Short Messages
The article is devoted to the history of the development of the Endocrinology Research Centre.
The Laboratory of Experimental Morphology was founded in 1925, when the founder of the current Endocrinology Research Center (ERC) of the RAMS was an institution called the State Institute of Experimental Endocrinology. Among the leaders of this laboratory were a corresponding member. USSR Academy of Medical Sciences B.I. Lavrentiev, professors V.I. Kedrovsky, A.V. Rumyantsev, B.V. Aleshin, Y.M. Kabak, E.M. Vermel, E.I. Cockroaches. Over the past years, the structure and scientific interests of the laboratory have constantly changed, determined by the preferences of its leaders. From 1969 to the present, the laboratory was headed by I. G. Akmaev, whose scientific interests were firmly determined during his internship with the outstanding neuroendocrinologist J. Szentagotai at the University of Budapest. Continuing the traditions of this scientist, I.G. Akmaev focused the work of the laboratory on experimental studies that shed light on the poorly understood mechanisms of the hypothalamic nervous regulation of endocrine functions.
Since the creation in 1925 of the State Institute of Experimental Endocrinology under the People's Commissariat of Health of the RSFSR, the founder and first director of which was prof. V.D.Shervinsky, serious attention was paid to the problem of endemic goiter.
Clinical endocrinology
Flow cytometry (FACS-analysis), light and electron microscopy, and cytotoxic test were used to study the leukocytic composition, content, ultrastructure, and function of different lymphocytic populations (CD3+, CD4+, CD8+, CD20+, and CD56+ cells) in the blood of 90 children aged 8 to 15 years who had untreated new-onset type 1 diabetes mellitus. A control group consisted of 45 apparently healthy normoglycemic children. The sick children were observed to have a slight, but statistically significant reduction in the relative and absolute blood content of CD3+, CD4+, and CD56+ cells, CD4/CD8 index and particularly large granule-containing lymphocytes (the morpho-logical homologue of natural Idller (NK) cells). Ultrastructurally, CD20+4 cells (lymphocytes containing Gall's bodies) showed the signs of a high functional activity while NK cells (large granule-containing lymphocytes) exhibited a low one, which was confirmed by the decreased cytotoxic activity of these cells determined in vitro. Three-month insulin therapy leading to the restoration of the blood content of glucose and glycosylated hemoglobin fails to normalize the detected changes in the parameters of T- and NK-cell immunity.
То study the psychological factors determining the subjective assessment of the level ofglycemia, the authors examined 40 patients with type 1 diabetes mellitus (DM), including 18 males and 22 females aged 21 to 52 years, in whom the history of the disease averaged 16.3± 7.6 years. The study used a structured clinicopsychological interview; psychosemantic procedures for examining the organization of a bodily test; and a procedure for a comprehensive personality study (the MMPI test adapted by F.B. Beretin). The patients having high bodily test scores were established to make a more precise subjective assessment of their own level ofglycemia that those having low scores and they were found to have better glycemic control parameters (p ≤ 0.01). Psychological diagnosis of the "bodily attention" in patients with type 1 DM permitted description of 2 different strategies (rational and sensitive) for making a decision as to the subjective assessment of the level ofglycemia. Inclusion of special trainings aimed at improving the recognition of the symptoms of hypo- and hyperglycemia.
The purpose of this investigation was to make a comprehensive study of intravascular lipofysis, including extrahepatic lipoprotein lipase and hepatic triglyceride lipase in the serum, and the responsiveness of the heparin system in insulin resistance. Patients with arterial hypertension (n = 14), type 2 diabetes mellitus (n = 16), or metabolic syndrome (n = 10) were found to have higher serum lipolytic activity, triglyceridemia, lipidemia (in type 2 diabetes mellitus and metabolic syndrome) and hyperglycemia (in type 2 diabetes mellitus) than controls (10 healthy donors). Excessive blood intracellular reserve heparin secretion-induced release of extrahepatic lipoprotein lipase and hepatic triglyceride lipase into the vascular bed as a prerequisite for increasing the baseline level of lipolytic activity in insulin resistance pathology is discussed. The effects ofheparin (50 U/ml of serum) and insulin (2 U/ml of serum) on total lipoprotein lipase activity were not revealed in vitro. It is suggested that enhanced extracellular lipofysis and depleted endogenous heparin system result in the body's insulin resistance
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare monogenous disease with autosomal-recessive inheritance. The gene responsible for the development of this disease is designated as the gene AIRE and encodes for the protein autoimmune regulator whose function is unknown. The disease more frequently manifests itself in childhood. Its typical manifestations are chronic cutaneous and mucous candidiasis, hypoparathyroidism, and chronic adrenal insufficiency. The presence of 2 of these signs gives ground to establish its clinical diagnosis. However, the clinical manifestations of this disease are highly polymorphic. Thirty-nine patients with the established diagnosis of APS-1 were followed up. There was a high frequency of R2S7X mutation in the gene AIRE. Its clinical picture is untypical in 26% of cases despite the presence of the identical R257X mutation. The molecular genetic diagnosis permits diagnosis of untypical cases of APS-1.
То study the impact of gestational hypothyroxinemia on the neurointellectual prognosis in infants living in an industrial megapolis who had mild-to-moderate iodine deficiency, the authors used a "Gnome" mental development scale to assess cognitive function in 13 babies bom to mothers who had first-trimester gestational hypothyroxinemia corrected with thyroid hormonal preparations and in 10 babies born to mothers who had normal free thyroxine levels when the babies were 6,9, and 12 months old. The study indicated that the maternal level of free thyroxine in early (at weeks 5-9) pregnancy significantly correlated with the mental development index of babies at the age of 6,9, and 12 months, i.e. it is one of the determinants of offspring's nervous and mental development. Moreover, early (not later than 9 weeks of pregnancy) correction of gestational hypothyroxinemia with levothyroxine in a mean daily dose of at least 1.2 fig/kg improves the prognosis of progeny's neurointellectual prognosis, by increasing the mental development index up to 92-97 scores in babies in the first year of life, which are consistent with that in babies bom to mothers having normal thyroxine levels.
In the Russian Federation, there are virtually all areas whose population is at risk for iodine-deficiency disorders. During 2003, we made epidemiological studies of iodine-deficiency disorders within the framework of the Thyromobile project supported by the pharmaceutical company "Nycomed"in 12 regions of the Russian Federation. A total of 2673 individuals were examined. According to the WHO recommendations, the study covered prepubescent children aged 8 to 11 years. It involved physical examination, thyroid ultrasound study, blood sampling for ioduria, intelligence test, and sodium chloride iodine assay. The findings indicated that the tension of goiter endemia corresponded to the level of iodine deficiency, which was in the range of mild iodine deficiency, in most regions other than some districts of the Volgograd, Astrakhan, Nizhni Novgorod regions where the median of ioduria in schoolchildren corresponded severe iodine deficiency. The studies indicated that the population's use ofiodinated salt is not up to the recommendations of international expert organizations. Intelligence tests revealed an 11-18% IQ decrease in children from virtually all study areas. According to the strategy of iodine deficiency control in the Russian Federation, it is advisable to use iodinated salt for mass prevention and drugs containing a physicological dose of iodine for group and individual prevention.
То assess the prevalence and pattern of thyroid disease in Moscow, a mild iodine-deficiency area, the authors examined a random sample of 1103 individuals (1004 females and 99 males) during 14 months. The examinees' age ranged from 17 to 80 years; the mean age was 36.7±14.05; median was 37 years. The survey involved a physical examination with thyroid palpation, brief history data collection, and thyroid ultrasound study on a "Mysono"portable apparatus with a 7.5-MHz linear transducer, operating on a real-time basis. Among the examinees the echographic signs of these or those thyroid changes were found in 36% of cases. The most common abnormalities were focal thyroid tissue changes, whose prevalence was 12.4%. Thyroid nodular masses were encountered at a slightly less frequency (10.5%). Of them, nodular and multinodular goiter accounted for 6 and 4.5%, respectively. The third group of changes is presented by a diffuse decrease in thyroid tissue echogenicity (9%). Diffuse goiter was less frequently identified; its frequency was 5%. A minor proportion (0.1%) of the examinees had a history of operations for this or that thyroid disease.
For practitioners
The guidelines presented do not pretend to be a systematic presentation of all aspects of the diagnosis and treatment of nodular goiter and are not intended to replace guidelines for various medical disciplines. In real clinical practice, situations may arise that are beyond the scope of the recommendations presented, in connection with which the final decision regarding a specific patient and responsibility for him lies with the attending physician.
The recommendations presented are mainly devoted to the diagnosis and treatment of nodular (multinodular) euthyroid colloid, differently proliferating goiter in adults (over 18 years of age) and are the agreed opinion of the RAE experts who developed them. Nodular (multinodular) toxic goiter, tumors (malignant and benign), as well as other diseases that can manifest themselves by nodular formations of the thyroid gland (thyroid gland), are discussed mainly in the context of differential diagnosis. The recommendations also do not affect the features of diagnosis and treatment of nodular goiter in children and adolescents.
Case Reports
Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of growth hormone. There are 50–70 cases of this disease per 1 million people. In the vast majority of cases, the cause of the disease is a pituitary adenoma from somatotrophic cells. With the advent in clinical practice of prolonged analogues of somatostatin, endocrinologists have new therapeutic options. In the article we present a clinical case of the patient with the diagnosis: acromegaly, active form; Endosuprasellar pituitary adenoma (somatotropinoma); Hypopituitarism (secondary adrenal insufficiency, secondary hypothyroidism); Chronic pyelonephritis in the acute phase; Hypertension of the II stage, ischemic heart disease, angina pectoris II functional class; Common atherosclerosis with a primary lesion of the aorta, coronary vessels and cerebral vessels.
Experimental endocrinology
The effects of 16α, 17α -cyclohexanodihydroprogesterone, the structural analogues of the closest progesterone metabolites (4,5-dihy-droprogesterones) on the uterine tissues of intact, impregnated, and pseudopregnant rats has demonstrated that they cause uterine epithelial destruction. This effect does not affect the rate and completeness of fetal implantation, but it may play a role during labor, by facilitating fetal rejection. Earlier studies have indicated that the above analogues of the metabolites of progesterone eliminate the latter-induced oxytocin receptor blockade and cause myometrial destruction in pseudopregnant animals. These facts suggest that by accumulating by the end of pregnancy, the natural progesterone metabolites (4.5-dihydroprogesterones) can act as trigger compounds - "labor hormones".
The authors studied a role of β-endorphin during the blockade of opiate receptors and selective μ- and δ-receptor agonists DAMGO and DADLE to the reaction of lymphocytic blast-cell transformation (RLBCT) and to the production of IL-1β, γ-IFN, and IL-4 in the presence of phytohemagglutinin (PHA). It was found that β-endorphin, naloxone, and the selective μ- and δ-receptor agonists stimulated PHA-induced RLBCT, without affecting a spontaneous proliferative response. During opiate receptor blockade, the effect of β-endorphin was not abolished, but, on the contrary, enhanced as naloxone exerted a stimulating effect on RLBCT. A proliferative response was not recorded during preliminary one-hour opioid treatment, β-endorphin, naloxone, and DADLW enhanced the PHA-induced production of IL-4. Naloxone exerted a heterodirectional effect on the synthesis of this cytokine, by inhibiting it spontaneously. The opioid peptides and naloxone produced no effect on the production of IL-1β) and γ-IFN. It is suggested that β-endorphin, naloxone, and the selective μ- and δ-receptor agonists promote the differentiation of Т lymphocytes towards Th2-cells.
Reviews
Wolfram syndrome - a progressive neurodegenerative disease that combines nonautoimmune insulin-dependent diabetes mellitus and optic atrophy.

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