased the mRNA levels of c-fos and jun B in the medial prefrontal cortex, nucleus accumbens and posterior cingulate cortex, while leaving the striatum and hippocampus unaffected. CPA pretreatment significantly attenuated the PCP-induced increase in c-fos mRNA levels in the medial prefrontal cortex and nucleus accumbens. CPA also significantly attenuated the PCP-induced arc expression in the medial prefrontal cortex and posterior cingulate cortex. When administered alone, CPA decreased the mRNA levels of all IEGs examined in the nucleus accumbens, but not in other brain regions. Based on the ability of CPA to inhibit PCP-induced hyperlocomotion and its interaction with neural systems in the medial prefrontal cortex, posterior cingulate cortex and nucleus accumbens, the present results provide further evidence for a significant antipsychotic effect of the adenosine A(1) receptor agonist.     

The influence of controlled occlusal overload on peri-implant tissue. part 4: a histologic study in monkeys

PURPOSE: The purpose of this study was to observe, after removing occlusal trauma and conducting plaque control, possible macroscopic and histologic changes in peri-implant tissue that had deteriorated resulting from experimental peri-implantitis, and to investigate the necessity for treatment procedures for peri-implantitis. MATERIALS AND METHODS: Four monkeys (Macaca fascicularis) in good general health were used in this experiment. Three months after the second premolar and the first molar were extracted from the right mandible, 2 IMZ experimental implants were placed in each monkey. After a 3-month osseointegration period, a second surgery was conducted, followed by making an impression for fabrication of the prosthesis. Excessive occlusal height of the prosthesis was adjusted to 250 microm, and the experiment was continued for 8 weeks after placement of the prosthesis. Three models were created: (1) A superstructure with an excessive occlusal height was used for 8 weeks without any brushing (positive control, model P); (2) after the first 4 weeks with a prosthesis with excessive occlusal height and no brushing, the superstructure was removed and not used for the last 4 weeks while brushing was conducted (experimental model, model E); and (3) for 8 weeks, a prosthesis with an appropriate occlusal height was used with brushing (negative control, model N). RESULTS: When these 3 models were compared with each other, macroscopic findings indicated inflammation only in model P. Mobility of implants was not seen in any model. Histopathologic observations revealed a slight difference between model E and model P in terms of the degree of inflammatory cell infiltration in the connective tissue. DISCUSSION: No difference was found in the degree of bone resorption. Partial tearing was observed at the contact region between epithelial tissue and implant surfaces. CONCLUSIONS: (1) The contact between implants and epithelial or connective tissue is fragile; (2) inflammation and occlusion must be controlled more prudently than in the case of natural teeth; and (3) once peri-implantitis has progressed, the control of occlusion and inflammation is probably not sufficient to promote the healing mechanism.     

Premenstrual disappearance of aminopeptidase A in endometrial stromal cells around endometrial spiral arteries/arterioles during the decidual change

Aminopeptidase A (APA, BP-1) is a membrane-bound zinc metallopeptidase that converts angiotensin II (AngII) into AngIII by selectively hydrolyzing the N-terminal aspartyl residue. AngII has been proposed as a candidate for the initial vasoconstrictor of endometrial spiral arteries/arterioles in the preliminary step of menstruation. In the late secretory phase, endometrial stromal cells (ESC) around the blood vessels begin to differentiate into decidual cells, and AngII has been reported to accumulate around such vessels. However, whether there is a concurrent increase in renin or angiotensin-converting enzyme in this area has not been determined. We hypothesized that APA may be involved in the metabolism of AngII in the cycling endometrium. Western blot analysis in the present study demonstrated that a considerable amount of APA was present in the secretory phase endometrium. ESC in the secretory phase showed strong expression of APA by immunohistochemical analysis and of APA mRNA by in situ hybridization. In contrast, both APA mRNA and protein were absent in decidual cells. The enzyme activity and the biosynthesis of [(35)S]methionine-labeled APA significantly decreased during the in vitro decidualization of cultured ESC. These results suggest that the perivascular disappearance of APA is a differentiation-specific change that occurs along with the decidualization, and that the disappearance of APA might accelerate the accumulation of AngII around the vessels.     

Decreased blood flow of the left thalamus during somnolent episodes in a case of recurrent hypersomnia

A 24-year-old male with recurrent hypersomnia associated with decreased blood flow in the thalamus on single photon emission computed tomography (SPECT) is reported. In the hypersomnolent period, the decrease of blood flow in the left thalamus was revealed in the SPECT and slow waves appeared sporadically or sometimes as a burst on the electroencephalogram (EEG). In a phase of insomnia in the convalescent period there were almost no slow waves in the resting EEG but many slow waves appeared on hyperventilation EEG and the power spectrum at this hyperventilation resembled the power spectrum at the resting EEG in the hypersomnolent period. In the remission period there was no abnormal data in these testings.     

Histopathology and tumor markers

Serum tumor markers are useful for detection and diagnosis of cancer. Recent advances in cellular and molecular biology have developed procedures of immunohistochemistry including high sensitivity staining and epitope retrieval. Using the immunohistochemical analyses, we can detect various tumor markers, i.e., not only serum tumor markers (serum protein, carbohydrates), but also cellular skeletons, lymphocyte surface antigens, cytoplasmic markers, oncogene products and cell adhesion molecules. This article focuses on several immunohistochemical tumor markers. Carcinoembryonic antigen(CEA) is one of the good markers of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathway, such as modulation of immune responses, facilitation of intercellular adhesion and cellular migration. CA19-9 (sialyl Le antigen), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Le is a ligand for E-selectin and may play an important role in tumor metastasis. Stromal immunoreactivities of CEA or CA19-9 were correlated with lymph node metastasis and/or vascular invasion. p53 is one of the most important tumor suppressor genes, and the p53 gene product is known to regulate cell growth and proliferation. Mutation of the p53 gene can be detected immunohistochemically as overexpression of its protein in the nucleus. Diffuse p53 immunoreactivity was a histological marker of adenocarcinoma. In conclusion, immunohistochemical tumor markers are useful for histopathological diagnosis and can be prognostic predictors of cancer.