Significance of Serum Vascular Endothelial Growth Factor Level in Patients with Idiopathic Pulmonary Fibrosis

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar–arterial difference of oxygen (AaDO₂) levels were significantly elevated than those with low AaDO₂ levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO₂ value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease’s progression.     

Species characterization in the genus Pestivirus according to palindromic nucleotide substitutions in the 5'-untranslated region

The palindromic nucleotide substitutions (PNS) at the three variable loci (V1, V2 and V3) in the 5'-untranslated region (UTR) of the Pestivirus genome have been considered for taxonomical segregation of the species, through the evaluation of 534 strains. On the basis of qualitative and quantitative secondary structure characteristics, species have been identified within the genus, determining genetic distances between species isolates, clarifying borderline and multirelated sequences, and characterizing and clustering the Pestivirus strains showing unexpected genomic sequences. Nine genomic groups have been identified: the species Bovine viral diarrhea virus 1 (BVDV-1), Bovine viral diarrhea virus 2 (BVDV-2), Border disease virus (BDV) and Classical swine fever virus (CSFV) and the tentative species Pronghorn, Giraffe, Bovine viral diarrhea virus 3 (BVDV-3) (HoBi group), Border disease virus 2 (BDV-2) (Italian small ruminant isolates) and Bungowannah. Palindromic positions have been characterized according to changes in nucleotide base-pairs identifying low variable positions (LVP) including base-pairs present in less than 80% of the genus. The determination of divergence between single strain sequences or genetic groups was obtained easily by comparing base-pairing combinations from aligned secondary structures. This provided clear information such as the level of heterogeneity within a species, the relatedness between species, or facilitating the characterization and clustering of specific strains. The BVDV-1 and BDV species resulted heterogeneous, showing isolates located on a borderline in the species. Within the BVDV-2 species, two main genogroups were identified, with strains showing common sequence characteristics to both groups (multirelated strains). They could be allocated correctly by quantitative analysis. Similarly, the relation between CSFV and BDV species appeared very clearly. Also in this case, ambiguous strain sequences could be clustered in the species showing the lowest divergence values. In conclusion, the proposed taxonomical procedure is based on the evaluation of only the strategic and highly conserved genome regions in the 5'-UTR. Furthermore, the application of quantitative analytical procedure allowed for a better determination of relation among species.     

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma （BSC） of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil （5-FU） and cisplatin （CDDP）. A 57-year-old woman was diagnosed as having SCluamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.     

Seizures lead to elevation of intracranial pressure in children undergoing invasive EEG monitoring

PURPOSE: To study the effects of intracranial subdural grid electrode placement and seizures on intracranial pressure (ICP) in children undergoing invasive EEG monitoring. METHODS: Sixteen children with pharmacoresistant epilepsy who underwent two-stage epilepsy surgery with subdural grid placement were included in the study. The ICP was recorded at baseline and with each seizure prospectively. A variety of seizure parameters including type of seizure, length of seizure, extent of seizure spread, and number of subdural grid electrodes inserted were analyzed retrospectively and correlated with the change in ICP. RESULTS: A total of 48 seizures in 16 children were studied. The mean baseline ICP correlated positively with age of the child. Generalized tonic-clonic seizures were associated with the highest rise in ICP. Similarly, ICP rise was associated with seizures involving more electrodes indicating a larger area of brain participating in the seizure. CONCLUSION: Seizures in general and generalized tonic-clonic seizures, in particular, increase ICP temporarily in patients who are undergoing invasive EEG monitoring with subdural grids.     

Encouragement to contribute to peer-review process in clinical neurology journals

OBJECTIVE: To determine whether the chance of peer-review assignment as expected from the amount of publications in "Japanese" and "Arabic" investigators differed from that for "Other" investigators in mainstream clinical neurology journals in 2004. METHODS: Fifteen clinical neurology journals with the impact factor in 2004 greater than 2.5 and with the full list of reviewers available in public were analyzed. Thereby, "Japanese", "Arabic", and "Other" investigators were defined as those with Japanese-sounding last names, those with Arabic-sounding last names, and others. The ratio of number of reviewers to number of original articles was compared between "Japanese" and "Other" groups as well as "Arabic" and "Other" groups. In addition, we described how "Japanese" and "Arabic" investigators were assigned peer-review in Brain and Development in 2004. RESULTS: In the above-mentioned 15 clinical neurology journals, the mean ratio of number of reviewers to number of original articles was smaller in "Japanese" compared to "Other" investigators (paired t-test: df=14; t-value=6.85; p-value<0.001) but failed to demonstrate a difference in the mean ratio between "Arabic" and "Other" investigators (df=11; t-value=-0.36; p=0.7). In Brain and Development, the number of peer-reviewers relative to the amount of publications was larger in "Japanese" compared to "Other" group (Fisher's exact probability test: p-value<0.001). CONCLUSION: More "Japanese" investigators are encouraged to contribute to peer-review process in clinical neurology journals other than Brain and Development. More "Non-Japanese" investigators are encouraged to contribute to peer-review process in Brain and Development.     

Stored autologous blood from a pregnant woman showing a considerable amount of agglutinates

A 30-year-old woman was admitted to our hospital to undergo simultaneous cesarean section and radical hysterectomy when the pregnancy became 30 weeks. An ultrasonic examination had found hypoechoic region at the cervix uteri. Because she wished autologous blood transfusion, 100 ml each of her own blood was obtained 3 times preoperatively. All the stored blood was returned to the patient through a filtering system (40 microm in the pore size) during surgery. However, we found paste-like agglutinates floating in the bags. We transfused the blood carefully while confirming that there were no agglutinates in the reservoir below the filter. The paste-like agglutinates were also found on the filter. By microscopic observation fibrin-like substances attached by blood cells were detected. When the autologous blood from pregnant women is returned, special care should be taken because the blood is likely to form agglutinates even though the blood test data are within normal ranges.     

Intracranial Recording and Source Localization of Auditory Brain Responses Elicited at the 50 ms Latency in Three Children Aged from 3 to 16 Years

Maturational studies of the auditory-evoked brain response at the 50 ms latency provide an insight into why this response is aberrant in a number of psychiatric disorders that have developmental origin. Here, using intracranial recordings we found that neuronal activity of the primary contributors to this response can be localised at the lateral part of Heschl’s gyrus already at the age of 3.5 years. This study provides results to support the notion that deviations in cognitive function(s) attributed to the auditory P50 in adults might involve abnormalities in neuronal activity of the frontal lobe or in the interaction between the frontal and temporal lobes. Validation and localisation of progenitors of the adults’ P50 in young children is a much-needed step in the understanding of the biological significance of different subcomponents that comprise the auditory P50 in the adult brain. In combination with other approaches investigating neuronal mechanisms of auditory P50, the present results contribute to the greater understanding of what and why neuronal activity underlying this response is aberrant in a number of brain dysfunctions. Moreover, the present source localisation results of auditory response at the 50 ms latency might be useful in paediatric neurosurgery practice.     

Salacia reticulata inhibits differentiation of 3T3-L1 adipocytes

Aim of the study

The purpose of this study was to define antidiabetic effects of fruit of Vaccinium arctostaphylos L. (Ericaceae) which is traditionally used in Iran for improving of health status of diabetic patients.

Materials and methods

Firstly, we examined the effect of ethanolic extract of Vaccinium arctostaphylos fruit on postprandial blood glucose (PBG) after 1, 3, 5, 8, and 24 h following a single dose administration of the extract to alloxan-diabetic male Wistar rats. Also oral glucose tolerance test was carried out. Secondly, PBG was measured at the end of 1, 2 and 3 weeks following 3 weeks daily administration of the extract. At the end of treatment period the pancreatic INS and cardiac GLUT-4 mRNA expression and also the changes in the plasma lipid profiles and antioxidant enzymes activities were assessed.Finally, we examined the inhibitory activity of the extract against rat intestinal α-glucosidase.

Results

The obtained results showed mild acute (18%) and also significant chronic (35%) decrease in the PBG, significant reduction in triglyceride (47%) and notable rising of the erythrocyte superoxide dismutase (57%), glutathione peroxidase (35%) and catalase (19%) activities due to treatment with the extract. Also we observed increased expression of GLUT-4 and INS genes in plant extract treated Wistar rats. Furthermore, in vitro studies displayed 47% and 56% inhibitory effects of the extract on activity of intestinal maltase and sucrase enzymes, respectively.

Conclusions

Findings of this study allow us to establish scientifically Vaccinium arctostaphylos fruit as a potent antidiabetic agent with antihyperglycemic, antioxidant and triglyceride lowering effects.     

Cortical glucose metabolism correlates negatively with delta-slowing and spike-frequency in epilepsy associated with tuberous sclerosis

The mechanism of altered glucose metabolism seen on positron emission tomography (PET) in focal epilepsy is not fully understood. We determined the association between interictal glucose metabolism and interictal neuronal activity, using PET and electrocorticography (ECoG) measures derived from 865 intracranial electrode sites in 11 children with focal epilepsy associated with tuberous sclerosis complex (TSC) (age: 0.5-16 years) undergoing epilepsy surgery. A multiple linear regression analysis was applied to each patient, to determine whether the glucose uptake at each electrode site on interictal PET was predicted by ECoG amplitude powers and interictal spike-frequency measured in the given electrode site. The regression slopes as well as R-square values (an indicator of fitness of the regression models) were finally averaged across the 11 patients. The mean regression slope for delta amplitude power was -0.0025 (95% CI: -0.0045 to -0.0004; P = 0.02 based on one-sample t-test) and that for spike frequency was -0.023 (95% CI: -0.042 to -0.0038; P = 0.02). On the other hand, the mean regression slopes for the remaining ECoG amplitude powers (theta, alpha, sigma, beta, and gamma activities) were not significantly different from zero. The mean R-square value was 0.39. These results suggest that increased delta-slowing and frequent spike activity were independently and additively associated with glucose hypometabolism in children with focal epilepsy associated with TSC. Association between frequent interictal spike activity and low glucose metabolism may be attributed to slow-wave components following spike discharges on ECoG recording, and a substantial proportion of the variance in regional glucose metabolism on PET could be explained by electrophysiological traits derived from conventional subdural ECoG recording.     

Predictive parameters for granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization

To improve the selection of donors for allogeneic stem cell transplantation, it is important to identify reliable parameters that predict CD34+-cell yields after granulocyte-colony stimulating factor (G-CSF)-induced peripheral blood stem cell (PBSC) mobilization. We retrospectively investigated the peripheral blood (PB) kinetics of white blood cells (WBCs), CD34+ cells, matrix metalloproteinases (MMP)-9 and -2, and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 in 15 healthy donors during their treatment with G-CSF. All donors received 10 microg/kg of recombinant human G-CSF once a day subcutaneously. Leukapheresis was initiated after 4 days of G-CSF treatment, and G-CSF treatment continued until the last day of leukapheresis. WBC and CD34+ cell numbers in the PB rose after 2 and 3 or 4 days of G-CSF treatment, respectively. The PB CD34+ cell numbers on day 4 correlated weakly with the increase in WBC counts from day 1 to day 2 (R(2) = 0.254, P = 0.056). There were also positive correlations between the CD34+ cell numbers in the PBSC products on day 4 and the CD34+ cells in the PB on days 1 and 4 (R(2) = 0.768, P < 0.0001 and R(2) = 0.816, P < 0.0005, respectively). The MMP-9 plasma levels on days 1 and 4 also correlated positively with the day 4 circulating CD34+ cell numbers (R(2) = 0.393, P < 0.05 and R(2) = 0.406, P = 0.01, respectively). In conclusion, the CD34+ cell numbers in the PB steady state may be a useful parameter selecting allogeneic PBSC donors.