Age changes in the tigroid substance of neutrons of the lateral preoptic nucleus of hypothalamus under different light modes

The article presents analysis of the results of the original histochemical studies of tigroid substance of neurons of the lateral preoptic nucleus of  hypothalamus in mature and old rats under the influence of different light modes. In all observations, the tigroid substance was located in the cytoplasm of neurons of the lateral preoptic nucleus of hypothalamus in the form of individual granular formations of different sizes and shapes. The amount of tigroid substance of neurons of the lateral preoptic nucleus of hypothalamus in mature rats is greater than in older rats. At the same time, it should be noted that different experimental conditions significantly affected the amount of tigroid substance in neurons of the lateral preoptic nucleus of hypothalamus in old rats. In particular, under conditions of light deprivation, the optical density of specific histochemical staining for tigroid substance in neurons of the lateral preoptic nucleus of hypothalamus increased significantly (p<0,001), and under conditions of light stimulation, on the contrary, probably decreased (p<0,001)

Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial

Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m−2 b.i.d. on days 1–14, docetaxel 40 mg m−2 i.v. day 1, mitomycin C 4 or 6 mg m−2 i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received ⩾3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m−2) and mitomycin C (4 mg m−2). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising

Effects of deer density on tick infestation of rodents and hazard of tick-borne encephalitis. I: Empirical assessment.

Tick borne encephalitis (TBE) is endemic to eastern and central Europe with broad temporal and spatial variation in infection risk. Although many studies have focused on understanding the environmental and socio-economic factors affecting exposure of humans to TBE, comparatively little research has been devoted to assessing the underlying ecological mechanisms of TBE occurrence in enzootic cycles, and therefore TBE hazard. The aim of this study was to evaluate the effect of the main ungulate tick hosts on the pattern of tick infestation in rodents and TBE occurrence in rodents and questing adult ticks. In this empirical study, we considered three areas where endemic human TBE occurs and three control sites having no reported human TBE cases. In these six sites located in Italy and Slovakia, we assessed deer density using the pellet group count-plot sampling technique, collected questing ticks, live-trapped rodents (primarily Apodemus flavicollis and Myodes glareolus) and counted ticks feeding on rodents. Both rodents and questing ticks were screened for TBE infection. TBE infection in ticks and rodents was positively associated with the number of co-feeding ticks on rodents and negatively correlated with deer density. We hypothesise that the negative relationship between deer density and TBE occurrence on a local scale (defined by the minimum overlapping area of host species) could be attributed to deer (incompetent hosts) diverting questing ticks from rodents (competent hosts), know as the ‘dilution effect hypothesis’. We observed that, after an initial increase, the number of ticks feeding on rodents reached a peak for an intermediate value of estimated deer density and then decreased. Therefore, while at a regional scale, tick host availability has already been shown to be directly correlated with TBE distribution, our results suggest that the interactions between deer, rodents and ticks are much more complex on a local scale, supporting the possibility of a dilution effect for TBE

Effects of deer density on tick infestation of rodents and the hazard of tick-borne encephalitis. I: Empirical assessment

Tick borne encephalitis (TBE) is endemic to eastern and central Europe with broad temporal and spatial variation in infection risk. Although many studies have focused on understanding the environmental and socio-economic factors affecting exposure of humans to TBE, comparatively little research has been devoted to assessing the underlying ecological mechanisms of TBE occurrence in enzootic cycles, and therefore TBE hazard. The aim of this study was to evaluate the effect of the main ungulate tick hosts on the pattern of tick infestation in rodents and TBE occurrence in rodents and questing adult ticks. In this empirical study, we considered three areas where endemic human TBE occurs and three control sites having no reported human TBE cases. In these six sites located in Italy and Slovakia, we assessed deer density using the pellet group count-plot sampling technique, collected questing ticks, live-trapped rodents (primarily Apodemus flavicollis and Myodes glareolus) and counted ticks feeding on rodents. Both rodents and questing ticks were screened for TBE infection. TBE infection in ticks and rodents was positively associated with the number of co-feeding ticks on rodents and negatively correlated with deer density. We hypothesise that the negative relationship between deer density and TBE occurrence on a local scale (defined by the minimum overlapping area of host species) could be attributed to deer (incompetent hosts) diverting questing ticks from rodents (competent hosts), know as the ‘dilution effect hypothesis’. We observed that, after an initial increase, the number of ticks feeding on rodents reached a peak for an intermediate value of estimated deer density and then decreased. Therefore, while at a regional scale, tick host availability has already been shown to be directly correlated with TBE distribution, our results suggest that the interactions between deer, rodents and ticks are much more complex on a local scale, supporting the possibility of a dilution effect for TBE

BILITRANSLOCASE MEMBRANE TRANSPORTER: A DRUG TARGET STUDIED IN BOTH ANIMAL AND PLANT SPECIES

Bilitranslocase (TC 2.A.65.1.1) is a membrane protein localised in absorptive epithelia (intestine), excretory epithelia (liver and kidney), and vascular endothelium and probably ubiquitous. It transports water-soluble organic anions. These are bilirubin, dietary flavonoids (anthocyanins) and natural nucleotides. A QSAR model with strong predictive capacity has been built. A battery of functional assays in membrane vesicles, isolated cells and organ fragments, is available. One anti-sequence monoclonal antibody has been produced. Two additional monoclonal antibodies are in production, with the property of inhibiting transport function and allowing for immune-detection of fixed samples. The QSAR model, coupled with established biological assays, allows screening new bilitranslocase ligands and assessing them for transport and bioactivity. Thus, new drugs can be developed, based on their ability to be transported by bilitranslocase. Particularly promising is the perspective to develop nucleotide-like drugs to be used in anti-cancer, anti-viral therapy or flavonoid-based drugs, able to interact with enzymes involved in intracellular signalling pathways and interfering with bilirubin transport. In plants, bilitranslocase-like homologues are found in various species. In grape berries, it has been shown to transport flavonoids and to be up-regulated under water stress