Preventing facial pressure ulcers in patients under non-invasive mechanical ventilation: a randomised control trial.

OBJECTIVE: To comparatively assess the efficacy of four different therapeutic strategies to prevent the development of facial pressure ulcers (FPUs) related to the use of non-invasive mechanical ventilation (NIV) with oro-nasal masks in critically ill hospitalised patients. METHOD: This randomised control trial was performed at the high dependency unit in the University General Hospital Gregorio Marañón in Madrid, Spain. Overall, 152 patients with acute respiratory failure were recruited. All patients were hospitalised and received NIV through oro-nasal masks. The Norton tool was used to evaluate the general risk of developing pressure ulcers (PUs). Subjects were divided into four groups, each of them receiving a different treatment. Tissue assessment and preventive care were performed by a member of the research team. RESULTS: The incidence of FPUs was significantly lower in the group receiving a solution of hyperoxygenated fatty acids (HOFA) when compared with each of the other therapeutic strategies: direct mask (p=0.055), adhesive thin dressing (p=0.03) and adhesive foam dressing (p<0.001). CONCLUSION: The application of HOFA on the facial skin in contact with the oro-nasal masks showed the highest efficacy in the prevention of NIV-related FPUs.

Real world comparison of the MGuard Stent versus the bare metal stent for ST elevation myocardial infarction (the REWARD-MI study).

AIM: The MGuard Stent (MGS) was designed to prevent distal embolization of thrombus and has been shown to improve microcirculation in ST-elevation myocardial infarction (STEMI). However, there are no real world data comparing it with the bare metal stent (BMS). The aim of this study is to determine the efficacy and safety of the MGS in STEMI in the real world compared to the BMS. METHODS AND RESULTS: In total, 262 patients were included from a single centre, of which 35.9% had an MGS implanted. Two groups of 79 patients were established after propensity score matching, and they were similar in terms of baseline and periprocedural variables. The mean follow-up was 321 ± 12.94 days. There was no difference in mortality (7.6% in both groups), major adverse cardiac events (20.3% vs. 12.7%, P = 0.198), non-cardiac mortality, or non-fatal myocardial infarction (6.3% in both groups). Target lesion revascularization (TLR) was significantly higher in the MGS group (11.4% (9) vs. 1.3% (1) P < 0.01; RR 10.02 [1.23-81.16]). CONCLUSION: Our study is the first to compare the MGS with the BMS in STEMI in the real world, and it also appears to confirm that although the MGS is a safe device in STEMI that is not associated with increased mortality, it is associated with a higher long-term TLR rate. © 2014 Wiley Periodicals, Inc.

Expression of proliferative markers in ameloblastomas and malignant odontogenic tumors.

OBJECTIVE: To compare the proliferative activity in ameloblastoma and malignant odontogenic tumors, as assessed by Ki-67 immunostaining and determine whether expression of substance P (SP) and NK-1 receptor (NK-1R) is related to cell proliferation in these tumors. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate protein expression in 44 benign and malignant odontogenic tumors from 39 patients. Immunohistochemistry was performed with anti-SP, anti-NK-1R, and anti-Ki-67 monoclonal antibodies, and the clinical and pathological data of the patients with odontogenic tumor were evaluated. RESULTS: Expression of Ki-67 in malignant odontogenic tumors was significantly higher than in ameloblastomas (P < 0.001), and the expression level was associated with higher expression of NK-1R. Among the ameloblastomas, there was significantly higher expression of Ki-67 in peripheral ameloblastic-like cells (3.3 ± 4.1) than in stellate reticulum-like cells (2.6 ± 3.7) (P = 0.04). In the majority of tissue locations of the malignant tumors, expression of SP and NK-1R was positively correlated with higher expression of Ki-67. CONCLUSION: These findings show that the expression level of Ki-67 in ameloblastomas was positively correlated with the rate of growth of odontogenic tumors. Overexpression of NK-1R complex in malignant odontogenic tumors could be part of the trigger stimulus that results in higher proliferative activity of the tumor.

[Risk factors associated with SARS-CoV-2 infection among health professionals in Spain].

BACKGROUND: Occupational infection rates for SARS-CoV-2 among health professionals in Spain are high in comparison to other countries. The objective of the study was to describe and analyze the risk factors associated with this transmission. METHODS: Cross-sectional study with non-probabilistic snowball sampling of health professionals (medicine, nursing, physiotherapy, auxiliary care) of different levels of care (primary care, hospital, nursing homes, etc.), who were in contact or not with patients with COVID-19, in June 2020 in Spain. We prepared an electronic survey of 81 questions structured in four blocks: sociodemographic variables, knowledge about COVID-19, availability and use of personal protective equipment (PPE), and environmental protection measures and training received. RESULTS: 855 health workers responded, 81.5% women and the mean age was 44 years (28-68). 93.4% knew the main symptoms but 40.4% did not identify the route of transmission via droplets and contact. 67.5% of them cared for COVID-19 patients without adequate PPE and 29.1% wore the same PPE continuously for more than 4 hours. 25.6% of workers had not received any type of training in donning and removing the PPE and 61.2% of them were unable to previously practice the process. The frequency of coronavirus infection among health professionals was 19.4%, which is higher in those professionals who had not received specific training (25.8 vs 17.2%, p=0.009). CONCLUSION: Training, drafting protocols and screening programs, supervising the situations of greatest risk, ensuring the availability of material and increasing the commitment of health institutions to support health personnel should be implemented as contagion prevention strategies.

Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth.

The growth of A-1 fibroblasts depends on exogenous amyloid beta/A4 protein precursor (APP), providing a simple bioassay to study the function of APP. Our preliminary study, testing the activity of a series of fragments derived from the secreted form of APP-695 (sAPP-695) on this bioassay, has shown that at least one of the active sites of sAPP-695 was localized within a 40-mer sequence (APP296-335, Kang sequence; Roch, J.-M., I. P. Shapiro, M. P. Sundsmo, D. A. C. Otero, L. M. Refolo, N. K. Robakis, and T. Saitoh. 1992. J. Biol. Chem. 267:2214-2221). In the present study, to further characterize the growth-promoting activity of sAPP-695 on fibroblasts, we applied a battery of synthetic peptides on this bioassay and found that: (a) the sequence of five amino acids, RERMS (APP328-332), was uniquely required for the growth-promoting activity of sAPP-695; (b) the activity was sequence-specific because the reverse-sequence peptide of the active domain had no activity; and (c) the four-amino-acid peptide RMSQ (APP330-333), which partially overlaps the COOH-terminal side of the active sequence RERMS, could antagonize the activity of sAPP-695. Furthermore, a recombinant protein which lacks this active domain (APP20-591 without 306-335) did not promote fibroblast cell growth, suggesting that this domain is the only site of sAPP-695 involved in the growth stimulation. The availability of these biologically active, short peptides and their antagonists should prove to be an essential step for the elucidation of APP involvement in regulation of cellular homeostasis.

[Myocardial revascularization in patients with chronic renal failure]. / Revascularización miocárdica en pacientes con insuficiencia renal crónica.

The incidence of chronic renal failure has increased in the last years in industrialized countries. In Spain the prevalence of this pathology is estimated at 10-12% of the population, and the stages III-V of the disease, corresponding to the estimated glomerular filtration rate less than 60 ml/min/m2, represent the 5%. From the cardiovascular point of view, both chronic and acute coronary syndrome is a very important subgroup of patients because of the increased association between chronic renal failure and coronary artery disease. In fact, ACS is the main cause of death in patients with advanced chronic renal failure. Frequently, this kind of patients are excluded from prospective randomized clinical trials, consequently scientific evidence is not available to guide the therapy of coronary revascularization.

Percutaneous endovascular treatment of an iatrogenic superior cava vein syndrome during the immediate post-operative period after mitral-aortic valve replacement. / Tratamiento endovascular percutáneo de un síndrome de vena cava superior en el postoperatorio inmediato de recambio valvular mitroaórtico.

Superior vena cava syndrome (SVCS) results from superior vena cava obstruction, causing a decrease in venous return from the head, neck, and upper extremities. Although the most frequent cause is still malignant tumour processes, in recent years an increase has been observed in non-tumour causes, such as thrombosis of intravascular devices or iatrogenic causes during cardiac surgery. A case is presented of SVCS after cardiac surgery treated satisfactorily by an endovascular technique and systemic anticoagulation.

Actuación de enfermería en el infarto cerebral agudo / Nursing performance in acute cerebral stroke

La enfermedad vascular cerebral (EVC) es una patología caracterizada por un déficit neurológico súbito, secundario a oclusión o ruptura de un vaso sanguíneo cerebral; se divide en isquémica o infarto cerebral (IC) y hemorrágica. La EVC es reconocida como la primera causa de discapacidad y la quinta causa de muerte en México, registrándose cerca de 170 mil casos nuevos al año. Existe amplia evidencia que demuestra una reducción en los desenlaces negativos, como muerte y discapacidad, al realizar intervenciones rápidas, incluyendo la administración de trombolisis intravenosa con rt-PA (activador tisular de plasminógeno recombinante) y trombectomía mecánica. La coordinación multidisciplinaria del equipo de salud y los cuidados efectivos de enfermería, son vitales durante todas las etapas de atención de la EVC. Esta revisión da a conocer un panorama general del manejo del infarto cerebral e identificar las intervenciones indispensables del profesional de enfermería realiza durante las etapas prehospitalarias, pretrombolisis, durante trombolisis y postrombolisis.

Cerebralvascular disease (CVD) is a pathology characterized by a sudden neurological deficit secondary to occlusion or rupture of a cerebral blood vessel; it is divided into ischemic or cerebral infarction (CI) and hemorrhagic. CVD is recognized as the first cause of disability and the fifth cause of death in Mexico, with nearly 170,000 new cases registered each year. There is ample evidence that shows a reduction in negative outcomes, such as death and disability, with rapid interventions, including the administration of intravenous thrombolysis with rt-PA (recombinant tissue plasminogen activator) and mechanical thrombectomy. Multidisciplinary coordination of the health care team and effective nursing care are vital during all stages of CVD care. This review provides an overview of the management of cerebral infarction and identifies essential nursing interventions during the prehospital, prethrombolysis, during thrombolysis, and postthrombolysis stages.

Long-term changes in glutamatergic synaptic transmission in phenylketonuria.

The cellular mechanisms that underlie impaired brain function during phenylketonuria (PKU), the most common biochemical cause of mental retardation in humans, remain unclear. Acute application of L-Phe at concentrations observed in the PKU brain depresses glutamatergic synaptic transmission but does not affect GABA receptor activity in cultured neurons. If these depressant effects of L-Phe take place in the PKU brain, then chronic impairment of the glutamate system, which may contribute to impaired brain function, could be detected as changes in postsynaptic glutamate receptors. This hypothesis was tested by using a combination of liquid chromatography-mass spectrometry, patch-clamp, radioligand binding and western blot approaches in forebrain tissue from heterozygous and homozygous (PKU) Pah(enu2) mice. Brain concentrations of L-Phe were nearly six-fold greater in PKU mice (863.12 +/- 17.96 micromol/kg) than in their heterozygous counterparts (149.32 +/- 10.23 micromol/kg). This concentration is significantly higher than the K(B) of 573 microM for L-Phe to compete for N-methyl-D-aspartate (NMDA) receptors. Receptor binding experiments with [3H]MK-801 showed significant up-regulation of NMDA receptor density in PKU mice. Consistent with the depressant effects of L-Phe, expression of NMDA receptor NR2A and (RS)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor Glu1 and Glu2/3 subunits was significantly increased, whereas expression of the NR2B subunit was decreased. There was no change in GABA alpha1 subunit expression. Given the role of the glutamatergic system in brain development and function, these changes may, at least in part, explain the brain disorders associated with PKU.

Atención del paciente con EPOC mediante un programa de e-salud / E-health for copd patients

La e-salud, apoyada en el uso de las nuevas tecnologías, nos da las herramientas necesarias para innovar en la asistencia a nuestros pacientes y ha permitido evolucionar el concepto de la relación profesional sanitario-paciente. Sus aplicaciones son prácticamente ilimitadas y los estudios avalan su eficacia, si bien, existen una serie de cuestiones que limitan su implementación real (dificultad para la comparación metodológica, factores asociados al profesional o al paciente, aspectos éticos y legales, etc.). Una de las aplicaciones más interesantes desde el punto de vista clínico es la tele-consulta, especialmente en la actual situación de pandemia por la COVID-19. En este trabajo revisamos las posibilidades de implementación de un programa de tele-consultas en pacientes con EPOC, la selección de candidatos, las posibles herramientas tecnológicas y las limitaciones de este tipo de programas (AU)

E-health using new technologies is a new way to attend our patients and creates a new scenario in the relation between patients and their health carers. Their applications are uncontable and many articles support their efficacy, although some questions still make difficult its implementation. One of the most interesting applications for clinicians is teleconsultation, specially nowadays with COVID pandemic. We review the possible implementation of a tele-consultation program for COPD patients, the right selection of patients, technological tools and its limitations (AU)

Factores de riesgo asociado a la infección por SARS-CoV-entre los profesionales sanitarios de España / Risk factors associated with SARS-CoV-2 infection among health professionals in Spain

Fundamento: Las tasas de contagio ocupacional porSARS-CoV-2 entre profesionales sanitarios en España sonelevadas respecto a otros países. El objetivo del estudio fuedescribir y analizar los factores de riesgo asociados a estatransmisión. Material y métodos: Estudio transversal con muestreo noprobabilístico en bola de nieve de profesionales sanitarios(medicina, enfermería, fisioterapia, cuidados auxiliares) dediferentes niveles asistenciales (atención primaria, hospitalaria, sociosanitaria u otra), en contacto o no con pacientescon COVID-19 en junio de 2020 en España. Se elaboró unaencuesta electrónica de 81 preguntas estructurada en cuatro bloques: variables sociodemográficas, conocimientossobre COVID-19, disponibilidad y uso de equipos de protección individual (EPI), y medidas de protección del entornoy formación recibida. Resultados: Respondieron 855 sanitarios, 81,5% mujeres,edad media 44años (28-68). El 93,4% conocía los principalessíntomas pero el 40,4% no identificó la vía transmisión por gotas y contacto. El 67,5% atendieron a pacientes con COVID-19sin EPI adecuado y el 29,1% usó el mismo EPI de manera continuada más de 4 horas. El 25,6% no había recibido formaciónsobre colocación y retirada del EPI y el 61,2% no pudo practicar previamente el proceso. El 19,4% sufrió infección porcoronavirus, más frecuente en profesionales que no habíanrecibido formación específica (25,8 vs 17,2%, p = 0,009). Conclusión: Como estrategias de prevención de contagiose deben implementar la formación, redactar protocolos yprogramas de cribado, supervisar las situaciones de mayorriesgo, asegurar la disponibilidad de material, y aumentarel compromiso de las instituciones sanitarias para apoyaral personal sanitario.(AU)

Background: Occupational infection rates for SARS-CoV-2among health professionals in Spain are high in comparison to other countries. The objective of the study was todescribe and analyze the risk factors associated with thistransmission. Methods: Cross-sectional study with non-probabilisticsnowball sampling of health professionals (medicine, nursing, physiotherapy, auxiliary care) of different levels ofcare (primary care, hospital, nursing homes, etc.), whowere in contact or not with patients with COVID-19, inJune 2020 in Spain. We prepared an electronic survey of81 questions structured in four blocks: sociodemographicvariables, knowledge about COVID-19, availability and useof personal protective equipment (PPE), and environmentalprotection measures and training received. Results: 855 health workers responded, 81.5% women and themean age was 44 years (28-68). 93.4% knew the main symptoms but 40.4% did not identify the route of transmission viadroplets and contact. 67.5% of them cared for COVID-19 patients without adequate PPE and 29.1% wore the same PPEcontinuously for more than 4 hours. 25.6% of workers had notreceived any type of training in donning and removing thePPE and 61.2% of them were unable to previously practicethe process. The frequency of coronavirus infection amonghealth professionals was 19.4%, which is higher in thoseprofessionals who had not received specific training (25.8 vs17.2%, p = 0.009). Conclusion: Training, drafting protocols and screening programs, supervising the situations of greatest risk, ensuringthe availability of material and increasing the commitmentof health institutions to support health personnel should beimplemented as contagion prevention strategies.(AU)

Medidas de protección individual y colectiva en la COVID-19 / Individual and collective protection measures in COVID-19

Las vías de transmisión del SARS-CoV-2 aún no están claras, siendo seguro su contagio por contacto y gotas. Los equipos de protección individual (EPI) deben ser utilizados de forma completa y correcta para disminuir el contagio entre los profesionales sanitarios, sin olvidar las medidas básicas de protección, prevención, aislamiento de los casos confirmados y cuarentena de sus contactos estrechos hasta determinar su diagnóstico. No hay que minimizar esfuerzos en realizar compañas publicitarias en educación sanitaria a fin de favorecer el correcto uso y adherencia de la sociedad a las medidas de prevención, destinando recursos humanos y materiales proporcionados para favorecer el control de la transmisión y romper las rutas de contagio conocidas

The routes of transmission of SARS-CoV-2 are not yet clear, being contagious by contact and drops. Personal protective equipment (PPE) must be used completely and properly to reduce contagion among healthcare professionals, without forgetting the basic measures of protection, prevention, isolation of confirmed cases and quarantine of their close contacts until their diagnosis is determined. Efforts should not be minimized in carrying out publicity campaigns in health education in order to favor the correct use and adherence of society to prevention measures, allocating human and material resources provided to favor the control of transmission and break known routes of contagion

Fully automatic rhythm analysis during chest compression pauses.

AIM: Chest compression artefacts impede a reliable rhythm analysis during cardiopulmonary resuscitation (CPR). These artefacts are not present during ventilations in 30:2 CPR. The aim of this study is to prove that a fully automatic method for rhythm analysis during ventilation pauses in 30:2 CPR is reliable an accurate. METHODS: For this study 1414min of 30:2 CPR from 135 out-of-hospital cardiac arrest cases were analysed. The data contained 1942 pauses in compressions longer than 3.5s. An automatic pause detector identified the pauses using the transthoracic impedance, and a shock advice algorithm (SAA) diagnosed the rhythm during the detected pauses. The SAA analysed 3-s of the ECG during each pause for an accurate shock/no-shock decision. RESULTS: The sensitivity and PPV of the pause detector were 93.5% and 97.3%, respectively. The sensitivity and specificity of the SAA in the detected pauses were 93.8% (90% low CI, 90.0%) and 95.9% (90% low CI, 94.7%), respectively. Using the method, shocks would have been advanced in 97% of occasions. For patients in nonshockable rhythms, rhythm reassessment pauses would be avoided in 95.2% (95% CI, 91.6-98.8) of occasions, thus increasing the overall chest compression fraction (CCF). CONCLUSION: An automatic method could be used to safely analyse the rhythm during ventilation pauses. This would contribute to an early detection of refibrillation, and to increase CCF in patients with nonshockable rhythms.

The L2 loop peptide of RecA stiffens and restricts base motions of single-stranded DNA similar to the intact protein.

The L2 loop in the RecA protein is the catalytic center for DNA strand exchange. Here we investigate the DNA binding properties of the L2 loop peptide using optical spectroscopy with polarized light. Both fluorescence intensity and anisotropy of an etheno-modified poly(dA) increase upon peptide binding, indicate that the base motions of single-stranded DNA are restricted in the complex. In agreement with this conclusion, the peptide-poly(dT) complex exhibits a significant linear dichroism signal. The peptide is also found to modify the structure of double-stranded DNA, but does not denature it. It is inferred that strand separation may not be required for the formation of a joint molecule.

Reduction in glucose levels in STZ diabetic rats by 4-(2,2-dimethyl-1-oxopropyl)benzoic acid: a prodrug approach for targeting the liver.

The overproduction of glucose by the liver in NIDDM patients markedly contributes to their fasting hyperglycemia and is a direct consequence of the increased oxidation of excess free fatty acids (FFA) being released from the adipocyte. 2-(1,1-Dimethylethyl)-2-(4-methylphenyl)[1,3]dioxolane (SAH51-641, 1) has previously been demonstrated to reduce glucose levels in animal models of diabetes by reducing fatty acid oxidation and hence depriving the system of the energy and cofactors necessary for gluconeogenesis. However, attempts at lowering glucose levels in vivo with 1 have been associated with toxicity in other organs such as the testes. An approach was developed utilizing the natural processing of triglyceride-like intermediates as a basis for selectively targeting the absorption, processing, and delivery of a prodrug to the liver. Compounds were identified by this method which lowered glucose levels in vivo without releasing toxic amounts of the active metabolites of 1 into circulation.

Hypoglycemic prodrugs of 4-(2,2-dimethyl-1-oxopropyl)benzoic acid.

SAH 51-641 (1) is a potent hypoglycemic agent, which acts by inhibiting hepatic gluconeogenesis. It is a prodrug of 4-(2, 2-dimethyl-1-oxopropyl)benzoic acid (2) and 4-(2, 2-dimethyl-1-hydroxypropyl)benzoic acid (3), which sequester coenzyme A (CoA) in the mitochondria, and inhibits medium-chain acyltransferase. 1-3 and 4-tert-butylbenzoic acid all cause testicular degeneration in rats at pharmacologically active doses. 14b (FOX 988) is a prodrug of 3, which is metabolized in the liver at a rate sufficient enough to have hypoglycemic potency (an ED50 of 65 micromol/kg, 28 mg/kg/day, for glucose lowering), yet by avoiding significant escape of the metabolite 3 to the systemic circulation, it avoids the testicular toxicity at doses up to 1500 micromol/kg/day. 14b was selected for clinical studies.

Irreversible binding of a carbostyril-based agonist and antagonist to the beta-adrenoceptor in DDT1 MF-2 cells and rat aorta.

1. The chemoreactive ligands 5(2-(((1'-(4'-isothiocyanatophenylamino)thiocarbonyl)-amino) -2-methylpropyl)amino-2-hydroxypropoxy)-3,4-dihydrocarbostyril (DCITC) and 8-hydroxy-5(2-(((1'-(4'-isothiocyanatophenylamino)thiocarbonyl+ ++)amino)-2-methylprop-2-yl)amino-1-hydroxyethyl)-carbostyril++ + (HCITC) were synthesized and shown to be potent irreversible antagonist and agonist ligands, respectively, for the beta-adrenoceptor in DDT1 MF-2 (DDT) cells and the rat isolated aorta. 2. In DDT cell membranes DCITC and HCITC inhibited (-)[125I]-iodocyanopindolol (CYP) binding to the beta-adrenoceptor with IC50 values of 1.1 and 18 nM, respectively. (-)-Isoprenaline inhibited [125I]-CYP binding with an IC50 of 355 nM. Pretreatment of membranes with either chemoreactive ligand produced a time- and concentration-dependent decrease in the beta-adrenoceptor content, indicating irreversible receptor binding. DCITC at concentrations up to 10 microM did not stimulate cyclic AMP accumulation in DDT cells nor did it amplify forskolin-stimulated cyclic AMP accumulation. 3. In the rat isolated aorta, DCITC (0.1 microM) did not affect either the phenylephrine-mediated tissue contraction or the acetylcholine-mediated relaxation. DCITC attenuated the maximal (-)-isoprenaline-mediated relaxation of a phenylephrine contracted aorta in a concentration-dependent manner and shifted the dose-response curves for (-)-isoprenaline to the right. The DCITC-induced decrease in maximal response was not reversed by extensive tissue washing. By use of the operational model of agonism, the calculated dissociation constant for (-)-isoprenaline ws 286 nM and the estimated receptor reserve for this agonist was 23% at the maximal response. 4. HCITC and (-)-isoprenaline stimulated cyclic AMP accumulation in DDT cells with pD2 values (negative logarithm to base 10 of EC50) of 7.95 and 7.97, respectively, and both mediated the same maximal stimulation. In the rat isolated aorta, HCITC produced a concentration-dependent relaxation of the tissue with a pD2 value of 6.62, whereas the pD2 for (-)-isoprenaline was 7.03. However, HCITC produced a greater maximal relaxation of the tissue than (-)-isoprenaline. The HCITC-mediated stimulation of cyclic AMP accumulation and relaxation of the isolated tissue were blocked when the beta-antagonist propranolol was added concurrently. In contrast, once the HCITC-mediated responses were established, the addition of propranolol did not result in any attenuation indicating that HCITC is an irreversible beta-agonist.

Inspiratory muscle training in patients with COPD: effect on dyspnea, exercise performance, and quality of life.

OBJECTIVE: The aim of the study was to assess the effect of target-flow inspiratory muscle training (IMT) on respiratory muscle function, exercise performance, dyspnea, and health-related quality of life (HRQL) in patients with COPD. PATIENTS AND METHODS: Twenty patients with severe COPD were randomly assigned to a training group (group T) or to a control group (group C) following a double-blind procedure. Patients in group T (n = 10) trained with 60 to 70% maximal sustained inspiratory pressure (SIPmax) as a training load, and those in group C (n = 10) received no training. Group T trained at home for 30 min daily, 6 days a week for 6 months. MEASUREMENTS: The measurements performed included spirometry, SIPmax, inspiratory muscle strength, and exercise capacity, which included maximal oxygen uptake (VO(2)), and minute ventilation (VE). Exercise performance was evaluated by the distance walked in the shuttle walking test (SWT). Changes in dyspnea and HRQL also were measured. RESULTS: Results showed significant increases in SIPmax, maximal inspiratory pressure, and SWT only in group T (p < 0.003, p < 0.003, and p < 0.001, respectively), with significant differences after 6 months between the two groups (p < 0.003, p < 0.003, and p < 0.05, respectively). The levels of VO(2) and VE did not change in either group. The values for transitional dyspnea index and HRQL improved in group T at 6 months in comparison with group C (p < 0.003 and p < 0.003, respectively). CONCLUSIONS: We conclude that targeted IMT relieves dyspnea, increases the capacity to walk, and improves HRQL in COPD patients.

Neuroprotective effect of retro-inverso Prosaptide D5 on focal cerebral ischemia in rat.

Prosaposin (the precursor of saposins A-D) has been identified as a neurotrophic factor in vitro and in vivo. In this study, a novel 11-mer retro-inverso peptidomimetic, Prosaptide D5, was injected i.m. to assess its effectiveness in a rat ischemic model produced by reversible total occlusion of the left middle cerebral artery (MCA). Prosaptide (300 microg/kg, i.m.) injected 3 h after reversible occlusion reduced brain infarct area by 56% compared with a saline group (p < 0.01) at 21 h of reperfusion. A similar injection of D5 6h after occlusion produced a 32% decrease.

Effects of 4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid (AH5183) on rat cortical synaptosome choline uptake, acetylcholine storage and release.

The cholinergic vesicular uptake blocker, 4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid (AH5183), had several effects on presynaptic cholinergic function that depended on the duration of treatment and dose. The synthesis, storage and release of newly synthesized [3H]ACh were monitored because the vesicular uptake of this pool of transmitter may be preferentially affected by the drug. Initially, high concentrations of AH5183 (over 10 microM) increased the spontaneous release but decreased the K+ depolarization-induced release of newly synthesized transmitter. [3H]Choline efflux was not altered by the drug. High affinity choline uptake was slightly (10-20%) inhibited by AH5183 in an apparently competitive but time-dependent manner. In contrast to its initial effects on [3H]ACh release, AH5183 (50nM-100 microM) very potently inhibited both the spontaneous and K+-induced release of [3H]ACh but not of [3H]choline after a 60 min preincubation. [3H]ACh levels in cytoplasmic (S3) and crude membrane (P3) fractions were not affected by a 2-min incubation with 10 microM AH5183. After a 60-min preincubation with this drug dose, however, the P3 and S3 levels of newly synthesized transmitter were decreased and increased, respectively. Subsequent fractionation of synaptosomes by sucrose-density gradient centrifugation revealed that these reductions in P3 [3H]ACh-levels were referable to reductions in two subfractions D and H that have been reported to contain low density vesicles and denser vesicles associated with plasma membranes, respectively.