- PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window. [Journal Article]
- AAutophagy 2017 Jan 19; :0
- Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a...
Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons. Inhibition of mitophagy compromises neuroprotection conferred by APC. Furthermore, mitophagy and neuroprotection are abolished in Park2 knockout mice, indicating that APC-induced mitophagy is facilitated by the recruitment of PARK2 to mitochondria. Importantly, in MCAO mice, APC treatment extended the effective reperfusion window from 2 to 4 h, and this window was further extended to 6 h by exogenously expressing PARK2. Taken together, we found that PARK2-dependent APC-induced mitophagy renders the brain resistant to ischemic injury. APC treatment could be a favorable strategy to extend the thrombolytic time window for stroke therapy.
- Strategies to Prevent Cast Formation in Patients with Plastic Bronchitis Undergoing Heart Transplantation. [Journal Article]
- PCPediatr Cardiol 2017 Jan 19
- Plastic bronchitis, a rare complication after Fontan palliation, carries a high morbidity and mortality risk. Heart transplantation is an effective treatment option, but casts may occur in the early ...
Plastic bronchitis, a rare complication after Fontan palliation, carries a high morbidity and mortality risk. Heart transplantation is an effective treatment option, but casts may occur in the early post-operative period. We present a case series detailing peri-operative management strategies to minimize morbidity and mortality related to plastic bronchitis in patients undergoing heart transplantation. Patient 1 received no treatment pre-, intra-, or post-transplant for prevention of bronchial casts and developed severe respiratory acidosis 18 h following transplant. Emergent bronchoscopy was performed and a large obstructive cast was removed. The patient recovered and received inhaled tissue plasminogen activator (tPA) for 5 days. Patient 2 received inhaled tPA before, during, and for 5 days after transplantation and no bronchial casts developed. Patient 3 underwent intraoperative bronchoscopy just prior to implantation revealing no casts. The patient underwent non-urgent, preemptive bronchoscopy on post-transplant days 1, 3, and 4, removing several partially obstructive bronchial blood clots/casts, with no casts thereafter. Heart transplantation results in eventual resolution of plastic bronchitis. Residual bronchial casts can still be problematic in the peri-operative period. Airway clearance with inhaled tPA or bronchoscopy may prevent the need for prolonged mechanical ventilation and reduce post-operative morbidity in this unique population.
- Novel predictive biomarkers for cervical cancer prognosis. [Journal Article]
- MCMol Clin Oncol 2016; 5(6):792-796
- High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the prese...
High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets.
- Sepsis-related acute respiratory distress syndrome in children with cancer: the respiratory dynamics of a devastating condition. [Journal Article]
- RBRev Bras Ter Intensiva 2016 Oct-Dec; 28(4):436-443
- CONCLUSIONS: In most of our children with cancer, sepsis and acute respiratory distress syndrome progressed with deteriorating ventilation indexes and escalating organic dysfunction, making this triad nearly fatal in children.
- The evaluation of the relationship between serum levels of Interleukin-6 and Interleukin-10 and metabolic acidosis in hemodialysis patients. [Journal Article]
- SJSaudi J Kidney Dis Transpl 2017 Jan-Feb; 28(1):23-29
- Chronic kidney disease is defined as progressive kidney dysfunction. The levels of various cytokines increase in hemodialysis (HD) patients. High levels of interleukins (ILs) and presence of metaboli...
Chronic kidney disease is defined as progressive kidney dysfunction. The levels of various cytokines increase in hemodialysis (HD) patients. High levels of interleukins (ILs) and presence of metabolic acidosis are described as independent risk factors for morbidity and mortality in these patients. This study was designed to evaluate the relationship between IL-6 and IL-10 and serum bicarbonate and metabolic acidosis in HD patients. In this analytical crosssectional study, patients referred to the HD units of Loghman Hakim and Shahid Ashrafi Esfahani Hospitals were randomly selected. Demographic and laboratory data, such as albumin, creatinine, calcium, phosphorus, parathormone, C-reactive protein, complete blood count, ferritin, ILs-6 and -10, and arterial blood gas analysis, were recorded for each patient. The correlation between IL and serum bicarbonate and other variables were evaluated by SPSS software. The patients were compared for the presence of acidosis and positivity for IL. A total of 84 patients with a mean age of 60.98 years and mean body mass index of 24.86 kg/m were evaluated (53% male and 57% female). The mean dialysis duration was 24.86 ± 3.98 months. Overall, 41.7% of the patients had diabetes mellitus and 36.9% of them had hypotension. The mean serum levels of IL-6 and IL-10 were 6.036 and 17.46 pg/ml, respectively. There was a significant correlation between IL-6 and IL-10 levels and serum bicarbonate and the incidence of metabolic acidosis (P <0.05). Based on the results, metabolic acidosis and bicarbonate could be considered prognostic factors to differentiate the increased levels of IL-6 and IL-10 and associated morbidity and mortality.
- [A regenerative anemia in infants: 2 cases of Pearson´s syndrome]. [Case Reports]
- AAArch Argent Pediatr 2017 02 01; 115(1):e24-e27
- Anemia is very common in infants. Although its causes are usually not severe and treatable, proper etiologic diagnosis should be established. When anemia is non-regenerative, it can be caused by apla...
Anemia is very common in infants. Although its causes are usually not severe and treatable, proper etiologic diagnosis should be established. When anemia is non-regenerative, it can be caused by aplastic anemia, myelodysplastic syndrome, bone marrow infiltration or hematopoietic factors deficiencies. Another possible cause is Pearson's syndrome, a rare mitochondrial disease that causes non-regenerative anemia associated with other cytopenias, pancreatic insufficiency, lactic acidosis and great variability in clinical presentation conditioned by heteroplasmy. It is characteristic to find in bone marrow studies variable vacuolization in erythroblastic progenitors and ring sideroblasts. The diagnosis is established by genetic study of mitochondrial deoxyribonucleic acid performed by Southern blot analysis (complete mitochondrial deoxyribonucleic acid amplification by polymerase chain reaction -long), obtaining 70-80% deletion of 4977 bp (NMD 8343-13459). There is no curative therapy and support treatment is the only available nowadays. Death is frequent in early years of life.
- Disseminated adenovirus infection causing severe ARDS. [Journal Article]
- BCBMJ Case Rep 2017 Jan 17; 2017
- A previously healthy young man with a rare genetic condition presented with severe acute respiratory distress syndrome secondary to pneumonia with septic shock. He did not improve with conventional t...
A previously healthy young man with a rare genetic condition presented with severe acute respiratory distress syndrome secondary to pneumonia with septic shock. He did not improve with conventional therapy for his known causal organism thus prompting further workup. He was found to be profoundly immunosuppressed raising our suspicion for atypical organisms. A bronchoalveolar lavage sample was positive via PCR for adenovirus which we suspect exacerbated a pre-existing bacterial pneumonia and led to a severe and non-responsive respiratory failure. His serum adenovirus load was markedly elevated. Treatment was started once the diagnosis of disseminated adenovirus infection was made; however, at that time patient was suffering from refractory hypoxaemia, respiratory acidosis, right heart failure and septic shock. Despite maximal supportive measures our patient ultimately expired over the course of 6 days.
- Non-invasive respiratory support for infants with bronchiolitis: a national survey of practice. [Journal Article]
- BPedBMC Pediatr 2017 Jan 17; 17(1):20
- CONCLUSIONS: Despite lack of randomised trial evidence, nCPAP and HFNC are commonly used in British hospitals to support infants with acute bronchiolitis. HFNC appears to be currently the preferred first-line modality for non-invasive respiratory support due to perceived ease of use.
- Clinical indicators of blood gas disturbances, elevated L-lactate concentration and other abnormal blood parameters in newborn beef calves. [Journal Article]
- VJVet J 2017; 219:49-57
- Blood gas disturbances, commonly resulting from dystocia, are associated with failed transfer of passive immunity, morbidity and mortality in newborn calves. Modified APGAR scores intended to identif...
Blood gas disturbances, commonly resulting from dystocia, are associated with failed transfer of passive immunity, morbidity and mortality in newborn calves. Modified APGAR scores intended to identify compromised calves are not widely adopted due to lack of practicality and inconsistent associations with blood parameters. The objective of this study was to determine clinical indicators of acidemia in newborn beef calves. Blood parameters at 10 min and 24 h after birth were compared to at-birth clinical examination parameters and calving characteristics in 77 commercial beef calves. There were no associations between heart rate or respiratory rate and blood pH or blood L-lactate concentration (LAC; r < 0.25); however, LAC was highly correlated with blood pH (r, -0.86). Abnormal mucous membrane color (red, white or blue) was associated with increased LAC (P = 0.002) but not decreased blood pH (P = 0.07). Abnormal results for tests of muscle tonicity and reflexes, namely inability to completely withdraw the tongue when pinched and a weak suckle reflex, were associated with decreased blood pH and increased LAC (P <0.05). Calves born to primiparous dams or from an assisted calving also had decreased blood pH and increased LAC (P <0.05). Differences in blood pH between at-birth categories resolved for all parameters by 24 h after birth, except for tongue withdrawal (P= 0.04). In conclusion, traditional APGAR parameters, heart rate, respiratory rate and mucous membrane color were not useful for the identification of acidemic calves; however, tongue withdrawal, calving ease, and parity should be included in such an assessment. Utilizing hand-held LAC meters may be a practical method to quickly identify compromised calves with acidemia in a field setting.
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- Renal tubular acidosis. [Journal Article]
- COCurr Opin Pediatr 2017 Jan 13
- CONCLUSIONS: We briefly update the current information on RTA, put forward the need of additional studies in children to validate urinary indexes used in the diagnosis of RTA and offer a perspective on diagnostic genetic tests.