Adherence to Medical Appointments Among Living Kidney Donors After Donation Under a Monitored Approach and Long-term Clinical Outcomes: A Brazilian Single-center Cohort Study.

BACKGROUND: There is little information about living donor long-term follow-up among Brazilian living donors. The aim of this study was to evaluate the main outcomes among living donors and to measure their adherence to regular medical appointments. METHODS: This is a Brazilian single-center cohort study that included 397 living donors with 87.1 months of follow-up and measured adherence to clinical appointments. Before 2010, the appointments were scheduled only spontaneously; after that an approach was structured to check the returns of donors, who were monitored actively. We also evaluated long-term outcomes such as survival and chronic kidney disease development and, secondarily, the incidences of hypertension, diabetes mellitus (DM), and dyslipidemia after donation. RESULTS: The donors' adherence to annual clinical appointments was 75.8% (54.7% of them presenting annual regularity). Before 2010 the adherence was lower than 40%; 10-year cumulative incidences of hypertension, DM, and dyslipidemia were 20.4%, 5.7%, and 23.5%, respectively. The crude mortality was 1% and 10-year donor survival was 98.5%. The incidence of chronic kidney disease 5 years after donation was 19%, with 16.4% of patients staged in 3a and 2.6% in 3b. CONCLUSION: A structured approach to check donor returns to long-term clinical appointments has doubled the adherence to visits returns (compared to historical data). We identified lower incidence of arterial hypertension and DM among donors as compared with the incidence of arterial hypertension and DM in the Brazilian general population, but the 5-year chronic kidney disease incidence was considered high, taking into consideration data that have been published in the last years.

Evaluation of cell toxicity and DNA and protein binding of green synthesized silver nanoparticles.

Silver nanoparticles (AgNPs) were prepared by GREEN chemistry relying on the reduction of AgNO3 by phytochemicals present in black tea extract. AgNPs were fully characterized by transmission electron microscopy (TEM), ultraviolet-visible spectroscopy ((UV-vis)), X-ray diffraction (XRD) and energy dispersive absorption spectroscopy (EDS). The synthesized AgNPs induced a decrease of the cell viability in a dose-dependent manner with a low IC50 (0.5 ±â€¯0.1 µM) for an ovarian carcinoma cell line (A2780) compared to primary human fibroblasts (IC50 5.0 ±â€¯0.1 µM). The DNA binding capability of CT (calf thymus) DNA was investigated using electronic absorption and fluorescence spectroscopies, circular dichroism and viscosity titration methods. Additionally, the AgNPs strongly quench the intrinsic fluorescence of BSA, as determined by synchronous fluorescence spectra.

In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi.

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.

Frequency of human papillomavirus types 16, 18, 31, and 33 and sites of cervical lesions in gynecological patients from Recife, Brazil.

Human papilloma virus (HPV) is a well-established cause of cervical cancer. While many studies have been performed so far on HPV viral biology, mode of infection and prevention measures, scanty information is available on lesion sites of infected women and the incidence of viral types at specific locations. We looked for a possible relationship between the most common viral types (HPVs 16, 18, 31, 33) found in Recife, PE, Brazil, and lesion sites. We examined 396 HPV-positive women at the Gynecological Unit of the IMIP at Recife; 288 women were positive for HPV 16, 18, 31, or 33, present as a single-virus type or as co-infection. HPV 16 was the most frequent virus type found in the vulva, vagina, uterine cervix-vagina, and uterine cervix. HPV 31 was the second prevalent virus type in vulva, vagina, uterine cervix-vagina, uterine cervix, and mole. HPVs 18 and 33 were present with similar frequencies in the mole-vulva region. Among the co-infections, HPV 16/18 and HPV16/31 were the most frequent in our study group, followed by HPV 16/33.

Heart transplantation in 107 cases of Chagas' disease.

INTRODUCTION: Chagas' disease is endemic in South America. OBJECTIVE: This research reviewed the experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas' disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. RESULTS: The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n = 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas' disease in the central nervous system (n = 1; 7.1%). CONCLUSIONS: Transplantation in Chagas' disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.

Detection of uncommon rotavirus A strains P[8]G8 and P[4]G8 in the city of Rio de Janeiro, 2002.

Group A rotaviruses (RV-A) are the major cause of gastroenteritis in infants and young children around the world. Each year RV-A causes approximately 11 million episodes of severe diarrhea, with an estimated of 611,000 deaths. Epidemiologic surveys have identified P[8]G1, P[4]G2, P[8]G3, P[8]G4, and P[8]G9 as the most common global genotypes associated with diarrhea in children up to 5-year old. Surveillance studies and documentation of RV-A G and P genotypes is necessary for a comprehensive evaluation of the evolution of new strains, and assessing the capability of vaccines to provide heterotypic protection. It is known that reassortments are the driving force for genetic diversity through sudden changes in RV-A genome. In this study, we identified two unusual P/G combinations, P[8]G8 and P[4]G8, occurring in Rio de Janeiro during 2002. Results obtained in this study suggest that P[8]G8 RV-A strain originated from a reassortment event that occurred between RV-A P[4]G8 and P[8]G9 strains circulating in Rio de Janeiro in the same year. G8 strains identified in this study, as well as G8 strains detected in Recife by Montenegro et al. [Montenegro et al. (2007) J Med Virol 79: 335-340], showed a close genetic relationship with strains from Africa, where this genotype have become prevalent.

Efficiency of RAPD versus SSR markers for determining genetic diversity among popcorn lines.

Using only one type of marker to quantify genetic diversity generates results that have been questioned in terms of reliability, when compared to the combined use of different markers. To compare the efficiency of the use of single versus multiple markers, we quantified genetic diversity among 10 S(7) inbred popcorn lines using both RAPD and SSR markers, and we evaluated how well these two types of markers discriminated the popcorn genotypes. These popcorn genotypes: "Yellow Pearl Popcorn" (P1-1 and P1-5), "Zélia" (P1-2 and P1-4), "Curagua" (P1-3), "IAC 112" (P9-1 and P9-2), "Avati Pichinga" (P9-3 and P9-5), and "Pisankalla" (P9-4) have different soil and climate adaptations. Using RAPD marker analysis, each primer yielded bands of variable intensities that were easily detected, as well as non-specific bands, which were discarded from the analysis. The nine primers used yielded 126 bands, of which 104 were classified as polymorphic, giving an average of 11.6 polymorphisms per primer. Using SSR procedures, the number of alleles per locus ranged from two to five, giving a total of 47 alleles for the 14 SSR loci. When comparing the groups formed using SSR and RAPD markers, there were similarities in the combinations of genotypes from the same genealogy. Correlation between genetic distances obtained through RAPD and SSR markers was relatively high (0.5453), indicating that both techniques are efficient for evaluating genetic diversity in the genotypes of popcorn that we evaluated, though RAPDs yielded more polymorphisms.

HPV31 and HPV33 incidence in cervical samples from women in Recife, Brazil.

Human papillomavirus (HPV) has been extensively studied concerning genomic structure, infection mechanisms, and diversity of types, as well as disease progression stages and development of vaccines. HPV type prevalence can differ in specific populations in different countries, according to ethnicity. This is the first report of an integrated project to evaluate the incidence of HPV types in different regions in Brazil in order to obtain data for vaccine development. Cervical samples were collected from women seen at a public hospital in Pernambuco, Northeast Brazil, for routine evaluation of genital alterations. Selection of the patients was random. There was a strong prevalence of HPV16 and a high incidence of HPV types 31 and 33. These data foster the discussion about the need to evaluate viral prevalence in each geographic region in order to develop targeted vaccine programs.

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr.

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.

Genetic selection for resistance or susceptibility to oral tolerance imparts correlation to both Immunoglobulin E level and mast cell number phenotypes with a profound impact on the atopic potential of the individual.

BACKGROUND: Immunological oral tolerance is being studied with great interest due to its therapeutic potential in allergy and autoimmunity processes, although the cellular and molecular mechanisms linking these different phenomena remain elusive. In the present study, two mouse lines with extreme phenotypes for susceptibility [TS Line] or resistance [TR Line] to oral tolerance and their [TS x TR]F2 segregants were used in order to evaluate the impact of these traits on the atopic potential of the individuals. OBJECTIVE: Demonstrate whether the tr and ts genes, cumulated during 18 generations of bidirectional genetic selection, influence expression of two important immunobiological traits (IgE and mast cell) critical to allergic response. METHODS: Mice with extreme phenotypes for oral tolerance to ovalbumin (OVA), produced by assortative mating (TS and TR Line), and their (TS x TR)F2 segregating were used. Serum IgE levels assayed by ELISA, and mastocytes counted with toluidine blue staining were evaluated in naïve mice. Anaphylaxis was induced by intravenous injection of OVA, intestinal inflammation by oral administration of OVA 7 days after immunization, and pulmonary inflammation by intranasal and nebulization OVA challenges. Specific IgE was dosed by passive cutaneous anaphylaxis. RESULTS: The naïve TS mice have a 20-fold lower serum IgE level and two- to threefold diminished mast cell numbers in mucosal sites, when compared with TR-mice, which were highly susceptible to allergic inflammation and anaphylactic shock. The associations of oral tolerance, serum IgE levels and mast cell numbers in naïve animals were confirmed analysing the simultaneous presence of these traits in individuals of a [TS x TR]F2 -segregating population. CONCLUSION: The results suggest that the complex of genes controlling TS and TR phenotypes play a main role in the regulation of the atopic potential of the individual. The studies of these traits in interline F2 segregants demonstrated a co-segregation of TS and TR phenotypes with IgE responsiveness and mast cell numbers. Thus, the opposite capacity of the genetically modified mice may be involved in co-adaptative mechanisms reflecting a dynamic relation between gene frequencies in a natural population. These correlations give circumstantial evidence to support clinical applications of oral tolerance in allergic and autoimmune diseases.

Screening of Leishmania APRT enzyme inhibitors.

Adenine phosphoribosyltransferase (APRT) enzyme from Leishmania tarentolae has been proposed as a target for the rational search of new leishmanicidal drugs. In this paper, we describe the evaluation of the inhibitory activity on L. tarentolae APRT enzyme of 46 crude extracts of Meliaceae and Rutaceae plants, besides three furoquinolone alkaloids. The results showed that 21 extracts were able to decrease the APRT enzymatic activity (IA% > or = 50). The methanolic extracts from roots and leaves of Cedrela fissilis and from fruits, branches and leaves of Cipadessa fruticosa have showed strong activities. Therefore, these species could be a promising source of lead compounds for the rational design of new leishmanicidal drugs. The phytochemical investigation of an active fraction from Almeidea rubra afforded the alkaloids isodutaduprine, isoskimmianine and isokokusagine, which showed low to moderate activity on APRT.

Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A resolution.

The structure of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X-ray crystallography to 1.95 A resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed.

Sesquiterpene pyridine alkaloids from Peritassa campestris.

An investigation of the methanol and ethyl acetate extracts from the roots of Peritassa campestris (Hippocrateaceae) afforded the sesquiterpene pyridine alkaloid, 4-hydroxy-7-epi-chuchuhuanine E-V, and nine known alkaloids, forrestine, euonimine, ebenifoline E-I, wilforine, euojaponine F, euonine, wilforjine, neowilforine, and wilforzine. The structures of the isolates were elucidated on the basis of spectral data, particularly HMQC and HMBC experiments.

Separation and NMR studies on lignans of Raulinoa echinata.

Investigation of the leaves of Raulinoa echinata Cowan (Rutaceae) has led to the isolation of several furofuran (2,6-diaryl-3,7-dioxabicyclo[3.3.0]-octane) lignan derivatives, namely (+)-sesamin, (+)-eudesmin, (+)-methylpiperitol (= kobusin), (+)-piperitol-gamma,gamma-dimethylallylether and the corresponding epi compounds: (+)-asarinin, (+)-epieudesmin, (+)-methylxanthoxylol, (+)-methylpluviatilol, (+)-xanthoxylol-gamma,gamma-dimethylallylether and (+)-pluviatilol-gamma,gamma-dimethylallylether. This is the first report of the chromatographic separation of the epimers (+)-methylxanthoxylol/(+)-methylpluviatilol and (+)-xanthoxylol-gamma,gamma-dimethylallylether/(+)-pluviatilol-gamma,gamma- dimethylallylether and of their NMR nOe difference studies.

Studies towards the detection and identification of sesquiterpene pyridine alkaloids in Peritassa campestris by mass spectrometry.

Sesquiterpene pyridine alkaloids were analysed in Peritassa campestris by mass spectrometric techniques such as ESI-MSMS and GCMS. Ten alkaloids previously isolated from this plant and fully identified by other physical methods, including NMR spectroscopy and X-ray diffraction, were carefully studied by MS. It was observed that the low mass ions detected at m/z 178 and 206 in both MS technique tested were characteristic of evoninic and wilfordic acids, which are part of the macrolactone in these sesquiterpene alkaloids. The intensity of a fragment ion detected at m/z 93 in CAD, and especially in EI, spectra was found to be diagnostic in distinguishing between evoninoates and wilfordates. Running parent/daughter or GCMS experiments enabled these substances to be detected in crude fractions of P. campestris. Parent ion scans of m/z 206 were very as a first analysis of an alkaloid mixture.

Limonoids from the endemic Brazilian species Raulinoa echinata.

Phytochemical survey of stems and leaves of the South Brazilian endemic Raulinoa echinata Cowan, Rutaceae led to the isolation of five limonoid derivatives: the widespread limonin, limonexic acid, kihadalactone B, a methoxylated limonexic acid derivative and a degraded limonoid structurally related to fraxinellone. The two latter compounds have been isolated for the first time. These compounds displayed weak inhibitory activity when assayed in vitro against trypomastigote forms of Trypanosoma cruzi. In this paper, the isolation, structure elucidation and bioactivity of these compounds are reported.

Toxicity of synthetic piperonyl compounds to leaf-cutting ants and their symbiotic fungus.

The development of Leucoagaricus gongylophorus, the fungus cultured by the leaf-cutting ant Atta sexdens was inhibited in vitro by synthetic compounds containing the piperonyl group. In addition, worker ants that were fed daily on an artificial diet to which these compounds were added had a higher mortality rate than the controls. The inhibition of the fungal growth increased with the size of the carbon side chain ranging from C1 through C8 and decreasing thereafter. 1-(3,4-Methylenedioxybenzyloxy)octane (compound 5) was the most active compound and inhibited the fungal development by 80% at a concentration of 15 micrograms ml-1. With worker ants the toxic effects started with compound 5 and increased with the number of carbons in the side chain. Thus, for the same concentration (100 micrograms ml-1) the mortality rates observed after 8 days of diet ingestion were 82%, 66% and 42%, for 1-(3,4-methylenedioxybenzyloxy)decane, 1-(3,4-methylenedioxybenzyloxy)dodecane and compound 5, respectively, whereas with commercial piperonyl butoxide the mortality was 68%. The latter compound, which is known as a synergist insecticide, was as inhibitory to the symbiotic fungus as the synthetic compound 5. The possibility of controlling these insects in the future using compounds that can target simultaneously both organisms is discussed.

Magnetic resonance of a dextran-coated magnetic fluid intravenously administered in mice.

Magnetic resonance was used to investigate the kinetic disposition of magnetite nanoparticles (9.4 nm core diameter) from the blood circulation after intravenous injection of magnetite-based dextran-coated magnetic fluid in female Swiss mice. In the first 60 min the time-decay of the nanoparticle concentration in the blood circulation follows the one-exponential (one-compartment) model with a half-life of (6.9 +/- 0.7) min. The X-band spectra show a broad single line at g approximately 2, typical of nanomagnetic particles suspended in a nonmagnetic matrix. The resonance field shifts toward higher values as the particle concentration reduces, following two distinct regimes. At the higher concentration regime (above 10(14) cm(-3)) the particle-particle interaction responds for the nonlinear behavior, while at the lower concentration regime (below 10(14) cm(-3)) the particle-particle interaction is ruled out and the system recovers the linearity due to the demagnetizing field effect alone.

Azametallacycles from Ag(I)- or Cu(II)-promoted coupling reactions of dialkylcyanamides with oximes at Pt(II).

The dialkylcyanamide complexes cis-[PtCl(NCNR(2))(PPh(3))(2)][BF(4)] 1 and cis-[Pt(NCNR(2))(2)(PPh(3))(2)][BF(4)](2) 2 (R = Me or Et) have been prepared by treatment of a CH(2)Cl(2) solution of cis-[PtCl(2)(PPh(3))(2)] with the appropriate dialkylcyanamide and one or two equivalents of Ag[BF(4)], respectively. Compounds 2 can also be obtained from 1 by a similar procedure. Their reaction with oximes, HON=CR'R' ' (R'R' ' = Me(2) or C(4)H(8)), in CH(2)Cl(2) and in the presence of Ag[BF(4)] or Cu(CH(3)COO)(2), leads to the novel type of azametallacycles cis-[Pt(NH=C(ON=CR'R")-NR2)(PPh3)2][BF4]2 4 upon an unprecedented coupling of the organocyanamides with oximes, in a process that proceeds via the mixed oxime-organocyanamide species cis-[Pt(NCNR(2))(HON=CR'R' ')(PPh(3))(2)][BF(4)](2) 3, and is catalyzed by either Ag(+) or Cu(2+) which activate the ligating organocyanamide by Lewis acid addition to the amide group. In contrast, in the organonitrile complexes cis-[Pt(NCR)(2)(PPh(3))(2)][BF(4)](2) 5 (R = C(6)H(4)OMe-4 or Et), obtained in a similar way as 2 (but by using NCR instead of the cyanamide), the ligating NCR is not activated by the Lewis acid and does not couple with the oximes. The spectroscopic properties of those complexes are reported along with the molecular structures of 2b (R = Et), 4a1 (R = Me, R'R' ' = Me(2)), and 4b1 (R = Et, R'R' ' = Me(2)), as established by X-ray crystallography which indicates that in the former complex the amide-N-atoms are trigonal planar, whereas in the latter (4a1 and 4b1) the five-membered rings are planar with a localized N=C double bond (imine group derived from the cyanamide) and the exocyclic amide and alkylidene groups (in 4b1) are involved in two intramolecular H-bonds to the oxygen atom of the ring.

Syntheses, structure, and reactivity of chiral titanium compounds: procatalysts for olefin polymerization.

Titanium complexes with chelating alkoxo ligands have been synthesised with the aim to investigate titanium active centres in catalytic ethylene polymerisation. The titanium complexes cis-[TiCl2(eta2-maltolato)2] (1, 89%), and cis-[TiCl2(eta2-guaiacolato)2] (2, 80%) were prepared by direct reaction of TiCl4 with maltol and guaiacol in toluene. The addition of maltol to [Ti(OiPr)4] in THF results in the formation of species [Ti(OiPr)2(maltolato)2] (3, 82%). The titanium compound cis-[Ti(OEt)2(eta2-maltolato)2] (4, 74%) was obtained by the transesterification reaction of species 3 with CH3CO2Et. When compound 4 is dissolved in THF a dinuclear species [Ti2(mu-OEt)2(OEt)4-(eta2-maltolato)2] (5, 45%) is formed. Reaction of [Ti(OiPr)4] with crude guaiacol in THF yields a solid, which after recrystallisation from acetonitrile gives [Ti4(mu-O)4(eta2-guaiacolato)] x 4CH3CN (6, 55%). In contrast, reaction of TiCl4 with crude guaiacol in tetrahydrofuran affords [Ti2(mu-O)Cl2(eta2-guaiacolato)4] (7, 82%). Crystallographic and electrochemical analyses of these complexes demonstrate that maltolato and guaiacolato ligands can be used as a valuable alternative for the cyclopentadienyl ring. These complexes have been shown to be active catalysts upon combination with the appropriate activator.