[Ectopic acromegaly due to bronchial neuroendocrine tumors: the first description in Russia of three clinical cases].

 Acromegaly is a neuroendocrine disorder caused by excessive production of growth hormone (GH). In the majority of cases the cause of acromegaly is a pituitary tumor producing GH. Cases of ectopic acromegaly are much rarer. Ectopic acromegaly occurs in cases of tumors which produce growth hormone-releasing hormone (GHRH) or extrapituitary tumors which produce GH. The main sources of excessive GHRH production are neuroendocrine tumors (NETs) of the lung or pancreas. Treatment of ectopic acromegaly consists of surgical removal of the source of GHRH hyperproduction and in cases where surgery is not an option, somatostatin analogues, pegvisomant, chemotherapy, immunotherapy or radiation therapy are used.In this article three cases of ectopic acromegaly due to GHRH-producing lung NETs are presented, each of them being notable for a number of features. In the first two cases, clinical symptoms were mild, besides in the second case ectopic acromegaly was accompanied by primary hyperparathyroidism. In the third case ectopic acromegaly was accompanied by pituitary macroadenoma, and after surgical removal of the lung NET remission of acromegaly was not achieved. In all three cases, lung NETs were detected incidentally on radiologic chest screening for other conditions.

[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous hypercortisolism].

AIM: To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to control catheter position with or without the ACTH/prolactin normalized ratio calculation in the differential diagnosis of ACTH-dependent endogenous hypercortisolism, and the diagnostics performance of ectopic ACTH-syndrome (EAS) visualization. MATERIALS AND METHODS: A single-center diagnostic study with a retrospective analysis of the data was carried out. The study included patients with ACTH-dependent endogenous hypercorticism with no visualization of pituitary adenoma on MRI or adenoma sizes less than 6 mm. All patients underwent BIPSS with and without calculation of the ACTH/prolactin normalized ratio. Visualization of an EAS included pituitary MRI (to exclude EAS), whole-body CT scan with contrast, and somatostatin receptor scintigraphy with 99mTc-Tectrotide and CT (99mTc-Tectrotide SPECT). The final verification was based on immunohistochemical confirmation of the tumor or stable remission of Cushing's disease (CD) after surgical treatment. Statistical data processing was carried out by using IBM SPSS Statistics 23. Confidence intervals were calculated using the JavaStat online calculator. RESULTS: 230 BIPSS were performed in 228 patients (166 women, 62 men), of which 178 patients were verified as CD and 50 cases were EAS of various localization. The effectiveness of catheterization of petrosal sinuses was 96.9%. The sensitivity of BIPSS without ACTH/prolactin ratio calculation (n=70) was 95.9% (95% CI 86.3-98.9), specificity was 92% (95% CI 75.0-97.8), for the BIPSS with additional determination of ACTH/prolactin-normalized ratio (n=51) - 97.3% (95% CI 86.2-99.5) and 93.8% (95% CI 71.7-98.9), respectively. The use of the MRI method for this sample of patients had a sensitivity of 60.2% (95% CI 52.6-67.5), specificity of 59.2% (95% CI 44.2-73.0), the total body CT with contrast has a sensitivity of 74% (95% CI 59.7-85.4), specificity of 100% (95% CI 97.95-100). The diagnostic accuracy for 99mTc-Tectrotide SPECT in NET visualization has a sensitivity of 73.3% (95% CI 44.9-92.2), specificity of 100% (95% CI 95.3-100). CONCLUSION: BIPSS with desmopressin stimulation and prolactin measurements to control catheter position, as well as the additional calculation of the ACTH/prolactin-normalized ratio, is an optimal method for the differential diagnosis of EAS. Patients who are identified an EAS on BIPSS may be further referred for 99mTc-Tectrotide SPECT and CT for tumor visualization.

[Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland]. / Skleroziruyushchii mukoepidermoidnyi rak shchitovidnoi zhelezy s eozinofiliei stromy.

Sclerosing mucoepidermoid carcinoma with stromal eosinophilia of thyroid gland is represented less than 100 cases in the world literature. We present a rare case of sclerosing mucoepidermoid carcinona with stromal eosinophilia in a 69-year-old woman who has been observed for multinodular goiter for more than 3 years. Cytological examination revealed a picture most of all corresponding to a malignant neoplasm (Bethesda V). The patient underwent a thyroidectomy. Pathomorphological examination revealed a neoplasm of mixed structure with foci of cribriform structures and squamous metaplasia with areas of keratinization. According to the IHC study, the expression of TTF-1, p63, cytokeratins 5/6 were positive, while there were no expression of thyroglobulin with its positive reaction in the thyroid tissue. Additional histochemical staining with Alcian blue revealed a positive reaction with a homogeneous acellular substance of the tumor. A comprehensive morphological study with the use of additional stains made it possible to accurately establish the diagnosis, which will determine the further tactics of managing the patient.

[Casuistic cases of parathyroid carcinoma with a verified mutation in the MEN1 gene].

Parathyroid cancer (PTC) is usually sporadic; however, it could be presented as a component of hereditary syndromes. The prevalence of PTC among patients with primary hyperparathyroidism (PHPT) is about 1% cases. The lack of reliable preoperative predictors significantly complicates the diagnosis of PTC. The clinical course is non-specific and in most cases is determined by severe hypercalcemia. The final diagnosis can only be made on the basis of invasive histopathologic features, while an analysis immunohistochemical (IHC) one can be used only as an additional method. Given the rarity the diagnosis of MEN1-related PTC a challenge. We present two clinical cases of patients with PTC and a verified heterozygous mutation in the MEN1 gene. The described cases demonstrate the complexity of morphological diagnosis for PTC, the heterogeneity of clinical manifestations in patients with the MEN1 mutation, as well as the need for timely screening to identify other components of MEN1 syndrome and mutations of the MEN1 gene among first-line relatives.

Oxidant Potential of Krunidon In Vitro and In Vivo.

We studied the effect of Fe2+ ions in polymerized hemoglobin (Krunidon blood substitute) and in molecular hemoglobin (Sigma) on OH• radical initiation in the Fenton system. It was found that polymerized hemoglobin, as a component of Krunidon preparation, in contrast to hemoglobin tetramer, did not intensify OH• radical generation. The oxidant potential of Krunidon was evaluated in vivo by measuring malondialdehyde level in dog blood plasma after repeated intravenous administration (5 days in a dose of 114 mg/kg) as a biomarker. Administration of the preparation did not significantly increased malondialdehyde content on days 1 and 4 after exposure and did not affect total protein content in blood plasma. Our findings suggest that polymerized hemoglobin in the Krunidon preparation exhibits no pro-oxidant activity and can be used as the basis for the development of non-oxygenic forms of blood substitutes.

[The biomarkers of cerebral ischemia as a new method for the validation of the efficacy of cytoprotective therapy]. / Biomarkery ishemii golovnogo mozga kak novyi metod dokazatel'stva éffektivnosti neirotsitoprotektorov.

AIM: To study blood plasma concentrations of NR2-peptide in patients with ischemic stroke (IS) to assess its diagnostic value as a biomarker of cerebral ischemia and determine the dynamics of the biomarker during treatment with cortexin. MATERIAL AND METHODS: One hundred and twenty patients, aged from 18 to 70 years, including 36 with transient ischemic attack (TIA) and 84 with IS in the carotid territory (n=70) and vertebral/basilar territory with the Wallenberg-Zakharchenko syndrome (n=14), were enrolled. The National Institute of Health Stroke scale (NIHSS) was used to assess neurological status. Blood plasma concentration of NR2-peptide was measured in all patients at admission and after treatment. All laboratory results were compared with neuroimaging (MRI, CT) data. RESULTS: Concentrations of NR2-peptide detected in all patients were higher than in controls (>1.5 ng/ml), p<0.0001. The direct correlation between NR2-peptide (from 3.38 ng/ml to 15.6 ng/ml) and ischemic lesion (from few to 80 mm) was observed. A decrease in NR2-peptide concentration (from 8.5 to 5,.9 ng/ml, p<0.0001) was noted in patients treated with cortexin after 10-day treatment course. CONCLUSION: NR2-peptide blood assay is a reliable hemotest of brain ischemia. Cortexin has a sufficient therapeutic efficacy.

[A case of cutaneous protothecosis]. / Nablyudenie prototekoza kozhi.

The paper describes a case of a rare opportunistic infection, such as skin lesion caused by achlorophyllic unicellular algae of the genus Prototheca. It provides a detailed pathologic description of the foci of cutaneous protothecosis, such as pandermal inflammatory infiltrate, granulomas, pseudoepitheliomatous hyperplasia, and intraepidermal abscesses. Criteria for pathogen detection in histological sections are given.

[Results of Investigation of MRSA Susceptibility to Vancomycin in Clinical Units of Large Multifunctional Hospital and Recommendations on Optimization of Antibacterial Therapy of Staphylococcal Infection].

The frequency of MRSA and MRSE isolates in various units of the Voronezh Regional Hospital was investigated by the results of the local microbiological monitoring for 2014. The maximum position of MRSA was recorded in the ICU (38 to 75% of the strains). The MRSA strains were characterized by higher methicillin resistance, mainly from the cardiosurgical units (60 to 91% of the isolates). The use of the E-test for MRSA susceptibility to vancomycin allowed to estimate the validity of the use of various antibiotics active against MRSA in the treatment of inpatients and to reduce the risk of ineffective therapy.

[Metabolic disorders in elderly patients with hypertension and their correction with melatonin].

The incidence of dysmetabolic factors in 100 elderly patients with hypertension stage II and the role of melatoninproducing function of epiphysis (pineal gland) in the development of these disorders were studied. It was found that the decrease of melatoninproducing function is one of the factors causing disorders of carbohydrate and lipid metabolism in elderly patients with hypertension. Simultaneous application of Melatonin with lisinopril or amlodipine have the normalizing effect on metabolic parameters affected in patients with arterial hypertension.

[Association study of polymorphic markers of F12, PON1, PON2, NOS2, PDE4D, HIF1a, GPIba, CYP11B2 genes with ischemic stroke in Russian patients].

Allele and genotype frequencies of 10 single nucleotide polymorphisms in F12, PON1, PON2, NOS2, PDE4D, HIF1a,GPIba, CYP11B2 genes were studied in a group of Russian patients with ischemic stroke (IS) from central regions of the Russian Federation and healthy donors matched for sex, age and ethnicity. The genotyping procedure included the amplification of selected DNA sequences with the following hybridization of fluorescently-labeled regions with allele-specific DNA-probes immobilized on a biochip. An analysis of allele and genotype frequencies for each gene in IS patients and controls did not reveal any significant differences. The pair-wise comparison of genes demonstrated that the frequency of the combination PON1A/-x PON2 GG was higher in the group of patients (p=0.044, OR=3.4 95% CI 1.06 − 10.4) compared to the controls and, thus, was associated with the higher risk for stroke.

[Association study of renin-angiotensin system genes and hemostasis system genes with ischemic stroke among Russians of Central Russia].

The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin-angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin-angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control.

Prospects of using pancragen for correction of metabolic disorders in elderly people.

We examined two groups of older persons: 30 healthy and 33 patients with type 2 diabetes mellitius. Nocturnal melatonin production was significantly reduced by 70% in patients with DM2 compared to healthy individuals of the corresponding age. In patients with DM2, pancragen significantly decreased glucose level on an empty stomach and in standard glucose tolerance test and reduced plasma concentrations of insulin and insulin resistance index. In patients receiving no pancragen, no changes in carbohydrate metabolism indices were observed. Thus, disturbances in the melatonin-producing function of the pineal gland in elderly individuals contribute to the development of insulin resistance. Administration of the tetrapeptide pancragen is a promising approach to the correction of insulin resistance in elderly individuals.

Phytochemical study of the north caucasian Rosa spinossima L. fruit.

Qualitative composition and content of anthocyanins in the Rosa spinossima L. fruit were studied. The anthocyanin sum was isolated by talc adsorption with subsequent desorption. The presence of anthocyanins in the resultant fraction was confirmed by thin layer chromatography. Three spots corresponding to anthocyanins were found. Anthocyanins were identified by mass spectrometry. Ion peaks corresponding to glycoside cyanidin and delphinidin were found. Position of sugar in the glycoside structure was determined by UV spectrophotometry with aluminum chloride. The content of anthocyanins was measured by direct UV spectrophotometry by the anthocyanins absorption. Anthocyanin content in raw material in conversion to cyanidin-3-glucoside was 1.46±0.03%.

[Pineal gland melatonin-producing function in elderly patients with hypertensive disease: age peculiarities].

This work was aimed at study changes of the epiphyseal melatonin-producing function in elderly patients with hypertensive disease, as well as the relationships of those changes with the degree of arterial hypertension and 24-hour arterial pressure profile disorders. Examination of 18 young (20-34 years) and 20 elderly (60-74 years) healthy people has documented the decrease of melatonin-producing function in aging. In the group of 100 hypertensive disease patients, the nocturnal 6-hydro-oxymelatonin-sulafate (6-HMS) excretion was significantly lower (by 26.5%) than in their healthy age-matched individuals, thus evidencing for more pronounced disturbance of the melatonin-producing function in the former. It is noteworthy that lower melatonin-producing function of the epiphysis was revealed in the patients with the higher level of average 24-hour arterial pressure value and in the patients with a disturbed 24-hour arterial pressure profile "non-dippers".

[Polymorphism of Y-chromosomal microsatellites in Russian population from Southern Federal district of the Russian Federation].

Haplotype frequencies and allele distributions at 11 STR loci of the Y chromosome were evaluated in 180 unrelated individuals from Russian population of Southern Federal district of the Russian Federation (Rostov oblast, Krasnodar krai, and Stavropol krai). Among 153 Y-chromosomal haplotypes discovered, 63 were unique. In the sample of Russian population, the most frequent haplotype (frequency of 5.56%) was 16-11,14-13-30-25-11-11-13-14-11-10 (for the loci DYS19, DYS385a,b, DYS3891, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, and DYS439, respectively). Despite the high diversity of Y-chromosomal haplotypes in the Russian populations from the south of Russia (the h value was 0.997, 0.995, and 0.994 in Rostov, Krasnodar, and Stavropol samples, respectively), analysis of molecular variance (AMOVA) showed the absence of differentiation between the populations (phiQST = 0.1%, P=0.36). Comparative differentiation analysis performed for 13 Russian populations from the European part of Russia pointed to low among-population differentiation in Y-chromosomal lineages (phiST = 0.52%, P=0.03).