Therapeutic effect of iodised serum milk protein, lycopene and their combination on benign prostatic hyperplasia induced in rats.

Benign prostatic hyperplasia (BPH) is a common chronic disease in ageing men. Synthetic inhibitors of 5α-reductase commonly used in BPH treatment have limited effectiveness and may cause side effects. Evaluation of iodised serum milk protein and lycopene therapeutic effect in rat BPH model was the aim of the present study. BPH was induced in male Wistar rats by surgical castration and subsequent testosterone administrations (25 mg/kg, 7 injections). Rats with induced BPH received lycopene (5 mg/kg), iodised serum milk protein (200 µg/kg) or their combination for 1 month daily. The efficacy of the treatment was evaluated by the prostate weight, prostatic index and ventral lobe epithelium thickness. In lycopene and iodised serum milk protein-treated rats, prostate weight and prostatic index were significantly reduced compared to control group; and lycopene and iodised serum milk protein used in combination yielded an additive effect. Thus, further investigation of combined supplementation with micronutrients and plant-derived substances in BPH models may help to find new opportunities or its safe and effective treatment.

Detection of Neprilysin-Derived BNP Fragments in the Circulation: Possible Insights for Targeted Neprilysin Inhibition Therapy for Heart Failure.

BACKGROUND: Entresto™ is a new heart failure (HF) therapy that includes the neprilysin (NEP) inhibitor sacubitril. One of the NEP substrates is B-type natriuretic peptide (BNP); its augmentation by NEP inhibition is considered as a possible mechanism for the positive effects of Entresto. We hypothesized that the circulating products of BNP proteolysis by NEP might reflect NEP impact on the metabolism of active BNP. We suggest that NEP-based BNP cleavage at position 17-18 results in BNP ring opening and formation of a novel epitope with C-terminal Arg-17 (BNP-neo17 form). In this study, we use a specific immunoassay to explore BNP-neo17 in a rat model and HF patient plasma. METHODS: We injected BNP into rats, with or without NEP inhibition with sacubitril. BNP-neo17 in plasma samples at different time points was measured with a specific immunoassay with neglectable cross-reactivity to intact forms. BNP-neo17 and total BNP were measured in EDTA plasma samples of HF patients. RESULTS: BNP-neo17 generation in rat circulation was prevented by NEP inhibition. The maximum 13.2-fold difference in BNP-neo17 concentrations with and without sacubitril was observed at 2 min after injection. BNP-neo17 concentrations in 32 HF patient EDTA plasma samples ranged from 0 to 37 pg/mL (median, 5.4; interquartile range, 0-9.1). BNP-neo17/total BNP had no correlation with total BNP concentration (with r = -0.175, P = 0.680) and showed variability among individuals. CONCLUSIONS: BNP-neo17 formation is NEP dependent. Considering that BNP-neo17 is generated from the active form of BNP by NEP, we speculate that BNP-neo17 may reflect both the NEP activity and natriuretic potential and serve for HF therapy guidance.

The inhibitory effect of Filipendula ulmaria (L.) Maxim. on colorectal carcinogenesis induced in rats by methylnitrosourea.

ETHNOPHARMACOLOGICAL RELEVANCE: Meadowsweet (Filipendula ulmaria (L.) Maxim.) is a medicinal plant with a variety of therapeutic properties, traditionally used in various diseases including treatment and prevention of tumors. The aim of this study was to present an ethnomedicinal justification that a meadowsweet decoction is able to inhibit colorectal carcinogenesis induced by the methylnitrosourea (MNU) in rats. MATERIALS AND METHODS: The chemical composition of meadowsweet extracts was studied by traditional methods. In animal experiments adult outbred female rats received four intrarectal instillations of MNU, one per week, at dose 4 mg in 0.5 ml saline (the total dose of MNU during the 4-week exposure was 16 mg/rat). After carcinogenic exposure one group (MNU) of rats continued to receive standard feed and tap water throughout life. In another group (MNU+meadowsweet), rats were given daily a decoction of the meadowsweet instead of drinking water and standard feed. RESULTS: Meadowsweet extracts showed a sufficiently high content of flavonoids and tannins and also some individual phenolic compounds and salicylic acid. In rats after administration of MNU the overall incidence of tumors was 91% with tumor multiplicity of 3.5. The majority of rats (86%) developed multiple tumors of large intestine (most often adenocarcinomas:88 from 107; index of multiplicity - 2.0). In rats from the group MNU+meadowsweet there was a statistically significant decrease of the overall tumor incidence and multiplicity-by 1.4 and 2.9 times, respectively, and the incidence and multiplicity of colon tumors - by 2.0 and 2.8 times, respectively; the incidence and multiplicity of malignant tumors of other localizations was also reduced-by 2.2 and 3.0 times, respectively. CONCLUSIONS: Meadowsweet extract is an effective inhibitor of colorectal carcinogenesis in experiment, that provides support for the traditional use of this plant in the oncology.

Short-term fluctuations of sugar beet damping-off by Pythium ultimum in relation to changes in bacterial communities after organic amendments to two soils.

Previously, oscillations in beet seedling damping-off by Pythium ultimum, measured as area under the disease progress curve (AUDPC), were demonstrated after incorporation of organic materials into organic and conventional soils. These periodic fluctuations of P. ultimum infections were cross-correlated with oscillations of copiotrophic CFU at lags of 2 to 4 days. For this article, we investigated whether bacterial communities and microbial activities fluctuated after a disturbance from incorporation of organic materials, and whether these fluctuations were linked to the short-term oscillations in AUDPC of beet seedling damping-off and bacterial populations (CFU) in soil. Soil microbial communities studied by polymerase chain reaction-DGGE analysis of 16S DNA after isolation of total DNA from soil and microbial activities measured as CO(2) emission rates were monitored daily for 14 days after addition of grass-clover (GC) or composted manure (CM) into organic versus conventional soils. Similar to our previous findings, AUDPC and density of copiotrophic bacteria oscillated with time. Fluctuations in species richness (S), Shannon diversity index (H), and individual amplicons on DGGE gels were also detected. Oscillations in AUDPC were positively cross-correlated with copiotrophic CFU in all soils. Oscillations in AUDPC were also positively cross-correlated with 19 to 35% of the high-intensity DNA fragments in soils amended with GC but only 2 to 3% of these fragments in CM-amended soils. AUDPC values were negatively cross-correlated with 13 to 17% of the amplicons with low average intensities in CM-amended soils, which were not correlated with densities of copiotrophic CFU. CO(2) emission rates had remarkable variations in the initial 7 days after either of the soil amendments but were not associated with daily changes in AUDPC. The results suggest that infection by P. ultimum is hampered by competition from culturable copiotrophic bacteria and some high-intensity DGGE amplicons, because AUDPC is cross-correlated with these variables at lags of 1 to 4 days. However, negative cross-correlations with low-intensity DNA fragments indicate that P. ultimum infection could also be suppressed by antagonistic bacteria with low densities that may be nonculturable species, especially in CM amended soil. The organic soil generally had lower AUDPC values, higher bacterial diversity, and negative cross-correlations between AUDPC and low-intensity DNA fragments (after CM amendment), indicating that specific bacteria that do not attain high densities may contribute to P. ultimum suppression in organic soils.

Comparative analysis of bacterial communities in a potato field as determined by pyrosequencing.

BACKGROUND: Plants selectively attract particular soil microorganisms, in particular consumers of root-excreted compounds. It is unclear to what extent cultivar type and/or growth stage affect this process. METHODOLOGY/PRINCIPAL FINDINGS: DNA-based pyrosequencing was used to characterize the structure of bacterial communities in a field cropped with potato. The rhizospheres of six cultivars denoted Aveka, Aventra, Karnico, Modena, Premiere and Desiree, at three growth stages (young, flowering and senescence) were examined, in addition to corresponding bulk soils. Around 350,000 sequences were obtained (5,700 to 38,000 per sample). Across all samples, rank abundance distributions best fitted the power law model, which indicates a community composed of a few highly dominant species next to numerous rare species. Grouping of the sequences showed that members of the Actinobacteria, Alphaproteobacteria, next to as-yet-unclassified bacteria, dominated. Other groups that were consistently found, albeit at lower abundance, were Beta-, Gamma- and Deltaproteobacteria and Acidobacteria. Principal components analyses revealed that rhizosphere samples were significantly different from corresponding bulk soil in each growth stage. Furthermore, cultivar effects were found in the young plant stage, whereas these became insignificant in the flowering and senescence stages. Besides, an effect of time of season was observed for both rhizosphere and bulk soils. The analyzed rhizosphere samples of the potato cultivars were grouped into two groups, in accordance with the allocation of carbon to starch in their tubers, i.e. Aveka, Aventra and Karnico (high) versus Premiere and Desiree (low) and thus replicates per group were established. CONCLUSIONS: Across all potato cultivars, the young plant stages revealed cultivar-dependent bacterial community structures, which disappeared in the flowering and senescence stages. Furthermore, Pseudomonas, Beta-, Alpha- and Deltaproteobacteria flourished under different ecological conditions than the Acidobacteria.

Daily changes of infections by Pythium ultimum after a nutrient impulse in organic versus conventional soils.

Bacterial populations (CFU) have been shown to oscillate in wavelike patterns after nutrient impulses in previous studies. The amplitudes and periods of oscillations could possibly be used as indicators of soil health analogous to the stability and resilience of biological populations widely accepted as indicators for ecosystem health. Limited plant and animal disease outbreaks can also be viewed as a manifestation of a healthy soil ecosystem. Two pot experiments were carried out to verify whether damping-off of beet seedlings by Pythium ultimum, measured as area under the disease progress curve (AUDPC), fluctuated over time after incorporation of organic materials into organic versus conventional soils, and to investigate whether daily dynamics of AUDPCs were linked to the dynamics of microbial populations and chemical parameters. AUDPCs oscillated significantly over time when Pythium bioassays were initiated daily after addition of ground grass and clover shoots (GC) into unplanted soils. Similar oscillations with significant harmonics of AUDPC were also observed in composted manure (CM)-amended soils but with smaller amplitudes than in GC-amended soils. The AUDPC harmonics in amended soils had periods similar to those of CFU of copiotrophic bacteria. Cross-correlation analysis demonstrated that periodic fluctuations of P. ultimum infections (AUDPCs) did not coincide with those of copiotrophic CFU but were shifted in phase. It appears that competition or antagonism from some fast-growing bacteria influenced pathogen infections, because these bacterial populations were growing and dying. Soil chemical variables, including pH, dissolved organic carbon, and NO(3)(-)-N, and NH(4)(+)-N contents, changed significantly in the initial 7 days after a nutrient impulse into soils. These changes were cross-correlated with copiotrophic CFU with time lags of approximately 1 to 2 days but were seldom associated with daily changes in AUDPCs. Organically managed soils always had lower AUDPC ratios of amended to nonamended treatments, indicating that organic materials showed stronger suppressive abilities to P. ultimum in organic than in conventional soils. The oscillations in AUDPCs and copiotrophic CFU in amended organic soil also had smaller amplitudes than in amended conventional soil. These results suggested that organically managed soils had a greater resistance and resilience to the disturbance of the amendments and, therefore, could be considered healthier than conventionally managed soils.