Pielonefritis xantogranulomatosa secundaria a litiasis obstructiva en un paciente pediátrico / Pyelonephritis Xanthogranulomatous Secundary to Obstructive Lithiasis in Pediatric Patient

Introducción La pielonefritis xantogranulomatosa (XGPN), es una enfermedad inflamatoria crónica del parénquima renal, de rara presentación en pediatría. Su etiología es multifactorial comenzando con un proceso obstructivo del tracto urinario por litiasis e infección hasta el daño renal crónico. Su diagnóstico se logra por sospecha clínica, estudio imagenológico e histopatológico, lo que require tratamiento definitivo en la mayoría con nefrectomía simple. Materiales y métodos Paciente masculino de 4 años de edad con infección de la vía urinaria y dilatación de pelvis y uréter causada por cálculos que genera un proceso inflamatorio crónico y destrucción del parénquima renal. Sin respuesta clínica a tratamiento antibiótico quien requirió manejo en unidad de cuidados intensivos y nefrectomía. Discusión Se presenta entre la cuarta a sexta década de vida, con reportes de caso en edad pediátrica. Cursa con fiebre, dolor abdominal y masa palpable. Puede presentar en cambio de cursar con leucocitosis, anemia y piuria. Estudio radiológico de XGPN se puede apreciar de forma focal o difusa. A la histopatología se evidencia necrosis tisular crónica con macrófagos espumosos en su interior entremezclados con células inflamatorias. El tratamiento definitivo requiere nefrectomía de unidad renal disfuncional. Conclusiones Se presenta el caso de paciente pediátrico con XGPN por obstrucción urinaria litiásica; entidad de baja frecuencia en ese grupo poblacional, requiere una adecuada correlación clínico-imagenológica e histológica para lograr el diagnóstico final y puede ser tratado con manejo médico y quirúrgico.

Introduction Xanthogranulomatous pyelonephritis (XGPN) is a chronic inflammatory disease of the renal parenchyma, rare in pediatrics. Etiology is multifactorial ranging from an obstructive urinary tract process through lithiasis and infection generating chronic kidney amage. Its diagnosis is achieved by clinical suspicion, imaging and histopathology, which requires definitive treatment in the majority with simple nephrectomy Materials and Methods A 4-year-old male patient with urinary tract infection and dilation of the pelvis and ureter caused by calculus that generate a chronic inflammatory process and destruction of the renal parenchyma. No clinical response to antibiotic treatment that required management and intensive care unit and nephrectomy. Discussion It occurs between the fourth and sixth decade of life, with case reports in pediatric age. Patients have fever, abdominal pain and palpable mass. They can occur with leukocytosis, anemia and pyuria. Radiological study of XGPN can be seen in focal or diffuse form. Histopathology looks a chronic tissue necrosis with foamy macrophages and inflammatory cells. Definitive treatment requires nephrectomy of damaged renal unit. Conclusions We report the case of pediatric patients with XGPN due to urinary obstruction of the lithiasis; Low frequency entity in this population group, requires an adequate clinical-imaging and histological correlation to achieve final diagnosis and can be treated with medical and surgical management.

Following the Kinetics of Barium Titanate Nanocrystal Formation in Benzyl Alcohol Under Near-Ambient Conditions.

In complex chemical syntheses (e.g., coprecipitation reactions), nucleation, growth, and coarsening often occur concurrently, obscuring the individual processes. Improved knowledge of these processes will help to better understand and optimize the reaction protocol. Here, a form-free and model independent approach, based on a combination of time-resolved small/wide-angle X-ray scattering, is employed to elucidate the effect of reaction parameters (such as precursor concentration, reactant stoichiometry, and temperature) on the nucleation, crystallization, and growth phenomena during the formation of nanocrystalline barium titanate. The strength of this approach is that it relies solely on the total scattered intensity (i.e., scattering invariant) of the investigated system, and no prior knowledge is required. As such, it can be widely applied to other synthesis protocols and material's systems. Through the scattering invariant, it is found that the amorphous-to-crystalline transformation of barium titanate is predominantly determined by the total amount of water released from the gel-like barium hydroxide octahydrate precursor, and three rate-limiting regimes are established. As a result of this improved understanding of the effect of varying reaction conditions, elementary boundary conditions can be set up for a better control of the barium titanate nanocrystal synthesis.

Thermochemical Stability and Friction Properties of Soft Organosilica Networks for Solid Lubrication.

In view of their possible application as high temperature solid lubricants, the tribological and thermochemical properties of several organosilica networks were investigated over a range of temperatures between 25 and 580 °C. Organosilica networks, obtained from monomers with terminal and bridging organic groups, were synthesized by a sol-gel process. The influence of carbon content, crosslink density, rotational freedom of incorporated hydrocarbon groups, and network connectivity on the high temperature friction properties of the polymer was studied for condensed materials from silicon alkoxide precursors with terminating organic groups, i.e., methyltrimethoxysilane, propyltrimethoxysilane, diisopropyldimethoxysilane, cyclohexyltrimethoxysilane, phenyltrimethoxysilane and 4-biphenylyltriethoxysilane networks, as well as precursors with organic bridging groups between Si centers, i.e., 1,4-bis(triethoxysilyl)benzene and 4,4'-bis(triethoxysilyl)-1,1'-biphenyl. Pin-on-disc measurements were performed using all selected solid lubricants. It was found that materials obtained from phenyltrimethoxysilane and cyclohexyltrimethoxysilane precursors showed softening above 120 °C and performed best in terms of friction reduction, reaching friction coefficients as low as 0.01. This value is lower than that of graphite films (0.050 ± 0.005), a common bench mark for solid lubricants.

Conditional postnatal deletion of the neonatal murine hepatic circadian gene, Npas2, alters the gut microbiome following restricted feeding.

BACKGROUND: We have recently shown in both non-human primates and in rodents that fetal and neonatal hepatic expression of the circadian transcription factor, Npas2, is modulated by a high fat maternal diet and plays a critical role in establishing life-long metabolic homeostasis. Similarly, we and others have also established the importance of the maternal and early postnatal diet on establishment of the early gut microbiome. OBJECTIVE: We hypothesized that altered circadian gene expression solely in the neonatal liver would result in gut microbiome dysbiosis, especially with diet-induced metabolic stress (ie, restricted feeding). Using a murine model in which we conditionally knock out Npas2 in the neonatal liver, we aimed to determine the role of the circadian machinery in gut dysbiosis with restricted feeding. STUDY DESIGN: We collected fecal samples from liver Npas2 conditional knockout (n = 11) and wild-type (n = 13) reproductive-aged mice before (study day 0) and after the restricted feeding study (study day 17). Extracted DNA was sequenced using the MiSeq Illumina platform using primers specific for the V4 region of the 16S ribosomal DNA gene. The resulting sequences were quality filtered, aligned, and assigned taxonomy. Principal coordinate analysis was performed on unweighted and weighted UniFrac distances between samples with a permutation analysis of variance to assess clustering significance between groups. Microbial taxa that significantly differ between groups of interest was determined using linear discriminate analysis effect size and randomForrest. RESULTS: Principal coordinate analysis performed on weighted UniFrac distances between male conditional knockout and wild-type cohorts revealed that the gut microbiome of the mice did not differ by genotype at the start of the restricted feeding study but did differ by virtue of genotype at the end of the study (P = .001). Moreover, these differences could be at least partially attributed to restricted feeding-associated alterations in relative abundance of the Bacteroides genus, which has been implicated as crucial to establishing a healthy gut microbiome early in development. CONCLUSION: Here we have provided an initial key insight into the interplay between neonatal establishment of the peripheral circadian clock in the liver and the ability of the gut microbiome to respond to dietary and metabolic stress. Because Npas2 expression in the liver is a target of maternal high-fat diet-induced metabolic perturbations during fetal development, we speculate that these findings have potential implications in the long-term metabolic health of their offspring.

Hybrid n-Alkylamine Intercalated Layered Titanates for Solid Lubrication.

The intercalation of different primary n-alkylamines in the structure of a layered titanate of the lepidocrocite type (H1.07Ti1.73O4) for application in high-temperature solid lubrication is reported. The intercalation process of the amines was explored by means of in situ small-angle X-ray scattering (SAXS), with variations in alkyl chain length (3-12 carbon atoms) and the amine/titanate ratio. The intercalation process was found to be completed within 5 min after mixing of the precursors in water at 80 °C. The topotactic transformation of the layered titanate is driven by an acid-base reaction. The thermal degradation of the modified titanates was investigated by thermogravimetric analysis (TGA), and the chemical changes were investigated by temperature-dependent infrared spectroscopy (DRIFTS). The coefficient of friction of the lubricants was assessed by means of high-temperature pin-on-disc experiments up to 580 °C. The intercalation of amine rendered a deformable layered ceramic upon heating. It was found that the hydrocarbon chain length exerts an influence on the mechanical properties of the titanates, resulting in lower friction forces for lubricants with longer intercalated amine molecules. Films of solid lubricants with longer amine chain lengths showed coefficients of friction as low as 0.01, lower than that of the state-of-the-art material graphite.

Tribochemistry of Bismuth and Bismuth Salts for Solid Lubrication.

One of the main trends in the past decades is the reduction of wastage and the replacement of toxic compounds in industrial processes. Some soft metallic particles can be used as nontoxic solid lubricants in high-temperature processes. The behavior of bismuth metal particles, bismuth sulfide (Bi2S3), bismuth sulfate (Bi2(SO4)3), and bismuth oxide (Bi2O3) as powder lubricants was studied in a range of temperatures up to 580 °C. The mechanical behavior was examined using a high-temperature pin-on-disc setup, with which the friction force between two flat-contact surfaces was recorded. The bismuth-lubricated surfaces showed low coefficients of friction (µ ≈ 0.08) below 200 °C. Above the melting temperature of the metal powder at 271 °C, a layer of bismuth oxide developed and the friction coefficient increased. Bismuth oxide showed higher friction coefficients at all temperatures. Bismuth sulfide exhibited partial oxidation upon heating but the friction coefficient decreased to µ ≈ 0.15 above 500 °C, with the formation of bismuth oxide-sulfate, while some bismuth sulfate remained. All surfaces were studied by X-ray diffraction (XRD), confocal microscopy, high-resolution scanning electron microscopy (HR-SEM), and energy-dispersive X-ray spectroscopy (EDS). This study reveals how the partial oxidation of bismuth compounds at high temperatures affects their lubrication properties, depending on the nature of the bismuth compound.

Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR).

BACKGROUND: The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. OBJECTIVE: In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. STUDY DESIGN: F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. RESULTS: Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P < .05); however, essential nutrient supplementation diet abrogates this difference (4.995 vs 5.100; P > .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P < .05) on the control diet, an effect that was repressed with essential nutrient supplementation. CONCLUSION: Heritable growth restriction is associated with changes in H19 gene expression; these changes are reversible with diet supplementation to favorably impact adult metabolic syndrome.

Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1-carbon intermediates.

Metabolic syndrome (MetS), following intrauterine growth restriction (IUGR), is epigenetically heritable. Recently, we abrogated the F2 adult phenotype with essential nutrient supplementation (ENS) of intermediates along the 1-carbon pathway. With the use of the same grandparental uterine artery ligation model, we profiled the F2 serum metabolome at weaning [postnatal day (d)21; n = 76] and adulthood (d160; n = 12) to test if MetS is preceded by alterations in the metabolome. Indicative of developmentally programmed MetS, adult F2, formerly IUGR rats, were obese (621 vs. 461 g; P < 0.0001), dyslipidemic (133 vs. 67 mg/dl; P < 0.001), and glucose intolerant (26 vs. 15 mg/kg/min; P < 0.01). Unbiased gas chromatography-mass spectrometry (GC-MS) profiling revealed 34 peaks corresponding to 12 nonredundant metabolites and 9 unknowns to be changing at weaning [false discovery rate (FDR) < 0.05]. Markers of later-in-life MetS included citric acid, glucosamine, myoinositol, and proline (P < 0.03). Hierarchical clustering revealed grouping by IUGR lineage and supplementation at d21 and d160. Weanlings grouped distinctly for ENS and IUGR by partial least-squares discriminate analysis (PLS-DA; P < 0.01), whereas paternal and maternal IUGR (IUGR(pat)/IUGR(mat), respectively) control-fed rats, destined for MetS, had a distinct metabolome at weaning (randomForest analysis; class error < 0.1) and adulthood (PLS-DA; P < 0.05). In sum, we have found that alterations in the metabolome accompany heritable IUGR, precede adult-onset MetS, and are partially amenable to dietary intervention.

Dexamethasone protects neonatal hypoxic-ischemic brain injury via L-PGDS-dependent PGD2-DP1-pERK signaling pathway.

BACKGROUND AND PURPOSE: Glucocorticoids pretreatment confers protection against neonatal hypoxic-ischemic (HI) brain injury. However, the molecular mechanism remains poorly elucidated. We tested the hypothesis that glucocorticoids protect against HI brain injury in neonatal rat by stimulation of lipocalin-type prostaglandin D synthase (L-PGDS)-induced prostaglandin D2 (PGD2)-DP1-pERK mediated signaling pathway. METHODS: Dexamethasone and inhibitors were administered via intracerebroventricular (i.c.v) injections into 10-day-old rat brains. Levels of L-PGD2, D prostanoid (DP1) receptor, pERK1/2 and PGD2 were determined by Western immunoblotting and ELISA, respectively. Brain injury was evaluated 48 hours after conduction of HI in 10-day-old rat pups. RESULTS: Dexamethasone pretreatment significantly upregulated L-PGDS expression and the biosynthesis of PGD2. Dexamethasone also selectively increased isoform pERK-44 level in the neonatal rat brains. Inhibitors of L-PGDS (SeCl4), DP1 (MK-0524) and MAPK (PD98059) abrogated dexamethasone-induced increases in pERK-44 level, respectively. Of importance, these inhibitors also blocked dexamethasone-mediated neuroprotective effects against HI brain injury in neonatal rat brains. CONCLUSION: Interaction of glucocorticoids-GR signaling and L-PGDS-PGD2-DP1-pERK mediated pathway underlies the neuroprotective effects of dexamethasone pretreatment in neonatal HI brain injury.

Fetal hypoxia increases vulnerability of hypoxic-ischemic brain injury in neonatal rats: role of glucocorticoid receptors.

Gestational hypoxia is a common stress to the fetal development and increases the risk of neonatal morbidity. The present study tested the hypothesis that fetal hypoxia results in heightened brain vulnerability to hypoxic-ischemic (HI) injury in neonatal rats via down-regulation of glucocorticoid receptor (GR) in the developing brain. Time-dated pregnant rats were exposed to hypoxia (10.5% O2) from days 15 to 21 of gestation. Brain HI injury was determined in day 10 pups. Maternal hypoxia resulted in asymmetric intrauterine growth restriction in the fetus. The brain HI injury was significantly increased in maternal hypoxia-treated pups as compared with the normoxia control in both males and females. Activation of brain GR by dexamethasone injection into the right lateral ventricle produced a concentration-dependent reduction of HI-induced brain injury in control pups. Maternal hypoxia significantly decreased GR mRNA and protein abundance in the fetal brain and neonatal hippocampus and abolished the dexamethasone-mediated neuroprotective effect in pup brains. This decreased GR expression was resulted from increased DNA methylation, decreased binding of transcription factors Egr-1 and Sp1 to GR gene exon 17 and 111 promoters, and reduced expression of GR exon 17 and 111 mRNA variants. The results demonstrate that gestational hypoxia causes epigenetic repression of GR gene expression in the developing brain resulting in the heightened brain vulnerability to HI injury in neonatal rats.

Fetal hypoxia results in programming of aberrant angiotensin ii receptor expression patterns and kidney development.

AIMS: The present study tested the hypothesis that fetal hypoxia adversely affects kidney development in fetal and offspring rats and alter the expression patterns of angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors. METHODS: Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 last period of gestation) groups. Protein expression, in the offspring, was determined using western blot. RESULTS: Hypoxic treatment significantly decreased body and kidney weight in 21-day fetuses (E21) and 7-day neonates (P7). In 3-month-old offspring there were no significant differences in body and kidney weight between hypoxic and control animals. Fetal hypoxia had no effect on kidney AT1R density in E21 or P7, but significantly decreased kidney AT1R protein and mRNA abundance in both male and female adults. In contrast, kidney AT2R density was not affected by fetal hypoxia throughout the developmental stages studied. The hypoxia-mediated reduction of nephron numbers was progressively from P7 worsened into the adulthood with females affected more than males. CONCLUSION: The results suggest that fetal hypoxia causes programming of aberrant kidney development and accelerates the aging process of the kidney during the postnatal development, which may contribute to an increased risk of cardiovascular disease.