Detection of Mycobacterium angelicum in Human Urinary Tract, French Polynesia.

We definitively characterized Mycobacterium angelicum, an aquatic zoonotic opportunistic pathogen of the M. szulgai complex, using a polyphasic approach that included whole-genome sequencing. The sequence was obtained on the island of Tahiti, French Polynesia, from a urine specimen collected from a patient experiencing a urinary tract infection.

Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease.

Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

Topography, Composition and Structure of Incipient Randall Plaque at the Nanoscale Level.

PURPOSE: Randall identified calcium phosphate plaques in renal papillae as the origin of kidney stones. However, little is known about the early steps of Randall plaque formation preceding the onset of urolithiasis. Our objective was to characterize the composition and the initial formation site of incipient Randall plaque in nonstone forming, living patients. MATERIALS AND METHODS: Median patient age was 67.7 years. A total of 54 healthy papillae from kidneys removed for cancer and without stones were analyzed by immunohistochemistry and von Kossa staining, field emission-scanning electron microscopy with energy dispersive x-ray analysis, µ-Fourier transform infrared spectroscopy, cryo-transmission electron microscopy coupled to selected area electron diffraction and electron energy loss spectroscopy. RESULTS: Incipient Randall plaque was observed in 72.7% of kidneys. As expected, carbonated apatite was the main component of microcalcifications but amorphous calcium phosphate and whitlockite were identified in 80% and 40% of papillae, respectively. Incipient plaques were noted in the deepest part of the papillae around the loop of Henle tip as well as around the vasa recta, representing 62.4% and 37.2% of microcalcifications, respectively. Plaques were rarely close to collecting ducts. At the nanoscale level incipient calcifications were often composed of several nanocrystals in organic material that looked like microvesicles. CONCLUSIONS: Incipient Randall plaque is frequent. It appears not only at the extreme tip of the renal papillae around the hairpin structure of the loop of Henle but also around the vasa recta. Nanoscale analyses suggest a local nucleation process promoting nanocrystal growth in a supersaturated milieu. In addition, plaques contain various calcium and magnesium phosphates, and not only carbonated apatite.

Hybolites Revisited.

BACKGROUND: Hyperstructures are large assemblies of molecules and macromolecules that perform functions such as metabolism (including RNA and protein synthesis and degradation), transport, DNA replication, cell division, signalling and chemotaxis. METHODS: Such hyperstructures might be manipulated by hybrid metabolites or hybolites made by a pairwise, covalently linked combination of the thousands of small molecules involved in metabolism and signalling. RESULTS: Here, we review recent evidence for hyperstructures in prokaryotes and for interactions between hyperstructures as a determinant of the phenotype. We also mention extending hybolite therapy to eukaryotes, consider new designs for hybolites, and discuss relevant patents.

Decrease in and management of urolithiasis after kidney transplantation.

PURPOSE: Urolithiasis after kidney transplantation can involve several contributing factors and the treatment strategy is open to question. We determined the incidence and management of urolithiasis in kidney recipients. MATERIALS AND METHODS: We retrospectively reviewed a single center series of 3,000 kidney graft recipients during 32 years to identify those with urolithiasis. We analyzed data by the prevalence per decade, including perioperative procedures (preoperative assessment, anastomosis type and urinary drainage) and long-term followup (urinary stenosis, time to presentation, size, site, treatment type, renal function and survival). RESULTS: We identified 31 cases and noted a significant decrease in incidence from 2.1% to 0.6% during the 3 decades. Excluding 4 cases of donor in situ stones the mean time to diagnosis was 8.5 years. Surgical risk factors were ureteral obstruction in 41% of cases, infravesical obstruction in 14% and urinary-digestive anastomosis in 14%. A total of 12 cases (38%) were observed exclusively with 2 of spontaneous passage. With minor adaptations all mini-invasive procedures, including extracorporeal shock wave lithotripsy, endoscopy and percutaneous nephrolithotomy, were feasible in graft recipients. Antegrade procedures were facilitated by the ventral position of the graft. Eight patients (25%) were treated with open surgical ureteroureteral anastomosis. CONCLUSIONS: Prevention with a perioperative Double-J® stent and early treatment of ureteral obstruction have decreased and stabilized the urolithiasis rate at around 0.6%. Careful surveillance or any currently available instrumental treatments of urinary stones can be valid options.

Mechanism selection for regiocontrol in base-assisted, palladium-catalysed direct C-H coupling with halides: first approach for oxazole- and thiazole-4-carboxylates.

Both base-assisted non-concerted metallation-deprotonation (nCMD) and concerted metallation-deprotonation (CMD) have been identified as two potent operating mechanisms in palladium-catalysed direct C-H coupling of oxazole and thiazole-4-carboxylate esters with halides through base- and solvent-effect experiments. Novel C2- and C5-selective CMD direct arylation procedures in oxazole- and thiazole-4-carboxylate series were then designed by controlling the balance between electronic and steric factors. Notably, charge interactions between the palladium catalyst and substrate were identified as a parameter for controlling selectivity and reducing the impact of steric factors in the CMD reaction.

DPO and POPOP carboxylate-analog sensors by sequential palladium-catalysed direct arylation of oxazole-4-carboxylates.

Sequential palladium-catalysed direct (het)arylation of oxazole-4-carboxylates is achieved to give rapid access to DPO and POPOP (di)carboxylate-analogs. Three novel DPO- and POPOP-type sensors with unusual Stokes shifts and high quantum yields are discovered.

Recent advances in direct C-H arylation: Methodology, selectivity and mechanism in oxazole series.

Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki-Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented.

Direct palladium-catalyzed alkenylation, benzylation and alkylation of ethyl oxazole-4-carboxylate with alkenyl-, benzyl- and alkyl halides.

The ethyl oxazole-4-carboxylate was directly and regioselectively alkenylated, benzylated and alkylated with alkenyl-, benzyl-, allyl- and alkyl halides in the presence of catalytic amounts of palladium acetate with caesium carbonate using Buchwald's JohnPhos ligand.

Palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate: an efficient access to (hetero)aryloxazoles.

A straightforward route toward 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics followed by a two-step hydrolysis/decarboxylation sequence was described. The method was applied here to a neat synthesis of two 2,5-di(hetero)aryloxazole natural products, balsoxin and texaline.

Direct C-2 arylation of alkyl 4-thiazolecarboxylates: new insights in synthesis of heterocyclic core of thiopeptide antibiotics.

The Pd(0)-catalyzed regioselective C-2 (hetero)arylation of tert-butyl 4-thiazolecarboxylate with a broad (hetero)aryl halide is reported, including the direct coupling of pyridinyl halides. The process has allowed the preparation of valuable 2-pyridynyl-4-thiazolecarboxylates which are components of the complex heterocyclic core of thiopeptides antibiotics. As a first application, a synthesis of a tert-butyl sulfomycinamate thio-analogue from tert-butyl 4-thiazolecarboxylate is here described through a three-step direct pyridinylation, halogenation, and Stille cross-coupling sequence.