5 research outputs found
Renal handling of calcium and phosphorus in experimental renal hyperparathyroidism in dogs
Twenty-four hour urinary excretion, fractional excretion and the filtered load of calcium
and phosphorus were monitored as hyperparathyroidism evolved in a model of progressive canine
renal failure. Thirteen beagles of both sexes aged four and a half months were used. Nine of
them
were subjected to a renal damaging schedule (neomycine, 60 mg/kg/48 h, IM, 32 weeks)
in order to
induce chronic renal failure leading to secondary hyperparathyroidism (2HPT
group). The
remaining four were kept as the control group. The experiment was conducted
over 32 weeks. Blood
and 24 h urine were collected every four weeks. Calcium, phosphorus
and creatinine were analyzed.
Plasma parathormone and calcitonin were determined at weeks
0, 12, 24 and 32. The level of renal
function in the 2HPT animals was reduced to 25% of
that of the controls (endogenous creatinine
clearance was 0.45 0.22 mL/min/kg as
opposed to 1.81 0.54 mL/min/kg). Hyperparathyroidism
was confirmed by a progressive
increase in the levels of the parathyroid hormone. Calcitonin levels
were not modified. A
tendency to hypocalcaemia was observed, reaching statistically significant
levels from the
twenty-eighth week of the study, when hyperphosphataemia also became
significant. Daily
urinary excretion of calcium and phosphorus remained at values considered normal throughout
the experiment with no alteration imputable to the impaired renal function. This
is
explained by the decrease in the filtered load of these elements (in both cases statistically
significant from the 24th week on) being associated with an increase in their fractional
excretion.
Thus, calcium and phosphorus urinary excretion values could be maintained in a
normal range up
to the end of the experiment, showing that renal calcium handling in dogs
with experimentally
induced renal failure seems to differ from that observed in human
patients
Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome
[Background]: Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental alterations and multiple basal cell carcinomas. Mutations in PTCH1, which encodes a membrane receptor for Sonic Hedgehog, are associated with the development of the disease. Most of them produce a truncated protein, which is unable to suppress Smoothened protein and continuously activates the downstream pathway. [Objectives]: We aimed to characterize 22 unrelated Spanish patients with NBCCS, the largest cohort with Gorlin syndrome reported to date in Spain. [Methods]: Genomic analysis of PTCH1 was performed in patients with NBCCS and controls, and mutations were analysed using bioinformatics tools. [Results]: We report for the first time two young patients, one each with uterus didelphys and ganglioneuroma, within the context of NBCCS. One patient showing a severe phenotype of the disease had developed basal cell carcinomas since childhood. Sanger sequencing of PTCH1 in this cohort identified 17 novel truncating mutations (11 frameshift, five nonsense and one mutation affecting an exon–intron splice site) and two novel missense mutations that were predicted to be pathogenic. The patients showed great clinical variability and inconsistent genotype–phenotype correlation, as seen in relatives carrying similar mutations. [Conclusions]: This study contributes to increase the pool of clinical manifestations of NBCCS, as well as increasing the number of pathogenic mutations identified in PTCH1 predisposing to the condition. The inconsistencies found between phenotype and genotype suggest the involvement of other modifying factors, genetic, epigenetic or environmental.This project was funded by Fundación Rodríguez Pascual, Consejería de Sanidad de la Junta de Castilla y León‐FEDER (GRS165/A/07) and ISCIII‐FEDER (PI10/00219 and PI13/01741). The research at the Melanoma Unit in Barcelona was partially funded by grants 12/00840 from Fondo de Investigaciones Sanitarias, Spain; by the CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the AGAUR 2014_SGR_603 of the Catalan Government, Spain; by a grant from ‘Fundació La Marató de TV3, 201331‐30’, Catalonia, Spain; and by the European Commission under the 6th Framework Programme, contract no. LSHC‐CT‐2006‐018702 (GenoMEL), under the 7th Framework Programme (Diagnoptics). J.C. is partially supported by grant GRS 1342/A/16 (Gerencia Regional de Salud de Castilla y León) and by the program INT/M/16/17 from the Gerencia Regional de Salud de Castilla y León.Peer Reviewe