Evaluating the appropriateness of a community pharmacy model for a colorectal cancer screening program in Catalonia (Spain).

Background The traditional model of community pharmacy has changed, with patients, caregivers and consumers having access to many cognitive services other than the traditional dispensing and supply of medicines. In December 2009, a population-based colorectal cancer screening program started in Barcelona, introducing the community pharmacist and the professional expertise of the pharmacist into the organisational model. Aim To evaluate the program implementation process in the pharmacies, identify barriers and facilitators, and know the opinion of the professionals involved in the colorectal cancer screening program in Catalonia (Spain). Methods Cross-sectional study of the pharmacies that participated in the first round of the program during the first and second trimester of 2010 in Barcelona. A validated questionnaire was used to analyse several functional aspects in the implementation process. Qualitative aspects about the opinion of the pharmacist were studied. A descriptive and bivariate analysis was performed. Results All the pharmacies involved in the program (n = 74) participated in the study. The majority of the sample population was composed of women (70.3%), mean age 44.9 years, and most of them (74%) had attended a specific training session. Pharmacists considered their participation in the program to be an added value to their professional role and a way to increase consumer's confidence on this kind of services. The average time to provide the service was estimated to be less than 10 minutes per consumer. Only three (4.1%) pharmacists considered that the program involved a lot of extra work in the daily activities of the pharmacy. The level of satisfaction of the pharmacists was very high. Conclusions Community pharmacies can be a successful alternative and great resource to implement a population cancer screening program. This functional model can improve the accessibility and participation rates on target population. The level of motivation of the community pharmacist, the specific training program and the perception to give a better care for their patients can be an enabler.

The P2 promoter of the IGF1 gene is a major epigenetic locus for GH responsiveness.

Short children using growth hormone (GH) to accelerate their growth respond to this treatment with a variable efficacy. The causes of this individual variability are multifactorial and could involve epigenetics. Quantifying the impact of epigenetic variation on response to treatments is an emerging challenge. Here we show that methylation of a cluster of CGs located within the P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is inversely closely correlated with the response of growth and circulating IGF1 to GH administration. For example, variability in CG-137 methylation contributes 25% to variance of growth response to GH. Methylation of CGs in the P2 promoter is negatively associated with the increased transcriptional activity of P2 promoter in patients' mononuclear blood cells following GH administration. Our observation indicates that epigenetics is a major determinant of GH signaling (physiology) and of individual responsiveness to GH treatment (pharmacoepigenetics).

Onset of photosynthesis in spring speeds up monoterpene synthesis and leads to emission bursts.

Emissions of biogenic volatile organic compounds (BVOC) by boreal evergreen trees have strong seasonality, with low emission rates during photosynthetically inactive winter and increasing rates towards summer. Yet, the regulation of this seasonality remains unclear. We measured in situ monoterpene emissions from Scots pine shoots during several spring periods and analysed their dynamics in connection with the spring recovery of photosynthesis. We found high emission peaks caused by enhanced monoterpene synthesis consistently during every spring period (monoterpene emission bursts, MEB). The timing of the MEBs varied relatively little between the spring periods. The timing of the MEBs showed good agreement with the photosynthetic spring recovery, which was studied with simultaneous measurements of chlorophyll fluorescence, CO2 exchange and a simple, temperature history-based proxy for state of photosynthetic acclimation, S. We conclude that the MEBs were related to the early stages of photosynthetic recovery, when the efficiency of photosynthetic carbon reactions is still low whereas the light harvesting machinery actively absorbs light energy. This suggests that the MEBs may serve a protective functional role for the foliage during this critical transitory state and that these high emission peaks may contribute to atmospheric chemistry in the boreal forest in springtime.

Decrease in clinical hypoglycemia in young children with type 1 diabetes treated with free-mixed aspart and detemir insulin: an open labeled randomized trial.

OBJECTIVE: To compare the effectiveness of a free-mix of aspart (A) and detemir (D) insulins (ADIM) with a commonly used premixed fixed-ratio aspart and neutral protamine Hagedorn (NPH) insulin mixture (ANIM) in young children with type 1 diabetes (T1D) treated with twice-daily injections. The trial thus compares not only D vs. NPH, but also flexible, personalized insulin preparations vs. a fixed premixed preparation. RESEARCH DESIGN AND METHODS: This single-center, open-label, randomized trial included 82 children with T1D. Patients stayed on ANIM for 1 yr of optimization of disease management, then were randomized to either ANIM (N = 41) or ADIM (N = 41) for another year. OUTCOMES: Frequency of severe or symptomatic episodes, glycated hemoglobin A1c (HbA1c), and blood glucose (BG) values. RESULTS: Compared with ANIM, ADIM decreases symptomatic hypoglycemia by approximately 2 fold (p < 0.001) and severe hypoglycemia by 7-10 fold (p = 0.04). ADIM somewhat reduced BG variation. Mean HbA1c was comparable on ADIM (7.9 ± 0.8 %; 63 ± 9 mmol/mol) and ANIM (8.2 ± 0.7 %; 66 ± 8 mmol/mol). CONCLUSIONS: Using a free-mixing preparation of aspart and detemir insulin decreases hypoglycemia in young children with type 1 diabetes.

Connexin 30.2 is expressed in mouse pancreatic beta cells.

Nowadays, connexin (Cx) 36 is considered the sole gap junction protein expressed in pancreatic beta cells. In the present research we investigated the expression of Cx30.2 mRNA and protein in mouse pancreatic islets. Cx30.2 mRNA and protein were identified in isolated islet preparations by qRT-PCR and Western blot, respectively. Immunohistochemical analysis showed that insulin-positive cells were stained for Cx30.2. Confocal images from double-labeled pancreatic sections revealed that Cx30.2 and Cx36 fluorescence co-localize at junctional membranes in islets from most pancreases. Abundant Cx30.2 tiny reactive spots were also found in cell cytoplasms. In beta cells cultured with stimulatory glucose concentrations, Cx30.2 was localized in both cytoplasms and cell membranes. In addition, Cx30.2 reactivity was localized at junctional membranes of endothelial or cluster of differentiation 31 (CD31) positive cells. Moreover, a significant reduction of Cx30.2 mRNA was found in islets preparations incubated for 24h in 22mM as compared with 3.3mM glucose. Therefore, it is concluded that Cx30.2 is expressed in beta and vascular endothelial cells of mouse pancreatic islets.

Interest of the association retinaldehyde/glycolic acid in adult acne.

BACKGROUND: Topical retinoids have been successfully used in the treatment of acne vulgaris but may induce irritation when used twice daily. The association of retinaldehyde (RAL) with glycolic acid (GA) have complementary activities, which could be of interest for adult women with acne because of a better tolerance/efficacy ratio. The aim of this study was to evaluate the tolerance and the efficiency of RAL (0.1%)/GA (6%) in adult women with acne when used alone or in combination with their usual acne products except retinoids. METHODS: Three hundred ninety-seven women with acne (aged between 30 and 40 years old) were included in this open multicentric study. They had to apply cream containing RAL/GA for 90 days without stopping their previous acne treatment (except topical retinoids). The tolerance was the main criteria and the second one is the efficacy, which was assessed by counting inflammatory and retentional lesions after 30 and 90 days of treatment. RESULTS: Used alone or in association with other anti-acne treatments, RAL/GA was considered to be highly tolerated. A significant decrease in both inflammatory and retentional lesions between day 0 and day 90 indicates that RAL/GA can be used as monotherapy for mild acne or could potentate the efficiency of other anti-acne products used at the same time by patients suffering from moderate acne. Complaints about side-effects were rare. The subjective evaluation of the preparation's efficacy by investigators and patients was strongly favourable. CONCLUSION: These data show that a combination of RAL 0.1% and GA 6% may be used in association with other topical anti-acne treatments with an excellent tolerance.

OCO-2 advances photosynthesis observation from space via solar-induced chlorophyll fluorescence.

Quantifying gross primary production (GPP) remains a major challenge in global carbon cycle research. Spaceborne monitoring of solar-induced chlorophyll fluorescence (SIF), an integrative photosynthetic signal of molecular origin, can assist in terrestrial GPP monitoring. However, the extent to which SIF tracks spatiotemporal variations in GPP remains unresolved. Orbiting Carbon Observatory-2 (OCO-2)'s SIF data acquisition and fine spatial resolution permit direct validation against ground and airborne observations. Empirical orthogonal function analysis shows consistent spatiotemporal correspondence between OCO-2 SIF and GPP globally. A linear SIF-GPP relationship is also obtained at eddy-flux sites covering diverse biomes, setting the stage for future investigations of the robustness of such a relationship across more biomes. Our findings support the central importance of high-quality satellite SIF for studying terrestrial carbon cycle dynamics.

Immunocytochemical, ultrastructural and neurochemical evidences on synaptogenesis and dopamine release of rat chromaffin cells co-cultured with striatal neurons.

The results reported herein address the question of synaptogenesis between adrenal chromaffin cells and striatal neurons. The release of dopamine from chromaffin cells in the presence of striatal neurons was also examined. Co-culture of newborn rat chromaffin cells and striatal neurons at 1:1 ratio was made. Cultures were examined morphologically using immunocytochemistry and ultrastructural techniques (transmission electron microscopy), while quantitation of dopamine in the culture media by HPLC-ECD was also determined. Neurite outgrowth from chromaffin cells was enhanced in the presence of striatal neurons and numerous synaptic-like contacts between these two cell types were observed. Higher concentration of dopamine was also present in the co-culture medium as compared with those containing only chromaffin cells. The development of synapses between these two types of cells may give support to the functionality of transplants in human cases of Parkinson disease (PD).

L-DOPA-induced neurotoxic and apoptotic changes on cultured chromaffin cells.

Adrenal chromaffin cell (ACC) transplantation has been considered as one of the therapeutic strategies for Parkinson disease (PD). This strategy involves the administration of L-DOPA, although in reduced doses, to ACC-transplanted patients. Using cytochemical and morphological methods, we examined the effects of clinically applicable concentrations of L-DOPA on cultured chromaffin cells. We found an increase of cell death in both necrotic and apoptotic patterns. These data suggest that therapeutic preventive measures during ACC transplantation processes for PD should be taken.

Using mathematical morphology to determine left ventricular contours.

The aim of this study is to investigate the use of mathematical morphology for the determination of left ventricular contours in scintigraphic images using multigated radionuclide angiography. We have developed a completely automatic method that first restores the image with a Wiener filter, then finds the region where the left ventricle is contained, and finally segments the left ventricle contour and a background zone. The contours depend on the values of the parameters that appear in the mathematical morphology method, which are related to the height and the slope of the count distribution. Results obtained with this method are compared with the contours and the background zones outlined by experts on the basis of the number of counts. We study the values of the parameters with which the optimum correlation is obtained.

[Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth]. / L'axe GH-IGF-I dans la croissance.

Normal human linear growth results from an evolutionary process expressing the sum effect of multiple genes. The growth hormone (GH) - insulin like growth factor (IGF)-I axis is one of the main actors in the growth process. Defects in this axis can be responsible for short or tall stature. Short stature is defined as smaller than - 2 standard deviations (SD). It is a very common reason for consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple causes make diagnosis difficult. In this article, we detail the most common constitutional causes of small size, including those related to a defect in the GH-IGF-I axis. Then, we report, the first results of the clinical and genetic study conducted on 213 patients with gigantism. Tall stature is defined by a height superior to 2 SD. Finally, recent work linking epigenetics and growth - via signaling pathways of GH-IGF-I axis - will be presented.

Vascular placental abnormalities and newborn death in a pregnant diabetic woman with familial partial lipodystrophy type 3: a possible role for peroxisome proliferator-activated receptor γ.

The peroxisome proliferator-activated receptor protein gamma (PPARγ), a nuclear receptor involved in adipocyte differentiation, energy homoeostasis and fat storage, can lead, in rare cases of coding mutations, to familial partial lipodystrophy type 3 (FPLD3) with severe insulin resistance. PPARγ is also highly expressed in the syncytiotrophoblast and extravillous cytotrophoblast cells. It has a key role in trophoblast invasion, as shown by studies in vitro, but its precise role during placentation remains to be elucidated, and fetomaternal outcomes of FPLD3 pregnancies also need to be assessed. This report is of a novel missense heterozygous mutation of PPARγ identified during pregnancy in a young diabetic woman who, at 3weeks of amenorrhoea, prematurely delivered a baby who died 24 h later. Histopathological analysis revealed important vascular placental abnormalities. The presence of the PPARγ mutation in placental tissues in the absence of fetal malformations and maternal hypertension suggests that FPLP3 pregnancies may be at high-risk, especially if the fetus has inherited the mutation. It also supports a physiological role for PPARγ during placentation.

[Post-menopausal ovarian hyperthecosis]. / Hyperthécose ovarienne post-ménopausique.

Ovarian hyperthecosis is infrequent but it represents the first cause of post-menopausal hyperandrogenia. Pathophysiology of ovarian hyperthecosis remains poorly understood but the metabolic syndrome observed in most patients suggests that insulin resistance associated with high, postmenopausal LH levels, might play a role as in polycystic ovarian syndrome. We report here four patients who presented post-menopausal hyperandrogenia. Although high, tumoral, plasma testosterone levels, lack of focused radiological lesions except enlarged ovaries, associated to the metabolic syndrome, suggested ovarian hyperthecosis. Bilateral annexectomy allowed histological confirmation of hyperthecosis showing specific luteinized stromal cells and led to the complete suppression of the inappropriate androgen secretion.

Characterization of melittin effects in synaptosomes.

The effects of melittin at increasing concentrations on: [3H]GABA release from mouse brain synaptosomes; on the radioactivity released from [3H]arachidonic acid labeled synaptosomal membranes; on synaptosomes ultrastructure and on the leakage of the cytoplasmic marker, lactate-dehydrogenase (LDH) was investigated. Melittin 0.3, 1, 3, 7, and 10 microM progressively increases [3H]GABA release, but the efficacy of melittin is decreased when the amount of tissue exposed to a constant concentration of the toxin increases. The release of [3H]GABA induced by melittin below 3 microM is Ca2+ dependent, but not that induced by the higher concentrations. The Ca2+ dependent fraction of the [3H]GABA released by 0.3 microM melittin is selectively inhibited by 10 microM quinacrine and 1 microM nordihydroguaiaretic acid (NDGA) and facilitated by 3 microM indomethacin, whereas the Ca2+ independent fraction of the [3H]GABA released by melittin is not. In the presence of Ca2+, melittin 0.3, 1 and 10 microM progressively increases [3H]arachidonic acid release over control release, but the effectiveness of melittin is also decreased as the amount of tissue increases. No apparent changes in synaptosomes ultrastructure are observed in 0.3 microM treated synaptosomes, but a noticeable disorganization is produced in 10 microM melittin-treated synaptosomes, independently on the presence of external Ca2+. LDH activity only increases over control activity in the supernatant solutions of 10 microM melittin treated synaptosomes, also in a Ca2+ independent manner. Our interpretation of these results is that the Ca2+-dependent, pharmacologic sensitive component of melittin-induced release of [3H]GABA, unmasked when 0.3 microM melittin was used, involves the activation of a Ca2+-dependent type of membrane PLA2. The Ca2+-independent release of [3H]GABA is in contrast, highly probable to be due to the membrane perturbation produced by complex melittin/lipid interactions.

Langerhans-like cells in amphibian epidermis.

Langerhans cells have been described in epidermis and other stratified epithelia of mammals. In other vertebrates equivalent cells have not been found. Amphibians show skin graft rejection, so it is possible that these animals have epidermal cells homologous to Langerhans cells. In this work we demonstrate the existence of ATPase-positive dendritic cells in frog epidermis that are similar ultrastructurally to mammalian Langerhans cells, except for the absence of Birbeck granules.

Comparison of agar dilution, microdilution, and disk elution methods for measuring the synergy of cefotaxime and its metabolite against anaerobes.

The activities of cefotaxime (CTX) and desacetyl cefotaxime (des-CTX) were tested both singly and in combination against 173 anaerobic clinical isolates. The MIC of CTX for 50% of 60 Bacteroides fragilis isolates was 22.4 micrograms/ml in broth, compared with 47.4 micrograms/ml in agar. This reduced efficacy in agar was seen with all species tested and is in apparent conflict with reported clinical efficacy of the drug. Synergy between CTX and des-CTX was observed with 70 to 100% of the isolates, including 60% of all Bacteroides spp. tested. The susceptibility results in a synergy system correlated well with those noted in a broth-disk elution method incorporating 32 micrograms of CTX and 8 micrograms of des-CTX per ml. The correlation was poorer when the broth-disk method contained 16 micrograms of CTX and 8 micrograms of des-CTX per ml.

Morphometric analysis of mice uteri treated with the preservatives methyl, ethyl, propyl, and butylparaben.

The alkyl esters of p-hydroxybenzoic acid (PHBA) known as parabens (Pbens) are widely used as preservatives in food, pharmaceuticals, and cosmetics. Several in vivo and in vitro studies have shown these compounds to be estrogenic. Here, for the first time, we present evidence of their estrogenicity using a morphometric analysis of uteri from mice treated with the preservatives methylparaben (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben (BuPben) compared with estradiol (E2). Different groups of adult ovariectomized (Ovx) CD1 mice were subcutaneously (sc) treated daily for three days with two different equimolar doses (362 and 1086 micromol/kg) of the Pbens: MePben (55 and 165 mg/kg), EtPben (60 and 180 mg/kg), PrPben (65 and 195 mg/kg), BuPben (70 and 210 mg/kg), E2 (10 microg/kg; 0.036 micromol/kg), and vehicle (propyleneglycol; V, 10 mL/kg). On the fourth day, uteri were dissected, blotted, weighed, and placed in a fixative solution for 24 h. The paraffin embeded uteri were cut to obtain 7 microm thick transversal sections. Luminal epithelium heights (LEH), glandular epithelium heights (GEH), and myometrium widths (MW) were measured. The highest Pbens dose was able to produce uterotrophic effects (38 to 76%) compared to E2 efects (100%). The relative uterotrophic potency to E2 (100) was from 0.02 to 0.009. Significant increases (P < 0.05) in LEH, GEH, and MW as compared with V were obtained: LEH from 87 to 113% (E2 153%), GEH from 10 to 40% (E2 60%), and MW from 35 to 43% (E2 88%). These results confirm that Pbens at the doses assayed here induce estrogenic histological changes in the uteri of Ovx mice.