Difference in absorption of the two structurally similar flavonoid glycosides, hyperoside and isoquercitrin, in rats.

The present study was to investigate oral absorption of the two similar flavonoid glycosides, isoquercitrin (IQ, quercetin-3-O-glucoside) and hyperoside (HP, quercetin-3-O-galactoside) in rats. Two groups of male SD rats received an oral dose of either IQ (4.5 mg/kg) or HP (6.0 mg/kg). Blood samples were collected via jugular vein at time intervals after drug administration and the plasma concentrations of the studied compounds were analyzed by HPLC. The stability of IQ and HP in the GI tract was also measured by incubation with various GI contents from rats. The results showed that unchanged IQ was barely detectable whereas the glucuronidated quercetin (the aglycone of IQ) was found to be the major form in plasma after oral administration of IQ. In contrast, HP could not be detected in plasma neither as unchanged form nor its aglycone or conjugated aglycone form. Additional in vitro stability studies demonstrated that HP is more stable than IQ in the GI tract. This suggests that IQ could be hydrolyzed easier than HP to its aglycone in GI tract before being absorbed. In conclusion, IQ, as a flavonoid glucoside, could be rapidly absorbed and transformed into glucuronidated quercetin and such absorption might be related to the hydrolysis of the type of sugar moieties attached to its aglycone molecule.     

An adenoviral vector expressing the glucose transporter protects cultured striatal neurons from 3-nitropropionic acid

Considerable interest has focused on the possibility of using gene transfer techniques to introduce protective genes into neurons around the time of necrotic insults. We have previously used herpes simplex virus amplicon vectors to overexpress the rat brain glucose transporter, Glut-1 (GT), and have shown it to protect against a variety of necrotic insults both in vitro and in vivo, as well as to buffer neurons from the steps thought to mediate necrotic injury. It is critical to show the specificity of the effects of any such transgene overexpression, in order to show that protection arises from the transgene delivered, rather than from the vector delivery system itself. As such, we tested the protective potential of GT overexpression driven, in this case, by an adenoviral vector, against a novel insult, namely exposure of primary striatal cultures to the metabolic poison, 3-nitropropionic acid (3NP). We observed that GT overexpression buffered neurons from neurotoxicity induced by 3NP.     

Limitations in the neuroprotective potential of gene therapy with Bcl-2

Considerable attention has focused on the therapeutic transfer of genes with viral vectors into neurons for the purpose of protecting against neurological insults. A number of papers have reported that overexpression of the anti-apoptotic protein Bcl-2 can protect neurons both in vitro and in vivo against a variety of necrotic insults. An emerging literature suggests that the availability of energy tends to modulate a neuron towards dying apoptotically, rather than necrotically, in the aftermath of an insult. This suggests that an anti-apoptotic protein such as Bcl-2 should be minimally protective, at best, against purely energetic insults. In support of this idea, we report that overexpression of Bcl-2 with a herpes simplex viral vector fails to protect hippocampal neurons, either in vitro or in vivo, against the electron transport uncoupler 3-acetylpyridine (3AP). As a positive control, the same vector significantly protected against the excitotoxin kainic acid. This finding supports the view that neurotoxicity induced by 3AP is likely to have only minimal apoptotic facets. On a broader level, it suggests some limitations in the neuroprotective potential of gene therapy with Bcl-2.     

Hypereosinophilic Syndrome: CT Findings in Patients with Hepatic Lobar or Segmental Involvement

Objective

The purpose of this study was to describe the CT findings of hepatic hypereosinophilic syndrome in which hepatic lobes or segments were involved.

Materials and Methods

Seven patients with hypereosinophilic syndrome with hepatic lobar or segmental involvement were included in our study. In all seven, diagnosis was based on liver biopsy and the results of corticosteroid treatment. CT findings were retrospectively reviewed by three radiologists, who reached a consensus. Biopsy specimens were examined, with special reference to portal and periportal inflammation.

Results

CT demonstrated well-defined, homogeneous or heterogeneous low attenuation with a straight margin limited to a hepatic lobe (n = 2), segments (n = 3), or subsegments (n = 2), particularly during the portal phase. Where there was subsegmental involvement, lesions were multiple, ovoid or wedge-shaped, and showed low attenuation. In two patients with lobar or segmental involvement, segmental portal vein narrowing was observed. Histopathologic examination disclosed eosinophilic infiltration in the periportal area, sinusoids and central veins, as well as portal phlebitis.

Conclusion

Hypereosinophilic syndrome may involve the presence of hepatic lobar, segmental, or subsegmental low-attenuated lesions, as seen on CT images. Their presence may be related to damage of the liver parenchyma and to portal phlebitis.     

Prevention of encephalomyocarditis virus-induced diabetes by live recombinant Mycobacterium bovis bacillus Calmette-Guérin in susceptible mice

The D variant of encephalomyocarditis (EMC-D) virus causes diabetes in susceptible mice by direct cytolysis of pancreatic beta-cells. cDNA covering the major outer capsid protein (VP1) of the EMC-D virus was cloned into Mycobacterium bovis bacillus Calmette-Guerin (BCG). None of the SJL/J mice immunized with live recombinant BCG-VP1 (rBCG-VP1) became diabetic when challenged with the highly diabetogenic EMC-D virus, but the control mice inoculated with normal BCG developed diabetes during the same challenge. VP1-specific antibodies (including neutralizing antibodies) were markedly increased over time and reached the maximum titer at week 10 after a single immunization. The plateau of the titer lasted longer than 4 weeks. Mice and guinea pigs immunized with live rBCG-VP1 showed strong delayed-type hypersensitivity to the VP1 of the EMC-D virus. The preventive immunity still worked effectively 10 months after the primary immunization. At that time, the VP1-specific antibody was almost undetectable in the bloodstream, but a large number of VP1-specific lymphocytes was found in the spleen of the immunized mice. Our results show that live rBCG-VP1 elicits effective humoral and long-lasting cellular immune responses against EMC-D virus infection that results in the prevention of virus-induced diabetes in susceptible mice.     

The use of an ambulatory,automatic sleep recording device (QUISI™ Version 1.0) in the evaluation of primary snoring and obstructive sleep apnoea

The use of an ambulatory, automatic sleep recording device (QUISI? Version 1.0) in the evaluation of primary snoring and obstructive sleep apnoea Electroencephalogram (EEG) evaluation with polysomnography (PSG) according to the Rechtschaffen & Kales (R&K) rules is time and cost consumptive, but ambulatory polygraphy systems do not allow EEG recording routinely. As a consequence, the number of sleep disordered events cannot be calculated exactly. QUISI is a one‐channel, self‐applicable ambulatory EEG recording device. The present study was designed as a prospective, non‐randomized clinical trial. This investigation evaluated the results of 40 patients with primary snoring and obstructive sleep apnoea measured with level 1 PSG and QUISI simultaneously. Fifteen patients (37.5%) were primary snorers with normal sleep profiles, whereas 25 patients (62.5%) suffered from obstructive sleep apnoea (OSA) with a Respiratory Disturbance Index (RDI) of 38.6 ± 23.8. The mean total sleeping time (TST) was underestimated by 4.5%, while Sleep Efficiency Index (SEI) was understimated by 4.6% by the QUISI device compared with PSG. The correlation between the QUISI and the PSG estimates for single sleep stages demonstrated only moderate correlation. The statistical significance for sleep stage 2 was r = 0.42, P = 0.002; for sleep stage 3/4, r = 0.31, P = 0.02; and for WAKE, r = 0.33, P = 0.01. Sleep stage 2 as well as sleep stage 3/4 were underestimated by QUISI substantially (difference: ?5.6% and ?10.3%), while WAKE was overestimated by QUISI to a larger amount (difference: +10.4%). Sensitivity and specificity of QUISI to recognize pathological sleep profiles compared with PSG/R&K were 0.92 and 0.96 respectively. QUISI is able to evaluate normal versus altered sleep profiles in patients with primary snoring and OSA. Comparing the quartile ranges, we found substantial differences between QUISI and PSG/R&K. QUISI gives an impression of sleep architecture and objective verification of a sleep disturbance in an ambulant setting but cannot replace the sleep laboratory‐based PSG.     

Spectacle use and reduced unaided vision in third grade students: a comparative study in different educational settings

Background: The development of myopia is influenced by hereditary factors, environmental factors and geneenvironment interaction. Reading and near‐work activity are associated with myopia and myopic progression. This study sought to determine and compare the prevalence of reduced unaided vision and spectacle use among third grade Israeli students from three different educational settings. Method: A sample of 917 students (mean age 8.5 years, range seven to 10 years) was drawn from the three Israeli educational streams: secular, Orthodox and ultra‐Orthodox. Children in the ultra‐Orthodox education pathway begin studying at the age of three years and their daily reading involves sustained near work with increased accommodative effort accompanied by head‐rocking movements. Reduced distance vision was used to indicate the likely development of or an increase in the amount of myopia. Spectacle lenses were measured to determine the prevalence of myopia. Results: Of the 917 students studied, 103 (11.2 per cent) wore spectacles (14.2 per cent of the males and eight per cent of the females); 82.5 per cent of those who wore spectacles were myopic. Males from ultra‐Orthodox schools had the highest rate of reduced unaided vision (72.5 per cent) compared with males from secular schools (27.3 per cent), males from Orthodox schools (59.3 per cent) or with females from all three groups (average of 34.8 per cent, p < 0.0001, chi squared). Males had a higher rate of reduced unaided vision, especially in the Orthodox and ultra‐Orthodox schools. Conclusions: Our study suggests that Jewish ultra‐Orthodox males have a higher prevalence and degree of myopia. The study habits of young children, including exposure to prolonged near tasks, high accommodative demands and possibly optical defocus induced by body sway, may contribute to the development of myopia.     

Genetic polymorphism of p53 and XRCC1 in cervical intraepithelial neoplasm in Taiwanese women.

BACKGROUND AND PURPOSE: Many epidemiological studies have investigated the relationship between p53 codon 72 polymorphism and cervical cancer risk, but the findings are still conflicting. In contrast, data are lacking on the relationship between XRCC1 polymorphism and cervical neoplasm risk. This community-based nested case-control study examined the association between genetic polymorphisms of p53 codon 72 and XRCC1 codons 194, 280, and 399 and cervical intraepithelial neoplasm (CIN) susceptibility in Taiwanese women. METHODS: Women living in Chiayi City, located in southwestern Taiwan, who had received Papanicolau (Pap) smear screening between October 1999 and December 2000 (n = 32,466) were included. Potential cases were women having lesions with cervical intraepithelial neoplasm II (CIN2) and over (> or = CIN2) reconfirmed by cervical biopsy. Potential controls (case:control = 1:2) were age matched (+/- 2 years) and residency matched women who had normal Pap smears. DNA samples were extracted from peripheral blood specimens and genetic polymorphisms of p53 and XRCC1 were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In total, 100 cases [97 high-grade squamous intraepithelial lesion (HSIL) and 3 invasive cancer] and 196 controls had complete demographic and clinical questionnaire data and data of analysis of XRCC1 polymorphism, whereas only 99 cases and 193 controls had complete data for p53 polymorphism. The frequency of pro/pro, pro/arg, and arg/arg in p53 codon 72 in cases was 15% (15/99), 58% (57/99), and 27% (27/99) and in controls was 17% (34/193), 48% (92/193), and 35% (67/193), respectively, which was not significantly different. The frequency of arg/arg, arg/gln, and gln/gln in XRCC1 codon 399 in cases was 54% (54/100), 38% (38/100), and 8% (8/100) and in controls was 58% (114/196), 37% (73/196), and 5% (9/196), respectively, which was not significantly different. No associations were found between XRCC1 codon 194 and 280 genotypes and HSIL risk. The joint effect of p53 and XRCC1 polymorphisms remained insignificant. CONCLUSIONS: Our data suggest that p53 codon 72 and XRRC1 codon 194, 280 and 399 genotypes do not influence CIN risk in the Taiwanese population.