Histidine Self-assembly and Stability on Mineral Surfaces as a Model of Prebiotic Chemical Evolution: An Experimental and Computational Approach.

The abiotic synthesis of histidine under experimental prebiotic conditions has proven to be chemically promising and plausible. Within this context, the present results suggest that histidine amino acid may function as a simple prebiotic catalyst able to enhance amino acid polymerization. This work describes an experimental and computational approach to the self-assembly and stabilization of DL-histidine on mineral surfaces using antigorite ((Mg, Fe)3Si2O5(OH)4), pyrite (FeS2), and aragonite (CaCO3) as representative minerals of prebiotic scenarios, such as meteorites, and subaerial and submarine hydrothermal systems. Experimental results were obtained through polarized-light microscopy, IR spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC). Molecular dynamics was performed through computational simulations with the MM + method in HyperChem software. IR spectra suggest the presence of peptide bonds in the antigorite-histidine and aragonite-histidine assemblages with the presence of amide I and amide II vibration bands. The FTIR second derivative inspection supports this observation. Moreover, DSC data shows histidine stabilization in the presence of antigorite and aragonite by changes in histidine thermodynamic properties, particularly an increase in histidine decomposition temperature (272ºC in antigorite and 275ºC in aragonite). Results from molecular dynamics are consistent with DSC data, suggesting an antigorite-histidine closer interaction with decreased molecular distances (cca. 5.5 Å) between the amino acid and the crystal surface. On the whole, the experimental and computational outcomes support the role of mineral surfaces in prebiotic chemical evolution as enhancers of organic stability.

Bottom-Up Copper Filling of Large Scale Through Silicon Vias for MEMS Technology.

An electrodeposition process for void-free bottom-up filling of sub-millimeter scale through silicon vias (TSVs) with Cu is detailed. The 600 µm deep and nominally 125 µm diameter metallized vias were filled with Cu in less than 7 hours under potentiostatic control. The electrolyte is comprised of 1.25 mol/L CuSO4 -0.25 mol/L CH3SO3H with polyether and halide additions that selectively suppress metal deposition on the free surface and side walls. A brief qualitative discussion of the procedures used to identify and optimize the bottom-up void-free feature filling is presented.

The cost-effectiveness of paliperidone extended release in Spain.

BACKGROUND: Paliperidone Extended Release OROS (ER) is a new atypical antipsychotic for the treatment of schizophrenia. The objective is, based on a previously published model, to analyze the clinical and economic effects of Paliperidone ER in a Spanish setting compared to olanzapine oral and aripiprazole. METHODS: An existing discrete event simulation model was adapted to reflect the treatment of schizophrenia in Spain in terms of costs, resource use, and treatment patterns. Inputs for the model were derived from clinical trial data, literature research, database analysis and interviews with local clinical experts. The time horizon is 5 years and Spanish discount rate was applied. Outputs include direct medical costs and Quality Adjusted Life-Years (QALYs). Extensive sensitivity analyses were carried out to assess the robustness of the results, using ordinary least squares analysis and cost-effectiveness scatter plots. RESULTS: The results show that the mean incremental QALYs (95% CI) compared to olanzpine is 0.033 [-0.143, 0.304] and compared to aripiprazole 0.029 [-0.107, 0.300]. The corresponding mean incremental costs and corresponding confidence intervals are -€1425 [-€10,247, €3084] and -€759 [-€10,479, €3404], respectively. The probability that paliperidone ER is cost-saving and health gaining compared to olanzapine and aripiprazole is 76% and 72%, respectively. Paliperidone ER was estimated to have 80% and 81% probability of being cost-effective compared to olanzapine at a willingness to pay of €20,000 and €30,000 and 73% and 74% compared to aripiprazole, respectively. LIMITATIONS: Some of the modeled inter-relationships had to be based on expert opinion due to a lack of information. Also, foreign sources for the disutility of adverse events had been used due to a lack of Spanish data. Prolactin-related side-effects, indirect costs, and potential compliance advantages of paliperidone ER were not considered. It is unlikely that these limitations affected the conclusions. CONCLUSION: Based on differences in drug acquisition costs, side-effects, and risk of relapse, the model predicts that, in the Spanish healthcare setting, paliperidone ER dominates oral olanzapine and aripiprazole, with a probability of 76% and 72%, respectively.

The effect of biomaterials and antifungals on biofilm formation by Candida species: a review.

Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are able to form biofilms on virtually any biomaterial implanted in a human host. Biofilms are a primary cause of mortality in immunocompromised and hospitalized patients, as they cause recurrent and invasive candidiasis, which is difficult to eradicate. This is due to the fact that the biofilm cells show high resistance to antifungal treatments and the host defense mechanisms, and exhibit an excellent ability to adhere to biomaterials. Elucidation of the mechanisms of antifungal resistance in Candida biofilms is of unquestionable importance; therefore, this review analyzes both the chemical composition of biomaterials used to fabricate the medical devices, as well as the Candida genes and proteins that confer drug resistance.

[Diagnostic errors and temporal stability in bipolar disorder]. / Errores de diagnóstico y estabilidad temporal en el trastorno bipolar.

INTRODUCTION: The diagnosis of bipolar disorder is frequently modified during the course of the illness. MATERIAL AND METHODS: Diagnostic changes and associated errors are described for 1,153 patients diagnosed as bipolar disorder, aged over 18 years and with at least ten follow-up visits. Data was extracted from a clinical registry of out-patient care specialized in Psychiatry and psychiatric hospitalizations of 25,152 patients representative of an urban area of 240,000 inhabitants. Limit for diagnostic stability was established as the maintenance of the bipolar disorder diagnosis in at least 75% of the visits. RESULTS: A total of 158 (46.1 %) out of 342 patients diagnosed as having a bipolar disorders in the first visit kept this diagnostic constant in subsequent evaluations. Infradiagnostic initial error was committed with 108 stable patients who were not diagnosed in the first visit. 184 patients diagnosed in the first visit with bipolar disorder had less than 75 % concordant diagnosis along the follow-up and could be considered as initial overdiagnosis. Two hundred and nine out of the 443 patients who were diagnosed as bipolar disorder in their last visit did not keep stability criteria in their follow-up and could be considered therefore as final overdiagnosis. Thirty two stable patients not diagnosed in their last visit could be considered as infradiagnosis final error. Diagnosis from schizophrenia spectrum (F2) appears in one of every four psychiatric visits of the patients included in this study. Overlap was seen in three other categories: anxiety disorders (F4), personality disorders (F6) and substance abuse disorders. CONCLUSION: Initial course of bipolar disorder causes difficulties in the diagnosis.

[Gender differences in clinical profile, response and remission of depressive patients treated with venlafaxine extended release]. / Diferencias de género en el perfil clínico, respuesta y remisión de pacientes depresivos tratados con venlafaxina retard.

INTRODUCTION: The primary objectives of this study are to evaluate gender-specific differences in the clinical profile of primary care depressive patients as well as in the clinical response and remission to venlafaxine extended release. METHODS: We have analyzed a sample of 6,719 adult outpatients (1,713 men and 4,925 women) with diagnosis of depressive syndrome with associated anxiety symptoms included in an observational, prospective, multicenter and open study. Venlafaxine extended release was administered for 24 weeks at a dosage of 75-225 mg/day. RESULTS: In this study we have not found overall differences regarding the baseline severity of the depressive episode, as assessed by means of the HAM-D17 and Clinical Global Impression Scale of Severity (CGI-S). However, women showed higher scores on items of the HAM-D17 and HAM-A scales related with anxious and somatic complaints at baseline and endpoint. The percentage of remission on the HAM-D17 scale reached 75.4 % for men and 74.3 % for women (p = 0.4339) at week 24. In the case of HAM-A: 84.1% vs. 80.6% (men vs. women, p=0.004). CONCLUSIONS: We did not observe baseline differences in the mean score of the HAM-D17 nor the remission rates between women and men (HAM-D17) at the final visit. Women showed lower anxiety remission rates (HAM-A) and maintained more anxious and somatic complaints throughout the study.

Ziprasidona: de la farmacología a la práctica clínica. Un año de experiencia / Ziprasidone: from pharmacology to the clinical practice. One year of experience

Transcurridos más de 2 años desde la comercialización del antipsicótico atípico ziprasidona, los datos procedentes de estudios de investigación y de la práctica clínica han proporcionado abundante información útil para su manejo práctico en el tratamiento de la esquizofrenia. Sus características farmacodinámicas y los resultados de los estudios clínicos con dosis flexible parecen justificar la necesidad de administrar dosis en el rango superior de las inicialmente previstas, con un mínimo inicial de 120 mg/día y una rápida titulación hasta 160 mg/día. Dichas dosis permiten alcanzar concentraciones plasmáticas que permiten ocupar al menos el 60 % de los receptores D2 del que se derivará el efecto antipsicótico. Además, se confirma su actividad antidepresiva y su perfil no sedante, con un posible efecto favorable sobre la atención y otras funciones cognitivas del paciente, en relación con la elevada afinidad frente a receptores 5HT1A y D1 y la inhibición de la recaptación de serotonina y noradrenalina.Por último, la escasa afinidad de este fármaco frente a receptores alpha-adrenérgicos, histamínicos y muscarínicos favorece un buen perfil de tolerabilidad, con un efecto neutro sobre el peso y falta de efectos anticolinérgicos. Los resultados de diversos ensayos clínicos muestran que el uso de dosis en el rango superior se asocia a una mejoría clínica más rápida y pronunciada que dosis inferiores, sin añadir un mayor riesgo de efectos adversos

More than a year after the marketing of the atypical anti-psychotic ziprasidone, data from research studies and clinical practice have provided a fair amount of useful information for its practical use in the treatment of schizophrenia. Its pharmacodynamical characteristics and the results from clinical trials with a flexible dose seem to justify the need to administer doses in a range higher than what was initially foreseen, with an initial minimum of 120 mg per day and a fast titulation up to 160 mg per day. Such doses make it possible to achieve sufficient plasma concentrations to occupy at least 60 % of the D2 receptors from which the anti-psychotic effect derives. Moreover, its anti-depressive activity and its non-sedative profile have been confirmed, with a favorable effect on attention and other cognitive functions of the patient, according to its high affinity for 5HT1A and D1 receptors and the inhibition of serotonin and noradrenaline re-uptake.Finally, the low affinity of this drug for á-adrenergic, histaminergic and muscarinic receptors favors a good tolerability profile, with a neutral effect on weight, and a lack of anti-cholinergic effects. Results from different clinical trials show that the use of doses in the higher range is associated to a faster and more pronounced clinical improvement without adding a higher risk of adverse events

Ziprasidone: from pharmacology to the clinical practice. One year of experience.

More than a year after the marketing of the atypical anti-psychotic ziprasidone, data from research studies and clinical practice have provided a fair amount of useful information for its practical use in the treatment of schizophrenia. Its pharmacodynamical characteristics and the results from clinical trials with a flexible dose seem to justify the need to administer doses in a range higher than what was initially foreseen, with an initial minimum of 120 mg per day and a fast titulation up to 160 mg per day. Such doses make it possible to achieve sufficient plasma concentrations to occupy at least 60 % of the D2 receptors from which the anti-psychotic effect derives. Moreover, its anti-depressive activity and its non-sedative profile have been confirmed, with a favorable effect on attention and other cognitive functions of the patient, according to its high affinity for 5HT1A and D1 receptors and the inhibition of serotonin and noradrenaline re-uptake. Finally, the low affinity of this drug for alpha-adrenergic, histaminergic and muscarinic receptors favors a good tolerability profile, with a neutral effect on weight, and a lack of anti-cholinergic effects. Results from different clinical trials show that the use of doses in the higher range is associated to a faster and more pronounced clinical improvement without adding a higher risk of adverse events.

[Impact of olanzapine on quality of life of patients with schizophrenia: one-year follow-up with the Seville Quality of Life Questionnaire]. / Impacto de la olanzapina sobre la calidad de vida en pacientes con esquizofrenia: seguimiento a un año con el Cuestionario Sevilla de Calidad de Vida.

INTRODUCTION: Our objective is to present the impact on quality of life of long-term olanzapine treatment in a significant number of schizophrenics as determined by the Seville Quality of Life Questionnaire (SQLQ), an instrument that addresses the aspects that particularly affect these patients, and to evaluate the sensitivity of this instrument to the changes induced by this treatment. METHODS: Three hundred and seventy two patients with the diagnosis of schizophrenia as per the ICD-10 classification were evaluated in a 1 year prospective study after switching to olanzapine. The SQLQ, Lehman's structured interview and short version of the discapacity assessment scale were used to evaluate patient's subjective experience; in addition, other instruments were used to evaluate psychopathology. RESULTS: Significant increases in the scores of the favorable scale and decreases in the unfavorable scale of the SQLQ were found. There were also significant improvements in quality of life as measured with Lehman's structured interview. This improvement continued until the end of the 1 year follow-up after switching to olanzapine. Both instruments show a good correlation. Changes in psychopathology were also remarkable, including the negative symptoms. CONCLUSIONS: The SQLQ has proven to be a sensitive instrument to measure quality of life in schizophrenic patients treated with olanzapine. It focuses on aspects that are relevant for patients that were frequently overlooked by treating physicians. This drug has been proven to have a favorable subjective impact upon patients, besides improving psychopathology.

Impacto de la olanzapina sobre la calidad de vida en pacientes con esquizofrenia: seguimiento a un año con el Cuestionario Sevilla de Calidad de vida / Impact of olanzapine on quality of life of patients with schizophrenia: one year follow-up with the Seville Quality of Life Questionnaire

Introducción. Nuestro objetivo es presentar el impacto sobre la calidad de vida del tratamiento a largo plazo con olanzapina en un número importante de pacientes esquizofrénicos, medido con el Cuestionario Sevilla de Calidad de Vida (CSCV), un instrumento que recoge los aspectos que afectan especialmente a estos pacientes, y evaluar la sensibilidad de este instrumento a los cambios inducidos por este tratamiento. Métodos. Se evaluaron 372 pacientes diagnosticados de esquizofrenia según la clasificación CIE-10 en un estudio prospectivo de 1 año después de cambiar a olanzapina. Para evaluar la experiencia subjetiva se utilizaron el CSCV, la entrevista estructurada de Lehman y la versión abreviada de la escala de evaluación de la discapacidad; además se utilizaron otros instrumentos para evaluar la psicopatología. Resultados. Se observaron aumentos significativos en las puntuaciones de la escala favorable y reducciones significativas en las puntuaciones de la escala desfavorable del CSCV. También se observó una mejoría significativa en la calidad de vida medida con la entrevista estructurada de Lehman. Esta mejoría continuó hasta el final del seguimiento 1 año después del cambio a olanzapina: Ambos instrumentos muestran una buena correlación. Los cambios en la psicopatología también fueron considerables, incluyendo los síntomas negativos. Conclusiones. El CSCV ha demostrado ser un instrumento sensible para medir la calidad de vida en pacientes esquizofrénicos tratados con olanzapina. Se centra en los aspectos que son importantes para los pacientes y que los médicos frecuentemente han pasado por alto. Este fármaco ha demostrado tener un impacto subjetivo favorable en los pacientes además de mejorar la psicopatología (AU)

[Terrorist attacks and short-long time psychiatric morbidity]. / Impacto de los atentados terroristas en la morbilidad psiquiátrica a corto y largo plazo.

BACKGROUND: The victims of terrorist attacks have a lower level of mental health than general population. However this effects has been only demonstrated in short term after the terrorist attack. METHODS: 2998 people from 544 families who have suffered a terrorist attacks. General Health Questionnaire-28 (GHQ-28) as a psychopathological screening was used in 1094 people. This sample was divided in direct victims (DV), direct victims' relatives (DVR) and people who meet these two conditions (DVRDV). RESULTS: 39.6% of the sample were probable psychiatric cases. Psychiatric prevalence was higher in DRVDV (54.5%) and DV (52.0%) than in DRV and general population (10-25%). The sample presented worse level of mental health than the general population in short term (0-2 years) (DVR 40%, DV 66.7%, DRVDR 75%) and in long term 18-20 años) (DVR 35.70%, DV 37%, DRVDR 37.5%). CONCLUSION: Both those suffering a terrorist attack as well as their family members have worse levels of mental health than the general population in both the short and long term.

Impacto de los atentados terroristas en la morbilidad psiquiátrica a corto y largo plazo / Terrorist attacks and short-long time psychiatric morbidity

Introducción. Las víctimas de atentados terroristas tienen niveles de salud mental inferiores a la población general. La mayoría de las investigaciones que soportan esta afirmación son de estudios realizados a corto plazo. Métodos. Se entrevistó a 2.998 personas pertenecientes a 544 familias de víctimas de 426 atentados terroristas. Unas 1.094 entrevistas incluyeron el General Health Questionaire28 (GHQ-28) como instrumento de screening de patología psiquiátrica. Se dividió la muestra por sus distintas características en víctimas directas (VD) familiares de víctimas directas (FV) y víctima directa además de familiar de víctima directa (VDFV). Resultados. El 39,6 por ciento de la muestra estudiada eran probables casos psiquiátricos. La prevalencia era más alta en VDFV (54,5 por ciento) y VD (52,0 por ciento). Teniendo en cuenta el tiempo transcurrido desde el atentado FV, VD y VDFV presentaban peores niveles de salud mental que la población general tanto a corto plazo (0-2 años) (FV 40 por ciento, VD 66,7 por ciento, VDFV 75 por ciento) como a largo plazo (hasta 18-20 años) (FV 35,70 por ciento, VD 37 por ciento, VDFV 37,5 por ciento). Conclusiones. Tanto las personas que sufren un atentado terrorista como sus familiares tienen peores niveles de salud mental que la población general a corto y a largo plazo (AU)

Risperidona en el tratamiento de la manía aguda: rapidez de la respuesta y tiempo de estancia / Risperidone in the treatment of acute mania: speed of onset of response and length of stay

Fundamento: La asociación de neurolépticos con estabilizadores del ánimo es de primera elección en los episodios agudos de manía. Se ha comprobado que risperidona es eficaz en la tratamiento de la manía. Por otro lado, la reducción de los días de estancia hospitalaria para este tipo de pacientes se ha relacionado con la mejoría psicofarmacológica. El objetivo del presente estudio fue comprobar la eficacia a corto plazo de risperidona asociada en el tratamiento de los episodios agudos de manía, y si la eficacia a corto plazo guarda relación con los días de estancia hospitalaria. Métodos: Se incluyó a 15 pacientes ingresados en la unidad de agudos con diagnóstico de trastorno bipolar, episodio actual maníaco según criterios de la CIE-10, en un estudio observacional no controlado con muestreo aleatorio. Se administró risperidona (dosis media, 6,68 ñ 2 mg/día) asociada a un estabilizador del ánimo y a benzodiacepinas, según criterio clínico. Se evaluó a los pacientes mediante la escala de Young para la Manía (YMRS) al ingreso y la semana del tratamiento. Se estableció el criterio de mejoría en una reducción del 50 por ciento o más en dicha escala. Para el análisis de la rapidez de acción del tratamiento en relación con los días de estancia hospitalaria, se realizó un análisis de supervivencia entre los pacientes que respondieron y los que no lo hicieron mediante las curvas de Kaplan-Meier y la prueba de rangos logarítmicos. Resultados: Risperidona asociada con estabilizadores del ánimo y benzodiacepinas resultó eficaz a corto plazo en el tratamiento de los episodios agudos de manía (p = 0,001). Las limitaciones del tamaño de la muestra no permitieron encontrar diferencias estadísticamente significativas en los días de estancia hospitalaria entre los pacientes que respondieron a corto plazo a risperidona y los que no lo hicieron. Conclusiones: Risperidona asociada es un neuroléptico eficaz a corto plazo en el tratamiento de los episodios agudos de manía. Se necesitan más estudios centrados específicamente en los días de estancia hospitalaria para determinar qué variable o variables influyen en ésta (AU)

[Validation of the Spanish version of PRIME-MD: a procedure for diagnosing mental disorders in primary care]. / Validación de la versión española del PRIME-MD: un procedimiento para el diagnóstico de trastornos mentales en atención primaria.

INTRODUCTION: Psychiatric disorders occurs in at least 20% of patients attending Primary Care settings, however, only 50% of them are detected by primary care physicians. Therefore a tool is required which can help primary care physicians to detect and diagnose psychiatric disorders. PRIME-MD (Primary Care Evaluation of Mental Disorders) is a questionnaire designed with this aim. In this article the results of the validation study of the Spanish version of this questionnaire are presented. MATERIALS AND METHODS: 312 patients were interviewed by primary care physicians using PRIME-MD and by psychiatrists using SCAN (Schedules for Clinical Assessment in Neuropsychiatry). RESULTS: The time most frequently spent in questionnaire application by the physician was 10 minutes. PRIME-MD detected the presence of at least one psychiatric disorder in 44.3% of patients. PRIME-MD diagnoses agree well with SCAN diagnoses for mood disorders (coefficient of agreement: 0.50) and for anxiety disorders (coefficient of agreement: 0.35), but not for somatoform disorders or alcohol-related disorders. CONCLUSIONS: The Spanish version of PRIME-MD questionnaire in a useful tool to identify and diagnose mood and anxiety disorders in Primary Care settings.

Increased serum levels of N-telopeptides (NTx) of bone collagen in postmenopausal Nigerian women.

Serum levels of cross-linked N-telopeptides (NTx) of bone collagen, alkaline phosphatase (ALP), and intact parathyroid hormone (PTH) were determined in 64 premenopausal (PRM) and 86 postmenopausal (PSM) women living in northern Nigeria. Serum NTx values were correlated with ALP activity (r = 0.31-0.58, P < 0.01) and PTH (0. 32-0.35, P < 0.01)) in all of the subjects studied, and were also related to age (-0.47, P < 0.001) and body mass index (-0.45, P < 0. 001) in PRM women. Menopause had the effect of increasing the circulating concentrations of NTx and ALP activity by 15% (P = 0. 001) and 11% (P = 0.02), respectively; however, serum levels of PTH were not different between these two groups of women. Compared with Caucasian counterparts matched for age and body mass index, PSM Nigerian women had significantly increased circulating concentrations of NTx (21.7 versus 16.2 nmol BCE/liter, P = 0.01) and demonstrated a trend towards higher ALP activities and PTH levels. These results indicate that (1) discrete reference intervals should be defined for biochemical markers of bone metabolism in African populations, (2) Nigerian women have relatively higher rates of bone turnover, and (3) further investigation of the implications of increased serum NTx should be undertaken using physical methods such as dual X-ray absorptiometry (DXA) and bone ultrasound attenuation.

[Seville Quality of Life Questionnaire: historic outlook of its establishment]. / El Cuestionario Sevilla de Calidad de Vida: Perspectiva histórica de su instauración.

We describe how we developed a new instrument for measuring quality of life, the Seville Quality of Life Questionnaire (SQCQ), and the results we obtained when we applied it to a group of schizophrenic patients. The questionnaire was designed by a group of researchers who set out from the premise that the quality of life of schizophrenic patients is perceived differently from that of healthy people, and tried first of all to demarcate the kind of area which is abnormal in these patients. We then devised a set of items which were assessed for clarity and pertinence by a series of experts, and the questionnaire was assembled in the form of a set of statements, response to which is in the form of a Lickert-type 5-stage scale. The finished questionnaire was administered to 279 schizophrenic patients. At the same time, these patients were also evaluated using the AMDP Psychopathology Scale, the positive and negative symptoms evaluation scale (PANS), Lehman's structured quality of life interview (QOLY), Ruiz and Baca's quality of life questionnaire (QLQ), Camberwell's scale of needs analysis (CANr) and the WHO's handicap assessment scale (DDS). These questionnaires were used to judge the different types of validity of the Seville Questionnaire. The reliability of the questionnaire was measured using Cronbach's alpha coefficient (internal consistency: 0,85 scale of favourable aspects, 0,96 scale of unfavourable aspects). As far as validity was concerned, both scales of the questionnaire were found to have a high level of validity. We also examined the extent to which the psychopathological disorders affected the quality of the schizophrenic person's life, the extent to which his/her needs were being met by the health services, and the patient's degree of disability. From the results obtained, we can say that the SQCQ is a reliable and valid instrument, which is sufficiently sensitive to the clinical changes produced in the course of the natural history of the disease. The SQCQ stands out from the other quality of life questionnaires in that it takes into account aspects of the disease which the patient him/herself is aware of as affecting his/her quality of life.

Effects of Ixodes scapularis and Borrelia burgdorferi on modulation of the host immune response: induction of a TH2 cytokine response in Lyme disease-susceptible (C3H/HeJ) mice but not in disease-resistant (BALB/c) mice.

Previous studies have demonstrated that both Ixodes scapularis saliva and Borrelia burgdorferi antigens modulated lymphokines and monokines in vitro. The studies presented here were designed to delineate the role of I. scapularis and B. burgdorferi in modulation of the host immune response in vivo. Infestation of C3H/HeJ mice with infected I. scapularis resulted in an up regulation of IL-4 as early as 8 days after tick infestation, while the levels of T helper cell type 1 (TH1) cytokines, interleukin-2 (IL-2) and gamma interferon (IFN-gamma), were significantly decreased by days 10 to 12. In contrast, the cytokine profile of BALB/c mice exposed to infected nymphal ticks resulted in only transient alterations in IL-4, IL-2, and IFN-gamma production throughout a 12-day period postinfestation. Although the IL-10 level was elevated in both C3H/HeJ and BALB/c mice infested with infected nymphal ticks, no significant difference in the levels of IL-10 was noted between the mouse strains. Flow-cytometric analysis demonstrated increases in the numbers of splenic B-cell and CD4+ lymphocytes in C3H/HeJ but not BALB/c mice exposed to infected ticks. Cell depletion experiments with C3H/HeJ mice demonstrated that CD4+ cells were the sole producers of IFN-gamma and IL-10 while both CD4+ and CD8+ splenocytes contributed to the production of IL-2 and IL-4. These findings suggest that B and CD4+ splenocytes are activated, increase in number, and produce a polarized TH2 response in C3H/HeJ mice exposed to infected I. scapularis. Given that C3H/HeJ mice are susceptible to Lyme disease and the initial TH2 polarization is not evident in BALB/c mice, effective control of this response may have ramifications for spirochete transmission in vivo.