Tranilast ameliorated subchronic silver nanoparticles-induced cerebral toxicity in rats: Effect on TLR4/NLRP3 and Nrf-2.

Silver nanoparticles (AgNPs) are widely applied in various aspects of life. However, recent studies reported their potential toxicity both on environment and human health. The present study aimed to unravel the underlying molecular mechanisms involved in AgNPs-induced brain toxicity. Moreover, chemopreventive effect of tranilast, an analogue of tryptophan metabolite and a mast cell membrane stabilizer was evaluated. Thirty Sprague Dawley rats were enrolled equally into Normal control group, AgNPs-intoxicated group (50 mg/kg, 3 times/week) and tranilast (300 mg/kg, 3 times/week)+AgNPs group. AgNPs administration triggered brain oxidative stress as depicted by reduced Nrf-2 expression, decreased TAC and GSH as well as upregulated brain lipid peroxidation. The apparent brain oxidative damage was accompanied by elevated levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α). Moreover, brain levels of TLR4, NLRP3 and caspase-1 were up-regulated. Additionally, histological study indicated marked cellular injury in cerebrum and cerebellum specimens. This was concomitant with elevated serum CK activity and CK-BB level. On the other hand, tanilast administration remarkably alleviated AgNPs-induced brain toxicity. The present study shed the light on implication of TLR4/NLRP3 axis and NrF2 in AgNPs-induced brain toxicity. In addition, it explored the potential protective effect of tranilast on AgNPs-induced brain injury via antioxidant and anti-inflammatory efficacies.

The Effect of High-Dose Vitamin C on Biochemical Markers of Myocardial Injury in Coronary Artery Bypass Surgery.

OBJECTIVE: To evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG). METHODS: This is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals. RESULTS: High doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups. CONCLUSION: Vitamin C has significantly improved the patients' ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group. IRCT CODE: IRCT2016053019470N33.

The effect of high-dose vitamin c on biochemical markers of myocardial injury in coronary artery bypass surgery

Abstract Objective: To evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG). Methods: This is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals. Results: High doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups. Conclusion: Vitamin C has significantly improved the patients' ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group. IRCT code: IRCT2016053019470N33

Ellagic acid protects against arsenic trioxide-induced cardiotoxicity in rat.

Arsenic trioxide (As2O3) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against As2O3-induced heart injury in rats. Thirty-two male Wistar rats were randomly divided into four treatment groups, that is, control (0.2 mL of normal saline, intraperitoneally (ip)), As2O3 (5 mg/kg, ip), As2O3 plus ellagic acid, and ellagic acid (30 mg/kg, orally) groups. The drugs were administered daily for 10 days and pretreatment with ellagic acid was performed 1 h prior to As2O3 injection. Cardiotoxicity was characterized by electrocardiological, biochemical, and histopathological evaluations. Our results showed that ellagic acid pretreatment significantly ameliorated As2O3-induced increase in glutathione peroxidase activity and malondialdehyde concentration ( p < 0.05 and p < 0.001, respectively) and also diminished QTc prolongation ( p < 0.0001) and cardiac tissue damages. Pretreatment with ellagic acid also lowered the increased troponin I ( p < 0.0001) and creatine kinase isoenzyme MB ( p < 0.01) levels in response to As2O3. In conclusion, results of this study demonstrated that ellagic acid has beneficial cardioprotective effects against As2O3 toxicity. It is suggested that the protective effects were mediated by antioxidant properties of ellagic acid.

Screening for Duchenne muscular dystrophy in Germany, 1977-2011: A personal story.

EDITOR'S NOTE: This article by Dr. Günter Scheuerbrandt is a fascinating personal account and historical narrative of the birth and development of a screening program for Duchenne Muscular Dystrophy in Germany, beginning 40 years ago. As the author notes, approval of an institutional review board or ethics committee was not required for this type of scientific investigation in one's field at the time this program was begun, but we have removed all personal data from any of the materials presented in here in order to conform to current concepts of ethical publication. This article is about the screening of 528,410, mostly 4-6-week-old, boys in Germany between 1977 and 2011 for high levels of creatine kinase (CK) to identify those with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). During these 34 years of infant screening, 147 boys with confirmed, probable, and possible DMD (incidence 1:3,600 male births) and 33 boys with confirmed, probable, and possible BMD (incidence 1:15,500 male births) were found. Research reports about DMD were sent to families and pediatricians participating in the screening, and, on request, to families and scientists everywhere. It is hoped that screening programs used as the basis for future therapies will be able to modify the natural history of boys with DMD. New dystrophin mutations will continue to occur, necessitating screening and early therapy. Abstract Submitted for Presentation at the 10th International Society for Neonatal Screening-Asia Pacific Regional Meeting, August 2017, Ulaanbataar, Mongolia. Muscle Nerve 57: 185-188, 2018.

Protective effect of 5, 7-dihydroxyflavone on brain of rats exposed to acrylamide or γ-radiation.

5, 7-Dihydroxyflavone (DHF), a natural plant flavonoid, have shown a variety of beneficial effects. Neurotoxic effects of acrylamide (ACR) or gamma irradiation (IR) have been established in humans and animals. The current study was designed to evaluate whether DHF could restrain ACR or IR induced neurotoxicity in rats and to explore the underlying mechanisms. The study was carried out by investigating some biochemical and biophysical parameters as well as histopathological examination. The daily oral administration of ACR (25mg/kg b.wt.) for 21days or exposure to single dose of IR (5Gy) induced brain damage throughout the significant decrease in catecholamine contents and brain derived neurotrophic factor (BDNF) in brain tissue with a concomitant significant decrease in serum activity of creatinine kinase-BB. Moreover, the brain levels of MDA and ß-amyloid and activities of acetylcholinesterase and caspase-3 were remarkably augmented in ACR-induced rats. Additionally, the electrical properties of erythrocytes membrane were significantly disturbed. The administration of DHF (50mg/kg b.wt. daily for 21day) to rats exposed to either ACR or IR significantly reversed the alteration in all studied parameters. Histopathological investigation of brain tissues supported the neuroprotective effect of DHF on brain. From the obtained data, it can be concluded that the DHF has neuroprotective effect against ACR or IR induced-neurotoxicity.

A blood-based biomarker panel to risk-stratify mild traumatic brain injury.

Mild traumatic brain injury (TBI) accounts for the vast majority of the nearly two million brain injuries suffered in the United States each year. Mild TBI is commonly classified as complicated (radiographic evidence of intracranial injury) or uncomplicated (radiographically negative). Such a distinction is important because it helps to determine the need for further neuroimaging, potential admission, or neurosurgical intervention. Unfortunately, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are costly and not without some risk. The purpose of this study was to screen 87 serum biomarkers to identify a select panel of biomarkers that would predict the presence of intracranial injury as determined by initial brain CT. Serum was collected from 110 patients who sustained a mild TBI within 24 hours of blood draw. Two models were created. In the broad inclusive model, 72kDa type IV collagenase (MMP-2), C-reactive protein (CRP), creatine kinase B type (CKBB), fatty acid binding protein-heart (hFABP), granulocyte-macrophage colony-stimulating factor (GM-CSF) and malondialdehyde modified low density lipoprotein (MDA-LDL) significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.975 and a negative predictive value (NPV) of 98.6. In the parsimonious model, MMP-2, CRP, and CKBB type significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.964 and a negative predictive value (NPV) of 97.2. These results suggest that a serum based biomarker panel can accurately differentiate patients with complicated mild TBI from those with uncomplicated mild TBI. Such a panel could be useful to guide early triage decisions, including the need for further evaluation or admission, especially in those environments in which resources are limited.

Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats / Efeitos do Hormônio do Crescimento na Remodelação Cardíaca Durante Treinamento Resistido em Ratos

Abstract Background: Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. Objective: To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Methods: Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). Results: There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). Conclusion: GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.

Resumo Fundamento: Apesar de os efeitos benéficos do treinamento resistido (TR) sobre o sistema cardiovascular estarem bem estabelecidos, poucos estudos têm investigado os efeitos crônicos da administração de hormônio do crescimento (GH) sobre a remodelação cardíaca durante um programa de TR. Objetivo: avaliar os efeitos do GH sobre a remodelação cardíaca em suas características morfológicas e na expressão dos genes do trânsito de Ca2+ em ratos submetidos ao TR. Métodos: Ratos Wistar machos foram divididos em 4 grupos (n = 7 por grupo): controle (CT), GH, TR e TR com GH (TRGH). A dose de GH foi de 0,2 UI/kg, a cada dois dias, por 30 dias. O modelo de TR utilizado foi o salto vertical em água (4 séries de 10 saltos, 3 vezes/semana) durante 30 dias consecutivos. Após o período experimental, as seguintes variáveis foram analisadas: peso corporal final (PCF), peso do ventrículo esquerdo (PVE), razão PVE/PCF, área seccional de cardiomiócitos (ASC), fração de colágeno, creatina quinase fração músculo-cérebro (CK-MB) e expressão gênica de SERCA2a, fosfolambam (PLB) e rianodina (RyR). Resultados: Não houve diferença significativa (p > 0,05) entre os grupos para PCF, PVE, razão PVE/PCF, ASC, e expressão gênica de SERCA2a, PLB e RyR. O grupo TR mostrou um significativo aumento (p < 0,05) da fração de colágeno em comparação aos outros. Além disso, os grupos treinados (TR e TRGH) apresentaram maiores níveis de CK-MB em comparação aos não treinados (CT e GH). Conclusão: Esses resultados indicam que o GH pode atenuar os efeitos negativos do TR na remodelação cardíaca por contrabalançar o aumento da síntese de colágeno, sem afetar a expressão de genes que regulam o trânsito de Ca2+ cardíaco.

Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats.

BACKGROUND: Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. OBJECTIVE: To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. METHODS: Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). RESULTS: There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). CONCLUSION: GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.

Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment.

BACKGROUND: Creatine kinase (Ck) catalyzes the reversible transfer of high-energy phosphate groups between adenosine triphosphate and phosphocreatine. The brain isoform (Ckbb) is greatly induced in mature osteoclasts, playing an important role in bone-resorbing function during osteoclastogenesis. High Ckbb serum level has been found in patients with osteopetrosis and in patients with bisphosphonate (BP)-induced osteopetrosis. BPs are considered the treatment of choice for children with osteogenesis imperfecta (OI), acting as potent inhibitors of bone resorption by suppressing the activity of osteoclasts. METHODS: We determined total serum Ck and isoform activity in 18 prepubertal children with type I OI, before and during treatment with the BP neridronate infusions. RESULTS: Basal serum Ckbb levels were slightly elevated with respect to controls (mean ± SD = 3.0 ± 2.7 vs. 2.0 ± 2.2) and progressively increased after neridronate treatment (t0 vs. t4: mean ± SD = 3.0 ± 2.7 to 10.8 ± 8.1), with significant increment after first, second, and fourth infusions (P < 0.01). An inverse correlation was found between serum Ckbb and serum CTx at basal level. CONCLUSION: Our results support previous observations that increased serum Ckbb reflects failure of osteoclasts or, at least, suppression of osteoclasts. Upon considering that BPs are long acting, this information could be useful to prevent the risk of overtreatment after long-term BP exposure in pediatric patients with OI.

Disturbance in venous outflow from the cerebral circulation intensifies the release of blood-brain barrier injury biomarkers in patients undergoing cardiac surgery.

OBJECTIVE: Disturbances in venous outflow from the cerebral circulation may result in brain injury. Severe increases in brain venous pressure lead to brain ischemia and, subsequently, brain edema and intracranial hemorrhages. The purpose of this study was to determine the effect of changes in jugular venous bulb pressure (JVBP) on plasma blood brain-barrier biomarkers concentration and disturbances in arteriovenous total and ionized magnesium (a-vtMg and a-viMg) in brain circulation in patients undergoing coronary artery bypass grafting surgery (CABG) with cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Department of Cardiac Surgery at a Medical University Hospital. PARTICIPANTS: Ninety-two adult patients undergoing elective CABG with CPB under general anaesthesia were studied. METHODS: Central venous pressure (CVP) was measured using a pulmonary artery catheter. The right jugular vein was cannulized retrogradely for jugular venous bulb pressure (JVBP) measurement. Concentrations of plasma S100ß protein, matrix metalloproteinase 9 (MMP-9), creatine kinase isoenzyme BB (CK-BB) a-vtMg and a-viMg were measured as the markers of blood-brain barrier dysfunction. All of them were analyzed in comparison with JVBP during surgery and the early postoperative period. RESULTS: Elevated JVBP was noted after CPB and after surgery. Its increase above 12 mmHg intensified release of S100ß, MMP-9 and CK-BB as well as disorders in a-vtMg and a-viMg. CVP correlated with JVBP, S100ß, and MMP-9. Moreover, JVBP correlated with S100ß and MMP-9. CONCLUSIONS: Cardiac surgery increased JVBP, and JVBP elevated above 12 mmHg intensified an increase in biomarkers of plasma blood-brain barrier disruption.

Susceptibility to myocardial ischemia reperfusion injury at early stage of type 1 diabetes in rats.

BACKGROUND: Large body of evidences accumulated in clinical and epidemiological studies indicate that hearts of diabetic subjects are more sensitive to ischemia reperfusion injury (IRI), which results in a higher rate of mortality at post-operation than that of non-diabetes. However, experimental results are equivocal and point to either increased or decreased susceptibility of the diabetic hearts to IRI, especially at the early stage of the disease. The present study was designed to test the hypothesis that the duration/severity of the indexed ischemia is a major determinant of the vulnerability to myocardial IRI at early stage of diabetes. METHODS: Four weeks streptozotocin (STZ)-induced diabetic (D) and non-diabetic (C) Sprague-Dawley rats were randomly assigned to receive 30 or 45 min of left anterior descending artery ligation followed by 2 or 3 hours of reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume (PV) conduction system. Myocardial infarct size was determined with triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and nitrotyrosine formation, 15-F(2t)-Isoprostane and plasma superoxide dismutase (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was assessed by TUNEL staining. Myocardial TNFα, Caspase-3, STAT3, Akt, and GSK-3ß were determined by Western blotting. RESULTS: Prolongation of ischemia but not reperfusion from 30 min to 45 min significantly increased infarct size in D compared to C rats (P < 0.05), accompanied with significantly increased plasma CK-MB (P < 0.05). Prolongation of the duration of either ischemia or reperfusion significantly increased plasma LDH release and myocardial 15-F(2t)-Isoprostane and reduced plasma SOD activity, with concomitant reduction of myocardial NO and increase of nitrotyrosine formation in D relative to C (P < 0.05). Prolongation of ischemia and reperfusion significantly reduced left ventricular ejection fraction and increased the peak rate of pressure, accompanied with increased end systolic pressure in D relative to C rats (P < 0.05) but reduced phosphorylations of myocardial STAT3 at site Ser727 and Akt at site Ser473 as well as GSK-3ß at Ser 9 (P < 0.05). CONCLUSIONS: Diabetic hearts, even at early stage of the disease are more sensitive to IRI, and this increased severity of post-ischemic myocardial injury depends more on the duration of ischemia than that of reperfusion.

Alpha actinin is specifically recognized by Multiple Sclerosis autoantibodies isolated using an N-glucosylated peptide epitope.

Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MuS), e.g. neurofascin, contactin, CNPase, and other T-cell receptor membrane anchored proteins. These putative antigens, although differing from the conventional myelin derivatives, are conceptually based on an animal model of experimental autoimmune encephalomyelitis. In this report we describe the identification of putative antigens based on their recognition by autoantibodies isolated from MuS patient serum. In a previous work from this laboratory we have shown that a peptide probe, named CSF114(Glc), specifically identifies serum autoantibodies in a subset of MuS patients, representing ∼30% of the patient population. The autoantibodies, purified from MuS patients' sera (six), through CSF114(Glc) affinity chromatography, detected three immunoreactive protein bands present in the rat brain. Proteomic analysis of the immunoreactive bands, involving MALDI and MS/MS techniques, revealed the presence of four proteins distinguishable by their mass: alpha fodrin, alpha actinin 1, creatine kinase, and CNPase. The immunoreactive profile of these rat brain proteins was compared with that of commercially available standard proteins by challenging against either CSF114(Glc) purified MuS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by the following procedure: whereas monoclonal antibodies recognized all rat brain proteins, isolated MuS specific antibodies recognize only alpha actinin 1 as a putative antigen. In fact, alpha actinin 1 displayed a robust immunoreactive response against all MuS patients' sera examined, whereas the other three bands were not consistently detectable. Thus, alpha actinin 1, a cytoskeleton protein implicated in inflammatory/degenerative autoimmune diseases (lupus nephritis and autoimmune hepatitis) might be regarded as a novel MuS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.

Aminophylline, administered at usual doses for rodents in pharmacological studies, induces hippocampal neuronal cell injury under low tidal volume hypoxic conditions in guinea-pigs.

OBJECTIVES: To establish whether aminophylline, administered at usual doses for rodents in pharmacological studies, induces brain injury in systemic hypoxaemia in guinea-pigs. METHODS: A hypoxaemia (partial oxygen tension of arterial blood (PaO2) = 40-60 mmHg) model was developed by low tidal volume mechanical ventilation in guinea-pigs. KEY FINDINGS: Under hypoxic conditions, aminophylline significantly increased the concentration of brain-specific creatine kinase in the serum in a dose- and time-dependent manner. A reduced number of hippocampal neuronal cells in the CA1 region, an increase in the concentration of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF), an increase in lipid hydroperoxides and a decrease in the ratio of glutathione to glutathione disulfide in the brain tissues were also observed. These effects were not observed when aminophylline at the same doses was administered under normoxic conditions (PaO2 = 80-100 mmHg). There was no difference in either serum or CSF concentrations of theophylline between normoxic and hypoxic conditions. Another methylxanthine, caffeine, did not increase the concentration of NSE in CSF. CONCLUSIONS: Aminophylline potentially induces brain damage under hypoxic conditions. We suggest that aminophylline treatment has adverse effects in patients with hypoxaemia subsequent to respiratory disorders such as asthma.

[Update regarding the role of biomarkers in early diagnosis of non-small cell bronchopulmonary cancer]. / Actualitati privind rolul markerilor tumorali in detectia precoce a neoplasmului bronhopulmonar NSCC.

Early diagnosis of lung cancer by non-invasive methods has a low sensibility: 60% of peripheral cancers could be diagnosed by computed tomography, 60% of the central ones by sputum cytology. More specific for detecting central microinvasive lesions could be bronchoscopy with autofluorescence, but this is a method with a low number of patients to be performed on, because of the specific technique. For all these reasons there are some other methods to be tried in this respect--one of them is to find one or more molecules--tumoral markers--which have to be specific in establishing the risk of developing lung cancer, to make an early diagnosis of cancer and to predict the evolution under treatment. The detecting tumoral markers in sputum, blood, bronchoalveolar lavage was not so largely explored related to the final goal--the possibility of identifying and quantifying the most specific ones for the screening of lung cancer. The present paper has as purpose to make an review of tumoral markers--"classical" markers as: CEA, NSE, TPA, beta2 microglobulina, CA 125, CA 15-3--considered not such a high sensibility and specificity for lung cancer screening versus new molecules, studied intensively as: SCC-Ag, CYFRA 21-1, ferritin, sIL-2R, CCK-BB, glycosyltransferases. Those new molecules have a higher sensibility, but also could have a higher specificity for each type of lung cancer.

Electrophoretic fractionation of creatine kinase isoenzymes and macroenzymes in clinically healthy dogs and cats and preliminary evaluation in central neurologic disease.

BACKGROUND: Information about the electrophoretic distribution of CK-MM, CK-MB, and CK-BB, serum creatine kinase (CK) isoenzymes that are indicators of skeletal muscle, cardiac muscle, and brain lesions, respectively, and CK macroenzymes (macro-CK1 and macro-CK2) in dogs and cats with and without central neurologic disease is scant and equivocal. OBJECTIVES: The objectives of this study were to describe the electrophoretic distribution of CK isoenzymes and macroenzymes in healthy dogs and cats and to provide a preliminary assessment of the utility of CK enzymatic electrophoresis in dogs and cats with central neurologic disease. METHODS: Electrophoretic separation of serum CK isoenzymes and macroenzymes was performed on freeze-thawed serum samples from 20 healthy dogs and 3 dogs with central neurologic disease and from 14 healthy cats and 6 cats with neurologic feline infectious peritonitis (FIP). Electrophoretic separation was also performed on supernatants of homogenized brain, skeletal muscle, and cardiac muscle from both species, to assess the tissue distribution of isoenyzmes in dogs and cats. RESULTS: CK-MM was the predominant isoenzyme in the serum of healthy dogs and cats, followed by macro-CK2 and CK-BB in dogs and by both macroenzymes in cats. In dogs, CK-MB was essentially absent from both serum and homogenized hearts. CK-BB increased in dogs with neurologic disease. In cats, CK-BB was essentially absent from serum, but was present in brain homogenates. Two of 6 cats with FIP had increased macro-CK1 and increased CK-BB activity. CONCLUSIONS: This study identified the electophoretic distribution of CK isoenzymes and macroenzymes of dogs and cats and provided encouraging data about the possible use of CK-BB as a biomarker for canine neurologic disorders, but not for FIP.

Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease.

A major goal of current clinical research in Huntington's disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients. Brain CK-BB levels were significantly reduced in R6/2 mice by approximately 18% to approximately 68% from 21 to 91 days of age, while blood CK-BB levels were decreased by approximately 14% to approximately 44% during the same disease duration. Similar findings in CK-BB levels were observed in the 140 CAG mice from 4 to 12 months of age, but not at the earliest time point, 2 months of age. Consistent with the HD mice, there was a grade-dependent loss of brain CK-BB that worsened with disease severity in HD patients from approximately 28% to approximately 63%, as compared to non-diseased control patients. In addition, CK-BB blood buffy coat levels were significantly reduced in both premanifest and symptomatic HD patients by approximately 23% and approximately 39%, respectively. The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from HD mice and HD patients may provide a powerful means to assess disease progression and to predict the potential magnitude of therapeutic benefit in this disorder.