Effect of hyperbaric oxygen in hepatopulmonary syndrome: an innovative experimental study.

OBJECTIVE: This study aimed to analyze the effect of hyperbaric oxygen treatment (HBOT) in hepatopulmonary syndrome (HPS). MATERIALS AND METHODS: Five-month-old female Wistar-Albino rats were randomly divided into three groups: Group I, the control group; Group II, the cirrhosis group; and Group III, the cirrhosis group + HBOT group. Rats were exposed to HBO sessions (2.4 atm./60 min) for 20 days. Animals were sacrificed 24 hours after the last HBO session. Biochemical analysis, oxygenation parameters, NO and NO synthase (NOS) levels, histopathological changes in the liver and lungs, and pulmonary artery diameter were measured. RESULTS: A total of 24 rats (10 rats were included in Group I, six rats in Group II, and eight rats in Group III) weighing 220-250 g were included in the study. Significant differences were observed for NO and NOS (9.10±1.05 to 12.17±1.85 µmol/L, p<0.05 and 0.46±0.31 to 1.17±0.39 U/ml, p<0.05, respectively) at baseline and day 36 only in group II. Inflammatory cell infiltration and bronchial injury were significantly increased in group II compared to group I (p=0.007 and p=0.008, respectively) but not in group III (p=0.266 and p=0.275, respectively). Pulmonary artery diameter was significantly lower in group III compared with group II at all sites in both lungs (p<0.05). CONCLUSIONS: HBOT may be a promising treatment for HPS by reducing NO and NOS activity, perialveolar arteriolar dilation, lung inflammation, and injury and guiding future clinical trials.

A QSAR study to predict the survival motor neuron promoter activity of candidate diaminoquinazoline derivatives for the potential treatment of spinal muscular atrophy.

Spinal Muscular Atrophy is a genetic neuromuscular disease that leads to muscle weakness and atrophy and it is characterized by the loss of α-motor neurons in the spinal cord's anterior horn cells. The disease appears due to low levels of the survival motor neuron protein. There are continuing clinical trials for the treatment of Spinal Muscular Atrophy. Quinazoline-based compounds are promising since they were tested on fibroblasts derived from the patients and found to increase the survival motor neuron protein levels. In this study, using multiple linear regression, we generated robust and valid quantitative structure- activity relationship models to predict the survival motor neuron-2 promoter activity of the new candidate compounds using the experimental survival motor neuron-2 promoter activity values of 2,4-diaminoquinazoline derivatives taken from the literature. The novel compounds designed by combining the pyrido[1,2-α]pyrimidin-4-one moeity of the known drug Risdiplam with that of 2,4 - diaminoquinazoline scaffold were predicted to exhibit strong promoter activities.

QSAR models for antioxidant activity of new coumarin derivatives.

This study presents 37 new antioxidant coumarin derivatives and strategies for structural modification to improve their antioxidant activities, the main ferric-reducing antioxidant power (FRAP) assay used to evaluate their antioxidant properties and the generation of validated quantitative structure-activity (antioxidant activity) relationship (QSAR) models. In an attempt to generate QSAR models, structures of all coumarin derivatives in the data set were fully optimized by semi-empirical PM6 method using SPARTAN 10 software. Descriptors were calculated by DRAGON 6.0 software. Multiple linear regression (MLR) models were developed with different training/test set combinations using QSARINS 2.2.1 software. Robustness, reliability and predictive power of the models were tested by internal and external validations. Applicability domain of the best two-descriptor model (nTR = 30; r(2) = 0.924; RMSETR = 0.213; nTEST = 7; r(2)ext = 0.887; RMSEext = 0.255; CCCext = 0.939) was determined. Descriptors appeared in the model revealed that complexity, H-bond donor and lipophilic character are important parameters in describing the antioxidant activity. Apart from the compounds in the data set, we also designed 31 new antioxidant coumarin derivatives and predicted their antioxidant activity using the best two-descriptor model. Most of these compounds are promising antioxidants.

Levels of arginine and its products in dialysis patients.

OBJECTIVES: Chronic renal failure is among significant public health problems all over the world. Despite advances in diagnosis and treatment approaches, cardiovascular morbidity and mortality is still high in chronic renal failure patients on dialysis. The aim this study is to investigate the importance of arginine, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) levels in the pathophysiology of cardiovascular morbidity and mortality in patients with dialysis treatment program. PATIENTS AND METHODS: 53 patients with chronic renal failure receiving hemodialysis treatment and 34 healthy persons were participated to the study. Arginine and ADMA levels were measured by high-performance liquid chromatography (HPLC) fluorescence detector. NO levels were assessed by a colorimetric method. Albumin, urea, creatinine levels was performed using the spectrophotometric method. RESULTS: Arginine levels were similar in dialysis patients when compared to the control group. Similarly NO levels did not show any difference between patient group and the control group. ADMA levels were found to be significantly high in dialysis patients compared to the control group (p < 0.005). Arginine/ADMA ratio was lower in the patient group compared to the control group (p < 0.001). Dialysis patients who have diagnosed coronary artery disease had low levels of albumin and creatinine. Arginine levels, ADMA levels and NO levels did not show any difference in the patients with coronary artery disease or not (p > 0.05). Arginine levels were significantly higher in men compared to women. Pearson correlation analysis showed that there was a correlation between NO and arginine levels. Arginine and Arginine/ADMA showed a positive correlation while ADMA and arginine/ADMA levels showed a negative correlation. CONCLUSIONS: As a result, our data showed that ADMA clearance was impaired in hemodialysis patients. Increase in ADMA levels may play a role in atherosclerosis dependent morbidity and mortality.

Ischaemia-modified albumin levels in newborn jaundice before and after phototherapy.

The aim of our study was to assess the effect of phototherapy (PT) on ischaemia-modified albumin (IMA) and malondialdehyde (MDA) levels in hyperbilirubinemic full-term newborns. The study was performed on 36 full-term infants exposed to PT. The babies were aged 3 to 13 days. IMA and MDA levels of the babies were determined before and after PT, by a colorimetric assay. IMA levels before and after PT were found as 0.424 ± 0.290 and 0.531 ± 0.262 absorbance units, respectively. Although IMA levels after PT were slightly higher, the difference was not statistically significant (p > 0.131). MDA levels before and after PT were found as 8.4 ± 1.8 µmol/l and 9.4 ± 1.5 µmol/l, respectively. Serum MDA concentrations were significantly higher after PT than before PT (p < 0.000). In previous studies, conflicting findings have been reported about the effect of PT on oxidant and antioxidant systems. However, we have found no study investigating IMA levels in hyperbilirubinaemia in newborns before and after PT. Our results shows that PT does not affect IMA levels significantly. IMA increases as a result of oxidative stress. We believe that the lack of significant difference between our IMA levels before and after PT may resulted from hyperbilirubinaemia, which has antioxidant effect.

The aromatic cage in the active site of monoamine oxidase B: effect on the structural and electronic properties of bound benzylamine and p-nitrobenzylamine.

Computational studies using the ONIOM methods have been performed to probe the catalytic roles of tyrosine residues 398 and 435 which constitute the "aromatic cage" in the active site of MAO-B. The results presented here provide additional new insights into the interactions that take place on activation of the amine substrate by the aromatic cage residues in MAO-B catalysis and have relevance to the MAO-A catalytic mechanism.

Physico-chemical properties of PCDD/PCDFs and phthalate esters.

QSPR models for water solubility (S), n-octanol/water partition coefficient (K(OW)), and Henry's law constant (H) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo-p-furans (PCDFs) and phthalates have been established based on two different sets of parameters. Those parameters were topology based characteristic root index (CRI) and three semi-empirical molecular descriptors, namely--energies of the highest occupied and the lowest unoccupied molecular orbital (E(HOMO) and E(LUMO)), and dipole moment (mu). The best fit equation found by "forward multiple linear regression" showed that the topology based CRI was the most important parameter for the modelling of solubility and n-octanol/water partition coefficient. For n-octanol/water partition coefficient a two-parameter equation including the CRI and E(HOMO) with a correlation coefficient of r = 0.992 was obtained whereas a three-parameter equation for solubility and Henry's law constant including the CRI, E(LUMO) and mu with a correlation coefficient of r = 0.986 and r = 0.933 was obtained, respectively. E(HOMO) and mu didn't appear in the same model because of the collinearity. The results of modified jackknife tests indicated that the three models were statistically robust. Mean deviation of calculated values from experimental data amounted to 0.27, 0.17, and 0.28 log units for the three properties mentioned. The developed models have been used to predict the S, K(OW) and H of compounds not included in the training sets.