The Effect of Prostaglandin Analogs and Prostamide on Central Corneal Thickness

Objective: The aim of this study was to verify the influence of prostaglandin analogs and prostamide on central corneal thickness (CCT). Methods: A prospective analysis was done of CCT in glautomatous patients submitted to monotherapy with prostaglandin analogs (latanoprost 0.005% or travoprost 0.004%) or prostamide (bimatoprost 0.03%) during an 8-week period. A control group of patients without any ocular medication was also evaluated. CCT measurements were performed with a commercially available ultrasound pachymeter. A total of 73 patients were included in this study. Mean age was 68.5 +/- 9.2 (range, 48-85) years old. Results: A statistically significant reduction in CCT was observed in all groups, except the control group (n = 21): Bimatoprost 0.03% group (n = 21): 544.41 +/- 35.4 vs. 540.35 +/- 35.9 mu m (P = 0.039); travoprost 0.004% group (n = 17): 538.47 +/- 32.0 vs. 532.25 +/- 30.4 mu m (P = 0.009); latanoprost 0.005% group (n = 14): 548.57 +/- 32.4 vs. 543.88 +/- 35.6 mu m (P = 0.036). Conclusion: Topical therapy with prostaglandin analogs and bimatoprost is associated with CCT reduction over a period of at least 8 weeks.

Novel and facile solution-phase synthesis of 2,5-diketopiperazines and O-glycosylated analogs

This work describes the synthesis in Solution of a series of related diketopiperazines with potential biological activities: cyclo(L-Pro-L-Ser), cyclo(L-Phe-L-Ser), cyclo(D-Phe-L-Ser) and the corresponding glycosylated analogs of the latter, cyclo[D-Phe-L-Ser(alpha GlcNAc)] and cyclo[D-Phe-L-Ser(beta GlcNAc)]. The synthetic approach involved coupling reactions of -OH or O-glycosylated serine benzyl esters with NFmoc-protected amino acids (Pro or Phe), followed by one-pot deprotection-cyclization reaction in the presence of 20% piperidine in DMF. (C) 2009 Elsevier Ltd. All rights reserved.

Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropin-releasing hormone analogs

Context: Several factors can affect adult height (AH) of patients with gonadotropin-dependent precocious puberty (GDPP) treated with depot GnRH analogs. Objective: Our objective was to determine factors influencing AH in patients with GDPP treated with depot GnRH analogs. Patients: A total of 54 patients (45 girls) with GDPP treated with depot GnRH analog who reached AH was included in the study. Design: Univariate and multivariate analyses of the factors potentially associated with AH were performed in all girls with GDPP. In addition, clinical features of the girls who attained target height (TH) range were compared with those who did not. Predicted height using Bayley and Pinneau tables was compared with attained AH. Results: In girls the mean AH was 155.3 +/- 6.9 cm (-1.2 +/- 1 SD) with TH range achieved by 81% of this group. Multiple regression analysis revealed that the interval between chronological age at onset of puberty and at the start of GnRH analog therapy, height SD scores (SDSs) at the start and end of therapy, and TH explained 74% of AH variance. The predicted height at interruption of GnRH therapy, obtained from Bayley and Pinneau tables for average bone age, was more accurate than for advanced bone age in both sexes. In boys the mean AH was 170.6 +/- 9.2 cm (-1 +/- 1.3 SDS), whereas TH was achieved by 89% of this group. Conclusions: The major factors determining normal AH in girls with GDPP treated with depot GnRH analogs were shorter interval between the onset of puberty and start of therapy, higher height SDS at the start and end of therapy, and TH. Therefore, prompt depot GnRH analog therapy in properly selected patients with GDPP is critical to obtain normal AH.

Immunohistochemical Expression of HLA-DR in the Conjunctiva of Patients Under Topical Prostaglandin Analogs Treatment

Purpose: Subclinical inflammation may be observed in patients, using topical antiglaucomatous drugs. The objective,e of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of a immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. Subjects and Methods: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides. and Prepared for immunohistochemical analysis. Results: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression (of HLA-DR in the conjunctiva (mild). After 1 month oil prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was round (P 0.27). Conclusions: The use of prostaglandin analogs eye drops provokes, a reaction, observed by HLA-DR subclinical inflammatory expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

In vitro wear, surface roughness and hardness of propanal-containing and diacetyl-containing novel composites and copolymers based on bis-GMA analogs

Objective. To evaluate the effect of two additives, aldehyde or diketone, on the wear, roughness and hardness of bis-GMA-based composites/copolymers containing TEGDMA, propoxylated bis-GMA (CH(3)bis-GMA) or propoxylated fluorinated bis-GMA (CF(3)bis-GMA). Methods. Fifteen experimental composites and 15 corresponding copolymers were prepared combining bis-GMA and TEGDMA, CH3bis-GMA or CF3bis-GMA, with aldehyde (24mol% and 32 mol%) or diketone (24 mol% and 32 mol%) totaling 30 groups. For composites, hybrid treated filler (barium aluminosilicate glass/pyrogenic silica; 60 wt%) was added to monomer mixtures. Photopolymerization was affected by 0.2 wt% each of camphorquinone and N,N-dimethyl-p-toluidine. Wear (W) test was conducted in a toothbrushing abrasion machine (n = 6) and quantified using a profilometer. Surface roughness (R) changes, before and after abrasion test, were determined using a rugosimeter. Microhardness (H) measurements were performed for dry and wet samples using a Knoop microindenter (n = 6). Data were analyzed by one-way ANOVA and Tukey`s test (alpha = 0.05). Results. Incorporation of additives led to improved W and H values for bis-GMA/TEGDMA and bis-GMA/CH(3)bis-GMA systems. Additives had no significant effect on the W and H changes of bis-GMA/CF(3)bis-GMA. With regard to R changes, additives produced decreased values for bis-GMA/CH3bis-GMA and bis-GMA/CF3bis-GMA composites. Bis-GMA/TEGDMA and bis-GMA/CH(3)bis-GMA copolymers with additives became smoother after abrasion test. Significance. The findings correlate with additives ability to improve degree of conversion of some composites/copolymers thereby enhancing mechanical properties. Published by Elsevier Ltd on behalf of Academy of Dental Materials

Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes

Androgens play an important role in regulating the central obesity that is a strong risk factor for cardiovascular disease and insulin resistance. This study confirms that androgen receptors are present in subcultured human preadipocytes, with androgen receptor gene expression and saturable specific dihydrotestosterone binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 - 55.7 fmol/mg protein. There was an intrinsic regional difference in androgen receptor complement, with more androgen receptors in visceral than in subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human preadipocytes, with more androstanediol produced by subcutaneous than visceral preadipocytes. While dihydrotestosterone metabolism was insufficient to explain the regional variation in androgen binding, both of these differences would reduce the androgen responsiveness of the subcutaneous preadipocytes compared with visceral preadipocytes. There were no gender differences in androgen binding or metabolism. While the direct effects of androgens on human PAS remain uncertain, these regional differences suggest that AR-mediated regulation of certain PA functions influences adipose tissue distribution.

Procedures for monitoring recombinant erythropoietin and analogs in doping.

Hemoglobin concentration is one of the principal factors of aerobic power and, consequently, of performance in many types of physical activities. The use of recombinant human erythropoietin is, therefore, particularly powerful for improving the physical performances of patients, and, more generally, improving their quality of life. This article discusses procedures for monitoring recombinant erythropoietin and its analogues in doping for athletic performance.

Analogs of Cuntz algebras on Lp-spaces

Vegeu el resum a l'inici del document del fitxer adjunt.

Clinical and Virological Efficacy of Etravirine Plus Two Active Nucleos(t)ide Analogs in an Heterogeneous HIV-Infected Population.

Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION ClinicalTrials.gov NCT01437241.

Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures.

An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to study the maturation-dependent sensitivity of brain cells to two organophosphorus pesticides (OPs), chlorpyrifos and parathion, and to their oxon derivatives. Immature (DIV 5-15) or differentiated (DIV 25-35) brain cells were treated continuously for 10 days. Acetylcholinesterase (AChE) inhibitory potency for the OPs was compared to that of eserine (physostigmine), a reversible AChE inhibitor. Oxon derivatives were more potent AChE inhibitors than the parent compounds, and parathion was more potent than chlorpyrifos. No maturation-dependent differences for AChE inhibition were found for chlorpyrifos and eserine, whereas for parathion and paraoxon there was a tendency to be more effective in immature cultures, while the opposite was true for chlorpyrifos-oxon. Toxic effects, assessed by measuring protein content as an index of general cytotoxicity, and various enzyme activities as cell-type-specific neuronal and glial markers (ChAT and GAD, for cholinergic and GABAergic neurons, respectively, and GS and CNP, for astrocytes and oligodendrocytes, respectively) were only found at more than 70% of AChE inhibition. Immature compared to differentiated cholinergic neurons appeared to be more sensitive to OP treatments. The oxon derivates were found to be more toxic on neurons than the parent compounds, and chlorpyrifos was more toxic than parathion. Eserine was not neurotoxic. These results indicate that inhibition of AChE remains the most sensitive macromolecular target of OP exposure, since toxic effects were found at concentrations in which AChE was inhibited. Furthermore, the compound-specific reactions, the differential pattern of toxicity of OPs compared to eserine, and the higher sensitivity of immature brain cells suggest that the toxic effects and inhibition of AChE are unrelated.

Deposits of the sandy braided South Saskatchewan River: Implications for the use of modern analogs in reconstructing channel dimensions in reservoir characterization

Estimation of the dimensions of fluvial geobodies from core data is a notoriously difficult problem in reservoir modeling. To try and improve such estimates and, hence, reduce uncertainty in geomodels, data on dunes, unit bars, cross-bar channels, and compound bars and their associated deposits are presented herein from the sand-bed braided South Saskatchewan River, Canada. These data are used to test models that relate the scale of the formative bed forms to the dimensions of the preserved deposits and, therefore, provide an insight as to how such deposits may be preserved over geologic time. The preservation of bed-form geometry is quantified by comparing the Alluvial architecture above and below the maximum erosion depth of the modem channel deposits. This comparison shows that there is no significant difference in the mean set thickness of dune cross-strata above and below the basal erosion surface of the contemporary channel, thus suggesting that dimensional relationships between dune deposits and the formative bed-form dimensions are likely to be valid from both recent and older deposits. The data show that estimates of mean bankfull flow depth derived from dune, unit bar, and cross-bar channel deposits are all very similar. Thus, the use of all these metrics together can provide a useful check that all components and scales of the alluvial architecture have been identified correctly when building reservoir models. The data also highlight several practical issues with identifying and applying data relating to cross-strata. For example, the deposits of unit bars were found to be severely truncated in length and width, with only approximately 10% of the mean bar-form length remaining, and thus making identification in section difficult. For similar reasons, the deposits of compound bars were found to be especially difficult to recognize, and hence, estimates of channel depth based on this method may be problematic. Where only core data are available (i.e., no outcrop data exist), formative flow depths are suggested to be best reconstructed using cross-strata formed by dunes. However, theoretical relationships between the distribution of set thicknesses and formative dune height are found to result in slight overestimates of the latter and, hence, mean bankfull flow depths derived from these measurements. This article illustrates that the preservation of fluvial cross-strata and, thus, the paleohydraulic inferences that can be drawn from them, are a function of the ratio of the size and migration rate of bed forms and the time scale of aggradation and channel migration. These factors must thus be considered when deciding on appropriate length:thickness ratios for the purposes of object-based modeling in reservoir characterization.

Identification of pyridine analogs as new predator-derived kairomones.

In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG), an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a "from the wild to the lab" approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogs. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogs, implicated in interspecies danger communication.