Clinical endocrinology
The purpose of the study was to investigate the effect of L-arginine metabolism on the development and healing of ulcerative foot defects in patients with diabetes mellitus (DM) concurrent with polyneuropathy of the diabetic foot syndrome.
Seventy patients were examined. These included 25 patients with DM and clinical signs of diabetic polyneuropathy (Group 1), 25 patients with DM and neuropathic ulcerative foot defects (Group 2), and 20 healthy individuals (a control group). High performance liquid chromatography was used to determine plasma nitrites and nitrates. To study the activity of enzymes controlling L-arginine conversion, biopsy was performed from the skin of the dorsum of the foot in control individuals and Group 1 patients and from a portion of the skin from the edges of ulcerative defect and from granulation tissue in Group 2 patients. The activity (inducible and endothelial) of NO syntheses was regarded as the capacity of tissue enzymes to convert 3H-L-arginine into 3H-L-citrullin. The activity of arginase in the biopsy specimens was determined by its ability to convert L-arginine into urea. The concentration of transforming growth factor-/}/ (TGF-B/ was measured by using a BIOTRAK kit (Amersham, UK) after special pretreatment of the specimens. In Group 2 patients, the plasma level of NO was more than twice higher than that in the control group and almost 4 times than that in Group 1 [79.68 (55.41; 95.08), 39.03 (28.04; 41.32), and 20.98 (13.46; 29.79) pmol/l, respectively; p < 0.05]. There was a marked expression of iNO-synthase in the biopsy specimens from patients with trophic ulcers as compared with the controls and in patients without ulcerative defects [5.92 (4.63; 7.97), 3.36 (2.71; 3.9), and 1.59(1.05; 2.74) V/T/mgof protein, respectively; p < 0.05]. There was a reduction in the activity of eNO-synthase in the biopsy specimens from patients with peripheral neuropathy as compared with the controls and in patients without ulcerative defects of foot defects [1.22 (1.04; 2.14), 3.41 (2.36; 4.07), and 3.17(2.9; 4.34) V/T/mg protein, respectively; p < 0.05]. The content of arginase in the skin and granulation tissue biopsy specimens taken from the edge of ulcerative defects was much higher than that in the control group and its level in patients without ulcers did not dijfer from that in healthy individuals [1.96 (1.63; 2.65), 0.28 (0.14; 0.37), and 0.52 (0.35; 0.59) pg/mg of protein, respectively; p < 0.05]. A rather low concentration ofTGF-p, was found in the tissues of DM patients with trophic ulcers than in the control group [0.88 (0.58; 1.33) ng/mg of protein versus 2.48 (2.21; 3.17) ng/mg of protein, p < 0.01].
Thus, metabolism of the amino acid L-arginine and its regulation, TGF-/3, in particular, play an important role during wound healing.
Population surveys are of high informative value and reflect the actual prevalence of diabetic polyneuropathy (DPN) in society. The purpose of the present study was to examine the spread of DPN among patients with type 1 diabetes mellitus (DM) and to assess the diagnostic value of used diagnostic methods. Three hundred and forty-six patients (100 children and adolescents and 246 adults) with type 1 DM, living in Moscow and its region were examined. The criteria adopted at the Conference on Standardization of DPN Diagnosis in Saint Antonio in 1992 were used to diagnose DPN. The criteria proposed by P. Dyck et al. were applied to define DPN stages. The prevalence of DPN in the children and adolescents was 40%, the vast majority (75%) of the patients having subclinical (la and lb) stages of DPN. Autonomic deficit was revealed in 17% of the children and adolescents with type 1 DM. In the adults, the prevalence of DPN was 66.3% with a predominance (61%) of the clinical stages (2a and 2b) stages of DPN. Autonomic deficit was detected in 25.6% of the adults with type 1 DM. The most sensitive diagnostic tests in the examination of children and adolescents were found to be a neurological examination by using the NIS-LL scale (for neuropathic disorders), as well as temperature sensitivity study, and stimulation EMG. While examining the adults, an active detection of complaints showed a high sensitivity (79%) by applying the existing scales, which makes it possible to use this method at the first stage of a diagnostic search. The study of temperature sensitivity by employing the Thioterm tool increased the diagnostic value of a neurological examination by means of the NIS-LL in all age groups.
То enhance the efficiency of treatment of patients with diabetic nephropathy, to prolong survival, and to improve life quality in them, the specific features of the clinical cause and the pattern of morbidity, the authors studied 28 patients with diabetes mellitus and the priority factors aggravating the course of diabetic nephropathy during renal replacement therapy. Their experience in treating patients with diabetes mellitus with programmed hemodialysis and peritoneal dialysis was analyzed. Cardiovascular diseases, the dyslipidemic syndrome that signals about progressive atherosclerosis of the aorta and coronary arteries rank first among a diversity of factors that aggravate prognosis, deteriorate life quality in patients with diabetic nephropathy, and promote the development of a fatal outcome. Hyper-b2-microglobulia develops along with dialysis amyloidosis. Immunity tension decreases and infectious complications develop in the respiratory and gastrointestinal tract. Cardiovascular diseases in patients with diabetic nephropathy are poor factors leading to sudden coronary death in severe cases. An individual approach to treating patients with diabetes mellitus complicated by nephropathy resulting in chronic renal failure makes it possible to optimize the success rates of programmed hemodialysis or peritoneal dialysis and to prolong their life span by 4-5 years.
The paper deals with the diagnosis of latent autoimmune diabetes in adults (LADA). The study was undertaken to evaluate the functional activity of fi-cells, to define immunological and clinicobiochemical features in patients with LADA. Fifty-eight patients with the primary diagnosis of type 2 diabetes mellitus (DM). According to the results of the immunological study involving the determination of autoantibodies to cytoplasmic antigen (ICA), the isoform of glutamate decarboxylase with a molecular mass of 6500 (GAD), to insulin (IA), the patients were divided into 2 groups: 1) those with positive autoantibodies and 2) those with negative autoantibodies. In each group, the clinical and biochemical parameters, including the age at the onset of the disease, body-mass index, HbAlc, the levels of cholesterol and triglycerides, the incidence of arterial hypertension, coronary heart disease, diabetic retinopathy, were analyzed. To evaluate the secretory function of ft-cells, 13 patients who had positive autoantibodies and a history of the disease of not more 5 years, and did not receive insulin performed an oral glucose tolerance test (OGTT) using 75 g of glucose; the levels of insulin and C-peptide were measured during the test. The findings have lead to the following conclusions:
- Autoantibodies to GAD and ICA, rather than clinical and biochemical characteristics, are the main basic markers of latent autoimmune diabetes in adults.
- Patients with LADA form a group at high risk for insulin uptake.
- Decreased insulin secretion is revealed just in the first years of the disease when OGTT is carried out. With this, some patients have signs of the metabolic syndrome and, to all appearances, peripheral insulin resistance.
Life quality (LQ) is a multifaceted concept that implies how a human being satisfies his/her physical, mental, and social state. LQ is an indicator that depends on the severity of disease, on therapeutic exposures and reflects his/her subjective assessment of the status during treatment or disease. Life quality was assessed in 60 patients with the metabolic syndrome before and 24 weeks after xenical therapy in combination with a moderate low-calorie diet. The study has revealed that the patients have a low life quality that greatly increases after a complex therapy with xenical and a low-calorie diet.
The study was undertaken to assess a potential risk of the elevated levels of dioxins in the town of Chapayevsk on reproductive function in adolescents during sexual maturation and in adults. It was ascertained that there was a regular trend for retarded sexual development by the Tanner stages in the adolescents living in the polluted areas as compared with control individuals of the same age. The incidence of cryptorchidism, varicocele, and inguinal hernias was 2-3 times higher in the boys from Chapayevsk than in those from Samara. However, the level of gonadotropic hormone was much higher in the Chapayevsk adolescents than that in the control group. Polluted area-living males with normal levels of reproductive hormones showed a drastic deterioration in the quality of sperm, mainly the morphological index with a characteristic reduction of the acrosomal area of the head of spermatozoons. They also displayed a decrease in the levels of dehydroepiandrosterone (DHEA) sulfate and increases in the level of cortisol and in cortisol/ DHEA sulfate ratios. The above deviations in the balance of corticosteroids suggest impaired adaptive homeostasis, which is one of the mechanisms responsible for a potential human health risk of polychlorinated hydrocarbons.
The paper presents the results of treatment in 45 adult patients with somatotropic insufficiency. The study was undertaken to compare the efficiency of treatment of the patients with different doses of the human growth hormone Humatrop and to evaluate its safety. The treatment lasted 6 months. Within the first 3 months, Group 1 patients (n = 24) received Humatrop in a dose of 3.0 pg/kg/day, Group 2 patients (n = 24) had its dose of 6.0 pg/kg/day. Later on the dose was doubled in both groups. The criteria for therapeutic efficiency were changes in the body’s structure (LBM, FM), insulin-like growth factor 1 (IGF-1), and IGF-binding protein-3. In both groups, there was an increase in lean body mass (p < 0.001 in Group 1 and p < 0.018 in Group 2) and a decrease in fatty body mass (p — 0.005 and p < 0.001, respectively) by the end of treatment. The levels of IGF-1 and IGF-binding protein-3 were higher just by the end of the third month of treatment (p < 0.001). There were group differences in all the indices of therapeutic efficiency throughout the treatment period. Side effects were slightly more frequently observed in Group 2 patients. The findings allow Humatrop to be recommended in a dose 3 pg/kg/day within the first 3 months of treatment since the dose is as effective as the larger dose (6 pg/kg/day). Further, the dose of the agent should be changed on an individual basis depending on the levels of IGF-1 and the presence of adverse reactions.
Recently, there is strong evidence that insulin resistance and additive hyperinsulinemia are unique features of the polycystic ovary syndrome (PCOS). Additional studies evaluating the effect of agents affecting hyperinsulinemia are no doubt to be required before making official recommendations on their use in clinical practice. The paper presents data of 12-week metformin therapy in 65 females with PCOS, by analyzing the results of studies of insulinemia and glycemia during oral glucose tolerance tests (OGTT) performed prior to and following the therapy. Insulin resistance and sensitivity, p-cell functions, and a secretory response of insulin to glucose stimulation were evaluated by using mathematical models and by calculating surrogate OGTT indices validated with the reference clamp test. Metformin was found to exert a positive effect on metabolic disorders in females with PCOS via increased insulin sensitivity and a decreased integral secretory response on insulin to oral glucose stimulation, by creating conditions for an adequate response to the stimulus as better insulin-mediated glucose uptake with decreased compensatory hyperinsulinemia. Recovery of adequacy of a secretory response to glucose stimulation promotes a reduction in additive hyperinsulinemia only in PCOSfemales with p-cell dysfunction caused by a predominance of decreased peripheral insulin sensitivity, rather than secretory defect.
The effect of the biguanide siofor (metformin) on the menstrual function of the endometrium and on hormonal and metabolic parameters was studied in 27 patients with ovarian polycystosis (OPC), of them 15 patients (mean age 30.7±1.7 years) were treated with the antidiabetic biguanide siofor (Berlin-Chemi) for 3 months. Siofor (metformin) used alone in patients with OPC was effective in restoring a regular menstrual cycle in 60% of cases and concurrently showed a moderate decrease in body weight. There was a significant reduction in the blood level of luteinizing hormone (LH) in most siofor-treated patients with OPC (more frequently in obese patients), which is indicative of that it is important to correct the states of central parts of the reproductive system, which are involved (along with insulin resistance and impaired steroidogenesis) in the development and formation of a clinical picture of the disease. The elevated concentration of C-peptide was found in the blood, which might be one of the manifestations of overcoming insulin resistance.
For practitioners
Currently, the main therapeutic goals for diabetes are defined as follows: achieving and maintaining compensation for carbohydrate metabolism, as well as controlling risk factors for the development of cardiovascular diseases. These goals are convincingly substantiated by research
recent years. It is also well known that
it is impossible to realize them without involving patients in active participation in the process of diabetes control and treatment.
Discussion
In the scientific literature quite a lot has been written about the hormonal regulation of sexual behavior in mammals (rats, hamsters, guinea pigs, primates), and not only scientific journals are filled with the problems of sexual behavior of people. However, in our opinion, there are a number of issues that do not fit into more or less generally accepted schemes.
Experimental endocrinology
The study was undertaken to examine the time course of changes in the parameters of collagen metabolism in the bone of rats with alloxan diabetes under chronic stress. The levels of free hydroxyproline, total collagen and its fractions were comparatively studied in the bone of rats with alloxan diabetes alone and in combination with immobilization stress. The concentrations of C-peptide and insulin were measured in the serum of experimental animals. In the studied tissues of rats with alloxan diabetes exposed to stress, the content of a neutrally salt-soluble fraction of collagen was less and that of the citrate-soluble fraction was higher than that in rats with isolated diabetes. The concentration of a neutrally salt-soluble fraction of collagen in the studied tissues correlated with the blood level of insulin in both experimental groups of animals throughout the experiment. The content of total collagen in the bone of rats with alloxan diabetes and an additional stress load was less than that in rats with isolated diabetes.
Reviews
Iodine deficiency diseases (IDD) are the most common non-infectious human pathology. In general, 1.5 billion people live on the Earth in regions of iodine deficiency in the environment, 600 million of them have an increase in the thyroid gland, and 40 million have severe mental retardation as a result of iodine deficiency.
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