Effectiveness and safety of ertapenem used in hospital-at-home units: data from Spanish Outpatient Parenteral Antimicrobial Therapy Registry.

AIM: To evaluate the effectiveness and safety of ertapenem in patients hospitalized at home. PATIENTS & METHODS: Retrospective analysis of data from Spanish Outpatient Parenteral Antimicrobial Therapy (OPAT) registry. RESULTS: Data from 1428 patients (median age 70 years; 5.4% institutionalized) and 1547 infectious processes (24% self-administration) were analyzed. Clinical cure or improvement was achieved in 93.8% of cases. Rate of related readmissions was 4.2%, of clinically important complications -3.9%, and of adverse drug reactions -3.2%. High comorbidity burden, contagion in nursing home and certain types of infection were associated with worse prognosis. Self-administration was effective and safe, except in case of nursing home-acquired infections. CONCLUSION: Ertapenem OPAT was effective and safe. Caregivers in nursing homes should be better trained in OPAT-related procedures.

Utilización de escalas en el laboratorio de evaluación integral sicomotriz del Centro Internacional de Restauración Neurológica a pacientes que padecen de esclerosis múltiple / Utilization of scales laboratory psychomotor comprehensive assessment of the International Center for Neurological Restoration patients suffering from Multiple Sclerosis

La evaluación y diagnóstico de las funciones motrices se erige en un aspecto importante y vital para los especialistas y oacientes que acuden a nuestra nstitución a fin de valorar sus posibilidades neurorrestaurativas para cumplimentar un plan de rehabilitación, encaminado a recuperar parcial o totalmente estas funciones, teniendo en cuenta sus potencialidades; de ahí que la evaluación antes y después del tratamiento neurorrestaurativo cobre vital importancia en pacientes con patologías neurológicas como la Esclerosis Múltiple; por ello el objetivo de nuestro trabajo fue valorar la sensilibidad de los test que se aplican para dicha patología en el Laboratorio de Evaluación Integral Sicomotriz (LEIS), del Centro Internacional de Restauración Neurológica (CIREN), a través de la compacación de los resultados obtenidos en las evaluaciones (inicial y final al tratamiento neurorrestaurativo) para el conocimiento del estado real de los pacientes. La muestra estuvo conformada por 25 pacientes atendidos en la Clínica de Lesiones Raquimedulares y Enfermedades Neuromusculares, a los que se les aplicaron los test evaluativos antes y después del tratamiento neurorrestaurativo, comparándose ambos resultados, para ello también se utilizó la prueba de Significación Estadística: Wilcoxon matched pairs test, evidenciándose que los test aplicados en el LEIS permitieron definir los puntos de partida para el tratamiento de rehabilitación física y se cuantificaron de manera objetiva los cambios en la capacidad física ocurridos en los pacientes en el desarrollo de su rehabilitación.

Regulation of GPR55 in rat white adipose tissue and serum LPI by nutritional status, gestation, gender and pituitary factors.

The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with obesity in humans. We have investigated the regulation of GPR55 in rat white adipose tissue (WAT) in different physiological and pathophysiological settings involved in energy balance. We compared GPR55 expression with Cannabinoid Receptor type 1 (CB1), which mediates the metabolic actions of endocannabinoids, by real time PCR and western blotting. Circulating levels of lysophosphatidylinositol (LPI), the endogenous ligand of GPR55, were measured by liquid chromatography-mass spectrometry. Both WAT CB1 and GPR55 levels were increased after fasting and recovered after leptin treatment. Their expression was decreased during gestation and increased throughout lifespan. Orchidectomy diminished WAT CB1 and GPR55 expression whereas ovariectomized rats showed increased GPR55 but decreased CB1 levels. Alterations in pituitary functions also modified WAT CB1 and GPR55 levels. Serum LPI levels were inversely regulated by fasting and gonadectomy in comparison to WAT GPR55. Our findings indicate that GPR55 and LPI are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in energy status.

Hyperthyroidism differentially regulates neuropeptide S system in the rat brain.

Thyroid hormones play an important role in the regulation of energy balance, sleep and emotional behaviors. Neuropeptide S (NPS) is a recently discovered neuropeptide, regulating feeding, sleep and anxiety. Here, we examined the effect of hyperthyroidism on the gene and protein expression of neuropeptide S and its receptor (NPS-R) in the hypothalamus, brainstem and amygdala of rats. Our results showed that the expression of NPS and NPS-R was differentially modulated by hyperthyroidism in the rat brain. NPS and NPS-R mRNA and protein levels were decreased in the hypothalamus of hyperthyroid rats. Conversely NPS-R expression was highly increased in the brainstem and NPS and NPS-R expression were unchanged in the amygdala of these rats. These data suggest that changes in anxiety and food intake patterns observed in hyperthyroidism could be associated with changes in the expression of NPS and NPS-R. Thus, the NPS/NPS-R system may be involved in several hyperthyroidism-associated comorbidities.

Leptin and fasting regulate rat gastric glucose-regulated protein 58.

The stomach secretes a wide range of peptides with essential metabolic functions, and thereby plays an important role in the regulation of energy homeostasis. Disulfide isomerase glucose-regulated protein 58 (GRp58) is a molecular chaperone member of the endoplasmic reticulum (ER) stress signaling pathway, which is a marker for human gastric cancer. Since GRp58 seems to be regulated by a phosphorylation/dephosphorylation pattern shift, we used the 2DE gel methodology and peptide mass fingerprinting-protein identification by means of MALDI-TOF mass spectrometry. We show that gastric mucosa GRp58 is dephosphorylated by fasting, and this effect is blunted when fasted rats are treated with leptin. Furthermore, we assessed the gene expression of GRp58 under different physiological settings known to be associated with energy homeostasis (fasting, leptin treatment and leptin deficiency). We found that intraperitoneal administration of leptin increases whereas leptin deficiency decreases GRp58 mRNA levels. However, GRp58 expression remains unchanged after fasting, indicating that leptin actions on GRp58 are no direct sensitivity to fasting. Dissection of the molecular pathways mediating the interactions between ER stress-related factors and nutrient availability, as well as their target genes, may open a new avenue for the study of obesity and other metabolic disorders.

Hypothalamic AMP-activated protein kinase as a mediator of whole body energy balance.

The AMP-activated protein kinase (AMPK) is the downstream constituent of a kinase cascade that acts as a sensor of cellular energy levels. Current data unequivocally indicate that hypothalamic AMPK plays a key role in the control of the whole body energy balance, by integrating peripheral signals, such as hormones and metabolites, with central signals, such as neuropeptides, and eliciting allostatic changes in energy homeostasis. Although the molecular details of these interactions are not fully understood, recent evidence has suggested that the interaction between AMPK with hypothalamic lipid metabolism and other metabolic sensors, such as the uncoupling protein 2 (UCP-2), the mammalian target of rapamycin (mTOR) and the deacetylase sirtuin 1 (SIRT1), may play a main role in the hypothalamic control of feeding and energy expenditure. Here, we summarize the role of hypothalamic AMPK as whole body energy gauge. Understanding this key molecule and especially its functions at central level may provide new therapeutic targets for the treatment of metabolic alterations and obesity.

AMP-activated protein kinase: 'a cup of tea' against cholesterol-induced neurotoxicity.

Disturbances in brain cholesterol metabolism have been linked to Alzheimer's disease (AD) pathology. A high-cholesterol diet increases fibrillar amyloid ß peptide (Aß) deposition, inflammation, and apoptosis that eventually results in neurodegeneration and learning and memory impairments. In the October 2010 issue of The Journal of Pathology, Lu and colleagues provided a novel and interesting mechanism that explains how quercetin, a flavonoid found at high concentrations in green and black teas, may help to protect against cholesterol-induced neurotoxicity through activation of AMP-activated protein kinase (AMPK), a metabolic energy gauge. Further work will be necessary to address whether AMPK may be a potential target to combat neurodegenerative diseases.

Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

Artrogriposis múltiple congénita: presentación de un caso / Congenital múltiple arthrogryposis: case presentation

La artrogriposis múltiple congênita - AMC, es la presencia de contracturas en las articulaciones en el nacimiento, que tiene su origen durante el periodo de gestación, produciendo deformidades osteomioarticular. Foi aplicado un Programa Neurorrestaurativo durante 28 dias numa nina de 4 anos con retardo del desarrollo