Chromosome Segregation Analysis in Human Embryos Obtained from Couples Involving Male Carriers of Reciprocal or Robertsonian Translocation

The objective of this study was to investigate the frequency and type of chromosome segregation patterns in cleavage stage embryos obtained from male carriers of Robertsonian (ROB) and reciprocal (REC) translocations undergoing preimplantation genetic diagnosis (PGD) at our reproductive center. We used FISH to analyze chromosome segregation in 308 day 3 cleavage stage embryos obtained from 26 patients. The percentage of embryos consistent with normal or balanced segregation (55.1% vs. 27.1%) and clinical pregnancy (62.5% vs. 19.2%) rates were higher in ROB than the REC translocation carriers. Involvement of non-acrocentric chromosome(s) or terminal breakpoint(s) in reciprocal translocations was associated with an increase in the percent of embryos consistent with adjacent 1 but with a decrease in 3∶1 segregation. Similar results were obtained in the analysis of nontransferred embryos donated for research. 3∶1 segregation was the most frequent segregation type in both day 3 (31%) and spare (35%) embryos obtained from carriers of t(11;22)(q23;q11), the only non-random REC with the same breakpoint reported in a large number of unrelated families mainly identified by the birth of a child with derivative chromosome 22. These results suggest that chromosome segregation patterns in day 3 and nontransferred embryos obtained from male translocation carriers vary with the type of translocation and involvement of acrocentric chromosome(s) or terminal breakpoint(s). These results should be helpful in estimating reproductive success in translocation carriers undergoing PGD.     

The role of iNOS inhibitors on lung injury induced by gastrointestinal decontamination agents aspiration

Aspiration is a devastating complication during decontamination procedure in poisoning patients. We have investigated whether S-methylisothiourea protects different pulmonary aspiration gastrointestinal decontamination agent-induced lung injury in rats. Forty-two male Sprague-Dawley rats were assigned to one of six groups (n = 7): normal saline, activated charcoal, polyethylene glycol, normal saline + S-methylisothiourea treated activated charcoal + S-methylisothiourea treated and polyethylene glycol + S-methylisothiourea treated. Normal saline, activated aharcoal and polyethylene glycol were instilled into the lungs. The rats received S-methylisothiourea i.p twice daily for 7 days. Serum surfactant protein D, oxidative stress products and inducible nitric oxide synthase expression in the lung were investigated. The aspiration of activated charcoal significantly increased all histopathological scores (P < 0.01). Only peribronchial inflammatory cell infiltration, alveolar edema, and alveolar histiocytes were increased in the polyethylene glycol groups as compared to the normal saline group (P < 0.05). Pulmonary aspiration increased serum malondialdehyde (P < 0.001), and surfactant protein D (P < 0.05) levels and decreased serum superoxide dismutase levels (P < 0.05). S-methylisothiourea treatment decreased all histopathological scores in the activated charcoal treated S-methylisothiourea group (P < 0.01) and only decreased alveolar edema and alveolar histiocytes in the polyethylene glycol-treated S-methylisothiourea group (P < 0.05). S-methylisothiourea treatment reduced elevated oxidative factors, inducible nitric oxide synthase activity and serum surfactant protein D levels. Our findings showed that S-methylisothiourea may be a protective drug against Activated Charcoal and Polyethylene Glycol-induced lung injury.     

Small-molecule inhibitors of bacterial AddAB and RecBCD helicase-nuclease DNA repair enzymes

The AddAB and RecBCD helicase-nucleases are related enzymes prevalent among bacteria but not eukaryotes and are instrumental in the repair of DNA double-strand breaks and in genetic recombination. Although these enzymes have been extensively studied both genetically and biochemically, inhibitors specific for this class of enzymes have not been reported. We developed a high-throughput screen based on the ability of phage T4 gene 2 mutants to grow in Escherichia coli only if the host RecBCD enzyme, or a related helicase-nuclease, is inhibited or genetically inactivated. We optimized this screen for use in 1536-well plates and screened 326,100 small molecules in the NIH molecular libraries sample collection for inhibitors of the Helicobacter pylori AddAB enzyme expressed in an E. coli recBCD deletion strain. Secondary screening used assays with cells expressing AddAB or RecBCD and a viability assay that measured the effect of compounds on cell growth without phage infection. From this screening campaign, 12 compounds exhibiting efficacy and selectivity were tested for inhibition of purified AddAB and RecBCD helicase and nuclease activities and in cell-based assays for recombination; seven were active in the 0.1-50 μM range in one or another assay. Compounds structurally related to two of these were similarly tested, and three were active in the 0.1-50 μM range. These compounds should be useful in further enzymatic, genetic, and physiological studies of these enzymes, both purified and in cells. They may also lead to useful antibacterial agents, since this class of enzymes is needed for successful bacterial infection of mammals.     

Phototherapy increases DNA damage in lymphocytes of hyperbilirubinemic neonates

Phototherapy is commonly used in the treatment of hyperbilirubinemia in newborns. No serious side effects related to phototherapy have been observed, but concerns regarding its potential to damage DNA have been expressed, based on animal or cell-culture studies. The aim of this study was to investigate, in neonates with hyperbilirubinemia, the possible relation between phototherapy and DNA damage. The study included 33 full-term newborns with non-physiological jaundice and 14 healthy newborns with physiological jaundice as controls. Phototherapy was performed with an array of six fluorescent lamps producing radiation with wavelengths of 480-520 nm at 12 microW/cm(2)/nm. DNA damage in lymphocytes was determined by use of the alkaline comet assay. The DNA damage increased significantly with the duration of phototherapy, as shown by measurements at 24, 48, and 72 h (P<0.001). These findings indicate that phototherapy, widely used in neonatology units, increases DNA damage in newborns. It remains to be seen whether the genotoxic effect observed in the present study can cause any long-term health effect in phototherapy-treated infants in later life.     

Topotecan Treatment and Its Toxic Effects on Hematologic Parameters and Trace Elements

The aim of this study was to investigate the effects of topotecan, a topoisomerase I-inhibiting anticancer agent, on hematologic parameters and serum levels of trace elements. The study was conducted on three groups consisting of 16 and 18 rabbits in the study groups and 15 rabbits in the control group. Rabbits in group I (n = 16) received high-dose topotecan intravenously (i.v.; 0.5 mg/kg once daily), while rabbits in group II (n = 18) received low-dose topotecan i.v. (0.25 mg/kg once daily) for 3 days. The 15 rabbits comprising the control group did not receive topotecan. Serum samples were collected from each rabbit on the first day, before the treatment, and on the 15th day of treatment. Erithrocytes, hemoglobin, white blood cell count, thrombocyte count, and trace elements such as selenium, copper, lead, zinc, and cobalt were analyzed. Hemoglobin levels and erythrocyte counts were lower in both study groups than in the control group. However, thrombocyte and leukocyte counts were similar in all three groups (p > 0.005). Serum trace element levels (copper, lead, zinc, and cobalt) did not differ significantly between groups. However, serum selenium levels were significantly lower in both study groups than the control group (p < 0.001). The results revealed that topotecan treatment causes a decrease in erythrocyte counts and hemoglobin levels due to bone marrow suppression, and these effects must be taken into account during treatment. In addition, selenium supplementation might be helpful in cancer patients receiving topotecan to increase the effect of the chemotherapeutic agent.     

Renoprotective effect of Erdosteine in rats against gentamicin nephrotoxicity: a comparison of 99mTc-DMSA uptake with biochemical studies

Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.     

Anatomy, palynology and nutlet micromorphology of Turkish endemic Teucrium sandrasicum (Lamiaceae)

In this study, the anatomical features of the leaf and stem, besides the pollen and nutlet characteristics of Teucrium sandrasicum are investigated. T. sandrasicum, belonging to sect. Teucrium, is an endemic perennial herb growing on serpentine around Muğla province. The anatomical studies on T. sandrasicum revealed that the stem shares the general characteristics of the Labiatae family. The leaves clearly exhibit xeromorphy due to features such as the distribution of stomata on the lower surface (hipostomatic), the occurrence of guard cells below the epidermis (xeromorphic type), inrolled margins, thick cuticle layer, thick outer epidermal cell wall, a high density of trichomes and thick palisade layer of the mesophyll. The anatomical studies showed that the upper epidermal cells of the leaf include many spherocrystals. The pollen grains are prolate, medium in size, 3-colpate with verrucate ornamentation. The nutlets are ellipsoid with a reticulate-verrucate surface. The results have proven that T. sandrasicum is different from the other species of the sect. Teucrium because of the branched trichomes on the stem and the lack of eglandular trichomes on the nutlets.     

Phytogeographical distribution of <Emphasis Type="Italic">Vipio</Emphasis> Latreille, 1804 (Hymenoptera: Braconidae: Braconinae) in Turkey,with a key to the species in Turkey and adjacent regions

The distribution of Vipio Latreille, 1804 species (Hymenoptera: Braconidae: Braconinae) within eight phytogeographical provinces in Turkey is presented on the basis of field studies during 1980–2004. A total of twelve species were found, and the majority of species were associated with the Subeuxin, Euxin, Xeroeuxin and Mediterranean provinces. Vipio humerator (Costa, 1885), V. longicauda (Boheman, 1853) and V. tentator (Rossi, 1790) were the most common species in Turkey, and V. mlokossewiczi Kokoujev, 1898 is a new record for the Turkish fauna. An identification key is provided for 18 species of Vipio from Turkey and adjacent regions with relevant figures of the wings and metasoma.     

<Emphasis Type="Italic">Bracon (Lucobracon) iskilipus</Emphasis> sp. n. (Hymenoptera: Braconidae: Braconinae) from the Central Black Sea region of Turkey

During the studies on the Turkish Braconidae, a new species Bracon (Lucobracon) iskilipus sp. n. from the Turkish Central Black Sea region was recorded. Bracon (Lucobracon) iskilipus sp. n. was described, its morphological diagnostic characters were illustrated and it was compared with the related Bracon (Lucobracon) moczari Papp.