Clinical impact and immunological alterations in asthmatic patients allergic to grass pollen subjected to high urban pollution in Madrid.

BACKGROUND: The prevalence of asthma has increased in recent decades. Among the reasons for this increase is environmental pollution. Pollutants cause bronchial inflammation and introduce modifications in the pollen, making it more allergenic. OBJECTIVE: Assess symptoms and medication requirements of asthmatic patients with grass allergies in Madrid (high urban pollution) and Ciudad Real (low pollution), and simultaneously evaluate the in vitro effects that pollen collected in both areas has on the immune cells of patients. METHODS: During two pollen seasons, patients from both cities were included. The patients recorded their symptoms and the asthma medication they took daily. In both cities, pollen data, pollutants and meteorological variables were evaluated. The response to different cell populations from patients in both areas were analysed after "in vitro" stimulation with pollen from both cities. RESULTS: The symptoms and medication use of the patients in Madrid was 29.94% higher. The NO2 concentration in Madrid was triple that of Ciudad Real (33.4 vs. 9.1 µg/m3 of air). All other pollutants had very similar concentrations during the study period. Pollen from the high pollution area caused a significant enhancement of T-CD8+ and NK cells proliferation compared with pollen of low pollution area, independently of the patient's origin. CONCLUSION: Asthmatic patients from Madrid have a worse clinical evolution than those from Ciudad Real because of higher levels of urban pollution, and this could be driven by the higher capacity of pollen of Madrid to activate T-CD8+ and NK cells.

Characterization and Sodium Cations Sorption Capacity of Chemically Modified Biochars Produced from Agricultural and Forestry Wastes.

Excessive amounts of sodium cations (Na+) in water is an important limiting factor to reuse poor quality water in agriculture or industry, and recently, much attention has been paid to developing cost-effective and easily available water desalination technology that is not limited to natural resources. Biochar seems to be a promising solution for reducing high loads of inorganic contaminant from water and soil solution, and due to the high availability of biomass in agriculture and forestry, its production for these purposes may become beneficial. In the present research, wheat straw, sunflower husk, and pine-chip biochars produced at 250, 450 and 550 °C under simple torrefaction/pyrolysis conditions were chemically modified with ethanol or HCl to determine the effect of these activations on Na sorption capacity from aqueous solution. Biochar sorption property measurements, such as specific surface area, cation exchange capacity, content of base cations in exchangeable forms, and structural changes of biochar surface, were performed by FTIR and EPR spectrometry to study the effect of material chemical activation. The sorption capacity of biochars and activated carbons was investigated by performing batch sorption experiments, and adsorption isotherms were tested with Langmuir's and Freundlich's models. The results showed that biochar activation had significant effects on the sorption characteristics of Na+, increasing its capacity (even 10-folds) and inducing the mechanism of ion exchange between biochar and saline solution, especially when ethanol activation was applied. The findings of this study show that biochar produced through torrefaction with ethanol activation requires lower energy demand and carbon footprint and, therefore, is a promising method for studying material applications for environmental and industrial purposes.

Availability and perceived usefulness of guidelines and protocols for subcutaneous hydration in palliative care settings.

AIMS AND OBJECTIVES: To evaluate the availability of, adherence to, and perceived usefulness of guidelines and protocols for managing hydration and subcutaneous hydration in palliative care settings. BACKGROUND: Hydration at the end of life and the use of a subcutaneous route to hydrate generate some controversy among health professionals for different reasons. Having guidelines and protocols to assist in decision-making and to follow a standard procedure may be relevant in clinical practice. DESIGN: Cross-sectional telephone survey, with closed-ended and open-ended questions designed specifically for this study. METHODS: Data were obtained from 327 professionals, each from a different palliative care service. Mean, standard deviation, minimum and maximum were calculated for continuous variables; frequency distributions were obtained for categorical variables. A qualitative content analysis was performed on the open-ended questions. The article adheres to the STROBE guidelines for reporting observational studies. RESULTS: Only 24.8% of the participants had guidelines available to assist in making decisions regarding hydration, and 55.6% claimed to follow them 'always or almost always'. Of the participants, 38.8% had subcutaneous hydration protocols available, while 78.7% stated that they 'always or almost always' followed these protocols. The remaining participants considered the protocols as useful tools despite not having them available. CONCLUSIONS: Only 25% of the participants' services had guidelines for hydration, and less than 40% had protocols for subcutaneous hydration. However, adherence was high, especially in cases where protocols existed. Among the participants who did not have guidelines and protocols, attitudes were mostly favourable, but mainly as a reference and support for an individualised clinical practice. RELEVANCE TO CLINICAL PRACTICE: Guidelines and protocols on hydration in palliative care may be more useful as a solid reference and support for individualised practice than as instruments for standardising care. From this perspective, their development and availability in palliative care services are recommended.

Fibrilación auricular. Panorámica sobre un tema actualizado / Atrial fibrillation. An update review

La fibrilación auricular (FA) es la arritmia más común en el mundo, con altas mortalidad y morbilidad. Es la primera causa de eventos embólicos como: el deterioro cognitivo, los episodios de insuficiencia cardíaca y la disminución de la calidad de vida, con repercusión socioeconómica y sanitaria. Hoy, se conoce que la FA comienza por ráfagas de descargas eléctricas anormales, que activan rápida e irregularmente las aurículas. La reciente clasificación de la FA en paroxística, persistente o permanente, refleja el deterioro evolutivo de la arritmia. En la actualidad, existe una amplia gama de fármacos para tratar esta patología. Sobresalen los antiarrítmicos y anticoagulantes, aunque la técnica moderna de la ablación con catéter se ha incluido en las guías clínicas, como alternativa o complemento de los fármacos antiarrítmicos, en pacientes seleccionados con FA.

Atrial fibrillation (FA) it is the most common arrhythmia today, presenting high mortality and morbility levels. It is the first cause of embolic events and episodes of heart inadequacy, cognitive deteriorate and poor life quality. It also brings socioeconomic and sanitary consecuences. Today, FA trigers blasts of abnormal electric discharges, which activate auricles quickly and irregularly. Recent classification of the FA as sudden, persistent and permanent lead to an evolving arrhythmia deterioration. In present times, this pathology is treated using a wide range of drugs. Antiarrhythmics and anticoagulants stand out, although the modern technique of ablation with catheter has been included in the clinical guides, either alternative or complement of antiarrhythmics, in patients affected by FA.

Valorization of biochars from pinewood gasification and municipal solid waste torrefaction as peat substitutes.

Gasification and torrefaction have both gained significant interest as bioenergy techniques. During biomass gasification together with fuel gas, carbon-rich solid substances are produced, whereas torrefaction process is mainly used to prepare a final product with higher calorific value and carbon content than the feedstock, through a low temperature pyrolysis. Both materials (carbon wastes from gasification and torrefied product) could be classified as alternatives to biochar obtained from slow pyrolysis of biomass. The use of biochar, typically from the slow pyrolysis of biomass, as soil amendment and, more recently, as growing media components has been widely researched. However, to our knowledge, no studies have compared the use of biochar from gasification and torrefaction as growing media component for growing media formulation. The objective of this work was to study the effect of two biochars on peat-based growing media: a pinewood gasification biochar (BG) and a biochar (BT) obtained by torrefaction of the organic fraction of municipal solid waste. Growing media mixing PT (peat) with 50%vol of BG or BT were prepared and characterized according to their chemical, thermal and hydrophysical properties. Phytotoxic experiments and growth of Lolium perenne were also performed. Results indicated that peat substitution in growing media by BG and BT at a 50%vol ratio improved their hydrophysical properties. Specifically, bulk density increased more than 50%, air space increased by 43%, the increment of the total porosity was 20%, and, finally, the water holding capacity increased by 18.3%. Significantly, a positive effect on plant biomass production (yield increment: 274%) was observed after addition of BT, whereas no significant differences were observed after addition of BG biochar. Therefore, it can be concluded that both BT and BG could be used as peat substitutes in growing media formulation.

Infant growth and early adiposity depending on immigrant background and anthropometric standards; the CALINA Study.

OBJECTIVE: To compare infant growth and adiposity pattern up to 2 years of age in Spanish infants, depending on maternal origin and anthropometric standards. METHODS: Longitudinal study of a representative cohort of infants born at term in Aragon (Spain) (n = 1.430). Mean z-scores of weight, length, body mass index, triceps and subscapular skinfolds were calculated until 24 months of age using World Health Organization (WHO), Euro-Growth and Spanish growth standards and categorized by maternal origin (Spanish vs. immigrant). RESULTS: Infants of immigrant mothers had higher weight, length, body mass index, triceps and subscapular skinfolds than Spanish maternal origin infants during the first months of life. Mean z-scores significantly varied depending on growth standards used. At 18 months of age, all anthropometric differences between both groups disappeared, but only when using WHO growth standards. Mean triceps and subscapular skinfold z-scores substantially and progressively increased from 3 months to 24 months of age in both groups compared to WHO standards. At 24 months, the prevalence of infants at risk of overweight and overweight were similar in both groups (Spanish: 15.1% and 3.8%; immigrant: 14.7% and 4.9%, respectively). CONCLUSIONS: Infant growth, adiposity patterns and prevalence of overweight depend on maternal origin, showing initial differences which progressively disappeared at 24 months of life when WHO growth standards were used. Differences in infant mean anthropometric measurements depend on anthropometric standard used.

Infant growth and early adiposity depending on immigrant background and anthropometric standards; the CALINA Study / Crecimiento y adiposidad durante la primera infancia dependiendo del origen de la familia y de los estándares antropométricos; estudio CALINA

Objective: To compare infant growth and adiposity pattern up to 2 years of age in Spanish infants, depending on maternal origin and anthropometric standards. Methods: Longitudinal study of a representative cohort of infants born at term in Aragon (Spain) (n = 1.430). Mean z-scores of weight, length, body mass index, triceps and subscapular skinfolds were calculated until 24 months of age using World Health Organization (WHO), Euro-Growth and Spanish growth standards and categorized by maternal origin (Spanish vs. immigrant). Results: Infants of immigrant mothers had higher weight, length, body mass index, triceps and subscapular skinfolds than Spanish maternal origin infants during the first months of life. Mean z-scores significantly varied depending on growth standards used. At 18 months of age, all anthropometric differences between both groups disappeared, but only when using WHO growth standards. Mean triceps and subscapular skinfold z-scores substantially and progressively increased from 3 months to 24 months of age in both groups compared to WHO standards. At 24 months, the prevalence of infants at risk of overweight and overweight were similar in both groups (Spanish: 15.1% and 3.8%; immigrant: 14.7% and 4.9%, respectively). Conclusions: Infant growth, adiposity patterns and prevalence of overweight depend on maternal origin, showing initial differences which progressively disappeared at 24 months of life when WHO growth standards were used. Differences in infant mean anthropometric measurements depend on anthropometric standard used (AU)

Objetivo: comparar el patrón de crecimiento infantil y adiposidad temprana hasta los 2 años en los niños españoles, según el origen materno y los estándares antropométricos. Métodos: estudio longitudinal en una cohorte representativa de niños nacidos a término en Aragón (España) (n = 1.430). Se calcularon z-scores de peso, longitud, índice de masa corporal, pliegue tricipital y subescapular hasta los 2 años usando estándares de crecimiento de la Organización Mundial de la Salud (OMS), Euro-Growth y nacionales, y se categorizaron según el origen materno (español vs. inmigrante). Resultados: los niños de madre de origen inmigrante presentaron mayor peso, longitud, índice de masa corporal y pliegues tricipital y subescapular que los de origen español durante los primeros meses de vida. Los valores medios de z-score variaron significativamente según el estándar de crecimiento utilizado. A los 18 meses, las diferencias entre ambos grupos desaparecieron solo al emplear los estándares de la OMS. Los valores de z-score de pliegues tricipital y subescapular se incrementaron de manera sustancial y progresiva desde los 3 a los 24 meses comparándolos con los estándares de la OMS. A los 24 meses, la prevalencia de niños con riesgo de sobrepeso y sobrepeso fue similar en ambos grupos (español: 15,1% y 3,8%; inmigrante: 14,7% y 4,9%, respectivamente). Conclusiones: el patrón de crecimiento y la adiposidad durante la primera infancia, así como la prevalencia de sobrepeso mostraron diferencias según el origen de la madre que desaparecieron progresivamente a los 24 meses de vida al emplear los estándares de la OMS. Se objetivaron diferencias en los valores antropométricos según el estándar de crecimiento utilizado (AU)

Inhibidores de la dipeptidil peptidasa 4 y una nueva estrategia farmacológica en la diabetes mellitus tipo 2 / Inhibitors of dipeptidil peptidase 4 new pharmacologic strategic in the diabetes mellitus type 2

La diabetes mellitus sigue siendo una enfermedad temible. El uso adecuado de la farmacoterapia para el control metabólico, ayudaría a disminuir la incidencia de complicaciones. Actualmente se dispone de variados grupos farmacológicos para el control temporal de las cifras de glucemias de pacientes con diabetes mellitus tipo 2, entre ellos están los inhibidores de la dipeptidil peptidasa 4 caracterizados por estimular el aumento de la concentración del péptido similar a glucagón tipo 1 GLP-1 y la secreción de insulina en la célula beta del islote pancreático. La eficacia, en términos de hemoglobina glucosilada, ha mostrado ser inferior a la de la insulina, pero sin el potencial del peligro de hipoglucemia, así como el efecto neutro o la disminución del peso corporal. Se realizó esta revisión bibliográfica con el objetivo de actualizar los conocimientos sobre el papel de las sustancias con acción incretinas en el control metabólico de los pacientes con diabetes mellitus tipo 2 y específicamente la acción de los IDPP4, ya que es creciente el problema de dicha enfermedad y se requiere, cada vez más, una mejor información de los fármacos a utilizar, aunque en el futuro los datos obtenidos concluirán su efectividad(AU)

Diabetes mellitus remains a fearsome disease. Proper use of pharmacotherapy for metabolic control, would help reduce the incidence of complications. Currently there are various pharmacological groups for temporary control of blood glycemia of patients with diabetes mellitus type 2. One of them is dipeptidyl peptidase-4 inhibitor characterized by stimulating increased concentration like peptide glucagon type 1 GLP -1 and insulin secretion in pancreatic islet beta cell. The effectiveness in terms of glycosylated hemoglobin has shown to be less than that of insulin, but without the potential danger of hypoglycaemia and the neutral effect or decrease in body weight. These facts prompt this literature review which was conducted to update the knowledge on the role of substances with incretin action in the metabolic control of patients with diabetes mellitus type 2, specifically the action of IDPP4, as this disease is an growing problem requiring better information on drug use(AU)

Nuevas consideraciones en el tratamiento del tromboembolismo pulmonar: new considerations in its treatment / Pulmonary tromboembolismo: new considerations in its treatment

La enfermedad tromboembólica tiene altas cifras de morbilidad y mortalidad. Se presenta en un variado espectro de pacientes. Continúa siendo un diagnóstico importante en la atención de las urgencias médicas por lo que hemos decidido realizar esta revisión bibliográfica con el objetivo de actualizar los conocimientos cada vez más necesarios, sobre el diagnóstico y la conducta que se debe asumir en esos casos. Teniendo en cuenta que su diagnóstico por técnicas de imagen es cada vez más difícil, lo que evidencia el valor del método clínico en esta impactante enfermedad, así como su prevención. Sin olvidar que a pesar de estar estandarizada cada conducta, debe valorarse la individualidad del paciente(AU)

Thromboembolic disease has high morbidity and mortality. It comes in a wide spectrum of patients. It remains an important diagnosis in the care of medical emergencies so we decided to do this literature review in order to update the increasingly necessary knowledge about the diagnosis and behavior that must be undertaken in such cases. Given that its diagnostic by imaging is increasingly difficult, the clinical method is valuable in this shocking disease and its prevention. Not to mention that despite being standardized each patient's individuality must be evaluated(AU)

Tratamiento actual de la diabetes mellitus tipo 2 / Type 2 Diabetes Mellitus Current Treatment

La diabetes mellitus tipo 2 es una enfermedad crónica, degenerativa e incurable pero controlable. Existen varios objetivos en el tratamiento del diabético tipo 2, pero su esencia radica en el control metabólico y la prevención de las complicaciones. La revisión abordó la necesidad de modificar estilos de vida, sintetiza algunas características farmacológicas en cada grupo, se mostró un novedoso arsenal terapéutico como alternativa de impacto. Propuso la combinación de dos y tres medicamentos hipoglucemiantes con la finalidad de alcanzar niveles deseados de glucemias y disminuir reacciones adversas. Expuso un algoritmo integrador para el manejo práctico de la diabetes, que favorece el desempeño médico en la atención primaria y secundaria.

Type 2 diabetes mellitus is a chronic, degenerative and incurable disease, but it is manageable. There are several objectives in the treatment of type 2 diabetes, but its essence lies in the metabolic control and prevention of complications. The review addressed the need to change lifestyles and summarized some pharmacological characteristics in each group, a novel therapeutic collection as an alternative of impact was shown. A combination of two and three hypoglycemic drugs in order to achieve desired blood glucose levels and reduce adverse reactions was proposed. An integrating practical algorithm for diabetes management, which favors medical performance in primary and secondary care, was exposed.

Perceptions of health professionals on subcutaneous hydration in palliative care: A qualitative study.

BACKGROUND: Evidence indicates that hypodermoclysis is as safe and effective as intravenous rehydration in the treatment of the symptomatology produced by mild to moderate dehydration in patients for whom oral route administration is not possible. However, the knowledge about the use of the subcutaneous hydration and its correlates is still limited. AIM: To explore the perceptions, attitudes and opinions of health professionals in palliative care on the administration of subcutaneous hydration. DESIGN: This is a qualitative focus group study with health professionals of palliative care. Four focus groups were carried out until data saturation. A qualitative content analysis was performed. SETTING/PARTICIPANTS: A total of 37 participants, physicians and nurses, were recruited from different services of palliative care in Spain. RESULTS: In all, 856 meaning units were identified, from which 56 categories were extracted and grouped into 22 sub-themes, which were distributed among four themes: 'factors which influence the hydration decision', 'factors related to the choice of the subcutaneous route for hydration', 'the subcutaneous hydration procedure' and 'performance guidelines and/or protocols'. CONCLUSIONS: Variables which most often influence the use of subcutaneous route to hydration are those that are linked to the characteristics of the patient, the team and the family, and other like the context and professionals' subjective perceptions about this medical practice.

Sequential outbreaks in a Spanish hospital caused by multiresistant OXA-58-producing Acinetobacter baumannii ST92.

The aim of this study was to assess the epidemiology and molecular basis of the infection and dissemination of multidrug-resistant Acinetobacter baumannii (MDRAB) in three sequential outbreaks at the intensive care units (ICUs) of a tertiary university hospital in Granada, Spain, between 2009 and 2011. Strains from all patients infected and/or colonized by MDRAB during outbreak periods were characterized using PFGE and multilocus sequence typing (MLST). The first outbreak appeared in the summer of 2009 involving 38 ICU patients: 25 from a Traumatology-Rehabilitation hospital (TRH) and 13 from a Medical-Surgery hospital (MSH). Between 2010 and 2011, outbreaks were limited to the MSH-ICU, affecting 9 and 11 patients, respectively. Two PFGE types were detected. In the 2009 outbreak, two clones were identified: profile 1 strains were isolated at the TRH, whilst profile 2 was isolated at the MSH. Only one clone was identified in the 2010 and 2011 outbreaks: the profile 2 clone detected at the MSH in 2009. After MLST analysis, a single sequence type (ST92) was identified. This suggested that an endemic strain could evolve and cause localized outbreaks in vulnerable patients. Multiplex PCR for OXA group enzymes yielded a positive result for blaOXA-58-like and blaOXA-51-like genes, and gene sequencing showed the presence of blaOXA-58. However, the absence of ISAba1 upstream of the blaOXA-51-like gene suggested the absence of OXA-51 expression. The susceptibility pattern was not an appropriate method for MDRAB surveillance, as several susceptibility patterns were identified in a single clone. Consequently, molecular methods of characterization are recommended for epidemiological surveillance of MDRAB.

Violencia ejercida a la mujer en la relación de pareja. Policlínica Rolando Monterrey. Enero- Diciembre 2009. Moa / Exercised violence to the woman in the relation of couple. Policlinica Rolando Monterrey. January December 2009. Moa

Se realizó un estudio descriptivo, utilizando un diseño no experimental transversal, sobre la violencia ejercida a la mujer en la relación de pareja, en el Policlínico Rolando Monterrey (Enero- Diciembre 2009) en un universo de 245 mujeres y una muestra de 70. Aplicamos una encuesta con el objetivo de caracterizar sociopsicológicamente a las víctimas; describir la edad, escolaridad, ocupación, tipo y tiempo de la relación de pareja, funcionamiento familiar, las formas de violencia más frecuentes y los factores que la perpetúan, así como valorar las habilidades para la solución de situaciones de conflictos, utilizando para ello estadígrafos descriptivos, y determinar las características personológicas de la muestra. Encontramos que el tipo de violencia más empleada fue la psicológica, la cual fue utilizada en mujeres entre 35-44 años de edad, con un nivel preuniversitario; donde las trabajadoras resultaron las más afectadas, repercutiendo el fenómeno sobre aquellas mujeres con unión consensual, que tenían más de 10 años de duración con su pareja, que convivían en contextos de familias disfuncionales; poseían escasas habilidades para la solución de problemas, y que perduran en la relación por la dependencia económica que mantienen y por su seguridad personal. La caracterización personológica reveló que fueron mujeres dispensarizadas como supuestamente sanas, la mayoría manifestó ansiedad como estado y depresión en niveles altos, sin embargo la ansiedad como rasgo es bajo; poseen una autovaloración inadecuada, y sus necesidades giran en torno a su seguridad, autorrealización y afecto o estima. Recomendamos la participación de todos los grupos sociales, para profundizar y promover líneas de investigación sobre tal problemática(AU)

A descriptive study came true, using a design not experimental side road, on the exercised violence to the woman in the relation of couple, in the Polclinica Rolando Monterrey (January December 2009) in a universe of 245 women and a sample of 70. We applied an opinion poll for the sake of characterizing sociopsicológic to the victims; Describing the age, scholarship, occupation, type and time of the relation of couple, familiar functioning, more frequent the forms of violence and the factors that perpetuate her, as well as appreciating the abilities for the solution of situations of conflicts, using for it descriptive estadigrafs, and determining characteristics personologics of the sample. We found out that the type of more used violence was her psychological one, which was used in women between 35-44 years elderly, with a pre-university level; where workers gave results them more affected, having influence the phenomenon on those women with consensual union, that they had more of 10 years of duration with their couple, that they lived together in contexts of dysfunctional families; They had scarce abilities for the solution of problems, and that they last in the relation for the cost-reducing dependence that they hold and for their personal safety. Characterization personologic revealed that controlled were womanly as supposedly you heal, the majority manifested anxiety like status and depression in tall levels, however anxiety as feature is softly; they have an unsuitable self-appraisal, and your needs revolve around their certainty, self-actualization and affection or esteem. We recommended the participation of all the social groups, in order to deepen and to promote fact-finding trajectories on such problems(AU)

Effectiveness and safety of simplification therapy with once-daily tenofovir, lamivudine, and efavirenz in HIV-1-infected patients with undetectable plasma viral load on HAART.

OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.

In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells.

We assessed the in vitro toxicity of tenofovir (TFV) and compared it with those of zidovudine (AZT), didanosine (ddI), ritonavir (RTV), and lopinavir (LPV) alone and in combination in human renal proximal tubule epithelial cells (RPTECs). The cells were treated with various concentrations and combinations of the tested antiretrovirals for up to 22 days, and cytotoxicity was determined. In addition, we assessed the levels of mitochondrial DNA (mtDNA) and cytochrome oxidase II (COII) mRNA in RPTECs treated with reverse transcriptase inhibitors. TFV alone was not associated with significant cytotoxicity. ddI showed pronounced cytotoxicity that was greater than those of AZT (P = 0.002) and TFV (P = 0.0001). The combination of 10 muM RTV and 40 muM LPV significantly reduced RPTEC viability (P < 0.0001), and TFV tended to partially reduce this effect. TFV alone affected neither mtDNA nor COII mRNA levels, whereas ddI caused a profound depletion of mtDNA and a parallel reduction in COII mRNA expression. The effects of ddI, but not those of AZT, on mtDNA and COII mRNA were further enhanced in the presence of TFV, a finding consistent with the inhibition of ddI clearance by TFV. The addition of TFV to ddI or AZT appeared to slightly increase the COII mRNA/mtDNA ratio relative to that in cells treated with ddI or AZT alone. Together, these in vitro results indicate that combination with other antiretrovirals does not significantly increase the toxic potential of TFV in RPTECs.