Hereditary syndromes with signs of premature aging

Aging is a multi-factor biological process that inevitably affects everyone. Degenerative processes, starting at the cellular and molecular levels, gradually influence the change in the functional capabilities of all organs and systems. Progeroid syndromes (from Greek. progērōs prematurely old), or premature aging syndromes, represent clinically and genetically heterogeneous group of rare hereditary diseases characterized by accelerated aging of the body. Progeria and segmental progeroid syndromes include more than a dozen diseases, but the most clear signs of premature aging are evident in Hutchinson-Guilford Progeria Syndrome and Werner Syndrome. This review summarizes the latest scientific data reflecting the etiology and clinical picture of progeria and segmental progeroid syndromes in humans. Molecular mechanisms of aging are considered, using the example of progeroid syndromes. Modern possibilities and potential ways of influencing the mechanisms of the development of age-related changes are discussed. Further study of genetic causes, as well as the development of treatment for progeria and segmental progeroid syndromes, may be a promising direction for correcting age-related changes and increasing life expectancy

Injectable therapy in type 2 diabetes mellitus: strategies to improve therapeutic adherence

In recent years, the options in treatment of diabetes mellitus type 2 have substantially expanded (currently more than 40 molecules are approved), however, the number of patients with decompensation of diabetes for the period from 2003 to 2014 remains unchanged. In clinical guidelines injecting drugs are given the «final» role as the most effective drugs. However in clinical trials injecting drugs showed a lower adherence compared to oral drugs. Currently injectable glucose lowering drugs include not only insulin but also analogues of glucagon-like peptide-1 (aGLP-1). However, majority of studies of treatment compliance in type 2 diabetes mellitus considered only insulin. Reasons of low compliance are: 1) offering comprehensive programmes for education, monitoring and patient support by primary care physicians; 2) addressing cost and availability issues; 3) prescribing current insulin, also in combination with GLP-1 agonists; 4) use of more simple and convenient devices for injecting insulin

Neurocognitive aspects of hyperparathyroidism

The clinical features of primary hyperparathyroidism (PHPT) are characterized not only by typical end organ damage, including osteopenia/osteoporosis, nephrocalcinosis/renal calculi, pancreatitis, but also by neurocognitive changes, including weakness, easy fatigability, depression, inability to concentrate, memory impairment or subtle deficits, dementia, anxiety, irritability and sleep disturbances. The indications for the surgical treatment of PHPT are markedly elevated serum calcium, end organ damage, younger patients (less than 50 years). Cardiovascular and neurocognitive complications of PHPT are not currently an indication for surgical treatment. The results of the surgical treatment of PHTP are contradictory for neurocognitive symptoms. Some studies have demonstrated an improvement in neurocognitive symptoms after parathyroidectomy (PTE), including patients with mild PHPT. However, randomized trials have not demonstrated the benefits of PTE in patients with mild PHPT for neurocognitive symptoms. There are certain difficulties at evaluation of neurocognitive manifestations of PHPT, and therefore, it is actual to use a specific quality of life questionnaire, assessing cognitive function and memory deficit of the patient. Considering the prevalence of patients with asymptomatic course of PHPT and the absence of typical clinical manifestations of the disease, but with the presence of neurocognitive symptoms, the question of the appropriateness of surgical intervention in such cases remains relevant

Characteristics of calcium and phosphorous metabolism in patients after bariatric surgery and the role of vitamin d supplementation in the prevention and treatment of postoperative bone and mineral disorders

This article provides a review of current literature on the effect of various doses of vitamin D on the parameters of calcium and phosphorus metabolism in patients after bariatric surgery. The decrease of bone mineral density is one of the most frequent complications of the bariatric surgery, which increases the risk of fractures. There are many different mechanisms for impaired mineral metabolism after bariatric surgery, but a decrease in the absorption of calcium and vitamin D plays a key role in this process. Vitamin D is the most important endocrine regulator of calcium homeostasis in the body, which provides the absorption of 90% of calcium in the gut. Patients with morbid obesity have a high risk of vitamin D deficiency even before surgery, which may worsen after operation and in the absence of timely treatment lead to severe disturbances of calcium and phosphorus metabolism. It was found that high doses of vitamin D after bariatric surgery can improve parameters of bone metabolism, and, as a result, prevent fractures after surgery, which generally has a beneficial effect on the quality of life and labor prognosis. The results of the studies available to date open up new opportunities for the prevention and treatment of postoperative complications associated with impaired bone metabolism

Diagnostic value of salivary cortisol in 1-mg dexamethasone suppression test

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushing’s syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive. AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA). MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushing’s Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushing’s syndrome manifestation. RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,5–12,7 nmol/l (5–95 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST – 0,838 (95% СI 0,772–0,905), for blood cortisol in 1-mg DST – 0,965 (95% CI 0,939–0,992) and for late-night salivary cortisol – 0,925 (95% CI 0,882–0,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and – 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA. CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity