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Advanced prostate cancer cells preferentially metastasize to bone by acquiring a bone phenotype that allows metastatic cells to thrive in the skeletal environment. Identification of factors that promote the expression of ectopic bone genes—process known as osteomimicry—leading to tumor progression is crucial to prevent and treat metastatic prostate cancer and prolong life expectancy for patients. Here, we identify the extracelular matrix protein mindin in the secretome of prostate adenocarcinoma cells and show that mindin overexpression in human and mouse TRAMP-C1-induced prostate tumors correlates with upregulated levels of bone-related genes in the tumorigenic prostate tissues. Moreover, mindin silencing decreased osteomimicry in adenocarcinoma cells and in the prostate tumor mice model, as well as reduced tumor cell proliferation, migration and adhesion to bone cells. Inhibition of the extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation decreased the proliferative, migratory and pro-adhesion actions of mindin on prostate tumor cells. In addition, conditioned media obtained by crosstalk stimulation of either osteocytes or osteoblasts with the secretome of TRAMP-C1 cells promoted osteomimicry in prostate tumor cells; an effect inhibited by mindin silencing of TRAMP-C1 cells. In vivo, tibiae of primary tumor-bearing mice overexpressed the pro-angiogenic and pro-metastattic factor vascular endothelial growth factor receptor 2 (VEGFR2) in a mindin-dependent manner. Our findings indicate that mindin is a novel regulator of osteomimicry in prostate tumors and potentially mediates tumor-bone cell crosstalk, suggesting its promising role as a target to inhibit bone metastases.

SummaryBackground Prebiotics have been shown to reduce abdominal symptoms in patients with functional gut disorders, despite that they are fermented by colonic bacteria and may induce gas-related symptoms. Aim To investigate changes in the metabolic activity of gut microbiota induced by a recognised prebiotic. Methods Healthy subjects (n = 20) were given a prebiotic (2.8 g/day HOST-G904, HOST Therabiomics, Jersey, Channel Islands) for 3 weeks. During 3-day periods immediately before, at the beginning and at the end of the administration subjects were put on a standard diet (low fibre diet supplemented with one portion of high fibre foods) and the following outcomes were measured: (i) number of daytime gas evacuations for 2 days by means of an event marker; (ii) volume of gas evacuated via a rectal tube during 4 h after a test meal; and (iii) microbiota composition by faecal Illumina MiSeq sequencing. Results At the beginning of administration, HOST-G904 significantly increased the number of daily anal gas evacuations (18 ± 2 vs. 12 ± 1 pre-administration; P < 0.001) and the volume of gas evacuated after the test meal (236 ± 23 mL vs. 160 ± 17 mL pre-administration; P = 0.006). However, after 3 weeks of administration, these effects diminished (11 ± 2 daily evacuations, 169 ± 23 mL gas evacuation). At day 21, relative abundance of butyrate producers (Lachnospiraceae) correlated inversely with the volume of gas evacuated (r = −0.52; P = 0.02). Conclusion The availability of substrates induces an adaptation of the colonic microbiota activity in bacterial metabolism, which produces less gas and associated issues. Clinical trials.gov NCT02618239.

This paper discusses modelling of photovoltaic pumping system (PVPS) applications and presents a simple but accurate model for the evaluation of performance of a large-scale multi-pump off-grid PVPS’, with single axis solar tracking and variable frequency drive control of pumps. The presented model is validated on an example of an actual 357 kWp 2-pump PVPS installation, demonstrating its use for feasibility and planning studies. The results of a brief economic analysis of the considered off-grid PVPS suggest an estimated 10-year payback period, when compared to the cost of a grid-connected configuration.

The incidence of certain cancers, including prostate cancer, is considerably higher in western countries than in Southeast Asia. Many studies have linked soy consumption to the lower incidence of prostate cancer in these countries. Twenty male Sprague-Dawley rats were randomized and divided into a control group and a group treated with soy. The ventral prostates of each animal were sectioned and stained with hematoxilin-eosin for morphological description and immunostained to detect PCNA, cleaved caspase 3 and E-cadherin immunoreactivities. Estimates of the number of total epithelial cells and the number of epithelial cells immunoreactive to PCNA and cleaved caspase 3 were calculated using the optical disector technique. Measurement of E-cadherin was carried out by calculating the volume fraction of epithe- lium immunostained by E-cadherin. Soy treated group showed atrophy in the epithelium and a diminished expression of PCNA, cleaved caspase 3 and E-cadherin, which means there is a reduced cell proliferation, apoptosis through caspases way and cell adherence. It can be concluded that soy treatment induces atrophy in the epithelium by reducing cell prolif- eration.

Serotonin immunoreactive neuroendocrine cells and peptidergic nerves (NPY and VIP) could have a role in prostate growth and function. In the present study, rats grouped by stages of postnatal development (prepubertal, pubertal, young and aged adults) were employed in order to ascertain whether age causes changes in the number of serotoninergic neuroendocrine cells and the length of NPY and VIP fibres. Discriminant analysis was performed in order to ascertain the classificatory power of stereologic variables (absolute and relative measurements of cell number and fibre length) on age groups. The following conclusions were drawn: a) discriminant analysis confirms the androgen-dependence of both neuroendocrine cells and NPYVIP innervation during the postnatal development of the rat prostate; b) periglandular innervation has more relevance than interglandular innervation in classifying the rats in age groups; and c) peptidergic nerves from ventral, ampullar and periductal regions were more age-dependent than nerves from the dorso-lateral region.

Abnormal angiogenesis is a critical feature of many diseases, including cancers and their precursors. Although the association between prostate carcinogenesis and changes in microvascular architecture is well known, these changes are not well-documented from a quantitative point of view. The present work deals with stereological estimates of the number of quiescent and proliferative endothelial cells, and microvessel length in normal and prostate cancer tissues. Un- biased stereological measurements of numerical densities of proliferating cell nuclear antigen immunostained cells, non- proliferating endothelial cells, caspase 3 immunoreactive endothelial cells, and relative length (length density) of mi- crovessels, were performed in control and cancer specimens. There were no changes in either proliferation or apoptosis in carcinoma endothelial cells. A decrease of endothelial cell density, together with an increase of microvessel length den- sity, were detected in prostate cancer specimens. Therefore, the following conclusions can be drawn: a) The increase of angiogenetic activity in prostate carcinogenesis leads to an increment of the microvascular length; b) The amount of endothelial cells per vascular length decreases in prostate cancer; c) There is no decrease of endothelial apoptosis in cancer microvessels. d) The increase of the length den- sity of microvessels in prostate cancer is not directly associated to an enhancement of the endothelial proliferation; and e) The blood supply of epithelium was similar in both cancerous and normal prostate.

The interactions between steroid and nonsteroid hormones in the prostate are of special interest during the growth phase of the gland. The purpose of this work is to study the influence of prolactin (PL), with or without androgenic blockade, on epithelial cells from peripubertal rat ventral prostate. Twenty male peripubertal Sprague-Dawley rats were grouped as controls, or treated with cyproterone acetate (CA), CA plus PL (CA-PL), or PL. The total number (N total) of epithelial cells, and their labeling indices to proliferative cell nuclear antigen (LI PCNA), apoptosis (LI apoptosis) and androgen receptors (LI AR) were measured. CA and PL treatment significantly decrease the N total, but the LI PCNA was unchanged. We have observed a greater LI apoptosis in pharmacologically castrated animals without PL than in the rats with androgenic blockade with PL. The LI AR does not change with CA treatment in the ventral region, but the PL significantly increases it. Androgenic blockade and PL decrease the number of epithelial cells from the ventral prostate. These changes are not attributable to the decrease of cell proliferation, rather to the increase of epithelial apoptosis. The increase of cells expressing AR after treatment with PL might be attributed to the decrease of testosterone secretion caused by the hyperprolactinemia. PL does not modulate the size of the ventral prostate in prepubertal rats.

This work deals with the quantification of serotonin-immunoreactive prostate neuroendocrine cells (NECs) in rats exposed to prolactin in normal, cyproterone acetate-exposed, and bromocriptine-exposed animals to establish the possible influence of prolactin with or without androgenic blockade on this cell population. Thirty male peripubertal Sprague-Dawley rats were grouped as controls (CT) and those treated with cyproterone acetate (CA), cyproterone acetate plus prolactin, cyproterone acetate plus bromocriptine, prolactin (PL), and bromocriptine (BC). The volume of ductal epithelium (Vep) and total number (NSER) of the NECs serotonin-immunoreactive were measured. NECs were detected in the periurethral ducts. Compared to CT, Vep was increased in PL and BC and NSER was decreased in CA and increased in the prolactin or bromocriptine groups. The androgenic blockade decreases NSER in rat prostate; PL induces in normal and cyproterone acetate-treated rats the increase of NSER; and BC exerts a local effect over the prostate similar to that described for PL.

BACKGROUND This study was directed to evaluate the immunoexpression of markers for cell proliferation, apoptosis, nuclear androgen receptors, and Glutathione-S-Transferase P1 (GSTP1), in preneoplastic changes induced by cadmium chloride (Cd) and cadmium plus zinc chloride (Cd + Zn) in rat prostate. METHODS The following parameters were calculated in ventral prostate of normal rats and rats that received Cd or Cd + Zn in drinking water during 24 months: numerical densities of columnar, basal, and GSTP1 immunoreactive epithelial cells; percentages of cells immunoreactive to: PCNA, (LIPCNA), androgen receptors (LIAR), and of apoptotic cells. RESULTS The LIPCNA was significantly increased in the animals exposed to Cd + Zn, whereas the numerical densities of both columnar (NV columnar cells), and GSTP1 immunoreactive (NV GSTP1+) cells were significantly increased in the animals treated with metals in comparison with the controls. No significant differences between the two sources of dysplasias (Cd and Cd + Zn) respecting to LIPCNA, NV columnar cells, and NV GSTP1+ were observed. The two types of dysplasias considered together showed a significant increase for the NV basal, NV columnar, and NV GSTP1+ cells in comparison with normal acini of treated and controls. The percentage of apoptotic nuclei did not show significant differences among the three groups studied. CONCLUSIONS (1) The zinc has little influence in the development of the dysplastic changes of the rat prostate mediated by cadmium. (2) The decrease of apoptosis has little influence in the development of dysplasia. (3) GSTP1 could play a role in the response to the oxidative stress in the dysplastic changes caused by cadmium. © 2004 Wiley-Liss, Inc.

Amonafide- and elinafide-related mono and bisintercalators, modified by the introduction of a pi-excedent furan or thiophene ring fused to the naphthalimide moiety, have been synthesized. These compounds have shown an interesting antitumor profile. The best compound, 9, was 2.5-fold more potent than elinafide against human colon carcinoma cells (HT-29). Molecular dynamic simulations and physicochemical experiments have demonstrated that these compounds are capable of forming stable DNA complexes. These results, together with those previously reported by us for imidazo- and pyrazinonaphthalimide analogues, have prompted us to propose that the DNA binding process does not depend on the electronic nature of the fused heterocycle.

A series of analogues of butyrolactone I, a natural product isolated from Aspergillus terreus that selectively inhibits the CDK2 and CDK1 kinases and that has been found to exhibit an interesting antiproliferative activity, have been synthesized. Its antitumor activity has been tested. Molecular models of the complex between butyrolactone I and the CDK2 active site have been built using a combination of conformational search and automated docking techniques. The stability of the resulting complexes has been assessed by molecular dynamics simulations and the experimental results obtained for the synthesized analogues are rationalized based on the molecular models.

BACKGROUND This work was undertaken to study the prostate neuroendocrine cells (PNEC) during the post-natal development of rats. METHODS Forty male Wistar rats (pre-pubertals, pubertals, young, and aged adults) were used for immunohistochemistry of chromogranin A (cgA), serotonin (SER), and protein gene product 9.5 (PGP9.5). They were also evaluated for numerical cell density (NV SER) and PNEC number per prostate (N SER). Five additional young adult rats were used for a RT-PCR study (mRNA cgA detection). RESULTS Weak immunoreactivity to cgA was observed in pubertal rats. No PNEC immunostained to PGP 9.5 was observed. Cells expressing SER were detected in all the groups exclusively located in periurethral ducts. The NV SER increased significantly in pubertal animals. In aged animals, it decreased to levels observed in pre-pubertal rats. The N SER increased significantly from pre-pubertal to young adults, decreasing in aged adults. There was weak production of cgA mRNA, with more expression in the dorsal prostate. CONCLUSIONS PNEC differ in rats when compared to humans: they are weakly immunopositive to cgA, do not express PGP 9.5, only show immunoreactivity to SER, and do not appear in acini. The changes in the amount of rat PNEC during the post-natal development suggest an androgenic influx. PNEC might regulate the contractility of periurethral ducts. Prostate 57: 176–185, 2003. © 2003 Wiley-Liss, Inc.

Intensively cultivated lands of the Andalusian east coast (South of Spain) were sampled in 3 areas, with 3 plots and a non-cultivated control plot per area, and at two depths, 0–25 cm and 25–50 cm. In each plot and depth, 3 samples were taken, made up of 5 subsamples. The analysis of elements such as arsenium (As), cadmium (Cd), copper (Cu), mercury (Hg), and lead (Pb) were made by two different digestion methods: 2 hours with acqua regia in an oil bath at 140°C, or 10 minutes with nitric acid in closed recipients inside a microwave oven. Results show differences for most of the elements between areas and between methods, and sometimes between depths. Average values per plot were always below the critical levels accepted for agricultural use. A detailed exam of values for each plot suggests reliability on the determination of As and Cu, in each case. There were few occasional anomalies in the determination of Cd, Hg, and Pb. This could be related either to irregular distributions of the elements in the so...

Continental margins are important areas to be considered when studying the distributions and depositions of pollutants, both conventional and radioactive. Coastal sediments accumulate most of those contaminants which can be introduced following atmospheric and/or fluvial pathways. Moreover, their residence times within the water column are usually shortened due to their affinity to associate with the downward falling particulate matter, more abundant at shallower depths. In this paper, the distribution profiles and inventories of plutonium, americium and cesium are detailed, providing useful information about recent sedimentation phenomena such as sediment mixing, slumping processes and bioturbation. Unsupported 210Pb data are used as reliable indicators of enhanced/reduced deposition events. Also, the calculated inventories have enabled the estimation of the radiological contribution of the Spanish Mediterranean margin to the total radioactivity deposited onto the Mediterranean sea floor.

The choline-binding domain (ChoBD) of the carboxy-terminal region of the Streptococcus pneumoniae amidase LYTA (C-LYTA) presents a strong affinity for tertiary amines. We report a method for single-step purification of proteins expressed in the methylotrophic yeast Pichia pastoris based on the fusion of C-LYTA to the protein of interest. We show that C-LYTA can be efficiently expressed and secreted in this host. Tagged proteins fused to this binding domain can be purified on inexpensive DEAE matrices. It therefore provides a useful system for the purification of recombinant proteins with high specificity suitable for industrial purposes.

The aim of this study was to determine the main factor affecting mineralizing and nitrifying bacteria in a riparian bank, where alder ( Alnus glutinosa L. Gaertn., diazotrophic plant), willow (Salix alba L.) and poplar (Populus × hybrida Moench 1–214) were the main species of vegetation. This was investigated by estimating the most probable number of microorganisms in soil samples from roots collected in spring, summer, autumn, and winter. The numbers of the total microbial population and the ammonifying and proteolytic microorganisms were higher in the plant rhizosphere and rhizoplane than in the shaded soil, litter, and root‐free soil under the trees. Nitrifier densities were the lowest around alder roots. Principal components analysis showed that the main factor affecting microorganism density was the rhizosphere of alder trees. Our results suggest that roots favor microorganism colonization (proteolytic and ammonifying microorganisms) and that roots, particularly alder roots, inhibit nitrifying microo...

Background Lysophosphatidic acid (LPA) is a phospholipid growth factor involved in cell proliferation, differentiation, migration, inflammation, angiogenesis, wound healing, cancer invasion, and survival. This study was directed to evaluate the immunoexpression of LPA-1, cell proliferation, apoptosis, and angiogenesis markers in preneoplastic lesions induced with cadmium chloride in rat prostate. Methods The following parameters were calculated in ventral prostate of normal rats and rats that received Cd in drinking water during 24 months: percentages of cells immunoreactive to LPA-1 (LILPA1), PCNA (LIPCNA), MCM7 (LIMCM7), ubiquitin (LIUBI), apoptotic cells (LIAPO), and p53 (LIp53); volume fraction of Bcl-2 (VFBcl-2); and length of microvessels per unit of volume (LVMV/mm3). Data were analyzed using Student's t-test and Pearson correlation test. Results The LILPA1 in dysplastic lesions and normal epithelium of Cd-treated rats was significantly higher than those in the control group. Markers of proliferation were significantly increased in dysplastic lesions, whereas some apoptotic markers were significantly decreased. No significant differences between groups were found in VFBcl-2. Dysplastic lesions showed a significant increase of LIp53. The length of microvessels per unit of volume was elevated in dysplastic acini. Statistically significant correlations were found only between LILPA1 and LIUBI. Conclusions Our results suggest that LPA-1 might be implicated in dysplastic lesions induced by cadmium chloride development. More studies are needed to confirm its potential contribution to the disease.

Many proteins that bind to a 14-3-3 column in competition with a 14-3-3-binding phospho-peptide have been purified from plant and mammalian cells and tissues. New 14-3-3 targets include enzymes of biosynthetic metabolism, vesicle trafficking, cell signalling and chromatin function. These findings indicate central regulatory roles for 14-3-3s in partitioning carbon among the pathways of sugar, amino acid, nucleotide and protein biosynthesis in plants. Our results also suggest that the current perception that 14-3-3s bind predominantly to signalling proteins in mammalian cells is incorrect, and has probably arisen because of the intensity of research on mammalian signalling and for technical reasons.

The reasons for nitrification inhibition in some soils are controversial We studied the effect of Elaeagnus angustifolia leaf litter (a host plant able to fix atmospheric nitrogen via root‐nodule symbiosis with an actinomycete of the genus Frankia) on the density and activity of nitrifying microorganisms present in degraded soils. Soils were incubated with and without leaf litter, and it was seen that increased denitrification, CO2‐induced inhibition, or nitrite and ammonia fixation by organic matter did not decrease nitrification. Our results suggest allelopathic inhibition by leaf litter and indicate that the introduction of E. angustifolia could improve degraded soils because it stimulates nitrogen conservation.

KEYWORDS CLASSIFICATION: Animals;Apoptosis;biosynthesis;Biology;chemically induced;Cadmium;Cadmium Chloride;Carcinogens;Caspase 3;Caspases;Cell Proliferation;Chlorides;Immunohistochemistry;metabolism;Male;mechanisms of carcinogenesis;pathology;pharmacology;Precancerous Conditions;Proliferating Cell Nuclear Antigen;Prostate;Prostatic Intraepithelial Neoplasia;Prostatic Neoplasms;Proteins;Proto-Oncogene Proteins;Proto-Oncogene Proteins c-bcl-2;Rats;Rats,Sprague-Dawley;Research;Spain;toxicity;Time Factors;Tumor Suppressor Protein p53;Zinc;Zinc Compounds. This work was directed to evaluate immunoexpression of markers for apoptosis, resistance to apoptosis, and cell proliferation, as well as estimates of nuclear size in ventral prostate of rats treated with cadmium chloride and cadmium+zinc chloride because a possible protective effect of zinc has been postulated. The following variables were studied: volume fraction (VF) of Bcl-2 immunostaining, percentage of cells immunoreactive to proliferating cell nuclear antigen (LIPCNA) and p53 (LIp53), numerical density of caspase-3 immunoreactive cells (NV caspase-3), and estimates of volume-weighted mean nuclear volume (upsilonV). The LIPCNA and VF of Bcl-2 were significantly increased in the treated animals. The dysplasias (independent of their origin) showed a significant increase of the LIp53, NV caspase-3, and upsilonV in comparison with normal acini from treated and control animals. It can be concluded that cell proliferation is enhanced in long-term cadmium-exposed rats, and exposure to zinc combined with cadmium had no effect on any of the variables studied when comparing with normal acini. The increase of nuclear upsilonV could indicate a more aggressive behavior for pretumoral lesions.

Cadmium chloride (Cd) is a toxicant that has been implicated in human prostate cancer (PCA). The goal of the present study was to evaluate the immunoexpression of markers for cell proliferation, apoptosis, resistance to apoptosis, and to determine mutations on segments of the bcl-2 gene, in preneoplastic lesions induced in rat prostate after treatment with Cd alone or in combination with zinc chloride (Zn). We evaluated: 1) The % of cells positively immunostained for the proliferating cell nuclear antigen (PCNA), 2) The % of apoptotic cells (evaluated by TUNEL), 3) The volume fraction of Bcl-2 immunostaining. 4) The mutations on a segment of 253 pb of bcl-2, in the ventral prostate lobe of normal and treated rats with Cd alone or in the presence of Zn in the drinking water for 18 mo. Our results indicate that the % of PCNA positive nuclei was significantly increased in preneoplastic prostatic acini of Cd-treated rats alone and in combination with Zn, compared to the normal acini of untreated animals. No significant changes were detected on the apoptotic rate or the volume fraction of Bcl-2. Moreover, no significant changes in the band pattern of the amplified segment of bcl-2 gene were observed after Cd treatment. In summary, our data indicate that, prostate dysplasia induced in rats by Cd increases proliferative activity, without significant changes in either apoptosis or bcl-2 immunoreactivity.

Within an extensive multinational and multidisciplinary project carried out in Doñana National Park (Spain) to investigate its preservation and regeneration, the filling velocity of the salt marshes has been evaluated through the calculation of their average sediment accumulation rates. 239þ240Pu and 137Cs from weapons testing fallout and total 210Pb distribution profiles and inventories have been determined in some of the most characteristic zones of the park, namely, the ponds (or ‘‘lucios’’) and the waterjets (or ‘‘can˜os’’). Plutonium inventories range from 16 to 101 Bq m-2, 137Cs values fluctuate between 514 and 3758 Bq m-2 and unsupported 210Pb values comprise between 124 and 9398 Bq m-2. Average sedimentation rates range from 3 to 5 mm y -1 (1952-2002). These data are higher than those obtained by carbon dating for the period 6500 AD-present, estimated as 1.5-2 mmy-1, suggesting an increase in the accumulation of sediments and the alteration of the park’s hydrodynamics caused by the re-channeling of the major rivers feeding the salt marshes.

Four bioactive materials were tested for their ability to produce toxicity in vitro in two cell lines: rabbit corneal cells (SIRC) and human fibroblasts. These compounds are widely used by industries, causing toxic effects to ecosystems and particularly having an impact on human health. Different chemicals were chosen which were structurally unrelated: triethanolamine, zinc pyrithione, sodium lauryl sulfate, and oleamine. Cytotoxicity was evaluated measuring the total protein content (inhibition of cell growth). Results indicated that zinc pyrithione produced the highest inhibition of cell growth when two cell lines were treated in the two doses tested. The lowest cytotoxic effect was observed with oleamine. Triethanolamine and sodium lauryl sulfate produced a similar cytotoxic effect in Fe cells, although sodium lauryl sulfate revealed higher inhibition of cell growth than triethanolamine on SIRC cells. From these results, it can be concluded that some products as triethanolamine and zinc pyrithione should be observed in future special toxicological studies.

This study was directed to evaluate the immunoexpression of markers for cell proliferation, apoptosis, nuclear androgen receptors, and Glutathione-S-Transferase P1 (GSTP1), in preneoplastic changes induced by cadmium chloride (Cd) and cadmium plus zinc chloride (Cd + Zn) in rat prostate.The following parameters were calculated in ventral prostate of normal rats and rats that received Cd or Cd + Zn in drinking water during 24 months: numerical densities of columnar, basal, and GSTP1 immunoreactive epithelial cells; percentages of cells immunoreactive to: PCNA, (LI(PCNA)), androgen receptors (LI(AR)), and of apoptotic cells.The LI(PCNA) was significantly increased in the animals exposed to Cd + Zn, whereas the numerical densities of both columnar (N(V) columnar cells), and GSTP1 immunoreactive (N(V) GSTP1+) cells were significantly increased in the animals treated with metals in comparison with the controls. No significant differences between the two sources of dysplasias (Cd and Cd + Zn) respecting to LI(PCNA), N(V) columnar cells, and N(V) GSTP1+ were observed. The two types of dysplasias considered together showed a significant increase for the N(V) basal, N(V) columnar, and N(V) GSTP1+ cells in comparison with normal acini of treated and controls. The percentage of apoptotic nuclei did not show significant differences among the three groups studied.(1) The zinc has little influence in the development of the dysplastic changes of the rat prostate mediated by cadmium. (2) The decrease of apoptosis has little influence in the development of dysplasia. (3) GSTP1 could play a role in the response to the oxidative stress in the dysplastic changes caused by cadmium.

This work was undertaken to study the prostate neuroendocrine cells (PNEC) during the post-natal development of rats.Forty male Wistar rats (pre-pubertals, pubertals, young, and aged adults) were used for immunohistochemistry of chromogranin A (cgA), serotonin (SER), and protein gene product 9.5 (PGP9.5). They were also evaluated for numerical cell density (NV SER) and PNEC number per prostate (N SER). Five additional young adult rats were used for a RT-PCR study (mRNA cgA detection).Weak immunoreactivity to cgA was observed in pubertal rats. No PNEC immunostained to PGP 9.5 was observed. Cells expressing SER were detected in all the groups exclusively located in periurethral ducts. The NV SER increased significantly in pubertal animals. In aged animals, it decreased to levels observed in pre-pubertal rats. The N SER increased significantly from pre-pubertal to young adults, decreasing in aged adults. There was weak production of cgA mRNA, with more expression in the dorsal prostate.PNEC differ in rats when compared to humans: they are weakly immunopositive to cgA, do not express PGP 9.5, only show immunoreactivity to SER, and do not appear in acini. The changes in the amount of rat PNEC during the post-natal development suggest an androgenic influx. PNEC might regulate the contractility of periurethral ducts.

A novel series of mono and bisnaphthalimides was synthesized and their antiproliferative activities were evaluated against three tumor cell lines. Bisnaphthalimides 3 and 4, bearing a pyrazine ring fused to the naphthalimide system, showed activities in the order of 10(-8) microM, similar to elinafide. DNA binding properties and the ability to induce DNA damage were studied for some of the most active compounds.

The hepatic oxidative metabolism is essential for the biotransformation of a large number substances, among which are found many drugs which are commonly used in clinical practice. The nutritional status of individuals has been shown to be of influence on this function. Aging produces a deterioration of the hepatic oxidative metabolism, without the cause for this situation having been clarified. Also, aging modifies the body composition of the individuals. The objective of this study is to evaluate whether the modifications which arise in the nutritive status due to age, can alter the hepatic oxidative capacity.165 elderly people of both sexes were studied, with an average age of 82 years, and 24 young people, with an average age of 29 years. All participants were subjected to a clinical questionnaire, along with an evaluation of anthropometric, biochemical, and immunological nutritive parameters. The study of the oxidative metabolism was conducted by evaluating the kinetics of antipyrine.The elderly people showed a decrease in the antipyrine clearance rate (Ap Cl) (P0.001), and a lengthening of their life-span (P0.05) with respect to the younger people. There was a significant correlation in the elderly people, between the Ap Cl and age, weight, size, the distribution volume, and the muscular area of the arm. A multiple regression analysis showed a predictive value which was independent for age, the AST, the lymphocytes, and size.Elderly people have a marked depression of the hepatic oxidative metabolism. The factors which participate in their nutritional situation, are of influence on this function. It is necessary to keep all the above in mind when it comes to prescribing drugs which require this type of biotransformation, in order to avoid adverse effects or drug interactions.

The distribution and behaviour of the radionuclides 210 Pb, 210 Po and 226 Ra in the Odiel and Tinto river estuaries, southwest Spain, have been studied. This system receives large quantities of solid and liquid effluents in the form of phosphogypsum waste from the phosphate industry containing natural radionuclides. Ranges of activities from 20 to 5000 Bq kg −1 (d.w.) in riverine sediments were observed. The ratios of radionuclides were also determined (uncertainties quoted to 2 σ), showing clear disequilibria in the effluents from the factories ( 210 Pb/ 210 Po = 2.7±0.6, 210 Pb/ 226 Ra = 0.6±0.1, 210 Po/ 226 Ra = 0.24±.03) and from the phosphogypsum piles ( 210 Pb/ 210 Po = 2.1±0.6, 210 Pb/ 226 Ra = 1.5±0.6, 210 Po/ 226 Ra = 0.7±0.2). However, the sampling sites on the rivers affected directly by the discharges exhibit activity ratios other than those found in the effluents, manifesting their different behaviour in the estuarine environment. The estimated inventory in sediments for these radionuclides was 0.92±0.20 TBq (1993) which can be compared with the annual release of 0.52±.04 TBq (1993) from the phosphogypsum piles and factories. Preferential deposition of 210 Po and 210 Pb rather than 226 Ra onto the river bed was observed. The proportion of total sediment 210 Pb activity associated with particles less than 2 μm in diameter, which is one of the most resuspendable and transportable sizes, is 5%-15%.

A strong teratogen-6-aminonicotinamide (6-AN)-was tested for its ability to induce cytotoxicity and mutagenicity in Chinese hamster ovary (CHO) cells. Tests were performed in the presence and absence of a metabolic activation system (S-9 mix). Cytotoxicity was evaluated in CHO cells by the total protein content. The two single-gene mutation systems in CHO cells have been investigated. Both involve evaluating the response of the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus and specific inhibitors of the cellular (Na2+K+)-ATPase using 6-thioguanine and ouabain as selective agents, respectively. From our results, 6-AN showed a higher cytotoxic effect at concentrations over 1 x 10(-1) mg/ml. Cytotoxicity was significantly different with and without S-9 mix. 6-AN was cytotoxic per se, however, when 6-AN was biotransformed, in the presence of S-9 mix no biological activity (cytotoxic) was detected. Non-significant mutagenic activity was detected with 6-AN in the presence and in the absence of the metabolic activation system.

The concentrations of 5-fluorouracil, 5-fluoro-5,6-dihydrouracil, 5-fluorouridine and 5-fluoro-2'-deoxyuridine in plasma, liver, kidney, lung and heart of rabbits were determined by high-performance liquid chromatography (HPLC) after drug administration by two different routes. HPLC was carried out by using a Spherisorb 5 ODS 2 column and 0.05 M phosphate buffer as the mobile phase with UV detection at 200 nm. The pH of the mobile phase, organic modifier content and column temperature were found to have a profound influence on the results, hence it was necessary to optimize a procedure for each matrix. A comparison of the efficiency of intravenous and peritoneal administration revealed that the latter provides higher drug concentrations in the liver and minimal contents in plasma and all other tissues studied.

Two strains of the rotifer Brachionus plicatilis (L-type) differing in the levels of mictic female and male production, were grown in batch cultures with the alga Nannochloropsis gaditana as food, at two low (2.5 and 10‰), and two high (40 and 50‰) salinities. While both the low (strain S-l) and the high (strain S-3) sexual reproducing strains developed similar growth cycles at 2.5 and 10‰, the population growth response at 40 and 50‰ showed that; l)in strain S-l, mixis can be suppressed in conditions that still allow asexual reproduction, and 2) in strain S-3 mictic female and male production are possible at nearly zero asexual population growth rates. In strain S-3, a double log linear relationship between the densities of males and females was found. These results show that mixis can occur over a wide ranges of female population density, and support the hypothesis that sexual reproduction is a strain dependent component of the general reproductive response.

Plants, especially actinorhizal, regulate edaphic microflora through various ways, modifying thus nutrients recycling. Myrica gale effect on microorganisms in the carbon cycle is studied in this work by comparing soil samples collected under the canopy in summer and control samples. The results indicate that under M. gale C-organic and N-total concentration and anaerobic cellulolytic, hemicellulolytic and amilolytic density increase, and pH, C/N ratio and aerobic cellulolytic microorganisms density decrease. Microbial activity in soil is also modified.

The free fixing microorganisms acting as intermediaries between the atmospherical and edaphic nitrogen carry out regulating action on the total nitrogen available at soil level. On the other hand, plants can influence the physiological activity of these microorganisms through the formation of microclimates by canopy effect and by means of organic material input. Thus, in the rhizosphere there are from 5–10 times more microorganisms than in the soil because the organic compounds liberated by the roots are used directly by the microbial population as substratum for their growth. Dinitrogen fixation in the rhizosphere of some plants also increases because this area is a most favourable place for diazotrophic microflora development.