Stereoselective determination of midodrine and desglymidodrine in culture medium: Application to a biotransformation study employing endophytic fungi

A CE method was developed and validated for the stereoselective determination of midodrine and desglymidodrine in Czapek culture medium to be applied to a stereoselective biotransformation study employing endophytic fungi. The electrophoretic analyses were performed using an uncoated fused-silica capillary and 70 mmol/L sodium acetate buffer solution (pH 5.0) containing 30 mmol/L heptakis (2, 3, 6-tri-O-methyl)-beta-CD as running electrolyte. The applied voltage and temperature used were 15 kV and 15 C, respectively. The UV detector was set at 200 nm. The sample preparation was carried out by liquid-liquid extraction using ethyl acetate as extractor solvent. The method was linear over the concentration range of 0.1-12 mu g/mL for each enantiomer of midodrine and desglymidodrine (r >= 0.9975). Within-day and between-day precision and accuracy evaluated by RSDs and relative errors, respectively, were lower than 15% for all analytes. The method proved to be robust by a fractional factorial design evaluation. The validated method was used to assess the midodrine biotransformation to desglymidodrine by the fungus Phomopsis sp. (TD2), which biotransformed 1.1% of (-)-midodrine to (-)-desglymidodrine and 6.1% of (+)-midodrine to (+)-desglymidodrine.

Enantioselective Analysis of Fluoxetine and Norfluoxetine by LC in Culture Medium for Application in Biotransformation Studies Employing Fungi

A liquid chromatography method is described for the analysis of fluoxetine and norfluoxetine enantiomers in fungi cultures. The analytes were separated simultaneously by LC employing a serial system. The resolution was performed using a mobile phase of ethanol: 15 mM ammonium acetate buffer solution, pH 5.9: acetonitrile (77.5:17.5:5, v/v/v). UV detection was at 227 nm. Hexane: isoamyl alcohol (98:2, v/v) was used as extractor solvent. The calibration curves were linear over the concentration range of 12.5-3,750 ng mL(-1) (r a parts per thousand yen 0.996). The values for intra- and inter-day precision and accuracy were a parts per thousand currency sign10% for all analytes. The validated method was used to evaluate fluoxetine biotransformation to its mammalian metabolite, norfluoxetine, by selected endophytic fungi. Although the desired biotransformation was not observed in the conditions used here, the method could be used to evaluate the biotransformation of fluoxetine by other fungi or to be extended to other matrices with adequate procedures for sample preparation.

Photoreactions of n-alkyl-3-nitrophenyl ethers with aromatic amines in SDS micelles: A laser flash photolysis study

The quenching of the triplet state of three n-alkyl 3-nitrophenyl ethers: 3-nitroanisol (3-NA), n-butyl 3-nitrophenyl ether (3-NB) and n-decyl 3-nitrophenyl ether (3-ND) by four aniline derivatives: aniline (AN), N,N-dimethylaniline (DMA), 2,4,6-trimethylaniline (TMA), and 4-tetradecylaniline (TDA), was investigated in aqueous micellar SDS solutions by laser flash photolysis. The transient absorption spectra for 3-NA and 3-NB reveal the formation of long-lived intermediate species in the presence of all four quenchers. while for 3-ND no amine-induced intermediates are observed. Comparison of the transient absorption spectra of the probe 3-NA in the presence of DMA in aqueous and micellar solutions shows that the intermediate species are favored by the SDS micelles. With DMA and TMA as quenchers the intermediates are suggested to be the ion radicals generated by single electron transfer from the amine to the probe in the triplet excited state. For the quenchers AN and TDA, the intermediates may be a-complexes. The relative quenching efficiencies generally decrease as the affinity of the quencher for the micellar phase (AN < DMA < TMA < TDA) increases and the mobility of the excited probe (3-NA > 2-NB) decreases. (C) 2011 Elsevier B.V. All rights reserved.

Does Cyclophosphamide Play a Protective Role Against Neuronal Loss in Chronic T. cruzi Infection?

In this study, we verified the possible role of cyclophosphamide (CY) in protecting or not against neuronal losses in young and aged male Calomys callosus chronically infected with the MORC-1 strain of Trypanosoma cruzi through numerical quantification of neurons from the myenteric plexus of the colon and quantification of nitric-oxide concentration (NO) during the acute and chronic phase of infection. For this purpose, groups of young C. callosus were infected with the MORC-1 strain of T. cruzi. A group of infected animals received i.p. 0.2 mg/ml genuxal dissolved in distilled water treatment with CY. NO concentration in aged animals displayed reduced levels when compared to those found in young animals. No significant alterations in the number of neurons were observed in young animals, but for aged ones, a protective role of CY in reducing neuron loss was noted, in addition to enhancing the neuronal volume, area, and perimeter. These results suggest that CY administration, depending on the dose and time span, can act as a protective agent against neuronal losses.

Could Cyclophosphamide exert a protective role avoiding esophagic neuron loss in Calomys callosus infected with Trypanosoma cruzi?

The protective role of Cyclophosphamide was studied in this work. Young male Calomys callosus were infected with Trypanosoma cruzi and allowed to age. Cyclophosphamide therapy was administered to animals during acute and late chronic phases of infection. Esophageal neurons were counted, displaying enhanced neuronal loss for the young and treated infected groups. For aged and cyclophosphamide treated animals, a protection was observed through a reduced loss of neurons as compared to the young and infected groups. Enhanced nitric oxide concentrations were observed for young animals as compared to aged counterparts. Splenocyte proliferation was reduced during the acute phase in comparison with those found in the chronic phase. Morphometry of neuronal body displayed a significant reduction concerning the area, perimeter, diameter and volume for aged animals as compared to young groups. These results indicate that the protective effects of cyclophosphamide together with process of neuroplasty of peripheral nervous system could lead to a protection against neuronal loss.

Multiple conformational epitopes are recognized by natural and induced immunity to the E7 protein of human papilloma virus type 16 in man

The reactivity of sera from patients with cervical cancer with the E7 protein of human papilloma virus type 16 (HPV16) was estimated using a novel non-radioactive immunoprecipitation assay and four established protein-and peptide-based immunoassays. Six of 14 sera from patients with cervical cancer and 1 of 10 sera from healthy laboratory staff showed repeated reactivity with E7 in at least one assay. Four of the 7 reactive sera were consistently reactive in more than one assay, but only one was reactive in all four assays. Following immunization with E7, 2 of 5 patients with cervical cancer had increased E7-specific reactivity, measurable in one or more assays. No single assay was particularly sensitive for E7 reactivity, or predictive of cervical cancer. Mapping of E7 reactivity to specific E7 peptides was unsuccessful, suggesting that natural or induced E7 reactivity in human serum is commonly directed to conformational epitopes of E7, These results suggest that each assay employed with is study measures a different aspect of E7 reactivity, and that various reactivities to E7 may manifest following HPV infection or immunization. This finding is of significance for monitoring of E7 immunotherapy and for serological screening for cervical cancer. Copyright (C) 2000 S.Karger, AG. Basel.

Debt Maturity: Is Long-Term Debt Optimal?

We model and calibrate the arguments in favor and against short-term and long-term debt. These arguments broadly include: maturity premium, sustainability, and service smoothing. We use a dynamic-equilibrium model with tax distortions and government outlays uncertainty, and model maturity as the fraction of debt that needs to be rolled over every period. In the model, the benefits of defaulting are tempered by higher future interest rates. We then calibrate our artificial economy and solve for the optimal debt maturity for Brazil as an example of a developing country and the US as an example of a mature economy. We obtain that the calibrated costs from defaulting on long-term debt more than offset costs associated with short-term debt. Therefore, short-term debt implies higher welfare levels.

Optimal reserve management and sovereign debt

Most models currently used to determine optimal foreign reserve holdings take the level of international debt as given. However, given the sovereign`s willingness-to-pay incentive problems, reserve accumulation may reduce sustainable debt levels. In addition, assuming constant debt levels does not allow addressing one of the puzzles behind using reserves as a means to avoid the negative effects of crisis: why do not sovereign countries reduce their sovereign debt instead? To study the joint decision of holding sovereign debt and reserves, we construct a stochastic dynamic equilibrium model calibrated to a sample of emerging markets. We obtain that the reserve accumulation does not play a quantitatively important role in this model. In fact, we find the optimal policy is not to hold reserves at all. This finding is robust to considering interest rate shocks, sudden stops, contingent reserves and reserve dependent output costs. (c) 2008 Elsevier B.V. All rights reserved.

Nominal versus indexed debt: A quantitative horse race

The main arguments in favor and against nominal and indexed debts are the incentive to default through inflation versus hedging against unforeseen shocks. We model and calibrate these arguments to assess their quantitative importance. We use a dynamic equilibrium model with tax distortion, government outlays uncertainty, and contingent-debt service. Our framework also recognizes that contingent debt can be associated with incentive problems and lack of commitment. Thus, the benefits of unexpected inflation are tempered by higher interest rates. We obtain that costs from inflation more than offset the benefits from reducing tax distortions. We further discuss sustainability of nominal debt in developing (volatile) countries. (C) 2010 Elsevier Ltd. All rights reserved.

Hippolyte obliquimanus (Decapoda : Caridea : Hippolytidae): a gonochoric or hermaphroditic shrimp species?

Several studies have reported the occurrence of hermaphroditism in caridean shrimps of the family Hippolytidae. Here we provide the first observations of population traits from the small Western Atlantic shrimp, Hippolyte obliquimanus, to determine its sexual system using descriptive and experimental approaches. Specimens were collected at 2-month intervals from March 2005 to May 2006 in Ubatuba Bay on the northern coast of the state of Sao Paulo, Brazil. The sex of individuals was checked and morphometric dimensions (carapace length, maximum pleura of second abdominal segment width, appendix masculina length, maximum propodus width, and dactyl length of the third pereopod) were also analyzed. The gonads were dissected and examined for signs of abnormalities. The possibility of sex change was experimentally evaluated under laboratory conditions. A total of 674 specimens were collected: 211 males, 339 non-ovigerous females, and 124 ovigerous females. The carapace length ranged from 0.55 to 3.20 mm, with females being significantly larger than males. Hippolyte obliquimanus showed sexual dimorphism in the third pereopod, absence of cincinnuli in the first pleopod, and no reduction of the appendix masculina in the largest males. All males examined had only testes, and all females had only ovaries. There was no sex change observed in the experiments. Together, these data indicate a population with females reaching larger sizes than males, males with a well-developed appendix masculina, and no transitional individuals. The results presented allow characterizing H. obliquimanus as a gonochoric species.

Shelter association between the hermit crab Sympagurus dimorphus and the zoanthid Epizoanthus paguricola in the southwestern Atlantic Ocean

Schejter, L. and Mantelatto, F.L. 2011. Shelter association between the hermit crab Sympagurus dimorphus and the zoanthid Epizoanthus paguricola in the southwestern Atlantic Ocean. -Acta Zoologica (Stockholm) 92: 141-149. The available literature on zoanthid-hermit crab associations deals only with records of this phenomenon, providing no detailed information. We describe, for the first time, the shell-like colonies of Epizoanthus paguricola associated with the hermit crab Sympagurus dimorphus from benthic samples taken in the Argentine Sea, between 85 and 131 m depth, and provide information about morphometric relationships between the hermits and the zoanthids. In total, 260 specimens (137 males and 123 females) of S. dimorphus were collected, 240 (92.3%) of which were living in symbiosis with E. paguricola. The remaining 20 (7.7%) were living inside gastropod shells. As the initial structure of the pseudoshell, 12 different gastropod species were found (all were almost totally covered with colonies of E. paguricola). The hermit crab lives in the spiral cavity inside the soft colony, which seemed to be slightly different depending on the initial gastropod. Aperture pseudoshell morphology did not seem to be related to the sex of the hermit crab host, although males showed larger apertures for a given colony size. This fact is probably related to a larger size of male`s cheliped (sexual dimorphic character) used like a gastropod operculum and that may serve as a template for the growing of the aperture pseudoshell edge. The number of epizoanthid polyps per colony increased in relation to the weight of the colony and to the size of the hermit crab. A process of selection of the initial shell was evident, because species of Naticidae were not the most common gastropods in this benthic community, but were those most used by hermit crabs (> 60%). The puzzling association between hermit crab, shell and zoanthid presumably occurs during the hermit juvenile phase, when the crab occupies a small shell, and a zoanthid larva settles on it. Given the close relationship between S. dimorphus and E. paguricola found in this region, we support the idea that due to the low availability of adequate gastropod shells for hermit life cycle, this association allows the establishment and the continuity of the hermit crab population in the studied area.

MORPHOLOGICAL CASTE DIFFERENCES IN POLYBIA AEQUATORIALIS (HYMENOPTERA: VESPIDAE: POLISTINAE: EPIPONINI), A SOCIAL WASP OF THE HIGHLANDS OF COSTA RICA

Many aspects of the biology and organization of Neotropical social wasps in the highlands are unknown. Polybia aequatorialis is a highland wasp of Costa Rica distributed between 1, 150 and 3,200 m in altitude, and little information on this species is recorded. We investigated the size of a colony of P. aequatorialis in the Cerro de la Muerte region of Costa Rica, and studied the morphological differences between queens and workers. Measures were taken from 248 reproductive and non-reproductive females, and caste differentiation was analyzed by Discrimination Function Analysis. We did not find a highly pronounced caste distinction in P. aequatorialis, even though ANOVA showed that queens and workers differed in all morphometric measures. The morphological differences between the reproductive and non-reproductive females probably results from a developmental switch, which is a characteristic caste syndrome of Polybia.

Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy*

In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.

EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria

Objectives To validate the previously proposed classification criteria for Henoch-Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). Methods Step 1: retrospective/prospective webdata collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis <= 18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and.-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.