Cystinuria in a patient with 19q12q13.1 deletion.

Cystinuria is a genetic cause of kidney stones with a prevalence of 1 in 7000 births. So far, two genes have been described responsible for this disorder (SLC3A1 and SLC7A9). We report a patient with an SLC7A9 gene mutation located in 19q13.1 on one allele and with a 19q12q13 region deletion on the other allele. The characteristic clinical features of the 19q13.1 microdeletion syndrome include facial dysmorphism, signs of ectodermal dysplasia, growth retardation, neurologic features and genitourinary anomalies. Cystinuria has not yet been described as part of this syndrome, although one of its responsible genes (SLC7A9) is in the same genomic location. The index case is a 6-year-old male presented with distinctive facial features, cutis aplasia of the scalp, rudimentary teeth, microcephaly, intrauterine and postnatal growth retardation, psychomotor developmental delay, speech delay, epilepsy, inguinal hernias and cystinuria. An array-CGH analysis was performed, finding a large deletion of the 19q12q13.11 cytobands, which affects 19 genes. Two of them are involved in the 19q13.11 deletion syndrome and another affected gene is SLC7A9, responsible for type B cystinuria. Sanger sequencing was performed as well, detecting a heterozygous mutation of the SLC7A9 gene, located in 19q13.1. As far as we know, this is the first described case of cystinuria in a patient with SLC7A9 gene mutation located in 19q13.1 on one allele and with 19q12q13 region deletion on the other allele. Although this patient can be classified as a type B heterozygote and, therefore, his renal prognosis is not severe, the occasional nephrolithiasis found in such patients justifies a close follow-up with regular testing of urinary cystine excretion. We suggest that the recessive behavior of this case, explains the clinical features regarding cystinuria. We propose that in the face of patients affected of a phenotype matchable with 19q13.11 syndrome and cystinuria, a mutational or sequencing study of the SLC7A9 gene should be performed to allow an early onset of diagnosis and treatment.

Influence of the number of nanoparticles on the enhancement properties of surface-enhanced Raman scattering active area: sensitivity versus repeatability.

In the present work, the combination of chemical immobilization with electron beam lithography enables the production of sensitive and reproducible SERS-active areas composed of stochastic arrangements of gold nanoparticles. The number of nanoparticles was varied from 2 to 500. Thereby a systematic analysis of these SERS-active areas allows us to study SERS efficiency as a function of the number of nanoparticles. We found that the experimental parameters are critical, in particular the size of the SERS-active area must be comparable to the effective area of excitation to obtained reproducible SERS measurements. The sensitivity has also been studied by deducing the number of NPs that generate the enhancement. With this approach we demonstrates that the maximum enhancement, the best sensitivity, is obtained with the smallest number of nanoparticles that is resonant at a given excitation wavelength.

Cilastatin attenuates cisplatin-induced proximal tubular cell damage.

A major area in cancer therapy is the search for protective strategies against cisplatin-induced nephrotoxicity. We investigated the protective effect of cilastatin on cisplatin-induced injury to renal proximal tubular cells. Cilastatin is a specific inhibitor of renal dehydrodipeptidase I (DHP-I), which prevents hydrolysis of imipenem and its accumulation in the proximal tubule. Primary cultures of proximal cells were treated with cisplatin (1-30 microM) in the presence or absence of cilastatin (200 microg/ml). Apoptosis and mitochondrial injury were assessed by different techniques. Cisplatin uptake and DNA binding were measured by inductively coupled plasma spectrometry. HeLa cells were used to control the effect of cilastatin on the tumoricidal activity of cisplatin. Cisplatin increased cell death, apoptotic-like morphology, caspase activation, and mitochondrial injury in proximal tubular cells in a dose- and time-dependent way. Concomitant treatment with cilastatin reduced cisplatin-induced changes. Cilastatin also reduced the DNA-bound platinum but did not modify cisplatin-dependent up-regulation of death receptors (Fas) or ligands (tumor necrosis factor alpha, Fas ligand). In contrast, cilastatin did not show any effects on cisplatin-treated HeLa cells. Renal DHP-I was virtually absent in HeLa cells. Cilastatin attenuates cisplatin-induced cell death in proximal tubular cells without reducing the cytotoxic activity of cisplatin in tumor cells. Our findings suggest that the affinity of cilastatin for renal dipeptidase makes this effect specific for proximal tubular cells and may be related to a reduction in intracellular drug accumulation. Therefore, cilastatin administration might represent a novel strategy in the prevention of cisplatin-induced acute renal injury.