Localization of mRNA for inflammatory cytokines in radicular cyst tissue by in situ hybridization, and induction of inflammatory cytokines by human gingival fibroblasts in response to radicular cyst contents

The expression of mRNA encoding the inflammatory cytokines interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) have been examined in radicular cysts by in situ hybridization. Furthermore, the biological activity of the contents of radicular cysts (RCC) has been assayed by adding extracts of RCC to cultured human gingival fibroblasts (HGFs) and analyzing the culture medium for the release of inflammatory cytokines. In the epithelial layer, keratinocytes expressed all cytokine mRNAs examined at various levels. Basal layer cells expressed mRNA for each cytokine. In the subepithelial granulation tissue of the cysts, fibroblasts and macrophages expressed mRNA for IL-6, IL-8, IL-1β and TNF-α mRNA at varying levels; especially clear expression of TNF-α and IL-1β mRNA was detected on macrophages. The infiltrating lymphoid cells, largely composed of T cells and plasma cells, expressed these cytokine mRNAs, especially those encoding IL-6 and IL-8, at various levels. In vitro analysis indicated dose-dependent release of both IL-6 and IL-8 by HGFs in response to RCC. After heating to 100°C for 10 min, RCC almost completely failed to stimulate IL-6 release from HGFs. Furthermore, anti-IL-1β antibody (neutralization test) did not prevent the stimulation of IL-6 release by RCC. Significant amounts of IL-6 and IL-8 were detected in RCC in two cases, and a trace amount of IL-1β was detected in one case. This study demonstrated the wide expression of mRNA encoding inflammatory cytokines in radicular cyst tissues, and RCC itself was capable of stimulating 1L-6 and 1L-8 production from HGFs.     

Two cases of psychotic state following normal-dose benzodiazepine withdrawal

We report two cases of severe withdrawal symptoms after abrupt discontinuation of a long-term normal-dose benzodiazepines (BZD) administration. Case 1, a 61-year-old man, suffered from delirium on the 7th day after abrupt discontinuation of nitrazepam, 10 mg/day. Case 2, a 49-year-old woman, suffered from auditory hallucination on the 4th day and visual cognitive disorder on the 5th day after abrupt discontinuation of nitrazepam, 5 mg/day, and triazolam, 0.5 mg/day. A withdrawal syndrome after discontinuation of normal-dose BZD is uncommon, and a psychotic withdrawal reaction is even more uncommon. We show how a continuous administration of BZD for a period of longer than 6 months and the presence of severe insomnia are risk factors predictive of a psychotic reaction. We also explain the predictive method used to determine the onset time of such a severe state. In the case of a psychotic state, we recommend intravenous diazepam injection. To prevent withdrawal reaction, we also recommend a gradual reduction after administration of normal-dose BZD.     

The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice.

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.     

Change in body image of patients with alcohol dependence during treatment process]

In order to find useful information for the establishment of new treatment method to alcohol dependence, we investigated the change of the body image of patients with alcohol dependence before and after the treatment. HABIT (Haga Body Image Test), a questionnaire about body image developed in department of psychiatry in Kyoto Prefectural University of Medicine, was used to examine the change of body image between pre- and post-3-month conventional treatment program in 46 patients with alcohol dependence hospitalized into special institutions for treatment of the disease in Kyoto. Patients with poor outcome of the treatment showed improvement of body image on visceral function, feeling of appetite and outward appearance, while patients with good outcome indicated no significant change in these aspects. This finding likely suggests that the treatment would result in good outcome in patients having stable feeling of physical health, and the cognitive treatment approach about these aspects of body image should be performed on the patients with poor treatment outcome. On the other hand, the body image about motor function showed significantly higher score in the patients approach for the patients with poor outcome to become aware of their physical activity would be effective.     

Effect of 5-lipoxygenase inhibitor on experimental delayed cerebral vasospasm

Experimental delayed cerebral vasospasm was produced in canine basilar arteries by 2 successive injections, 2 days apart, of fresh autogenous arterial blood into the cisterna magna. When angiographic evidence of delayed vasospasm was confirmed 7 days after the initial intracisternal blood injection, a selective inhibitor of 5-lipoxygenase, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), was infused intravenously at 6.5 X 10(-4) mg/kg/min for 2 hours. However, angiographic evidence of delayed vasospasm was not reversed, and mean regional cerebral blood flow was not significantly increased. In other studies, oral doses of AA-861 at 100 mg/kg/day were given twice a day for 7 days after the initial intracisternal blood injection. In the treated group, angiographic evidence of delayed vasospasm was significantly reduced, and the contractile property of excised basilar arteries in response to vasoconstrictor agents was significantly improved. It is suggested that leukotrienes, 5-lipoxygenase products of arachidonic acid, might be important etiologic factors responsible for the development of delayed vasospasm and that AA-861 would have a therapeutic effect not on the reduction of delayed vasospasm once developed but on the prevention of the development of delayed vasospasm.     

Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome.

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.