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ID PMID Title PublicationDate abstract
18466574 Gene x gene and gene x environment interactions for complex disorders. 2007 The restricted partition method (RPM) provides a way to detect qualitative factors (e.g. genotypes, environmental exposures) associated with variation in quantitative or binary phenotypes, even if the contribution is predominantly an interaction displaying little or no signal in univariate analyses. The RPM provides a model (possibly non-linear) of the relationship between the predictor covariates and the phenotype as well as measures of statistical and clinical significance for the model.Blind to the generating model, we used the RPM to screen a data set consisting 1500 unrelated cases and 2000 unrelated controls from Replicate 1 of the Genetic Analysis Workshop 15 Problem 3 data for genetic and environmental factors contributing to rheumatoid arthritis (RA) risk. Both univariate and pair-wise analyses were performed using sex, smoking, parental DRB1 HLA microsatellite alleles, and 9187 single-nucleotide polymorphisms genotypes from across the genome. With this approach we correctly identified three genetic loci contributing directly to RA risk, and one quantitative trait locus for the endophenotype IgM level. We did not mistakenly identify any factors not in the generating model. All the factors we found were detectable with univariate RPM analyses. We failed to identify two genetic loci modifying the risk of RA. After breaking the blind, we examined the true modeling factors in the first 50 data replicates and found that we would not have identified the additional factors as important even had we combined all the data from the first 50 replicates in a single data set.
18466565 Exploiting gene x gene interaction in linkage analysis. 2007 When two genes interact to cause a clinically important phenotype, it would seem reasonable to expect that we could leverage genotypic information at one of the loci in order to improve our ability to detect the other. We were therefore interested in extending the posterior probability of linkage (PPL), a class of linkage statistics we have been developing over the past decade, in order to explicitly allow for gene x gene interaction. In this report we utilize a new implementation of the PPL incorporating liability classes (LCs), which provide a direct parameterization of gene x gene interaction by allowing the penetrances at the locus being evaluated to depend upon measured genotypes at a known locus. With knowledge of the generating model for the simulated rheumatoid arthritis (RA) data, we selected two loci for examination: Locus A, which in interaction with the HLA-DR antigen locus affects risk of the dichotomous RA phenotype; and Locus E, which in interaction with DR affects quantitative levels of the anti-CCP phenotype. The data comprised nuclear families of two parents and an affected sib pair (ASP). Our results confirm theoretical work suggesting that gene x gene interactions CANNOT be leveraged to improve linkage detection for dichotomous traits based on affecteds-only data structures. However, incorporation of DR-based LCs did lead to appreciably higher quantitative trait PPLs. This suggests that gene x gene interactions could be effectively used in quantitative trait analyses even when families have been ascertained as ASPs for a related dichotomous trait.
18466480 One-stage design is empirically more powerful than two-stage design for family-based genom 2007 Finding a genetic marker associated with a trait is a classic problem in human genetics. Recently, two-stage approaches have gained popularity in marker-trait association studies, in part because researchers hope to reduce the multiple testing problem by testing fewer markers in the final stage. We compared one two-stage family-based approach to an analogous single-stage method, calculating the empirical type I error rates and power for both methods using fully simulated data sets modeled on nuclear families with rheumatoid arthritis, and data sets of real single-nucleotide polymorphism genotypes from Centre d'Etude du Polymorphisme Humain pedigrees with simulated traits. In these analyses performed in the absence of population stratification, the single-stage method was consistently more powerful than the two-stage method for a given type I error rate. To explore the sources of this difference, we performed a case study comparing the individual steps of two-stage designs, the two-stage design itself, and the analogous one-stage design.
18289065 Small molecules anti-HIV therapeutics targeting CXCR4. 2008 HIV cellular entry is a multistep process that requires the interaction of a viral envelope glycoprotein (gp120) and a host receptor (CD4) followed by binding to a co-receptor. The CC-chemokine receptor 5 (CCR5) and CXC-chemokine receptor 4 (CXCR4) have been identified as the major HIV co-receptors and therefore are promising targets for the development of new anti-HIV drugs. CXCR4 is also involved in several diseases such as angiogenesis, metabolic and neurological disorders, rheumatoid arthritis and in different forms of metastatic cancer. Herein, we present a review focusing on small molecule CXCR4 antagonists. These compounds are divided into 11 classes that include cyclic penta- and tetrapeptides, diketopiperazine mimetics, bicyclams, non-bicyclams, tetrahydroquinolines, thiazolylisothiourea derivatives, benzodiazepines, alkyl amine analogs and non-peptides derivatives, dipicolylamine-zinc(II) complexes, ampelopsin and distamycin analogs. The most advanced CXCR4 antagonists documented are bicyclam derivatives, which are specific CXCR4 antagonists and exhibit potency in the nanomolar range. Further development of selective CXCR4 antagonists continues to be crucial for the design of second generation of anti-HIV drugs. We aim to provide a comprehensive summary of diverse structural templates that could be useful for optimization and discovery of novel CXCR4 antagonists.
18220768 Strategies for novel therapeutic approaches targeting cytokines and signaling pathways of 2008 For many bone and joint diseases in humans, including postmenopausal osteoporosis, rheumatoid arthritis, and ankylosing spondylitis, an immune-mediated etiology has either been proven or is considered as a co-factor in pathogenesis. The identification of the receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG)-interplay and the in-depth characterization of the signaling pathways induced upon RANK activation, including molecules such as TNF receptor-associated factor 6 (TRAF6), nuclear factor-kappaB (NF-kappaB), and signal transducer and activator of T cells (STAT)-3, now promise to give the opportunity to target osteoclastogenesis specifically. Additionally, many byways influencing osteoclastogenesis have been elucidated, thus giving rise to additional therapeutic approaches. These are based mainly upon the effects of diverse cytokines on osteoclast differentiation with interleukin (IL)-17 and interferone (IFN)-gamma being most prominent at the moment. The same applies for the recently established signaling pathways in osteoblastogenesis, which have attracted much attention in the recent years. In this respect, much attention has been attributed towards bone morphogenetic proteins (BMPs) and the Wnt signaling cascade. In this review, an overview on the key molecules, which (could) serve as promising targets for novel therapeutic interventions with the aim of enhancing osteoblast formation or suppressing osteoclast development, is given. Further on, antibody-based therapeutical schemes as well as methodologically novel, albeit predominantly theoretical at the moment, strategies in the fight against immune-mediated osteopathologies are discussed.
18197449 Persistence of weekly alendronate: a real-world study in Croatia. 2008 May Long-term treatment of osteoporosis is required for optimal efficacy, but adherence to therapy is suboptimal with daily and weekly oral bisphosphonates. The aim of this study was to assess real-world persistence (long-term adherence) with weekly alendronate. Persistence data were collected according to World Health Organization criteria for the prior month and year for 102 consecutive patients with osteoporosis at three outpatient clinics in Croatia. Persistence was assessed using medication possession ratios (MPR). Adequate persistence was defined as sufficient medication supply to ensure antifracture efficacy (MPR >or=80%). Self-reported persistence data were compared with resupply prescription data from primary care physicians (PCPs). The effect of patient age, co-therapy, co-morbidity, and time since osteoporosis was diagnosed were evaluated. A diagnosis of osteoporosis was established 3.21+/-1.83 years prior for the 96 women and six men enrolled (mean age 66.92+/-8.05 years). During the previous year, 86.3% patients reported not missing any tablets. Age correlated with the number of missed tablets, with older patients missing more tablets (p=0.038). Patients with co-therapy (p=0.042) missed more tablets. PCPs reported that 65.7% of the patients were issued prescriptions for 52 tablets. A total of 68.7% had MPR >80%. Patients with rheumatoid arthritis did not impact MPR (p=0.936). Previous fractures or number of fractures were not associated with persistence (p>0.05). In Croatia, persistence was superior with weekly-administered alendronate than has been reported elsewhere, perhaps due to socio-cultural factors. Larger, longitudinal studies are needed to confirm these results.
18089676 Review: vitamin D, immunity and lupus. 2008 Jan The identification of vitamin D receptor in cells involved in the immune response and the discovery that activated dendritic cells produce vitamin D hormone suggested that vitamin D could exert immunoregulatory effects. Patients with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus (SLE) show low 25-OH vitamin D serum levels. In particular, SLE patients have multiple risk factors for vitamin D deficiency and disease severity seems correlated with lower 25-OH vitamin D serum levels. Treatment of vitamin D deficiency could be particularly important in SLE patients due to concomitant insults on their tissues such as bone, and in view of the possible immunomodulatory effects exerted by vitamin D.
18071943 Anti-TNF antibodies: lessons from the past, roadmap for the future. 2008 Tumor necrosis factor alpha (TNF) is an important cell-signaling component of the immune system. Since its discovery over 20 years ago, much has been learned about its functions under normal and disease conditions. Nonclinical studies suggested a role for TNF in chronic immune-mediated inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis, and therefore neutralizing monoclonal antibodies specific to human TNF were developed for clinical evaluation. Treatment with anti-TNF monoclonal antibodies (infliximab, adalimumab, and certolizumab pegol) has been shown to provide substantial benefit to patients through reductions in both localized and systemic expression of markers associated with inflammation. In addition, there are beneficial effects of anti-TNF treatment on markers of bone and cartilage turnover. Further exploration of changes in these markers and their correlation with clinical measures of efficacy will be required to allow accurate prediction of those patients most in need of these treatments. Both the clinical and commercial experience with these anti-TNF antibodies provide a wealth of information regarding their pharmacological effects in humans.
18039330 The health status burden of people with fibromyalgia: a review of studies that assessed he 2008 Jan OBJECTIVE: The current review describes how the health status profile of people with fibromyalgia (FM) compares to that of people in the general population and patients with other health conditions. METHODS: A review of 37 studies of FM that measured health status with the 36-item Medical Outcomes Study Short-Form Health Survey (SF-36) or the 12-item Short-Form Health Survey (SF-12). RESULTS: Studies performed worldwide showed that FM groups were significantly more impaired than people in the general population on all eight health status domains assessed. These domains include physical functioning, role functioning difficulties caused by physical problems, bodily pain, general health, vitality (energy vs. fatigue), social functioning, role functioning difficulties caused by emotional problems and mental health. FM groups had mental health summary scores that fell 1 standard deviation (SD) below the general population mean, and physical health summary scores that fell 2 SD below the general population mean. FM groups also had a poorer overall health status compared to those with other specific pain conditions. FM groups had similar or significantly lower (poorer) physical and mental health status scores compared to those with rheumatoid arthritis, osteoarthritis, osteoporosis, systemic lupus erythematosus, myofacial pain syndrome, primary Sjögren's syndrome and others. FM groups scored significantly lower than the pain condition groups mentioned above on domains of bodily pain and vitality. Health status impairments in pain and vitality are consistent with core features of FM. CONCLUSIONS: People with FM had an overall health status burden that was greater in magnitude compared to people with other specific pain conditions that are widely accepted as impairing.
18034851 Impact of local and systemic factors on the incidence of failures up to abutment connectio 2008 Jan AIM: This study aimed to assess the influence of systemic and local bone and intra-oral factors on the occurrence of early TiUnite implant failures. MATERIAL AND METHODS: A total of 283 consecutive patients (187 females; mean age 56.2), who received a total of 720 TiUnite implants, at the Department of Periodontology of the University Hospital of the Catholic University of Leuven, were prospectively followed. The following aspects were particularly assessed: hypertension, cardiac problems, gastric problems, osteoporosis, hypo- or hyperthyroid, hypercholesterolaemia, asthma, diabetes types I or II, Crohn's disease, rheumatoid arthritis, chemotherapy, hysterectomy and intake of medication (antidepressants, steroids, hormone replacement), radiotherapy of the concerned area, breach of sterility during surgery, implant parameters, bone (quality, quantity, dehiscence or perforation), type of edentulism, antibiotics prescription, fenestration of the implant in the sinus/nasal cavity, immediate implant placement, apical lesion detection and insertion torque. RESULTS AND CONCLUSION: A global failure rate of 1.9% was recorded. Owing to the very few failures, no definitive conclusion concerning statistical significance can be achieved. However, a tendency for more failures was noticed for apical lesions, vicinity with natural dentition, smoking, hormone replacement, gastric problems, Crohn's disease, diabetes I and radical hysterectomy.
17909932 Poor results of the cementless total hip arthroplasty with a nonporous coated acetabular c 2007 Sep BACKGROUND: This study followed patients for a minimum of 7 years after primary total hip arthroplasty using cementless acetabular components and evaluated their outcomes. METHODS: We followed 73 patients (75 hips), who had undergone total hip arthroplasty with cementless nonporous coated acetabular components (3M AcSys Shearer Cup) for a mean of 9.8 years (range 7-13 years). There were 61 women and 12 men with a mean age of 53 years (range 27-69 years) at surgery. The diagnosis was primary osteoarthritis in 9 hips, osteoarthritis secondary to developmental dysplasia in 58 hips, osteonecrosis of the femoral head in 6 hips, and rheumatoid arthritis in 2 hips. RESULTS: Three cups were revised because of aseptic loosening, and one cup was revised following removal of the prosthesis due to deep infection. Radiographic loosening was observed in 22 hips at the latest follow-up. The survival rate at 10 years was 94.7% with revision as the endpoint and 72% with radiographic loosening as the endpoint. The Merle d'Aubigné and Postel hip score showed significant improvement postoperatively and was maintained well even in cases showing radiographic loosening. CONCLUSIONS: The intermediate radiological results with the AcSys Shearer Cup were unsatisfactory because of the high loosening rate, although the revision rate was low. The nonporous outer surface and the poor fixation mechanism between the metal shell and liner may have contributed to the high failure rate. Regular radiological review is recommended when this cup is used because early loosening is often painless.
17785330 Clinical significance of anti-histidyl-tRNA synthetase (Jo1) autoantibodies. 2007 Aug The clinical significance of a discovery of anti-histidyl-tRNA synthetase (Jo1) autoantibodies patients was established in the early diagnosis of antisynthetase syndrome (ASS) as the common form of this pathology is characterized by interstitial lung disease (ILD), inflammatory muscle disease, and production of anti-Jo1 autoantibodies. However, the specificity of such autoantibodies has to be evaluated in daily clinical practice. In this study, the clinical and prognostic profiles of 45 patients displaying anti-Jo1 autoantibodies were determined. Among 36 patients with a titer of anti-Jo1 autoantibodies above the cutoff value suggested by the manufacturer (40 AU/mL), three different groups were identified. The first group (n = 26) suffered from a complete or incomplete ASS and showed anti-Jo1 autoantibodies mostly above 60 AU/mL. A second group (n = 7) suffered from another autoimmune disease, that is, a systemic lupus erythematosus, cutaneous lupus and rheumatoid arthritis, and Crohn's disease with anti-Jo1 autoantibodies mostly below 60 AU/mL. The third group (n = 3) did not suffer from any autoimmune disease and presented anti-Jo1 autoantibodies below 60 AU/mL. The nine doubtful cases (titer of anti-Jo1 autoantibodies of 30-39 AU/mL) were from patients with no ASS nor myositis. Only 27 out of 45 patients showed antinuclear antibodies with 15 sera showing a pattern characteristic of anti-Jo1 autoantibodies by indirect immunofluorescence on HEp2 cells. In conclusion, this study underlines the need to search for anti-Jo1 autoantibodies even if antinuclear antibodies are negative by indirect immunofluorescence and underlines the usefulness of anti-Jo1 antibodies of titer above 60 AU/mL in the diagnosis of complete or incomplete ASS.
17597260 [Aging: role and control of glycation]. 2007 Dec PURPOSE: Advanced glycation end-products (AGEs) accumulate in aging tissues and organs during rheumatoid arthritis and Alzheimer disease. These aging toxins are especially involved in cell alteration during diabetes mellitus (glycotoxin) and renal failure (uremic toxin). AGEs participate to the endothelial dysfunction leading to diabetic macro but also micro-angiopathy. AGEs binding to cell receptors are critical steps in the deleterious consequences of AGE excess. AGE-receptor activation altered cell and organ functions by a pro-inflammatory, pro-coagulant and pro-fibrosis factors cell response. CURRENT KNOWLEDGE AND KEY POINTS: Non-enzymatic glycation and glycoxidation with glucose auto-oxidation represent the two main pathways resulting in AGE formation. No exclusive AGE classification is actually available. Pathophysiological mechanisms are described to explain AGE toxicity. AGEs bind to cell receptors inducing deleterious consequences such as endothelial dysfunction after endothelial RAGE activation. AGEs can also have deleterious effects through glycated protein accumulation or in situ protein glycation. FUTURE PROSPECTS AND PROJECTS: Many in vitro or animal studies demonstrated that AGE deleterious effects can be prevented by glycation inhibitors, AGE cross-link breakers or AGE-RAGE interaction inhibition. New molecules are actually studied as new strategy to prevent or treat the deleterious effects of these aging toxins.
17588137 Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-kappaB a 2007 May OBJECTIVE AND DESIGN: Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce production of pro-inflammatory cytokines with immune regulatory properties. We investigated the effect of quercetin on the expression of pro-inflammatory cytokines in human mast cell line, HMC-1. METHODS: HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 (PMACI). RESULTS: Quercetin decreased the gene expression and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 in PMACI-stimulated HMC-1 cells. Quercetin attenuated PMACI-induced activation of NF-kappaB and p38 mitogen-activated protein kinase. CONCLUSION: Our study provides evidence that quercetin may suitable for the treatment of mast cell-derived allergic inflammatory diseases.
17581796 Lack of correlation between satisfaction and knowledge in clinical trials participants: a 2007 Nov OBJECTIVES: To address participants' knowledge of informed consent and to explore whether knowledge level is related to clinical trial satisfaction. METHODS: One hundred and fourteen patients enrolled in three ongoing randomized controlled trials of osteoarthritis and rheumatoid arthritis were asked to complete a mailed form. The survey was related to aspects of the informed consent process: quality of information given during the informed consent process, participants' self perception of knowledge, objective evaluation of participants' knowledge and participants' overall trial satisfaction. These four aspects were categorized as high, intermediate or low. Correlation between participants' knowledge and satisfaction was measured using the Spearman's Rho test and variables associated with knowledge by standard univariable analyses. A p value< or =0.05 was considered significant. RESULTS: One hundred and five participants answered the questionnaire. The quality of information given during the informed consent process was rated as being high by 81% participants, intermediate by 15.2% and low by 3.8%. Fifty-one percent of the participants believed they had a good level of knowledge, but, objective evaluation qualified as high in only 14.3% of them. Overall trial satisfaction was high in 95% of the participants. No significant correlation was found between knowledge and satisfaction (r=0.16; p=0.086). Age was negatively associated with a higher level of knowledge (48 vs. 58 years old, p=0.008). CONCLUSIONS: We found a lack of correlation between satisfaction and knowledge in clinical trials participants. During a randomized controlled trial the investigator should consider encouraging activities to improve not only participants' satisfaction, but also their level of knowledge.
17544120 Clinical spectrum of gammadelta+ T cell LGL leukemia: analysis of 20 cases. 2008 Jan We report on the clinico-biological characteristics of 20 cases of gammadelta T cell large granular lymphocyte (LGL) leukemia. All the data were compared to that of 196 cases with alphabeta T cell subtype, which represents the majority of T cell LGL leukemias. Clinical findings were quite similar in the two groups regarding age, sex ratio, recurrent infections, and association with auto-immune diseases especially rheumatoid arthritis. Gammadelta LGL predominantly expressed a CD3+/CD4-/CD8+/CD16+/CD57+ phenotype, in 50% of cases. Clinical outcome was favorable for these patients with overall survival of 85% at 3 years. Fifty percent of gammadelta patients required treatment and the response to therapy was estimated at 55%. gammadelta and alphabeta T cell LGL leukemia harbor a very similar clinico-biological behavior and represent part of an antigen-driven T cell lymphoproliferation.
17399748 Anti-inflammatory and immunosuppressive compounds from Tripterygium wilfordii. 2007 Apr The extract of Tripterygium wilfordii Hook F. (TwHF), which showed anti-inflammatory and immunosuppressive activities in human clinical trials for rheumatoid arthritis, was subjected to the activity-guided fractionation and spectroscopic characterization of bioactives. A tetrahydrofuran lignan, tripterygiol (1), and eight known compounds, all capable of suppressing pro-inflammatory gene expression were identified. Most of the pharmacological activity of the extract can be attributed to triptolide, its most abundant and active component, with some contribution from tripdiolide.
17357109 70-kDa heat shock proteins: specific interactions with HLA-DR molecules and their peptide 2007 Apr Heat shock protein 70 (HSP70):peptide complexes are involved in MHC class I and class II-restricted antigen presentation enabling enhanced activation of antigen-specific T cells. Here, we investigated the potential of bacterial and mammalian HSP70 molecules to interact with peptide fragments from HLA-DR and the corresponding complete HLA-DR molecules. Peptide fragments were found to interact with DnaK, the HSP70 homologue from E. coli, but less with stress-inducible human Hsp70. Only a peptide sequence exclusively found in rheumatoid arthritis-protective HLA-DR molecules did not interact with DnaK. Subsequently, we investigated the interaction of complete HLA-DR molecules with HSP70 and detected a specific HSP70:HLA-DR interaction, with highest affinity for human stress-inducible Hsp70. In contrast to the peptide fragments, no allele-specific differences in Hsp70 affinity were detected with complete HLA-DR molecules. Interaction with HLA-DR molecules was increased at lowered pH values, whereas HSP70-chaperoned peptides were released at acidic pH, thus HSP70 could serve as scanner and carrier for antigenic peptides of self or foreign origin and transfer chaperoned peptides onto MHC class II molecules in acidic late endosomal compartments. Our findings indicate that direct interaction between mammalian HSP70 and HLA-DR molecules could be involved in the HSP70-mediated enhancement of MHC class II-restricted peptide presentation and CD4(+) T cell activation.
17250993 Increased serum levels of a proliferation-inducing ligand in patients with bullous pemphig 2007 Apr BACKGROUND: B cells have been demonstrated to have critical roles in developing autoimmune bullous diseases. Recently identified tumor necrosis factor-like molecules, B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are essential molecules for B cell development, survival, and proliferation. Although the functions of APRIL have not been fully evaluated, recent studies suggest that circulating levels of APRIL are increased in various autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVES: To determine serum APRIL levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and compare those with clinical findings and laboratory findings. PATIENTS/METHODS: Sera from 15 PV patients, 43 BP patients, and 15 normal controls were subjected to ELISA assays to measure serum APRIL, BAFF, Dsg3, and BP180 levels. RESULTS AND CONCLUSIONS: Circulating APRIL levels were significantly elevated in BP patients but not in PV patients, and correlated with serum BAFF levels. Our study revealed that serum APRIL levels tended to be increased in the quite early stage of disease. In conclusion, circulating APRIL levels may be a useful marker for early activation of autoimmune diathesis, and furthermore, an effective therapeutic target molecule in patients with BP.
17209307 Some histological effects of chronic administration of chloroquine on the medial geniculat 2006 Jun Some histological effects of chronic administration of chloroquine commonly used for prophylaxis or treatment of malaria. rheumatoid arthritis and lupus erythematosus on the medial geniculate body (MGB) of adult wistar rats was carefully studied. The rats of both sexes (n= 18), average weight of 184g were randomly assigned into treatment (n= 10) and control (n=7) groups. The rats in the treatment group received 2mg/kg body weight of chloroquine base dissolved in distilled water daily for fourteen days through the orogastric tube administration while the control rats received equal volume of distilled water daily through the same route. The rats were fed with rat pellets purchased from Topfeed Ltd. Sapele. Delta State. Nigeria and given water liberally and were then sacrificed on day fifteen of the experiment. The MGB were carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H & E and thionin methods. The histological findings after H & E methods indicated that the treated sections of the MGB showed faintly reduced nuclei size, with the presence of many autophagic vacuoles and degenerative neurons when compared to the control sections. On the other hand. the thionin method indicated that the treated sections showed sparsely distributed neurons, which stain less intensely when compared with the control. The nissl substance in some of the neurons appeared degenerative while some hypertrophied with some vacuolations. These findings indicated that chronic administration of chloroquine has a deleterious effect on the neurons and nissl substance of the MGB. Chloroquine may probably have adverse effects on auditory sensibilities by its deleterious effects on the nerve cells and nissl substances of the MGB of the adult wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.