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The association between exacerbation aetiology and exacerbation frequency is poorly understood. We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years. The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1–81.7%) in year 1 and 78.6% (53.4–94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71–2.91) versus 0.63 (0.40–1.01), p=0.06) and PCR (1.76 (95% CI 0.88–3.51) versus 0.56 (0.37–0.86), p

The status of the tree Pisonia sechellarum F. Friedmann (Nyctaginaceae) endemic to the western Indian Ocean is reviewed. Five populations have been located: four in the Seychelles Islands (three on Silhouette Island and one on Mahe) and one on Mayotte. The species is associated with montane forest and ravine habitats and the genetic identity of different populations remains to be investigated. This species is considered to be endangered.

Background: Bacterial infections are associated with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but the mechanism is incompletely understood., Method: In a COPD observational study (NCT01360398), sputum samples were collected monthly at the stable state and exacerbation. Post-hoc analyses of 1307 non-typeable Haemophilus influenzae (NTHi) isolates from 20 patients and 756 Moraxella catarrhalis isolates from 38 patients in one year of follow-up were conducted by multilocus sequence typing (MLST). All isolates came from cultured sputum samples that were analyzed for bacterial species presence, apparition (infection not detected at the preceding visit), or acquisition (first-time infection), with the first study visit as a baseline. Strain apparition or new strain acquisition was analyzed by MLST. The odds ratio (OR) of experiencing an exacerbation vs. stable state was estimated by conditional logistic regression modelling, stratified by patient., Results: The culture results confirmed a significant association with exacerbation only for NTHi species presence (OR 2.28; 95% confidence interval [CI]: 1.12-4.64) and strain apparition (OR 2.38; 95% CI: 1.08-5.27). For M. catarrhalis , although confidence intervals overlapped, the association with exacerbation for first-time species acquisition (OR 5.99; 2.75-13.02) appeared stronger than species presence (OR 3.67; 2.10-6.40), new strain acquisition (OR 2.94; 1.43-6.04), species apparition (OR 4.18; 2.29-7.63), and strain apparition (OR 2.78; 1.42-5.42). This may suggest that previous M. catarrhalis colonization may modify the risk of exacerbation associated with M. catarrhalis infection., Conclusions: The results confirm that NTHi and M. catarrhalis infections are associated with AECOPD but suggest different dynamic mechanisms in triggering exacerbations.

BackgroundWhile human-to-human transmission of Clostridioides difficile occurs often, other infection sources, including food, animals and environment, are under investigation.AimWe present a large study on C. difficile in a food item in Europe, encompassing 12 European countries (Austria, France, Greece, Ireland, Italy, the Netherlands, Poland, Slovakia, Spain, Sweden, Romania and the United Kingdom).MethodsPotato was selected because of availability, ease of sampling and high C. difficile positivity rates. Identical protocols for sampling and isolation were used, enabling a direct comparison of the C. difficile positivity rate.ResultsFrom C. difficile -positive potato samples (33/147; 22.4%), we obtained 504 isolates, grouped into 38 PCR ribotypes. Positivity rates per country varied (0-100%) and were at least 10% in 9/12 countries. No geographical clustering of samples with high positivity rates or in PCR ribotype distribution was observed. The most frequently detected PCR ribotypes (014/020, 078/126, 010 and 023) are also commonly reported in Europe among human clinically relevant isolates, in animal isolates and in the environment. Whole genome sequencing revealed several genetically related strain pairs (Spain/RT126, France/RT010, Austria and Sweden/RT276) and a cluster of very similar strains in RT078/126.ConclusionOur results suggest, the high potato contamination rates could have public health relevance. They indicate potatoes can serve as a vector for introducing C. difficile spores in the household environment, where the bacterium can then multiply in sensitive hosts with disrupted or unmature microbiota. Potato contamination with PCR ribotypes shared between humans, animals and soil is supportive of this view.

The objective of this study was to determine the effects of pituitary hormones (luteinizing hormone [LH], follicle-stimulating hormone [FSH], growth hormone [GH], and prolactin [PRL]) on interstitial cell proliferation and differentiation in the testis of immature hypophysectomized rats. Macrophages, Leydig cells, precursor mesenchymal cells, endothelial lymphatic cells, and myoid cells were studied. Our experimental approach was aimed at determining whether changes in a cellular subpopulation observed after pituitary hormone treatments were the result of division of existing cells in the population, of differentiation of interstitial precursor cells, or both. In this context, it must be stressed that our data reflected the effects of hormones to prevent the decline of cells due to hypophysectomy rather than their recovery. Macrophage proliferation was taken into account because macrophages closely resemble Leydig cells and are known to proliferate after hormonal treatment. A double-labeling procedure (acid phosphatase and anti-bromodeoxyuridine [anti-BUdR]) revealed that LH, FSH, and PRL increased the number of testicular macrophages 105-, 104-, and 103-fold, respectively, in hypophysectomized rats compared to hypophysectomized control animals. BUdR incorporation in testicular macrophages was greater after PRL treatment than after LH and FSH supplementation. In contrast, we were unable to demonstrate any effect of rat GH on the macrophage population. Light microscopic analysis of plastic embedded sections of treated rat testis revealed that LH increased the numbers of Leydig, precursor mesenchymal, and myoid cells 6-, 4-, and 1.3-fold, respectively. LH also stimulated BUdR incorporation into all interstitial cell types. PRL administration increased both the number of Leydig and precursor mesenchymal cells (each 3-fold) but decreased the number of endothelial lymphatic cells (1.5-fold) when compared to the control animals. In contrast, FSH did not increase the number and proliferation of Leydig cells but exerted a slight proliferative effect on the other interstitial cell populations. In GH-treated rats, the number of precursor mesenchymal cells increased two fold above the control rats. GH also exerted slight proliferative effects on both precursor mesenchymal and myoid cells. Immunohistochemical studies of steroidogenic enzymes in the testicular interstitium of treated rats demonstrated the presence of steroidogenic enzymes, not only in Leydig and precursor mesenchymal cells, but also in some (1%-2%) endothelial lymphatic cells and myoid cells. This may indicate that both of these cell types are also constitutively equipped to perform steroidogenesis or that they are precursor cells undergoing differentiation. Taken together, changes in the number of Leydig cells in our animal model appeared more likely to be dependent on the transformation of precursor cells than on division of preexisting mature Leydig cells.

In this study, we have examined the respective roles of androgens and prolactin (Prl) on rat prostate development and function. Hypophysectomized immature rats, castrated or not after hypophysectomy and treated or not with a 5 alpha-reductase inhibitor, were used to study the different aspects of Prl action on the rat prostate and its synergy with androgens in vivo. Using Northern blot analysis and quantitation of prostatic mRNAs, we have shown that Prl significantly increases the steady-state levels of transcripts coding for several lobe-specific proteins: the C3 subunit of prostatein, probasin, and RWB. We have confirmed these observations in vitro, on explants of immature rat prostate treated with either saline, Prl, or testosterone. In addition, we have demonstrated by a nuclear run-on assay that Prl significantly enhances the transcription rate of the C3 gene in the rat prostate. We conclude that the effects of Prl concern all lobes of the organ and are, at least in part, androgen-independent. Moreover, Prl is able, via an androgen-independent pathway, to increase the rate of transcription of the C3 gene, one of the major products of the rat prostate.

Benign prostatic hyperplasia (BPH) is so common in elderly men that the development of adenomatous nodules in this organ can be seen as a normal age-dependent process. In this work, we used Northern blotting to compare the levels of androgen, estrogen, and insulin-like growth factor-I (IGF-I) receptor in young (age range, 23-33; n = 3), old normal (age range, 52-80; n = 3), and BPH-affected subjects (age range, 66-87; n = 15). We have also investigated in these groups the expression of genes coding for the two 5 alpha-reductases (types I and II), aromatase, IGF-I, and IGF-II. Our results show significantly increased levels of IGF mRNA in old healthy and BPH-affected subjects; the respective rises for IGF-I, IGF-II, and IGF-I receptor mRNAs were 3.0-, 2.9-, and 1.5-fold (BPH) and 2.7-, 2.4-, and 1.8-fold (old normal controls). For estrogen receptor, androgen receptor, and type I and II 5 alpha-reductase mRNAs, a marked but opposite effect was observed in adenomatous tissues only; the respective levels were 2.2-, 1.8-, 3.9-, and 1.7-fold lower than those in young adult subjects, whereas no significant differences were recorded between the two normal groups. Morphometric analysis of each tissue specimen confirmed the significantly lower epithelium/stroma ratio in adenomas compared to young or old healthy tissues. Together, these observations suggest that prostatic adenomas may result from at least two conjugate processes: one characterized by a drop in the mRNA levels of steroid hormone receptors, which might be associated with a lower epithelium/stroma ratio, and another characterized by normal aging phenomena, of which the increased production of IGFs and IGF-I receptor transcripts could be biochemical markers.

In this study we investigated the involvement of several different pituitary hormones on rat prostate development. 22-day-old Wistar rats, hypophysectomized (hypox) at 19 days of age were supplemented with highly purified human prolactin (hPRL), human luteinizing hormone (hLH), porcine follicle-stimulating hormone (pFSH), and bovine growth hormone (bGH) or with saline. Quantitative analysis of RNAs shows that treatment with either PRL or GH increases significantly steady-state mRNAs levels of the following genes in the prostate: androgen receptor (AR) (respectively 3.5- and 4.8-fold above hypox controls), IGF-I (5- and 2.7-fold), and IGF-I receptor (2.9- and 2.3-fold). LH and FSH, by contrast, have negative effects on these parameters. To test whether the enhancing effect of PRL and GH on AR-mRNA abundance was followed by increased content in the protein itself, binding assays were performed with the androgen agonist [3H]R1881 (131 and 153 fmol/mg protein while hypox controls contained 110 fmol/mg protein). In addition to the well-documented presence of prolactin receptors in prostatic tissues, we have further demonstrated, by means of nuclease S1 protection assays plus dot- and Northern-blot analyses, that a GH receptor mRNA is produced in the immature rat prostate. Moreover, we observed not only strong lactogenic but also purely somatogenic binding to be occurring in the immature prostates. Finally, we have studied IGF-I mRNA content in separated epithelial/stromal cell fractions and have concluded that IGF-I expression is principally located in the prostatic stroma. Taken together, these results suggest that PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. In this context IGF-I appears as a paracrine factor playing a role in epithelium/stroma interactions during prostatic development.

IGF-I and II genes expression has been localized by in situ hybridization in testis and epididymis of immature hypophysectomized rats treated in vivo with either pFSH, hLH, bGH, hPRL or with saline. IGF-I mRNA expression was found in both Sertoli and Leydig cells after treatment with either FSH or LH. IGF-I mRNA was highly expressed in germ cells after FSH stimulation and to a lesser extent after GH or LH treatments. However, its expression was very low in hypophysectomized control or PRL treated rats. IGF-I mRNA was also expressed in stromal cells of epididymis after LH treatment and to a lesser extent after GH stimulation. In contrast, IGF-II mRNA expression was detected in all testicular cell types whatever the hormonal treatment (FSH, LH, GH, PRL). For each hormonal treatment testicular sections were examined after immunohistochemical staining with specific antisera against IGF-I and IGF-II. Both in situ hybridization and immunohistochemical data were examined in order to determine the testicular sites of synthesis of IGF-I and IGF-II.

We have studied dose-dependent effects of highly purified human PRL (39 IU/mg) on the testis of immature (22-day-old) hypophysectomized rats daily supplemented for 7 days with 2, 10, or 30 micrograms hormone. Dose-dependent stimulation was observed for all parameters: testis weight (1.6- and 2-fold above control for 10 and 30 micrograms PRL), basal and hCG-stimulated testosterone (14- and 21-fold), intratesticular testosterone (7- and 21-fold) and estradiol (1.2- and 1.5-fold), LH receptor concentration (1.8- and 2.5-fold), in vitro pregnenolone production by cholesterol side-chain cleavage enzyme (3-, 5- and 7-fold), and aromatase activity (2.1- and 2.4-fold). The number of Leydig cells exhibiting immunoreactivity toward anti-P450scc, anti-P450(17 alpha), and anti-3 beta-hydroxysteroid dehydrogenase antibodies also underwent a dose-dependent increase (under conditions revealing many immunopositive cells in hypox control animals). The respective increases were 8- to 14-fold for anti-P450scc and P450(17 alpha) and 1.5- to 2-fold for anti-3 beta-hydroxysteroid dehydrogenase. The number of germ cells and the percentage of tubular sections containing late pachytene spermatocytes as most advanced stages of spermatogenesis were subject to similar dose-dependent effects. These results suggest that during puberty PRL stimulates testicular function by promoting multiplication and differentiation of Leydig cells (acting at various steps of steroidogenesis and on tissue responsiveness to LH) and germ cells.

Bacteriophage-T4 UV endonuclease nicks the C(3')-O-P bond 3' to AP (apurinic or apyrimidinic) sites by a beta-elimination reaction. The breakage of this bond is sometimes followed by the nicking of the C(5')-O-P bond 5' to the AP site, leaving a 3'-phosphate end; delta-elimination is proposed as a mechanism to explain this second reaction. The AP site formed when this enzyme acts on a pyrimidine dimer in a polynucleotide chain undergoes the same nicking reactions. Micrococcus luteus UV endonuclease also nicks the C(3')-O-P bond 3' to AP sites by a beta-elimination reaction. No subsequent delta-elimination was observed, but this might be due to the presence of 2-mercaptoethanol in the enzyme preparation.

Since insulin-like growth factors I (IGF-I) and II (IGF-II) appeared involved in paracrine or autocrine regulation of both cell multiplication and differentiation of the rat testis, we have investigated the pituitary hormonal dependence of IGF-I and IGF-II mRNA production in the testis of immature hypophysectomized rats (22 days old) supplemented with highly purified FSH, LH, GH or PRL. Our data show that testicular expression of IGF-I mRNA as measured by dot-blot hybridization, is increased by LH, FSH or GH treatments of 7-, 6-, and 4-fold, respectively, above controls. Intensity of the signal was 3-fold lower after PRL treatment than in hypophysectomized control rats. On the contrary, IGF-II mRNA expression, was found low in the immature hypophysectomized rat testis and unmodified by any hormonal treatment. In contrast to the increase of IGF-I expression in the testis no significant change in the IGF-I plasma concentration was observed after LH or FSH supplementation. GH treatment, as expected, increased 4-fold the IGF-I plasma concentration of the experimental animals. Since we have previously shown that LH, FSH, and GH exhibit selective cell multiplication and differentiation in the testis of our animal model, it is proposed that testicular IGF-I expression could be the tissue response to pituitary hormone in these phenomena.

We have studied the specific effects of highly purified pituitary hormones on testicular cell multiplication and differentiation in the immature hypophysectomized rat. LH exhibits multiplicative effects on Leydig cells and, curiously, regressive effects on germ cells. Seminiferous tubules are the main site of action of FSH which induces direct differentiation of Sertoli cells and paracrine effects on germ cells resulting in their multiplication to the pachytene stage (in the absence of androgen). Through interstitium-directed paracrine effects, FSH promotes the differentiation of Leydig cells. Prolactin and lactogenic growth hormones are capable of exerting both differentiative and multiplicative effects on Leydig cells. The purity of the hormone preparations permit to define their specific and direct effects and those mediated by paracrine or autocrine factors synthetized locally under their control. Among these potential factors, we have demonstrated the pituitary-dependent expression of IGF-I, c-myc, c-fos proteins. The purity of the preparations used in this work permits to distinguish clearly the specific and direct effect of each pituitary hormone from those mediated by paracrine or autocrine factors.