Effect of oral CDP-choline on visual function in young amblyopic patients

Purpose The purpose of the study was to evaluate the effect on visual function of orally administered CDP-choline in addition to patching for the treatment of amblyopia in children. Methods This was an open label parallel group study comparing patching plus oral CDP-choline with patching alone. Sixty-one participants (aged between 5 and 10 years) suffering from anisometropic or strabismic amblyopia were divided at random into two groups: Group A, 800 or 1,200 mg (according to the body weight) of orally administered CDP-choline and 2-h patching a day; Group B, 2-h patching a day. Both groups were treated for 30 consecutive days. A follow-up visit was set 60 days after the treatment was discontinued. The main outcome measure was the change in visual acuity of amblyopic eyes as measured by Snellen’s E charts. The secondary outcome measures were changes in the visual acuity of amblyopic eye as measured by isolated letters (Snellen’s E) and changes in the contrast sensitivity of amblyopic eyes. Results The addition of CDP-choline to patching therapy was not found to be more effective than patching alone after 30-day treatment. The present results showed that adding CDP-choline to patching stabilised the effects obtained during the treatment period. In fact, whereas the participants treated only with patching showed a decrease in visual acuity at 90 days, these receiving CDP-choline and patching combined appeared to maintain the results obtained (two-way ANOVA: P = 0.0042). Similar results were obtained when measuring visual acuity by isolated Snellen’s E letters. Conclusions In amblyopic patients, CDP-choline combined with patching contributes to obtaining more stable effects than patching alone. Fabio De Gregorio works as an advisor for Tubilux Pharma S.p.A. The authors have full control of all primary data and they agree to allow Graefe’s Archives for Clinical and Experimental Ophthalmology to review their data if requested.     

2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

A recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH(4) (the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MS-MS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.     

PDX1-MODY: A rare missense mutation as a cause of monogenic diabetes

Maturity-Onset Diabetes of the Young type 4 is a rare form of diabetes mellitus, caused by mutations in the PDX1 gene. However, only a few mutations in this gene have been associated as a cause of monogenic diabetes up to date. It makes difficult to create a clinical manifestation profile of this disease and, consequently, to improve the therapeutic management for these patients. Here we report a normal weight woman, diagnosed with diabetes mellitus at 27 years old, during her first pregnancy. At the time of the recruitment, she was 40 years old and had a body mass index of 23.9 kg/m², glycated hemoglobin level of 9.6%, and fasting plasma glucose (FPG) of 254 mg/dL. She presented no diabetic complications and she was being treated with insulin. She reported a family history of diabetes mellitus characteristic of an autosomal dominant mode of inheritance. Molecular analysis of the PDX1 gene revealed the missense variant c.532G > A (p.(Glu178Lys)) segregating from the patient to her son, reported as diabetic. It was absent in her healthy daughter. The c.532G > A seems to be a rare variant, absent in human variants databases, and among 86 normoglycemic controls. Eight in silico algorithms classified this variant as probably pathogenic. Additionally, analysis of the evolutionary conservation showed the glutamic acid in the position 178 of PDX-1 protein as conserved among several species. Our findings reinforce the importance of screening rare MODY genes among families with suspicion of monogenic diabetes to help better understand the clinical manifestations of this disease.     

Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.     

Consistency of vendor-specified activity values for 192Ir brachytherapy sources

A long-term comparison was done between the manufacturer-stated ¹⁹²Ir activity and the measured ¹⁹²Ir activities determined with a well-type ionization chamber. Sources for a Nucletron Micro Selectron high-dose-rate (HDR) unit were used for this purpose. The radioactive sources reference activities were determined using a PTW well-type ionization chamber traceable to the National Institute of Standards and Technology Primary Calibration Laboratory. The measurements were taken in a period of 56 months with 17 different radioactive sources. The manufacturer stated activities were taken from the source calibration certificate provided by the manufacturer. These values were compared with the measured activities. The results have shown that both the percentage deviation of the monthly control measurements with the well-type chamber and the ratio between the measured activities to the manufacturer-stated value lie within ± 2.5%. These results were compared with similar published data and with uncertainty level (3% of the mean and 5% maximum deviation from mean) for brachytherapy sources calibration recommended by the AAPM. It was concluded that a threshold level of ±2.5% can be used as a suitable quality assurance indicator to spot problems in our department. The typical ±5% uncertainty as provided by the manufacturers may be tightened to ±3% to be more in line with published AAPM reports.