J.A. Lorente

Aging increases the susceptibility to injurious mechanical ventilation

ObjectiveTo test the hypothesis that aging increases the susceptibility to organ dysfunction and systemic inflammation induced by injurious mechanical ventilation.Design and settingExperimental study in an animal model of ventilator-induced lung injury in the animal research laboratory in axa0university hospital.MethodsYoung (3–4u202fmonths old) and old (22–24u202fmonths old) anesthetized Wistar rats were ventilated for 60u202fmin with axa0protective lung strategy (VTu202f=u202f9u202fml/kg and PEEPu202f=u202f5u202fcm H2O, control) or with an injurious strategy (VTu202f=u202f35u202fml/kg and PEEPu202f=u202f0u202fcm H2O, overventilated; nu202f=u202f6 for each group).Measurements and resultsMean arterial pressure and airway pressures (PAW) were monitored. Arterial blood gases and serum AST, ALT, lactate, and IL-6 were measured. Vascular rings from the thoracic aorta were mounted in organ baths for isometric tension recording. We studied relaxations induced by acetylcholine (10u202fnM–10u202fμM) in norepinehrine-precontracted rings, and contractions induced by norepinephrine (1u202fnM–10u202fμM) in resting vessels. Lungs were examined by light microscopy. Injurious ventilation in young rats was associated with hypoxemia, lactic metabolic acidosis, increased serum AST, hypotension, impairment in norepinephrine and acetylcholine-induced vascular responses ex vivo and hyaline membrane formation. The high-VT induced hypotension, increase in mean PAW, AST, and IL-6, and the impairment in acetylcholine-induced responses were significantly more marked in aged than in young rats.ConclusionsElderly rats showed increased susceptibility to injurious mechanical ventilation-induced pulmonary injury, vascular dysfunction, and systemic inflammation.

Lung histopathological findings in fatal pandemic influenza A (H1N1)

OBJECTIVEnTo describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue.nnnMETHODS AND PATIENTSnLight microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens.nnnRESULTSnAge ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy.nnnCONCLUSIONSnLung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes.

Lesión pulmonar aguda y síndrome de distrés respiratorio agudo: una perspectiva genómica

Genomics have allowed important advances in the knowledge of the etiology and pathogenesis of complex disease entities such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Genomic medicine aims to personalize and optimize diagnosis, prognosis and treatment by determining the influence of genetic polymorphisms in specific diseases. The scientific community must cope with the important challenge of securing rapid transfer of knowledge to clinical practice, in order to prevent patients from becoming exposed to unnecessary risks. In the present article we describe the main concepts of genomic medicine pertaining to ALI/ARDS, and its currently recognized clinical applications.

Kidney histopathological findings in fatal pandemic 2009 influenza A (H1N1)

Dear Editor, A new pandemic was originated by a novel influenza A (H1N1) virus [1– 3]. Severe cases were characterized by acute respiratory distress syndrome (ARDS), shock, and acute kidney injury (AKI) [3]. Lung histopathological changes in fatal cases showed signs of diffuse alveolar damage, necrotizing bronchiolitis, and occasional alveolar hemorrhage [2]. However, histopathological changes in organs other than the lungs are not known. Here we report kidney histopathological findings and describe for the first time the specific kidney cell type targeted by pandemic 2009 influenza A (H1N1) virus infection. With the approval of our Ethics Committee and with closest relative informed consent, renal biopsies from four patients who died in the intensive care unit (ICU) with diagnosis of confirmed influenza A (H1N1) virus infection were studied by microscopy after hematoxylin and eosin (HE), Masson’s or periodic acid-Schiff (PAS) staining. Cell nuclei were revealed by staining with 4’,6-diamidino-2-phenylindole (DAPI). Localization of viral antigen and specific kidney cells was carried out by double immunofluorescence (IF) labeling [4] using antibodies (Santa Cruz) specific for either: (1) aquaporin 1, a marker of proximal tubular cells; (2) CD10, a marker of proximal tubular cells; (3) cytokeratin 7, a marker of distal tubular cells; or (4) CD34, a marker of endothelial cells, and a rabbit antiserum specific for influenza nucleoprotein (NP). This antibody was generated by immunization of rabbits with purified recombinant NP and validated by IF, Western blotting, and immunoprecipitation of control and influenzainfected human cells [5]. This antibody is cross-reactive with several influenza A virus subtypes (data not shown). Secondary antibodies were fluorescein isothiocyanate (FITC)labeled goat anti-mouse immunoglobulin G (IgG) (Santa Cruz) and Alexa 546-conjugated goat anti-rabbit IgG. Sections were studied under confocal microscopy (Leica SP5), and single optical sections are presented. Only cases 3 and 4 were diagnosed with AKI. Cases 3 and 4 had focal changes consistent with acute tubular necrosis (ATN) in the distal tubules (epithelial cell swelling, individual cell necrosis, and shedding of

Determinantes genéticos del riesgo y pronóstico del daño renal agudo: una revisión sistemática

INTRODUCTIONnAcute renal damage (ARD) is a frequent syndrome in hospitalized patients. It is well accepted that ARD susceptibility and outcome are related to environmental risk factors and to the patient premorbid status. Recently, host factors have also been recognized as important in ARD predisposition and evolution.nnnOBJECTIVEnTo analyze genetic influences related to the risk and severity of ARD.nnnDATA SOURCEnMEDLINE search.nnnSELECTION OF STUDIESnarticles published in English or Spanish between 1/1/1995 and 31/5/2011, analyzing the association between genic polymorphisms and (a) ARD susceptibility in patients versus healthy controls or within groups of patients; or (b) ARD severity.nnnEXCLUSION CRITERIAnstudies published only in abstract form, case reports or including patients less than 16 years of age, on chronic dialysis or having received a renal transplant.nnnDATA EXTRACTIONnat least one investigator analyzed each manuscript and collected the information using a predefined form.nnnRESULTSnWe identified 12 relevant studies that included 4835 patients. Eleven genes showed polymorphisms related to ARD susceptibility or severity. They were related to cardiovascular regulation (ACE I/D, eNOS, FNMT and COMT), inflammatory response (TNFα, IL10, IL6, HIP-1α, EPO), oxidative stress (NAPH oxidase) and lipid metabolism (APO E). Only APO E, ACE and AT1 receptor have been analyzed in more than one study.nnnCONCLUSIONnARD susceptibility and severity is influenced by genetic factors, which are multiple and involve different physiopathological mechanisms.

El virus del Ébola: comprendiendo el brote de 2014

Ebola virus (EV) epidemics are not new to Africa. EV was first identified in 1976, the current one being the 25th known outbreak of EV infection.1,2 As of November 28, a total of 16 933 cases have been reported (10 585 laboratory-confirmed), including 6 002 deaths.3 Reported cases are from countries with widespread transmission (16 899 cases in Guinea, Liberia and Sierra Leone); countries with an initial case or limited transmission (4 cases in the US, 8 cases in Mali); and previously affected countries (1 in Senegal, 20 in Nigeria, 1 in Spain, where the outbreaks were declared over on 17 October,19 October, and 2 December 2014, respectively). A national EV disease (EVD) outbreak is considered to be over when twice the 21-day incubation period (42 days) has elapsed since the last patient in isolation became laboratorynegative. The clinical manifestations, illness duration, degree of transmissibility and mortality of EVD in the current epidemics do not differ from those in earlier epidemics. Thus the public health impact of the current outbreak is not due to the biological characteristics of the virus, but rather to a combination of social factors such as deficient health care systems, population mobility, local customs (e.g. traditional burials) and lack of international awareness.1,4 EVD is caused by infection with one of the Ebola virus strains that can cause disease in humans and nonhuman primates (monkeys, gorillas, and chimpanzees). Ebola viruses belong to the Filoviridae family, which are enveloped, nonsegmented, negative-strand RNA viruses and also include Marburgvirus, and “Cuevavirus”. Originally identified in 1976 in Yambuku, Zaire (now the Democratic Republic of Congo), and Nzara, South Sudan, EV (named after a river in Zaire) includes five separate species: Zaire ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus, Sudan ebolavirus, and Reston ebolavirus.5 All known African EVs can infect humans and cause similar symptoms, but they vary in terms of disease progression and virulence. The strain causing the current epidemics in West