Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy.

AIM: The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women. MATERIALS AND METHODS: The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. RESULTS: Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. CONCLUSIONS: Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.     

Climacteric obesity: from genesis to clinic.

The etiology of obesity is multifactorial and still unclear. Genetic factors play a significant role and include several gene candidates: polymorphisms of genes for ss(2)-adrenoreceptor, resistin, estrogen receptor-a and peroxisome proliferator-activated receptor-gamma. Moreover, peptides regulating hunger and satiety, e.g. leptin, galanin, cholecystokinin and neuropeptide Y, and altered nutritional patterns have been implicated. Also, factors associated with aging, e.g. decreased levels of growth hormone and dehydroepiandrosterone, and the activity of the sympathetic nervous system (resting metabolism and thermogenesis) cannot be disregarded. Participation of the sex steroids and inflammatory factors has also been postulated in the etiology of obesity. Three phenotypes of obesity are postulated; however, the visceral (abdominal) phenotype is typical of postmenopausal women and is characterized by several metabolic disorders with high risks of diabetes mellitus type 2 and cardiovascular disease. On the basis of personal experience and data from evidence-based medicine, diagnostic-therapeutic algorithms of climacteric obesity are presented.     

A comparative study of angiogenic and cytokine responses after laparoscopic cholecystectomy performed with standard- and low-pressure pneumoperitoneum

Background  Surgical procedures enhance production of pro- and anti-inflammatory cytokines and angiogenic factors that play a pivotal role in the immunological response to surgical trauma and take part in the pathogenesis of tumor growth and adhesions formation. The purpose of the study was to access the influence of low-pressure CO₂ pneumoperitoneum on the inflammatory and angiogenic responses during the postoperative period after laparoscopy. Methods  The study group consisted of 40 patients, operated on due to cholelithiasis using standard-pressure (n = 20) and low-pressure (n = 20) CO₂ pneumoperitoneum. Serum concentration of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF)-A, and endostatin were measured before and at 6, 24, and 48 h after surgery with commercially available enzyme-linked immunosorbent assay (ELISA). Results  Concentrations of IL-6 increased significantly after the operations in both groups. No differences were observed between the groups in regards to IL-6, IL-8, and IL-10 levels. Concentrations of VEGF-A measured at 6 and 48 h were significantly lower in patients who underwent laparoscopies performed with low-pressure pneumoperitoneum. No significant variations were observed in endostatin serum concentration. Concentrations of the studied parameters were not influenced by duration of surgery or by age, gender, or body mass index (BMI) of the patients. Conclusions  The results obtained in our study do not show any significant differences between studied operative procedures with regards to systemic inflammatory response. Changes in the concentrations of VEGF-A and endostatin observed in the studied population may suggest this technique is more favorable with regards to angiogenesis process intensity, along with all its consequences and implications.     

Ethanol and nicotine consumption and preference in transgenic mice overexpressing the bovine growth hormone gene

Transgenic mice overexpressing the phosphoenolpyruvate carboxykinase/bovine growth hormone (PEPCK/ bGH) hybrid gene and normal (nontransgenic) littermate controls (10 males + 10 females/group) were given access to tapwater and an ascending series of concentrations of ethanol (1.0–22.0%), then a similar ascending series of concentrations of nicotine (1.0–40.0 μg/ml), in a two-bottle choice test. Male transgenic mice consumed more and exhibited greater preferences for ethanol and nicotine than control males; transgenic females consumed less and showed lower preferences for ethanol, but not nicotine, than control females. These results suggest that chronic exposure to high levels of bGH may modulate the rewarding effects of ethanol and nicotine in mice in a gender-specific fashion.     

Mechanism of UV-related carcinogenesis and its contribution to nevi/melanoma

Melanoma consists 4-5 % of all skin cancers, but it contributes to 71-80 % of skin cancers deaths. UV light affects cell and tissue homeostasis due to its damaging effects on DNA integrity and modification of expression of a plethora of genes. DNA repair systems protect cells from UV-induced lesions. Several animal models of melanoma have been developed (Xiphophorus, Opossum Monodelphis domestica, mouse models and human skin engrafts into other animals). This review discusses possible links between UV and genes significantly related to melanoma but does not discuss melanoma genetics. These include oncogenes, tumor suppressor genes, genes related to melanocyte-keratinocyte and melanocyte-matrix interaction, growth factors and their receptors, CRH, ACTH, α-MSH, glucocorticoids, ID1, NF-kappaB and vitamin D3.     

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

The influence of erythropoietin on cytokines in haemodialysis patients

Summary: In this study, the administration of erythropoietin to haemodialysis patients revealed its immunomodulating properties. to dissociate the immunological effects of erythropoietin action from its haematological effects the patients in our study were administered recombinant human erythropoietin (rhEpo) at the doses that would not affect erythropoiesis. After baseline data had been obtained, six haemodialysis patients were given rhEpo (Eprex-Cilag) at the dose 7-10 U/kg bodyweight/s.c., three times a week, for 12 weeks. All patients maintained a stable haemoglobin concentration; no blood transfusions were required. Serum levels of tumour necrosis factor (TNF), IL-2 and IL-6 levels of the study patients and the four control patients, not receiving rhEpo, were monitored every 2 weeks. the levels of IL-6 and TNF remained unchanged; however, a low serum level of IL-2, recorded before therapy, increased gradually for 10 weeks until it reached the values observed in normal healthy humans (P<0.01). After that it dropped to the initial values. During the study the red blood cell numbers did not change. This study supports the thesis that erythropoietin administered to haemodialysis patients not only corrects anaemia but also independently modulates immunological response.     

A retrospective comparative study of surgery followed by chemotherapy vs. non-surgical management in limited-disease small cell lung cancer.

OBJECTIVE: The role of surgery in limited SCLC is still a matter of controversy. Even though the response rates to chemotherapy are very high, prognosis of SCLC patients has remained poor with a median survival of only 12-14 months for limited disease. High incidence of local relapses after chemotherapy in limited-stage SCLC led to reassessment of the role of local treatment in the multimodality management of this tumor. METHODS: We performed retrospective comparative analysis of survival in a series of 134 limited-stage SCLC patients treated between 1984 and 1996 with either complete resection followed by chemotherapy (67 patients), or with conventional non-surgical management (67 patients). In all patients who underwent resection, the diagnosis of SCLC was established only postoperatively. The control (non-surgical) group was selected using 'pair-matched case-control' methodology, out of 176 limited-stage patients potentially suitable for surgery (i.e. with no pleural effusion or other local advancement, no supraclavicular lymph node involvement and good performance status), but treated without resection. The major prognostic factors were well balanced between these two groups. Total series included 109 males and 25 females, 20 patients with T1 and 114 patients with T2 disease, 51 N0, 43 N1 and 40 N2 disease. RESULTS: Median survival in patients treated with and without surgery was 22 months and 11 months, respectively, (P < 0.001). The two-year and five-year survival probabilities were 43 and 27%, respectively, in the surgical group, and 17 and 4%, respectively, in the non-surgical group. Subset analysis confirmed significantly longer survival with surgery in all T and N categories, except for N2 disease. Local relapse occurred in 15 and 55% of patients treated with and without surgery, respectively, (P < 0.001). Distant relapse probabilities were similar in both groups (36 and 40%, respectively). The most common site of metastases in the entire series was brain, followed by liver, lymph nodes, bone, lung and skin. CONCLUSIONS: Our results suggest a possible role of surgery in limited-stage SCLC. Thus, a randomised study addressing this issue seems to be justified.     

Utilization of a sol-gel method for encapsulation of doxorubicin

The sol-gel pre-doping method was used to encapsulate doxorubicin in silica gels and optimum conditions of preparation of drug-loaded gel were established, ensuring both reproducible and effective results of quantitative encapsulation of doxorubicin and its gradual but complete release. Doxorubicin was encapsulated in polysiloxane polymers using the method based on sol-gel encapsulation without a catalyst, with an acid catalyst (HCl) and a base catalyst (NH3). The time of gelation of the gel loaded with doxorubicin, encapsulation efficiency of the drug and the degree of release of the drug from the gel are all affected by the kind of catalyst (acidic or basic) or its absence at the gel preparation stage, and the temperature of the gelation process. The time of sol gelation when using the NH3 or HCl catalyst was 9 days at 21 degrees C, 2 days at 30 degrees C and 1.5 days at 37 degrees C, while for the gel prepared without a catalyst it was 90 days at 21 degrees C, 75 days at 30 degrees C and 70 days at 37 degrees C. The efficiency of doxorubicin encapsulation was 99.5 +/- 0.5% (w/w) for acid-catalyzed gel, 98.9 +/- 1.01% (w/w) for base-catalyzed gel and 86.4 +/- 11.6% (w/w) for non-catalyzed gel. A 100% (w/w) release of doxorubicin by diffusion through pores was found only in the case of base-catalyzed gel after a 140-h incubation time. For acid-catalyzed gel and non-catalyzed gel, the total amounts of released doxorubicin after 140 h of incubation were 3-5% (w/w) and 9-11% (w/w), respectively. The stability of doxorubicin encapsulated in the three kinds of gel matrices was found to be improved compared to the stability of a free form of the drug in solution.     

Alternating copolymerization of carbon dioxide and propylene oxide in the presence of organometallic catalysts

Carbon dioxide and propylene oxide (PO) were copolymerized using diethylzinc in addition with benzenedi- and triols, aliphatic diols and triols, and aminophenols as catalyst systems. A large amount of CO₂/PO alternating copolymer, {poly(propylene carbonate), poly(oxycarbonyloxypropylene), of high molecular weight was obtained using the homogeneous (C₂H₅)₂Zn/pyrogallol (2:1 by mole) system ( 1 ). The (C₂H₅)₂Zn/o-aminophenol system ( 2 ) (also homogeneous) appeared to be much less active in the copolymerization of CO₂ with PO than the former one. From the other studied systems, that appeared to be heterogeneous, (C₂H₅)₂Zn/resorcinol (1:1 by mole) was the most active one, but less active than the system 1 . Further, the copolymerization of CO₂ and PO was studied in the presence of the (C₂H₅)₂Zn/resorcinol (1:1 by mole) system at various temperatures and in reaction media of different basicity. On the basis of the obtained results of the copolymerization of CO₂ with PO and of measurements of the quantity of ethane evolved in the reactions between the catalytic systems' components, structures of several catalysts, particularly homogeneous ones, are suggested and some aspects of the copolymerization mechanism are discussed.