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Biomedical subjects

I Jiménez

Publications and source records attributed to I Jiménez.

At least 19 recordsLinked to original sources

Identification of a plum pox virus CI-interacting protein from chloroplast that has a negative effect in virus infection.

The cylindrical inclusion (CI) protein of potyviruses is involved in virus replication and cell-to-cell movement. These two processes should rely on multiple plant-virus interactions; however, little is known about the host factors that are involved in, or that may interfere with, CI functions. By using a yeast two-hybrid system, the CI protein from Plum pox virus (PPV) was found to interact with the photosystem I PSI-K protein, the product of the gene psaK, of Nicotiana benthamiana. Coexpression of PPV CI was shown to cause a decrease in the accumulation level of PSI-K transiently expressed in N. benthamiana leaves. To test the biological relevance of this interaction, we have analyzed the infection of PPV in N. benthamiana plants in which psaK gene expression has been silenced by RNA interference, as well as in Arabidopsis thaliana psaK knockout plants. Our results show that downregulation of the psaK gene leads to higher PPV accumulation, suggesting a role for the CI-PSI-K interaction in PPV infection.

Chloroplasts↗

Effects of spinal and peripheral nerve lesions on the intersegmental synchronization of the spontaneous activity of dorsal horn neurons in the cat lumbosacral spinal cord.

In the anesthetized and paralyzed cat, spontaneous negative cord dorsum potentials (nCDPs) appeared synchronously in the L3 to S1 segments, both ipsi- and contralaterally. The acute section of both the intact sural and the superficial peroneal nerve increased the variability of the spontaneous nCDPs without affecting their intersegmental coupling. On the other hand, the synchronization between the spontaneous nCDPs recorded in segments L5-L6 was strongly reduced following an interposed lesion of the left (ipsilateral) dorsolateral spinal quadrant and it was almost completely abolished by an additional lesion of the contralateral dorsolateral quadrant at the same level. Our observations support the existence of a system of spontaneously active dorsal horn neurons that is bilaterally distributed along the lumbosacral segments and affects, in a synchronized and organized manner, impulse transmission along many reflex pathways, including those mediating presynaptic inhibition.

Action Potentials↗

Mutant prevention concentration: comparison of fluoroquinolones and linezolid with Mycobacterium tuberculosis.

OBJECTIVES: The mutant prevention concentration (MPC) has recently been defined to characterize the capacity for severely restricting the selection of resistant mutants during antibiotic treatment. We determined this parameter for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid in Mycobacterium tuberculosis clinical isolates in our setting. METHODS: We determined the antibiotic concentration that prevents the selection of resistant mutants following inoculation with a high mycobacteria inoculum on Middlebrook 7H11 plates with serial dilutions of the antibiotics in 224 M. tuberculosis isolates. RESULTS: Fifty percent of the strains exhibited values of MPC (MPC(50)) lower than 0.8, 0.6, 0.4, 0.4 and 0.6 mg/L for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid, respectively. If 90% of the strains are considered (MPC(90)), the values are seen to rise to 2, 1.8, 1, 1.2 and 1.2 mg/L, respectively. CONCLUSIONS: When we compare this parameter with the drug levels in serum and tissue, it can be seen that ciprofloxacin is the least useful of the fluoroquinolones studied, whereas moxifloxacin appears to be the most active. Linezolid exhibits excellent activity against this microorganism (MPC(90) 1.2 mg/L and AUC 140.3 mg.h/L) and this makes us consider that its usefulness in the treatment of this pathology should be thoroughly evaluated.

Acetamides↗

Conduction failure of action potentials in sensory sural nerves of undernourished rats.

In order to determine possible functional and morphometrical alterations produced by perinatal undernourishment on peripheral nerves, sensory sural nerves from control and undernourished rats of 30 and 90 postnatal days of age were dissected and divided in two segments, one for recording the compound action potential (CAP) and the other for histological examination. Nerves from undernourished animals showed maximal CAP responses of smaller amplitude and area, larger trial-to-trial variability in area, and a significant reduction in axonal myelin sheath thickness than nerves from control animals. It is suggested that perinatal undernourishment produces changes in axonal myelin sheath structure, resulting in severe alterations in the generation and propagation of action potentials (block and/or intermittent conduction) in sensory afferent fibers in the rat.

Action Potentials↗

[Evaluation of a pharmaceutical care program to improve adherence to antiretroviral therapy].

OBJECTIVE: To establish the impact of a pharmaceutical care program on the improvement of adherence to antiretroviral therapy, and on patient immunologic and virologic outcome. MATERIALS AND METHODS: A multicenter, observational, prospective study in a HIV-infected patient cohort under treatment with antiretrovirals selected by random sampling in 19 Spanish hospitals. The study lasted 12 months, in which the program was applied through a baseline preprocedural visit and 4 quarterly visits. Adherence estimation was based on pill counting. An adherence > or = 90, or > or = 95% was considered adequate (in two time points). RESULTS: 541 patients were included, most of them were males (68.8%) between 20 and 78 years of age. Major risk groups included injecting drug users (43.4%) and heterosexuals (29.4%). Sixty percent had already received treatment for more than 3 years. Mean baseline viral load and CD4 count values were 32,866 copies/ml and 485 cells/mm3, respectively. Throughout the study a slight increase in the percentage of adherent patients was seen; however, statistical significance was not reached (64.3 and 79.2% of patients showed an adherence > 95 and > 90%, respectively, during the fourth quarter, versus 59.8 and 75.5% at baseline). A statistically significant decrease in viral load and increase in CD4 cells was seen following program application. The percentage of patients with a viral load < 200 copies/ml was 72.2, 76.7, and 75.0% at the 2nd, 3rd, and 4th quarters, respectively, versus 64.2% at baseline. CD4 cell counts increased by 50 cells/mm3 on average from the start to the end of follow-up. CONCLUSIONS: Patients included in the program had a good immunologic and virologic outcome, and a trend towards an increased percentage of patients with good adherence was also seen. These results confirm the need to implement follow-up programs for patients receiving antiretrovirals in order to ensure maximum therapeutic benefits.

Adult↗

[Comparison between two 13C-urea breath tests for the diagnosis of Helicobacter pylori infection: isotope ratio mass spectrometer versus infrared spectrometer].

OBJECTIVES: To compare the accuracy of the breath test using the isotope ratio mass spectrometer (IRMS) versus the nondispersive isotope-selective infrared spectrometer (NDIRS) in the diagnosis of Helicobacter pylori infection. METHOD: Multicenter study in 4 Spanish hospitals. One group of dyspeptic patients who had not undergone prior eradication therapy and another group of patients with gastric ulcer or gastrointestinal bleeding due to gastroduodenal ulcer receiving H. pylori eradication therapy were included in the study. A reference standard based on histology and the rapid urease test was used. The breast test (TAU-KIT, Isomed S.L., Madrid, Spain) was performed with citric acid and 100 mg of 13C-urea. Samples of expired air were collected in tubes and bags for reading with the IRMS (ABCA, PDZ, Crewe, Manchester, England) and the NDIRS (UBiT-IR200, Otsuka Electronics, Co, Osaka, Japan), respectively. The endoscopist, pathologist and person responsible for reading the urease test and both breath tests were blinded to the results of the other diagnostic methods. RESULTS: Forty-one patients were included. The prevalence of H. pylori was 26%. No differences were found on comparing the mean values obtained with the IRMS and the NDIRS: 13 (standard deviation) (24) and 14 (25) delta units, respectively. The area under the ROC curve for the IRMS and the NDIRS was 0.96. The diagnostic accuracy for the best cut-off point with the IRMS and the NDIRS was, respectively: sensitivity (90 and 100%), specificity (96 and 89%), positive predictive value (90 and 77%), negative predictive value (96 and 100%), + likelihaod ratio (25 and 9.3) and (0.1 and 0). A close correlation was found between the values of the IRMS and those of the NDIRS (lineal regression equation, Y = 1.1 + 1.004. X; r = 0.97). CONCLUSION: Both the spectrometers used to evaluate the breath test, the IRMS and the NDIRS, offer a high degree of accuracy in the diagnosis of H. pylori infection.

Breath Tests↗

Validation of the 13c-urea breath test for the initial diagnosis of helicobacter pylori infection and to confirm eradication after treatment.

OBJECTIVES: the breath test with 13C-urea (UBT) is a method widely used in Spain, but its diagnostic accuracy has not been evaluated in a clinical trial until now. Our objective was to validate the UBT (TAU-KIT) both as an initial diagnostic method for the detection of H. pylori infection and as a method to confirm eradication. METHODS: a multi-centre study in 7 Spanish hospitals was performed. A group of dyspeptic patients who had not previously received eradication treatment was included, and a second group of patients with gastric ulcer or upper gastrointestinal bleeding due to peptic ulcer was also included (eradication of H. pylori was confirmed 6 to 8 weeks after treatment completion with omeprazole, clarithromycin and amoxycillin). In both groups an endoscopy was performed with biopsies for histology and rapid urease test. Patients were considered infected if both tests yielded positive results, and not infected when both tests were negative. The UBT 13C-urea (TAU-KIT, Isomed S.L., Madrid, Spain) was performed with citric acid and 100 mg of 13C-urea. The pathologist and persons responsible for endoscopy, urease test and UBT were all unaware of the results from the other diagnostic methods. RESULTS: in the pre-treatment group (36 patients) the prevalence of H. pylori was 72%, the area under the ROC curve for the diagnosis of infection with the UBT was 0.99, and the best cut-off point was 5 units, with the following results: sensitivity= 96% (95% CI = 81-99%), specificity= 100% (69-100%), positive predictive value (PPV) = 100% (87-100%), negative predictive value (NPV) = 92% (59-100%), likelihood ratio (LR) + = infinity, and LR- = 0.04. In the post-treatment group (85 patients) the prevalence of H. pylori was 16%, the area under the ROC curve was 0.99, and the best cut point was 4.6, with the following results: sensitivity= 100% (77-100%), specificity = 97% (90-99%), PPV = 88% (62-98%), NPV = 100% (95-100%), LR+ = 35, and LR- = 0. CONCLUSION: UBT provides excellent accuracy both for the initial diagnosis of H. pylori infection and to confirm eradication after treatment.

Adult↗

Intersegmental synchronization of spontaneous activity of dorsal horn neurons in the cat spinal cord.

Extracellular recordings of neuronal activity made in the lumbosacral spinal segments of the anesthetized cat have disclosed the existence of a set of neurons in Rexed's laminae III-VI that discharged in a highly synchronized manner during the occurrence of spontaneous negative cord dorsum potentials (nCDPs) and responded to stimulation of low-threshold cutaneous fibers (<1.5x T) with mono- and polysynaptic latencies. The cross-correlation between the spontaneous discharges of pairs of synchronic neurons was highest when they were close to each other, and decreased with increasing longitudinal separation. Simultaneous recordings of nCDPs from several segments in preparations with the peripheral nerves intact have disclosed the existence of synchronized spontaneous nCDPs in segments S1-L4. These potentials lasted between 25 and 70 ms and were usually larger in segments L7-L5, where they attained amplitudes between 50 and 150 micro V. The transection of the intact ipsilateral hindlimb cutaneous and muscle nerves, or the section of the dorsal columns between the L5 and L6, or between the L6 and L7 segments in preparations with already transected nerves, had very small effects on the intersegmental synchronization of the spontaneous nCDPs and on the power spectra of the cord dorsum potentials recorded in the lumbosacral enlargement. In contrast, sectioning the ipsilateral dorsal horn and the dorsolateral funiculus at these segmental levels strongly decoupled the spontaneous nCDPs generated rostrally from those generated caudally to the lesion and reduced the magnitude of the power spectra throughout the whole frequency range. These results indicate that the lumbosacral intersegmental synchronization between the spontaneous nCDPs does not require sensory inputs and is most likely mediated by intra- and intersegmental connections. It is suggested that the occurrence of spontaneous synchronized nCDPs is due to the activation of tightly coupled arrays of neurons, each comprising one or several spinal segments. This system of neurons could be involved in the modulation of the information transmitted by cutaneous and muscle afferents to functionally related, but rostrocaudally distributed spinal interneurons and motoneurons, as well as in the selection of sensory inputs during the execution of voluntary movements or during locomotion.

Action Potentials↗

Chronic exposure of HepG2 cells to excess copper results in depletion of glutathione and induction of metallothionein.

Metallothionein (MT) and reduced glutathione (GSH) play an important role in the intracellular handling of copper by preventing the generation and favouring the removal of copper-derived free radicals. The present study addressed the changes in MT and GSH that follow chronic (2 or 5 weeks) exposure of human hepatoblastoma cells (HepG2) to excess copper. Copper treatment (100 microM, 2 weeks) led to a 28-fold elevation in intracellular copper. Concomitantly, cells exhibited a seven-fold increase in total MT and an increment in its saturation with copper from 45 to 86%. Around 38% of copper in the cytosolic fraction could be accounted for by MT. GSH equivalents were substantially lowered (to 37% of basal levels) in treated cells, with only part of it being accounted for by an increase in GSSG. Copper-treatment induced no changes in catalase or GSH-peroxidase activities but it was associated with a small reduction in SOD (20%) and GSH-reductase (26%) activities. Copper-loaded cells did not differ from controls in their basal oxidative tone; however, when exposed to tert-butylhydroperoxide they exhibited a markedly greater susceptibility to undergo both oxidative stress and cell lysis. It is proposed that chronic exposure of HepG2 cells to excess copper is accompanied by "adaptive changes" in GSH and MT metabolism that would render cells substantially more susceptibility to undergo oxidative stress-related cytotoxicity.

Adaptation, Physiological↗

Multiple sclerosis in the tropics: genetic association to STR's loci spanning the HLA and TNF.

Clear evidence has been presented correlating gene polymorphisms at 6p21.3-21.4 (containing HLA and TNF) and the predisposition to acquire multiple sclerosis (MS). In a previous study, we found that polymorphisms at HLA DQAI were associated with being or not being predisposed to MS in individuals inhabiting the tropics, where the prevalence of MS is significantly lower than in subtropical areas. Here, we tested the hypothesis that polymorphisms at D6S276, D6S265, D6S273 and D6S291 microsatellite loci are in strong linkage disequilibrium with a major genetic factor predisposing to MS. These microsatellites span the 6p21.3 region with intervals of 5 cM establishing particular landmarks for the HLA and TNF loci. Thirty-five MS patients and 35 controls, age, sex, social, ethnically and geographically matched healthy individuals, were studied. After testing the fit of gene frequencies to the normal distribution and performing the correlation for multiple comparisons, we found significant differences among the case and the control frequencies for the allele 202 belonging to the marker D6S276 (Pc=0.00455) and for the allele 114 belonging to the marker D6S265 (Pc=0.0084). For these two alleles at different loci, we found higher frequencies in the cases than in the controls. A nonsignificant p value was found in testing the existence of linkage disequilibrium among the studied loci in the cases and in the controls. In conclusion, the current study adds evidence to the established association among polymorphisms of genes located at 6p21.3-21.4 and MS. Furthermore, because of the distribution of the tested microsatellite loci, the more probable critical region could be correlated with the TNF neighborhood.

Adult↗

Effect of perinatal food deficiencies on the compound action potential evoked in sensory nerves of developing rats.

The aim of this study was to analyze the possible alterations produced by inadequate perinatal food intake, in quantity (undernutrition) or quality (malnutrition), on the generation and propagation of the compound action potential (CAP) evoked in sensory sural nerves, during the postnatal development of the rat. Low intensity stimulation (2-3 times the threshold of the most excitable nerve fibers; xT) of the sural nerve evoked an early potential (CAP-A component) which is due to activation of low-threshold, fast-conducting myelinated group A afferent fibers. Meanwhile, at higher stimulus intensity (20-30T) it produced a second, long-lasting potential (CAP-C component) probably due to activation of high-threshold, slow-conducting group Adelta or C afferent fibers. Compared to control nerves, the CAP-A component, but not the CAP-C component of undernourished and malnourished nerves showed significant changes in amplitude, area, electrical threshold and conduction velocity (except absolute refractory period) at several postnatal ages. Our results may suggest that a relative large number of myelinated group A afferent fibers in the sural nerve of undernourished and malnourished animals suffer severe alterations on their electrophysiological properties of generation and propagation of the action potential during the postnatal development of the rat.

Action Potentials↗

Clinical features of multiple sclerosis in a genetically homogeneous tropical population.

Individuals affected with multiple sclerosis (MS) from a genetically homogeneous Caucasian population in Antioquia, a tropical region of Colombia, were evaluated in order to observe the clinical behavior of the disease. The frequency of clinical manifestations in 65 patients with definite MS from Antioquia was compared with those reported from temperate regions. The most common manifestations were optic neuritis and motor symptoms with absence of cerebellar symptoms. This presentation is significantly different from the frequency distribution at onset in series from temperate regions. These differences suggest that environmental factors could modify the clinical expression of MS in this population.

Asia↗

Free-radical-induced inactivation of lysozyme and carbonyl residue generation in protein are not necessarily associated.

The 2,2'-azobis(2-amidinopropane) (AAPH)-induced inactivation and oxidative modification of lysozyme, as determined by the loss of tryptophan-associated fluorescence (TAF) and the increase in dinitrophenylhydrazine-reactive carbonyl groups (CO), were studied in the absence and in the presence of antioxidants. AAPH induced a progressive inactivation of the enzyme and a parallel decrease of its TAF. Both changes were closely correlated (R2 = 0.97); however, the inactivation was only partially associated with an increase in CO. The latter reached maximal values at times half those needed to attain maximal losses in both lysozyme activity and TAF. A stoichiometric comparison reveals that whereas over 74% of the enzyme molecules had lost their activity, only 5% exhibited an increment in CO. CO formation was affected differentially by boldine and trolox. Both antioxidants fully protected against the early inactivation and loss of TAF; however, the increase in CO was completely unaffected by trolox. Exposure of lysozyme to Fe3+/ascorbate induced no loss of activity or TAF, but it led to an accumulation of CO similar to that induced by AAPH. Results indicate that CO formation and lysozyme inactivation are two mechanistically dissociable events and that changes in the former parameter can perfectly occur in the absence of changes in the latter.

Amidines↗

Biological disposition of boldine: in vitro and in vivo studies.

Boldine is a natural compound with well-established free radical scavenger and hepatoprotective properties. The further exploration of its actual therapeutic potential as an antioxidant is, however, partially limited by the absence of knowledge on its pharmacokinetics. In the present studies, we provide information on the in vitro and in vivo biological disposition of boldine. The addition of 200 microM boldine to an isolated rat hepatocyte suspension was followed by a time-dependent (0-60 min) disappearance of boldine from the extracellular medium. This decline was associated with an early (first 2 min) and swift accumulation (1600 microM) of boldine within the cells. Although the intracellular concentration of boldine diminished, boldine was always found to occur within the cells at concentrations substantially higher than those initially added to the preparation. Boldine was also concentration-dependently removed from the extracellular medium by isolated rat livers portally perfused with the antioxidant. In vivo studies, conducted in rats, revealed that following either its oral or its intravenous administration, plasma boldine concentrations declined rapidly and according to an apparently first order type of kinetics. After its oral administration (50 or 75 mg/kg), boldine was rapidly (within 30 min) absorbed and preferentially concentrated in the liver, with substantially lower concentrations being found in the brain and heart. Maximal hepatic concentrations of boldine were found to be equal to or greater than those needed to afford antioxidant and hepatoprotective effects in vitro.

Animals↗

Protective effects of boldine against free radical-induced erythrocyte lysis.

Boldine, an aporphine alkaloid extracted from the leaves and bark of boldo (Peumus boldus Mol.), has been shown to exhibit strong free-radical scavenger and antioxidant properties. Here, we report the in vitro ability of boldine to protect intact red cells against the haemolytic damage induced by the free radical initiator 2, 2'-azobis-(2-amidinopropane) (AAPH). Boldine concentration-dependently prevented the AAPH-induced leakage of haemoglobin into the extracellular medium. Substantial and similar cyto-protective effects of boldine were observed whether the antioxidant was added 1 h prior to, or simultaneously with, the azo-compound. The delayed addition of boldine, by 1 h relative to AAPH, diminished but did not abolish its cytoprotective effect. However, negligible effects of boldine were observed after its addition to erythrocytes previously incubated with AAPH for 2 h. The data presented demonstrate that, in addition to its well-established antioxidant effects, boldine also displays time-dependently strong cytoprotective properties against chemically induced haemolytic damage.

Animals↗

Effects of copper ions on the free radical-scavenging properties of reduced gluthathione: implications of a complex formation.

The interaction between glutathione (GSH) and copper ions was investigated in vitro to determine whether such interaction could affect the free-radical scavenging properties of the tripeptide. To this end, the bleaching (decrease in OD734 nm) of a coloured solution containing the stable free-radical cation ABTS+, (which results from the addition of thiols to such a solution) was employed as an in vitro indication of the ability of the tripeptide to scavenge free radicals. While GSH bleached concentration-dependently (1.0-7.5 gM) the ABTS+-containing solution, its prior incubation (5 microM) in the presence of Cu+1 or Cu+2 ions (1-7.5 M) led to a metal concentration-dependent decrease of the bleaching capacity. At a ratio equal to one (5 microM each), the bleaching capacity of the copper plus GSH mixture was 50% of that seen for GSH alone. Further additions of copper (reaching ratios up to 2) did not result in greater decreases in the GSH-bleaching capacity. Noteworthy at the ratio of onewas that the copper plus GSH solutions maintained their bleaching capacity despite the lack of any DTNB-reactivity, i. e., the complete absence of thiols in the mixture. Mixtures of increasing concentrations of a fixed ratio (equal to 2) of copper plus GSH, which were found not to exhibit any DTNB-reactivity, showed a linear and concentration-dependent increase in bleaching capacity. The bleaching capacity remained unaltered when TRIEN, EDTA or histidine were added to pre-incubated (1:1) mixtures of copper plus GSH. However, the incubation of copper with TRIEN or EDTA (but not histidine) prior to GSH addition, totally prevented the loss of the original GSH-bleaching capacity. The present data supports the formation of a copper-glutathione complex which is stable to the presence of some copper-chelators, lacks all thiol reactivity, but fully conserves the free-radical scavenging properties of GSH.

Benzothiazoles↗

13C-urea breath test for the diagnosis of Helicobacter pylori infection: are basal samples necessary?

AIM: The 13C-urea breath test (13C-UBT) is one of the best methods for the diagnosis of Helicobacter pylori infection. Basal breath samples are usually obtained, in addition to those obtained after urea intake, as it has been suggested that basal values may oscillate among a population (e.g. depending on diet). However, the superiority of this strategy has not been sufficiently demonstrated. The elimination of basal samples in the 13C-UBT protocol would have the advantages of higher simplicity and speed. METHODS: The 13C-UBT was performed in 714 consecutive patients. Mean age was 48 +/- 16 years, 49% were males, and in 48% of the patients previous H. pylori eradication therapy had been administered. Basal samples (13C-basal) and at 30 min after taking 100 mg of urea labelled with 13C (13C-post-urea) were obtained, delta over baseline (13C-DOB) being the algebraic difference between the ratio 13C/12C at these two points (which is the parameter usually given in studies, being considered positive when > 5%). A citric acid solution was used prior to urea intake. RESULTS: The prevalence of H. pylori infection was 48%. Mean values of 13C-basal, 13C-post-urea, and 13C-DOB were, respectively, -19 +/- 2, 5.9 +/- 33, and 25 +/- 33. 13C-basal values oscillated between -25 and -14, being between -21 and -16 in 90% of the cases. Linear correlation coefficient for 13C-post-urea and 13C-DOB was 0.999 (determination coefficient, 0.998; P< 0.0001). The area under the receiver operating characteristic (ROC) curve for the diagnosis of infection when only 13C-post-urea was used (taking 13C-DOB >5% as the 'gold standard') was 0.997. Best results were obtained with 13C-post-urea cut-off point set at -13, with sensitivity of 97.4% (95% CI, 95-99%), specificity of 99.5% (98-100%), and positive likelihood ratio of 180. The concordance kappa value for both tests (13C-post-urea and 13C-DOB) using the aforementioned cut-off point was 0.97. CONCLUSION: When performing the 13C-urea breath test it is sufficient to obtain samples 30 min after urea intake. Basal breath samples would not be necessary, which further simplifies this diagnostic method.

Adult↗

[The recommendations of GESIDA/SEFH/PNS for improving adherence to antiretroviral treatment. AIDS Study Group of the Spanish Society of Hospital Pharmacy and the National Plan on AIDS of the Minister of Health and Consumers].

The main objective of HAART is to achieve a complete suppression of the viral replication for long time. However, when the therapeutic drug levels are low, HIV can replicate and it can develop resistances. This fact can be the reason of treatment failure, HIV transmission of resistant strains and therefore an inappropriate use of the economical resources. In order to get the adequate therapeutic drug levels it is necessary to have a good adherence to the treatment. We review the factors that influence the adherence, the evaluation methods and we recommend the possible intervention strategies which should be given by a multidisciplinary team, integrated by physicians, pharmacists, nurses, psychologists and other personal support. To start HAART is not an emergency. For this reason is very important to prepare to the patient and to identify the non-adherence factors in order to correct it. Once the HAART is indicated it is very important to offer information during the medical prescription and when the drugs are dispensed. During the therapy is necessary to follow actively all patients on HAART. In order to make therapeutical decisions we need to know the patient drug adherence rate. We recommend to use several methods to calculate the drug adherence rate, being the most commonly used the patient interview, the patient questionnaire, the refill count, the pharmacy visits rate together with the viral load evolution of the patient. In order to get all this information it is necessary to have a very good communication between all the people involved in HIV infected patients care. If non-adherence is detected it is necessary to start the intervention strategies to correct it and if they fail it might be necessary in some cases to stop HAART. The potential benefits of the adherence programs can justify the economical spend in human and hospital facilities resources.

Anti-HIV Agents↗