Biomedical subjects
W W Shen
Publications and source records attributed to W W Shen.
Omega-3 fatty acids as a psychotherapeutic agent for a pregnant schizophrenic patient.
Because of the potential adverse events and teratogenesis of antipsychotic drugs, it is important to find a safe and effective treatment for pregnant women with severe mental illness. The membrane hypothesis of schizophrenia provides a rationale to treat symptoms of schizophrenia with omega-3 PUFAs. We report a 30-year-old married woman with chronic schizophrenia, who experienced an episode of acute exacerbation of psychotic symptoms during pregnancy. After entering into an open trial of omega-3 PUFAs monotherapy, she showed a dramatic improvement in both positive and negative symptoms of schizophrenia and a significant increase of omega-3 PUFA composition in erythrocyte membrane. There were no adverse effects in this treatment. Thus, omega-3 PUFAs could be both beneficial and therapeutic to pregnant schizophrenic women.
Polymer-supported lipid bilayers on benzophenone-modified substrates.
Solid-supported lipid membranes are important for their roles in fundamental biophysical research as well as in applications such as biosensors. In our study, lipopolymers containing alkyl side chains were synthesized and a mixture of the lipopolymer and free lipids was preorganized at the air-water interface and then transferred to a solid substrate using the Langmuir-Blodgett technique. A photochemical reaction between a substrate-functionalized benzophenone and C-H bonds on the lipopolymer was used to attach the lipopolymers to the substrate. The final assembly of the membrane was completed by vesicle fusion. Langmuir film experiments at the air-water interface indicate tighter molecular packing for the lipopolymers with 28 mol % alkyl side chains than for the ones with 22 mol %. Atomic force microscopy images point to phase separation of lipopolymers on the substrates due to their dewetting from hydrophobic surfaces. However, a mixture of lipopolymers and free lipids formed a smooth film on the same substrate. After the addition of the second lipid layer on the lipopolymer/free lipid layer, the fluorescence images of the polymer-supported bilayer suggested that the distal lipid layer is homogeneous on the micrometer scale. The relaxation of the fluorescent probe lipids was analyzed after application of an electric field to determine their diffusion coefficient; the distal lipid layer was mobile with an average diffusion coefficient of approximately 0.1 microm(2)/s. Moreover, the immobile fraction of the lipids in the distal layer was estimated to be around 15%.
Magnetic resonance imaging findings in patients with delusional disorder due to diffuse cerebrovascular disease: a report of seven cases.
Delusions associated with cerebrovascular diseases have been sporadically reported. Although both psychiatrists and neurologists attempted to link delusions with anatomical locations of the brain lesion, comorbid psychiatric and neurological disorders make the interpretation of delusions difficult. The purpose of the present paper is to report the clinical features and magnetic resonance imaging (MRI) characteristics in patients with delusional disorder due to diffuse cerebrovascular diseases, and to redefine the concept of 'vascular delusion'. The clinical features and MRI findings were reviewed retrospectively in a series of seven patients with 'delusional disorder due to cerebrovascular disease' as defined in Diagnostic and Statistical Manual of Mental Disorders (DSMIV). The average age of onset is 64. No patient had a prior personal or family history of major psychiatric illness. The illness is presented as acute, subacute or stepwise course. Hypertension was present in all patients. Two had diabetes mellitus, and one had atrial fibrillation. Three had clinical evidence of previous cerebrovascular attacks, only one showed minor neurological deficits. Three had diffuse cortical slow wave in electroencephalogram. No patient had significant cognitive impairment but had multiple cortical and subcortical cerebrovascular lesions in MRI, with white-matter lesions (WML) in bilateral frontal areas. Delusional disorder due to diffuse cerebrovascular change is characterized by late-onset, stepwise course, and comorbid medical and neurological diseases. The results of vascular changes in the present study did not establish a cause-effect relationship and should be considered as multifactorial in pathogenesis. The findings suggested the hypothesis of neural circuit theory. Further studies in larger numbers of patients and newer neuroimaging techniques are needed to expand the knowledge learned from these findings.
The Chinese version of the Davidson Trauma Scale: a practice test for validation.
The Chinese version of the Davidson Trauma Scale (DTS-C) was developed to respond to the need of Chinese-speaking individuals. The DTS is a validated self-rating scale used in the diagnosis of posttraumatic stress disorder (PTSD). The DTS-C is translated from DTS through a two-stage translation. Subjects were drawn from a sample of 210 survivors of the 21 September 1999, Chi-Chi Earthquake. The scale showed good internal consistency (Cronbach's alpha = 0.97) and test-retest reliability (r = 0.88). Concurrent validity was obtained against the clinical diagnostic interview, with a diagnostic accuracy of 0.85 at DTS-C score of 44. It showed that the sensitivity was 0.9, specificity 0.81, positive likelihood ratio 4.74, and negative likelihood ratio 0.12. The recommended stratum-specific likelihood ratios were 0.10 (95% CI: 0.05-0.20) for the score range 0-39, 4 (2.22-7.23) for the score range of 40-59, and 6.14 (3.42-11.02) for the scores above 60. In PTSD diagnosed subjects, the factor structures closely resembled the DSM-IV grouping of PTSD symptoms. The psychometric strength of DTS-C is reliable for its future use, particularly for screening for subjects with possible diagnosis of PTSD.
Lipid abnormalities induced by novel antipsychotic drugs.
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Soy isoflavone supplementation in postmenopausal women. Effects on plasma lipids, antioxidant enzyme activities and bone density.
OBJECTIVE: To investigate isoflavone supplementation on plasma lipids, erythrocyte antioxidant enzyme activities and bone mineral density in postmenopausal women. STUDY DESIGN: Thirty-seven postmenopausal women were given 150 mg/d of isoflavone supplements twice daily for six months. Blood was sampled before and after supplementation, at three and six months. RESULTS: There were no significant differences in plasma total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride concentrations or erythrocyte antioxidant enzyme activities after three and six months of supplementation when compared with the baseline. No significant changes were noted in calcaneus bone mineral density after supplementing isoflavones for six months. CONCLUSION: The antioxidant effect of isoflavones in normal postmenopausal women is not obvious, and supplementation with isoflavone alone may not have a hypocholesterolemic effect. Since the duration of this study was too short with respect to bone density, longer studies are needed to clarify the bone-sparing effect of isoflavone supplementation.
Are omega3 fatty acids beneficial in depression but not mania?
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Functional tethered lipid bilayers.
Our strategy to provide the structural basis for the build-up of functional tethered membranes focuses on three approaches: the first one is based on the pre-organization of a monomolecular layer of a lipopolymer at the water/air interface which is then transferred to a solid support. Prior to deposition, the substrate is coated with a layer of benzophenone-derivatized silane molecules that allow for a stable covalent attachment by photo-cross-linking of some of the monomer units of the lipopolymer to the support. An alternative concept realizes a layer-by-layer deposition of the various structural elements: (1) the attachment layer with the reactive sites for the chemical stabilization; (2) a polymer 'cushion' prepared by adsorption and simultaneous or subsequent partial covalent binding to the reactive sites; and (3) a lipid monolayer transferred from the water/air interface, that contains a certain amount of lipids with reactive headgroups which, upon binding to the polymer tether, act as anchor lipids stabilizing the whole monolayer/cushion-composite. And finally, we build peptide-supported monolayers by first (self-) assembling amino acid sequences of various lengths via a SH-group near their N-terminus onto Au substances and use then their COO(-)-terminus to chemically attach phosphatidyl-ethanolamine lipids to form a stable monolayer of lipid-peptide conjugates. All the individual preparation steps and the various resulting (multi-) layers are characterized by surface plasmon spectroscopy, X-ray and neutron-reflectometry, contact angle measurements, IR spectroscopy, fluorescence microscopy, scanning probe microscopies, as well as, electrochemical techniques. For all tethering systems, the final membranes' architecture is obtained by fusing lipid vesicles onto the lipid monolayer. Proteins can be incorporated by either fusing vesicles that are loaded with the respective receptors, pores, or ion pumps via a reconstitution procedure, or via a transfer directly from a micellar solution to the pre-formed lipid bilayer at the solid support by a dialysis step. Two structural/dynamical features of tethered membranes which are considered to be of particular functional relevance, i.e. the degree of water uptake and, hence, the degree of swelling of the polymer support, as well as the lateral mobility of the lipid molecules in the membrane, are tested by surface plasmon optics and by measurements of the fluorescence recovery after photobleaching (FRAP), respectively. The results confirm that the presented preparation protocols yield fluid bilayers that mimic certain relevant properties of biological membranes. The functional characterization of tethered membranes, which is briefly summarized, is based on various electrochemical techniques, in particular, impedance spectroscopy, cyclic voltammetry, and chronoamperometric studies. The results obtained for reconstituted H(+)-ATPase from chloroplasts and E. coli and for cytochrome oxidase (with and without cytochrome c) confirm the incorporation of the proteins in an active form, thus, opening opportunities for novel sensor formats or offering a completely new model membrane system.
Effects of polyunsaturated fatty acids on psychiatric disorders.
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Is episodic obsessive compulsive disorder bipolar? A report of four cases.
Several reports have noted cases of OCD which were unusual in showing an abrupt remission. We report longitudinal clinical observation of four cases of acute onset OCD without major depression through a variety of treatments. These patients had prominent feelings of shamefulness; compared to patients with typical OCD they were ill for months rather than years and were older. Two had previous episodes of psychiatric illness with full recovery. Full and persistent recovery occurred in response to lithium or an acute course of ECT but not to tricyclic or SSRI antidepressants. The generalizability of these observations is limited by its uncontrolled nature and the small numbers. The courses observed were consistent with episodic OCD as a possible expression of bipolar disorder and consideration of corresponding treatments. This perspective offers a new rationale for reported observations of remissions of acute onset OCD in response to lithium without lithium effectiveness for typical OCD.
The metabolism of atypical antipsychotic drugs: an update.
This paper reviews the current literature describing the metabolism of both multi-receptor clozapine analogue atypical antipsychotic drugs (clozapine, olanzapine, and quetiapine) and serotonin-dopamine antagonist atypical antipsychotic drugs (risperidone, sertindole and ziprasidone), to highlight the significance of those data in the context of clinical practice. The former group of atypical antipsychotic drugs shares a similar tricyclic structural nucleus and are metabolized through three major categorical metabolic pathways--N+-oxidation, N-glucuronidation, and phases 1 and 2 biotransformation with final glucuronidation before renal excretion. Differing in clozapine and olanzapine, quetiapine has incomplete data describing its metabolism. The latter group of atypical antipsychotic drugs has diversified chemical structures and absence of data on N+-oxidation and N-glucuronidation in the literature. But their metabolic routes in phase 1 biotransformation are versatile although current data are far from completion. No apparent significant drug interactions in clinical practice are reported, although QT prolongation is implicated in all those three drugs. None of all six atypical antipsychotic drugs are identified as significant inhibitors or inducers to any co-administered medication. The author suggests the need for more research to address some pertinent clinical issues in the metabolism of those drugs.
Sildenafil in the treatment of female sexual dysfunction induced by selective serotonin reuptake inhibitors.
OBJECTIVE: To review the literature describing female orgasmic disorder and impaired sexual desire disorder by selective serotonin reuptake inhibitors (SSRIs) and their treatment, including the use of sildenafil. STUDY DESIGN: Literature reviews of all available published articles on this topic from 1989 to 1996 were done. This paper also includes a sample case of a 38-year old woman who suffers from fluoxetine-induced arousal and orgasmic disturbance. RESULTS: Treatment approaches include the use of "antidotes," such as cyproheptadine, yohimbine, amantadine, granisetron and ginkgo biloba. This article also reports a case of successful female use of sildenafil, which was released by the Food and Drug Administration in March 1998 for erectile dysfunction in men. CONCLUSION: Sildenafil is beneficial in reversing female sexual dysfunction induced by SSRIs. This paper also discusses sildenafil's action in the background of nitric oxide and cyclic guaninosine monophosphate in penile/clitoral erection.
The need for depot atypical antipsychotics in the U.S.
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Psychotropic drug-induced sexual function disorders: diagnosis, incidence and management.
The human sexual response can be divided into 3 phases: desire (libido), excitement (arousal) and orgasm. The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) classifies sexual disorders into 4 categories: (i) primary; (ii) general medical condition-related; (iii) substance-induced; and (iv) 'not otherwise specified' sexual dysfunctions. Each of the 4 DSM-IV categories has disorders in all 3 sexual phases. Substance-induced sexual dysfunctions are caused by the use of either substances of abuse [alcohol (ethanol), amphetamines, cocaine, opioids or sedatives/hypnotics/anxiolytics], or prescription medications which include psychotropic drugs. Patients with psychiatric difficulties tend to experience more frequent sexual function disturbances. The literature provides more than anecdotal evidence that psychotropic drugs can induce sexual function disorders in the epidemiologically vulnerable population of psychiatric patients. Sexual dysfunctions caused by psychotropic drugs can be divided into 2 groups: sexual inhibition (inhibited desire, inhibited arousal and inhibited orgasm) and increased sexual function disorders (increased sexual desire, priapism and premature ejaculation). The diagnosis of psychotropic drug-induced sexual function disorders is easy if the psychiatrist is sensitive to the existence of these adverse effects. This mostly involves careful history taking, although several questionnaires have been developed for reliable and valid quantification of sexual functioning. Diagnosis is usually established if the sexual function disorders develop when the patient is receiving a psychotropic drug and then disappear when the offending drug is discontinued. The management of psychotropic-drug induced sexual inhibition can be divided into 6 steps: inform the patient about the possibility of sexual inhibition occurring before prescribing a psychotropic agent; wait for remission or tolerance of sexual inhibition; reduce the dosage of the psychotropic drug; switch the medication to one less likely to cause sexual inhibition; if possible, adjust the concomitant nonpsychotropic drugs; and add various pharmacological agents to the existing psychotropic drug to treat the sexual inhibition. Physicians should take sexual histories as a routine practice when prescribing psychotropic drugs. Through careful management and patience on the part of both the patient and the physician, psychotropic drug-induced sexual function disorders can be improved so that the patient's compliance with medication and quality of life can be optimised.
The discoverers of the therapeutic effect of chlorpromazine in psychiatry: qui étaient les vrais premiers praticiens?
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The metabolism of psychoactive drugs: a review of enzymatic biotransformation and inhibition.
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Activation of the tumor necrosis factor-alpha system in the liver in chronic hepatitis B virus infection.
To determine the status of the tumor necrosis factor-alpha (TNFalpha) system in the liver in chronic hepatitis B virus (HBV) infection, hepatic expression of TNFalpha, its two receptors (TNFR-A, TNFR-B), HLA class I antigens (HLA-I), and HBV core antigen (HBcAg) were studied by immunohistochemistry in 24 patients with chronic HBV infection. TNFalpha was detected exclusively in the infiltrating mononuclear cells (MNC) in 19 of 24 patients. The expression of TNFalpha in infiltrating MNC correlated with serum markers of HBV replication and liver histology. TNFR were detected in hepatocytes, sinusoidal cells, and infiltrating MNC. The expression of TNFR correlated with liver histology (p < 0.01) but had no bearing on viral replication. There was a parallel expression of TNFalpha and TNFR (p < 0.01). Hepatocytic expression of HLA-I was increased, and this was related to liver histology but not with TNF alpha nor TNFR. These data indicate that the TNFalpha system is activated in the liver in chronic HBV infection.