Effects of Immunosuppressive Drugs on Serum Fatty Acids of Phospholipids Fraction in Renal Transplant Recipients.

BACKGROUND: Immunosuppressive medications often cause posttransplant hyperlipidemia. The effects of cyclosporine (CsA) and tacrolimus (Tac) on lipid profile is well-known; however, there are very few studies related to the effect of these immunosuppressants on fatty acids (FA) of phosholipids fraction (PL) in renal transplant recipients (RTR). We sought to analyze the FA profile in PL fraction of RTR treated with Tac or CsA. METHODS: The study included 65 renal transplant patients on CsA (n = 24, group I) or Tac (n = 41, group II), and 14 healthy controls. Individual serum FA concentrations were measured by gas chromatography. Chemstation software was used to analyze the data. RESULTS: No differences between studied groups and controls were noted for monounsaturated FA, polyunsaturated n-3 FA (PUFA n-3), PUFA n-6, or the ratio of PUFA n-6 to PUFA n-3. The following mean values of FA were significantly higher in the CsA-RTR and Tac-RTR as compared with controls: total FA (P < .01 in both cases), saturated FA (SFA; P < .02 in both cases), C12 (P < .003 in both cases), C18 (P < .003 in both cases), and C18:2 (P < .01 for CsA RTR; P < .02 for Tac RTR). No differences between the measurements in patients on CsA and in patients on Tac were noticed. Significant correlation between SFA and eGFR was observed only in the CsA RTR group (P < .05). A negative relationship between PUFA n-6 and the estimated glomerular filtration rate was seen, but the correlation was not significant. CONCLUSIONS: Immunosuppressive drugs may affect FA metabolism, but the FA profile does not depend on the type of immunosuppressive drug administered.

High-performance Liquid Chromatography Measured Metabolites of Endogenous Catecholamines and Their Relations to Chronic Kidney Disease and High Blood Pressure in Heart Transplant Recipients.

BACKGROUND: Patients after solid organ transplantation, especially heart and kidneys, are prone to be hypertensive. Recently chronic kidney disease and renalase metabolism of endogenous catecholamines are thought to make major contribution to the pathogenesis of hypertension. MATERIALS AND METHODS: We analyzed 75 heart recipients (80% male, 20% female), medium age 54.9 years (range, 25-75) at 0.5 to 22 years after heart transplantation (median, 10.74). Diagnosis of hypertension was made on the basis of ambulatory blood pressure monitoring. Complete blood count, urea, creatinine, estimated glomerular filtration rate (eGFR), renalase in serum, and levels of metanefrine, normetanefrine, and 3-metoxytyramine in 24-hour urine collection calculated with a high-performance liquid chromatography were recorded. RESULTS: Urine endogenous catecholamine metabolites were estimated according to creatinine clearance. Normetanefrine was correlated with age (r = 0.27; P < .05), urea (r = 0.64; P < .01), creatinine (r = 0.6; P < .01), eGFR (r = -0.51; P < .01), renalase (r = 0.5; P < .01), and diastolic blood pressure (r = 0.26; P < .05). Metanefrine was correlated with urea (r = 0.43; P < .01), creatinine (0.32; P < .01), eGFR (r = -0.4; P < .01), renalase (r = 0.34; P < .05), height (r = -0.26; P < .05), weight (r = -0.23; P < .05), and time after heart transplantation (r = 0.27; P < .05). 3-Metoxytyramine was correlated with urea (r = 0.43; P < .01), creatinine (r = 0.32; P < .01), and the eGFR (r = -0.24; P < .05). Creatinine was correlated with age (r = 0.36; P < .01), diastolic blood pressure (r = 0.26; P < .05), time after heart transplantation (r = 0.24; P < .05), and renalase (r = 0.69; P < .01). Systolic blood pressure was correlated with proteinuria (r = 0.26; P < .05). CONCLUSIONS: Chronic kidney disease and concomitant hypertension are the most prevalent comorbidities in the population of heart transplant recipients. Urine catecholamine metabolites were related to kidney function but not to blood pressure level in the studied population.

Basic and Meal Stimulated Plasma GIP Levels are Higher in Lean PCOS Women with FAI over 5.

OBJECTIVE: Glucose dependent insulinotropic peptide (GIP) belongs to the incretins which are responsible for 70% of the insulin release after oral glucose intake. Its impaired secretion was noted in several conditions involving insulin resistance, including polycystic ovary syndrome (PCOS), known as the state with increased testosterone level. This paper considers a possible relationship between the free androgen index (FAI) and basal as well as meal stimulated level of GIP in lean women affected by PCOS. To our knowledge, no previous study has evaluated the matter so far. DESIGN: cross-sectional study METHODS: 50 age-matched lean women (BMI=20.76±1.83) were enrolled to the study and divided into 2 groups. Patients with phenotype with FAI<5 were classified as group 1, PCOS patients with FAI>5 formed group 2. All subjects underwent standard meal test. Serum GIP concentration was determined both at fasting and at 60 min of the test. Calculations were carried out using Statistica 10. RESULTS: Mann-Whitney test indicated a statistically significant difference in medians values of GIP plasma levels between groups on fasting (36.4 pg/ml vs. 59.6 pg/ml; p=0.0007) and at 60 min after meal test (50.1 pg/ml vs. 72.5 pg/ml; p=0.006). Spearman test indicated significant positive correlation between FAI and GIP levels at 0' and 60' in total study population (0':R=0.37;p=0.008; 60':R=0.28; p=0.049). CONCLUSION: Excess androgen activity might be a factor contributing to alter secretion of incretins in lean PCOS women. However it could not be ruled out that it is also possible that increased GIP levels might induce hyperandrogenemia in PCOS. An increased GIP levels may induce hyperinsulinemia and play an additive to insulin resistance role in progression to diabetes mellitus type 2 (DMT2).

Effect of immunosuppressive therapy on the serum fatty acids of phospholipids fraction in patients after heart transplantation.

BACKGROUND: The effects of tacrolimus (Tac) and cyclosporine (CsA) on lipid profile is well known; however, little is known about the changes in fatty acids (FA) of phosholipids fraction (PL) in heart transplant patients after treatment with these immunosuppressants. This study aimed to investigate the effect of Tac and CsA on serum FA of PL in heart transplant patients. METHODS: The study included 23 patients after heart transplantation on Tac (n = 14; group II) or CsA (n = 9; group I). Eleven healthy persons served as a control group. Serum FA of PL were extracted, separated on Sep-Pak NH2, methylated, and measured with the use of gas chromatography. Chemstation software was used to analyze the data. RESULTS: No differences between the studied groups and control were noted for saturated FA, monounsaturated FA, polyunsaturated FA (PUFA), total FA, and PUFA n-6. The mean value of PUFA n-3 was significantly higher in the CsA group compared with the Tac group (P < .015) and control (P < .002) as well as in the Tac group compared with control (P < .001). For individual FA, higher mean concentration, compared with control, was found for C24, C20:2, C20:4, and C22:6 (P < .001 in all cases) and lower for C18:2cis (P < .001 in both groups) and for C18:3 in the Tac group. The mean values of PUFA n-6 to PUFA n-3 ratios were lower than in control (both P < .001). CONCLUSIONS: Different pattern of FA of PL may indicate the different FA metabolism in heart transplant patients treated by different immunosuppressants. This should be taken into account when FA supplementation in these patients is considered.

Associations between bone, fat tissue and metabolic control in children and adolescents with type 1 diabetes mellitus.

AIMS: To investigate the relationship between bone-derived osteocalcin (OC), osteoprotegerin (OPG), Receptor Activator of Nuclear Factor NF-ĸB ligand (RANKL), and fat tissue-derived leptin and adiponectin with a clinical outcome of type 1 diabetes mellitus (T1DM) in children and adolescents. METHODS: 78 patients (43 girls and 35 boys), aged 11.5±4.3 years with T1DM and 11 age- and BMI-matched controls were included into the study. Patients were divided into 3 groups according to HbA1c level, I - below 7% [53 mmol/mol], II - 7-9% [53-75 mmol/mol] and III - above 9% [75 mmol/mol]. Blood samples for biochemical measurements were drawn at 8.00 AM, when the patients were in a fasting state. HbA1c was measured by the standardized IFCC method. OC, OPG, RANKL, leptin and adiponectin were measured by ELISA. ANOVA, and multiple regression analysis were used for statistical analysis. RESULTS: Significant differences in leptin and osteocalcin levels between groups with different HbA1c values were observed (p=0.03, p=0.04). Multiple regression analysis adjusted for age showed that serum OC and leptin negatively correlated with HbA1c levels (r=-0.22, p=0.004 and r=-0.27, p=0.0001, respectively). In contrast, serum OPG correlated positively with HbA1c (r=0.26, p=0.02) as well as with adiponectin (r=0.26, p=0.02) and RANKL (r=0.27, p=0.02) levels. The correlation of OC with HbA1c was the strongest in group I - patients with good metabolic control of DM (r=-0.43, p=0.03). In that group, in multiple regression analysis adjusted for age and BMI leptin correlated positively with daily dose of insulin (r=0.52, r=0.009). In group II and III in multiple regression analysis adjusted for age and BMI OC correlated negatively with leptin (r=-0.37, p=0.01). CONCLUSIONS: Our data suggest significant relationships between bone, fat tissue and glucose metabolism in pediatric patients with T1DM. The results can confirm that poor metabolic control is associated with reduced bone formation. On the other hand fat and bone tissue can influence glucose metabolism, potentiality in insulin-dependent manner. From these data leptin or OC may be potentially used as additional therapeutic agents for T1DM.

IGF-I, IGF-II, IGFBP2, IGFBP3 and acid-labile subunit (ALS) in colorectal cancer patients before surgery and during one year follow up in relation to age.

PURPOSE: To investigate the changes of IGF system in colon cancer patients in relation to age, the serum IGF-I, IGF-II, IGFBP2, IGFBP3 and ALS were measured by immunochemistry before surgery, as well as one and six months after surgery. MATERIAL AND METHODS: One hundred and twenty six patients were included into the study: group I (<50 yrs, N=21); group II (50 to <55 yrs, N=16) ; group III (55 to <65 yrs, N=34); group IV (65 to <75 yrs, N=42) and group V (> or =75 yrs, N=13). RESULTS: Before surgery: only the mean value of IGF-I concentration in group I was significantly higher as compared to group V (p<0.01). One month after surgery: 1) a decrease in the mean values of IGF-I, IGF-II, IGFBP3 and ALS levels was observed, but only for IGF-II (groups II-V), IGFBP3 (groups II-V) and ALS (groups III-V) the changes were significant; 2) the mean value of ALS level in group I was higher as compared to group III-V (p<0.05 to 0.02); 3) higher mean values of IGF-I/alb, IGFBP3/alb and ALS/alb were noted for group I as compared to group V (p<0.01 to 0.001); 4) the mean levels of IGFBP2 were significantly lower in group I as compared to groups II, III, IV and V (p<0.001 in all cases). CONCLUSIONS: In colon cancer patients IGF-I, IGFBP3 and ALS decrease with age, but the relation between them exists regardless the patient's age and time of observation. Lower IGFBP2 level together with higher IGF-I might contribute to more aggressive course of disease in colon cancer patients below 50 years of age.

Total plasma homocysteine correlates in women with gestational diabetes.

AIM: We aim to assess serum total homocysteine (tHcy) associations with metabolic syndrome components and B-vitamins in women with gestational diabetes mellitus (GDM). METHODS: We studied 61 consecutive pregnant women, 44 with GDM and 17 with normal glucose tolerance (CG). Serum homocysteine levels were analyzed by ELISA, using Bio-Rad reagents. Serum folates and vitamin B(12) concentrations were determined by chemiluminescent immunoassay, free fatty acids (FFA) and lipids enzymatically. RESULTS: Serum homocysteine levels were similar in both the GDM and the CG groups (8+/-2.0 vs 7.4+/-1.1 micromol/l, respectively). Women with GDM in comparison to CG women were characterized by higher values of homeostasis model of insulin resistance (HOMA-IR) (2.8+/-1.7 vs 1.6+/-0.9, P<0.01), serum triglycerides (2.7+/-0.9 vs 1.9+/-0.5 mmol/l, P<0.01) and FFA (0.6+/-0.2 vs 0.46+/-0.2 mmol/l, P<0.05). In GDM women serum tHcy correlated with vitamin B(12) (r= -0.47, P<0.01) and folates (r= -0.51, P<0.001); in CG women with HOMA-IR, a marker of insulin resistance (r= -0.49, P<0.05). In multiple regression analysis with serum tHcy as a dependent variable, folate and vitamin B(12) entered the analysis in GDM women (beta= -0.42 and -0.34, respectively, P<0.05), whereas in CG cystatin C and HOMA-IR entered the analysis (P<0.05). CONCLUSIONS: In women with GDM, serum homocysteine is significantly associated with vitamin B(12) and folate levels, while in healthy pregnant women with HOMA-IR and with kidney function. The results suggest the importance of the B-group vitamins in regulation of serum tHcy levels in women with insulin resistance/gestational diabetes, what might be relevant in protection against pregnancy complications associated with elevated tHcy in GDM women.

The effect of endurance training on muscle strength in young, healthy men in relation to hormonal status.

The objective of this study was to establish the effect of moderate intensity endurance training on muscle strength in relation to hormonal changes in the body. Fifteen young, healthy men took part in 5 week endurance training performed on a cycloergometer. Before and after training program, exercise testing sessions were performed involving all participants. Training program significantly increased V(O2 max) (P<0.05) and time to fatigue at 50% of maximal voluntary isometric contraction (TTF 50% MVC), P<0.03, but it did not affect maximal voluntary isometric contraction (MVC). This was accompanied by an increase (P<0.001) in total plasma testosterone (T) and free testosterone (fT) concentrations, whereas a decrease in sex hormone-binding globulin (SHBG) (P<0.02), growth hormone (P<0.05), free triiodothyronine (P<0.001) and free thyroxine (P<0.02) concentrations was observed. No changes were found in plasma cortisol (C) and insulin-like growth factor-I (IGF-I) concentrations. Additionally, MVC was positively correlated to T/C, fT/C and IGF-I/C ratios after the training, whereas time to fatigue at 50% of MVC was closely positively correlated to the SHBG concentration, both before and after endurance training. We have concluded that moderate intensity endurance training resulting in a significant increase in V(O2 max), did not affect the MVC, but it significantly increased time to fatigue at 50% of MVC. This index of local muscular endurance was greater in subjects with higher concentration of SHBG, both before and after the training.

Kinetics of plasma heat shock protein HSP-70 release in coronary artery surgery: on-pump versus off-pump.

AIM: Heat shock protein HSP-70 is known as protective chaperone molecule synthetized in response following ischemia and stress agents. It is detected in the myocardium and endothelium as well as in the circulation. Damaged as well as viable but exposed to stress cells contribute to the release of HSP-70 into the circulation. The aim of the study was to investigate if cardiopulmonary bypss (CPB) leads to more circulating HSP-70, on the basis of comparison dynamics of plasma concentration HSP-70 in 8 men undergoing procedures with the use of CPB (coronary artery bypass grafting, CABG group) and 8 men undergoing off-pump surgery (OPCAB group). METHODS: Blood samples were taken preoperatively, twice intraoperatively, immediately after surgical procedure (1 h) and 24-hours thereafter. The concentration of plasma HSP-70 was measured by means of immunoassay. The derived results were compared statistically with the frequency of incidence postoperative atrial fibrillation (AF). RESULTS: In CABG group was observed continuous gradual increase of plasma HSP-70 concentration during the operation with the peak 1 h after surgery (P<0.01), in striking contrast to OPCAB group, in which was detected small, but non statistically significant increase of HSP-70 1 h after operation. Significantly more of circulating HSP-70 it was detected in CABG group during the operation and 1 h after surgery (CABG vs OPCAB, respectively P<0.015 and P<0.028). In both groups among patients witch AF it was found higher postoperative values of circulating HSP-70 compared with the non-AF group (P=0.0415). CONCLUSIONS: The use of CPB leads to significant more release of HSP-70 into the circulation. According to our findings high plasma concentration of HSP-70 may be the measure of operative cellular stress, ischemia or injury and may be related with greater onset of postoperative AF. High circulating HSP-70 levels is connected with higher incidence of postoperative AF after open heart surgery.

Progesterone but not estradiol 17beta potentiates local GH secretions by hormone-dependent breast cancer explants. An in vitro study.

The aim of this study was to evaluate the effects of treatment of breast cancer explants with tamoxifen (TMX) or RU486 on GH secretory dynamics in the presence of exogenous estrogen (E2), progesterone (P4) or both. Explants obtained during surgery were divided according to their sex steroid hormone receptor status. P4 (10(-7) M) or 17beta-estradiol (10(-5) M) or both were tested in vitro for their ability to induce hGH secretion and cell proliferation. TMX (10(-7) M) was added to E2, RU486 (10(-7) M) to P4, and both were applied to E2 plus P4-supplemented cultures. The stimulatory action of P4 on GH secretion was noted in hormone-dependent (ER+/PR+) but not in hormone-independent explants (ER-/PR-). RU486 did not abolish this effect. The stimulatory action of P4 on GH release was not parallel to the stimulation of cell proliferation. E2 alone was without effect on GH secretion by both types of breast cancer explants. Combined treatment with both steroids stimulated GH secretion and cell proliferation by (ER+/PR+) explants. Both TMX and RU486 reversed this effect on cell proliferation while only RU486 abolished augmentation of GH secretion. In none of the hormone-dependent breast cancers, the combined treatment with E2 and P4 had any effect on GH secretion and cell proliferation. Taken together, these results lead us to the hypothesis that P4 but not E2 potentiates local GH secretion by hormone-dependent breast cancer explants. The fact that RU486 reversed neither GH secretion nor cell proliferation in hormone-dependent explants indicates its non-receptor-mediated mechanism of action.

Interleukin-6 (IL-6) and IGF-IGFBP system in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: Some studies suggest that IL-6 is connected with glucose metabolism and insulin action, so like IGF-IGFBPs system it could play the role in diabetes etiopathogenesis. AIM: The aim of the study was therefore to test the hypothesis that in children and adolescents IL-6 is of importance for the etiopathogenesis of diabetes mellitus type 1 and that IL-6 is connected with carbohydrate metabolism and IGF-IGFBPs action. METHODS: There were 49 patients with type 1 diabetes: 10 persons at onset diabetes and 39 with disease lasted at least 1 year and 33 age-matched healthy children included into the study. Serum IGF-I concentrations were measured by RIA; IGFBP-1 and IGFBP-2 by IRMA and IL-6 concentrations using quantitative ELISA immunoassays. HbA1c was measured by HPLC method. Multiple regression, ANOVA, and Student's t-test were used for statistical analysis. RESULTS: IL-6 and IGF-I, IGFBP-1 and IGFBP-2 levels did not differ statistically significant between diabetic patients and controls. IL-6 concentrations were statistically higher at onset diabetes than in diabetic patients with long-term disease. IL-6 did not correlate with IGF-I and its binding proteins - 1 and - 2 in examined groups. At onset of disease IL-6 correlated with insulin requirement. There were not found correlations between IL-6 and HbA1c in diabetic groups. IGF-I positively correlated with age and growth in both groups and with IGFBP-2 in diabetic patients. IGFBP-2 correlated negatively with BMI in all examined groups. CONCLUSIONS: IL-6 might play a significant role in type 1 diabetes mellitus etiopathogenesis. It seems that IL-6 does not regulate IGF-IGFBP system in diabetic children and adolescents or IL-6 maybe cooperate with IGF-I, but their significant dependence on insulin action influences their mutual relationships.

Cyproterone, norethindrone, medroxyprogesterone and levonorgestrel are less potent local human growth hormone and insulin-like growth factor I secretion stimulators than progesterone in human breast cancer explants expressing the estrogen receptor.

The aim of the present study was to compare the ability of natural progesterone and synthetic progestins to stimulate local growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion by breast cancer explants. Explants obtained during surgery were divided according to their estrogen/progesterone receptor phenotype - ER(+)PR(-); ER(+)PR(+); ER(-)PR(+) - as determined by immunocytochemistry. Natural progesterone (10(-5) mol/l) and synthetic progestins (cyproterone acetate (5 x 10(-7) mol/l), norethindrone (10(-5) mol/l), medroxyprogesterone acetate (10(-7) mol/l), and levonorgestrel (10(-7) mol/l) were tested in vitro for their ability to induce secretion of proliferation-promoting agents such as human GH (hGH) and IGF-I. All hormone-dependent breast cancer cell types responded to progesterone stimulation with increased local hGH secretion, while in the non-malignant tissue this effect was observed only in PR(+) cells. Moreover, progesterone in only PR(+) cells in vitro stimulated local IGF-I secretion by both malignant and non-malignant tissue. Medroxyprogesterone and levonorgestrel increased GH secretion by both malignant and non-malignant ER(-)PR(+) breast cancer explants, while cyproterone stimulated it only in non-malignant tissue. None of the synthetic progestins tested in this experiment exerted an effect on GH secretion by both malignant and non-malignant tissue of ER(+) breast cancer explants. The present data additionally showed that, apart from cyproterone, which increased IGF-I secretion in the same manner as progesterone by both malignant and non-malignant ER(-)PR(+) breast explants, other progestins tested had either no effect on IGF-I local secretion or decreased it. Medroxyprogesterone and levonorgestrel induced a decrease in IGF-I secretion noted in ER(+) explants of non-malignant tissue and in malignant ER(-)PR(+) breast tissue. All progestins tested decreased IGF-I secretion by malignant ER(+)PR(+) explants. Taken together, the tested synthetic progestins widely used as oral contraceptives and in hormone replacement therapy were less potent than progesterone in inducing secretion of proliferation-promoting agents such as hGH and IGF-I in ER-containing breast tissue. Despite the lack of confirmation of the link between the use of progestins and breast cancer risk, patients should be informed that the use of certain estrogen/progestin preparations is of no influence on breast cancer risk while others may increase it.

GLP-1 as a satiety factor in children with eating disorders.

GLP-1, with its insulinotropic properties and direct action on satiety center in the brain, may be the main hormone regulating the amount of ingested food. In this study, GLP-1 secretion was investigated in age-matched adolescent girls (14 +/- 2 years): 13 with anorexia nervosa (BMI 14.8 +/- 1.4 kg/m(2)), 13 with simple obesity (BMI 33.0 +/- 3.3 kg/m(2)) and 10 healthy girls as a control group (BMI 21.6 +/- 0.7 kg/m(2)). Each girl was subjected to OGTT and standard meal tests after a 12 h overnight fast. Blood samples were collected before and 15, 30, 60, and 120 min after the stimulation. The mean fasted GLP-1 levels in simple obesity group (1.6 +/- 0.3 pmol/l) and in anorexia nervosa group (1.7 +/- 0.3 pmol/l) were significantly lower than those in the control group (2.6 +/- 0.4 pmol/l) (p < 0.05 in both cases). The highest peak concentration of GLP-1 was observed in the control group after both stimuli. In each group, the mean integrated GLP-1 outputs were almost twice as high after OGTT than after the test meal (p < 0.001 in each case). In our opinion, low secretion of GLP-1 in girls with simple obesity may seriously and negatively influence the course of this disease. On the other hand, low GLP-1 levels in girls with anorexia nervosa are beneficial and promote appetite.

[Platelet activation and endothelial factors in standard exercise test before and after menopause]. / Aktywacja plytek i wybrane parametry funkcji sródblonka w trakcie standardowego wysilku fizycznego u kobiet w okresie okolomenopauzalnym.

OBJECTIVES: Postmenopausal lack of estrogens may accelerate cardiovascular atheromatic changes. Standard exercise test (SET) challenges hidden signs of the vascular involvement. Although the test is known not to carry a risk of thromboembolic complications, it may influence plasma concentrations of endothelial and platelet factors. The question is if and to what extend the menopause aggravates the SET induced changes. AIM: Plasma concentrations of nitric oxide, endothelin-1, beta-thromboglobulin and von Willebrand factor activity before, at the maximum exercise and 15 minutes after the SET referred to, as a recovery time were estimated. METHOD: SET was performed according to Bruce protocol in group of 31 premenopausal and 57 postmenopausal women. Standard RIA kits for plasma beta-thromboglobulin (beta-TG) (Boehringer Mannheim) and endothelin-1 (Et-1) (Blotrack) concentration were used. The von Willebrand factor (vWF) activity was assayed by ELISA system (Boehringer Manheim). Plasma nitric oxide (NO) concentration was calculated from nitrides/nitrates levels, by Griess reaction, modified by use of NADPH reductase. RESULTS: Mean plasma levels of beta-TG, Et-1, NO and vWF activity do not differ between pre and postmenopausal women. The standard exercise test significantly increases both beta-TG plasma concentration and vWF activity (p < 0.00001). During the 15 minutes rest period the changed values do not return to preexercise levels. Neither plasma NO nor Et-1 plasma concentrations change during the exercise test. There was a similar increase in beta-TG plasma levels and vWF activity during the SET in pre- and postmenopausal women and a slighter increase of plasma Et-1 levels in postmenopausal women (p < 0.04). The close relationships between NO plasma concentration and both vWF activity (p < 0.002) and vascular endothelial growth factor (VEGF) level (p < 0.04) were observed in postmenopausal women. The vWF activity in postmenopausal; women inversely correlates with insulin-like growth factor-I (IGF-I) concentration (p < 0.001). In premenopausal women the important modulators of vWF activity were: body mass (p < 0.04), serum total cholesterol (p < 0.02) and sex hormone binding globulin (SHBG) levels (p < 0.04). The postmenopausal beta-TG increase during SET depends on body mass (p < 0.02), whereas the preexercise levels seem to be related to VEGF level (p < 0.03) and inversely to Et-1 (p < 0.007) and dehydroepiandrosterone sulfate (DHEAS) concentration (p < 0.03) Both the basal and stimulated by exercise vWF activity are higher in obese women (p < 0.003), but the net increase is larger in lean group (BMI < 30 kg/m2). In premenopausal women plasma NO concentration depends on 17 beta-estradiol serum level (p < 0.02). The higher VEGF (p < 0.01) levels as well as vWF activity was observed (p < 0.03) in hypercholesterolemic women. CONCLUSION: The standard exercise test increases the procoagulatory von Willebrand factor activity so as the platelets activity (beta-thromboglobulin concentration) in both pre and postmenopausal women. The slight endothelin-1 rise has been found at the maximum exercise in postmenopausal women. The close relation between plasma nitric oxide and endothelin-1 levels was found in postmenopausal women. Obesity and hypercholesterolemia may contribute to the observed changes.

Composition of free fatty acid and triglyceride fractions in human necrotic pancreatic tissue.

BACKGROUND: Lipolytic enzymes, such as lipase, phospholipase A(2), lipoprotein lipase, and hormone-sensitive adipocyte lipase are probably implicated in the pathogenesis of acute pancreatitis. The increased activity of these enzymes can cause specific changes in fatty acid composition, both to free fatty acid (FFA) and triglyceride (TG) fractions in necrotically changed pancreatic tissue. MATERIAL AND METHODS: Specimens of necrotically changed pancreatic tissue taken intraoperatively from 13 patients operated for serious necrotic acute pancreatitis were analysed. The Fölsch extraction method and separation of lipids by thin-layer chromatography was used, and the final fatty acid composition was determined after methylation by gas liquid chromatography. RESULTS: The changes in the FFA fraction are more definite than those for the triglyceride fraction and refer mostly to the increased percentage distribution of unsaturated fatty acids. CONCLUSIONS: These studies lead to the hypothesis that fatty acids released in the process of lipolysis play a key role in the pathogenesis of acute pancreatitis.

Progesterone-induced secretion of growth hormone, insulin-like growth factor I and prolactin by human breast cancer explants.

The aim of the study was to evaluate the potential of human breast cancer tissue to secrete growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin in response to 10(-7) M progesterone stimulation. Explants were divided according to estrogen receptor (ER)/progesterone receptor (PR) phenotype (ER(-)PR(-); ER(+)PR(-); ER(+)PR(+); ER(-)PR(+)). Our results show distinct differences in cultured breast cancer tissue responses to progesterone stimulation with regard to secretion of proliferative agents such as GH, IGF-I and prolactin. All but ER(-)PR(-) breast cancer cell types responded in vitro to progesterone stimulation with an increase in local GH secretion, while in non-malignant tissue progesterone induced local GH secretion only in PR(+) cells. Moreover, only in PR(+) cells did progesterone stimulate local IGF-I and prolactin secretion, in both malignant and non-malignant tissue. This study provides evidence for the first time that in PR(+) breast cancer tissue, progesterone may increase GH, prolactin and IGF-I secretion in both malignant and surrounding non-malignant tissue. These hormones may act as local growth factors that stimulate the proliferation of mammary tumors.

Serum free fatty acid concentration in patients with acute pancreatitis.

BACKGROUND: The involvement of lipolytic enzymes and liberated fatty acids in ethiology of acute pancreatitis (AP) has been implicated. AIM: To analyze the level of FFA in the patients with AP in relation to severity of the disease. MATERIAL AND METHODS: The study included 36 patients with acute edematous AP (group I), 29 patients with necrotizing AP: 16 without (group IIA) and 13 with complications (group IIB), and 12 control subjects. Serum levels of total FFA (by enzymatic method) and the individual fatty acids of the FFA pool (by gas-liquid chromatography) were measured during the first 4 days after admission. RESULTS: A significant increase in the mean total serum FFA was noted for all the groups with the highest values on admission (p < 0.02-0.01). The per cent contribution was significantly higher as compared to control group for oleic acid (group I, p < 0.02, group IIA, p < 0.05, group IIB, p < 0.005), linoleic acid (group IIB, p < 0.02) and arachidonic acid (group IIA, p < 0.05, group IIB, p < 0.02). Significantly lower percentage was noted for stearic acid (all three groups: p < 0.01, p < 0.005, p < 0.01, respectively) and for palmitic acid (only group IIB: p < 0.005). The ratio of saturated to polyunsaturated fatty acids was significantly lower than in control group on each day of study for group IIB only (p < 0.005-p < 0.001). CONCLUSION: Polyunsaturated fatty acids, mainly linoleic and arachidonic, may be involved in the development of complications in acute pancreatitis.

[Alpha-L-fucosidase activity in patients with ductal cholelithiasis]. / Alfa-L-fukozydaza u chorych z przewodowymi postaciami kamicy zólciowej.

Alpha-L-fucosidase (ALF), AST, ALT and GGT activities were measured in blood serum of 36 patients with recurrent cholelithiasis (group I), 32 patients with ductal and/or bladder cholelithiasis (group II), 24 patients with focal changes in the liver (group III) and in 22 patients without disturbances of gastrointestinal tract (control group). A statistically significant increase in ALF activity was found in the patients with recurrent cholelithiasis as compared to the control group (p < 0.001), the patients of group II (p < 0.001) and the patients of group III (p < 0.05). The AST and ALT activities were higher both in group I and in group II than in the control group (p < 0.001 and p < 0.02 for group I and group II, respectively), whereas the mean GGT activity was significantly higher in all three patients groups as compared to the control group (p < 0.001 in all cases). On the basis of the observed differences in the activities of the enzymes studied it was postulated that the determination od ALF activity in blood serum of patients with cholelithiasis may provide the means for early diagnosis of the predisposition to recurrent stones.

[Incorrect caloric-nitrogen composition of parenteral nutrition solutions as a factor for causing liver damage--an animal model]. / Nieprawidlowy sklad kaloryczno-azotowy roztworów do odzywiania pozajelitowego jako czynnik wywolujacy uszkodzenie watroby--model zwierzecy.

The experiment were carried out on 40, 3-week old rats who received solutions of aminoacids, glucose, fat, electrolytes, trace elements and vitamins. The ratio of non-protein calories to grams of nitrogen was: Group I-75:1, Group II-200:1, Group III-500:1. Control Group IV was on standard Murigan chow. The analysis included the following parameters: body mass, serum albumin concentration, GOT, GPT and ECH, and microscopic liver studies. The results show that body mass increases in Group I-III (7.5 g, SD 2.18; 1.45 g, SD 2.33; 1.85 g, SD 1.56 respectively) were significantly lower when compared to the controls (11.6 g, SD 2.72), with p < 0.001. Blood serum albumin concentration values were lower in Group I, II and III, and transaminase activity was elevated in comparison to the controls. Histological analysis showed mitochondrial damage and parenchymal degeneration with proliferation of Browicz-Kupfer cells in Group I and III animals, and no structural hepatic changes in Group II and in the controls. The results suggest a relationship between the above disturbances and the composition of the administrated solutions.