8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanosine levels in human urine do not depend on diet

In the present study, we used the method involving HPLC pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection for the determination of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in human urine. The mean levels of 8-oxoGua and 8-oxodGuo in the urine samples of the subjects on unrestricted diet were respectively 1.87 nmol/kg 24 h (±0.90) and 0.83 nmol/kg 24h (±0.49), and in the case of the groups studied, they did not depend on the applied diet. The sum of the amounts of both compounds in urine can give information about the formation rate of 8-oxoGua in cellular DNA. It is also likely that the levels of modified nucleo-base/side in urine sample are reflective of the involvement of different repair pathways responsible for the removal of 8-oxodGuo from DNA, namely base excision repair (BER) and nucleotide excision repair (NER).     

Anticonvulsant Effectiveness and Neurotoxicity Profile of 4-butyl-5-[(4-chloro-2-methylphenoxy)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) in Mice

Neurochemical Research - Protective (antiseizure) effects of 4-butyl-5-[(4-chloro-2-methylphenoxy)-methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) and acute neurotoxic effects were...     

The impact of different plant extracts on biological parameters of Housefly [Musca domestica (Diptera: Muscidae)]: Implications for management

Housefly is a significant domestic pest, which causes nuisance. The use of insecticides is discouraged to manage housefly; therefore, alternative management strategies are inevitable. The current study investigated the impact of different plant extracts, i.e., Moringa oleifera (moringa), Allium sativum (garlic) and Piper nigrum (black pepper) on biological parameters of house fly. Two different concentrations (i.e., 25 and 50%) of the extracts were blended in larval diet made through mixing of wheat bran, yeast and dried milk powder. The results indicated significant differences for larval duration. Maximum larval duration was recorded for garlic followed by black pepper and moringa, respectively. In case of pupal duration, non-significant differences were observed among plant extracts. Increase rate of oviposition was noticed with moringa at 25% concentration, while decreased oviposition rate was noted for garlic with 50% concentration. Egg hatching percentage remained non-significant for the botanical extracts. The highest survival was observed with moringa, while garlic resulted in the lowest survival. The highest repellency was noticed for garlic followed by black pepper, whereas moringa resulted in the lowest repellency after 30, 60 and 90 min. Prolonged developmental time was observed for bot concentrations of garlic, whereas moringa noted the shortest developmental time. Thus moringa was found to be a promoter of housefly development. Minimum adult emergence was found with both concentrations of garlic followed by 50% concentration of black pepper. The 50% concentration of black pepper promoted the population of adult males, while both concentrations of moringa and 25% concentration of black pepper encouraged the population of female adults. Study outcomes depicted that tested botanical extracts had significant potential for disturbing biological parameters of housefly. The garlic extracts can potentially be used to manage housefly. However, further investigations on the larval and adult mortality are needed.     

Thrombin impairs the angiogenic activity of extravillous trophoblast cells via monocyte chemotactic protein-1 (MCP-1): A possible link with preeclampsia

Cytokines’ secretion from the decidua and trophoblast cells has been known to regulate trophoblast cell functions, such as Extravillous trophoblasts (EVTs) cell migration and invasion and remodeling of spiral arteries. Defective angiogenesis and spiral arteries transformation are mainly caused by proinflammatory cytokines and excessive thrombin generation during preeclampsia. Monocyte chemotactic protein-1 (MCP-1), a crucial cytokine, has a role in maintaining normal pregnancy. In this study, we explored whether thrombin regulates the secretion of MCP-1 in HTR-8/SVneo cells; if yes, what is its function? We used HTR-8/SVneo cells, developed from ?rst trimester villous explants of early pregnancy, as the model of EVTs. MCP-1 gene silencing was performed using gene-specific siRNA. qPCR and ELISA were performed to estimate the expression and secretion of MCP-1. Here, we found that thrombin enhanced the secretion of MCP-1 in HTR-8/SVneo cells. Proteinase-activated receptor-1 (PAR-1) was found as the primary receptor, regulating MCP-1 secretion in these cells. Furthermore, MCP-1 secretion is modulated via protein kinase C (PKC) α, β, and Rho/Rho-kinase-dependent pathways. Thrombin negatively regulates HTR-8/SVneo cells’ ability to mimic tube formation in an MCP-1 dependent manner. In conclusion, we propose that thrombin-controlled MCP-1 secretion may play an essential role in normal placental development and successful pregnancy maintenance. Improper thrombin production and MCP-1 secretion during pregnancy might cause inadequate vascular formation and transformation of spiral arteries, which may contribute to pregnancy disorders, such as preeclampsia.     

Missense mutations and polymorphisms of the <Emphasis Type="Italic">MC4R</Emphasis> gene in Polish obese children and adolescents in relation to the relative body mass index

Extensive studies of the MC4R gene polymorphism showed that, among numerous variants, there are mutations responsible for monogenic obesity, as well as polymorphisms negatively correlated with the risk of obesity. In this report, we present the first studies of the whole coding sequence of the MC4R gene in 243 Polish obese children and adolescents (the mean relative body mass index [RBMI] was 163.6). In addition, 101 non-obese adults were also analyzed. Direct sequencing facilitated the identification of six missense (K73R, V103I, T112M, S127L, M215L, and I251L) and one silent (c.756 C > T) single-nucleotide polymorphisms (SNPs). Two non-synonymous polymorphisms (K73R and M215L) appeared to be novel and one was found in obese patients (M215L, one patient) and one in non-obese adults (K73R, one person). The overall frequency of non-synonymous variant carriers reached 4.1% and 6.9% in obese patients and non-obese adults, respectively. Only one obesity-associated variant (127L) was found in two obese patients (0.82%) and in two non-obese adults (1.98%). The obesity-protecting variants (103I and 251L) appeared to be the most common in both groups: 3.3% and 4.0%, respectively. It was also observed that the RBMI in obese children and adolescents carrying the minor variants did not differ significantly from the non-carriers; however, the expected trends for the associated and protecting variants were observed. We conclude that the contribution of the MC4R gene variants to the pathogenesis of obesity in Polish children and adolescents is low.     

Thermal boost combined with interstitial brachytherapy in breast conserving therapy – Assessment of early toxicity

Background

Hyperthermia (HT) causes a direct damage to cancerous cells and/or sensitize them to radiotherapy with usually minimal injury to normal tissues. Adjuvant HT is probably one of the most effective radiation sensitizers known and works best when delivered simultaneously with radiation. In breast conserving therapy, irradiation has to minimize the risk of local relapse within the treated breast, especially in an area of a tumor bed. Brachytherapy boost reduces 5-year local recurrence rate to mean 5,5%, so there still some place for further improvement. The investigated therapeutic option is an adjuvant single session of local HT (thermal boost) preceding standard CT-based multicatheter interstitial HDR brachytherapy boost in order to increase the probability of local cure.

Aim

To report the short-term results in regard to early toxicity of high-dose-rate (HDR) brachytherapy (BT) boost with or without interstitial microwave hyperthermia (MV HT) for early breast cancer patients treated with breast conserving therapy (BCT).

Materials and methods

Between February 2006 and December 2007, 57 stage IA–IIIA breast cancer patients received a 10 Gy HDR BT boost after conservative surgery and 42.5–50 Gy whole breast irradiation (WBI) ± adjuvant chemotherapy. 32 patients (56.1%) were treated with additional pre-BT single session of interstitial MW HT to a tumor bed (multi-catheter technique). Reference temperature was 43 °C and therapeutic time (TT) was 1 h. Incidence, severity and duration of radiodermatitis, skin oedema and skin erythema in groups with (I) or without HT (II) were assessed, significant p-value ≤ 0.05.

Results

Median follow-up was 40 months. Local control was 100% and distant metastasis free survival was 91.1%. HT sessions (median): reference temperature 42.2 °C, therapeutic time (TT) 61.4 min, total thermal dose 42 min and a gap between HT and BT 30 min. Radiodermatitis grades I and II occurred in 24 and 6 patients, respectively, differences between groups I and II were not significant. Skin oedema and erythema occurred in 48 (85.7%) and 36 (64.3%) cases, respectively, and were equally distributed between the groups. The incidence and duration of skin oedema differed between the subgroups treated with different fractionation protocols of WBI, p = 0.006. Skin oedema was present up to 12 months. No difference in pattern of oedema regression between groups I and II was observed, p = 0.933.

Conclusion

Additional thermal boost preceding standard HDR BT boost has a potential of further improvement in breast cancer local control in BCT. Pre-BT hyperthermia did not increase early toxicity in patients treated with BCT and was well tolerated. All side effects of combined treatment were transient and were present for up to 12 months. The increase in incidence of skin oedema was related to hypofractionated protocols of WBI. The study has to be randomized and continued on a larger group of breast cancer patients to verify the potential of local control improvement and to assess the profile of late toxicity.     

Luminescent properties of europium complexes with bis(diphenylphosphino)alkane dioxides

Eu(NO₃)₃?5H₂O and EuCl₃?6H₂O were allowed to react with bis(diphenylphosphino)alkane dioxides Ph₂P(O)(CH₂)_nP(O)Ph₂ (n = 2, 4, 6) to obtain polymeric and binuclear complexes. The prepared compounds were structurally characterized by X‐ray diffraction. Luminescence measurements (emission and excitation spectra, quantum yields, lifetimes) were compared with crystallographic data in order to find a relationship between luminescent properties of the Eu(III) complexes and their structures. The Eu(III) polymers, especially [Eu(dpphO₂)₂Cl₂]⁺Cl^–}_n, have shown extremely long luminescence lifetimes, up to 3.73 ms, as a result of a highly protecting hydrophobic shield. Copyright © 2011 John Wiley & Sons, Ltd.