bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory Burst by Dengue-Virus-Induced Cytotoxic Factor
Authors: Misra Anita , Mukerjee Ruma , Chaturvedi U.C.
Published: April 2003

Objective: This study investigates the induction and release of the superoxide anion (O–2) and hydrogen peroxide (H2O2) by mouse spleen cells on stimulation with dengue type 2 virus (DV) and a DV-induced cytokine, the cytotoxic factor (mCF). Methods: Normal mice or their spleen cell cultures were inoculated with DV or mCF. At different time periods, the spleen cell supernatants were assayed for the production of O–2 and H2O2. Results: Inoculation of DV in spleen cell cultures resulted in peak production of O–2 and H2O2 at 48 and 72 h, respectively, while in DV-infected mouse spleen, the maximum production was on days 7 and 8, which correlated with the appearance of mCF in the milieu. Maximum O–2 and H2O2 production occurred at 45 min and 1 h after inoculation of 5 µg of mCF. Pretreatment of mCF with anti-mCF-antiserum inhibited O–2 and H2O2 release indicating the specificity of the induction by mCF. The enriched subpopulations of macrophages and T cells produced O–2 and H2O2 and not B cells. Treatment of the cells with superoxide dismutase increased H2O2 release but inhibited O–2 release and the cytotoxicity in a dose-dependent manner. Conclusion: This showed that O–2 is responsible for the cytotoxic activity of mCF and not H2O2. In conjunction with our earlier findings that pretreatment with NG-monomethyl-L-arginine inhibited mCF-induced production of NO and the cytotoxicity, it is concluded that the presence of both O–2 and NO is required for the cytotoxic activity of mCF, thereby indicating a possible role of peroxynitrite.
Malaria in Non-Endemic Kuwait: Detection of Very Low Level Plasmodium falciparum Infections Using Polymerase Chain Reaction
Authors: Iqbal Jamshaid , Sher Ali , Hira Parsotam Ravjee
Published: April 2003

Objective: Imported malaria continues to be a problem in Kuwait since most patients present with very low levels of parasitaemia. The diagnosis is often delayed or missed because of the low sensitivity of the standard stained blood smear test used for the identification of malarial parasites. In this study, we standardized a highly sensitive polymerase chain reaction (PCR) to detect malarial parasites. Methods: A total of 100 individuals presenting with various forms of infection were screened with the standard Giemsa-stained smears and were compared with the PCR for diagnosis and the sensitivity of the two methods. Results: Our results show that PCR is a highly sensitive and specific technique to detect low levels of Plasmodium falciparum parasites in clinical samples, and at least 6 cases (12%) who were microscopically negative had PCR-detectable parasitaemia. Conclusion: The PCR is a highly sensitive assay which can detect very low levels of malarial parasites and thus is of great value to obtain accurate detection of chronic, residual and sub-patent infections in Kuwait.
Ultrasound-Guided Core Biopsy of the Kidneys in Infants and Children: Kuwait Experience
Authors: Sheikh M. , Al-Essa A. , Francis I.
Published: April 2003

Objective: Ultrasound-guided core renal biopsies were performed in children to describe the accuracy of this technique and compare it with the other techniques. Methods: Forty-six children, aged 9 months to 13 years, were biopsied with 14 G and 18 G Tru-cut needles, using a real-time ultrasound sector scanner. Results: Adequate biopsy samples were obtained from 88.2 and 86.9% of the biopsy procedures with 14 G and 18 G Tru-cut needles, respectively. No major complications were encountered. Minor complications were also minimal and seen in only 3 of our patients who were managed conservatively. Conclusion: Ultrasound-guided Tru-cut renal biopsy is a safe and efficient method for performing renal biopsies in pediatric patients. The use of small needles (18 G) would reduce the complication rate while allowing retrieval of sufficient tissue for histological diagnosis.
Salmonella Septic Arthritis Complicating Rheumatoid Arthritis in a Patient with Total Knee Replacement
Authors: Boland Fareeda , Kaushik Prashant , Udo Edet E. , Rotimi Vincent O. , Malaviya Anand N.
Published: April 2003

Objective and Importance: Salmonella septic arthritis (SSA) in any age group is a relatively rare disease. The prime objective of this communication is to report a relatively uncommon presentation of SSA in a prosthetic knee joint of a patient with rheumatoid arthritis. Clinical Presentation: We report a 51-year-old lady with rheumatoid arthritis and total knee replacement who, while on methotrexate and azathioprine, developed Salmonella enteritidis bacteraemia complicated by septic monoarthritis of the left prosthetic knee. The same organism, using pulsed-field gel electrophoresis typing method, was isolated from the blood, joint aspirate and stool. Intervention: She was aggressively treated with antibiotics by giving the maximum dose of ceftriaxone, 2 g intravenously every 8 h for 4 weeks. In addition, close drainage with syringe and needle was also done on a few occasions. She responded well to this regimen. Follow-up for approximately 1 year at the clinic has been uneventful. Conclusion: SSA in a patient with a history of diarrhoea and a recent visit to the Indian subcontinent should be investigated for salmonella infection. Adequate antibiotic therapy, with repeated close drainage of the joint, is recommended for SSA in a prosthetic joint.
Psychiatric Morbidity among the General Hospital Medical Patients in Kuwait: Characteristics of Psychiatric Patients
Authors: Zahid M.A. , Razik M.A. , Motaal M.M.A.
Published: April 2003

Objectives: A considerable number of medical out-patients seen in a general hospital are known to suffer from psychiatric rather than/in addition to the physical disorder. Moreover, a substantial number of such patients, passing undetected by the physicians, end up being physically examined and investigated, at times far too extensively. This study was aimed at determining the prevalence of such patients in a general hospital in Kuwait. Methods: The sample consisted of 100 new medical out-patient clinic attenders. Each patient was administered a semi-structured interview. The items of the interview were derived from the Present State Examination, and the 10th revision of the International Classification of Diseases was used to assign psychiatric diagnoses. Results: Fifty-one out of the 100 patients suffered from psychiatric disorders. In only 5 cases was the disorder recognized. Psychiatric disorders were commoner in females and were not related to the nature of the physical disorders. Conclusions: Inclusion of some screening questions about mood disorders in the standard medical interview may help detect some of the psychiatric patients presenting in the general medical out-patient clinics. In addition, periodic clinical meetings between psychiatrists and physicians may enhance physicians’ awareness of the potential psychiatric morbidity amongst the medical out-patients.
Sonographic Diagnosis of Papillary Thyroid Carcinoma
Authors: Al-Tamami Mohi Al-Tamami , Al-Khawari Hanaa , Al-Sayer Hilal , Jumaa Taleb
Published: April 2003

Objective: To assess the value of ultrasonography (US) in reliably differentiating benign from malignant thyroid nodules, and in defining the malignant nature and the histotype of papillary thyroid carcinomas (PTC). Methods: A high-resolution real-time US system with a 7.5-MHz linear probe was used. The sonographic features of 39 histopathologically proven PTC cases were retrospectively reviewed and compared with the US features of 52 benign thyroid nodules (BTN). The US identification of PTC malignancy was based on the simultaneous presence of multiple US features seen exclusively in PTC and not in BTN. Results: Based on the simultaneous presence of exclusive malignant US features seen in PTC but not in BTN, identification of the malignant nature of PTC was certain in 74% of the cases and less certain in 8% of the cases. In a third group, 15% of the cases showed predominantly benign US features, while 1 patient (3%) was operated as a case of multinodular goiter and diagnosed histologically as having occult PTC. No malignant features were seen by US and it was not associated with metastasis. US identification of the histological type of PTC was based on the finding that a thyroid lesion presenting as a predominant cyst with a punctately calcified endoluminal projecting solid mural nodule was an exclusively specific feature of cystic primary PTC. Both, totally cystic and microcalcified predominantly cystic metastatic lymph nodes were also characteristically seen in metastatic PTC. Accordingly, the histotype of PTC was only identified in its cystic form, whether it was primary (13%) or metastatic (31%). Both constituted 44% of the 39 PTC cases. Conclusion: High-resolution real-time ultrasonography was found to be a useful first line diagnostic modality of PTC. It was reliable in differentiating benign from malignant thyroid nodules and in identifying the histotype of PTC in cases with cystic metastasis or where the primary or the metastatic nodule is cystic with microcalcified projecting solid mural nodule. Fine needle aspiration biopsy is to be resorted to, mainly in equivocal cases.
Distribution of Human Papillomaviruses in Women
Authors: George Sara Shirly , Luthra Usha K. , Chishti Mariam , Shaheen Azza Abdul Aziz , George Josely
Published: April 2003

Objectives: To study the distribution of human papillomviruses (HPV) in women in Kuwait using hybrid capture assay and their correlation with the severity of cervical lesions based on cytological diagnosis and to establish the relationship if any between the quantity of the viral load and the degree of severity of cervical lesions. Methods: Study sample included 181 women in the age range of 20–68 years, attending the Out-Patient Department of Gynaecology of the Al-Farwaniya Hospital and six polyclinics in Kuwait during the years 1997–1998. Cervical smears were interpreted according to the modified Bethesda System. HPV DNA was detected using a chemiluminescent-based Digene hybrid capture assay. Results: Of the 181 women studied, the cytodiagnosis was as follows: normal and inflammation 139 (76.8%), atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS) 26 (14.4%) and squamous intra-epithelial lesion (SIL) 16 (8.8%). High-risk HPV DNA had a very low prevalence in women with normal and inflammation cytology, i.e. 1.4% in contrast to women with SIL lesions which had a positivity of 68.8%. ASCUS and AGUS group had 7.7% high-risk HPV DNA positivity. The quantity of viral load was directly related to the increase in the severity of the lesions. Conclusion: High-risk HPV DNA was detected in a significantly higher proportion of women with SIL lesions as compared to those with normal cytology (p < 0.0001). Furthermore, the viral load of high-risk HPV DNA was directly related to the severity of the cervical lesions, relative light unit ratios being >20 in the majority of SIL lesions.
Serum Values of Copper, Zinc and Selenium in Adults Resident in Kuwait
Authors: Al-Sayer H. , Al-Bader A. , Khoursheed M. , Asfar S. , Hussain T. , Behbehani A. , Mathew A. , Dashti H.
Published: April 2003

Objective: The populations of Kuwait and other Arabian Gulf States are very heterogeneous. Expatriates with different dietary habits constitute approximately 60% of the Kuwaiti population. The aim of this study was to establish a reference range of trace element levels in the serum of the normal population in Kuwait. Method: A total of 379 healthy males (n = 262) and females (n = 117) of various nationalities living in the State of Kuwait were studied. The serum concentrations of zinc (Zn), copper (Cu) and selenium (Se) were measured and the copper/zinc (Cu/Zn) ratio was calculated. Results: The study established the serum Zn, Cu and Se levels in the studied population. The results showed that there was no significant difference in the serum levels of these elements among the different nationalities tested. A significantly higher serum Cu level and Cu/Zn ratio were seen in females. Conclusion: These findings can form the basis and reference for any future studies on trace elements in different pathologic conditions in the Arabian Gulf region.
Severe Fatal Group B Streptococcal Sepsis in an Adult
Authors: Habib A.G. , Al-Anazi A.R. , Mobeireek A. , Yousif A.I. , Azeem A.R.
Published: April 2003

Objective: Group B Streptococcus (GBS) sepsis is largely a disease seen in neonates and infants. It is uncommon in adults except during pregnancy and puerperium. We hereby present an adult diabetic patient with severe fatal GBS sepsis with a view to increasing clinical awareness of this bacterial infection among adult patients. Clinical Presentation: A 56-year-old male from Saudi Arabia presented initially with features of pyelonephritis. He discharged himself against medical advice after 1 day but returned to the hospital 24 h later, with symptoms of headache, neck stiffness, confusion and left flank tenderness. Clinical and laboratory evaluation, including analysis of cerebrospinal fluid, confirmed sepsis (urosepsis, bacteraemia and meningitis) with GBS spp. Intervention: The patient was managed with intravenous ceftriaxone, vancomycin and later penicillin G and supportive ICU care. The patient required intubation initially. He expired from marked irreversible anoxic brain damage resulting from the sepsis. Conclusion: The case is presented to help in increasing the awareness of clinicians to GBS as a potential cause of morbidity and mortality in adults, particularly in those with chronic comorbid states.
The Prevalence of Cognitive Impairment among Nursing Home Residents in Taipei, Taiwan
Authors: Wu Shwu Chong , Ke Dershin , Su Ting Li
Published: April 2003

A random sample of nursing home residents over 65 years of age were interviewed. Two hundred ninety-two participants received the Short Portable Mental Status Questionnaire. Two hundred eleven were unable to answer the questionnaire, but their caregivers provided information about their daily activities and performance ability. We found that 255 (50.9%) fit our criteria of cognitive impairment and 236 (47.7%) had both impaired cognition and impaired performance in activities of daily living. Similar to statistics in the US, the prevalence of cognitive impairment in Taipei nursing home residents was much higher than that observed in the community elderly and probably in Taiwan as well. Therefore, public health care policy for cognitively impaired elderly in Taiwan should not simply rely on data from community studies.
Modifiable Stroke Risk Factors in Volunteers Willing to Participate in a Prevention Program
Authors: Sitzer Matthias , Skutta Michael , Siebler Mario , Sitzer Gerhard , Siegrist Johannes , Steinmetz Helmuth
Published: April 2003

The current trends in stroke incidence require continued efforts to improve primary prevention. Compared to large-scale public health approaches, more limited programs targeting volunteers may offer some advantages. We invited all 12,824 members of a health insurance company program who lived within 50 km from one of two study sites to participate in a vascular screening program aimed at reducing modifiable risk factors. 1,837 persons registered and participated (14.3%, mean age 53 ± 12 years, 50% men). Using the Framingham stroke risk profile for persons aged 55 years or above (n = 961, 52.3%), 97 stroke events can be predicted for this age group within 10 years. The majority of these 97 events will occur in those with mean resting blood pressure values ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic; 420 persons, mean age 64 ± 7 years, 60 expected events), or with a particularly high age- and sex-adjusted risk (288 persons, mean age 68 ± 7 years, 60 expected events). Our pilot study provides an estimate of the prevalence of modifiable vascular risk factors among volunteer participants of a prevention program. Possible benefits of this approach will be investigated in a second step using a randomized intervention.
Low Cholesterol as a Risk Factor for Primary Intracerebral Hemorrhage: A Case-Control Study
Authors: Segal Alan Z. , Chiu Rosaleen I. , Eggleston-Sexton Paula M. , Beiser Alexa , Greenberg Steven M.
Published: April 2003

We performed a case-control study to assess the relationship between primary intracerebral hemorrhage (ICH) and low serum cholesterol. Prospectively recruited, fully evaluated patients with ICH were compared to two independent control groups, one based in a primary care practice and one population-based. Low cholesterol was defined by the sex-specific lowest quintile of the primary care controls. The proportion of ICH cases with low cholesterol >3 months posthemorrhage was significantly greater than in controls (42 vs. 20% in either control group, p < 0.01). Subgroup analysis showed an overrepresentation of low cholesterols in probable hypertensive hemorrhage (47%, p < 0.05) but not in probable cerebral amyloid angiopathy (27%, p = 0.5). Low cholesterol increased the odds for hemorrhage 2.25-fold (1.12–4.50) after adjustment for age and apolipoprotein E genotype. These data confirm an increased risk for primary ICH associated with low cholesterol, a relationship that may apply specifically to hemorrhages from hypertensive vasculopathy.
Dementia in Argentina and Other Latin-American Countries: An Overview
Authors: Mangone Carlos A. , Arizaga Raul L.
Published: April 2003

Latin-American countries are expected to experience an expansion of the elderly population, as life expectancy increases. We reviewed the literature to determine the frequency of dementia in our region and surveyed selected Latin-American countries to determine the availability of diagnostic and treatment services and long-term care facilities. Latin-American countries face a challenge to develop public health strategies to cope with the anticipated heightened number of elderly with cognitive impairment.
A Family History of Parkinson’s Disease and Its Effect on Other PD Risk Factors
Authors: Rybicki Benjamin A. , Johnson Christine C. , Peterson Edward L. , Kortsha Gene X. , Gorell Jay M.
Published: April 2003

Parkinson’s disease (PD) is likely a result of both inherited and exogenous factors. In a study of 144 PD cases and 464 controls, we used PD family history as a surrogate for inherited PD susceptibility. Cases were more likely to report a first- or second-degree relative with PD: 16.0 vs. 4.3%; odds ratio (OR) = 4.2; 95% confidence interval (CI) = 2.3–7.6. A PD family history was a greater risk factor for PD in subjects under age 70 (OR = 8.8; 95% CI = 3.4–22.8) compared with those over 70 (OR = 2.8; 95% CI = 1.3–6.1) and in men (OR = 8.1; 95% CI = 3.4–19.2) compared with women (OR = 2.6; 95% CI = 1.1–6.0). We also tested whether a PD family history modified the effects of other PD risk factors. In subjects with a PD family history, occupational exposure to copper, lead or iron increased the risk for PD (OR = 3.0; 95% CI = 0.7–13.3), but this was not the case for those without a family history (OR = 1.1; 95% CI = 0.7–1.6). Ever smoking cigarettes was inversely associated with PD in those without a PD family history (OR = 0.6; 95% CI = 0.4–0.9), but was positively associated with PD in those with a PD family history (OR = 1.7; 95% CI = 0.5–5.9). In summary, our results suggest that a PD family history, and perhaps, therefore, an inherited susceptibility, confers a greater risk for PD in men and individuals under 70 years of age and may modify the effects of environmental risk factors for PD.
Cost of Illness of Epilepsy in the US: Comparison of Patient-Based and Population-Based Estimates
Authors: Halpern Michael , Rentz Anne , Murray Miranda
Published: April 2003

Purpose: To analyze the direct medical costs associated with epilepsy in the US using a cost-of-illness analysis that incorporates both a patient-based approach and a population-based approach. Methods: Patient-based or ‘bottom-up’ analysis relied on information provided by a panel of experienced epilepsy clinicians to determine the number and type of medical resources used by individuals with epilepsy. Population-based or ‘top-down’ analysis relied on cost estimates from a nationally representative sample in the 1987 National Medical Expenditure Survey. Results: The average annual cost per individual in the patient-based analysis was $1,490. The average annual cost per individual in the population-based analysis was $1,510 with average yearly costs per adult of $1,480 and $1,740 per child. New cases of epilepsy are associated with costs of $362 million for the first year of treatment; existing cases of epilepsy are estimated to cost the US nearly $2 billion. Conclusions: The results of this study indicate incident cases are more than twice as expensive as prevalent cases, and the need to properly care for epilepsy patients is increasingly important in today’s health care environment, where the emphasis is on providing effective treatments while simultaneously lowering the costs.
Epidemiology of Primary Central Nervous System Tumors in Estonia
Authors: Liigant Aive , Asser Toomas , Kulla Andres , Kaasik Ain-Elmar
Published: April 2003

During the period from 1986 to 1996, 1,665 cases of primary central nervous system (CNS) tumors were identified in the resident population of Estonia. Histological verification was available in 81% of the cases. Gliomas were more common in men, while meningiomas and neurinomas were more common in women. No significant difference was observed between the sexes for all primary CNS tumors. The age-specific incidence increased from the age of 30, reached a maximum in the age range of 50–69 years and declined in the elderly which may reflect under-diagnosis. The age-adjusted incidence rate for CNS tumors was 8.5/100,000 population. A comparison of our results with those of a previous study carried out in Estonia revealed a significant histology-specific increase in incidence in all age groups.
Differential Effects of Neuropeptides on Cytokine Production by Mouse Helper T Cell Subsets
Authors: Kawamura Noriyuki , Tamura Hiroo , Obana Satoshi , Wenner Marcus , Ishikawa Toshio , Nakata Akinori , Yamamoto Hiroshi
Published: April 2003

Though immune outcome is known to be determined by which helper T cell response predominates, no local mechanism has yet been established which can explain how the neuronal system may control this. It is possible that the nervous system releases neuropeptides at specific local sites of infection or challenge, which triggers lymphocytes at those points to release specific cytokine profiles. These may then influence the direction of the Th1/Th2 response and therefore immune outcome. The aim of this study was to evaluate whether and if so how neuropeptides influence cytokine production by lymphocytes, especially T cells. We investigated the effects of neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal peptide (VIP) on the production of interferon-γ (IFN-γ) and interleukin-4 (IL-4) by stimulating nonadherent splenocytes and helper T cell clones with antigens in vitro in the presence or absence of these peptides. NPY greatly enhanced IL-4 production and inhibited IFN-γ. CGRP inhibited IFN-γ production markedly in a dose-dependent manner, but had no effects on IL-4 production. SP and VIP had no effects on IFN-γ production, but SP enhanced and VIP suppressed IL-4 production slightly but consistently. Therefore neuropeptides can influence cytokine production. This opens the door to speculations that these specific cytokine profiles might play a part in influencing the direction of the consequent Th1/Th2 cascade and immune outcome and possibly the pathogenesis of immune-related diseases.
Asymmetrical Distribution of Hippocampal Mineralocorticoid Receptors Depends on Lateralization in Mice
Authors: Neveu Pierre J. , Liège Stéphane , Sarrieau Alain
Published: April 2003

Previous experiments showed that the activation of the hypothalamic-pituitary-adrenal (HPA) axis during stress was associated with behavioral lateralization used as a marker of population heterogeneity in mice. Furthermore, brain asymmetries have been demonstrated in neurotransmitter metabolism and neuroendocrine modulation. As the hippocampus modulates the activity of the HPA axis in stress and basal conditions, we postulated that hippocampal corticoid receptors may be asymmetrically distributed and that asymmetry may differ according to behavioral lateralization of animals. In order to answer these questions, binding capacity of mineralocorticoid (MR) and glucocorticoid (GR) receptors was determined in right and left hippocampi of mice previously selected for paw preference. The results show that regardless of behavioral lateralization, there was a tendency for a right dominance in MR binding capacity in the hippocampus but interestingly, the percentage of right/total MR binding capacity was inversely correlated with individual paw preference scores. The affinity of MRs did not depend on behavioral lateralization. GR binding capacity was similar in each hemisphere and no relationship was found between GR binding capacity and paw preference scores. These results suggest that hippocampal receptors for corticoids may play an important role in the asymmetrical brain control of immune reactivity.
The Restraint Stress-Induced Elevation in Plasma Interleukin-6 Negatively Regulates the Plasma TNF-α Level
Authors: Nukina Hideyuki , Sudo Nobuyuki , Komaki Gen , Yu Xiao-Nian , Mine Kazunori , Kubo Chiharu
Published: April 2003

Although a considerable amount of evidence has shown that physical and psychological stress elevates the plasma interleukin 6 (IL-6) levels, the physiological significance of such an elevation remains to be elucidated. In this study, in order to determine whether the restraint stress-induced elevation of plasma IL-6 contributes to the activation of the hypothalamic-pituitary-adrenal axis, and whether or not such elevation can affect the inflammatory processes, the plasma levels of ACTH, corticosterone, interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) in mice pretreated with anti-IL-6 antibody (MP5-20F3 monoclonal antibody) were compared with those in mice pretreated with rat IgG (control antibody) both during and after stress. Both the anti-IL-6-antibody- and control-antibody-pretreated mice showed the same extent of plasma ACTH and corticosterone increases during stress, and no significant difference was found between the two groups of animals. On the other hand, the level of plasma TNF-α in the anti-IL-6-treated animals was also significantly higher than that in the control animals both immediately after cessation of stress and 60 min after the cessation of the 120-min period of restraint. Plasma IL-1 activity, however, did not reach a detectable level in either group of animals at any time point examined. These results thus indicate that the restraint-stress-induced elevation of plasma IL-6 negatively regulates the plasma TNF-α levels and may thus contribute to the maintenance of homeostasis.
Use of Cultured Thymic Tissues for the Regeneration of the Thymus
Authors: Jones G.V. , Botham C.A. , Kendall M.D.
Published: April 2003

An account of research conducted on the transplantation of thymic cells and tissues in order to restore the functional activity of the thymus is reviewed, and discussed in the context of current concepts. Although most rodent work has been conducted on the transplantation of cultured fragments under the kidney capsule, human transplantation studies and models have used other sites or other species such as the severe combined immunodeficient mouse as hosts. The factors affecting the growth of thymic cells in culture is considered in detail since the methodology can strongly influence the cells favoured under culture conditions. An extension of this work to characterize both thymic fragments implanted under the kidney capsule of rats and cultured thymic cells has recently led to the appreciation that the adult thymus must contain a small number of neural crest-like cells. These cells have a high level of proliferation in the implanted fragments, expand in culture, and belong to a family of cytokeratin-positive cells exhibiting immunoreactivity for a wide range of neuropeptides and transmitters. Thus primary cultures of thymus can contain a wide range of glia-like cells.This can be explained by the fact that the thymus, in addition to having a mesenchymal neural crest component, is probably derived from cardiac neural crest. Closely associated neural crest also has glia-like properties (the supporting cells of the enteric nervous system). These finding can account for the large number of reports of epithelial cells of the adult thymus being immunoreactive to antibodies raised to neuroendocrine and neurotransmitters. Neuroimmune interactions in the thymus are more fundamental than previous work had suggested.
Effects of Cholinergic Agonists and Antagonists on Interleukin-2-Induced Corticotropin-Releasing Hormone Release from the Mediobasal Hypothalamus
Authors: Karanth Sharada , Lyson Krzysztof , McCann S.M.
Published: April 2003

In previous research we found that interleukin-2 (IL-2)-induced corticotropin-releasing hormone (CRH) release in vitro is mediated by cholinergic activation of nitric oxidergic (NOergic) neurons. The NOergic neurons release nitric oxide that stimulates CRH release. To further characterize the mechanism of IL-2-induced CRH release, the possible role of nicotinic as well as muscarinic receptors in IL-2-stimulated CRH release was evaluated. Medial hypothalamic (MH) explants from adult male rats were preincubated in Krebs-Ringer (KRB) buffer for 45 min followed by incubation for an additional 30 min in fresh KRB or KRB containing various compounds. As previously reported, acetylcholine (ACH) stimulated CRH release in a dose-related fashion. IL-2 (10–13 M) stimulation of CRH release was unaffected by the lower concentration of ACH (10–9 M), but surprisingly was inhibited by a 100-fold higher concentration. Atropine (ATR) (10–7 M) blocked CRH release induced by ACH (10–7 M) and the release of CRH induced by IL-2. The cholinergic agonist carbachol (CAR) (10–7 M) also released CRH and this action was blocked by ATR (10–7 M). CRH release in the presence of CAR was lowered below basal when the concentration of ATR was increased to 10–6 M. In contrast to ACH, CAR had an additive effect to release CRH when combined with IL-2 (10–13 M). Nicotine (10–7 M) also stimulated CRH release and this stimulation was completely blocked by 10–6 M but not by 10–7 M of the nicotinic receptor blocker, hexamethonium (HEX). The lower concentration of HEX blocked the stimulatory effect of ACH (10–7 M) and IL-2 on CRH release. Combined blockade with ATR plus HEX completely blocked the action of ACH and even reduced the CRH concentration to below basal values. Furthermore, combined blockade completely blocked the release of CRH induced by IL-2. We conclude that nicotinic as well as muscarinic receptors play an important role in CRH release, and that they both act to mediate IL-2-stimulated CRH release.
Adrenergic Modulation of Apoptosis in Splenocytes of Xenopus laevis in vitro
Authors: Haberfeld Meredith , Johnson Rachel O. , Ruben Laurens N. , Clothier Richard H. , Shiigi Stanley
Published: April 2003

Impaired and healthy cells undergo suicide using an intrinsic genetic program. Exposure to stress-related α2- or β-adrenergics for 4 or 20 h in vitro had no effect on apoptosis in splenocytes of adult Xenopus laevis, while a 4-hour coincubation of clonidine, an α2-agonist, with a calcium ionophore (A23187) or a phorbol diester (PMA), enhanced apoptosis induced by each apoptogen alone. Clonidine did not affect apoptosis stimulated with dexamethasone (DEX), however. Comparable in vitro exposures to isoproterenol, a β-agonist, reduced apoptotic levels stimulated by all three apoptogens alone. Following 20 h coexposure, clonidine no longer affected A23187-induced apoptosis, but reduced PMA-induced apoptosis, while isoproterenol enhanced apoptosis stimulated with both. Neither agonist modulated apoptosis induced by 20 h of exposure to DEX. Thus, adrenergic agonists modulated apoptosis in cells coexposed to A23187 and PMA, in a time-dependent and adrenoceptor class-dependent fashion. These stress-induced products can affect concurrent apoptosis reversibly over time in vitro, and thus possibly in vivo.
Time-Dependent Effect of Cyclosporine on Mitogenic Responses and Lymphocyte Subset Populations in Rat Spleen and Submaxillary Lymph Nodes
Authors: Esquifino Ana I. , Arce Agustín , Selgas Laura , Cardinali Daniel P.
Published: April 2003

Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation and T lymphocyte subsets were measured in spleen and submaxillary lymph nodes of male rats injected with cyclosporine (5 mg/kg s.c. for 5 days, at 12.00 or 24.00 h; animals kept under light from 08.00 to 20.00 h daily). One hour before the third injection, Freund’s complete adjuvant or its vehicle was administered. A suppressive effect of cyclosporine on the mitogenic action of LPS was seen in the spleen of rats injected with cyclosporine at noon whereas the effect of ConA remained unaffected. CD4+, CD8+ and CD4+-CD8+ cells decreased in spleen and lymph nodes of Freund’s adjuvant-injected rats only with cyclosporine given at noon. The results further support occurrence of time-of-day-dependent effects of cyclosporine on lymphocyte subsets and proliferation.
Circulating Interleukin-1-Beta Levels after Acute and Prolonged Exposure to Low Temperatures: Human and Rat Studies
Authors: Tringali Giuseppe , Farrace Stefano , Ragazzoni Enzo , Dello Russo Cinzia , Piscitelli Roberta , Preziosi Paolo , Navarra Pierluigi
Published: April 2003

In this study we have investigated whether IL-1 acts as a mediator of stress responses elicited by exposure to low temperatures. We also sought whether IL-1 is released from the adrenal gland under basal conditions or after exposure to low temperatures. Normal and adrenalectomized (ADX) rats were used for acute studies, whereas the effects of a prolonged exposure were investigated in a group of human subjects during a 45-day stay in Antarctica. Circulating levels of interleukin-1β (IL-1β) were taken as a marker of systemic IL-1 production both in humans and rats. In the latter, serum corticosterone (Cort) was also estimated. In intact rats, exposure to low temperatures (–25 or –35°C) for 30 or 90 min did not modify circulating IL-1β levels with respect to controls taken at +20°C. Adrenalectomy was associated with an increase in cytokine levels only in the group exposed to –35°C for 90 min; such increase is statistically significant compared to all groups of normal rats, whatever the experimental condition, as well as to ADX rats exposed to +20°C and –25°C for 30 and 90 min. In normal rats, the increase in circulating Cort levels was already maximal after exposure to –25°C for 30 min. In humans, circulating IL-1β levels after 45 days in Antarctica were significantly lower than those measured on arrival in the same subjects. Thus, no change in circulating IL-1β was associated with acute low-temperature stress in rats, whereas a marked decrease in serum cytokine was observed in humans after prolonged exposure to a cold environment. Experiments with ADX rats indicated that the contribution of the adrenal glands to total-body IL-1β production is negligible or absent.
Modulation of Early Immune Responses and Suppression of Trypanosoma brucei brucei Infections by Surgical Denervation of the Spleen
Authors: Liu Yajuan , Mustafa Manal , Li Hu-Lun , Nuortio Lauri , Mustafa Amged , Bakhiet Moiz
Published: April 2003

Objective: To examine critical interactions between the nervous system and the immune system during experimental African trypanosomiasis. Methods and Results: Inoculation of Trypanosoma brucei brucei resulted in early interferon (IFN)-γ production, elevated corticosterone and prostaglandin E2 (PGE2) levels and increased splenocyte proliferation, as measured by enzyme-linked immunospot assay, radioimmunoassay and thymidine incorporation assay, respectively. Splenic denervation suppressed IFN-γ, corticosterone and PGE2 production, enhanced splenocyte proliferation, and significantly reduced parasitemia and prolonged rat survival. Conclusions: Our data show substantial effects of the nervous system on early immune responses that may influence the outcome of this disease. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. More investigations are required to understand the evident neural control over the immune system during infectious challenges, which may assist in novel therapeutic approaches.
Conditioned Immunosuppressive Effect of Cyclophosphamide on Delayed-Type Hypersensitivity Response and a Preliminary Analysis of Its Mechanism
Authors: Mei Lin , Li Lequn , Li Yifan , Deng Yulan , Sun Changwei , Ding Guifeng , Fan Shaoguang
Published: April 2003

In the present study, camphor odor and intraperitoneal (i.p.) injection of cyclophosphamide (CY) were used as conditioned stimulus (CS) and unconditioned stimulus (US), respectively. In the unconditioned group, mice were exposed to camphor odor for 1 h followed by an i.p. injection of CY (75 mg/kg). On the next day, the above CS/US association trial session was repeated followed by smearing dinitrochlorobenzene (DNCB) on mouse abdominal skin for sensitizing the animal for delayed-type hypersensitivity (DTH) response. Five days after DNCB sensitization, mice were exposed to camphor odor (1 h), followed by an i.p. injection of CY, and then DNCB was smeared on the left ear of mice for the challenge of DTH response. Both the left/right ear weight ratio and the activity of leukocyte migration inhibitory factor (LMIF) were used as the index of DTH response, which was done 24 h after DNCB challenge. In the conditioned group, the treatment was the same as that in the unconditioned group, except that normal saline was injected on day 5 instead of CY. Furthermore, in order to analyze the mechanism of the conditioned response (CR), the mouse serum from the conditioned group (CR serum) was injected into normal mice 6 h prior to DNCB challenge. Results showed that in the conditioned group, left/right ear weight ratio and LMIF activity were statistically lower than that in the DTH group, and there was no difference between conditioned and unconditioned groups. Thus, an animal model of conditioned immunosuppressive response had been established. The results also showed that after CR serum was injected into normal mice, DTH response was also significantly suppressed. However, if CR serum was treated with dialysis (10,000 molecular weight cut-off), the suppressive effect of CR serum on DTH response disappeared. Taken together, the data suggested that a chemical compound(s) in serum, with a molecular weight less than 10,000, was important in mediating the conditioned immunosuppressive response. This may be a very important molecule(s) that could be very critical to our understanding of the interaction between the central nervous system and immune function.
On the Use of Neural Network Techniques to Analyze Sleep EEG Data
Authors: Baumgart-Schmitt R. , Herrmann W.M. , Eilers R.
Published: April 2003

This is the third communication on the use of neural network techniques to classify sleep stages. In our first communication we presented the algorithms and the selection of the feature space and its reduction by using evolutionary and genetic procedures. In our second communication we trained the evolutionary optimized networks on the basis of multiple subject data in context with some smoothing algorithms in analogy of Rechtschaffen and Kales (RK). In this third communication we could demonstrate that the robustness concerning individual specific features of automatically generated sleep profiles could be reasonably improved by an additional modification of the procedure used by SASCIA (Sleep Analysis System to Challenge Innovative Artificial Networks). The outputs of nine different networks that were created by the data of 9 different subjects were used simultaneously for classification. The medians of the values obtained in each output measure were selected for the allocation to a sleep stage. The fitness criteria of 16 automatically generated sleep profiles showed reasonable concordance with the expert profile. Even though in single cases the concordance between conventional RK classifications and automatically generated profiles were a few percentages lower, the average correct classification of the 12 classified subjects improved substantially, thus proving that the classifier is more robust against individuum-specific variability. Despite the fact that the expert generally employs three channels (EEG, EMG and EOG), at least to build up sleep profiles, the SASCIA system was able to produce profiles on the basis of only one EEG channel with 80% concordance and a correlation coefficient of 0.86. The feature selections were performed by genetic algorithms and the topologies of the networks were optimized by evolutionary algorithms. This algorithm will now be used for larger sample forward classification.
Quantitative EEG Effects of Nicotine Replacement by Cigarette Smoking1
Authors: Newton Thomas F. , Cook Ian A. , Holschneider Daniel P. , Rosenblatt Martin R. , Lindholm Judith E.V.Z. , Jarvik Murray M.
Published: April 2003

The effects of cigarette smoking on the central nervous system can be assessed directly using the electroencephalogram (EEG). Nicotine withdrawal and subsequent replacement have been studied, but have produced conflicting effects on brain electrical activity. We studied the effect of smoking 2 cigarettes at subjects’ own pace in 20 subjects. EEG was recorded using the EEGSYS program in the eyes-closed awake state using a bipolar montage. Delta power decreased in central-posterior head regions. Theta power and power in the lower half of the alpha band decreased. Beta power and power in the upper half of the alpha band increased significantly over frontotemporal head regions. Examination of spectra underlying the usual frequency bands revealed that many effects of smoking on EEG power probably resulted from a shift of the overall power spectrum toward higher frequencies, rather than resulting from alterations in activity in specific frequency bands.
Gabapentin
Authors: Kelly Kevin
Published: April 2003

Gabapentin is an antiepileptic drug used in the treatment of partial and generalized tonic-clonic seizures. Its antiepileptic mechanism of action is not known. The transport of gabapentin across membranes and its demonstrated effects on voltage-gated ion channels (sodium, calcium), presynaptic mechanisms that can enhance GABAergic inhibition, and ligand-gated ion channels (GABA receptors and glutamate receptors) are reviewed.
A History of the Use of Anticonvulsants as Mood Stabilizers in the Last Two Decades of the 20th Century
Authors: Post R.M. , Denicoff K.D. , Frye M.A. , Dunn R.T. , Leverich G.S. , Osuch E. , Speer A.
Published: April 2003

Anticonvulsants have moved into an important position as alternatives and adjuncts to lithium carbonate in the treatment of bipolar illness. Work with the nonhomologous model of kindled seizures helped in the choice of carbamazepine as a potential mood stabilizer and in the study of the mechanisms of action of the second generation anticonvulsants carbamazepine and valproate, as well as the putative third generation psychotropic anticonvulsants lamotrigine and gabapentin. Anticonvulsant neuropeptides such as TRH and nonconvulsant approaches with repeated transcranial magnetic stimulation (rTMS) also appear promising.
Kindling: Separate vs. Shared Mechanisms in Affective Disorders and Epilepsy
Authors: Weiss Susan , Post Robert
Published: April 2003

Kindling is discussed in relation to affective illness as a nonhomologous model, which shares the feature of increasing illness severity and evolution over time following repeated exposures to certain forms of stimulation. This progressive aspect of kindling has proven useful in the study of approaches to pharmacotherapeutics, mechanisms and characteristics of drug tolerance, and, most recently, illness suppression through physiological rather than pharmacological strategies. Each of these themes is described and the mechanisms that have been uncovered using the kindling model are discussed in relation to how similar principles might apply in affective illness or epilepsy. It is hoped that some of the lessons from the kindling model will provide useful and novel insights into aspects of treatment and mechanisms of psychiatric and neurologic illnesses.
CSF Monoamine Metabolites in Relation to the Diagnostic Interview for Borderline Patients (DIB)
Authors: Chotai Jayanti , Kullgren Gunnar , Åsberg Marie
Published: April 2003

The cerebrospinal fluid concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol, and their ratios were studied in relation to the Diagnostic Interview for Borderline patients (DIB) evaluated retrospectively from hospital records for a sample of 202 patients participating in psychobiological programs on mood disorders. No correlations with the total DIB score were significant. Patients with borderline personality disorder (BPD) defined by a total DIB score of at least 7 or 6, respectively, did not differ significantly from non-BPD regarding the metabolites. However, for section II (impulse action pattern) of the DIB, those with an intermediate value of the section score had significantly higher levels of 5-HIAA and HVA, suggesting that such higher than normal concentrations may be protective against impulsive or suicidal behavior generated by an underlying psychiatric morbidity due to other risk factors.
Behavioral and Cognitive Effects Produced by Electrical Stimulation in the Medial Prefrontal Cortex:An Experimental Model for High Cortical Activation
Authors: Penna Assunta Maria , Lee Soo-Yang , Scheidegger da Silva Larissa , Oliveira Roney Welinton , de Freitas Gomes Cristiano , Ester Miyuki Nakamura-Palacios E.M.
Published: April 2003

An electrical stimulation (ES) session with ten 30-second trains of sine-wave stimuli (30–100 µA, 60 Hz) separated by 30-second intervals was conducted daily in rats with electrodes implanted in the left or right or in both sides of the medial prefrontal cortex (PFC; B = + 2 mmA, + or –0.6 unilateral or 1 mmL bilateral, + 2.7 mmV). The unilateral and bilateral ES in the medial PFC produced abnormal behaviors such as circling spying, body stretching and immobility, and did not affect either the acquisition or the performance of delayed tasks in the 8-arm radial maze conducted 8–10 h after the ES session. However, animals that showed convulsions when the bilateral ES was applied in the medial PFC showed significant deficits in spatial learning and in the performance of short-term (5-second delay) and long-term (1-hour delay) working memory. The behavioral and cognitive effects induced by repeated episodic ES in the medial PFC provide an experimental model to study the effects of increased cortical activation on cognitive processes.