Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness

BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.     

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.     

Synthesized TGF-beta s in RPE regulates cellular proliferation

Retinal pigment epithelial (RPE) cells transdifferentiate in culture, a transition which is accompanied by a shift in biological activity. The present study investigates whether transforming growth factor (TGF)-beta has the same effects on morphologically transformed RPE cells that it has on primary RPE cells. It also evaluates the autocrine and paracrine activities of TGF-beta s synthesized by RPE cells as well as the anti-TGF-beta effect of mannose-6-phosphate (M-6-P). RPE cells were subcultured at the sixth passage to induce morphological change. The effect of second passaged RPE-conditioned medium (CM) on DNA synthesis was evaluated by the incorporation of 3H-thymidine in rabbit subconjunctival fibroblasts (SCFs) and primary RPE cells. The presence of TGF-beta in RPE-CM was determined using immunoblotting analysis. And the inhibitory effect of M-6-P on cell proliferation mediated by RPE-CM was also analyzed using 3H-thymidine incorporation into DNA. TGF-beta 1, TGF-beta 2, and TGF-beta 3 inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, but the spindle-shaped sixth passaged RPE cells were not inhibited by these growth factors. The medium conditioned by RPE cells stimulated the proliferation of SCFs and inhibited the proliferation of primary RPE cells, in a manner similar to TGF-beta. When this medium was precipitated with either anti-TGF-beta 1, anti-TGF-beta 2, or anti-TGF-beta 3 antibodies, all three TGF-beta s, with an apparent molecular size of 25 kDa, were detected. Mannose-6-phosphate significantly blocked the effect of RPE-CM on cell proliferation. These findings indicate that RPE cells produce biologically functional TGF-beta s and that M-6-P can block the inhibitory effect of RPE-CM on cell proliferation.     

Acyl-CoA:Cholesterol Acyltransferase Inhibitory Activity of Lignans Isolated from Schizandra, Machilus and Magnolia Species

Fifteen lignans were isolated from the fruits of SCHIZANDRA CHINENSIS, the leaves of MACHILUS THUNBERGII, and the flower buds of MAGNOLIA DENUDATA. They were identified as gomisins, schizandrin, wuweizisu, schizantherin, licarins, and machilin, which inhibited rat liver ACAT with IC (50) values of 25-200 microM. Comisin N is the most potent inhibitor with IC (50) value of 25 microM in these lignans.     

Synthesis and analgesic and anti-inflammatory activities of 1,2-benzothiazine derivatives

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/anti-inflammatory efficacy and their effects on gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent analgesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.     

Metabolism-based anticancer drug design

Many conventional anticancer drugs display relatively poor selectivity for neoplastic cells, in particular for solid tumors. Furthermore, expression or development of drug resistance, increased glutathione transferases as well as enhanced DNA repair decrease the efficacy of these drugs. Research efforts continue to overcome these problems by understanding these mechanisms and by developing more effective anticancer drugs. Cyclophosphamide is one of the most widely used alkylating anticancer agents. Because of its unique activation mechanism, numerous bioreversible prodrugs of phosphoramide mustard, the active species of cyclophosphamide, have been investigated in an attempt to improve the therapeutic index. Solid tumors are particularly resistant to radiation and chemotherapy. There has been considerable interest in designing drugs selective for hypoxic environments prevalent in solid tumors. Much of the work had been centered on nitroheterocyclics that utilize nitroreductase enzyme systems for their activation. In this article, recent developments of anticancer prodrug design are described with a particular emphasis on exploitation of selective metabolic processes for their activation.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Two new lignans fromLindera obtusiloba blume

Two new furanolignans (3, 5), together with three known lignans (1, 2, 4), were isolated from the stem of Lindera obtusiloba (Lauraceae). The structures of the compounds were determined as actifolin (1), pluviatilol (2), 5,6-dihydroxymatairesinol (3), (+)-syringaresinol (4), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (5) on the basis of physicochemical and spectroscopic evidences. Compounds 1, 2, 3, and 5 showed cytotoxicity against a small panel of human tumor cell lines with ED50 values of 3.40 to approximately 19.27 microg/ml.     

Primary intramedullary spinal cord primitive neuroectodermal tumor with intracranial seeding in an infant

Primary spinal cord primitive neuroectodermal tumor (PNET) is a rare entity. In all, 13 cases have been reported in the literature, including 3 with intracranial seeding. A 3-month-old girl with involvement of the spinal cord below the mid-thoracic level is described. The brain MRI revealed findings indicative of seeding along the intracranial subarachnoid space. Biopsy, duraplasty and removal of laminotomy flap were done. In spite of a good response to the first cycle of postoperative 8-drugs-in-a-day chemotherapy, further treatment was refused. She died 21 days after the onset of leg weakness, which reveals the rapid progression of untreated cases. To our knowledge, this is the first case of spinal cord PNET with parenchymal involvement that has been described in an infant.