Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study.

BACKGROUND A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level. METHODS A case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction. RESULTS The mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group. CONCLUSIONS This is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis.

BACKGROUND The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. DESIGN AND METHODS Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. RESULTS Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. CONCLUSIONS This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.

Effectiveness of Pregabalin as Monotherapy or Combination Therapy for Neuropathic Pain in Patients Unresponsive to Previous Treatments in a Spanish Primary Care Setting

BACKGROUND AND OBJECTIVE Patients from a previous study of neuropathic pain (NP) in the Spanish primary care setting still had symptoms despite treatment. Subsequently, patients were treated as prescribed by their physician and followed up for 3 months. Since pregabalin has been shown to be effective in NP, including refractory cases, the objective of this study was to assess the effectiveness of pregabalin therapy in patients with NP refractory to previous treatments. METHODS This was a post hoc analysis of pregabalin-naïve NP patients treated with pregabalin in a 3-month follow-up observational multicenter study to assess symptoms and satisfaction with treatment. Patients were evaluated with the Douleur Neuropathique en 4 questions (DN4), the Brief Pain Inventory (BPI) and the Treatment Satisfaction for Medication Questionnaire (SATMED-Q) overall satisfaction domain. RESULTS 1,670 patients (mean age 58 years, 59 % women), previously untreated or treated with ≥1 drug other than pregabalin, were treated with pregabalin (37 % on monotherapy). At 3 months, pain intensity and its interference with activities decreased by half (p < 0.0001), while the number of days with no or mild pain increased by a mean of 4.5 days (p < 0.0001). Treatment satisfaction increased twofold (p < 0.0001). Patients with a shorter history of pain and those with neuralgia and peripheral nerve compression syndrome (PCS) as etiologies had the highest proportion on monotherapy and showed the greatest improvements in pain-related parameters in their respective group categories. CONCLUSION Treatment with pregabalin (as monotherapy or combination therapy) provides benefits in pain and treatment satisfaction in patients with NP, including refractory cases. Shorter disease progression and neuralgia and PCS etiologies are favorable factors for pregabalin treatment response.

Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

Organic geochemistry across the Permian-Triassic transition at the Idrijca Valley, Western Slovenia

Bulk and molecular stable C isotopic compositions and biomarker distributions provide evidence for a diverse community of algal and bacterial organisms in the sedimentary organic matter of a carbonate section throughout the Permian-Triassic (P/Tr) transition at the Idrijca Valley, Western Slovenia. The input of algae and bacteria in all the Upper Permian and Lower Scythian samples is represented by the predominance of C-15-C-22 n-alkanes, odd C-number alkylcyclohexanes, C-27 steranes and substantial contents Of C-21-C-30 acyclic isoprenoids. The occurrence of odd long-chain n-alkanes (C-22-C-30) and C29 steranes in all the samples indicate a contribution of continental material. The decrease of C-org and C-carb contents, increase of Rock-Eval oxygen indices, and C-13-enrichment of the kerogen suggest a decrease in anoxia of the uppermost Permian bottom water. The predominance of odd C-number alkylcycloalkanes, C-27 steranes, and C-17 n-alkanes with delta(13)C values similar to-30parts per thousand, and C-13-enrichment of the kerogens in the lowermost Scythian samples are evidence of greater algal productivity. This increased productivity was probably sustained by a high nutrient availability and changes of dissolved CO2 speciation associated to the earliest Triassic transgression. A decrease Of Corg content in the uppermost Scythian samples, associated to a C-13-depletetion in the carbonates (up to 4parts per thousand) and individual n-alkanes (up to 3.4parts per thousand) compared to the Upper Permian samples, indicate lowering of the primary productivity (algae, cyanobacteria) and/or higher degradation of the organic matter. (C) 2003 Elsevier Ltd. All rights reserved.

Acylation of chiral alcohols: a simple procedure for chiral GC analysis

The use of iodine as a catalyst and either acetic or trifluoroacetic acid as a derivatizing reagent for determining the enantiomeric composition of acyclic and cyclic aliphatic chiral alcohols was investigated. Optimal conditions were selected according to the molar ratio of alcohol to acid, the reaction time, and the reaction temperature. Afterwards, chiral stability of chiral carbons was studied. Although no isomerization was observed when acetic acid was used, partial isomerization was detected with the trifluoroacetic acid. A series of chiral alcohols of a widely varying structural type were then derivatized with acetic acid using the optimal conditions. The resolution of the enantiomeric esters and the free chiral alcohols was measured using a capillary gas chromatograph equipped with a CP Chirasil-DEX CB column. The best resolutions were obtained with 2-pentyl acetates (α = 3.00) and 2-hexyl acetates (α = 1.95). This method provides a very simple and efficient experimental workup procedure for analyzing chiral alcohols by chiral-phase GC.

Total synthesis of entecavir

Entecavir (BMS-200475) was synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (i) a stereoselective boron-aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (ii) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (iii) the coupling with a purine derivative by a Mitsunobu reaction.

Agentes complexantes: podante, coronante e criptante classificação e nomenclatura

The scientific and practical interest in crown ethers as complexing agents for actions as well as for anions and neutral low molecular species is undeniable. New molecules with crown ether properties are constantly synthesized and new application discovered. This paper presents classification and nomenclature of the classical oligoethers (crown ethers): monocyclic coronands; oligocyclic spherical cryptands; and acyclic podands.

Hückel and Möbius annulenes: relationships between their Hückel-level orbitals and their Hückel-level energies

The problem of convenient access to quantitative Hückel-level descriptions of Möbius and Hückel annulenes for undergraduate lectures about aromaticity is discussed. Frost circle, Zimmerman circle, double circle and Langler semicircular mnemonics are described. The relationship between spectra (complete sets of secular equation roots) for an isoconjugate pair of Hückel and Möbius annulenes and the corresponding acyclic polyene with one less carbon is fully developed. In addition to providing an alternative path to exact spectrum roots, this relationship provides immediate access to almost half of the eigenfunctions for an isoconjugate annulene pair. The remaining eigenfunctions may be obtained very easily.

A structural bridge between alternant and non-alternant hydrocarbons

A simple set of trimethylene-substituted even, fully-pi-bonded, non-alternant monocycles is shown to have several key features in common with acyclic, even alternant polyenes at the Hückel level. These non-alternant molecules provide a bridge between alternant and non-alternant hydrocarbons. This topic might serve as a useful addition to Hückel theory courses targeted at senior undergraduate students.

A Cartan-Eilenberg approach to Homotopical Algebra

In this paper we propose an approach to homotopical algebra where the basic ingredient is a category with two classes of distinguished morphisms: strong and weak equivalences. These data determine the cofibrant objects by an extension property analogous to the classical lifting property of projective modules. We define a Cartan-Eilenberg category as a category with strong and weak equivalences such that there is an equivalence of categories between its localisation with respect to weak equivalences and the relative localisation of the subcategory of cofibrant objects with respect to strong equivalences. This equivalence of categories allows us to extend the classical theory of derived additive functors to this non additive setting. The main examples include Quillen model categories and categories of functors defined on a category endowed with a cotriple (comonad) and taking values on a category of complexes of an abelian category. In the latter case there are examples in which the class of strong equivalences is not determined by a homotopy relation. Among other applications of our theory, we establish a very general acyclic models theorem.

Óleos voláteis de espécies de Myrcia nativas do Rio Grande do Sul

Essential oils from M. richardiana, M. arborescens, M. selloi, M. oligantha, M. rostrata, M. lajeana, M. obtecta, M. pubipetala and M. hatschbachii were obtained by hydrodistillation and analyzed by GC and GC/MS. Sixty-seven compounds have been identified ranging from 90-99% of the oil contents. All analyzed species were rich in cyclic sesquiterpenes (66-99%), mainly those from the cadinane, caryophyllane and germacrane cyclization pathway, among them b-caryophyllene, germacrene D, bicyclogermacrene, d-cadinene, spathulenol, caryophyllene oxide, globulol and a-cadinol. The acyclic sesquiterpene series was well represented by M. lajeana (32.1%), with 25,3% of (E)-nerolidyl acetate.

Síntese de novas amidas graxas a partir da aminólise de ésteres metílicos

Recent biochemical and pharmacological studies have led to the characterization of different fatty acid amides as a new family of biologically active lipids. Here, we describe the synthesis of new amides from C16:0, 18:0, 18:1 and 18:1, OH fatty acids (FFA) families with cyclic and acyclic amines and demonstrate for the first time that these compounds produce citotoxic effects. Application of this method to the synthesis of fatty acid amides was performed using the esters aminolysis as a key step and various carboxylic amides were prepared in good yield from fatty acid methyl esters (FAMEs).

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

Consistent House Allocation

In practice we often face the problem of assigning indivisible objects (e.g., schools, housing, jobs, offices) to agents (e.g., students, homeless, workers, professors) when monetary compensations are not possible. We show that a rule that satisfies consistency, strategy-proofness, and efficiency must be an efficient generalized priority rule; i.e. it must adapt to an acyclic priority structure, except -maybe- for up to three agents in each object's priority ordering.