Adenomas – Genetic factors in colorectal cancer prevention

Colorectal cancer is the second most common type of cancer both in Europe and Poland. During the last 30 years more than a 3-fold increase has been observed in Poland due to environmental and genetic factors. Almost all colorectal malignancies are related to the formation and malignant transformation of colorectal dysplasia and adenoma. Efforts aiming to decrease the number of colorectal cancer deaths are focused on the disease early detection. Genetic diagnosis for hereditary syndromes predisposing to colorectal cancer has been developed and is a part of the routine treatment. Most cancers are sporadic. They often develop from polyps in the colon. In addition to the genetic events described in the 1990s, showing the adenoma transformation into carcinoma that has been a prime example of malignant transformation for a long time, there are also other possibilities of neoplastic transformation. The recognition of colorectal cancer risk factors make sense as their nature is lifestyle- and diet-related. In this review paper those risk factors are presented and the prevention of colorectal cancer is discussed taking into account genetic factors.     

Karyotype reshufflings of <Emphasis Type="Italic">Festuca pratensis</Emphasis> × <Emphasis Type="Italic">Lolium perenne</Emphasis> hybrids

Many different processes have an impact on the shape of plant karyotype. Recently, cytogenetic examination of Lolium species has revealed the occurrence of spontaneous fragile sites (FSs) associated with 35S rDNA regions. The FSs are defined as the chromosomal regions that are sensitive to forming gaps or breaks on chromosomes. The shape of karyotype can also be determined by interstitial telomeric sequences (ITSs), what was recognized for the first time in this paper in chromosomes of Festuca pratensis × Lolium perenne hybrids. Both FSs and ITSs can contribute to genome instabilities and chromosome rearrangements. To evaluate whether these cytogenetic phenomena have an impact on karyotype reshuffling observed in Festuca × Lolium hybrids, we examined F₁ F. pratensis × L. perenne plants and generated F₂-F₉ progeny by fluorescent in situ hybridization (FISH) using rDNA sequences, telomere and centromere probes, as well as by genomic in situ hybridization (GISH). Analyses using a combination of FISH and GISH revealed that intergenomic rearrangements did not correspond to FSs but overlapped with ITSs for several analyzed genotypes. It suggests that internal telomeric repeats can affect the shape of F. pratensis × L. perenne karyotypes. However, other factors that are involved in rearrangements and have a more crucial impact could exist, but they are still unknown.     

Two new quill mite species of the genus <Emphasis Type="Italic">Psittaciphilus</Emphasis> Fain,Bochkov &amp; Mironov, 2000 (Acariformes: Syringophilidae) associated with pigeons and doves (Columbiformes: Columbidae)

Two new quill mite species of the genus Psittaciphilus Fain, Bochkov & Mironov, 2000 (Acariformes: Prostigmata: Syringophilidae) collected from columbiform birds (Columbiformes) are described: Psittaciphilus montanus n. sp. form the ruddy quail-dove Geotrygon montana Gosse from Trinidad and Tobago, Brazil and Panama, and Psittaciphilus patagioenas n. sp. from the band-tailed pigeon Patagioenas fasciata (Say) from Colombia and the scaled pigeon Patagioenas speciosa (Gmelin) from Surinam. A key to the species of the genus Psittaciphilus is provided. Our finding is the first record of the representatives of this genus on columbiform birds.     

Anandamide protects from low serum-induced apoptosis via its degradation to ethanolamine

Anandamide (AEA) is a lipid molecule belonging to the family of endocannabinoids. Various studies report neuroprotective activity of AEA against toxic insults, such as ischemic conditions and excitotoxicity, whereas some show that AEA has pro-apoptotic effects. Here we have shown that AEA confers a protective activity in N18TG2 murine neuroblastoma cells subjected to low serum-induced apoptosis. We have demonstrated that the protection from apoptosis by AEA is not mediated via the CB1 receptor, the CB2 receptor, or the vanilloid receptor 1. Interestingly, breakdown of AEA by fatty acid amide hydrolase is required for the protective effect of AEA. Furthermore, the ethanolamine (EA) generated in this reaction is the metabolite responsible for the protective response. The elevation in the levels of reactive oxygen species during low serum-induced apoptosis is not affected by AEA or EA. On the other hand, AEA and EA reduce caspase 3/7 activity, and AEA attenuates the cleavage of PARP-1. Taken together, our results demonstrate a role for AEA and EA in the protection against low serum-induced apoptosis.     

Dynamic changes in root hydraulic properties in response to nitrate availability

Changes in root hydraulic resistance in response to alterations in nitrate supply were explored in detail as a potential mechanism that allows plants to respond rapidly to changes in their environment. Sunflower (Helianthus annuus cv. Holiday) plants grown hydroponically with limited nitrate availability (200 micromol l(-1)) served as our model system. Experimental plants were 6-9-weeks-old with total dry mass of 2-4 g. Root pressurization of intact plants and detached root systems was used to elucidate the temporal dynamics of root hydraulic properties in sunflower plants following changes in external nitrate availability. The response was rapid, with a 20% decrease in hydraulic resistance occurring within the first hour after the addition of 5 mM nitrate and the magnitude of the effect was dependent on nitrate concentration. The change in root hydraulic resistance was largely reversible, although the temporal dynamics of the response to nitrate addition versus nitrate withdrawal was not symmetric (a gradual decrease in resistance versus its fast increase), raising the possibility that the underlying mechanisms may also differ. Evidence is presented that the observed changes in root hydraulic properties require the assimilation of nitrate by root cells. The hydraulic resistance of roots, previously stimulated by the addition of nitrate, increased more than in control plants in low nitrate under anoxia and that suggests a key role of aquaporin activity in this response. It is proposed that a rapid decrease in root hydraulic resistance in the presence of increased nitrate availability is an important trait that could enhance a plant's ability to compete for nitrate in the soil.     

Ecdysteroids and juvenile hormones of whiteflies, important insect vectors for plant viruses

Ecdysteroids and juvenile hormones (JHs) regulate many physiological events throughout the insect life cycle, including molting, metamorphosis, ecdysis, diapause, reproduction, and behavior. Fluctuation of whitefly ecdysteroid levels and the identity of the whitefly molting hormone (20-hydroxyecdysone) have only been reported within the last few years. An ecdysteroid commitment peak that is associated with the reprogramming of tissues for a metamorphic molt in many holometabolous and some hemimetabolous insect species was not observed in last nymphal instars of either the sweet potato whitefly, Bemisia tabaci (Biotype B), or the greenhouse whitefly, Trialeurodes vaporariorum. Ecdysteroids reach peak levels 1-2 days prior to the initiation of the nymphal-adult metamorphic molt. Adult eye and wing differentiation which signal the onset of this molt begin earlier in 4th instar T. vaporariorum (Stages 4 and 5, respectively) than in B. tabaci (Stage 6), and the premolt peak is 3-4 times greater in B. tabaci ( approximately 400 fg/microg protein) than in T. vaporariorum ( approximately 120 fg/microg protein). The JH of B. tabaci nymphs and eggs was found to be JH III, supporting the view that JHs I and II are, with rare exception, only present in lepidopteran insects. In B. tabaci eggs, JH levels were approximately 10 times greater on day 2/3 (0.44 fg/egg or 0.54 ng/g) than on day 5 (0.04 fg/egg or 0.054 ng/g) post-oviposition. Approximately, 1.4 fg/2nd-3rd instar nymph (0.36 ng/g) was detected. It is probable that the relatively high level of JH in day 2/3 eggs is associated with the differentiation of various whitefly tissues during embryonic development.     

Simultaneous LC-MS-MS determination of cyclosporine A, tacrolimus, and sirolimus in whole blood as well as mycophenolic acid in plasma using common pretreatment procedure

The purpose of the study was to develop rapid and simple procedure for simultaneous determination of cyclosporine A (CsA), tacrolimus (TCR), and sirolimus (SIR) in whole blood and mycophenolic acid (MPA) in plasma. Ascomycin (ASCO), cyclosporine D (CsD), and desmethoxysirolimus (DMSIR) were used as internal standards (IS) for TCR, CsA and MPA, and SIR, respectively. In the method development, six-level blood calibrators were used for CsA (range 47-1725 ng/ml), TCR (range 2.1-38.8 ng/ml), and SIR (range 2.4-39.6 ng/ml). Four-level calibrators were used for MPA (range 0.15-5.48 microg/ml). Four levels of quality control (QC) standards were used for blood samples, together with two levels of QC standards in plasma. All QC standards and calibrators were obtained from commercial sources. Sample preparation based on precipitation of 50 microl of sample in zinc sulfate-methanol-acetonitrile mixture containing IS, followed by centrifugation. HPLC was performed on ChromSpher pi column, 30 mm x 3 mm, in ballistic gradient of ammonium formate buffer-methanol at 0.8 ml flow rate. Following gradient elution profile was applied: 0-1.2 min at 30% methanol (divert valve to waste), 1.21-3.1 min 97% methanol (divert valve to detector), 3.11-3.7 min 30% methanol (divert valve to waste). ESI-MS-MS (MRM) was done on TSQ Quantum instrument with ESI source in positive ion mode. Ammoniated adducts of protonated molecules were used as precursor ions for all analytes but MPA. For this compound sodium adduct was used. Following transitions were monitored: for CsA m/z 1220-1203; for CsD 1234-1217; for SIR 931.6-864.5 and 882.6; for DMSIR 902-834.5; for TCR 821.5-768.5 and 785.5; for ASCO 809.5-756; for MPA 343-211.6; for MPA-glucuronide 514-306 and 211.6. The limits of quantitation were: 1 ng/ml for TCR and SIR, 20 ng/ml for CsA, and 0.1 microg/ml for MPA. Post-column infusion experiments showed that no positive or negative peaks appeared after injection of matrix in the elution range of target compounds. General signal suppression caused by matrix ranged from 20-40%, and was caused mainly by zinc sulfate present in deproteinizing solution. Extracted samples were stable for 2 days at 4 degrees C and for at least 20 days at -20 degrees C. MPA was fully separated from its glucuronide, which was eluted at around 0.7-0.8 min and directed to the waste. Some mutual cross-contribution of CsD and CsA was observed (below 1%), other IS did not contribute to target compounds and vice versa. Observations of chromatograms from patients taken single therapy demonstrated that possible metabolites of CsA, TCR, or SIR did not interfere with target compounds or IS.     

Dietary natural products as emerging lipoprotein(a)-lowering agents

Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy in reducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)-lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta-analyses, natural products, including l -carnitine, coenzyme Q ₁₀, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a) lowering.