Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model.

Introduction: Mutations in the NLRP3 gene are associated with the dominantly inherited cryopyrin-associated periodic syndrome (CAPS). The significance of the V198M variant is unclear; it has been reported in association with various CAPS phenotypes and as a variant of uncertain consequence. The aim of this study was to characterize the clinical phenotypes and treatments in individuals with V198M assessed in a single UK center. Methods: DNA samples from 830 subjects with fever syndromes or a family history of CAPS were screened for mutations in the NLRP3 gene with polymerase chain reaction (PCR) and sequencing. A detailed medical history was available in all cases. Inflammatory disease activity was monitored monthly with measurements of serum amyloid A protein (SAA) and C-reactive protein (CRP) in symptomatic individuals. Results: NLRP3 V198M was identified in 19 subjects. It was found in association with CAPS in five cases, in one patient with Schnitzler syndrome, in three patients who also had a nucleotide alteration in another fever gene, and in three other patients with evidence of an autoinflammatory phenotype. Seven asymptomatic individuals were detected during screening of family members. Conclusions: The NLRP3 V198M variant shows variable expressivity and reduced penetrance. It may be associated with classical inherited or apparently sporadic CAPS and with atypical autoinflammatory disease of varying severity, intriguingly including Schnitzler syndrome. The factors that influence the pathogenic consequences of this variant remain unknown. However, the remarkable response to interleukin 1 (IL-1) blockade in all but one individual in our series confirms that their clinical features are indeed mediated by IL-1.

Whey protein concentrate (WPC) is characterized by powerful antioxidant properties, but its effect on redox homeostasis of salivary glands of aging organisms is still unknown. In this study, we are the first to evaluate the antioxidant barrier of salivary glands of 14-month Wistar rats fed WPC-80. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) as well as concentrations of reduced glutathione (GSH) are estimated in the submandibular and parotid glands of rats administered WPC-80 intragastrically for a period of 7 and 14 days. We demonstrate a significant increase in GSH, GPx and SOD in the salivary glands of rats fed WPC-80 for 14 days and a significant increase in TAS, GPx and SOD in the parotid glands of rats fed WPC-80 for 7 days compared to control rats. The beneficial effects of WPC-80 on salivary glands are also demonstrated by lower TOS and OSI in the parotid glands of rats fed WPC-80 compared to the submandibular glands. In summary, we demonstrate that WPC-80 improves redox homeostasis in salivary glands, particularly in the parotid glands of old rats.