Worldwide, 70% of the adult population has limited expression of lactase enzyme with a wide variation among different regions and countries. Lactase deficiency may lead to lactose intolerance (LI). Depending both on the amount of lactose ingested and on the lactase activity, people who suffer from lactose malabsorption might experience numerous gastrointestinal and extra-intestinal symptoms and manifestations. Treatment of LI mainly consists of reducing or eliminating lactose from the diet until the symptoms disappear as well as supplementing lactase, and inducing colon microbiome adaptation by probiotics. Cow's milk is one of the major source of calcium and several other vitamins and minerals. Thus, a complete exclusion of dairy products may favor the development of bone diseases such as osteopenia and osteoporosis. Therefore, the dietetic approach has a crucial role in the management of LI patients. Additionally, the use of lactose and milk-derived products in non-dairy products (e.g., baked goods, breakfast cereals, drinks, and processed meat) has become widespread in the modern industry (the so-called "hidden lactose"). In this regard, a strict adherence to the lactose-free diet becomes challenging for LI patients, forced to continuous check of all products and food labels. In fact, lactose-free product labeling is still controversial. Considering that nowadays a specific cutoff value establishing "lactose-free" labeling policy is lacking and that there is no universal law regulating the production and commercialization of "delactosed" products, identification of specific safe and suitable products with a well-recognized lactose-free logo might help consumers. This narrative review aims to identify the dietary management for lactose intolerant people, avoiding symptoms and nutrients deficiencies, helped by the use of specific labelling to guide them to choose the safer product on the market.

Background and objective: Single nucleotide polymorphisms (SNPs) of the calcium-sensing receptor (CASR) gene at the regulatory region were associated with idiopathic calcium nephrolithiasis. To confirm their association with nephrolithiasis, we tested patients with primary hyperparathyroidism (PHPT). Design: A genotype-phenotype association study. Methods: In all, 332 PHPT patients and 453 healthy controls were genotyped for the rs7652589 (GOA) and rs1501899 (GOA) SNPs sited in the noncoding regulatory region of the CASR gene. Allele, haplotype, and diplotype distribution were compared between PHPT patients and controls, and in stone forming and stone-free PHPT patients. Results: The allele frequency at rs7652589 and rs1501899 SNPs was similar in PHPT patients and controls. The A minor alleles at these two SNPs were more frequent in stone forming (nZ157) than in stone-free (nZ175) PHPT patients (rs7652589: 36.9 vs 27.1%, PZ0.007; rs1501899: 37.1 vs 26.4%, PZ0.003). Accordingly, homozygous or heterozygous PHPT patients for the AA haplotype (nZ174, AA/AA or AA/GG diplotype) had an increased stone risk (odds ratio 1.83, 95% confidence interval 1.2-2.9, PZ0.008). Furthermore, these PHPT patients had higher serum concentrations of ionized calcium and parathyroid hormone (1.50G0.015 mmol/l and 183G12.2 pg/ml) than patients with the GG/GG diplotype (nZ145, 1.47G0.011 mmol/l (PZ0.04) and 150G11.4 pg/ml (PZ0.049)). Using a logistic regression model, the increase in stone risk in PHPT patients was predicted by AA/AA or AA/GG diplotype, the highest tertile of serum ionized calcium values and the lowest tertile of age. Conclusions: Polymorphisms located in the regulatory region of the CASR gene may increase susceptibility of the PHPT patients to kidney stone production.

The observed cytotoxic effect of RES on the human cholangiocarcinoma SK-ChA-1 cell line cultured two- and three-dimensionally suggests to further analyse its chemotherapic/chemopreventive possibilities for this kind of cancer.

We conclude that the simultaneous presence of the minor allele at rs1501899 and Arg990Gly may amplify the kidney stone risk in PHPT patients, despite their apparently opposite effects on CASR function in the kidney.

Calcium nephrolithiasis may be considered as a complex disease having multiple pathogenetic mechanisms and characterized by various clinical manifestations. Both genetic and environmental factors may increase susceptibility to calcium stones; therefore, it is crucial to characterize the patient phenotype to distinguish homogeneous groups of stone formers. Family and twin studies have shown that the stone transmission pattern is not mendelian, but complex and polygenic. In these studies, heritability of calcium stones was calculated around 50%Calcium-sensing receptor (CaSR) is mostly expressed in the parathyroid glands and in renal tubules. It regulates the PTH secretion according to the serum calcium concentration. In the kidney, it modulates electrolyte and water excretion regulating the function of different tubular segments. In particular, CaSR reduces passive and active calcium reabsorption in distal tubules, increases phosphate reabsorption in proximal tubules and stimulates proton and water excretion in collecting ducts. Therefore, it is a candidate gene for calcium nephrolithiasis.In a case-control study we found an association between the normocitraturic stone formers and two SNPs of CaSR, located near the promoters region (rs7652589 and rs1501899). This result was replicated in patients with primary hyperparathyroidism, comparing patients with or without kidney stones. Bioinformatic analysis suggested that the minor alleles at these polymorphisms were able to modify the binding sites of specific transcription factors and, consequently, CaSR expression.Our studies suggest that CaSR is one of the candidate genes explaining individual predisposition to calcium nephrolithiasis. Stone formation may be favored by an altered CaSR expression in kidney medulla involving the normal balance among calcium, phosphate, protons and water excretion.