Asymmetrical influence of a standard light/dark cycle and constant light conditions on the alanyl-aminopeptidase activity of the left and right retinas in adult male rats.

The retina acts as an independent clock informing the central pacemaker, the suprachiasmatic nucleus, under environmental light conditions, with consequences of such inputs for the central and peripheral nervous system. Differences in the behavior of the left and right retinas depending on environmental light conditions may influence the information projected to the brain hemispheres. The retina possesses neuropeptides that act as neurotransmitters or neuromodulators. Alanyl-aminopeptidase (AlaAP, EC 3.4.11.2) activity regulates some of these neuropeptides and therefore reflects their function. We analyzed AlaAP activity in the left and right retinas of adult male rats at successive time points under standard (12/12 h light/dark cycle) and nonstandard (constant light) conditions. AlaAP activity was measured fluorometrically using alanyl-beta-naphthylamide as the substrate. Under standard conditions, there were no differences in the left or right retina between time points, with the left retina predominating, particularly in the light period. In contrast, under constant light, no left versus right differences were observed, but significant differences between time points appeared. In comparison with standard conditions, constant conditions led to significantly higher AlaAP activity. Considering all the left retina data in comparison with all the right retina data, no correlation was found between the left and right retinas under standard conditions, but a significant positive correlation was observed under constant light. These results demonstrate an asymmetrical response of retinal AlaAP activity to changes in environmental light conditions, which may affect the functions in which the substrates of AlaAP are involved and the information projected to the brain hemispheres.

Triamcinolone acetonide-loaded lipid nanocapsules for ophthalmic applications.

Triamcinolone acetonide (TA) is an effective drug widely (off-label) used in the treatment of several ocular diseases involving inflammation and angiogenic processes. However, the use of TA ocular presents some limitations mainly related to its excipient composition, as in the case of benzyl alcohol. Thus, the aim of this work was to obtain an alternative TA formulation based on lipid nanocapsules (LNCs). Triamcinolone acetonide-loaded lipid nanocapsules (TA-LNCs) were obtained by the phase inversion temperature process without the use of irritating excipients, by combining lipids and surfactants generally recognized as safe. Pre-formulation studies were carried out to evaluate the TA solubility in different co-surfactants and to optimize the lipid core composition in order to enhance the drug loading and encapsulation rate in the LNCs. A stable final TA-LNC formulation was obtained with a mean particle size (MPS) of below 50 nm, a narrow size distribution (PDI < 0.2), a negative zeta potential (ZP) and a high encapsulation efficiency (%EE > 98%). In vitro cellular viability assays revealed that blank LNCs and TA-LNCs at 0.1 µg/mL did not affect the viability of the human corneal epithelial (HCE) cells. TA-LNCs showed a high anti-inflammatory activity below the toxicity level, with a reduction of 30% in interleukin (IL)-6 secretion observed in an in vitro model using the same cell line. More importantly, the TA-LNCs revealed a therapeutic efficacy in the endotoxin-induced uveitis (EIU) rabbit model with a significant attenuation of clinical signs of an inflammatory response. These findings make the TA-LNCs a safer and more efficient alternative for the treatment of eye disorders.

The reactivation time in the treatment of AMD: a forgotten key parameter?

OBJECTIVE: Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). METHOD: Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). RESULTS: Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). CONCLUSION: There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.

Influence of HLA class I, HLA class II and KIRs on vertical transmission and chronicity of hepatitis C virus in children.

BACKGROUND & AIM: There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children. METHODOLOGY: 79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex. RESULTS: MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033), whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011). In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011). Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027), KIR2DS1 (Pc = 0.011) or KIR3DS1 (Pc = 0.011) favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027) and KIR2DS3 (P = 0.056) in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011) and for the HLA-Bw4/Bw4 ligand (P = 0.027) is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027), the binding of KIR3DS1-HLA-Bw4 (P = 0.037) and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011) favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003). CONCLUSIONS: The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may influence viral clearance in infected children.

Handedness and gender influence blood pressure in young healthy men and women: A pilot study.

OBJECTIVE: The type and level of sex steroids influence blood pressure (BP). It has been suggested that functional brain asymmetries may be influenced by sex hormones. In addition, there are inter-arm differences in BP not yet related with handedness. In this study, we hypothesize a possible association between sex hormones, handedness, and inter-arm differences in blood pressure. METHODS: To analyze this hypothesis, we measured BP in the left and right arm of the left and right handed adult young men and women in menstrual and ovulatory phase and calculated their mean arterial pressure (MAP). RESULTS: Significant differences depending on sex, arm, handedness or phase of the cycle were observed. MAP was mostly higher in men than in women. Remarkably, in women, the highest levels were observed in the left handed in menstrual phase. Interestingly, the level of handedness correlated negatively with MAP measured in the left arm of right-handed women in the ovulatory phase but positively with the MAP measured in the right arm of right-handed women in the menstrual phase. CONCLUSIONS: These results may reflect an asymmetrical modulatory influence of sex hormones in BP control.

Foveal hemorrhage in an immunocompetent patient with visceral leishmaniasis.

OBJECTIVE: To report a case of foveal and macular intraretinal hemorrhages in an immunocompetent male patient with visceral leishmaniasis. CASE REPORT: An immunocompetent, 42 year-old male, presented with progressive visual loss and metamorphopsia in his right eye. The fundus examination showed a foveal round yellow lesion and intraretinal hemorrhages in the macula. The patient was hospitalized with fever, anorexia, weight loss, hepatosplenomegaly, and progressive anemia. Laboratory studies were conducted and a positive test for leishmaniasis and hepatitis A was reported. Treatment was begun with amphotericin B 50mg/day up to a total dose of 1400mg. CONCLUSION: Bilateral retinal hemorrhages in an endemic country could suggest the diagnosis of visceral leishmaniasis.

Therapeutic benefit of melatonin in refractory central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). METHODS: Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. RESULTS: At 1-month follow-up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. CONCLUSIONS: These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable.

Serum pyroglutamyl aminopeptidase activity: a promising novel biomarker candidate for liver cirrhosis.

OBJECTIVE: As a reflect of tissue damage, serum aminopeptidases have been proposed as biomarkers of various diseases. In order to search new serologic markers for liver cirrhosis we conducted a preliminary study in which we analyzed a broad range of aminopeptidase activities in serum of controls and patients diagnosed with pancreatitis, hepatitis, and liver cirrhosis without distinction among the etiological type or the degree of severity of each condition. METHODS: Alanyl-, arginyl-, glutamyl-, cystinyl- pyroglutamyl-, and aspartyl-aminopeptidase activities were analyzed fluorometrically, using aminoacyl-ß-naphthylamides as substrates. In addition, various parameters, such as alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, direct bilirubin, and gamma glutamyl transpeptidase were assayed as routine laboratory test for liver function. RESULTS: Compared with control group, alanyl- and arginyl-aminopeptidase activities increased nonspecifically in pancreatitis, hepatitis and liver cirrhosis, glutamyl- and cystinyl-aminopeptidases did not differ between groups and pyroglutamyl-aminopeptidase demonstrated that while pancreatitis and hepatitis did not differ between them and with controls, this activity decreased selectively in liver cirrhosis compared with all the rest of groups (p<0.001 vs. control and p<0.01 vs. pancreatitis and hepatitis). Aspartyl-aminopeptidase also decreased significantly (p<0.05) in liver cirrhosis compared with controls. Routine parameters for liver function test increased, as expected, in the three pathologies analyzed. CONCLUSIONS: Despite the heterogeneous composition of the three patient groups, the specific reduction of the levels of pyroglutamyl-aminopeptidase activity in serum of liver cirrhosis patients might be considered as a potential candidate to be included in a combination of markers for the diagnosis of this disease.

Trends in the dispensation of antidepressant drugs over the past decade (2000-2010) in Andalusia, Spain.

PURPOSE: To study antidepressant drug dispensation in the Spanish region of Andalusia and in the Almeria Health Area (AHA) over the past decade, analyzing the variability, trends, and influential factors. METHODS: We conducted an observational ecological study of antidepressant drug dispensation between 2000 and 2010 in Andalusia. Dispensation was measured as Defined Daily Dose (DDD) per 1,000 inhabitants per day. A multilevel analysis (STATA 11.1) was performed to determine the variability among the basic health zones (BHZs) (2004-2010) and influential factors. RESULTS: Between 2000 and 2010, the total dispensation of antidepressant drugs increased by more than 100 % in Andalusia and in the AHA. This increase was primarily caused by the greater dispensation of selective serotonin reuptake inhibitors (ATC-N06AB) and other antidepressants (ATC-N06AX). Multilevel analysis revealed a wide variability in the levels and trends of antidepressant dispensation among BHZs. Urbanicity and the percentage of immigrants in the BHZ were negatively associated with their dispensation, which was positively influenced by a higher proportion of women and over 65-year-olds in the population. CONCLUSIONS: The elevated dispensation of several groups of antidepressant drugs in this study population indicates the need for health policies to rationalize their use. Further research is required into the differences in antidepressant dispensations between immigrant and native populations and the implications for public health policies.

Variables associated with the use of coercive measures on psychiatric patients in Spanish penitentiary centers.

We have studied the use of coercive medical measures (forced medication, isolation, and mechanical restraint) in mentally ill inmates within two secure psychiatric hospitals (SPH) and three regular prisons (RP) in Spain. Variables related to adopted coercive measures were analyzed, such as type of measure, causes of indication, opinion of patient inmate, opinion of medical staff, and more frequent morbidity. A total of 209 patients (108 from SPH and 101 from RP) were studied. Isolation (41.35%) was the most frequent coercive measure, followed by mechanical restraint (33.17%) and forced medication (25.48%). The type of center has some influence; specifically in RP there is less risk of isolation and restraint than in SPH. Not having had any previous imprisonment reduces isolation and restraint risk while increases the risk of forced medication, as well as previous admissions to psychiatric inpatient units does. Finally, the fact of having lived with a partner before imprisonment reduces the risk of forced medication and communication with the family decreases the risk of isolation. Patients subjected to a coercive measure exhibited a pronounced psychopathology and most of them had been subjected to such measures on previous occasions. The mere fact of external assessment of compliance with human rights slows down the incidence of coercive measures.

Diagnostic accuracy of two questionnaires for the detection of neuropathic pain in the Spanish population.

BACKGROUND: Several questionnaires have been developed for the detection of neuropathic pain. OBJECTIVES: This study aimed to compare the diagnostic accuracy of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale and the Douleur Neuropathique en 4 questions (DN4) questionnaire for the detection of peripheral neuropathic pain in the Spanish population, and to analyse in detail the diagnostic quality of each item in these questionnaires. METHODS: A total of 192 patients were enrolled. We compared the validity of the DN4 and LANSS questionnaires by studying sensitivity and specificity and using receiver operating characteristic (ROC) curve analysis. We also analysed the validity of each item in the questionnaires. RESULTS: The sensitivity of the DN4 questionnaire with an accepted cut-off value of ≥ 4 was 95.04% and that of the LANSS questionnaire with an accepted cut-off value of ≥ 12 was 80.17%. The specificity of the DN4 instrument was 97.18% and that of the LANSS instrument was 100%. The estimated area under the ROC curve (95% confidence interval) was 0.989 (0.977-1) for the DN4 instrument and 0.973 (0.956-0.991) for the LANSS questionnaire. The area under the ROC curve was significantly larger for the DN4 than the LANSS questionnaire (p < 0.05). Analyses of specific items showed that tingling and numbness in the DN4 tool, and light touch pain and altered pinprick threshold in the LANSS scale, were the most important features of neuropathic pain. CONCLUSIONS: These results show that although both questionnaires are good screening tools, the DN4 questionnaire is particularly recommended for identifying patients with neuropathic pain in clinical practice and research studies.

Blood pressure increased dramatically in hypertensive rats after left hemisphere lesions with 6-hydroxydopamine.

Plasma angiotensinase activity, nitric oxide and systolic blood pressure (SBP) were differently affected after unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), depending on the brain hemisphere injured. Moreover, normotensive and hypertensive rats responded differently suggesting an asymmetry in the organization of the autonomic nervous system of the vessels. The aim of this study was to investigate the evolution of SBP and heart rate (HR) over time after nigrostriatal lesions in normotensive and hypertensive rat strains. Unilateral depletions of brain dopamine were performed by injecting 6-OHDA into the left or right striatum of normotensive and hypertensive rats. Vehicle without 6-OHDA was unilaterally injected in control (sham) groups. SBP and heart rate (HR) were measured in un-anesthetised animals 10 and 3 days before administration of 6-OHDA or vehicle and 3 and 25 days after treatment. In normotensive rats, at the end of study, SBP increased significantly from pre-lesioned values in left-lesioned animals but no differences were observed in right-lesioned or sham groups. Before sacrifice, there was a significant reduction from pre-lesion values in HR. In hypertensive animals, there was a highly significant increase of SBP in left-lesioned and sham left rats and a slight increase in right-lesioned but no differences were observed in sham right group. No differences in HR were observed throughout the study in the groups studied. The present results represent direct experimental evidence of an asymmetrical cardiovascular response to unilateral brain lesions, suggesting that left injury may have a worst prognosis.

Immunohistochemical localization of low density lipoprotein receptor-related protein 1 and alpha(2)-Macroglobulin in retinal and choroidal tissue of proliferative retinopathies.

The immunolocalization of the low density lipoprotein receptor-related protein 1 (LRP1) and its ligand alpha 2-Macroglobulin (alpha(2)M) was examined in tissues from human donor eyes of normal, diabetic and sickle cell disease subjects. Streptavidin alkaline phosphatase immunohistochemistry was performed with a mouse anti-human LRP1 and rabbit anti-human alpha(2)M antibodies. Retinal and choroidal blood vessels were labeled with mouse anti-human CD34 antibody in adjacent tissue sections. Mean scores for immunostaining from the pathological and control eyes were statistically compared. LRP1 immunoreactivity was very weak to negative in the neural retina of normal subjects except in scattered astrocytes. LRP1 expression in diabetic eyes was detected in the internal limiting membrane (ILM), astrocytes, inner photoreceptor matrix, choriocapillaris and choroidal stroma. The ligand alpha(2)M, however, was limited mainly to blood vessel walls, some areas of the inner nuclear layer (INL), photoreceptors, RPE-Bruch's membrane-choriocapillaris complex, intercapillary septa, and choroidal stroma. In sickle cell eyes, avascular and vascular retina as well as choroidal neovascularization (CNV) were analyzed. In avascular areas, LRP1 immunoreactivity was in innermost retina (presumably ILM, astrocytes, and Muller cells) and INL as well as RPE-Bruch's membrane-choriocapillaris complex and choroidal stroma. alpha(2)M was very weak in avascular peripheral retina compared to vascularized areas and limited to stroma in choroid. In contrast, in areas with CNV, LRP1 immunoreactivity was significantly decreased in overlying retina and in RPE-Bruch's membrane and choroidal stroma compared to the controls, while alpha(2)M was elevated in RPE-Bruch's membrane near CNV compared to normal areas in sickle cell choroid. The mean scores revealed that LRP1 and alpha(2)M in neural retina were significantly elevated in astrocytes and ILM in diabetic eyes (p < or = 0.05), whereas in sickle cell eyes scores were elevated in ILM and INL (p < or = 0.05). In addition, alpha(2)M immunoreactivity was in photoreceptors in both ischemic retinopathies. In choroid, the patterns of LRP1 and alpha(2)M expression were different and not coincident. This is the first demonstration of the presence of LRP1 and alpha(2)M in human proliferative retinopathies. Elevated LRP1 expression in sickle cell neural retina and diabetic inner retina and choroid suggests that LRP1 plays an important role in ischemic neovascular diseases.

Effects of risedronate on metabolic bone disease in patients with type 1 diabetes and osteoporosis

Evaluar el efecto de un antirresortivo sobre la masa ósea y los marcadores del remodelado óseo en pacientes con diabetes mellitus tipo 1 (DM-1) y osteoporosis(OP). El estudio incluyó 52 pacientes con DM-1 con una duración de 21 a 36 años y OP u osteopenia, con edades comprendidas entre los 26 y los 69 años. Los pacientes con OP recibieron 30 mg/semana de risedronato (n = 35) ycalcio + vitamina D; mientras que los pacientes con osteopenia y los que rechazaron el risedronato (n = 17) sólo recibieron calcio + vitamina D. A los 12meses, el grupo con risedronato demostró una mejora significativa en los niveles de fosfatasa ácida resistente al tartrato (FART) (p < 0,0001), proteína óseaGla (BGP por sus siglas en inglés) (p < 0,0001), fosfatasa alcalina ósea (FAO) (p < 0,0001) y hemoglobina A1c (HbA1c) (p < 0,0001). La densidad mineralósea (DMO) fue aumentada a 6 y 12 meses comparado con el nivel basal en la columna (CL) (p < 0,0001) y el cuello femoral (CF) (p < 0,0001). A los 12 meses, el grupo convencional demostró una mejora significativa en HbA1c (p < 0,012) y una reducción en BGP (p < 0,03) y en FAO (p<0,0001). El grupo con tratamiento convencional no demostró cambios significativos en la DMO en la CLy el CF durante el periodo de 12 meses. El tratamiento con risedronato mejora la DMO en pacientes con DM-1 crónica

To assess the effect of a antiresorptive on bone mass and remodeling markers in patients with type 1 diabetes mellitus (DM-1) and osteoporosis (OP). Studyincluded 52 patients with DM-1 of 21-36 years duration and OP or osteopenia, aged 29-69 years. OP patients received 30 mg/week risedronate (n = 35)and calcium + vitamin D; osteopenic patients and risedronate refusers (n = 17) received only calcium + vitamin D. At 12 months, the risedronate group showedsignificant improvements in tartrate resistant acid phosphatase (p < 0.0001), osteocalcin (BGP) (p < 0.0001), bone alkaline phosphatase (BAP) (p < 0.0001),and hemoglobin A1c (HbA1c) (p < 0.0001); bone mineral density (BMD) was increased at 6 and 12 months versus baseline in lumbar spine (LS) (p < 0.0001) and femoral neck (FN) (p < 0.0001). At 12 months, the conventional group showed a significant improvement in HbA1c (p < 0.012) and reduction in BGP (p < 0.03) and BAP (p < 0.0001). The conventional treatment group showedno significant changes in BMD at LS and FN during the 12-month period. Risedronate treatment improves BMD in long-term DM-1 patients (AU)

Radiation-induced DNA damage as a predictor of long-term toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy.

This 14-year-long study makes a novel contribution to the debate on the relationship between the in vitro radiosensitivity of peripheral blood lymphocytes and normal tissue reactions after radiation therapy. The aims were (1) to prospectively assess the degree and time of onset of skin side effects in 40 prospectively recruited consecutive patients with locally advanced breast cancer treated with a hyperfractionated dose-escalation radiotherapy schedule and (2) to assess whether initial radiation-induced DNA damage in peripheral blood lymphocytes of these patients could be used to determine their likelihood of suffering severe late damage to normal tissue. Initial radiation-induced DNA double-strand breaks (DSBs) were assessed in peripheral blood lymphocytes of these patients by pulsed-field electrophoresis. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity score. A wide interindividual variation was observed in toxicity grades and in radiation-induced DNA DSBs in peripheral blood lymphocytes (mean 1.61 +/- 0.76 DSBs/Gy per 200 MBp, range 0.63- 4.08), which were not correlated. Multivariate analysis showed a correlation (P < 0.008) between late toxicity and higher prescribed protocol dose (81.6 Gy). Analysis of the 29 patients referred to 81.6 Gy revealed significantly (P < 0.031) more frequent late subcutaneous toxicity in those with intrinsic sensitivity to radiation-induced DNA DSBs of >1.69 DSBs/Gy per DNA unit. Our demonstration of a relationship between the sensitivity of in vitro-irradiated peripheral blood lymphocytes and the risk of developing late toxic effects opens up the possibility of predicting normal tissue response to radiation in individual patients, at least in high-dose non-conventional radiation therapy regimens.

Pattern of care for schizophrenia patients in Granada (Spain): a case register study.

AIMS: This study sets out to explore the use flow of mental health services by a cohort of patients with schizophrenia located in Granada (Spain). METHODS: All cases (N = 844) included in the analysis were users of the community mental healthcare public service provided in the area. The Markov chain model was used to calculate the probability of transition from one type of contact with mental health services resources to another type of contact in the next month, over a three-year follow-up. RESULTS: For a given one-month period, for each level of service contact, most patients continued to use the same level of care. CONCLUSIONS: Our results can be interpreted as a reflection of adequate continuity of mental health care provided by the Andalusian community service.

The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort.

We report results from the PREDICT-Gene case-control study nested in a prospective cohort designed to identify predictors of the onset of depression among adult primary-care attendees. We tested the potential gene-by-environment interaction between 5HTTLPR genotype at the serotonin transporter gene and previous exposure to threatening life events (TLEs) in depression. A total of 737 consecutively recruited participants were genotyped. Additional information was gathered on exposure to TLEs over a 6-month period, socio-demographic data and family history of psychological problems among first-degree relatives. Diagnoses of depression were ascertained using the Composite International Diagnostic Interview (CIDI) by trained interviewers. Two different depressive outcomes were used (ICD-10 depressive episode and ICD-10 severe depressive episode). Both the s/s genotype and exposure to increasing number of TLEs were significantly associated with depression. Moreover, the 5HTTLPR s/s genotype significantly modified the risk conferred by TLEs for both depressive outcomes. Thus, s/s homozygous participants required minimal exposure to TLE (1 TLE) to acquire a level of risk for depression that was only found among l/s or l/l individuals after significantly higher exposure to TLEs (two or more TLEs). The interaction was more apparent when applied to the diagnosis of ICD-10 severe depressive episode and after adjusting for gender, age and family history of psychological problems. Likelihood ratios tests for the interaction were statistically significant for both depressive outcomes (ICD-10 depressive episode: LR X(2)=4.7, P=0.09 (crude), LR-X(2)=6.4, P=0.04 (adjusted); ICD-10 severe depressive episode: LR X(2)=6.9, P=0.032 (crude), LR-X(2)=8.1, P=0.017 (adjusted)).

Plasma aminopeptidase activities in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by a progressive motor disorder, but frequently is accompanied by autonomic symptoms such as hypotension. Together with the decrease of dopamine, significant decreases in aminopeptidase activities have been reported in PD brains. However, up to date there are no studies about changes of aminopeptidase activities in plasma of PD patients. We studied plasma activities of alanyl-, aspartyl-(AspAP), cystinyl-(CysAP) and glutamyl-aminopeptidase (GluAP) in two groups of subjects: control (n=41) and PD (n=48). Plasma activities of AspAP, CysAP, and GluAP showed significant decreases of 24.9% (p<0.05), 39.4% (p<0.01) and 33.3% (p<0.01), respectively, in PD group. These aminopeptidases are involved in the metabolism of circulating peptides such as the ones of the renin-angiotensin system. The importance of aminopeptidases in striatal dopamine content and in neuroendocrine system in PD is discussed.

Activity of tigecycline against clinical isolates of Staphylococcus aureus and extended-spectrum beta-lactamase-producing Escherichia coli in Granada, Spain.

We evaluated the in vitro activity of tigecycline using the Etest and disk diffusion method according to Clinical and Laboratory Standards Institute guidelines against clinical isolates of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) as well as for CTX-M-9 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and SHV ESBL-producing E. coli. All isolates were susceptible to tigecycline according to US Food and Drug Administration cut-off points. There were no differences in the activity of tigecycline between MSSA and MRSA isolates or between the presence of either type of ESBL. For each type of microorganism studied, we established the equation relating the minimum inhibitory concentration to the diameter of the zone of inhibition.

Levels of HSP70 in HIV(+) patients in different viroimmunological states.

The aim of the study was to establish an association between the viroimmunological status of HIV positive patients and their levels of the 70-kD heat shock protein (Hsp70). The longitudinal retrospective case study involved 61 patients at the University Hospital in Granada (Spain) from 1999 to 2002. Twenty-five patients were viroimmunologically stable, while the other 36 patients had suffered virological failure. A minimum of three blood samples were taken at intervals of at least 3 months for the patients who were stable virologically and immunologically, whereas four samples were taken for the virological failure group: two previous to the onset of virological failure, a third corresponding to the time of virological failure, and a fourth at least 3 months after remission of virological failure. Blood samples were also obtained from 20 healthy control subjects; Hsp70 levels in all were determined by enzyme immunoassay. The mean concentration of Hsp70 was 145.4 ng/ml in the HIV-infected patients as opposed to 72.1 ng/ml in the controls. While the viroimmunologically stable group showed levels similar to those of the controls (66.5 ng/ml), the mean value of Hsp70 in the virological failure group was nearly four times as high (249.1 ng/ml), yet this difference was not statistically significant. The patients treated with reverse transcriptase inhibitors were found to have significantly higher levels of Hsp70 than the other subjects. The transformed variable Hsp70/CD4(+) presents less variability than the Hsp70 value itself, giving a higher degree of statistical significance, and may be considered a useful parameter for diagnostic, prognostic, and therapeutic management of HIV positive patients.