Pharmacogenetic studies in Alzheimer disease.

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as ageing.

Pharmacogenetic studies in Alzheimer disease. / Estudios farmacogenéticos en la enfermedad de Alzheimer.

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as aging.

CSF analysis for protein biomarker identification in patients with leptomeningeal metastases from CNS lymphoma.

INTRODUCTION: Leptomeningeal metastases (LM) from lymphoma remain a difficult complication for oncologist due to the high incidence in morbidity and mortality. Early diagnostic and initiation of treatment are essential to prevent neurological deterioration. Areas covered: In this review, several proteomic approaches are described in order to help and provide the basis for the identification of biomarkers useful in early diagnosis, also in discovery novel targets for therapeutic agents. In fact, the identification of biomarkers will have a high potential to detect leptomeningeal lymphoma, as well as to predict its progression and treatment response. Expert commentary: In the case of LM by Central nervous system (CNS) lymphoma, these studies generated the first insights into the utility of proteomic analysis for biomarker identification and will be demonstrated that identifying specific proteins in cerebrospinal fluid (CSF) had much greater sensitivity for detecting LM in comparison to standard cytological protocols.

In vitro and in vivo Methods for the Evaluation of Natural Products against Dermatophytes.

Dermatomycoses are infections caused by fungi called dermatophytes; these affect 20-25% of the world population and the incidence continues to grow each year. Recently, an alternative for the treatment of these diseases is the use of natural products, thanks to the fact that they possess great chemical diversity and thus biological activity. However, to understand the therapeutic potential of natural products, their microbiological assessment presents certain limitations. Currently, there is no established reference method to determine the antifungal capacity in vitro and in vivo of natural products (i.e., essential oils). This review focuses on describing the various microbiological methods as well as the many adaptations used to evaluate the antifungal activity of natural products both in vitro and in vivo. In addition, the antifungal evaluation of natural products formulated in creams, gels, nanoemulsions, nanocapsules and solid lipid nanoparticles is included.

[THE INFLUENCE OF THE POLYUNSATURATED FATTY ACIDS IN THE PREVENTION AND PROMOTION OF CANCER]. / INFLUENCIA DE LOS ÁCIDOS GRASOS POLIINSATURADOS EN LA PREVENCIÓN Y PROMOCIÓN DEL CÁNCER.

INTRODUCTION: each year, almost eight million people die in the world due to cancer. Carcinogenesis is a process that involves a series of structural alterations of the DNA which affect its stability and prevents proper cell reproduction and development. There are many factors that influence the cancer etiology. Nutritional factors are included among them. The polyunsaturated fatty acids (PUFA) intake is associated more and more with the prevention and development of chronic diseases with an inflammatory component such as cancer. OBJECTIVE: this work reviews the latest bibliography on the PUFA and its relationship with the cancer, mainly of prostate, breast and colon cancer. METHODS: the preliminary search resulted in 92 selected references. But, after their review, 40 experimental studies, in animals and in vitro, and epidemiological studies have been included. RESULTS: experimental studies in animals and in vitro reviewed show a protective effect of ω3 PUFA against cancer. However, human studies are contradictory; although it is clear there is evidence of the protective effect of the ω3 PUFA in colon cancer prevention. CONCLUSION: the relationship between ω6 and ω3 PUFA of the diet against the cancer risk is becoming increasingly important, but further studies are needed to confirm their influence on the development of this disease.

Introducción: alrededor de ocho millones de personas mueren anualmente en el mundo debido al cáncer. La carcinogénesis es un proceso que conlleva, entre otras, una serie de alteraciones de la estructura del ADN, afectando su estabilidad e impidiendo la correcta proliferación celular. Son muchos los factores que influyen en la etiología del cáncer. Dentro de dichos factores están los nutricionales. La ingesta de ácidos grasos poliinsaturados (AGPI) se relaciona cada vez más con la prevención y el desarrollo de enfermedades crónicas con un componente inflamatorio, como el cáncer. Objetivo: revisar la bibliografía más reciente de los últimos cinco años sobre la ingesta de AGPI y su relación con el cáncer, principalmente de próstata, mama y colon, para concretar la posible existencia de una evidencia científica concluyente al respecto. Método: la búsqueda preliminar en la literatura proporcionó 92 referencias. Finalmente, tras su revisión, se han incluido 40 estudios directamente relacionados, conformados por estudios experimentales, en animales e in vitro, así como estudios epidemiológicos. Resultados: los estudios experimentales en animales e in vitro revisados concluyen un efecto protector de los AGPI omega-3 frente al cáncer. Sin embargo, los estudios en humanos son contradictorios, aunque sí parece existir una clara evidencia del efecto protector de los AGPI 3 en la prevención del cáncer de colon. Conclusión: la relación entre AGPI 6 y AGPI 3 de la dieta frente al riesgo de padecer cáncer cobra cada vez más importancia, si bien se necesitan más estudios para confirmar su influencia en el desarrollo de esta enfermedad.

[Endonasal tubes as cause of pressure ulcers in the critical patient]. / Sondas endonasales como causa de las úlceras por presión en el paciente crítico.

INTRODUCTION: One of the risks of using endonasal tubes (ET) is the appearance of pressure ulcers (PU). OBJECTIVE: To ascertain the proportion of patients with nasal PU, study the risk factors of appearance, and find predictive variables. MATERIAL AND METHODS: A six-month prospective, observational study of intensive care unit patients with ET. VARIABLES: Variable response: "the appearance of pu as a result of the use of ET". Explanatory variables: age, duration of stay, length of time with ET, gender, sedation, norepinephrine perfusion, mechanical ventilation, anemia, nutritional state. ANALYSIS: multivariate statistical techniques (multiple logistical regression). Statistics program g-stat 2.0. Significance level p < 0.05. RESULTS: Sample of 48 patients. Proportion of patients with PU: 29.2%. Those patients with PU had similar ages, duration of stay and longer length of time with ET. Results of the Logistic Regression model: only the variable "time with ET" was statistically significant (p = 0.03; odds ratio: 1.047). CONCLUSIONS: The length of time the patient is using an ET influences the appearance of nasal PU (risk increases 1.047 for each day with ET). None of the variables dealt with could be used as a predictive factor in the appearance of PU.

Improvement in strategies for the non-invasive prenatal diagnosis of Huntington disease.

PURPOSE: We focused on the improvements of prenatal diagnosis by the analysis of DNA from maternal plasma, using Huntington disease as a model of disease. METHODS: We studied plasma from a pregnancy at risk of having a fetus affected with Huntington disease by the use of two direct analysis of the mutation and polymorphic STRs. RESULTS: Direct methods were not informative. Analysis with STRs revealed the presence of the allele that does not co-segregate with the disease, thus the fetus was healthy. CONCLUSIONS: This strategy is very useful to face complex cases when the direct study is not informative not only for Huntington disease but also for many other disorders.

Efficacy of directly observed treatment of HIV infection: experience in AIDS welfare homes.

With the objective of analyzing the efficacy of directly observed treatment (DOT) of HIV infection in the management of severely immunodepressed patients, this method was examined in individuals cared for in two social welfare facilities for HIV-infected persons and compared to self-administered therapy in outpatients. Forty-seven patients with registered HIV infection, stage C, were assigned to DOT for 9 months, the majority of whom had previously received antiretroviral therapy. A group of 51 HIV-infected outpatients, who attended day clinics attached to the reference hospitals, served as a comparison group. Together with increases in weight (9.2+/-7.5 kg) and Karnofsky scores (16.9+/-12.2) in the DOT group, a significant improvement of surrogate markers, such as CD4+ T-cell counts (increase in DOT group, 113.4+/-151.0 cells/microl; control group, -2.8+/-114.1 cells/microl; P<0.001) and HIV load (decrease in DOT group, -1.7+/-2.3 log10 copies/ml; control group, -0.4+/-1.5 log10 copies/ml; P<0.01) was detected in the DOT group. Morbidity and mortality were similar in both groups. The results indicate that such welfare facilities provide a useful framework not only for social objectives but also for healthcare purposes.

[Graves' disease with associated thyroid nodules (nodular Graves' disease). Clinical, diagnostic and therapeutic considerations]. / Enfermedad de Graves-Basedow con nódulos tioideos asociados (enfermedad de Graves-Basedow nodular). Consideraciones clínicas, diagnósticas y terapéuticas.

BACKGROUND: Sometimes Graves disease (GD) can appear in association with thyroid nodules, which seems to increase the risk of carcinoma. In this article, we try to establish clinical characteristics, diagnostic means and appropriate treatment for Graves patients with co-existent nodules. METHOD: A retrospective study was made of 153 consecutive patients who underwent operation for GD between 1967 and 2000. Each patient was subject to a regular protocol including physical examination, diagnostic test, total or subtotal thyroidectomy and follow-up in the long term with the purpose of making a valuation of the postsurgical morbidity, evolution and relapses. Data were processed through computing in order to get the statistical information. RESULTS: 28.1% of GD had thyroid nodules and carcinoma was diagnosed in four patients (9.3%), all of them belonging to papillary variety. Surgery consisted of 57 subtotal thyroidectomies (37.3%) and 94 total thyroidectomies. Parathyroid and recurrent morbidity was established in 4.6 and 3.9%, respectively, a year later since the operation, though it had a strong tendency to decrease from 1980. 96% of cases showed no relapse. CONCLUSIONS: Nodular GD is very common in our setting, especially in Graves patients with late beginning who wait for ages until they are undergone surgery. Initial treatment should be by means of braking therapy with antithyroid drugs and clinical, cytologic and ultrasonographic control. Surgery would be advised, from the outset or during the follow-up, in view of either any suspicion about cancer or presence of local growth. The procedure of choice is total thyroidectomy performed with low morbidity.

Huntington disease-unaffected fetus diagnosed from maternal plasma using QF-PCR.

The discovery of fetal DNA in maternal plasma from early pregnancies has led to new opportunities for clinical application. In the last few years there have been numerous reported applications, mainly fetal gender and RhD genotyping. The prenatal diagnosis of some inherited genetic diseases such as Huntington disease is also very frequently required in the prenatal diagnosis routine. We have successfully diagnosed, with a non-invasive procedure, an unaffected HD fetus at the 13th week of gestation using fetal DNA from maternal plasma and the quantitative fluorescent PCR method, which is one of the most sensitive ways to detect fetal DNA in maternal plasma at such an early time of gestation.

Prenatal detection of a cystic fibrosis mutation in fetal DNA from maternal plasma.

OBJECTIVES: Maternal plasma and serum are being used to detect fetal DNA by PCR in order to determine certain conditions such as fetal gender and RhD without invasive procedures. Because of the presence of maternal DNA in plasma, these approaches are limited to paternally inherited disorders or those de novo present in the fetus. We have assessed the possibility of performing the detection of a single-gene disorder such as a fetal paternally inherited Cystic Fibrosis mutation (Q890X) in maternal plasma. METHODS: The analysis was performed at 13 weeks of gestation using DNA extracted from maternal plasma. We used a PCR amplification of the Q890X mutation and a posterior restriction analysis of the PCR product. RESULTS: We were able to detect the presence of the mutation and thus the fetal condition of being a carrier of the paternal mutation. CONCLUSIONS: We have made evident the possibility of detecting an inherited paternal mutation in a non-invasive way at the 13t(hr) weeks of pregnancy. This methodology could be very useful in cases of paternally inherited dominant disorders. The technical improvements in fetal DNA detection and analysis might lead to the development of new applications in the non-invasive prenatal diagnosis field.

[The fundus oculi in the hemiplegic patient]. / El fondo de ojo en el paciente hemipléjico.

INTRODUCTION AND OBJECTIVE: The fundus oculi is useful for observation of the interior of the eye and the retina. This study establishes a relationship between patients with established cerebral infarcts and the results observed in their fundi. PATIENTS AND METHODS: A retrospective study of the clinical histories of 177 patients seen in the rehabilitation department over a period of one year. RESULTS: The patients were aged between 29 and 85 years. The majority were men; 101 patients (57.06%) had systolic-diastolic arterial hypertension. On study of the fundus oculi there was a predominance of alterations of the blood vessels of the retina due to vascular sclerosis (93.1%) but only 24.4% had frank alterations caused by arterial hypertension. CONCLUSIONS: We found a slight relation between arterial hypertension and the alterations observed in the fundus oculi of these patients.

Chromosomal mosaicism for isochromosome 11q confined to CVS direct preparations.

OBJECTIVE: To analyse the discrepancy between the karyotype in direct preparations of chorionic villus sampling (CVS) and the fetal karyotype and its possible fetal phenotypic repercussion. METHODS: The karyotype was obtained from direct and cultured preparations of CVS. FISH was performed in direct CVS preparations and in four different areas of term placenta. RESULTS: Karyotype and FISH analysis in CVS revealed a 46,XX/47,XX,+i(11q) cell line. Cultured CVS preparations showed a 46,XX karyotype. Cytogenetic studies in term placenta did not reveal the abnormal cell line. Molecular studies did not detect uniparental disomy for chromosome 11 in the fetus. CONCLUSION: The fetus, at birth, had no phenotypic abnormalities. IUGR was not present during gestation, in accordance with the low proportion of aneuploid cells in term placenta, and UPD for chromosome 11 was not observed.

Nitric oxide synthase expression in the cerebral cortex of patients with epilepsy.

PURPOSE: Nitric oxide (NO), a short-lived radical synthesized from L-arginine by activation of the enzyme nitric oxide synthase (NOS), has been implicated in the pathophysiology of epilepsy by some investigators. However, the current data about NO and NOS in epilepsy are controversial and are derived only from animal models of epilepsy. In this study we investigated possible changes in NOS expression in the cerebral cortex of patients with epilepsy. METHODS: Qualitative and quantitative parameters of the immunolabeling pattern of the neuronal, endothelial, and inducible isoforms of NOS were analyzed in biopsy material obtained from patients with short and long seizure history and from patients without epilepsy. RESULTS: The comparative study showed that in the cerebral cortex of patients with epilepsy, particularly in those with a long seizure history, the number and labeling intensity of NOS-positive neurons increased, and that a subpopulation of nonpyramidal GABAergic neurons (type II NOS neurons) was responsible for this phenomenon. CONCLUSIONS: The fact that NOS upregulation is more evident in patients with a long seizure history suggests that this is a consequence of seizures, acting probably as an adaptative response to the sustained release of excitatory amino acids.