Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients (the Alantel study).

Objectives: Radiation-induced dermatitis (RD) is one of the most common toxicities in radiation therapy (RT) patients. Corticosteroids, immunosuppressants, and natural products (NPs) have been used as treatment. The objective was to evaluate the efficacy of a NPs-based cream (Alantel®) to reduce the incidence of RD in women with breast cancer undergoing RT treatment. Design: We conducted a controlled, randomized, double-blind clinical trial. Setting: Radiation Oncology Unit of the Reina Sofía Hospital and 5 Primary Care centers of the Cordoba and Guadalquivir Health District (Spain). Interventions: Patients assigned to the experimental group (GTA) were treated with Alantel, while those in the control group (GTE) were treated with a moisturizer and emollient cream. Main outcome measures: The primary outcome variable was the incidence of RD. RD-free time, duration of RD, quality of life, and product safety were also assessed. Results: Seventy patients were included in the study, 35 in the GTA and 35 in the GTE. The incidence of RD was lower in the GTA (71.4%) than in the GTE (91.4%) after 4 weeks of follow-up (RR = 0.78; NNT = 5; p < 0.031). The Skindex-29 questionnaire showed differences in the statement: "My skin condition makes it hard to work or do hobbies" (17.1% in the GTE vs. 2.9% in GTA; p = 0.024). Conclusions: The higher efficacy of Alantel® compared to the control cream in reducing the incidence of RD in women with breast cancer has been demonstrated.

Development of wild barley (Hordeum chilense)-derived DArT markers and their use into genetic and physical mapping.

Diversity arrays technology (DArT) genomic libraries were developed from H. chilense accessions to support robust genotyping of this species and a novel crop comprising H. chilense genome (e.g., tritordeums). Over 11,000 DArT clones were obtained using two complexity reduction methods. A subset of 2,209 DArT markers was identified on the arrays containing these clones as polymorphic between parents and segregating in a population of 92 recombinant inbred lines (RIL) developed from the cross between H. chilense accessions H1 and H7. Using the segregation data a high-density map of 1,503 cM was constructed with average inter-bin density of 2.33 cM. A subset of DArT markers was also mapped physically using a set of wheat-H. chilense chromosome addition lines. It allowed the unambiguous assignment of linkage groups to chromosomes. Four segregation distortion regions (SDRs) were found on the chromosomes 2H(ch), 3H(ch) and 5H(ch) in agreement with previous findings in barley. The new map improves the genome coverage of previous H. chilense maps. H. chilense-derived DArT markers will enable further genetic studies in ongoing projects on hybrid wheat, seed carotenoid content improvement or tritordeum breeding program. Besides, the genetic map reported here will be very useful as the basis to develop comparative genomics studies with barley and model species.

Tissue engineering with dental pulp stem cells: isolation, characterization, and osteogenic differentiation.

INTRODUCTION: Dental pulp stem cells (DPSCs) are adult mesenchymal stem cells that have the ability to differentiate into osteoblasts, a fact that is very interesting in the context of tissue engineering. Our purpose was to isolate and characterize DPSCs and to compare the differentiation potential of 3 different osteogenic media. PATIENTS AND METHODS: Human dental pulp extracted from healthy young adults was placed in flasks with a mesenchymal expansion medium. At passage 4 DPSCs were analyzed for cell-cycle stage, proliferation, viability, and immunophenotype. DPSCs were grown in 3 different osteogenic media for 40 days. Flasks were incubated at 37 °C in 5% CO2, and the medium was changed twice a week. At day 40, the mineralization of the matrix was determined with Alizarin Red S dye. RESULTS: After osteogenic induction, DPSCs developed mineralization nodules (clusters), as revealed by Alizarin Red staining. This staining was stronger in the Osteodiff (Miltenyi) medium when compared to the other osteogenic media. CONCLUSIONS: This study demonstrates the ability of DPSC to differentiate into osteoblasts, especially in the presence of Osteodiff (Miltenyi). DPSCs are therefore a good candidate model for the study of hard-tissue mineralization.

Mesenchymal stem cells derived from dental tissues.

Regeneration of tissues occurs naturally due to the existence of stem cells with the capacity to self-regenerate and differentiate; however, regenerative capacity decreases with age, and in many cases, regeneration is not sufficient to repair the damage produced by degenerative, ischaemic, inflammatory, or tumour-based diseases. In the last decade, advances have been made in the understanding of stem cells, the genes that control the alternative fates of quiescence and differentiation, and the niches that provide specific signals that modulate cell fate decisions. Embryonic stem-cell research is shedding light on the secrets of development. Adult stem cells (AS cells) are available from several sources. Bone marrow and connective tissue have been used in preliminary clinical trials for regenerative therapy. Recently, several types of AS cells have been isolated from teeth, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle progenitor stem cells and stem cells from apical papilla. Preliminary data suggest that these cells have the capacity to differentiate into osteoblasts, adipocytes, chondrocytes and neural cells. If confirmed, these data would support the use of these cells, which are easily obtained from extracted teeth, in dental therapies, including in regenerative endodontics, providing a new therapeutic modality.

Molecular and cytological characterization of an extra acrocentric chromosome that restores male fertility of wheat in the msH1 CMS system.

A new CMS system designated as 'msH1' has been reported in bread wheat using the cytoplasm of H. chilense. While testing this system in different wheat backgrounds, a highly fertile line with chromosome number 42 plus an extra acrocentric chromosome was obtained. The extra chromosome did not pair with any wheat chromosome at meiosis, and progeny from this line which lack the acrocentric chromosome showed pollen abortion and male sterility. In order to establish the origin of this chromosome, FISH using H. chilense genomic DNA as probe was used and showed that it had originated from H. chilense chromosome(s). The novel chromosome did not possess sequences similar to wheat rDNA; however, the probe pSc119.2 from S. cereale containing the 120 bp family was found to occur at the end of its long arm. Data obtained from FISH and EST molecular markers confirm that the long arm of the acrocentric chromosome is indeed, the short arm of chromosome 1H(ch) from H. chilense. We suggest that the novel chromosome originated from a deletion of the distal part of the long arm of chromosome 1H(ch). Neither the 1H(ch)S short arm, nor the whole chromosome 1H(ch) restores pollen fertility of the alloplasmic wheat. Therefore, the restorer gene on the acrocentric chromosome must be located on the retained segment from the hypothetical 1H(ch)L, while some pollen fertility inhibitor could be present on the deleted 1H(ch)L distal segment. Disomic addition of the acrocentric chromosome was obtained and this line resulted fully stable and fertile.

Ethanol synthesis from glycerol by Escherichia coli redox mutants expressing adhE from Leuconostoc mesenteroides.

AIMS: Analysis of the physiology and metabolism of Escherichia coli arcA and creC mutants expressing a bifunctional alcohol-acetaldehyde dehydrogenase from Leuconostoc mesenteroides growing on glycerol under oxygen-restricted conditions. The effect of an ldhA mutation and different growth medium modifications was also assessed. METHODS AND RESULTS: Expression of adhE in E. coli CT1061 [arcA creC(Con)] resulted in a 1.4-fold enhancement in ethanol synthesis. Significant amounts of lactate were produced during micro-oxic cultures and strain CT1061LE, in which fermentative lactate dehydrogenase was deleted, produced up to 6.5 +/- 0.3 g l(-1) ethanol in 48 h. Escherichia coli CT1061LE derivatives resistant to >25 g l(-1) ethanol were obtained by metabolic evolution. Pyruvate and acetaldehyde addition significantly increased both biomass and ethanol concentrations, probably by overcoming acetyl-coenzyme A (CoA) shortage. Yeast extract also promoted growth and ethanol synthesis, and this positive effect was mainly attributable to its vitamin content. Two-stage bioreactor cultures were conducted in a minimal medium containing 100 microg l(-1) calcium d-pantothenate to evaluate oxic acetyl-CoA synthesis followed by a switch into fermentative conditions. Ethanol reached 15.4 +/- 0.9 g l(-1) with a volumetric productivity of 0.34 +/- 0.02 g l(-1) h(-1). CONCLUSIONS: Escherichia coli responded to adhE over-expression by funnelling carbon and reducing equivalents into a highly reduced metabolite, ethanol. Acetyl-CoA played a key role in micro-oxic ethanol synthesis and growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Insight into the micro-oxic metabolism of E. coli growing on glycerol is essential for the development of efficient industrial processes for reduced biochemicals production from this substrate, with special relevance to biofuels synthesis.

Effects of reciprocal crosses on agronomic performance of tritordeum.

Tritordeums (Tritordeum Ascherson et Graebner) are the amphiploids derived from the crosses between Hordeum chilense and durum or bread wheats. Primary tritordeums are obtained using H. chilense as female parent and therefore they exhibit H. chilense cytoplasm. The effect of wheat cytoplasm on agronomic performance of tritordeums was investigated. We developed four pairs of reciprocal F1 lines only differing in their cytoplasm, donated from wheat or H. chilense alternatively. The agronomic performance of reciprocal F1 lines contrasting for their cytoplasm was evaluated. The following traits were assessed: leave and tillers number one month after sowing, plant height, anthesis date, total number of ears, number of spikelets per spike, fertility of the main spike, length and wide of the flag leaf in the main stem and thousand kernel weight. Reciprocal F1 lines did not differ for any of the agronomic traits evaluated with the exception of anthesis date in the pair THC1726/HTC1727. Therefore, both wheat and H. chilense cytoplasms can be used in tritordeum breeding.

Immunochemical detection of protein adducts in cultured human hepatocytes exposed to diclofenac.

The non-steroidal anti-inflammatory drug diclofenac is reported to cause, in rare cases, fulminant hepatic necrosis associated with chronic use of the drug. In order to investigate the possibility that covalent protein adducts of reactive metabolites of diclofenac might be responsible for the hepatotoxicity produced by this drug, we developed an antibody against a diclofenac-keyhole limpet hemocyanin adduct. The anti-diclofenac antibody did recognize diclofenac-protein adducts on Western blots of homogenates of cultured human hepatocytes exposed to diclofenac. The major detected adduct was a 60 kDa protein, which was present in both human and rat hepatocytes. These results suggest that binding of diclofenac to human hepatocytes is, like in rats, selective and that a 60 kDa protein appears to be the major target for alkylation. Immunoblots of homogenates of liver sinusoidal lining cells (LSLC) from rats treated with diclofenac also exhibited adducts with a 60 kDa protein. This fact suggest a role for LSLC in processing of chemically altered proteins in the liver.

[Thyroid dysfunction in pregnancy. Consensus document. Andalusian Society of Endocrinology and Nutrition (SAEN)]. / Abordaje del manejo de la disfunción tiroidea en la gestación. Documento de consenso de la Sociedad Andaluza de Endocrinología y Nutrición (SAEN).

A position statement on the diagnosis and treatment of thyroid dysfunction in pregnancy has been agreed on behalf of The Sociedad Andaluza de Endocrinología y Nutrición (SAEN), based on a review of the literature to date and all good clinical practice guidelines. The document is set out in different sections as regards the diagnosis and treatment of, overt and subclinical hypo- and hyperthyroidism, isolated hypothyroxinaemia and postpartum thyroiditis. It also justifies the implementation of universal screening for thyroid dysfunction in pregnancy, and provides practitioners who care for these patients with tool for rational decision making.

Gastric mucosal resistance to acute injury in experimental portal hypertension.

1. The gastric mucosa of portal hypertensive rats exhibits important microvascular changes and a nitric oxide (NO)-dependent hyperemia. This study analyses whether portal hypertensive mucosa exhibits changes in its ability to withstand aggression. 2. Portal hypertension was induced by partial portal vein ligation (PPVL) or common bile duct ligation (CBDL) and gastric damage was induced by oral administration of ethanol or aspirin. Experiments were performed in conscious or anaesthetized rats and some animals were pre-treated with the NO-synthesis inhibitor L-NAME. 3. Conscious PPVL or CBDL rats showed an increased resistance to the damaging effects of ethanol. Oral administration of aspirin produced less gastric damage in PPVL conscious rats than in the control group. 4. The protective effects of portal hypertension were maintained in animals anaesthetized with ketamine and absent when pentobarbital was employed. 5. Pre-treatment with L-NAME restored the damaging effects of ethanol and aspirin in PPVL rats without modifying the level of damage in control animals. 6. Gastric bleeding induced by oral aspirin, as measured by the luminal release of (51)Cr-labelled erythrocytes, was significantly greater in PPVL rats than in control animals. 7. Semi-quantitative analysis by RT--PCR of the mRNA for endothelial NO-synthase (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) levels showed that the expression of iNOS was slightly increased in both the gastric mucosa and smooth muscle of PPVL rats. No changes were observed in eNOS and nNOS expression. 8. Conscious portal hypertensive rats exhibit an enhanced resistance to acute gastric damage which is absent under the influence of some types of anaesthesia and seems related to an increased synthesis of nitric oxide. However, mucosal lesions in these animals show an augmented bleeding per area of injury.

Comparative effects of the novel vasotocin analogue F-180 vs. vasopressin and terlipressin on systemic and splanchnic isolated vessels from portal hypertensive rats.

F-180 has been proposed as a new vasopressin analogue for the treatment of portal hypertension. This study investigates the contractile profile of F-180 compared to vasopressin and its analogue terlipressin on isolated systemic and splanchnic vessels from sham-operated and partial portal vein ligated (PPVL) rats. F-180 (10(-9)-10(-6) M), vasopressin (10(-11)-10(-8) M) and terlipressin (10(-9)-10(-4) M) induced contraction of the mesenteric vein, aorta, iliac, tail and mesenteric arteries. The order of potency in these vessels was vasopressin (pD2 approximately 9) > F-180 (pD2 approximately 8) > terlipressin (pD2 approximately 6). Significant (P<0.01) differences between sham-operated and PPVL rats were noticed exclusively in the mesenteric vein, being the maximal effect of the three agonists at least twice greater in PPVL rats than in sham-operated rats. The order of sensitivity to the vasoconstrictors in vessels from PPVL rats was aorta < mesenteric artery << iliac artery approximately equal tail artery approximately equal mesenteric vein. The contractile profile of these peptides in each vessel from PPVL animals was quite similar, except in the mesenteric vein and the aorta. F-180 showed higher efficacy (P<0.01) than terlipressin in the mesenteric vein and lower (P<0.05) efficacy than vasopressin in the aorta. These findings suggest the existence of a vasoconstrictor territorial selectivity for vasopressin and its analogues, which could justify the efficacy of these drugs in portal hypertension therapy. In particular, F-180 appears to be a viable alternative to the classic vasopressin analogues.

[The effect of dietary supplementation with long-chain polyunsaturated fatty acids of the n-3 and n-6 series and with vitamin E on the plasma fatty acid profile]. / Efecto de la suplementación a la dieta de ácidos grasos poliinsaturados de cadena larga de las series n-3 y n-6 y de vitamina E sobre el perfil de ácidos grasos del plasma.

Dietary supplement with long-chain polyunsaturated fatty acids from the series n-3 and n-5 appears to be advisable in the nutritional repletion of a variety of conditions. It must be associated with the addition of a sufficient amount of an anti-oxidant to prevent the oxidative degradation of such fatty acids. The purpose of this study was to appraise the effect of the dietary addition of long-chain polyunsaturated fatty acids from the series n-3 and n-5 and of Vitamin E on the fatty acid profile of the plasma, and its lipidic fractions. Five groups of weaning rats were fed for a month as follows: Group A, a semipurified diet with 10% of fat [18:1(n-9) 40%; 18:2(n-6) 12%; 18:3(n-3) 1.2%]; Groups B and C, a semipurified diet with 7% of fat A and 3% of a marine oil concentrate; Groups D and E, a semipurified diet with 7% of fat A, 1.5% of a marine oil concentrate and 1.5% of a phospholipid concentrate of animal origin. Groups B and D were supplemented with 0.5 g of Vitamin E per kilogram of fat. The results obtained suggest that dietary supplement is necessary with long-chain polyunsaturated fatty acids from both the n-3 and n-5 series in order to maintain plasmatic levels of 20:4(n-6) and of 22:6(n-3) in the face of the tissular inability to produce them from their dietary precursors [18:2(n-6) and 18:3)], along with Vitamin E to prevent the oxidative malnutrition of these fatty acids.

Hypothalamic orexin, OX1, alphaMSH, NPY and MCRs expression in dopaminergic D2R knockout mice.

In 5-month-old male and female dopamine receptor 2 (D2R) knockout mice food intake per animal was unaltered while food per g BW was increased. We wished to evaluate the effect of D2R disruption on different components of energy balance and food intake regulation. We determined hypothalamic orexin precursor (PPO) expression, its receptor OX1, serum leptin levels, hypothalamic leptin receptor (OBR), circulating and pituitary alpha MSH levels, as well as central MC3 and MC4 receptors and NPY mRNA in wildtype and D2R knockout mice (KO). Loss of D2R caused a marked increase in serum prolactin levels, to higher levels in females compared to male KO mice. On the other hand, it produced a female-specific increase in circulating alphaMSH, and hypothalamic alphaMSH content, while neurointermediate alphaMSH content was decreased in both sexes. No differences were found in hypothalamic NPY, MC3R or MC4R concentration. Hypothalamic PPO mRNA expression was significantly decreased only in female KOs, while OX1 mRNA was not different between genotypes. Serum leptin levels were also similar in both genotypes. Our results show that in female and not in male mice disruption of the D2R produces two potentially anorexigenic events: an increase in serum and hypothalamic alphaMSH, and a decrease in hypothalamic orexin expression. Very high prolactin levels, which are orexigenic, probably counterbalance these effects, so that food intake is slightly altered. In males, on the other hand, hypothalamic PPO, and serum or hypothalamic alphaMSH are not modified, and increased prolactin levels may account for increased food intake per g BW. These results suggest a sexually dimorphic participation of the D2R in food intake regulation.

[Effects of acidosis and alkalosis on the sarcoplasmic reticulum of the heart]. / Efectos de la acidosis y alcalosis en retículo sarcoplásmico de corazón.

Some functions of dog cardiac sarcoplasmic reticulum have been studied in acidosis and alkalosis conditions in a range of pH from 6.0 to 7.8. Intravesicular water content at pH 6.0 is 4.7 microliter per mg of protein and diminished to 4 microliter, (15%) at pH 8.0; this correlates with a drop of 13.5% in turbidity. Ca2+-dependent ATPase has an optimal pH of 7.2 and a specific activity of 580 nanomoles of ATP hydrolyzed/min/mg protein. The activity of Basal ATPase or Mg2+-dependent is insensitive to changes of pH. Maximal calcium uptake attains 45.1 +/- 1.4 nanomoles per mg protein between pH 6.0 and 6.6. The accumulated calcium diminished progressively when pH was raised. The rate of calcium transport in steady state shows an optimal pH of 6.7. The calcium transport kinetics constants shows that reticulum has a maximal affinity for calcium between pH 6.87 and 7.02. The maximal velocity for transport diminished progressively between pH 6.1 to 7.16. During the calcium transport process pH is changed from acid to alkaline and the accumulated calcium is release proportionally to the pH increment. This effect shows to be reversible. Calcium accumulation and ATP hydrolysis are uncoupled at pH values higher than 6.6 because to the increase in the rate of calcium release. Values of pK and number of protons per mg of protein that dissociates from ionizable residues are 6.53 and 0.68 respectively for calcium dependent ATPase; 7.09 and 0.60 for calcium transport and 7.41 and 0.39 for calcium release. We conclude that the rate of transport and affinity of cardiac sarcoplasmic reticulum for calcium are optimal between pH 6.8 and 7.0 that is the reported range of intracellular pH of normal cardiac tissue. The data are in close agreement with the fall of contractility in acidosis. It is proposed a calcium release pathway sensitive to pH and different from that of calcium pump, exclusively for entrance.

Identification of intergenomic translocations involving wheat, Hordeum vulgare and Hordeum chilense chromosomes by FISH.

Intergenomic translocations between wheat, Hordeum chilense and Hordeum vulgare have been obtained in tritordeum background. Advanced lines from the crosses between three disomic chromosome addition lines for chromosome 2Hv, 3Hv, and 4Hv of barley (Hordeum vulgare) in Triticum aestivum cv. Chinese Spring (CS) and hexaploid tritordeum (2n = 6x = 42, AABBHchHch) were analyzed. Multicolor FISH using both genomic DNA from H. chilense and H. vulgare were used to establish the presence and numbers of H. vulgare introgressions into tritordeum. Interspecific H. vulgare/H. chilense and intergeneric wheat/H. vulgare and wheat/H. chilense translocations were identified. Frequencies of plants containing different kinds of intergenomic translocations between chromosome arms are presented. These lines can be useful for introgressing into tritordeum characters of interest from H. vulgare.

Structural differences between the repertoires of mouse and human germline genes and their evolutionary implications.

Although human and mouse antibodies are similar when one considers their diversification strategies, they differ in the extent to which kappa and lambda light chains are present in their respective variable light chain repertoires. While the Igk-V germline genes are preponderant in mice (95% or more), they comprise only 60% in humans. This may account for differences in the structural repertoire encoded in the Igk-V germline genes of these species. However, this subject has not been properly investigated, partially because a systematic structural characterization of the mouse Igk-V germline genes has not been undertaken. In the present study we compiled all available information on mouse Igk-V germline genes to characterize their structural repertoire. As expected, comparison with the structural repertoire of human Igk-V germline genes indicates differences. The most interesting is that the mouse Igk-V germline gene repertoire is more diverse in structural terms than its human counterpart: the mouse encodes seven canonical structure classes (combination of canonical structures in L1 and L3). In contrast, the human encodes only four. Analysis of the evolutionary relationships of human and mouse Igk-V germline genes led us to propose that the difference reflects a strategy of mice to compensate for the small lambda chain contribution to the repertoire of their variable light chains.

A fertile amphiploid between diploid wheat (Triticum tauschii) and crested wheat grass (Agropyron cristatum).

Alloploidy, one of the most efficient evolutionary mechanisms in nature, has not been extensively exploited in plant breeding programmes. Many genomic combinations remain to be created by plant breeders, to be used directly as new crops or indirectly to widen the genetic basis of crops. The Triticeae tribe, to which wheat belongs, is among the botanical groups in which this strategy has been successfully explored. However, there remain valuable genomic combinations that have not been obtained at the diploid level. The Agropyron complex (wheat-grasses) has recently been the focus of attention for interspecific hybridization, but intergeneric hybrids or amphiploids with wheat have not been reported at the diploid level. Here we report synthesis of a tetraploid amphiploid between Triticum tauschii and Agropyron cristatum by crossing two tetraploid accessions. Using total genome in situ hybridization (GISH) staining on metaphase I pollen mother cells, data on allosyndetic and autosyndetic chromosome pairing have been obtained. These data support the view that the A. cristatum tetraploid parent used in the synthesis of the amphiploid has a segmental alloploidy nature.