Side‐On Nematic Liquid Crystal Dendrimers Based on PAMAM and PPI as Dendritic Scaffolds: Synthesis and Characterization

The design, synthesis, and investigation of two series of side‐on dendrimers displaying nematic liquid crystal behavior at room temperature are described. The dendritic structures are derived from poly(amidoamine) (PAMAM‐(NH₂)_n) or poly(propylene imine) dendrimers (PPI‐(NH₂)_n) (with n = 4, 8, 16, 32, and 64) containing lateral attached mesogenic units in the periphery. The materials are characterized by ¹H, ¹³C nuclear magnetic resonance (NMR) spectroscopy, matrix‐assisted laser desorption/ionization‐mass (MALDI‐TOF MS) spectrometry, differential scanning calorimetry (DSC), polarized optical microscopy (POM), and x‐ray diffraction spectroscopy. All dendrimers exhibit nematic mesophase behavior at room temperature. Conoscopic studies reveal that the nematic phase is uniaxial. The relationship between the structure of the two dendrimer series and the mesomorphic behavior is discussed.

     

Addition of a second endoscopic treatment following epinephrine injection improves outcome in high-risk bleeding ulcers

BACKGROUND & AIMS: Endoscopic therapy reduces the rebleeding rate, the need for surgery, and the mortality in patients with peptic ulcer and active bleeding or visible vessel. Injection of epinephrine is the most popular therapeutic method. Guidelines disagree on the need for a second hemostatic procedure immediately after epinephrine; although it seems to reduce further bleeding, its effects on morbidity, surgery rates, and mortality remain unclear. The aim of this study was to perform a systematic review and meta-analysis to determine whether the addition of a second procedure improves hemostatic efficacy and/or patient outcomes after epinephrine injection. METHODS: An extensive search for randomized trials comparing epinephrine alone vs. epinephrine plus a second method was performed in MEDLINE and EMBASE and in the abstracts of the AGA Congresses between 1990 and 2002. Selected articles were included in a meta-analysis. RESULTS: Sixteen studies including 1673 patients met inclusion criteria. Adding a second procedure reduced the further bleeding rate from 18.4% to 10.6% (Peto odds ratio 0.53, 95% CI: 0.40-0.69) and emergency surgery from 11.3% to 7.6% (OR: 0.64, 95% CI: 0.46-0.90). Mortality fell from 5.1% to 2.6% (OR: 0.51, 95% CI: 0.31-0.84). Subanalysis showed that the risk of further bleeding decreased regardless of which second procedure was applied. In addition, the risk was reduced in all subgroups, although reduction was more evident in high-risk patients and when no scheduled follow-up endoscopies were performed. CONCLUSIONS: Additional endoscopic treatment after epinephrine injection reduces further bleeding, need for surgery, and mortality in patients with bleeding peptic ulcer.     

Characterization of melatonin binding sites in the brain and retina of the frog Rana perezi

The aim of this study was to characterize 2-[125I]iodomelatonin binding sites in the neural retina and central nervous system (telencephalon, diencephalon, and optic tectum) of the anuran amphibian Rana perezi. Saturation and kinetic studies and pharmacological characterization revealed the existence of a unique melatonin-binding site that belongs to the Mel 1 receptor subtype. The affinity of this site is similar in all tissues studied (Kd, 10.5-12.8 pM), but the density varied from diencephalon and optic tectum, which exhibit the highest density, to telencephalon with the lowest. Neural retina showed an intermediate receptor density. This melatonin-binding site fulfills the requirements of a real hormone receptor; the binding is saturable, reversible, and inhibited by different melatonin agonists and antagonists. The affinity order of ligands is: 2-phenyl-melatonin = 2-I-melatonin > 6-Cl-melatonin = melatoninz > luzindole. Additionally, specific binding is decreased by non-hydrolysable GTP analogue, sodium, and by pretreatment of membranes with pertussis toxin. All these results suggest the existence of a widely distributed and pharmacologically homogeneous melatonin receptor of the subfamily Mel 1 in the nervous system of Rana perezi coupled to a Gi/o protein.     

Short- and long-term hospital and community exercise programmes for patients with chronic obstructive pulmonary disease

OBJECTIVE: Pulmonary rehabilitation in patients with COPD has been shown to be beneficial but the optimal setting is not known. In the present study, the efficacy of a short-term community-based exercise programme was compared with a standard hospital outpatient programme. Additionally, the usefulness of community or home programmes in maintaining improvements in the longer term was studied. METHODOLOGY: Forty-three patients with moderate to severe COPD were randomized to one of the following three groups: a 3-month hospital programme then a 9 month home programme (Hospital/Home); a 3-month hospital programme then a 9-month community programme (Hospital/Community); or a 12-month community programme (Community/Community). The initial 3-month programme was analysed by comparing the Hospital group (Hospital/Home plus Hospital/Community) with the Community group (Community/Community). Six-minute walking distance (6MWD), quality of life (Guyatt chronic respiratory disease questionnaire, CRQ) and lung function were measured at 0, 3, 6 and 12 months and results were analysed using the Wilcoxon rank sum test. RESULTS: At 3 months, there was a significant improvement from baseline in 6MWD in the Hospital group (81.3 +/- 18.3 m, P < 0.05, anova) but not the Community group (14.4 +/- 28.5 m, not significant). The difference between the groups was not significant (P = 0.058). At 3 months, there was a significant improvement in quality of life in the Hospital group (CRQ +16.3 +/- 3.1, P < 0.01, anova) and in the Community group (CRQ +10.2 +/- 4.9, P < 0.05, anova) but the difference between the groups was not significant. Following the initial 3-month programme, the dropout rate was high overall (73% by 12 months), and therefore data from the maintenance programme could not be analysed. CONCLUSIONS: A 3-month community-based exercise programme for patients with COPD did not improve 6MWD. The long-term retention rates in the programmes were poor.     

HIV/STI co-infections, syphilis incidence, and hepatitis B vaccination: the Buenos Aires cohort of men who have sex with men

In a previous cohort study among 327 men who have sex with men (MSM) in Buenos Aires, an HIV incidence rate of 3.9 per 100 persons-year was reported. Using data from this study, we determined: (a) HIV/STI co-infections; (b) clinical manifestations of incident HIV infections; (c) syphilis incidence and its associated risk factors; and (d) adherence and immune response to hepatitis B virus (HBV) vaccine. During the cohort study, 12 incident HIV infections were found. Within this group, HIV infection alone was most frequent (42%), followed by co-infection of HIV/HBV (33%), and triple co-infection of HIV/HBV/syphilis (25%). The most frequent clinical manifestations among incident HIV cases were: pharyngitis, fever, lymphadenopathy, asthenia, and myalgia. Seven new syphilis infections were detected yielding an incidence rate of 2.4 (95% CI=1.07 - 4.73) per 100 persons-year. Sex work was the only significant risk factor associated with syphilis seroconversion (hazard rate=10.93, p-value=0.033). Only 7% of cohort participants reported having received HBV vaccine. Ninety-percent of the 204 cohort members who agreed to be vaccinated completed the HBV vaccination schedule with an immune response rate of 85%. Our findings suggest the need to increase the access to serologic testing for STI and HBV immunization, as well as the developing of effective HIV/STI behavioral and educational prevention programs among MSM in Buenos Aires.     

Fish with thermolabile sex determination (TSD) as models to study brain sex differentiation

As fish are ectothermic animals, water temperature can affect their basic biological processes such as larval development, growth and reproduction. Similar to reptiles, the incubation temperature during early phases of development is capable to modify sex ratios in a large number of fish species. This phenomenon, known as thermolabile sex determination (TSD) was first reported in Menidia menidia, a species belonging to the family Atherinopsidae. Since then, an increasing number of fish have also been found to exhibit TSD. Traditionally, likewise in reptiles, several TSD patterns have been described in fish, however it has been recently postulated that only one, females at low temperatures and males at high temperatures, may represent the “real” or “true” TSD. Many studies regarding the influence of temperature on the final sex ratios have been focused on the expression and activity of gonadal aromatase, the enzyme involved in the conversion of androgens into estrogens and encoded by the cyp19a1a gene. In this regard, teleost fish, may be due to a whole genome duplication event, produce another aromatase enzyme, commonly named brain aromatase, encoded by the cyp19a1b gene. Contrary to what has been described in other vertebrates, fish exhibit very high levels of aromatase activity in the brain and therefore they synthesize high amounts of neuroestrogens. However, its biological significance is still not understood. In addition, the mechanism whereby temperature can induce the development of a testis or an ovary still remains elusive. In this context the present review is aimed to discuss several theories about the possible role of brain aromatase using fish as models. The relevance of brain aromatase and therefore of neuroestrogens as the possible cue for gonadal differentiation is raised. In addition, the possible role of brain aromatase as the way to keep the high levels of neurogenesis in fish is also considered. Several key examples of how teleosts and aromatase regulation can offer more insight into basic mechanisms of TSD are also reviewed.