bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of organophosphate insecticide methidathion on lipid peroxidation and anti-oxidant enzymes in rat erythrocytes: role of vitamins E and C
Authors: Altuntas I , Delibas N , Sutcu R
Published: January 2003

The effects of organophosphate insecticide methidathion (MD) on lipid peroxidation and anti-oxidant enzymes and the ameliorating effects of a combination of vitamins E and C against MD toxicity were evaluated in rat erythrocytes. Experimental groups were: control group, MD-treated group (MD), and MD+vitamin E+vitamin Ctreated group (MD+Vit). MD and MD+Vit groups were treated orally with a single dose of 8 mg/kg MD body weight at 0 hour. Vitamins E and C were injected at doses of 150 mg/kg body weight, i.m. and 200 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the MD+Vit group. Blood samples were taken 24 hours after the MD administration. The level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were studied in the erythrocytes. MDA level increased significantly in the MD group compared to the control group (P <0.05) and decreased significantly in the MD+Vit group compared to the MD group (P <0.05). The activities of SOD, GSH-Px, and CAT decreased in the MD group compared to the control group (P<0.05). Only GSH-Px activity increased in the MD+Vit group compared with the MD group. These results suggest that treating rats with MD increases LPO and decreases anti-oxidant enzyme activities in erythrocytes. Furthermore, single-dose treatment with a combination of vitamins E and C 30 min after the administration of MD can reduce LPO caused by MD.
Cytotoxicity in ciprofloxacin-treated human fibroblast cells and protection by vitamin E
Authors: Gürbay A , Garrel C , Osman M , Richard M-J , Favier A , Hincal F
Published: January 2003

Quinolones (Qs) were shown to have cytotoxic effects in various cell lines including human carcinoma cells; however, mechanism of these effects was not fully understood. To investigate the possibility of the involvement of an oxidative stress induction in this mechanism of action, we examined viability of human fibroblast cells exposed to a Q antibiotic, ciprofloxacin (CPFX), and measured lipid peroxidation and total glutathione (GSH) levels, and activities of catalase (Cat), superoxide dismutases (SODs), glutathione peroxidase (GPx). The effects of vitamin E pretreatment on those parameters were also examined. Our results showed that the effect of CPFX on the viability of the cells, as determined by neutral red uptake assay, was time dependent. Cytotoxicity was not observed in the concentration range of 0.0129–0.387 mM CPFX when the cells were incubated for 24 hours. However, significant level of cytotoxicity was observed at concentrations 0.129 and 0.194 mM, and ¶ 0.129 mM, following 48 and 72 hours of exposure, respectively. When the cells were exposed to 0.194 mM CPFX for 48 hours, the level of lipid peroxidation increased and the content of total GSH decreased significantly; activities of total SOD, Mn SOD and CuZn SOD did not change; the decrease observed in the activity of Cat was not significant; and the activity of GPx was highly variable. Vitamin E pretreatment of the cells provided significant protection against CPFX-induced cytotoxicity; lowered the level of lipid peroxidation significantly, but increased the total GSH content only moderately; no change was observed in the activities of Cat and total SOD, but a significant increase in Mn SOD and a significant decrease in Cu Zn SOD were noticed. These results suggested that CPFX-induced cytotoxicity on human fibroblast cell cultures is related to oxidative stress, and vitamin E pretreatment can afford a protection.
The chelating treatment is not useful in human's intoxication with acute herbicidal organic arsenic
Authors: Chou C-J , Tsai M-S , Tsai J-L , Lee H-H , Lin T-J
Published: January 2003

The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.
Effects of ascorbic acid and a-tocopherol on arsenic-induced oxidative stress
Authors: Ramanathan K , Balakumar B S , Panneerselvam C
Published: January 2003

Arsenic is an ubiquitous element in the environment causing oxidative burst in the exposed individuals leading to tissue damage. Antioxidants have long been known to reduce the free radical-mediated oxidative stress. Therefore, the present study was designed to determine whether supplementation of a-tocopherol (400 mg/kg body weight) and ascorbic acid (200 mg/kg body weight) to arsenic-intoxicated rats (100 ppm in drinking water) for 30 days affords protection against the oxidative stress caused by the metalloid. The arsenic-treated rats showed elevated levels of lipid peroxide, decreased levels of non-enzymatic antioxidants and activities of enzymatic antioxidants. Administration of a-tocopherol and ascorbic acid to arsenic-exposed rats showed a decrease in the level of lipid peroxidation (LPO) and enhanced levels of total sulfhydryls, reduced glutathione, ascorbic acid and a-tocopherol and so do the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase to near normal. These findings suggest thata-tocopherol and ascorbic acid prevent LPO and protect the antioxidant system in arsenic-intoxicated rats.
Chemical necrotizing fasciitis due to household insecticide injection: is immediate radical surgical debridement necessary?
Authors: Terzi C , Bacakoglu A , Ünek T , Özkan M H
Published: January 2003

We describe two cases of chemical necrotizing fasciitis in the upper extremities, anterior chest wall and epigastric region of the abdominal wall caused by household insecticide injection. We suggest that surgical debridement can be successfully performed in the subacute period under close observation in hemodynamically stable patients.
The cytotoxic effects of a traditional Zulu remedy, impila (Callilepis laureola)
Authors: Stewart M J , Steenkamp V , Van der merwe S , Zuckerman M , Crowther N J
Published: January 2003

The traditional Zulu remedy impila (Callilepis laureola) can cause acute fatal hepatocellular necrosis, especially in children. We investigated the mechanism(s) of toxicity using HuH-7 hepatocytes. Impila tubers were extracted with boiling water and the aqueous extract was used at different concentrations to study the effects on the morphology of the cells. Flow cytometry and labelling with fluorescent antibodies to tubulin were also used. At high concentrations, necrosis occurred; however, at lower concentrations, the extracts gave rise to a variety of changes including hypercondensation of chromatin, multinucleate cells, nuclear fragmentation and apoptosis. In addition, we observed destruction of cytoplasmic tubulin. These findings give further insight into the mechanism of toxicity of herbal remedies containing atractyloside.
Modulation of antioxidant defence system by dietary fat in rats intoxicated with o-toluidine
Authors: Jodynis-Liebert J , Murias M
Published: January 2003

o-Toluidine was administered to rats in the diet for four weeks at levels approximately 40, 80 and 160 mg/kg b.w. per day. Two types of diet have been used, standard (4% fat) and high fat (14% fat). Activity of antioxidant enzymes, level of glutathione and thiobarbituric acid reactive substances were measured in liver. Glutathione peroxidase was significantly increased in all treated groups while glutathione S-transferase and glutathione reductase were elevated in rats fed high-fat diet. o-Toluidine slightly enhanced catalase activity regardless of the kind of diet. Superoxide dismutase was the only enzyme whose activity was lowered in almost all treated groups. Enzymatic and nonenzymatic microsomal lipid peroxidation was enhanced 2-to 3-fold in both diet groups. Reduced glutathione level in liver was 2.3-to 4.0-fold increased in all treated groups. Our findings indicate that free radical processes can be involved in the toxic effects of o-toluidine and dietary fat can modify the response of some antioxidant enzymes to this compound.
Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits
Authors: Klimtová Ivona , Šimůnek Tomáš , Mazurová Yvona , Hrdina Radomír , Gerš Vladimír , Adamcová Michaela
Published: January 2003

This study compares the chronic toxicity of two anthracyclines–daunorubicin and doxorubicin, commonly used for induction of anthracycline cardiomyopathy in the rabbit model. Such a comparative study has not been published until now. Both drugs were administered intravenously to male Chinchilla rabbits in doses at 3 mg/ kg (50 mg/m2) once weekly for 10 weeks. Selected biochemical, haematological and cardiovascular parameters and body weights were regularly monitored; additionally, a histological evaluation of heart, kidney and liver was performed at the end of the experiment. In the daunorubicin group, there were marked signs of the progressive development of heart failure, like the significant increases of the pre-ejection period/left ventricular ejection time index values (up to 134%)–and histological changes within the myocardium were also observed. On the other hand, the 10-week doxorubicin administration did not cause these changes that are typical for heart injury. Haematotoxicity, manifested particularly by aplastic anaemia, was apparent in both the experimental groups. Significant body weight loss (by 45.2%) and high premature mortality (100% versus 36.4%) reflected a greater general toxicity, especially nephrotoxicity of doxorubicin in comparison with daunorubicin. Further studies are necessary to find a possible explanation for these findings.
Pulmonary toxicity of dust generated during weaving of carpets
Authors: Ameen M , Ahmad I , Rahman Q
Published: January 2003

The dust generated during weaving (carpet dust) tibbati, knotted and tuffted carpets in carpet industry was studied for its toxicity in vitro and in vivo. Carpet dust (0.5, 1.0, 2.5 and 5.0 mg/1£10 6 cells) caused in vitro cytotoxicity in rat alveolar macrophages (AM) in a concentration-dependent manner. The cytotoxic, inflammatory and oxidative responses were observed in bronchoalveolar lavage fluid (BALF) of rats at 1, 4, 8 and 16 days after exposure. Rats were intratracheally exposed at 5 mg/rat individually to all three types of carpet dust. All types of carpet dusts produced increased AM, lymphocytes (PMN) population in BALF suggesting their inflammatory reactions. Cytotoxic nature of carpet dust was shown by the increased activities of lactate dehydrogenase (LDH) and acid phosphatase (AP) in BALF. Increased AM population and in vitro cytotoxicity due to carpet dusts have shown some correlation with the levels of LDH and AP activities in BALF. The gradual enhanced profile of hydrogen peroxide (H2O2) and nitric oxide (NO) along with depletion of reduced glutathione (GSH) in AM due to these carpet dusts are suggestive of their oxidant nature. The enzyme activities of both glutathione peroxidase (GPx) and glutathione reductase (GR) in AM were marginally reduced in exposed rats. In conclusion, the data suggest the cytotoxic, inflammatory and oxidant nature of carpet dusts. It is extrapolated that health effects on carpet weavers would be associated with the concentration and nature of airborne dust generated during weaving of carpets
Epileptic seizures, cranial neuralgias and paroxysmal symptoms in remitting and progressive multiple sclerosis
Authors: Eriksson M , Ben-Menachem E , Andersen O
Published: January 2003

The occurrence of a first epileptic seizure, spinal or brainstem paroxysmal symptom and cranial neuralgia during 25 years after onset was studied in a population-based multiple sclerosis (MS) cohort of 255 patients. Epileptic seizures occurred in 20, paroxysmal symptoms in 11 and cranial (trigeminal, intermedius, retroauricular or occipital) neuralgia in 11 patients. The yearly incidence of epileptic seizures in MS was estimated to be 349(-153)/100,000, approximately seven times higher than in the general population. The yearly incidence of a first paroxysmal symptom in the present material was calculated to be 190 cases in 100,000 MS patients, and the yearly incidence of cranial neuralgia was 189 cases in 100,000 MS patients. The epileptic seizures were more frequent during the progressive course than in the relapsing-remitting (RR) course. The frequencies of paroxysmal symptoms and cranial neuralgia did not differ between these two disease courses. A coincidence of epileptic seizures and a decline in cognitive functioning not seen among patients with paroxysmal symptoms was found. The relatively late occurrence of epileptic seizures indicates that the frequency of epileptogenesis, known to involve neuronal damage, increases in the later stages of MS.
The roles of blink reflex and sympathetic skin response in multiple sclerosis diagnosis
Authors: Nazhel B , İrkeç C , Koçer B
Published: January 2003

The neurological history and examination are important in multiple sclerosis (MS) diagnosis, but early and accurate diagnosis of MS often requires judicious use of paraclinical information. Electrophysiolgic techniques have an important role in demonstrating lesions that are clinically silent, but magnetic resonance imaging (MRI) is accepted as the most sensitive paraclinical test for detecting asymptomatic dissemination in space for MS patients. In order to test the sensitivity of electrophysiologic techniques in diagnosing asymptomatic MS lesions, we performed blink reflex (BR) and sympathetic skin response (SSR) studies on 13 female (mean age 39∓9 years) and 8 male (mean age 35∓14 years) patients with a diagnosis of definite MS who do not have any clinical symptoms nor signs referable to brainstem or autonomic system dysfunction. Forty three percent of patients on SSR testing and 40% of patients on BR testing demonstrated abnormal results. In countries with unfavorable economic conditions, diagnosis, especially the follow-up evaluation of MS patients, poses a major dilemma. The role of diagnostic techniques in MS diagnosis when MRI is available is an economic problem. Diagnostic evaluation adds to the cost of health expenses. We usually choose to perform MRI only at the initial diagnosis of MS and perform follow-up evaluations during remissions and exacerbations with the aid of electrophysiologic techniques. We stress the importance of electrophysiologic screenings in MS patients because they provide data that cannot be obtained through clinical evaluations, only with a little cost.
Central hyperacusis with phonophobia in multiple sclerosis
Authors: Weber H , Pfadenhauer K , Stöhr M , Rösler A
Published: January 2003

Hearing disorders are a well-described symptom in patients with multiple sclerosis (MS). Unilateral or bilateral hyperacusis or deafness in patients with normal sound audiometry is often attributed to demyelinating lesions in the central auditory pathway. Less known in MS is a central phonophobia, whereby acoustic stimuli provoke unpleasant and painful paresthesia and lead to the corresponding avoidance behaviour. In our comparison collective, patient 1 described acute shooting pain attacks in his right cheek, each time set off by the ringing of the telephone. Patient 2 complained of intensified, unbearable noise sensations when hearing nonlanguage acoustic stimuli. Patient 3 noticed hearing unpleasant echoes and disorders of the directional hearing. All patients had a clinical brainstem syndrome. ENT inspection, sound audiometry and stapedius reflex were normal. All three patients had pathologically changed auditory evoked potentials (AEPs) with indications of a brainstem lesion, and in magnetic resonance imaging (MRI) demyelinating lesions in the ipsilateral pons and in the central auditory pathway. The origin we presume in case 1 is an abnormal impulse conduction from the leminiscus lateralis to the central trigeminus pathway and, in the other cases, a disturbance in the central sensory modulation. All patients developed in the further course a clinically definite MS. Having excluded peripheral causes for a hyperacusis, such as, e.g., an idiopathic facial nerve palsy or myasthenia gravis, one should always consider the possibility of MS in a case of central phonophobia. Therapeutic possibilities include the giving of serotonin reuptake inhibitors or acoustic lenses for clearly definable disturbing frequencies.
Analyses of the minimum data set: comparisons of nursing home residents with multiple sclerosis to other nursing home residents
Authors: Buchanan R J , Wang S , Ju H
Published: January 2003

This research compares nursing home residents with multiple sclerosis (MS) at admission to other nursing home residents using the minimum data set (MDS). These comparisons include sociodemographic characteristics and health status measures, as well as treatments and procedures received. We analysed 14,009 admission assessments in the MDS for residents with MS between June 22, 1998 and December 31, 2000. We also analysed 440,642 MDS admission assessments for all residents admitted to nursing homes during the year 2000, with any admission assessments for residents with MS excluded from this comparison group. Residents with MS were significantly younger at admission than other recently admitted residents. In addition, residents with MS tended to be significantly more physically disabled and also less cognitively impaired than other residents at admission, based on analyses of several measures of physical disability and cognitive performance. Nursing homes caring for residents with MS should provide services and programs, including mental health care, that address the needs of these younger, more physically disabled, and more cognitively intact residents.
Simple phonic tic in multiple sclerosis
Authors: Lana-Peixoto M A , Teixeira A L ,   The Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS)
Published: January 2003

Movement disorders occurring in association with multiple sclerosis (MS) are rare. Among them paroxysmal dystonia is the most common, although chorea, ballism, palatal myoclonia, spasmodic torticollis, writer’s cramp and generalized dystonia have been reported. We describe a 34-year old woman with MS who developed simple phonic tic characterized by throat-clearing sounds. Magnetic resonance imaging showed demyelinating lesions involving the thalamus and basal ganglia. This is the first report of tic disorder occurring as a manifestation of MS.
TACE mRNA expression in peripheral mononuclear cells precedes new lesions on MRI in multiple sclerosis
Authors: Seifert T , Kieseier B C , Ropele S , Strasser-Fuchs S , Quehenberger F , Fazekas F , Hartung H-P
Published: January 2003

Tumor necrosis factor-a (TNF-a) is involved in the pathogenesis of multiple sclerosis (MS). It has to be released from its cell membrane-bound precursor by proteolytic cleavage. This is mainly performed by a member of the ADAM (a disintegrin and metalloproteinase) family of enzymes, TNF-a-converting enzyme (TACE, ADAM 17). In a longitudinal study on 11 relapsing-remitting MS patients, we qualitatively determined mRNA expression of TNF-a and TACE in peripheral blood mononuclear cells (PBMCs) without ex vivo stimulation. mRNA expression was related to disease activity as assessed by monthly gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI). Patients found positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan one month following PBMC sampling.
A comparative study of Japanese multiple sclerosis patients with and without oligoclonal IgG bands
Authors: Nakashima I , Fujihara K , Misu T , Fujimori J , Sato S , Takase S , Itoyama Y
Published: January 2003

The cerebrospinal fluid oligoclonal IgG bands (OB) are less frequently observed in Japanese multiple sclerosis (MS) patients compared with Caucasian patients. We studied 40 consecutive Japanese MS patients to investigate the differences in the clinical and magnetic resonance imaging (MRI) features of MS between OB-positive patients and OB-negative ones. Among the 40 patients, 22 (55%) patients were OB-positive by either agarose gel electrophoresis (AGE) or isoelectric focusing (IEF), and 18 (45%) patients were OB-negative by both AGE and IEF. There were differences between the two groups only in the clinical forms of MS, but not in terms of gender, onset age, disease duration, or disease severity. In the OB-negative group, nine (50%) of the patients had the optic-spinal form of MS (OS-MS), but only one patient (4.5%) in the OB-positive group had OS-MS. Although most OB-positive patients showed brain MRI lesions typical of MS, 13 (72%) of the OB-negative patients showed no or few brain MRI lesions and the rest of the OB-negative patients showed atypical MS lesions, such as diffuse white matter lesions or large ring-enhanced lesions. Our results suggest that the majority of OB-negative Japanese MS patients show either no or few brain MRI lesions or atypical brain MRI lesions.
Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters
Authors: Flachenecker P , Kümpfel T , Kallmann B , Gottschalk M , Grauer O , Rieckmann P , Trenkwalder C , Toyka K V
Published: January 2003

Objectives: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). To delineate more clearly the frequency and type of fatigue, we first compared four widely used fatigue scales in consecutive MS patients. Secondly, to further clarify the nature of fatigue, we investigated its relation to physical disability, course of the disease, immunotherapy, and depression. Patients and Methods: Between February and September 2000, 151 consecutive MS patients entering our outpatient clinic (94 relapsing-remitting, 50 secondary progressive, and 7 primary progressive patients; mean age 29.0-7.3 years, mean disease duration 9.9-6.7 years, median EDSS 3.5) filled in a standardized questionnaire including four fatigue scales - Fatigue Severity Scale (FSS), MS-specific FSS (MFSS), Modified Fatigue Impact Scale (MFIS), and Visual Analogue Scale (VAS). Patients were included in the ‘MS-related fatigue group’ (MS-F) when they stated in the questionnaire that fatigue: 1) is one of their three most disabling symptoms; 2) occurs daily or on most of the days; and 3) limits their activities at home or at work. Patients fulfilling none of these criteria were classified as ‘MS-related nonfatigue group’ (MS-NF). Depression was measured by Beck’s Depression Inventory (BDI). Results: Although all scales showed significant differences between MS-F and MS-NF, correlation between these scales was, at best, moderate (correlation coefficients ranging from 0.06 to 0.56). The most discriminative scales were FSS and MFIS, showing no overlap of the 10th and 90th percentiles for the MS-F and MS-NF groups, with cut-off values of 4.6 and 38, respectively. Depression (BDI≥18) was present in 24 of 148 patients who filled in the BDI (16%). FSS was significantly correlated with physical disability (r =0.33, p <0.0001) and BDI (r =0.41, p<0.0001), but not with age, disease duration, clinical activity, and treatment with interferon-b. In multivariate analysis, however, only BDI independently predicted fatigue. Conclusions: The association of fatigue and depression suggests that there might be either common underlying mechanisms or interdependence by a cause-and-effect relationship that requires further investigation. The weak correlation within various fatigue scales is best explained by the fact that fatigue is a multidimensional symptom and, therefore, the available tests measure and weight different aspects of fatigue. Our findings underline the necessity for a more exact definition of fatigue and the development of more valid tools if these are to be used to evaluate treatments.
An examination of the association between b2 adrenergic receptor polymorphisms and multiple sclerosis
Authors: Niino M , Kikuchi S , Miyagishi R , Fukazawa T , Yabe I , Tashiro K
Published: January 2003

In multiple sclerosis (MS), β-adrenergic receptor densities on peripheral blood mononuclear cells are enhanced, while the astrocytes present in plaques lack β2 adrenergic receptor (β2AR) expression. This differentially altered expression suggests that β2ARs may influence the pathogenesis of MS. In the present study, we investigated the association of polymorphisms of the β2AR gene with the occurrence of MS. Our results showed no significant differences in the distribution of the polymorphisms between MS patients overall and control subjects. Furthermore, no association was observed between the presence of β2AR gene polymorphisms and clinical characteristics, such as age at disease onset and disease severity. While a trend towards an increase of the Gly allele frequency in codon 16 was observed in the secondary-progressive MS, this result was not significantly different from that observed in relapsing-remitting MS patients or control subjects. Together, our findings suggest that the presence of β2AR gene polymorphisms may be inconclusive in the susceptibility to MS or in the clinical characteristics of Japanese patients with MS and, therefore, need further studies.
The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study
Authors: Kalkers N F , Barkhof F , Bergers E , van Schijndel R , Polman C H
Published: January 2003

Progressive axonal loss is the most likely pathologic correlate of irreversible neurologic impairment in primary progressive multiple sclerosis. In a run-in versus treatment trial, we show that the neuroprotective agent riluzole seems to reduce the rate of cervical cord atrophy and the development of hypointense T1 brain lesions on magnetic resonance imaging.
Susceptibility to Theiler’s murine encephalomyelitis virus-induced demyelinating disease in BALB/cAnNCr mice is related to absence of a CD4+ T-cell subset
Authors: Karls K A , Denton P W , Melvold R W
Published: January 2003

Two histocompatible substrains of BALB/c mice (BALB/cByJ, BALB/cAnNCr) are resistant and susceptible, respectively, to Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) - a model for viral etiology of human multiple sclerosis. BALB/cByJ mice become susceptible following low-dose irradiation given prior to infection. Resistance is restored by adoptive transfer of CD8+ (but not CD4+) splenic T cells from infected, unirradiated BALB/cByJ donors. In contrast, resistance is conferred to BALB/cAnNCr mice by adoptive transfer of either CD4+ or CD8+ T cells from resistant BALB/cByJ donors. T cells from BALB/cAnNCr mice cannot confer protection. To integrate these two observations, we hypothesized that the BALB/cAnNCr mice possess precursors of the regulatory CD8+ T cells, but fail to activate them because they lack a critical CD4+ T-cell subpopulation. We tested this model using serial transfers. The transfer of CD4+ T cells from the BALB/cByJ to the BALB/cAnNCr mice permitted development of BALB/cAnNCr CD8+ T cells that, in turn, provided resistance when transferred into susceptible recipients. The BALB/cByJ CD4+ T cells, which activated the CD8+ cells, were sensitive to low-dose irradiation, unlike CD4+ T cells involved in the later inflammatory demyelination. Thus, susceptibility of BALB/cAnNCr mice is due to a defective/absent CD4+ T -cell subset acting immediately after infection.
Quality of life in multiple sclerosis patients in Spain
Authors: Chang C-H , Cella D , Fernández O , Luque G , de Castro P , de Andrés C , Casanova B , Hernández M A , Prieto J M , Fernández V E , de Ramón E ,   Grupo Español de Calidad de Vida en Esclerosis Múltiple
Published: January 2003

Objective: The cross-sectional study evaluated the psychometric properties of the Functional Assessment of Multiple Sclerosis (FAMS) Spanish version and its use in measuring quality of life (QOL) of multiple sclerosis (MS) patients in Spain. Methods: The FAMS is a factorially derived self-report scale designed to assess six primary aspects of QOL of patients with MS: Mobility, Symptoms, Emotional Well-Being, General Contentment, Thinking and Fatigue, and Family/Social Well-Being. Its Spanish translated version was used to assess QOL of 625 MS patients recruited in an outpatient clinic setting from 58 hospitals in Spain. Internal consistency of the Spanish FAMS was evaluated. Multiple regression analyses were performed to identify significant predictors from demographic, clinical and treatment characteristics, and Kurtzke Expanded Disability Status Scale (EDSS) scores in predicting FAMS scale scores. Results: Most of the patients are females (66%), and 74% were of the relapsing-remitting (RR) clinical subtype. Cronbach’s alpha coefficients were high (range=0.78-0.96), indicating subscale homogeneity comparable to that of the original English version. Linear multivariate regression analyses revealed that the EDSS is a dominant variable in predicting all the FAMS subscales, especially mobility (R2=0.51) and the total scores. Conclusions: The Spanish FAMS is a psychometrically valid instrument that allows clinicians and clinical researchers the ability to measure the QOL concerns of MS patients in Spain.
Arthritis during interferon beta-1b treatment in multiple sclerosis
Authors: Altintas A , Alici Y , Melikoğlu M , Siva A
Published: January 2003

Interferon beta (IFN-β) is the most widely prescribed disease-modifying drug for multiple sclerosis (MS). Therapy with IFN-βmay be associated with a number of adverse reactions. The development or exacerbation of other autoimmune diseases is a rare but reported side effect of IFN-βtherapy. In this case report, we present clinical and laboratory findings of two MS patients who developed arthritis during IFN-β1b treatment, probably of autoimmune origin.
Low interferon gamma producers are better treatment responders: a two-year follow-up of interferon beta-treated multiple sclerosis patients
Authors: Petereit H F , Nolden S , Schoppe S , Bamborschke S , Pukrop R , Heiss W D
Published: January 2003

As response to interferon beta (IFNB) treatment, a 50% reduction of the mean relapse rate compared to pretreatment values has been reported. However, individual responses vary considerably, ranging from no reduction in exacerbation frequency to complete suppression of relapses for at least two years. At the moment, valid predictors for IFNB response are lacking. Here we present a prospective evaluation of 33 patients with primary relapsing multiple sclerosis, who were followed for two years of IFNB treatment. A low interferon gamma (IFG) production before treatment predicted a two-year term without exacerbations in 68.8% of cases correctly, whereas a high pretreatment IFG production implied the risk of at least one relapse in the first two years in 70.6%. These preliminary results encourage further evaluation of IFG as predictor of an IFNB treatment response.
Mature bone marrow-derived dendritic cells polarize Th2 response and suppress experimental autoimmune encephalomyelitis
Authors: Zhang G-X , Kishi M , Xu H , Rostami A
Published: January 2003

Distinct subsets of dendritic cells (DCs) based on the origin, phenotypes, and the nature of the signals that promote DC maturation can determine polarized immune responses of T cells. In this study, DCs were cultured from mouse bone marrow (BM) progenitors in granulocyte-macrophage colony-stimulating factor (GM-CSF). To generate mature DCs (mDCs), lipopolysaccharide (LPS) was used in the culture for 24 h. LPS-stimulated DCs were phenotypically mature, which exhibited strongly upregulated CD40, B7.1, and B7.2 compared to non-LPS-stimulated immature DCs (imDCs). Both mDCs and imDCs expressed high levels of MHC class II but low level of CD54. mDCs produced higher levels of IL-10 and lower IL-12 compared to imDCs. No IFN-g or IL-4 was found in both groups. When mDCs were injected intraperitoneally (i.p.) to the mice with experimental autoimmune encephalomyelitis (EAE), the severity of clinical signs and inflammation in the CNS was significantly suppressed compared to imDC-injected mice (p<0.01) and PBS-injected mice (p <0.02). Moreover, lymphocytes from mDC-injected mice produced lower level of IL-12, IFN-g, but higher level of IL-10, compared to imDC-injected and non-DC-injected mice. We conclude that BM-mDCs, but not BM-imDCs, promote Th2 differentiation and have the potential for suppression of inflammatory demyelination.
Retinol measurements and retinoid receptor gene expression in patients with multiple sclerosis
Authors: Royal W , Gartner S , Gajewski C D
Published: January 2003

Treatment with interferon (IFN)-β1a has been associated with decreased disease activity in patients with multiple sclerosis (MS). In several biological systems, type I IFNs and retinoids have been demonstrated to have synergistic effects. In these studies, we measured blood and cerebrospinal fluid (CSF) retinol levels and naïve and memory T-helper cell subset percentages in samples from a group of patients with MS. We also examined retinol receptor expression in peripheral blood cells from MS patients with or without a history of prior treatment with IFN-β1a. The mean plasma retinol level for untreated relapsing-remitting (RR) MS patients was lower than for patients with noninflammatory neurological disease. Among IFN-β1a-treated RR patients, mean levels were slightly higher than for RR patients not on treatment. Lower plasma retinol levels among the MS patients studied were associated with higher CSF retinol index measurements - a measure that was calculated to correct for nonspecific leakage of retinol from blood into CSF. For the MS samples examined, there was a borderline statistically significant direct correlation between CSF retinol index measurements and CSF memory T-helper cell percentages. Examination of peripheral blood from untreated RR patients for retinoid receptor mRNA expression revealed the expression of the retinoic acid receptor (RAR)-α, RAR-γ, and retinoic X receptor (RXR)-α receptor subtypes. For RR patients on IFN-β1a therapy, expression of the same RAR subtypes was noted as well as expression of RXR-βand RXR-γ. These studies suggest an association between plasma retinol levels and clinical disease activity in patients with MS and that treatment with IFN-β1a may be associated with activation of specific retinoid receptor subtypes.
Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis
Authors: Fazekas F , Ropele S , Enzinger C , Seifert T , Strasser-Fuchs S
Published: January 2003

Objective: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. Methods: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free) were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). Results: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p <0.0001) and of kfor (F7,166=105.2; p <0.0001), and by an increase of T1free (F7,166=57.3; p <0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. Conclusions: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event.
Effect of combined IFNb-1a and glatiramer acetate therapy on GA-specific T-cell responses in multiple sclerosis
Authors: Dhib-Jalbut S , Chen M , Henschel K , Ford D , Costello K , Panitch H
Published: January 2003

The combined treatment with interferon (IFN) and glatiramer acetate (GA) is of current interest in multiple sclerosis (MS). The therapeutic effect of GA in MS is believed to be mediated by GA-specific Th2 cells. IFN has a significant anti-proliferative effect on GA-induced lymphoproliferation in vitro. Therefore, we examined the possibility that IFN may interfere with the generation and phenotype of GA T-cell responses in MS patients receiving combined therapy. Sixty-six GA-specific T-cell lines (TCL) were generated ex vivo from five MS patients enrolled in an open-label clinical trial of combined IFN/GA treatment. Controls included 83 pretreatment and 131 on-treatment GA-TCL from 11 MS patients treated with GA only, and five GA-TCL generated from four patients receiving IFN -1a monotherapy. IFNg and IL-5 (markers of Th1 and Th2 responses, respectively) were assayed by ELISA in GA-TCL supernatants. Th1/Th2 bias was defined by the IFNg/IL-5 level ratio (> 2=Th1 bias, <0.5=Th2 bias, and 0.5- 2=Th0 bias). The frequency with which GA-reactive TCL were generated was 37.0% for the patients in the combination trial compared to 33.3% in the patients receiving GA alone. The mean stimulation index of the GA-TCL was 8.41 (range 2-42) for the combination compared to a mean of 6.29 (range 2-37) for the GA-treated group - a nonsignificant difference. Mean GA-TCL IFNg production was significantly lower in all treatment groups compared to pretreatment. IL-5 levels were enhanced in all treatment groups compared to pretreatment levels, but the change was not statistically significant. The Th1/Th0/Th2 distribution of GA-TCL was 7%/30%/63% for the GA+IFN group, 8%/9%/83% for the GA group, compared to 48%/21%/31% pre-GA treatment. All five GA-TCL from the IFN -1a monotherapy patients were Th2-biased. We conclude that IFN -1a does not affect the generation of GA-reactive T cells in vivo. Although more Th0 GA-TCL occurred with combination therapy than with GA treatment alone, both groups shared an overall Th2 bias. Therefore, we speculate that combined therapy is unlikely to reduce the efficacy of GA treatment in MS.
Classification of wear mechanisms/models
Authors: Kato K
Published: January 2003

Wear mechanisms may be briefly classified by mechanical, chemical and thermal wear whose wear modes are further classified into seven. Some of them have wear models and mathematical expressions of wear rate, but many of them have not satisfactory wear models and wear equations for reliable predictions. This paper reviews such present understanding on wear mechanisms and models.
Wear of metals: A consequence of stable/unstable material response
Authors: Biswas S. K.
Published: January 2003

Wear of metals in dry sliding is dictated by the material response to traction. This is demonstrated by considering the wear of aluminium and titanium alloys. In a regime of stable homogeneous deformation the material approaching the surface from the bulk passes through microprocessing zones of flow, fracture, comminution and compaction to generate a protective tribofilm that retains the interaction in the mild wear regime. If the response leads to microstructural instabilities such as adiabatic shear bands, the near-surface zone consists of stacks of 500nm layers situated parallel to the sliding direction. Microcracks are generated below the surface to propagate normally away from the surface though microvoids situated in the layers, until it reaches a depth of 10-20 μm. A rectangular laminate debris consisting of a 20-40 layer stack is produced. The wear in this mode is severe.
Wear transitions and tribochemical reactions in ceramics
Authors: Jahanmir S
Published: January 2003

Structural ceramics are used in diverse tribological applications due to their unique properties that include resistance to abrasion and erosion, resistance to corrosive wear, wear resistance at elevated temperatures, low density and unique electrical, thermal and magnetic properties. Applications include precision instrument bearings, cutting tool inserts, prosthetic articulating joints and engine components. Following a brief overview of the processing methods applied to alumina, silicon nitride and silicon carbide, the wear behaviour of these ceramics is reviewed. The wear behaviour changes as the load or the coefficient of friction is increased. This change is associated with a drastic increase in wear at a critical load that depends on the material and test conditions. This transition from mild to severe wear occurs through a microfracture process at the sliding contact. Contact mechanics is used to develop a simple model to determine whether contact failure occurs by a classical brittle process (i.e. cone cracking) or a quasi-plastic behaviour (i.e. small microcracks distributed below the contact surface). The model provides estimates of the transition load within a factor of two of the experimentally obtained values and indicates that the brittle behaviour dominates the observed transition from mild to severe wear in the three ceramics evaluated in this study. The limitations of the model and its use in design of tribological components are discussed. The role of lubrication and tribochemical reactions between ceramic surfaces and atmospheric moisture on the wear behaviour is discussed.
Friction and wear of diamond and diamond-like carbon films
Authors: Erdemir A
Published: January 2003

Detailed tribological studies on diamond and diamond-like carbon (DLC) films have confirmed that these films are inherently self-lubricating and resistant to abrasive, adhesive and corrosive wear. Because of their high chemical inertness, they are also resistant to corrosion and oxidation (even at elevated temperatures). The combination of such exceptional qualities in these films makes them ideal for a wide range of demanding tribological applications (such as microelectromechanical systems, cutting tools, mechanical seals, magnetic hard disks, etc.). These films, available for more than three decades, have been used extensively for tooling and magnetic hard disk applications. Their potential in other application areas is currently being explored around the world. With the development of new and more robust deposition methods in recent years, it is envisioned that the production of high quality diamond and DLC films will become very cost effective and highly reliable for large-scale applications in the transportation and manufacturing sectors. In this paper, sliding wear mechanisms of diamond and DLC films will be presented. Specifically, it will be shown that, in general, the wear of these films is extremely low (mainly because of their exceptional hardness and low friction characteristics). Specific test conditions established during each sliding test, however, may dramatically affect the wear performance of certain diamond and DLC films. One of the dominant wear mechanisms relates to a phase transformation that is primarily the result of very high mechanical and thermal loadings of sliding contact interfaces. The transformation products (such as disordered graphite) trapped at the sliding interface may transfer to the mating surface and significantly affect friction and wear. This paper describes, in terms of structural and fundamental tribological knowledge, the ideal film microstructures and chemistry, as well as operational conditions under which diamond and DLC films perform the best and provide superlow friction and wear properties in sliding tribological applications.
Wear of polymers
Authors: Briscoe B. J. , Sinha S. K.
Published: January 2003

This paper reviews some of the recent progress which has been made in the area of the sliding wear of polymers. Wear mechanisms are classified under three broad approaches which reflect primarily the way this subject has been historically studied. It is demonstrated here that the wear of polymers is influenced by the contact conditions, the bulk mechanical properties of the polymer and the properties of the ‘third body’, which generally appears in the form of transfer film or degraded polymer particles between two sliding surfaces. Further, this paper establishes a link between the different contact and material parameters and shows how they are important in elucidating the generic wear mechanisms for polymers. The effects of environment and lubrication upon polymer wear are briefly explained in terms of the chemical interactions between the liquid phase and the polymer. The capabilities and limitations of current predictive wear models for polymeric contacts are also highlighted.
Wear of polymer composites
Authors: Friedrich K , Reinicke R , Zhang Z
Published: January 2003

The use of polymers and polymer composites in various tribological situations has become state of the art. Nevertheless, new developments are still under way to explore new fields of application for these materials and to tailor their properties for more extreme loading conditions. Some of these developments can be followed when searching through the 56 references given at the end of this review. The present overview describes, in particular, some of the authors' approaches in designing polymeric composites in order to operate under low friction and low wear against steel counterparts. Special emphasis is focused on thermoplastics and thermosets reinforced with special fillers (including nanoparticles). An attempt is made to predict their wear properties and to carry out systematic parameters studies by the use of artificial neural networks. Further information will be given on the fibre orientation dependence of wear of continuous carbon fibre-polymer matrix composites, and on attempts to predict their load-bearing capacity and related wear mechanisms by the use of finite elements. In addition, some new steps towards the development of functionally graded tribomaterials are illustrated.
Wear in boundary lubrication
Authors: Hsu S. M. , Munro R , Shen M. C.
Published: January 2003

Wear is a complex subject. Wear studies under lubricated conditions can be classified into two categories: wear mechanisms study of the materials under ‘lubricated’ conditions, and the evaluation of the lubricant chemistry using the same materials. Much confusion exists in the literature because these two communities historically do not interact frequently to understand each other's views. In the 1980s, material science research was emphasized around the world. As a result, wear studies began to flourish, examining various new materials for potential applications in new technologies. Since new materials came in many different forms, a wide variety of wear test geometries and test methods were developed for solids, coatings and thin films. Many of the wear test methodologies were established under a ‘dry’ condition (without the use of liquid lubricants). In this paper, the dry condition will be used as a baseline to compare various wear phenomena under lubricated conditions. Within this context, wear test procedures, basic assumptions and associated data interpretations will be examined. Wear mechanisms under lubricated conditions will also be discussed. Finally the current state of modelling under lubricated wear conditions will be reviewed.