bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Calcium Channel Blockers, Nifedipine and Benidipine, on Death of Cultured Mouse Mesangi al Cells
Authors: Shike Toshihide , Tashiro Kyoichi , Gohda Tomohito , Funabiki Kazuhiko , Shirato Isao , Tomino Yasuhiko
Published: April 2003

We examined the effects of the short–acting calcium channel blocker (CCB) nifedipine and the long–acting CCB benidipine on the death of mouse cultured mesangial cells induced by tumor necrosis factor alpha (TNF–α) and/or cycloheximide (CHX). Cell death was evaluated by a morphological study using semithin sections. The dead cells were divided into three types, i.e., apoptotic cells (type 1), necrotic cells (type 3) and other types of dead cells, the so–called ‘secondary necrotic cells‘ or ‘postapoptotic necrotic cells’ (type 2). In the morphological study with semithin sections, cells in the presence of TNF–α or CHX and nifedipine or benidipine showed low percentages of all dead cell types with 24 h incubation. Both nifedipine and benidipine have protective effects against TNF–α or CHX. It is postulated that CCB might inhibit the apoptotic or necrotic processes by TNF–α or CHX with 24 h incubation. With 36 h incubation, CCB increased the percentages of all types of dead cells except for treatment with 1×10–5 M benidipine and CHX. It appears that these cell–protective effects might be decreased after treatment with TNF–α or CHX and CCB for 36 h. In conclusion, the short–acting CCB nifedipine and the long–acting CCB benidipine have protective effects on mouse cultured mesangial cells against TNF–α or CHX . However, nifedipine and benidipine did not inhibit specific types of cell death using semithin sections in this study.
Role of Nitric Oxide in the Autoregulation of Renal Blood Flow and Glomerular Filtration Rate in Aging Spontaneously Hypertensive Rats
Authors: Kvam Fred I. , Ofstad Jarle , Iversen Bjarne M.
Published: April 2003

Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is well maintained in the spontaneously hypertensive rat (SHR). In old SHR, the RBF autoregulation is dependent upon prostaglandins as well as the sympathetic nervous system. The purpose of this study was to examine the role of nitric oxide (NO) in the autoregulation of RBF and GFR in aging SHR (70 weeks) as compared with young SHR (10 weeks) and age–matched Wistar–Kyoto (WKY) rats using NO synthase (NOS) inhibition that has a minimal effect on the RBF. The autoregulation of RBF was examined using an adjustable aortic clamp above the renal arteries and an ultrasound Doppler flow probe on the left renal artery. The lower pressure limit of RBF autoregulation was examined before and after infusion of the NOS inhibitor NG–monometyl–L–arginine (L–NMMA; 500 μg·kg–1·min–1). Separate groups were given a coinfusion of L–NMMA and L–arginine (5 mg·kg–1·min–1) or Ringer solution. The autoregulation of the GFR was studied in continuously infused animals using the 125I–iothalamate clearance. Measurements of the GFR were done at control blood pressure, at a renal arterial pressure 10 mmHg above the lower pressure limit of RBF autoregulation and at a renal arterial pressure of about 60–65 mmHg. In both SHR and WKY rats, infusion of L–NMMA increased the mean arterial blood pressure, and the RBF decreased in young SHR, while the RBF was unchanged in the WKY groups and aged SHR. The autoregulation of RBF was maintained in all animals. The GFR was unchanged in all groups after infusion of L–NMMA, and the autoregulation of GFR was well maintained in all groups except in the 70–week–old SHR. In these animals, the fractional compensation of GFR decreased from 0.95 to ∼ 0 after infusion of L–NMMA, indicating that autoregulation of the GFR was lost during NOS inhibition. Coinfusion of L–NMMA and L–arginine normalized the GFR autoregulation in this group. The results indicate that in hypertensive rats with renal hypertensive damage, the GFR autoregulation is strongly NO dependent, as doses of L–NMMA that do not interfere with the RBF have an effect on the GFR autoregulation. As the GFR was unchanged during L–NMMA infusion, these observations suggest that postglomerular contraction during NOS inhibition may be involved in the regulation of GFR in 70–week–old SHR.
Risk Factors for Endometriosis: Menstrual and Life-Style Characteristics
Authors: Waller Kathleen G. , Shaw Robert W.
Published: April 2003

Objective: To investigate possible risk factors for the development of endometriosis. Study Design: A case control study of 147 women with a new diagnosis of endometriosis, and 131 normal controls recruited from well women clinics. Controls were screened for the presence of symptoms of endometriosis. The setting was two tertiary referral centres for endometriosis and surrounding community clinics. Results: There was a significant positive association between double protection at menses and endometriosis (OR = 3.1), and a significant trend for cases to have shorter menstrual cycles. There was a greatly increased risk of endometriosis in those with an affected first-degree relative. Conclusions: Menstrual patterns producing a greater number of bleeding days are shown to be associated with a greater risk of endometriosis.
‘Secondary’ Hughes (Antiphospholipid) Syndrome in Unusual Clinical Settings
Authors: Mourou M. , Abdella N. , Qurttom M.A.F. , Malaviya A.N.
Published: April 2003

Objectives and Importance: Hughes (antiphospholipid) syndrome is mainly seen among patients with systemic lupus erythematosus (SLE). This has been called ‘secondary’ in contrast to ‘primary’ where no obvious underlying disease is detectable. The objective of this report is to highlight the fact that Hughes syndrome can, however, also occur in association with other underlying diseases or, as a result of certain therapies. The importance of this report is in emphasizing the fact that secondary Hughes syndrome can occur in several settings other than SLE or SLE-like illness. Clinical Presentation: Here we describe 3 patients with clinical features of arterial or venous thromboses associated with significant levels of anticardiolipin antibodies. Their underlying diseases were, however, neither SLE nor ‘SLE-like’ illness. One of them had been on oral contraceptive pills, the 2nd patient had Behçet’s disease and the 3rd patient had liver carcinoma associated with hepatitis C infection. Thus, these patients could be classified under the category of ‘secondary’ Hughes (antiphospholipid) syndrome. Conclusion: The 1st patient recovered and remained well during a 12-month follow-up after the discontinuation of oral contraceptive pills combined with long-term low-dose aspirin therapy. The last patient remained normal in the 12-month follow-up period on long-term warfarin treatment at a dose adequate to keep the international normalized ratio above 3. The 2nd patient died of uncontrollable hypercoagulability associated with advanced extensive malignancy and related complications. It is, therefore, recommended that the possibility of Hughes syndrome be considered in any clinical situation characterized with hypercoagulable state. If proven, long-term anticoagulation may benefit the patient.
Epidemic Neuropathy in Cuba: A Public Health Problem Related to the Cuban Democracy Act of the United States
Authors: Román Gustavo C.
Published: April 2003

In 1992, the USA embargo on Cuba was tightened through the passage of the Cuban Democracy Act (CDA) that explicitly restricts food and medical supplies. The embargo has contributed to cause a number of public health problems in Cuba including: (1) an epidemic of more than 50,000 cases of optic and peripheral neuropathies in 1992–1993, resulting from dietary deficiency; (2) an epidemic of esophageal stenoses in toddlers who inadvertently drank liquid lye as a result of a soap shortage for which liquid lye was substituted; (3) an outbreak of Guillain-Barré syndrome in Havana, in June and July 1994, resulting from water contamination due to lack of chemicals for water treatment to eliminate Campylobacter sp.; (4) outbreaks of self-inflicted disease and injuries caused by rioting among Cubans detained at the US Naval base at Guantánamo Bay, and (5) a decline in medical practice standards and public health indicators in Cuba resulting from the enactment of the CDA, documented by the American Public Health Association in 1993 and confirmed in March 1997 by the American Association for World Health. Despite this evidence, the Cuban embargo remains a politically sensitive subject in the USA, resistant to public health concerns, as evidenced by the recent passage of the Helms-Burton Act. The public health effects of the CDA need to be reviewed with possible revocation or at least modification.
Factors Associated with the Time of Presentation of Acute Stroke Patients in an Israeli Community Hospital
Authors: Streifler Jonathan Y. , Davidovitch Simcha , Sendovski Uri
Published: April 2003

Recently it has been shown that effective treatment for acute stroke must be initiated within 3–6 h from onset. In order to determine whether this is feasible and the reasons for delayed presentation, a prospective study was conducted in a community hospital in Israel. Of the 216 patients enrolled, 18% arrived at the hospital within 90 min of stroke onset and 54% presented within 6 h. Important factors associated with early presentation included major stroke (as compared to mild stroke) and time of day of onset (afternoon as compared with nighttime). Further efforts must be made to shorten the delay in hospital arrival of acute stroke patients.
Alcohol, Coronary Heart Disease and Stroke: An Examination of the J-Shaped Curve
Authors: Wannamethee S. Goya , Shaper A. Gerald
Published: April 2003

The consistent findings of higher risk of coronary heart disease (CHD) and total mortality in non-drinkers compared to light to moderate drinking has been interpretated as showing that light or moderate drinking is beneficial to health. Non-drinkers, both ex-drinkers and lifelong teetotallers, have an increased prevalence of conditions likely to increase morbidity and mortality compared with occasional or light drinkers. In addition, regular light drinkers tend to have characteristics extremely advantageous to health. Whilst there is considerable evidence that alcohol intake at some level has a beneficial effect on CHD, the degree of protection claimed is almost certainly exaggerated by comparison with an inappropriate control group and by the limited adjustment procedures used to take into account the differing characteristics of the various alcohol intake groups. The benefit of light to moderate drinking for stroke and all-cause mortality is less convincing than the benefit for CHD. If occasional drinkers are used as a baseline, no benefit is seen for stroke or all-cause mortality in regular or light drinkers and all-cause mortality increases progressively from levels of 2 drinks a day. Non-drinkers or lifelong abstainers are unsuitable as a baseline group in studies of the effects of alcohol on morbidity and mortality. The public health message should emphasise the potential harm of heavier drinking rather than concentrating on the possible benefits of light drinking.
The Epidemiology of Parkinson’s Disease in an Australian Population
Authors: McCann Sally J. , LeCouteur David G. , Green Adele C. , Brayne Carol , Johnson Anthony G. , Chan Daniel , McManus Michael E. , Pond Susan M.
Published: April 2003

A prevalence study of Parkinson’s disease (PD) was conducted in the rural town of Nambour, Australia. There were 5 cases of PD in a study population of 1207, yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53–775). We performed a separate case-control study involving 224 patients with PD and 310 controls from South East Queensland and Central West New South Wales, to determine which factors increase the risk for PD in Australia. A positive family history of PD was the strongest risk factor for the development of the disease (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well water ingestion were inversely correlated with the development of PD. There was no significant difference between patients and controls for exposure to herbicides and pesticides, head injury, smoking or depression. The high prevalence of PD in Nambour may be explained by rural residency. However, the most significant risk factor for PD was a positive family hisotry. This demonstrates the need for improved understanding of the genetic nature of the disease.
Social Readjustment and Ischemic Stroke: Lack of an Association in a Multiethnic Population
Authors: Abel Gregory A. , Chen Xun , Boden-Albala Bernadette , Sacco RalphL.
Published: April 2003

Clinical experience has suggested that stressful life events and ongoing stressful illness, collectively termed ‘social readjustment’, may precipitate stroke. We investigated the association between a simple in-office evaluation of such stressors and stroke in an urban, multiethnic study population. Cases were patients from the Northern Manhattan Stroke Study with first ischemic stroke; controls were derived through random digit dialing with n:m matching for age, gender, and race-ethnicity. Social readjustment was measured through in-person interview using Amster and Krauss’ Geriatric Social Readjustment Rating Scale (GSRRS), a one-time, 35-item, checklist type weighted questionnaire of stressful life events occurring in the previous 6 months. Conditional logistic regression was used to analyze the GSRRS and its quartiles as well as stressful events subgroups, adjusting for education, hypertension, cardiac disease, diabetes, and number of weekly visits as a measure of socialization. Six hundred and fifty-five cases of ischemic stroke and 1,087 controls were utilized. The mean age of the cases was 69.8 years, with 55.4% women, 51.0% Hispanics, 28.4% blacks, and 19.1% whites. GSRRS scores ranged from 0 to 812; the mean score was 205.5 for the cases and 206.2 for the controls. The analysis showed no association between stroke and a 20-point increase on the GSRRS (OR = 1.01, 95% CI = 0.99–1.01). There was also no effect for the second, third or highest versus lowest quartile. No association was found in age, gender or race-ethnic subgroups, or when analyzing negative events, severely threatening events, or ongoing stressful illnesses separately. While this study does not preclude social readjustment as a stroke risk factor, it suggests that the one-time assessment often done in the medical office setting has little relevance for stroke prevention planning.
Validity of Telephone Interview Data for Vascular Disease Risk Factors in a Racially Mixed Urban Community: The Northern Manhattan Stroke Study
Authors: Kargman Douglas E. , Sacco Ralph L. , Boden-Albala Bernadette , Paik Myunghee C. , Hauser W. Allen , Shea Steven
Published: April 2003

The aims of our study were to assess the validity and reliability of a telephone survey instrument designed to measure vascular disease risk factors and to assess whether these measurements were influenced by age, gender, race/ethnicity, or other sociodemographic variables. Subjects were sampled and interviewed using random digit dialing methodology from the multiethnic community of northern Manhattan. For the validity study, 261 consecutive subjects were clinically assessed in-person within 60 days of the telephone interview. A retest reliability study of the telephone interview was conducted in 92 randomly selected subjects within 30 days of the initial interview. The telephone interview instrument had a sensitivity of more than 55% and a specificity of 74% or greater for various vascular disease risk factors. Sensitivity, specificity, and positive predictive value did not vary significantly or systematically among whites, blacks, and Hispanics, but subjects with access to health care were more likely to provide valid data. The reliability substudy indicated a good reliability for the telephone interview. These results support the validity of telephone interviews for estimating the prevalence of vascular risk factors in urban populations.
Temporal Trend and Factors Associated with Delayed Hospital Admission of Stroke Patients
Authors: Casetta Ilaria , Granieri Enrico , Gilli Giuseppe , Lauria Giuseppe , Tola Maria Rosaria , Paolino Ezio
Published: April 2003

The effectiveness of stroke treatment depends on the time interval between onset of symptoms and admission to hospital. The purpose of our investigation was to assess, over a 10-year period, the mean delay in admission to hospital in stroke patients to determine factors which might be associated with this delay, to define the putative number of patients available for accrual in clinical trials, and to identify strategies aimed at decreasing the time to admission. We collected data on all stroke patients consecutively admitted to our clinic from 1986 to 1995. The following variables were investigated: age, sex, educational and occupational level, home accommodation, family and personal history of vascular disease or factors known to affect the risk of vascular disease, and type and severity of stroke. The individual and independent contribution of these variables was assessed by univariate and multivariate analysis. The accurate time of stroke onset was established for 760 patients. Of these, 24.7% were admitted within 1 h from the onset of symptoms, 41% within 2 h, 54% within 4 h and 72.5% within 12 h. The mean delay was 21 ± 2 h (SE) and the median was 3.5 h. Acute onset of neurological deficits, stroke severity and family history of cerebrovascular disease were associated with earlier presentation. According to the current guidelines for thrombolytic therapy, only 16% of the patients could have been included in a clinical trial. This study suggests that despite a relatively short time to hospital admission in most patients and an altered help-seeking behavior over time, many stroke patients did not present early enough to be recruited for clinical trials or to benefit from new treatments. The majority of patients with timely presentation were not eligible for acute treatment, or were subjects with severe stroke for whom caution is advised before initiating thrombolytic therapy. It has been suggested that the patient’s indecision to seek medical help is the most important reason for a delayed hospital admission of stroke patients. These results underscore the importance of interventions aimed at reducing the delay in stroke treatment induced by patients who are unaware of the decisive role of the time of treatment induction. The finding that earliest admissions for stroke comprised patients with a previous history of cerebrovascular disease suggests that an education campaign might highlight the importance of an early admission.
Alcohol, Stroke and Coronary Heart Disease
Authors: Puddey I.B. , Croft K.D.
Published: April 2003

Anti-oxidant effects of polyphenolic flavonoid compounds found in alcoholic beverages, especially red wine, have been proposed to mediate, at least in part, protective effects of regular light-to-moderate alcohol use against stroke and coronary artery disease. The proposed mechanism is through the quenching of free radicals decreasing the oxidative modification of low-density lipoprotein cholesterol particles and hence reducing their atherogenicity. In this review, the extent and limitations of the evidence in support of such a hypothesis are outlined. In particular, the paucity of epidemiological evidence linking dietary flavonoids to stroke and coronary artery disease is highlighted. The competing notion that alcohol itself has direct and indirect pro-oxidant and pro-atherogenic effects is canvassed, and the limitations of the in vitro rather than in vivo nature of much of the evidence linking red wine polyphenolics to reduced lipid peroxidation and other relevant biological effects is discussed. Within this framework of current epidemiological evidence together with the results of basic laboratory studies, the conclusion at present is that while we may continue to speculate that there are anti-oxidants and pro-oxidants in alcoholic beverages that influence the development of atherosclerotic cardiovascular disease, this cannot yet be considered as an established scientific fact.
The Mississippi Stroke Education Consortium: A State-Based Template to Promote Stroke Awareness, Prevention and Emergency Treatment
Authors: Gordon David Lee
Published: April 2003

The Mississippi Stroke Education Consortium (MSEC) is a state-based volunteer advocacy group founded in 1994 consisting of specific policy-setting organizations dedicated to decreasing the impact of stroke on Mississippi’s inhabitants through a continuous educational process targeting both laypersons and healthcare professionals.
The Cladribine Trial in Secondary Progressive Multiple Sclerosis: A Reanalysis
Authors: Beutler Ernest , Koziol James A.
Published: April 2003

//8RIn a recent communication, Goodin [1] analyzes several clinical trials to point out serious flaws in both design and interpretation that may invalidate the conclusions that are drawn. We agree with Goodin [1] that the design of clinical studies, particularly of a disease as complex as multiple sclerosis, is extremely difficult. Indeed, a perfectly designed and executed clinical study is a goal that is never achieved because of the problems inherent in providing care to patients while attempting to evaluate a therapeutic modality. Specifically, in the study of multiple sclerosis, none of the clinical trials of the use of interferons could be considered fully satisfactory: blinding is actually impossible because of the symptoms that are experienced by patients when they receive active drug but not when they receive placebo. It is quite fashionable and not at all difficult to find problems in the conduct of clinical studies; indeed, if all clinical studies with flaws were discarded, there would be no acceptable clinical studies.
Seasonal Birth Patterns of Neurological Disorders
Authors: Torrey E. Fuller , Miller Judy , Rawlings Robert , Yolken Robert H.
Published: April 2003

Existing seasonal birth studies were reviewed for multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), epilepsy, cerebral palsy, congenital malformations of the central nervous system and mental retardation. Epilepsy appears to have the most consistent pattern, with an excess of births in winter and a deficit in September. MS, ALS and possibly Parkinson’s disease appear to have an excess of spring births. Studies of cerebral palsy are not conclusive, although there are suggestions that there may be an excess of summer births. The findings for Alzheimer’s disease, congenital malformations of the central nervous system, and mental retardation are contradictory and insufficient to draw any conclusions.
Peptide Modulation of Inflammatory Processes within the Brain
Authors: Lipton James M. , Catania Anna , Delgado René
Published: April 2003

It is clear that inflammatory processes contribute to neurodegenerative disease, stroke, closed head injury, encephalitis, and other CNS disorders. These inflammatory processes are marked by local increases in cytokines, in particular tumor necrosis factor-α (TNF-α). It is important to control such CNS inflammation in order to preserve neural function. The neuroimmunomodulatory peptide α-melanocyte-stimulating hormone (α-MSH) has been shown to modulate peripheral inflammation by acting on melanocortin receptors in host cells (macrophages, neutrophils) to inhibit production of such proinflammatory agents. Our results indicate that α-MSH likewise acts directly within the brain to modulate local inflammation. To determine if microglia are involved in anti-inflammatory responses to α-MSH within the brain, murine cells were tested; they produced TNF-α and nitric oxide in response to challenge, and production of both was reduced by α-MSH. In tests on human astrocytes, both α-MSH (1–13) and α-MSH (11–13) reduced TNF-α. Ischemia/reperfusion in the posterior circulation in dogs causes inflammatory reactions and disturbance of function, estimated from decreases in auditory-evoked potentials. These deficits were reduced by administering α-MSH systemically during reperfusion, moreso when the peptide was given during both ischemia and reperfusion. The results indicate that, much as for inflammation in the periphery, α-MSH modulates brain inflammatory responses mediated by proinflammatory agents.
HIV-1 Tat Molecular Diversity and Induction of TNF-α: Implications for HIV-Induced Neurological Disease
Authors: Mayne Michael , Bratanich Ana Christina , Chen Peiqin , Rana Farazana , Nath Avindra , Power Christopher
Published: April 2003

Activation and infection by HIV-1 of glial cells and infiltrating macrophages are cardinal features of AIDS-related neurological disease. Tumor necrosis factor-α (TNF-α) is released by these cell types, and increased TNF-α mRNA and protein levels are associated with the development and severity of HIV-induced neurological disease. HIV-1 proteins have been implicated in HIV neuropathogenesis including Tat which has been shown to be a potent inducer of TNF-α. We review our data showing the induction of TNF-α by Tat in primary human fetal astrocytes, human peripheral blood mononuclear cells, macrophages, and astrocytic and macrophage cell lines. TNF-α induction was NF-κB dependent and was eliminated by inhibiting protein kinase A, phospholipase C and protein tyrosine kinase activity. In addition, we examined the molecular diversity of the tat genome in the brains of HIV-infected patients from different HIV-1 clades. Comparison of matched brain- and spleen-derived tat sequences indicated that homology among brain-derived clones was greater than that between the brain- and spleen-derived clones. The brain-derived tat sequences were markedly heterogeneous in regions which influence viral replication and intracellular transport. Future studies using Tat, encoded by different sequences, will be necessary to determine the functional significance of tat molecular diversity. Nonetheless, these studies suggest that Tat is an important inducer of TNF-α production and thus may play a key role in the pathogenesis of HIV-related neurological disease.
The Thymic Repertoire of Neuroendocrine-Related Self Antigens: Biological Role in T-Cell Selection and Pharmacological Implications
Authors: Geenen Vincent , Kecha Ouafae , Brilot Fabienne , Charlet-Renard Chantal , Martens Henri
Published: April 2003

Thymic epithelium, including nurse cells (TEC/TNC), as well as other thymic stromal cells (macrophages and dentritic cells), express a repertoire of polypeptide belonging to various neuroendocrine protein families (such as the neurophypophysial, tachykinin, neurotensin and insulin families). A hierarchy of dominance exists in the organization of the thymic repertoire of neuroendocrine precursors. Oxytocin (OT) is more expressed in the TEC/TNC than vasopressin (VP); insulin-like growth factor 2 (IGF-2) thymic expression predominates over IGF-1, and much more over (pro)insulin. Thus, OT was proposed to be the self antigen of the neurohypophysial family, and IGF-2 the self antigen precursor of the insulin family. The dual role of the thymus in T-cell life and death is recapitulated at the level of the thymic neuroendocrine protein repertoire. Indeed, thymic polypeptides behave as accessory signals involved in T-cell development and positive selection according to the cryptocrine model of signaling. Moreover, thymic neuroendocrine polypeptides are the source of self antigens presented by thymic MHC molecules to developing pre-T cells. This presentation might induce the negative selection of T cells bearing a randomly rearranged antigen receptor (TCR) oriented against neuroendocrine families. Using an animal model of autoimmune type 1 diabetes (BB rat), we have shown a defect in intrathymic expression of the self antigen of the insulin family (IGF-2) and in IGF-2-mediated T-cell education to recognize and tolerate the insulin family. Altogether these studies have enlighted the crucial role played by the thymus in the induction of the central self tolerance of neuroendocrine families. The tolerogenic properties of thymic self peptides could be used in a novel type of vaccination for the prevention of autoimmune diseases.
Somatostatin and Substance P Induced in vivo by Lipopolysaccharide and in Peritoneal Macrophages Stimulated with Lipopolysaccharide or Interferon-Gamma Have Differential Effects on Murine Cytokine Production
Authors: Ryu Si-Yun , Jeong Kyu-Shik , Yoon Won-Kee , Park Sang-Joon , Kang Bit-Na , Kim Sung-Ho , Park Bae-Keun , Cho Sung-Whan
Published: April 2003

We have investigated whether lipopolysaccharide (LPS) induces substance P (SP) and somatostatin (SOM) in popliteal lymph nodes in vivo and whether macrophages are a source of SP and SOM in vitro. We have also investigated the effect of SP and SOM treatment on the production of cytokines. SP reached a maximum 3 days after injection of LPS (100 μg/footpad) and then declined. SOM expression after LPS injection reached a maximum at 5–7 days. Stimulation of thioglycolate-elicited peritoneal macrophages with LPS (20 μg/ml), recombinant interferon-γ (rIFN-γ, 100 U/ml), and LPS plus rIFN-γ induced SOM and SP. Thioglycolate-elicited, unstimulated peritoneal macrophages also synthesized these peptides. SOM (10–12–10–8 M) significantly inhibited IL-6 and IFN-γ production, whereas SP at those concentrations enhanced cytokine production by activated lymphocytes and macrophages. These findings suggest that neuropeptides which originate from macrophages and nerve fibers act as immunomodulators to mediate changes in the pattern of cytokine production.
Strain-Dependent Association between Lateralization and Lipopolysaccharide- Induced IL-1β and IL-6 Production in Mice
Authors: Gao Ming-Xia , Li Kang-Sheng , Dong Jing , Liège Stéphane , Jiang Bo , Neveu Pierre J.
Published: April 2003

Objective: The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mouse. We predicted that the production of cytokines, which are one of the molecular pathways for brain-immune interactions, should be linked to lateralization in a strain-dependent manner. Methods: We therefore measured plasma levels of interleukin (IL)-1β and IL-6 after an intraperitoneal injection of lipopolysaccharide (LPS) in two strains of mice (C3H and BALB/c) that were selected for their different profiles of cytokine production. Results: Plasma levels of IL-1β and IL-6 increased after LPS injection in both strains and this increase was dependent on paw preference in BALB/c but not in C3H mice. Increased levels of IL-1β were observed in left-pawed and ambidextrous but not in right-pawed mice. For IL-6, the LPS-induced increase was higher in ambidextrous than in left- and right-pawed animals. Conclusion: Cytokines may represent one of the factors responsible for interindividual differences in brain-immune interactions.
Season of Birth in Psychiatry
Authors: Castrogiovanni Paolo , Iapichino Sonia , Pacchierotti Claudia , Pieraccini Fulvio
Published: April 2003

Numerous studies suggest that seasonal birth may play a pathogenic role in the development of mental disorders. A birth excess of 10% during winter and spring has been shown in schizophrenia. The few studies carried out on affective disorders revealed a significant increase of births in the first quarter of the year in bipolar disorders and major depressive disorder. Subjects with seasonal affective disorder show a peak of births in May. Data on personality, eating and ‘neurotic’ disorders are less consistent. At the moment there are no data in the literature about anxiety disorders.
Grammatical Choice and Affective Experience in a Second-Language Test
Authors: Balaskó Márta , Cabanac Michel
Published: April 2003

This study measured the affective experience of 12 subjects reading grammatically correct and incorrect versions of 50 sentences, Questionnaire I, in their second language (French). This was followed by a multiple choice grammar test, Questionnaire II, using the same 50 sentences and offering the correct and incorrect answers. Subjects tended to choose correct as well as incorrect responses corresponding to their highest affective rating within each entry. In all cases the subjects’ behavior was higher than chance level and thus followed a trend to maximize pleasure. This result supports the hypothesis according to which the key to decision-making lies in the affective dimension of conscious experience.
Aberrant Functional Organization in Schizophrenia: Analysis of EEG Coherence during Rest and Photic Stimulation in Drug-Naive Patients
Authors: Wada Yuji , Nanbu Yuko , Kikuchi Mitsuru , Koshino Yoshifumi , Hashimoto Takuma
Published: April 2003

EEG coherence provides a measure of functional correlations between two EEG signals. The present study was conducted to examine intrahemispheric EEG coherence at rest and during photic stimulation (PS) in 18 drug-naive patients with paranoid schizophrenia and 30 control subjects. Compared with the controls, the schizophrenic patients had significantly higher intrahemispheric coherence of the resting EEG for the delta band, although no significant group differences were found for other frequency bands. EEG analysis during PS showed that the patients also had significantly higher EEG coherence over the left posterior regions. In this study, we also examined the changes in intrahemispheric coherence from rest to the stimulus condition (i.e., PS-related coherence reactivity); the patients were found to show significantly smaller changes, with significant group differences being also confined to the posterior regions in the left hemisphere. These findings provide evidence that schizophrenic patients have abnormal EEG coherence in both resting and stimulus conditions and suggest more diffuse, undifferentiated functional organization within hemispheres. In addition, diminished coherence reactivity suggests a failure of PS-related functional reorganization in schizophrenia.
Cellular and Molecular Actions of Lamotrigine: Possible Mechanisms of Efficacy in Bipolar Disorder
Authors: Xie Xinmin , Hagan Russell
Published: April 2003

Several clinical studies have investigated the use of the anticonvulsant lamotrigine (LTG) as a treatment for bipolar affective disorder. Evidence suggests that this drug may have a broad spectrum of utility in this illness, having both mood-stabilising (antimanic) and acute antidepressant properties. This makes this molecule of particular interest in helping to understand the underlying disease processes. In this review, we describe the cellular and molecular actions of LTG that may contribute to its action in bipolar disorder. LTG preferentially inhibits neuronal hyperexcitability and modifies synaptic plasticity via use- and voltage-dependent inhibition of neuronal voltage-activated Na+ channels and possibly high-voltage-activated CaÜcf6Ý2+Ücf1Ý channels. As a consequence, it reduces excessive transmitter release in the brain. Indirectly, these effects would be expected to regulate aberrant intracellular and intercellular signalling in critical regions of the limbic forebrain where hyperactivity may occur in mania, and thus may be directly relevant to its mood-stabilising properties. Whether other molecular actions of LTG, for example on monoamine disposition, could contribute to its antidepressant activity, are less clear at present but warrant further investigation.
Differential Treatment of Bipolar Disorder with Old and New Antiepileptic Drugs
Authors: Walden J. , Normann C. , Langosch J. , Berger M. , Grunze H.
Published: April 2003

Although lithium remains the preferred medication for bipolar disorders, new investigations suggest that only 60 to 80% of patients have a good response with a classical presentation. The antiepileptics carbamazepine and valproate are important alternatives. Several studies have shown that lithium, carbamazepine and valproate are effective in pure mania. Mixed mania and rapid cycling respond, however, well to valproate. One disadvantage of carbamazepine is its enzyme inducing property with the consequence of a decrease of plasma levels of other psychotropic medications and a worsening of psychopathology. First data indicate a good antimanic and antidepressive efficacy of the new antiepileptic drug lamotrigine.
Amisulpride versus Amineptine and Placebo for the Treatment of Dysthymia
Authors: Boyer P. , Lecrubier Y. , Stalla-Bourdillon A. , Fleurot O.
Published: April 2003

Amisulpride, a selective antagonist for D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a multicentre, 3-month, placebo-controlled study, amisulpride (50 mg/day) was compared to amineptine (200 mg/day) in the treatment of primary dysthymia. A total of 323 patients were enrolled. Amisulpride and amineptine were found to be statistically superior to placebo (p < 0.0001) on the Clinical Global Impression (item 2): 63, 64 and 33% responders, respectively; improvement of Montgomery-Asberg Depression Rating Scale and Scale for the Assessment of Negative Symptoms scores following amisulpride or amineptine treatment was twice as high as with placebo (p < 0.0001). The adverse event profile of amisulpride was similar to that of placebo except for endocrine symptoms in female patients; amineptine showed mainly events linked to psychic activation (insomnia, nervousness). Results show that amisulpride can improve symptoms of chronic depression in dysthymia.
Comparison of Risperidone and Mosapramine Addition to Neuroleptic Treatment in Chronic Schizophrenia
Authors: Takahashi Norito , Terao Takeshi , Oga Tetsuo , Okada Masakatsu
Published: April 2003

There is little information regarding the effects of risperidone addition to neuroleptic treatment in chronic schizophrenia. As a preliminary study, 10 neuroleptic-treated schizophrenic inpatients received risperidone (high 5HT2A/D2 ratio, i.e. the ratio between 5HT2A and D2 receptor occupancy) and mosapramine (low 5HT2A/D2 ratio) in a randomized, single-blind, crossover, add-on study consisting of 8 weeks of treatment each with risperidone and mosapramine. Although both additions resulted in significant, albeit modest, improvement, there was no significant difference in the scores on the Positive and Negative Syndrome Scale for Schizophrenia between risperidone and mosapramine addition. These results suggest that risperidone and mosapramine bring about comparable effects in add-on design. Thus, risperidone with a high 5HT2A/D2 ratio does not seem to be better than mosapramine with a low 5HT2A/D2 ratio when combined with conventional neuroleptics. Further studies including a large number of patients and a double-blind design are needed.
Effect of Two Antidepressant Drugs on REM Sleep and EMG Activity during Sleep
Authors: Jobert Marc , Jähnig Peter , Schulz Hartmut
Published: April 2003

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.
Spectral Structure and Brain Mapping of Human Alpha Activities in Different Arousal States
Authors: Cantero José Luis , Atienza Mercedes , Gómez Carlos M. , Salas Rosa M.
Published: April 2003

In a study with 10 young, healthy subjects, alpha activities were studied in three different arousal states: eyes closed in relaxed wakefulness (EC), drowsiness (DR), and REM sleep. The alpha band was divided into three subdivisions (slow, middle, and fast) which were analyzed separately for each state. The results showed a different spectral composition of alpha band according to the physiological state of the subject. Slow alpha seemed to be independent of the arousal state, whereas middle alpha showed a difference between REM and the other states. The fast-alpha subdivision appears mainly as a waking EEG component because of the increased power displayed only in wakefulness and lower and highly stable values for DR and REM. Scalp distribution of alpha activity was slightly different in each state: from occipital to central regions in EC, this topography was extended to fronto-polar areas in DR, with a contribution from occipital to frontal regions in REM sleep. These results provide evidence for an alpha power modulation and a different scalp distribution according to the cerebral arousal state.
Effects of Cholinergic Drugs on Neocortical EEG and Flash-Visual Evoked Potentials in the Mouse
Authors: Tebano M.T. , Luzi M. , Palazzesi S. , Pomponi M. , Loizzo A.
Published: April 2003

The effects of single intraperitoneal injection of two cholinesterase inhibitors, physostigmine (PHY; 0.01, 0.025, 0.05, 0.1, 0.2 mg/kg) and heptylphysostigmine (HEP; 0.5, 2, 6 mg/kg) on electroencephalographic (EEG) activity and flash visual evoked potentials (f-VEP) in the occipital cortex were compared in DBA/2 mice. EEG spectral analysis of awake periods showed that PHY at all doses and HEP at 2 mg/kg induced an increase of power in the 4.25- to 7-Hz frequency band. Furthermore, PHY at the higher doses and HEP at all doses induced a decrease of power in the 7.25- to 12-Hz frequency band, while the lower doses of PHY (0.01, 0.025 mg/kg) produced an increase of this band. EEG effects elicited by the two drugs were similar, when doses displaying analogous biochemical effects (acetylcholinesterase inhibition) were used (i.e. 0.01 and 0.025 mg/kg of PHY versus 0.5 and 2 mg/kg of HEP). PHY and HEP induced similar changes in f-VEPs. Amplitudes of early and late components (P1N1, N1P2, P4N4 and particularly N1P3) were enhanced, while amplitudes of middle components were depressed after all doses. The peak latency measures were generally delayed, even though, after the lower doses, a trend to a latency reduction was evident in late components. This finding might indicate a possible effect on stimulus speed diffusion by ‘low therapeutic’ doses, analogous to the ones used in men. Our data show that both drugs are effective in modifying EEG and f-VEP parameters connected with brain cholinergic function, although in a very narrow dose range.
Platelet Protein Kinase C alpha Levels in Drug-Free and Lithium-Treated Subjects with Bipolar Disorder
Authors: Young L. Trevor , Wang Jun-Feng , Woods Caroline M. , Robb Janine C.
Published: April 2003

Recent studies suggest that protein kinase C (PKC), particularly the α isoform, plays an important role in the action of lithium. There is, however, little evidence from patients with bipolar disorder (BD) to support this effect. The present investigation carried out comparative studies of PKC levels in platelets obtained from BD subjects including those with and without lithium treatment. All subjects met DSM-IV criteria for BD type I confirmed by structured interview (SCID-IV). Levels of PKC-α isoform in platelets from controls and from BD subjects were measured with immunoblotting analysis. No significant differences were found between controls, drug-free or lithium-treated BD subjects on membrane or cytosolic levels of PKC-α or in the membrane-to-cytosol ratio of this protein. The present study suggests that levels of PKC-α do not change in the peripheral tissues of BD subjects with or without lithium treatment.
Is Resting Anterior EEG Alpha Asymmetry a Trait Marker for Depression?
Authors: Debener Stefan , Beauducel André , Nessler Doreen , Brocke Burkhard , Heilemann Hubert , Kayser Jürgen
Published: April 2003

Several lines of evidence suggest that asymmetric anterior brain activation is related to affective style, linking left hemisphere activation to positive affect and right hemisphere activation to negative affect. However, previous reports of left frontal hypoactivation in depressed patients were not confirmed in recent studies. This study evaluated additional characteristics of resting EEG alpha (8–13 Hz) asymmetry in 15 clinically depressed patients and 22 healthy adults by recording EEG activity on two separate occasions, 2–4 weeks apart. Across both sessions, group differences in anterior EEG asymmetry were compatible with the original hypothesis. However, groups differed in temporal stability of anterior EEG asymmetry, which was retest reliable in controls but not depressed patients. In contrast, temporal stability of posterior EEG asymmetry was acceptable in both groups. Increased variability of anterior EEG asymmetry may be a characteristic feature for depression, and, if so, this would challenge the notion that anterior EEG alpha asymmetry is a trait marker for depression.
Appearance of Frontal Midline Theta Activity in Patients with Generalized Anxiety Disorder
Authors: Suetsugi Masatomo , Mizuki Yasushi , Ushijima Itsuko , Kobayashi Takayoshi , Tsuchiya Ken , Aoki Takeya , Watanabe Yoshifumi
Published: April 2003

The appearance of frontal midline theta activity (Fmθ), recognized as distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects feelings of relief from anxiety in humans. In the present study, EEGs were recorded, and the Hamilton Rating Scale for Anxiety and the state anxiety scale of Spielberger’s State-Trait Anxiety Inventory were evaluated once a week in 28 patients with generalized anxiety disorder. The Taylor Manifest Anxiety Scale and the trait anxiety scale of Spielberger’s State-Trait Anxiety Inventory were used to assess anxiety before and after the tests. The present results suggest that the appearance of Fmθ might be closely related to an improvement in the anxiety symptoms associated with generalized anxiety disorder.
Optic Neuritis and Human T-Lymphotropic Virus Type 1-Associated Myelopathy: A Case Report
Authors: Yoshida Yuriko , Saiga Toshikazu , Takahashi Hiroshi , Hara Akira
Published: April 2003

A 50-year-old woman with human T-lymphotropic virus type 1-associated myelopathy developed sudden loss of vision in her left eye. The patient had a relative afferent pupillary defect and a large central scotoma on visual field examination, but no abnormal findings were apparent upon slitlamp microscopy and funduscopic examination. A diagnosis of retrobulbar optic neuritis was made. We discuss the possible association of human T-lymphotropic virus type 1 infection.
Letter to the Editor
Authors: Recupero Santi Maria , Mollo Roberto , Abdolrahimzadeh Solmaz , Occhiuto Antonio , Tripodi Giuseppe
Published: April 2003

An unusual case of a 32-year-old woman with branch retinal artery occlusion is presented. The patient was affected by Ménière’s disease and had a history of occasional migraine headaches. A thorough clinical and laboratory investigation showed a high cholesterol level. Retinal arterial obstruction is rare in young people and it is difficult to establish the precise cause. The presumed multifactorial etiologic factors are discussed.