The evolution of colour pattern complexity: selection for conspicuousness favours contrasting within-body colour combinations in lizards.

Many animals display complex colour patterns that comprise several adjacent, often contrasting colour patches. Combining patches of complementary colours increases the overall conspicuousness of the complex pattern, enhancing signal detection. Therefore, selection for conspicuousness may act not only on the design of single colour patches, but also on their combination. Contrasting long- and short-wavelength colour patches are located on the ventral and lateral surfaces of many lacertid lizards. As the combination of long- and short-wavelength-based colours generates local chromatic contrast, we hypothesized that selection may favour the co-occurrence of lateral and ventral contrasting patches, resulting in complex colour patterns that maximize the overall conspicuousness of the signal. To test this hypothesis, we performed a comparative phylogenetic study using a categorical colour classification based on spectral data and descriptive information on lacertid coloration collected from the literature. Our results demonstrate that conspicuous ventral (long-wavelength-based) and lateral (short-wavelength-based) colour patches co-occur throughout the lacertid phylogeny more often than expected by chance, especially in the subfamily Lacertini. These results suggest that selection promotes the evolution of the complex pattern rather than the acquisition of a single conspicuous colour patch, possibly due to the increased conspicuousness caused by the combination of colours with contrasting spectral properties.

Using visual modelling to study the evolution of lizard coloration: sexual selection drives the evolution of sexual dichromatism in lacertids.

Sexual selection has been invoked as a major force in the evolution of secondary sexual traits, including sexually dimorphic colourations. For example, previous studies have shown that display complexity and elaborate ornamentation in lizards are associated with variables that reflect the intensity of intrasexual selection. However, these studies have relied on techniques of colour analysis based on human--rather than lizard--visual perception. Here, we use reflectance spectrophotometry and visual modelling to quantify sexual dichromatism considering the overall colour patterns of lacertids, a lizard clade in which visual signalling has traditionally been underrated. These objective methods of colour analysis reveal a large, previously unreported, degree of sexual dichromatism in lacertids. Using a comparative phylogenetic approach, we further demonstrate that sexual dichromatism is positively associated with body size dimorphism (an index of intrasexual selection), suggesting that conspicuous coloration in male lacertids has evolved to improve opponent assessment under conditions of intense male-male competition. Our findings provide the first evidence for the covariation of sexual dichromatism and sexual size dimorphism in lacertids and suggest that the prevalent role of intrasexual selection in the evolution of ornamental coloration is not restricted to the iguanian lineage, but rather may be a general trend common to many diurnal lizards.

Effectiveness of self-esteem and social skills group therapy in adolescent eating disorder patients attending a day hospital treatment programme.

OBJECTIVE: To evaluate self-esteem and social skills in adolescent eating disorder patients before and after specific group therapy as part of a Day Hospital Programme. METHOD: One hundred and sixty adolescent eating disorder patients, classified as anorexia nervosa and related disorders (AN-rd) (N = 116) or bulimia nervosa and related disorders (BN-rd) (N = 44) received structured group therapy for developing self-esteem and social skills. RESULTS: BN-rd patients had poorer perceptions of some self-esteem and social skills variables. After group therapy, both groups presented significant improvements in their perceptions of physical appearance, their self-concept related to weight and shape and to others, happiness and satisfaction, social withdrawal and leadership. BN-rd patients presented more changes on many of the variables. DISCUSSION: Specific self-esteem and social skills group therapy in patients with eating disorders can be useful in improving certain core features.

SEOM clinical guidelines for the treatment of non-small-cell lung cancer: an updated edition

The purpose of this article is to provide updated recommendations for the diagnosis and treatment of patients non-small-cell lung cancer (NSCLC). The staging system for lung cancer has recently been revised by the International Association for Study of Lung Cancer and patients with NSCLC shall now be staged according to the UICC system 7th edition. Recommendations for treatment were based on treatment strategies that improve overall survival. In functionally fit patients with stage I-II disease surgical resection is recommended. Four cycles of adjuvant cisplatin-based chemotherapy is recommended in patients with pathologic stage II-III. For patients with stage IIIA and non-bulky mediastinal lymph node survival was significantly improved with induction chemotherapy plus surgical resection. Patients with unresectable or bulky stage IIIA and those with stage IIIB, should be treated with platinum-based chemotherapy and thoracic radiotherapy. For patients with metastatic disease and performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For elderly patients and those with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with platinum-based chemotherapy, except for patients with certain clinical characteristics. Maintenance therapy with pemetrexed or erlotinib increases survival in patients who did not progress after 4 cycles of a platinum based chemotherapy. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs (AU)

Putting information back into biological communication.

At the heart of many debates on communication is the concept of information. There is an intuitive sense in which communication implies the transfer of some kind of information, probably the reason why information is an essential ingredient in most definitions of communication. However, information has also been an endless source of misunderstandings, and recent accounts have proposed that information should be dropped from a formal definition of communication. In this article, we re-evaluate the merits and the internal logic of information-based vs. information-free approaches and conclude that information-free approaches are conceptually incomplete and operationally hindered. Instead, we propose a functional notion of information that follows logically from previous adaptationist accounts. The ensuing definition of communication provides a wider, more inclusive theoretical scope that reflects more accurately the evolutionary scenario shaping animal signals. Additionally, it is a definition better equipped to deal with the extraordinary diversity of animal signals, facilitates the distinction of honest and deceptive signals at a proximate level and accommodates a number of conceptual and practical issues (e.g. redundancy, alerting components) that are lost when we fail to acknowledge the informative content of animal signals.

Comparación entre el «test combinado» y el «test combinado consecutivo» para la detección del síndrome de Down en el primer trimestre de la gestación / First trimester screening for Down syndrome. Comparation between «consecutive combined test» and «combined test»

Objetivos. Evaluar la eficacia del cribado del síndromede Down en el primer trimestre de la gestación comparandoel «test combinado consecutivo» con el «test combinado».Métodos. El «test combinado consecutivo» se ha ofrecidoa 10.080 mujeres embarazadas (edad materna [EM] 31,21± 4,95) y el «test combinado» o One Stop Clinics for Assessmentof Risk (OSCAR) a 1.535 (EM 31,14 ± 5,52). En el primergrupo, los marcadores bioquímicos (la subunidad β librede la gonadotrofina coriónica humana [fβhCG] y la proteínaplasmática A asociada al embarazo [PAPP-A]) se han determinadoentre las 7 y 12 semanas de gestación y la translucencianucal (TN) entre las 12 y las 13 semanas, mientrasque en el segundo grupo ambas determinaciones se hanefectuado en el mismo día, alrededor de la semana 12.Resultados. En el grupo «test combinado consecutivo», la tasa de falsos positivos fue de 1,90 % (192 embarazadas),significativamente menor al del grupo «test combinado»: 4,30 % (66 embarazadas). La tasa de detección fuedel 94,44 % (51/54) y del 94,52 % (69/73), respectivamente.La potencia discriminatoria de los múltiplos de la mediana(MoMs) de PAPP-A era mayor entre las semanas 8 y11, mientras que los de los MoMs de fβhCG y la TN a partirde la 13.Conclusiones. El «test combinado consecutivo» ennuestra serie de pacientes parece ser más eficiente que el«test combinado» al presentar una tasa de falsos positivosmenor con una tasa de detección similar, debido principalmenteal hecho de realizar los marcadores más sensibles(PAPP-A y TN) en el momento de su mayor eficacia (AU)

Objectives. To evaluate the performance of first-trimesterscreening for trisomy 21 comparing the «consecutivecombined test» in front of the «combined test».Methods. First-trimester «consecutive combinedtest» has been offered to 10,080 pregnant women (maternalage [MA] 31.21 ± 4.95) and the first-trimester «combinedtest» or One Stop Clinics for Assessment of Risk(OSCAR) to 1,535 pregnant women (MA 31.14 ± 5.52). Inthe first group, biochemical markers have been determinedat 7 to 12 weeks of gestation and the nuchal translucency(NT) at 12 to 13 weeks; meanwhile, in the secondgroup biochemical markers and NT have been determinedin the same day, close to 12 weeks.Results. In the first group (consecutive combinedtest) 10,080 pregnancies had been studied with a completefollow-up, with a screen positive rate of 1.91% (192pregnancies) and a detection rate of 94.44% (51/54Down syndrome pregnancies). In the second group (combinedtest) 1,535 pregnancies had been studied with acomplete follow-up, with a screen positive rate of 4.30%(66 pregnancies) and a detection rate of 94.52% (69/73Down syndrome pregnancies). Pregnancy-AssociatedPlasma Protein-A (PAPP-A) Multiples of the Median(MoMs) allows a better discriminatory power between 8and 11 weeks, meanwhile free β-chain of Human ChorionicGonadotropin (fβhCG) MoMs and NT MoMs allowsthis power after 13 week.Conclusion. The «consecutive combined test» appliedon our population seems to be more efficient with a lowerscreen positive rate than the «combined test» and asimilar detection rate, because the more sensitive markers(PAPP-A and NT) have been determined when theirpotential is higher (AU)

Quantity discrimination in Tenebrio molitor: evidence of numerosity discrimination in an invertebrate?

Numerosity discrimination, the ability to distinguish between sets with more and less items, is recognised as the foundation for higher numerical abilities. Understanding numerosity discrimination from a comparative perspective is hence pivotal in tracing the evolution of numerical representation systems. However, numerosity discrimination has been well studied only in vertebrates, where two innate systems of number representation have been described: an 'analog magnitude system' used to discriminate among numerosities by representing them as cardinal magnitudes and a 'parallel individualisation system' that allows precise discrimination among small arrays of items (< or =4) by representing objects individually. We investigated the existence of quantity discrimination in an insect species (Tenebrio molitor) by using a spontaneous two-choice procedure in which males were exposed to substrates bearing odours from different numbers of females (< or =4) in increasing numerosity ratios (1:4, 1:3 and 1:2). We show that males can discriminate sources of odours reflecting 1 versus 4 and 1 versus 3 females, but not 2 versus 4 or 1 versus 2, indicating that T. molitor males exhibit a marked preference for sources reflecting more female donors only when numerosity ratios are below 1:2. We discuss the functional significance of this finding and whether our pattern of results could be best explained by summation of a non-numerical continuous variable or by the existence of a numerosity discrimination mechanism with an operational signature ratio of 1:2.

Chemosensory assessment of sperm competition levels and the evolution of internal spermatophore guarding.

Males of many species adjust their reproductive behaviour according to the perceived risk of sperm competition. Although this phenomenon is widespread in insects and other animals, the mechanisms that allow mates to assess sperm competition levels remain largely unexplored. In this study, we analysed the mating behaviour of pairs of Tenebrio molitor beetles under three odour treatments representing increasing levels of sperm competition risk (SCR) and sperm competition intensity (SCI). Copula duration and male and female post-copulatory behaviour varied significantly with odour treatment. Both copula duration and post-copulatory associations (PCAs) increased significantly in odour treatments reflecting high male density. To our knowledge, this is the first study to report that insects may assess the actual density of potential competitors at the time of mating, a cue to SCR and SCI, on the basis of chemical cues. In T. molitor, males inhibit sperm release from the spermatophore of a rival male when remating takes place at short intervals. We show that, when sperm competition levels are high, PCAs increase female remating interval just above that necessary to prevent spermatophore inhibition by rival males. This finding strongly suggests that strategic male behaviour plays a 'spermatophore guarding' role in this species. Although common in insects with external spermatophore transfer, spermatophore guarding is not expected in species with rapid ejaculate transfer and internal spermatophore delivery. Our results reveal that spermatophore guarding may evolve, even under these circumstances, as an evolutionary response to short-term spermatophore inhibition or displacement mechanisms.

Los Tlv´s en la era del síndrome del edificio enfermo / Tlvs in the age of the ''Sick building syndrome''

El Síndrome del edificio enfermo (SEE) es una entidad inicialmente descrita en 1972, caracterizada por afectar a más del 20% de la población laboral del edificio implicado. Los motivos de consulta oscilan desde leves conjuntivitis irritativas hasta otras más graves, como neumopatías intersticiales. Todos los edificios afectados tienen en común: ser de reciente construcción, elevada hermeticidad y alta dependencia para su intercambio aéreo del aire acondicionado (AA). En este trabajo describiremos un fenómeno epidémico compatible con SEE, acaecido en un edificio industrial de estas características por el que fuimos consultados a lo largo de 2001, su metodología de estudio, así como las medidas preventivas emprendidas que lograron erradicar el problema. En todo momento las mediciones ambientales estuvieron por debajo de los valores de referencia y no tuvieron sensibilidad suficiente pata detectar alteraciones ambientales que explicaran las molestias de los trabajadores afectados (AU)

The '' sick building syndrome'' was first described in 1972 and it is characterised by involving over 20% of the population working within the suspect/affected building. the causes for medical consultation or for seeking medical help range from light irritative cojunctivitides to rather to rather more severe problems, such as interstitial pneumopathies. All the involved buildings share the following common features: recent construction, high hermeticity, and high dependence upon air conditioning for exchange. We here report an epidemic phenomenon that is compatible with the "sick building syndrome", which occurred in an industry-related building fulfilling the above characteristic features, causing us to be called for consultation over the year 2001. the sutdy methodoloy is reported, together with the preventive measures that finally led to the eradication of the problem. At all times, he environmental measurements and assessments yielded results bellow the reference threshold values and had not enough sensitivity for detecting environmental changes that might have explained the workers´complaints (AU)

Impression cytology of the conjunctival epithelium after antiglaucomatous treatment with latanoprost.

PURPOSE: To study nongoblet and goblet epithelial conjunctival cells after several treatment periods with latanoprost, a prostaglandin analogue. METHODS: Twelve patients (20 eyes) were studied before the onset of treatment and after 1, 3, and 6 months of latanoprost use. Impression cytology was carried out to analyze cellular density and morphologic parameters such as minimum and maximum diameter and area. RESULTS: Nongoblet epithelium cell density did not change over the treatment period. The density of goblet cells increased after 1 month of use, but returned to initial cell density after longer treatment periods. Nongoblet epithelial cells underwent a significant reduction in size after 1, 3, and 6 months of treatment. In addition, the minimum/maximum diameter ratio suggested that after 1 month there were some changes in shape (a slight elongation) when compared to cells of untreated patients. Nevertheless, after longer treatment periods, the cells regained their original shape. No changes in size were observed in goblet cells, except for a slight decrease in maximum diameter after 6 months of treatment, which suggests that the cells became more rounded. CONCLUSIONS: The density of nongoblet epithelial cells does not change after different treatment periods with latanoprost. However, their size decreases and after short treatment periods their shape also undergoes changes. The density of goblet cells increases after 1 month of treatment, but decreases again after longer periods. Their size does not undergo any modification, although there is a variation in shape after 6 months of treatment.

Effects of thrombolysis in the evolution of right bundle-branch block complicating an acute anterior myocardial infarction.

INTRODUCTION: There is scant information about the effects of thrombolysis in the evolution of right bundle-branch block (RBBB) in the setting of acute anterior myocardial infarction. The aim of this study has been to analyse these effects and its impact on prognosis. METHODS: We studied 54 patients who presented a RBBB related to an acute anterior myocardial infarction. We defined two groups: those who received thrombolytic treatment and those who did not. We analysed the evolution of RBBB (transience, moment of onset, moment of disappearance) and its relationship with in-hospital mortality.Twenty-one patients (39%) received thrombolytic treatment (groupT) and 33 patients (61%) (group NT) did not. RESULTS: The incidence of late appearance (> 6 h) of RBBB was less frequent in group T compared with group NT (10% vs. 33%, p = 0.04). The incidence of transient block was similar in the two groups (57% vs. 45%, p ns). However, early disappearance of RBBB (in < 6 hours) was more common in group T than in group NT (33% vs. 9%, p = 0.04). Mortality was higher in patients with RBBB present at 24 h after admission) than in those with RBBB resolved in less than 24 hours (in group NT, 55% vs. 8%, p = 0.02 and in group T 50% vs. 0%, p = 0.02, respectively). CONCLUSIONS: Thrombolysis seems to influence the moment of onset and disappearance of RBBB by promoting its early disappearance and avoiding its late appearance. Disappearance of RBBB is associated with a better prognosis.

A double-blind randomized comparative trial: eberconazole 1% cream versus clotrimazole 1% cream twice daily in Candida and dermatophyte skin infections.

In a double-blind phase III study the efficacy and tolerance of eberconazole 1% cream was compared with clotrimazole 1% cream, applied twice daily for four consecutive weeks in 157 patients, with mycologically proven cutaneous candidosis (24 patients, 25 infected sites) and in 133 patients with dermatophyte skin infections (141 treated sites). The analysis was carried out by number of infected and treated sites. The four groups of sites and the distribution of target lesions were similar. The distribution of the sum of clinical scores and infecting organisms were also similar. There were no differences between the groups in terms of the range and mean duration of infection. At the end of therapy and on follow-up in skin candidosis the proportion of patients with effective treatment was 73 and 50% for clotrimazole and eberconazole, respectively. Premature termination due to adverse effects was 26.7% for clotrimazole and 20% for eberconazole. At the end of treatment of dermatophyte infections the proportion of patients with effective treatment was 46% for clotrimazole and 61% for eberconazole. At the overall assessment (6 weeks after the end of treatment) eberconazole was judged effective in 72% of treated sites, whereas clotrimazole was effective in 61%, this difference was not statistically significant (P = 0.15). There were three relapses (4%) in the clotrimazole-treated group and one relapse (1%) in the eberconazole group. One patient treated with eberconazole cream (1%) had a premature termination due to adverse events attributable to the medication.

Neurogenesis and neuronal regeneration in the adult reptilian brain.

Evidence accumulated over the last few decades demonstrates that all reptiles examined thus far continue to add neurons at a high rate and in many regions of the adult brain. This so-called adult neurogenesis has been described in the olfactory bulbs, rostral forebrain, all cortical areas, anterior dorsal ventricular ridge, septum, striatum, nucleus sphericus, and cerebellum. The rate of neuronal production varies greatly among these brain areas. Moreover, striking differences in the rate and distribution of adult neurogenesis have been noted among species. In addition to producing new neurons in the adult brain, lizards, and possibly other reptiles as well, are capable of regenerating large portions of their telencephalon damaged as a result of experimentally-induced injuries, thus exhibiting an enormous potential for neuronal regeneration. Adult neurogenesis and neuronal regeneration take advantage of the same mechanisms that are present during embryonic neurogenesis. New neurons are born in the ependyma lining the ventricles and migrate radially through the brain parenchyma along processes of radial glial cells. Several lines of evidence suggest that radial glial cells also act as stem cells for adult neurogenesis. Once they reach their final destination, the young neurons extend axons that reach appropriate target areas. Tangential migration of neurons alongside the ventricular ependyma has also been reported. Most of these tangentially migrating neurons seem to be destined for the olfactory bulbs and are, thus, part of a system similar to the mammalian rostral migratory stream. The proliferation and recruitment of new neurons appear to result in continuous growth of most areas showing adult neurogenesis. The functional consequences of this continuous generation and integration of new neurons into existing circuits is largely conjectural, but involvement of these phenomena in learning and memory is one likely possibility.

[Anorexia nervosa: a multidisciplinary approach]. / Anorexia nerviosa. Abordaje multidisciplinar.

The childhood-adolescent psychiatrics field has, for various years, been confronted by a very significant increase in cases of nervous anorexia, a serious eating disorder characterized by a noticeable loss of weight. At the bottom of this situation lie complex biological, psychological and social-cultural problems, which demand an interdisciplinary approach to solve them. This article presents the predisposing factors, the initial factors, the factors which maintain this disorder...; what behaviors are considered to be normal; what the physical and psychological manifestations are; as well as what the medical evaluation carried out is ... to finalize with an explanation of the different functions to be performed by each member of a multidisciplinary team.

Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women.

BACKGROUND: Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation. METHODS: We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP). RESULTS: Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group. CONCLUSIONS: These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.

Bone disease in patients with long-term renal transplantation and normal renal function.

Renal osteodystrophy may persist during the early years after renal transplantation. However, information on bone status after a successful long-term renal transplantation is limited. We examined biochemical parameters, bone mineral density (BMD), and bone histomorphometry in 25 asymptomatic men with normal renal function after 7.5 +/- 5.7 years of a renal transplantation. Serum calcium, phosphorus, alkaline phosphatase, and 1,25(OH)(2)D(3) levels and urinary calcium level and cyclic andenosine monophosphate excretion were within normal range in all patients. Serum intact parathyroid hormone (PTH) level was elevated in 11 subjects (133.6 +/- 78 pg/mL) and normal in the other 14 subjects (47.9 +/- 13.6 pg/mL). Mean BMD at the lumbar spine and femoral neck was low in the entire group. However, it progressively increased as time after transplantation increased, approaching normal values after 10 years. Bone histomorphometric analysis showed bone resorption, osteoid volume, and osteoid surface greater than normal range in the majority of patients. Bone formation rate and mineralization surface were low, and mineralization time was delayed in most patients. These lesions were more severe in patients after 3 to 4 years of transplantation but improved with time and approached normal values after a period of 10 years. PTH values did not correlate with bone histological characteristics or BMD. These results show that the bone alterations observed after long-term renal transplantation consist of a mixed bone disease in which features of high bone turnover coexist with altered bone formation and delayed mineralization. These findings may result from the combined effect of preexisting bone disease and immunosuppressive therapy.

Anorexia nerviosa. Abordaje multidisciplinar / Nervous anorexia. A multidisciplinary approach

El ámbito de la psiquiatría infanto-juvenil se enfrenta desde hace algunos años a un aumento muy significativo de los casos producidos de anorexia nerviosa, un serio trastorno del comportamiento alimentario caracterizado por una notable pérdida de peso. En el fondo de esta situación subyacen complejos problemas biológicos, psicológicos y socioculturales, lo que exige un abordaje interdisciplinar para resolverlos. En el artículo se exponen cuáles son los factores predisponentes, los factores de inicio, los de mantenimiento...; qué conductas se consideran anormales; cuáles son sus manifestaciones físicas, psicológicas y la valoración médica efectuada... para concluir con la explicación de las diferentes funciones realizadas por cada uno de los miembros del equipo multidisciplinar (AU)

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review.

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV-infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.