Effects of antidepressants on plasma metabolites of nitric oxide in major depressive disorder: Comparison between milnacipran and paroxetine

Depression is a risk factor for coronary heart disease (CHD). It has been demonstrated that there is a potential role of nitric oxide (NO) in the relationship between depression and CHD risk as well as an effect of antidepressants on NO production. This study included 40 in- or outpatients in our university hospital who met the DSM-IV-TR criteria for major depressive disorder (M/F: 15/25, age: 47 ± 19 years) and 30 age- and sex-matched healthy controls (M/F: 10/20, age: 45 ± 15 years), and also examined the effects of the antidepressants on the plasma NOx levels in depressed patients. The baseline plasma NOx levels were significantly lower in the whole depressed group than in the control group (p < 0.01). Treatment with milnacipran, but not paroxetine, significantly increased the plasma NOx levels by 4 and 8 weeks. These results suggest that decreased plasma NOx levels might be partially associated with the pathophysiology of depression, and that treatment with milnacipran, a serotonin noradrenaline reuptake inhibitor, might increase those levels in depressed patients.     

Induction of high titers of anti-IgE by immunization of inbred mice with syngeneic IgE

We have generated high titers (up to 1 mg/ml) of antibodies to isotypic determinants of IgE by immunization of A/J mice with syngeneic monoclonal IgE conjugated to keyhole limpet hemocyanin. As much as 3 mg of anti-idiotypic antibodies per ml was induced at the same time. In contrast to conventional rheumatoid factors, the anti-isotypic antibodies are of moderately high affinity (10(7)-10(8) M-1). Assays of the anti-IgE antisera indicated the presence of IgE, both free and in the form of immune complexes; the latter values are minimum estimates owing to masking of isotypic determinants. Regulatory effects of these high titers of anti-IgE can now be investigated. Such studies will be facilitated by the availability of monoclonal, syngeneic anti-IgE antibodies.     

Helicobacter pylori-infected Japanese monkeys

Conclusion It is possible to establish persistentH. pylori infection in the gastric mucosa of Japanese monkeys and create acute and chronic gastritis similar to that found in humans; persistent infection causes atrophic changes in the gastric mucosa. Japanese monkeys, which age approximately flve times faster than humans, provide a valuable model for investigating the long-term effects ofH. pylori infection on the gastric mucosa and for the study of stages in the development of gastric cancer. H. pylori produces gastritis resulting in both local inflammation and a systemic immune response. Genes have been isolated that code for cytotoxic proteins such as CagA, VacA, and for heat-shock protein. A number of points remain unresolved concerning the pathology ofH. pylori infection, known to be closely related to the recurrence of peptic ulcers. Routes of infection are fecaloral and oral-oral, and humans can be infected from pets.⁵³ Gastroendoscopy can be a source of nosocomial infections. The natural habitat ofH. pylori in humans is limited almost exclusively to the surface layer of the gastric mucosa; it is rarely found in other locations. In the future, we should develop chemotherapeutic methods for curingH. pylori infections and a vaccine for their prevention. The present study was conducted in accordance with Oita Medical University guidelines for animal experimentation.     

Review of pharmacological efficacies and side effects of antidepressants

We reviewed the pharmacological efficacies and side effects of antidepressants. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) are most popularly prescribed for anxiety disorders as well as mild or moderate depression. These drugs have less orthostatic, cognitive, cardiovascular, and anticholinergic side effects. Tricyclic antidepressants are still important for treating severe depression, and mianserin and trazodone are useful for treating delirium. Clinicians should select antidepressants considering their pharmacologic profiles and avoiding adverse effects.     

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura in a woman with situs inversus: Report of a Case

A 51-year-old woman with previously diagnosed situs inversus (SI) totalis was admitted to our hospital with nasal bleeding. Blood tests showed severe thrombocytopenia, with a platelet count of 1.9 × 104/mm³, and idiopathic thrombocytopenic purpura (ITP) was diagnosed. She was refractory to medical treatment, so we performed laparoscopic splenectomy (LS). The mirrorimage anatomy made the procedure difficult for the right-handed surgeon, so we modified the technique to enable it to be performed via an anterior approach through the subxiphoid area using the right hand, with an ultrasonic dissecting device and an endostapling device. The operation was performed safely, the patient recovered uneventfully, and her platelet count normalized. To our knowledge, there has been no other report of LS in a patient with SI; however, it can be performed safely with careful management.     

Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis

Recent studies suggest that histone deacetylase (HDAC) inhibitors may therapeutically prevent cartilage degradation in osteoarthritis (OA). Matrix metalloproteinase-13 (MMP-13) plays an important role in the pathogenesis of this disease and in the present study we investigated the correlation between HDACs and MMP-13. Comparing the expression of different HDACs in cartilage from OA patients and healthy donors, HDAC7 showed a significant elevation in cartilage from OA patients. High level of HDAC7 expression in OA cartilage was also confirmed by immunohistochemistry. Knockdown of HDAC7 by small interference RNA (siRNA) in SW1353 human chondrosarcoma cells strongly suppressed interleukin (IL)-1-dependent and independent induction of MMP-13 gene expression. In conclusion, elevated HDAC7 expression in human OA may contribute to cartilage degradation via promoting MMP-13 gene expression, suggesting the critical role of MMP-13 in OA pathogenesis.     

Medulloblastoma with myogenic differentiation showing double immunopositivity for synaptophysin and myoglobin

Reported herein is a case of medulloblastoma with myogenic differentiation in a 3-year-old girl who died 1 year after appearance of clinical signs. Magnetic resonance imaging indicated a mass lesion in the cerebellar vermis. She underwent total resection of the tumor, followed by chemotherapy and radiotherapy in the brain and spinal cord. The resected specimen mainly consisted of densely packed cells with round-to-oval highly chromatic nuclei surrounded by scanty cytoplasm and focally of long spindle-shaped cells with elongated nuclei and eosinophilic cytoplasm showing discernible cross-striations. Immunohistochemistry indicated partial expression of synaptophysin in the former area and focal expression of desmin in the latter area. The diagnosis was medulloblastoma with myogenic differentiation, also known as medullomyoblastoma. Autopsy indicated disseminated proliferation of immature neuroglial cells with highly chromatic nuclei and scanty cytoplasm showing partial expression of synaptophysin, neurofilaments, and GFAP, and focal proliferation of round-to-oval immature cells showing immunoreactivity of myoglobin. The tumor cells had large nuclei, frequent mitoses, apoptoses, nuclear molding, and cell wrapping, indicating moderate anaplasia. Their Ki-67 labeling index was 54%. In addition, some tumor cells had double immunopositivity for synaptophysin or neurofilament and myoglobin, suggesting that the neuroectodermal cells may undergo differentiation into rhabdomyoblasts.     

Treatment with risperidone for 4 weeks increased plasma 3-methoxy-4-hydroxypnenylglycol (MHPG) levels, but did not alter plasma brain-derived neurotrophic factor (BDNF) levels in schizophrenic patients

In the present study, we investigated the effects of risperidone treatment for 4 weeks on plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain-derived neurotrophic factor (BDNF) in 89 schizophrenic patients. We also compared the plasma levels of BDNF and MHPG between the schizophrenic group and 103 sex-and age-matched normal controls. In addition, we investigated the effects of two SNPs of the noradrenaline transporter (NAT) gene on plasma levels of MHPG, BDNF, and clinical improvement. The mean dose of risperidone was 3.8+/-1.4 mg/day. We demonstrated that treatment with risperidone increased plasma MHPG levels, and this increase was associated with an improvement of the negative symptoms of schizophrenia. In contrast, plasma BDNF did not change after 4 weeks of risperidone treatment, and the two SNPs in NAT did not influence the response to risperidone treatment or plasma MHPG and BDNF levels. These results suggest that the enhancement of noradrenergic neurons by risperidone, which occurs independently of the two SNPs of NAT, plays a role in the clinical efficacy of the drug.     

The detection rates and tumor clinical/pathological stages of whole-body FDG-PET cancer screening

OBJECTIVE: FDG-PET has been used for cancer screening, mainly in East-Asia, and cancers are found not infrequently. However, their stages have not been clarified. We examined the detection rates of various cancers using whole-body PET for the screening of cancers in asymptomatic individuals, focusing on their clinical and pathological stages. METHODS: Whole-body PET was obtained as a part of our cancer screening program among 3,426 healthy subjects. All subjects participated in a course of PET examination in conjunction with conventional examinations including a medical questionnaire, tumor markers, immunological fecal occult blood test, neck and abdominal ultrasonography and whole body computed tomography. A diagnosis and staging was obtained by an analysis of the pathological findings or by an analysis of the clinical follow-up data. RESULTS: Malignant tumors were discovered in 65 lesions found in 3,426 participants (1.90%). The PET findings were true-positive in 46 of the 65 cancer cases. The cancers were found in the following organs: the colon 14; thyroid gland 10; stomach 7; lung 5; liver 3; breast 2; and one each in the kidney, gallbladder, esophagus, pancreas and retroperitoneum. The stages were as follows: stage 0 5, stage I 17, stage II 10, stage III 7, and stage IV 6. One was an unknown primary. There were 19 false-negative findings (0.6%) on PET. Six cancers (0.18%) were missed in our screening program. CONCLUSIONS: PET imaging has the potential to detect a wide variety of cancers at potentially curative stages. Most PET-negative cancers are early stage cancers, and thus can be detected using other conventional examinations such as endoscopy.