Metformin to treat Huntington disease: A pleiotropic drug against a multi-system disorder.

Huntington disease (HD) is a neurodegenerative disorder produced by an expansion of CAG repeats in the HTT gene. Patients of HD show involuntary movements, cognitive decline and psychiatric impairment. People carrying abnormally long expansions of CAGs (more than 35 CAG repeats) produce mutant huntingtin (mHtt), which encodes tracks of polyglutamines (polyQs). These polyQs make the protein prone to aggregate and cause it to acquire a toxic gain of function. Principally affecting the frontal cortex and the striatum, mHtt disrupts many cellular functions. In addition, this protein is expressed ubiquitously, and some reports show that many other cell types are affected by the toxicity of mHtt. Several studies reported that metformin, a widely-used anti-diabetic drug, is neuroprotective in models of HD. Here, we provide a review of the benefits of this substance to treat HD. Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others. These molecules regulate autophagy, chaperone expression, and more, which in turn reduce mHtt toxicity. Moreover, metformin alters gut microbiome and its metabolic processes. The study of potential targets, interactions between the drug, host and microbiome, or genomic and pharmacogenomic approaches may allow us to design personalised medicine to treat HD.

Angiotensin-(1-7), a protective peptide against vascular aging.

Vascular aging is a complex and multifaceted process that provokes profound molecular, structural, and functional changes in the vasculature. Eventually, these profound aging alterations make arteries more prone to vascular disease, including hypertension, atherosclerosis and other arterial complications that impact the organism beyond the cardiovascular system and accelerate frailty. For these reasons, preventing or delaying the hallmarks of vascular aging is nowadays a major health goal, especially in our aged societies. In this context, angiotensin(Ang)-(1-7), a major player of the protective branch of the renin-angiotensin system, has gained relevance over recent years as growing knowledge on its anti-aging properties is being unveiled. Here, we briefly review the main actions of Ang-(1-7) against vascular aging. These include protection against vascular cell senescence, anti-inflammatory and antioxidant effects together with the induction of cytoprotective systems. Ang-(1-7) further ameliorates endothelial dysfunction, a hallmark of vascular aging and disease, attenuates fibrosis and calcification and promotes protective angiogenesis and repair. Although further research is needed to better understand the anti-aging properties of Ang-(1-7) on the vasculature, this heptapeptide arises as a promising pharmacological tool for preventing vascular aging and frailty.

Mixing and matching methylotrophic enzymes to design a novel methanol utilization pathway in E. coli.

One-carbon (C1) compounds, such as methanol, have recently gained attention as alternative low-cost and non-food feedstocks for microbial bioprocesses. Considerable research efforts are thus currently focused on the generation of synthetic methylotrophs by transferring methanol assimilation pathways into established bacterial production hosts. In this study, we used an iterative combination of dry and wet approaches to design, implement and optimize this metabolic trait in the most common chassis, E. coli. Through in silico modelling, we designed a new route that "mixed and matched" two methylotrophic enzymes: a bacterial methanol dehydrogenase (Mdh) and a dihydroxyacetone synthase (Das) from yeast. To identify the best combination of enzymes to introduce into E. coli, we built a library of 266 pathway variants containing different combinations of Mdh and Das homologues and screened it using high-throughput 13C-labeling experiments. The highest level of incorporation of methanol into central metabolism intermediates (e.g. 22% into the PEP), was obtained using a variant composed of a Mdh from A. gerneri and a codon-optimized version of P. angusta Das. Finally, the activity of this new synthetic pathway was further improved by engineering strategic metabolic targets identified using omics and modelling approaches. The final synthetic strain had 1.5 to 5.9 times higher methanol assimilation in intracellular metabolites and proteinogenic amino acids than the starting strain did. Broadening the repertoire of methanol assimilation pathways is one step further toward synthetic methylotrophy in E. coli.

Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases.

Gestational diabetes mellitus (GDM) is defined as the presence of high blood glucose levels with the onset, or detected for the first time during pregnancy, as a result of increased insulin resistance. GDM may be induced by dysregulation of pancreatic ß-cell function and/or by alteration of secreted gestational hormones and peptides related with glucose homeostasis. It may affect one out of five pregnancies, leading to perinatal morbidity and adverse neonatal outcomes, and high risk of chronic metabolic and cardiovascular injuries in both mother and offspring. Currently, GDM diagnosis is based on evaluation of glucose homeostasis at late stages of pregnancy, but increased age and body-weight, and familiar or previous occurrence of GDM, may conditionate this criteria. In addition, an earlier and more specific detection of GDM with associated metabolic and cardiovascular risk could improve GDM development and outcomes. In this sense, 1st-2nd trimester-released biomarkers found in maternal plasma including adipose tissue-derived factors such as adiponectin, visfatin, omentin-1, fatty acid-binding protein-4 and retinol binding-protein-4 have shown correlations with GDM development. Moreover, placenta-related factors such as sex hormone-binding globulin, afamin, fetuin-A, fibroblast growth factors-21/23, ficolin-3 and follistatin, or specific micro-RNAs may participate in GDM progression and be useful for its recognition. Finally, urine-excreted metabolites such as those related with serotonin system, non-polar amino-acids and ketone bodies, may complete a predictive or early-diagnostic panel of biomarkers for GDM.

Single shot spinal anaesthesia with hypobaric bupivacaine for hip fracture repair surgery in the elderly. Randomized, double blinded comparison of 3.75 mg vs. 7.5 mg.

BACKGROUND: Arterial hypotension is the most frequent adverse effect of subarachnoid anaesthesia in the elderly sustaining a femoral proximal fracture. Decreasing the local anaesthetic dose reduces the incidence of hypotension but shortens sensory block duration that could be insufficient in some surgical procedures. Sensory block duration could be prolonged using hypobaric local anaesthetics. We evaluated whether low hypobaric bupivacaine doses were adequate for this type of surgery while maintaining the haemodynamic stability. METHODS: A prospective, randomized, double blinded study was designed. Patients over 65 years old, sustaining traumatic hip fracture, were assigned to one of two groups: B0.5 group, hypobaric bupivacaine 7.5mg 5mg/ml (control group), and B0.25 group, hypobaric bupivacaine 3.75 mg 2.5mg/ml (study group). After subarachnoid injection, sensory level and motor blockade degree were registered, as were blood pressure, and heart rate at basal time and at 2, 5, 10, 15, 20 and 30 min after injection. The doses of vasopressor needed were registered as well. Surgical conditions and the duration of the surgical procedure-whether rescue analgesia or anaesthesia was needed-and sensory level regression to T12, were registered as well. RESULTS: Sixty four patients was the calculated sample size. The study was stopped in an interim analysis because an elevated number of patients in the B0.25 group needed iv rescue anaesthesia. In the analyzed cases, blood pressure was significantly lower in the B0.5 group at the 15 and 30 min measurements. Vasopressor drugs needs were similar between groups [ephedrine accumulated mean (SD) doses 11.4 (5.2) mg vs. 9.1 (2.7) mg, p=0.045)]. Sensory block regression to T12 was faster in the B0.25 group, [(mean (SD) 68.2 (29.0) min vs. 112.8 (17.3) min in the B0.5 group, p<0.05]. Five out of 19 patients in the B0.25 group needed intravenous anaesthesia rescue before surgery started. CONCLUSION: Lowering hypobaric bupivacaine dose to 3.75 mg in subarachnoid anaesthesia for hip fracture repair surgery in elderly patients decrease intraoperative blood pressure, but in an important number of patients intravenous anaesthesia rescue was needed and preclude recommendation.

Single shot spinal anesthesia with very low hyperbaric bupivacaine dose (3.75 mg) for hip fracture repair surgery in the elderly. A randomized, double blinded study.

PURPOSE: Single shot spinal anesthesia is used worldwide for hip fracture repair surgery in the elderly. Arterial hypotension is a frequent adverse effect. We hypothesized that lowering local anesthetics dose could decrease the incidence of arterial hypotension, while maintaining quality of surgical anesthesia. METHODS: In a randomized double blinded study, 66 patients over the age of 65 years, with hip fracture needing surgical repair, were assigned to B0.5 group 7.5mg hyperbaric bupivacaine 5mg/ml (control group), and B0.25 group 3.75mg hyperbaric bupivacaine 2.5mg/ml (study group). Sensory and motor block level, and hemodynamic parameters including blood presure, heart rate and vasopressor dose administration were registered, along with rescue anesthesia needs, the feasibility of surgery, its duration, and regression time of sensory anesthesia to T12. RESULTS: After exclusions, 61 patients were included in the final analysis. Arterial hypotension incidence was lower in the B0.25 group (at the 5, 10, and 15min determinations), and a lower amount of vasopressor drugs was needed (mean accumulated ephedrine dose 1.6mg vs. 8.7mg in the B0.5 group, p<0.002). Sensory block regression time to T12 was shorter in the B0.25 group, mean 78.6±23.6 (95% CI 51.7-110.2)min vs. 125.5±37.9 (95% CI 101.7-169.4)min in the B0.5 group, p=0.033. All but one patient in the B0.25 group were operated on under the anesthetic procedure first intended. No rescue anesthesia was needed. CONCLUSION: Lowering bupivacaine dose for single shot spinal anesthesia for hip fracture repair surgery in elderly patients was effective in decreasing the occurrence of arterial hypotension and vasopressor use, while intraoperative quality remained.

Ranibizumab intravítreo en el tratamiento de membrana neovascular subretiniana en un caso de coroidopatía puntata interna / Intravitreal ranibizumab in the treatment of subretinal neovascularization in a case of punctate inner choroidopathy

CASO CLÍNICO: Se presenta el caso de una mujer de 28 años con disminución de agudeza visual en ojo izquierdo (OI) que presentaba una imagen sugestiva de membrana neovascular subretiniana en OI y lesiones coriorretinianas bilaterales compatibles con coroidopatía punctata interna (PIC) que fue tratada con ranibizumab intravítreo, obteniendo excelentes resultados. DISCUSIÓN: Debe realizarse el diagnóstico diferencial de la PIC con el resto de «síndromes de puntos blancos» y con el síndrome de presunta histoplasmosis ocular (SPHO). Los fármacos anti-VEGF pueden ser una buena alternativa como tratamiento de este tipo de enfermedades cuando desarrollan una membrana neovascular subretiniana

CASE REPORT: We report the case of a 28-year old woman suffering loss of visual acuity in her left eye, who presented an image suggestive of a subretinal neovascular membrane in her left eye, and bilateral retinal lesions compatible with punctate inner choroidopathy (PIC). She was treated with intravitreal ranibizumab obtaining excellent results. DISCUSSION: The differential diagnosis must be made between PIC and the rest of "white dot syndromes" and the presumed ocular histoplasmosis syndrome (POHS). Antiangiogenic drugs may be a good alternative for the treatment of such diseases when they develop a subretinal neovascular membrane

[Intravitreal ranibizumab in the treatment of subretinal neovascularization in a case of punctate inner choroidopathy]. / Ranibizumab intravítreo en el tratamiento de membrana neovascular subretiniana en un caso de coroidopatía puntata interna.

CASE REPORT: We report the case of a 28-year old woman suffering loss of visual acuity in her left eye, who presented an image suggestive of a subretinal neovascular membrane in her left eye, and bilateral retinal lesions compatible with punctate inner choroidopathy (PIC). She was treated with intravitreal ranibizumab obtaining excellent results. DISCUSSION: The differential diagnosis must be made between PIC and the rest of "white dot syndromes" and the presumed ocular histoplasmosis syndrome (POHS). Antiangiogenic drugs may be a good alternative for the treatment of such diseases when they develop a subretinal neovascular membrane.

El país de los ciegos, de H.G. Wells (1866-1946) / The country of the blind, by H.G. WELLS (1866-1946)

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Extracellular PBEF/NAMPT/visfatin activates pro-inflammatory signalling in human vascular smooth muscle cells through nicotinamide phosphoribosyltransferase activity.

AIMS/HYPOTHESIS: Extracellular pre-B cell colony-enhancing factor/nicotinamide phosphoribosyltransferase/visfatin (ePBEF/NAMPT/visfatin) is an adipocytokine, whose circulating levels are enhanced in metabolic disorders, such as diabetes mellitus and obesity. Here, we explored the ability of ePBEF/NAMPT/visfatin to promote vascular inflammation, as a condition closely related to atherothrombotic diseases. We specifically studied the ability of PBEF/NAMPT/visfatin to directly activate pathways leading to inducible nitric oxide synthase (iNOS) induction in cultured human aortic smooth muscle cells, as well as the mechanisms involved. METHODS: iNOS levels and extracellular signal-regulated kinase (ERK) 1/2 activity were determined by western blotting. Nuclear factor (NF)-kappaB activity was assessed by electrophoretic mobility shift assay. RESULTS: ePBEF/NAMPT/visfatin (10-250 ng/ml) induced iNOS in a concentration-dependent manner. At a submaximal concentration (100 ng/ml), ePBEF/NAMPT/visfatin time-dependently enhanced iNOS levels up to 18 h after stimulation. Over this time period, ePBEF/NAMPT/visfatin elicited a sustained activation of NF-kappaB and triggered a biphasic ERK 1/2 activation. By using the respective ERK 1/2 and NF-kappaB inhibitors, PD98059 and pyrrolidine dithiocarbamate, we established that iNOS induction by ePBEF/NAMPT/visfatin required the consecutive upstream activation of ERK 1/2 and NF-kappaB. The pro-inflammatory action of ePBEF/NAMPT/visfatin was not prevented by insulin receptor blockade. However, exogenous nicotinamide mononucleotide, the product of NAMPT activity, mimicked NF-kappaB activation and iNOS induction by ePBEF/NAMPT/visfatin, while the NAMPT inhibitor APO866 prevented the effects of ePBEF/NAMPT/visfatin on iNOS and NF-kappaB. CONCLUSIONS/INTERPRETATION: Through its intrinsic NAMPT activity, ePBEF/NAMPT/visfatin appears to be a direct contributor to vascular inflammation, a key feature of atherothrombotic diseases linked to metabolic disorders.

[Evaluation of patient satisfaction in outpatient pharmacy]. / Evaluación de la satisfacción y de la insatisfacción de pacientes atendidos en la unidad de atención farmacéutica a pacientes externos.

OBJECTIVE: To establish the level of satisfaction and dissatisfaction with the service received by patients attending the Outpatient Pharmacy regarding the care received. METHOD: Two-month long cross-sectional study. The study included all patients who had attended the Outpatient Pharmacy (OP) and had given their consent. Satisfaction was measured using a previously validated survey (Likert-type scale), with 5 possible closed answers (1: Disagree and 5: Strongly agree) and the Satisfaction Index established by the Regional Ministry of Health for the Autonomous Community of Valencia. Dissatisfaction was assessed via the complaints received by the Patient Service Department over the last 10 years. RESULTS: Patient satisfaction survey (nfinal=138). Overall Satisfaction Index (SI): 76% (95% CI: 72-80%). Greatest satisfaction: Pharmacists Skills (SI: 88%; 95% CI: 87-88%). Lowest satisfaction: dispensing area (SI: 63%; 95% CI: 60-66%) and dispensing process (SI: 68%; 95% CI: 67-70%). Complaints (n=22). Reasons for dissatisfaction: dispensing process (72%) and dispensing area (10%). CONCLUSIONS: Although the Satisfaction Index is a useful indicator for identifying improvements, the reasons for dissatisfaction are also required as a complement to this information. Those aspects in need of improvement are the dispensing area and process and increased structural and human resources are required.

Awareness with recall during general anaesthesia: a prospective observational evaluation of 4001 patients.

BACKGROUND: We have prospectively evaluated the incidence and characteristics of awareness with recall (AWR) during general anaesthesia in a tertiary care hospital. METHODS: This study involves a prospective observational investigation of AWR in patients undergoing general anaesthesia. Blinded structured interviews were conducted in the postanaesthesia care unit, on postoperative day 7 and day 30. Definition of AWR was 'when the patient stated or remembered that he or she had been awake at a time when consciousness was not intended'. Patient characteristics, perioperative, and drug-related factors were investigated. Patients were classified as not awake during surgery, AWR, AWR-possible, AWR-not evaluable. The perceived quality of the awareness episode, intraoperative dreaming, and sequelae were investigated. The anaesthetic records were reviewed to search for data that might explain the awareness episode. RESULTS: The study included 4001 patients. Incidence of AWR was 1.0% (39/3921 patients). If high risk for AWR patients were excluded, the incidence was 0.8%. After the interview on the seventh day, six patients denied having been conscious during anaesthesia; hence, the incidence of AWR in elective surgery was 0.6%. Factors associated with AWR were: anaesthetic technique incidence of 1.1% TIVA-propofol vs 0.59% balanced anaesthesia vs 5.0% O2/N2O-based anaesthesia vs 0.9% other anaesthetic techniques (mainly propofol boluses for short procedures), P=0.008; age (AWR 42.3 yr old vs 50.6 yr old, P=0.041), absence of i.v. benzodiazepine premedication (P=0.001), Caesarean section (C-section) (P=0.019), and surgery performed at night (P=0.013). More than 50% of patients reported intraoperative dreaming in the early interview, mainly pleasant. Avoidable human factors were detected from the anaesthetic records of most patients. Subjective auditory perceptions prevailed, together with trying to move or communicate, and touch or pain perception. CONCLUSIONS: A relatively high incidence of AWR and dreams during general anaesthesia was found. Techniques without halogenated drugs showed more patients. The use of benzodiazepine premedication was associated with a lower incidence of AWR. Age, C-section with general anaesthesia, and surgery performed at night are risk factors.

Evaluación de la satisfacción y de la insatisfacción de pacientes atendidos en la unidad de atención farmacéutica a pacientes externos / Evaluation of patient satisfaction in outpatient pharmacy

Objetivo: Conocer tanto el grado de satisfacción como los motivosde insatisfacción de los pacientes que acuden a la Unidad deAtención Farmacéutica a Pacientes Externos (UFPE) respecto a laatención recibida.Método: Estudio transversal de dos meses de duración. Se incluyerontodos los pacientes atendidos por la UFPE que dieron su consentimiento.La satisfacción se midió con una encuesta previamente validada,de tipo Likert, con 5 posibles respuestas cerradas (1: endesacuerdo, y 5: muy de acuerdo), utilizándose el indicador índice desatisfacción establecido por la Conselleria de Sanitat de la ComunidadValenciana. La insatisfacción se evaluó a través de las quejas formuladasen el Servicio de Atención e Información al Paciente en losúltimos 10 años.Resultados: encuesta de satisfacción (nfinal = 138). Índice de satisfacción(IS) global: 76% (IC 95%: 72-80%). Mayor satisfacción: habilidadesdel farmacéutico (IS: 88%; IC 95%: 87-88%). Menor satisfacción:zona de dispensación (IS: 63%; IC 95%: 60-66%) y proceso dedispensación (IS: 68%; IC 95%: 67-70%). Reclamaciones (n = 22).Motivos de insatisfacción: proceso de dispensación (72%) y zona dedispensación (10%).Conclusiones: Aunque el índice de satisfacción es un indicador útilpara poder establecer mejoras, es necesario conocer también losmotivos de insatisfacción como complemento a esta información.Los aspectos a mejorar son la zona y el proceso de dispensación,siendo necesario un aumento de los recursos estructurales y humanos

Objective: To establish the level of satisfaction and dissatisfactionwith the service received by patients attending the Outpatient Pharmacyregarding the care received.Method: Two-month long cross-sectional study. The study includedall patients who had attended the Outpatient Pharmacy (OP) andhad given their consent. Satisfaction was measured using a previouslyvalidated survey (Likert-type scale), with 5 possible closedanswers (1: Disagree and 5: Strongly agree) and the Satisfaction Indexestablished by the Regional Ministry of Health for the AutonomousCommunity of Valencia. Dissatisfaction was assessed via thecomplaints received by the Patient Service Department over the last10 years.Results: Patient satisfaction survey (nfinal=138). Overall SatisfactionIndex (SI): 76% (95% CI: 72-80%). Greatest satisfaction: Pharmacist’sSkills (SI: 88%; 95% CI: 87-88%). Lowest satisfaction: dispensingarea (SI: 63%; 95% CI: 60-66%) and dispensing process (SI: 68%;95% CI: 67-70%). Complaints (n=22). Reasons for dissatisfaction:dispensing process (72%) and dispensing area (10%).Conclusions: Although the Satisfaction Index is a useful indicator foridentifying improvements, the reasons for dissatisfaction are also requiredas a complement to this information. Those aspects in need ofimprovement are the dispensing area and process and increasedstructural and human resources are required

Pro-inflammatory effects of early non-enzymatic glycated proteins in human mesothelial cells vary with cell donor's age.

BACKGROUND AND PURPOSE: Diabetes mellitus is prevalent in the elderly population. It is also a disease causing tissue damage through several different mechanisms. Some of these mechanisms are also activated by ageing and this overlap raises questions about how diabetes induces damage in the elderly. Early products of non-enzymatic glycation of proteins (Amadori adducts), and the ageing process share the capacity to induce oxidative stress and inflammation in human peritoneal mesothelial cells (HPMCs). We have evaluated the interactions between the age of the donor of the HPMCs and the pro-inflammatory effects of Amadori adducts in those cells. EXPERIMENTAL APPROACH: HPMCs were isolated from 20 individuals (age range 21-81 years) and grown in culture. Using different experimental approaches we determined NF-kappaB dependent transcriptional activity and different NF-kappaB-related pro-inflammatory gene and protein expressions in basal (or non-stimulated) conditions and after stimulation with two Amadori adducts; highly-glycated haemoglobin and glycated bovine serum albumin. KEY RESULTS: Amadori-induced effects on NF-kappaB dependent-transcription and on the activity of NOS, COX and several NF-kappaB-related pro-inflammatory genes (iNOS, COX-2, TNF-alpha, IL-1beta, and IL6) diminished as the donor's age increased, being practically absent in cells from donors more than 65 years old. Such decreased effects were inversely correlated with an increased basal expression and activity of these pro-inflammatory markers with age. CONCLUSIONS AND IMPLICATIONS: Pro-inflammatory effects of Amadori-adducts in HPMCs were strongly dependent on cell donor's age. This may have significant implications for the mechanisms underlying diabetes-induced tissue damage in patients of different ages.

[Identifying improvement opportunities in the management of hepatitis C]. / Identificación de oportunidades de mejora del tratamiento de la hepatitis C.

OBJECTIVE: Hepatitis C represents a public health concern with more than 170 million carriers. The goal of this study was to identify improvement opportunities in the management of hepatitis C, and the pharmaceutical actions performed for the prevention and solution of medication-related problems in patients seen at the Pharmaceutical Care Outpatient Unit. METHOD: A longitudinal study (January to October 2005) with patients monoinfected by hepatitis C virus receiving ribavirin and peginterferon alfa (2a or 2b). Data collection took place during the interview at the time of antiviral dispensation. Adverse reactions were classified according to CTCEA v3.0 criteria. Iaser methodology was used to identify patients with improvement opportunities regarding treatment. RESULTS: In all 109 patients and 201 improvement opportunities were identified. Pharmacotherapeutic morbidity was identified from adverse events (blood toxicity, pseudoflu syndrome, etc.) in 425 occasions; 388 pharmaceutical actions were performed, 41.23% to prevent adverse effects and 39.95% to provide patients or carers with information. CONCLUSIONS: In all, 99.01% of patients had safety problems. Pharmacotherapeutic morbidity from adverse effects was less common than reported in clinical trials of these drugs. Most pharmaceutical actions were preventive in nature. Iaser methodology allows to identify patients with improvement opportunities regarding hepatitis C treatment and the prevention of pharmacotherapeutic morbidity.

[Bilateral axillary brachial plexus block guided by multiple nerve stimulation and ultrasound in a multiple trauma patient]. / Bloqueo axilar bilateral del plexo braquial guiado por neuroestimulación múltiple y ultrasonidos en una paciente con politraumatismo.

We present the case of a woman with multiple wounds and injuries after attempted suicide by jumping from a high place. She had multiple craniofacial injuries and fractures of both forearms requiring emergency osteosynthesis. The neurosurgeons requested that a level of consciousness be maintained for frequent assessment; therefore it was decided to provide a bilateral axillary brachial plexus block. The procedure was carried out with the aid of a nerve stimulator to locate a triple response in the left arm (radial, medial and musculocutaneous nerves) and with both ultrasound and double nerve stimulation in the right arm (medial and radial nerves). Surgery proceeded without adverse events. The location of nerves or nerve roots with both ultrasound and stimulators was highly useful in this patient in need of bilateral brachial plexus blockade. This combination, and ultrasound in particular, might be the technique of choice because it offers an image in real time and assessment of the least amount of anesthetic that seems to be needed for achieving a block.

Identificación de oportunidades de mejora del tratamiento de la hepatitis C / No disponible

Objetivo: El objetivo de este estudio es identificar las oportunidadesde mejora del tratamiento de la hepatitis C y las actuacionesfarmacéuticas realizadas para la prevención y resolución deproblemas relacionados con la medicación en los pacientes atendidosen la unidad de atención farmacéutica a pacientes externos.Método: Estudio longitudinal (enero a octubre de 2005) conpacientes monoinfectados por el virus de la hepatitis C en tratamientocon ribavirina y peginterferón alfa (2a o 2b). La recogidade datos se realizó durante la entrevista con el paciente en elmomento de la dispensación de los antivirales. Las reaccionesadversas se clasificaron según los criterios CTCEA v3.0. Para laidentificación de pacientes con oportunidades de mejora en sutratamiento se empleó la metodología Iaser®.Resultados: Se incluyeron 109 pacientes con 201 oportunidadesde mejora. Se identificó morbilidad farmacoterapéutica porefectos adversos (toxicidad hematológica, síndrome pseudogripal,etc.) en 425 ocasiones. Se realizaron 388 actuaciones farmacéuticas,el 41,23% para prevenir efectos adversos y el 39,95% paraproveer de información al paciente o cuidador.Conclusiones: El 99,01% de pacientes presentaba problemasde seguridad. La morbilidad farmacoterapéutica por efectosadversos es de menor frecuencia que la publicada en ensayos clínicoscon estos medicamentos. Las principales actuaciones farmacéuticasrealizadas fueron de tipo preventivo. La metodologíaIaser® permite la identificación de pacientes con oportunidades demejora del tratamiento de la hepatitis C y la prevención de morbilidadfarmacoterapéutica

Objective: Hepatitis C represents a public health concernwith more than 170 million carriers. The goal of this study was toidentify improvement opportunities in the management of hepatitisC, and the pharmaceutical actions performed for the preventionand solution of medication-related problems in patients seenat the Pharmaceutical Care Outpatient Unit.Method: A longitudinal study (January to October 2005) withpatients monoinfected by hepatitis C virus receiving ribavirin andpeginterferon alfa (2a or 2b). Data collection took place duringthe interview at the time of antiviral dispensation. Adverse reactionswere classified according to CTCEA v3.0 criteria. Iaser®methodology was used to identify patients with improvementopportunities regarding treatment.Results: In all 109 patients and 201 improvement opportunitieswere identified. Pharmacotherapeutic morbidity was identifiedfrom adverse events (blood toxicity, pseudoflu syndrome, etc.) in425 occasions; 388 pharmaceutical actions were performed,41.23% to prevent adverse effects and 39.95% to providepatients or carers with information.Conclusions: In all, 99.01% of patients had safety problems.Pharmacotherapeutic morbidity from adverse effects was lesscommon than reported in clinical trials of these drugs. Most pharmaceuticalactions were preventive in nature. Iaser® methodologyallows to identify patients with improvement opportunities regardinghepatitis C treatment and the prevention of pharmacotherapeuticmorbidity

Changes in the human peritoneal mesothelial cells during aging.

The number of older patients admitted to peritoneal dialysis (PD) programmes is growing. At the same time, there is increasing data about the role of mesothelial cells in determining the functional alteration of the peritoneum during PD. However, little is known about the functional changes accompanying the ageing process in mesothelial cells. We aimed to evaluate whether the aging process is accompanied by changes in some functional characteristic of the human peritoneal mesothelial cells (HPMC), which could account for the poor prognosis observed in old patients with PD. HPMCs were isolated from patients undergoing a nonurgent, nonseptic abdominal surgical procedure, without renal, vascular or inflammatory disease. Cytokine levels (by enzyme-linked immunosorbent assay (ELISA)), nitrates+nitrites, and cyclooxygenase (COX) activity (by a chemiluminescence assay), cytokines, COX, nitric oxide synthase (NOS), and nuclear factor (NF)-kappaB1, two messenger ribonucleic acid (mRNA) gene expressions (by reverse transcriptase (RT)-Multiplex PCR), COX, and NOS promoter gene activities, and NF-kappaB-dependent transcription (by transient transfection assays) were determined. Our data show a significant increase in cytokines, COX, and NOS activities, and mRNA expression of cytokines, COX-2, inducible nitric oxide synthase (iNOS) and precursors of NF-kappaB in HPMCs from old people. This was also the case for COX-2 and iNOS promoter gene activities and NF-kappaB-dependent transcription. There was a positive correlation between the age of the donor's cell and the proinflammatory profile of the HPMCs. Such age-dependent increase (around two-three times) is partially abolished by different antioxidant or free-radical scavengers. Thus, aging is accompanied by the presence of an inflammatory state in HPMCs, which involves the participation of different reactive oxygen species.