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Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels.

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UNLABELLED: PCOS is a complex disorder with variability of phenotypes, characterized by hyperandrogenic, anovulatory and metabolic components. The later is a result of specific insulin resistant state with compensatory hyperinsulinaemia. Oral hormonal contraceptives (OHC) are a treatment of first choice in hyperandrogenic PCOS women who do not desire conception. Addition of insulin sensitizers might counteract unfavourable metabolic consequences of OHC monotherapy and could result in additional benefits for treated PCOS women. AIM: To compare the effects of 3 therapeutic regimens widely used in practice--OHC alone and in combination with metformin or rosiglitazone on body weight and anthropometric proportions, hormonal and metabolic alterations. MATERIAL AND METHODS: The study comprised of 44 women with proven PCOS, divided in 3 therapeutic groups: 1st group--with Diane35 alone; 2nd group--with Diane35 + metformin; 3rd group--with Diane35 + rosiglitazone. Body weight, fat mass and distribution, hormonal levels, metabolic parameters (insulin and blood glucose during oGTT lipid profile) were studied before and after a 6-month treatment. RESULTS: Monotherapy with Diane35 did not lead to changes in body weight, fat mass and distribution; had beneficial influence on some of the hormonal alterations in PCOS, but did not achieved significant antiandrogenic effect; did not induce changes in carbohydrate tolerance while having mild negative effect on insulinaemia; had an unfavourable although mild influence on lipid parameters including atherogenic indices except the HDL-cholesterol; did not show side effects on liver and vascular function. Combined treatment with Diane35 and metformin led to reduction of weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not decrease blood glucose levels; supressed glucose-stimulated insulin levels; had beneficial effect on HDL-cholesterol and neutral effect on other lipid parameters and atherogenic indices; decreased diastolic blood pressure. Combined treatment with Diane 35 and rosiglitazone did not induce changes in body weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not influence fasting and postchalange glucose levels; suppressed fasting hyperinsulinaemia and HOMA-index, respectively; had neutral effect on the levels of lipid parameters and atherogenic indices.

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First choice therapy of microprolactinoma is drug treatment with dopamine agonists. Cabergoline is widely accepted in clinical practice as a first line therapy for tumor-induced pituitary hyperprolactinemia. This study assessed serum prolactin levels, tumor size and adverse events in 22 women treated with cabergoline for one year (mean age 43.5 +/- 6.6 years). Serum prolactin levels changed from a baseline mean of 1417 +/- 347 UI/L to 489 +/- 102 UI/L at study end (in the normal range). Tumor size reduction to tumor disappearance was found in 18 women (from a mean of 7.2 mm to 5.5 mm), and was absent in 4 participants. Adverse events were reported in 2 women. In conclusion, the excellent therapeutic efficacy and the lack of adverse events with Cabergoline promotes its use as a first line therapy of hyperprolactinemia due to pituitary microadenoma.

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Prostate-specific antigen (PSA) is a serine protease with chymotrypsin-like enzymatic activity. In males PSA is produced by the prostatic gland and it is present in prostatic tissue, seminal plasma and male serum. Initially, PSA was believed to be absent from all female tissues and fluids. However PSA has been detected recently in some female tissues (including breast, ovarian and endometrial tissues) and body fluids (serum, milk, amniotic fluid). The presence of PSA in these female tissues seems to be closely associated with steroid hormone regulation, especially androgens and progestins. Estrogen by itself seems to have no effect on PSA regulation, but it can impair androgen induced PSA production. In the tissues and fluids examined PSA is found in two molecular forms: free PSA is the enzymatically active form and in a complexed form bound to protease inhibitors. The data presented suggest that PSA can no longer be regarded as a specific prostatic marker, but as a protein that could be produced by cells bearing steroid hormone receptors under conditions of steroid hormone stimulation. Its biological role is not fully clarified, but PSA may be a candidate growth factor in normal tissues, pregnancy and tumors. At this point, PSA shows promise of being routinely used as a favorable prognostic indicator in female breast cancer.

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The outcome data from the United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive drug treatment of diabetes mellitus-type 2 and the tight control of glycaemia and blood pressure are associated with lower incidence of chronic diabetic complications and mortality. The economical analysis showed out that money invested in the intensive drug treatment of diabetes and arterial hypertension resulted in less expenses for the treatment of diabetic complications. These data are the reason to suggest an algorythm for the treatment of diabetes mellitus type 2. The main aims are to achieve fasting blood glucose < or = 6 mmol/l, 2 hour postprandial glucose < or = 8 mmol/l and glycated haemoglobin (HbA1c) < or = 7.0%. The steps in the treatment include: non-pharmacological treatment, monotherapy with an oral drug, combined oral treatment, insulin therapy, combined insulin and an oral drug therapy. The blood pressure control aims to achieve a figure below 140/85 mm Hg, using monotherapy or a combination of antihypertensive drugs from different pharmacological groups.

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The andropause (andropaenia) or PADAM-syndrome represents a combination of clinical and laboratory symptoms, developed during aging. The most frequently reported clinical feature is erectile dysfunction. From the laboratory parameters the most typical finding is low normal or reduced serum testosterone levels. Very useful questionnaires have been developed helping in diagnosing the PADAM syndrome. Nowadays the hormonal replacement therapy with testosterone derivatives is considered to be the "gold standard". It has positive impact on the cardiovascular risk profile and its different components. This therapy is being prescribed on clear indications and according to strict rules. Available preparations in our country are the injectable and oral ones. Replacement therapy with other hormones is still not a part of clinical practice.

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The test stripes Visidex for visual evaluation of glycemia were tested clinically. The results were compared with a reference laboratory method for blood sugar measurement. A correlation coefficient of r = 0.971 with 74% coincidence in the same glycemic interval was found. The test stripes are suitable for blood sugar self-control in domestic conditions.

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Metastases in the suprarenal glands are being found in patients with neoplasms but symptomatic hypocorticism is described in single cases only. Computed tomography allows the diagnosis of suprarenal metastases causing hypocorticism while the patients are still alive. A case of a man, 40 years of age, with rectal carcinoma and clinically manifested hypocorticism due to bilateral suprarenal metastases is presented.

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20 insulin-dependent diabetics, aged 17 to 52 years, duration of the diabetes from 1 to 22 years and mean value of the glycated hemoglobin 13.5 +/- 3.6% were studied. The 24 h insulin needs were determined with the help of an artificial pancreas (Biostator) at the following constants of the algorhithm: KR = 70, KF = 67, BI = 80, RI = 12, QI = 40, FI = 400, BD = 55, RD = 25, QD = 20, FD = 200 The insulin needs determined by the biostator were compared with those given subcutaneously which had, led to compensation of the diabetes before discharge of the patients. The mean insulin dose by the biostator was 1.0% U/kg and that of the subcutaneous insulin treatment was 0.86 U kg the difference is statistically insignificant). The above mentioned constants are recommended as being more physiological for the determination of 24-h insulin needs for a subcutaneous insulin treatment of diabetes.

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Glomerular filtration and effective renal plasma flow were studied in 24 patients with diabetes mellitus type I (mean age 29.8 +/- 10.5 years) and 20 patients with diabetes mellitus type II (mean age 54 +/- 11 years) and duration of diabetes 5.7 +/- 6 and 11.3 +/- 10 years respectively. There were no clinical signs of nephropathy in all patients studied (the albustick test was negative). The results were compared with those of 30 healthy controls. Out of the 24 patients with diabetes mellitus type I 10 (41%) were with hyperfiltration and from the 20 patients with diabetes mellitus type II only one was with hyperfiltration. The speed of albumin secretion in the diabetic patients with hyperfiltration was 39.9 +/- 42.9 micrograms/min and was significantly higher than that of the diabetic patients without hyperfiltration--26.2 +/- 22.7 micrograms/min. The albuminuria was in a moderate positive correlation with the glomerular filtration. The possible mechanism taking part in the development of hyperfiltration syndrome in diabetes are discussed.

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A case is presented of a 28-year-old man with Hand-Schüller-Christian's disease whose initial manifestations were skull bones lesions and a diffuse interstitial fibrosis. Three years later the patient developed diabetes insipidus without changes in the hypothalamic-hypophysial region on computed tomography. Some features of the clinical picture are discussed.

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40 diabetic patients (18 patients with diabetes mellitus type I and 22 patients with diabetes mellitus type II) were examined for an average period of 6 months (from 0.5 up to 24 months). The following glycemic parameters were determined: glycohemoglobin (HbA1), average glucose of 6 glucose profiles, fasting glucose, the average of two postprandial glucose concentrations and the M-value. Correlation coefficients between the HbA1 and the parameters studied were determined. In the course of suitable treatment all patients' data were significantly improved. High correlation coefficients were found between HbA1 and the average of the two postprandial glucose concentrations and between HbA1 and the M-value (r = 0.61 and r = 0.60 respectively). The average profile glucose, the average of two postprandial glucose concentrations and the M-value show as reliable parameters for a long-term control compared with the most reliable index HbA1.

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Human insulin was applied to three insulin resistant diabetic patients with moderate insulin needs of 1.9 U/kg body mass/24 hours. The mean level of the insulin antibodies was 61%. In all three patients biostator control was carried out before beginning the treatment with human insulin. After an 8 month treatment a satisfactory compensation of diabetes was achieved with an average insulin dose of 1.02 U/kg body mass, a considerable lowering of the mean blood sugar level and a reduction of the glycosilated hemoglobin examined in two of the patients. At the end of the 8 month period the level of the insulin antibodies was considerably lowered in all three patients. The advantage of human insulin as an alternative for the treatment of immunologic insulin resistance is pointed out.

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A 24 hour biostator control was carried out on 30 patients with insulin dependent diabetes, mean age 34 years (16-61 years) and mean duration of the disease 7 years (1-33 years). All patients had normal body mass (+/- 10% according to Broka's formula). The plasma levels of glucagon, growth hormone, cortisol and C-peptide were determined at the beginning and at the end of the biostator control. With the decrease of glycemia (from 12.71 +/- 4.3 to 5.75 +/- 1.5 mmol/l, p less than 0.001) only the cortisol level fell reliably (p less than 0.001), the growth hormone and glucagon levels fell statistically insignificantly. There is no reliable correlation between the contra-insulin hormones studied and the glycemia level.

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30 insulin-dependent, C-peptide negative diabetic patients were examined with the help of biostator. The mean age of the patients was 29 years, the mean duration of the diabetes was 7 years and the mean index of body mas was 22. For the period from 0 to 8 o'clock in the morning the blood sugar level and the speed of the insulin infusion in order to maintain euglycemic level were examined at 1/2 hour intervals. The mean blood sugar level for the period 5-8 o'clock (5.71 +/- 0.31 mmol/l) was reliably higher (p less than 0.05) than that for the period 0-5 o'clock (5.4 +/- 0.18 mmol/l). The speed of the insulin infusion for the period 5-8 o'clock (0.52 +/- 0.09 IU/kg/min) was also reliably higher (p less than 0.02) than that for the period 0-5 o'clock (0.4 +/- 0.06 IU/kg/min). These two indices were correlated with the somatotropic hormone and hydrocortisone levels at 2 and 8 o'clock. The possible pathogenetic mechanisms of this "morning phenomenon" in diabetes is discussed.

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The 24-h urine excretion and renal clearance of albumin, alpha I-acid glycoprotein, transferrin, IgG, IgA and haptoglobin were studied in 30 albustix-negative diabetics with no clinical data for diabetic nephropathy aiming at the precise characterization of proteinuria in patients with diabetes mellitus. The diabetic patients were divided into two groups - 15 patients with newly diagnosed diabetes and 15 - with a longer duration of diabetes. Thirteen healthy subjects, at the same mean age, served as a control group. The results reveal increase of the clearances and 24-h excretion of the proteins studied in the patients with diabetes mellitus, in those with a short duration of the disease including, with authentic difference for albumin, transferrin, IgG and haptoglobin among the patients with a longer duration of the disease and the healthy controls and authentic difference for albumin between those with the newly diagnosed diabetes and the healthy control. The possible prognostic significance of the indices studied is discussed as well as their importance for the early diagnosis of diabetic nephropathy.

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Via the artificial endocrine pancreas--apparatus "BIOSTATOR" 100 patients were studied and treated, namely: 90 with diabetes mellitus, 7 with hyperinsulinism and 3 with obesity. The 24-h insulin needs of the diabetics with insulin-dependent and non-insulin dependent with secondary exhaustion type of diabetes, were determined. The following subcutaneous insulin dosage was determined, depending on the insulin amount spent during the 24-h biostator control. It was established that the necessary reduction of the intravenously administered insulin is 30% on the average with the passing over to subcutaneous regime. The indices of lipid metabolism were also studied as well as numerous hormones with which the carbohydrate compensation leads to a change. The problem of the "morning" phenomenon is discussed.

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