Effect of etodolac on the prostaglandin concentrations in the kidney of the normal rat

The effect of acute and subchronic dosing with etodolac on the renal PGE₂ and 6-keto-PGF_1α concentrations in the normal rat were studied. Etodolac and other nonsteroidal antiinflammatory drugs (NSAIDs) were administered orally, at equieffective antiinflammatory doses, to normal rats either as a single dose or as seven daily doses. Whole kidney prostaglandin (PG) concentrations were measured. In the acute study, etodolac (3 mg/kg) did not significantly lower the PGE₂ levels for up to 4 hr postdosing. In contrast, naproxen (3 mg/kg) and piroxicam (0.5 mg/kg) significantly decreased the PGE₂ levels to about 20% and 60% of control, respectively. Similar reductions in 6-keto-PGF_1α concentrations were observed. In the subchronic study, etodolac (3 mg/kg/day) did not lower either PGF₂ or 6-keto-PGF_1α concentrations whereas naproxen (3 mg/kg/day), piroxicam (0.5 mg/kg/day), indomethacin (1 mg/kg/day), and aspirin (300 mg/kg/day) significantlydecreased both PGs. In both studies, the effect of etodolac was significantly different from that of the NSAIDs. It is concluded that etodolac possesses only a very weak capacity to lower renal PGs, and therefore is unlikely to cause any renal complications related to PG biosynthesis inhibition.     

Prenatal diagnosis of horseshoe kidney by measurement of the renal pelvic angle.

OBJECTIVE: The aim of this study was to evaluate the usefulness of measurement of the angle between bilateral renal pelves on axial views in the prenatal ultrasonographic diagnosis of horseshoe kidney. METHODS: We retrospectively measured the renal pelvic angle in 19 fetuses with horseshoe and 20 fetuses with normal kidneys in the second and third trimesters. Renal pelvic angle was defined as the angle between the long axis of the renal pelves on the axial view of the abdomen. We compared the renal pelvic angles of horseshoe and normal kidneys with unpaired t-test. Taking 140 degrees as a cut-off value, we calculated the sensitivity, specificity and accuracy of pelvic angle measurement for the prenatal diagnosis of horseshoe kidney. RESULTS: The mean pelvic angles in the fetuses with horseshoe kidney were 116 degrees and 110 degrees in the second and third trimester, respectively. In the normal fetuses, the equivalent angles were 172 degrees and 161 degrees. The difference between the two groups was statistically significant (P < 0.01). Using 140 degrees as the discriminating criterion, the sensitivity, specificity and accuracy of renal pelvic angle measurement for the prenatal diagnosis of horseshoe kidney were all 100%. Fifteen of 19 fetuses with horseshoe kidney had no other abnormality. Four (21%) fetuses had severe complex abnormalities which were associated with trisomy 18 in three cases. CONCLUSION: Observation and measurement of the renal pelvic angle is a simple and useful method in the prenatal diagnosis of the horseshoe kidney.     

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA₂ is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG₂ acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non‐parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti‐PCP and the IgG₂ anti‐PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG₂ anti‐PCP against IgA total anti‐PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age‐related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.     

The effect of cognitive-behavioral group therapy on the self-esteem, depression, and self-efficacy of runaway adolescents in a shelter in South Korea.

This study examined the effects of cognitive-behavioral group therapy (CBT) on the self-esteem, depression, and self-efficacy of runaway adolescents residing in a shelter in Seoul, South Korea. The study used a control group pretest-posttest design. The experimental group and the control group consisted of 14 and 13 male subjects, respectively, with subjects having been randomly assigned to these groups. The experimental group participated in a CBT that consisted of eight sessions over an 8-week period; the control group did not participate in the program. To examine the effects of the CBT on dependent variables, the Wilcoxon signed rank test was used. The scores on depression decreased significantly (z = -2.325, p = .02) and those on self-efficacy increased significantly (z = -2.098, p = .03) after the intervention in the experimental group. There was no significant change on self-esteem (z = -1.19, p = .23). In the control group, the scores on depression, self-esteem, and self-efficacy did not change significantly after the intervention period. The CBT developed in this study consisted of structured and specific content that could be usefully applied to runaway adolescents residing in a shelter.     

The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.