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991.
Clinical trials using autologous bone marrow and peripheral blood-derived progenitor cells in patients with acute myocardial infarction 总被引:4,自引:0,他引:4
Tendera M Wojakowski W 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2005,43(4):233-235
This paper discusses the current data concerning the results of major clinical trials using bone marrow-derived and peripheral blood-derived stem/progenitor cells in treatment of patients with acute myocardial infarction (AMI) and depressed left ventricular ejection fraction. In all major trials (TOPCARE-AMI, BOOST), the primary outcome measure was increase in left ventricular systolic function (LVEF) and left ventricle remodeling. The most consistent finding is the significant increase in LVEF. Some trials suggest also reduction of left ventricular remodeling. Although the absolute LVEF increase is small (6-9%), it may substantially contribute to the improvement of global LV contractility. None of the studies in AMI patients treated with intracoronary infusion of progenitor cells revealed excess risk of arrythmia, restenosis or other adverse effects attributable to the therapy. The exact mechanism of improved myocardial contractile function remains unknown, however, there are several possible explanations: therapeutic angiogenesis improving the blood supply to the infarct border zone, paracrine modulation of myocardial fibrosis and remodeling (e.g. inhibition of myocyte apoptosis) and transdifferentiation of stem/progenitor cells into functional cardiomyocytes. No study showed the superiority of the particular subpopulation of autologous progenitor cells in terms of left ventricular function improvement in AMI. In fact, most of the clinical trials used the whole population of mononuclear bone marrow-derived progenitor cells, peripheral blood derived progenitor cells (endothelial progenitors). 相似文献
992.
We present a case of 50 year-old man with feminizing adrenal carcinoma. He was admitted to the hospital because of weakness and one year history of gynecomastia and high blood pressure. Examinations revealed a large left adrenal mass and increased levels of estradiol. Patient underwent adrenalectomy and followed by mitotan therapy as the result of histopathological examination was adrenocortical carcinoma. One year after operation patient stays free from the recurrence of the disease and his estradiol, androstendion and DHEA levels are below the detection limits. We report this case because feminizing adrenal carcinoma is a very rare but serious disease and gynecomastia that could be its manifestation is quite frequent symptom in men's population and thus it could easily be missed. In every case of gynecomastia related to estradiol excess feminizing tumors of testis and adrenal gland should be ruled out. 相似文献
993.
In some patients with hyperprolactinaemia a large portion of circulating prolactin is bound to authologous gammaglobulin and therefore it is called macroprolactin or Big-Big-Prolactin (BB-PRL). THE AIM: of the study was to select patients with predominance of macroprolactin and to learn more about the natural course of this disorder, in particular about the possible dependence of the presence of clinical features from the amount of circulating "free" PRL level, and also to search whether the quantitative proportions of both forms of PRL are stable or they change parallel to changes of the total serum PRL level. MATERIAL AND METHODS: We identified 58 patients with hyperprolactinaemia, in whom BB-PRL consisted>or=60% of the total PRL concentration. The predominance of macroprolactin was settled using the well accepted method of polyethylene glycol (PEG) precipitation of large m.w. serum proteins, followed by contemporary immunoradiometric measurement of the total and free PRL levels, and calculation of BB-PRL. Repeating such measurements during the long term observation lasting 6-66 months (mean 33 months), which was possible in 18 our patients (13--with idiopathic hyperprolactinaemia and 5--with pituitary adenoma), we could analyze the relations between both forms of PRL during the specific treatment, after it's cessation and, in few cases--during pregnancy. Apart of that, in 18 patients selected from 53 with idiopathic hyperprolactinaemia, we analyzed the shortterm alterations in the ratio between free and complexed PRL during the metoclopramide PRL stimulation test. RESULTS AND CONCLUSIONS: 1. In hyperprolactinaemic patients with predominance of BB-PRL, there was no direct correlation between the presence of clinical features and the concentration of residual "free" PRL. 2. During the long-term observation, in spite of moderate changes in the total PRL concentration induced by the treatment or it's cessation (excluding pregnancy), the ratio of "free" PRL and BB-PRL remained stable. 3. During the short time of metoclopramide stimulation test, there was a marked rise mainly of the total and "free" PRL concentrations, and, in some tested subjects, the predominance of BB-PRL was lost temporally for 1 to 2 hours. 相似文献
994.
OBJECTIVES: The aim of this study was to analyze the influence of DHEA therapy on insulin resistance (FIRI, FG/FI) and serum lipids in men with angiographically verified coronary heart disease (CHD). MATERIAL AND METHODS: The study included thirty men aged 41-60 years (mean age 52+/-0.90 yr) with serum DHEA-S concentration<2000 microg/l, who were randomized into a double-blind, placebo-controlled, cross-over trial. Subjects completed the 80 days study of 40 days of 150 mg oral DHEA daily or placebo, and next groups were changed after 30 days of wash-out. Fasting early morning blood samples were obtained at baseline and after each treatment to determine serum hormones levels (testosterone, DHEA-S, LH, FSH estradiol and IGF-1) and also metabolic profile (total cholesterol, LDL-cholesterol, triglicerides, HDL-cholesterol, insulin, glucose, fasting insulin resistance index--FIRI and FG/FI ratio). RESULTS: Administration of DHEA was associated with 4.5-fold increase in DHEA-S levels. Relative to baseline DHEA administration resulted in a decrease in insulin levels by 40% (p<0.005) and fasting insulin resistance index (FIRI) by 47% (p<0.004). Also total cholesterol levels and LDL-cholesterol levels decreased significantly (from 222.9+/-6.6 mg/dL to 207.4+/-6.6 mg/dL and from 143.9+/-6.9 mg/dL to 130.5+/-6.0 mg/dL respectively; p<0.05). Glucose levels dropped significant below baseline values after DHEA (p<0.001). Estrogen levels significantly increased after DHEA (p<0.05). While changes of serum concentrations of testosterone, LH, FSH, IGF-I, HDL-cholesterol, triglycerides were not statistical significant. Tolerance of the treatment was good and no adverse effects were observed. CONCLUSIONS: DHEA therapy in dose of 150 mg daily during 40 days in men with DHEA levels<2000 microg/l decreased total cholesterol concentration, insulin and glucose levels and fasting insulin resistance index (FIRI). This therapy may be a beneficial against CHD risk factors. 相似文献
995.
The relationship between testosterone and dehydroepiandrosterone sulfate concentrations, insulin resistance and visceral obesity in elderly men 总被引:1,自引:0,他引:1
INTRODUCTION: Sex hormones deficiency--hypotestosteronemia (20-30% of men) and dehydroepian-drosterone sulfate deficiency (60-70% of men) are often observed in elderly men. In these men also changes of body composition (visceral obesity, increasing of fat mass), and metabolic disturbances (hypercholesterolemia, hyperinsulinism and insulin resistance) are common disorders. Visceral obesity and insulin resistance may be either reasons or effects of testosterone deficiency. Probably also DHEA-S deficiency is the risk factor of visceral obesity and insulin resistance, but it is not clear, whether this possible influence is independent from testosterone deficiency. OBJECTIVES: The aim of this study was to analyze the association between testosterone and DHEA deficiency and waist/hip ratio (WHR), levels of glucose and insulin resistance (HOMA and FG/FI) in elderly men as well as analysis, whether these sex hormones influent on measured parameters separately. MATERIAL AND METHODS: Together 85 men with age from 60 to 70 years men (mean 66.3+/-1.5 years; mean+/-SEM) was analyzed. Testosterone levels<4 ng/ml or DHEA levels<2000 ng/ml and BMI<30 kg/m2 were including criteria. Patients were divided into three groups: 52 with testosterone deficiency (L-T), 32 with DHEA deficiency (L-DHEA-S) and 67 with deficiency of both sex hormones (L-T/DHEA-S). Statistical analysis was made using Student-t, Kruskal-Wallis, and Mann-Whitney tests. RESULTS: Testosterone levels in L-T, L-DHEA and L-T/DHEA groups were respectively 3.19+/-0.23 ng/ml, 4.89+/-0.45 ng/ml and 3.25+/-0.34 g/ml (p<0.002). While DHEA-S levels were respectively 2498+/-98 ng/ml, 1435+/-1010 ng/ml and 1501+/-89 ng/ml). BMI values do not differ between groups. WHR ratio values were the highest in L-T/DHEA-S group (p<0.05 vs. L-T) group, significant lower in L-T group (p<0.005 vs. L-DHEA-S) and the lowest in L-DHEA-S group. Insulin fasting levels were lowest in L-DHEA-S group, higher in L-T group (p<0.01) and the highest in L-T/DHEA-S group (p<0.001 vs, L-T group). FG/FI values were the highest in L-DHEA-S group, lower in L-T group (NS) and lowest in L-T/DHEA group (p<0.002 vs. L-T group). HOMA ratio values similarly did not change significantly between L-T (6.6+/-3.21) and L-DHEA-S group (5.5+/-2.92), although tendency to higher values in L-T group was noticed, while WHR ratio values were significantly higher in L-T/DHEA group (7.3+/-2.45; p<0.002 vs. L-T group). CONCLUSIONS: DHEA-S and testosterone deficiency were independently associated with higher insulin resistance and obesity. WHR ratio seems to be more sensitive then BMI ratio to reflect the androgen deficiency on obesity and body composition in elderly men. 相似文献
996.
Miltyk W Surazynski A Kasprzak KS Fivash MJ Buzard GS Phang JM 《Journal of cellular biochemistry》2005,94(6):1210-1217
Occupational exposure to nickel has been epidemiologically linked to increased cancer risk in the respiratory tract. Nickel-induced cell transformation is associated with both genotoxic and epigenetic mechanisms that are poorly understood. Prolidase [E.C.3.4.13.9] is a cytosolic Mn(II)-activated metalloproteinase that specifically hydrolyzes imidodipeptides with C-terminal proline or hydroxyproline and plays an important role in the recycling of proline for protein synthesis and cell growth. Prolidase also provides free proline as substrate for proline oxidase, whose gene is activated by p53 during apoptosis. The inhibition of prolidase activity by nickel has not yet been studied. We first showed that Ni(II) chloride specifically inhibited prolidase activity in CHO-K1 cells in situ. This interpretation was possible because CHO-K1 cells are proline auxotrophs requiring added free proline or proline released from added Gly-Pro by prolidase. In a dose-dependent fashion, Ni(II) inhibited growth on Gly-Pro but did not inhibit growth on proline, thereby showing inhibition of prolidase in situ in the absence of nonspecific toxicity. Studies using cell-free extracts showed that Ni(II) inhibited prolidase activity when present during prolidase activation with Mn(II) or during incubation with Gly-Pro. In kinetic studies, we found that Ni(II) inhibition of prolidase varied with respect to Mn(II) concentration. Analysis of these data suggested that increasing concentrations of Mn(II) stabilized the enzyme protein against Ni(II) inhibition. Because prolidase is an important enzyme in collagen metabolism, inhibition of the enzyme activity by nickel could alter the metabolism of collagen and other matrix proteins, and thereby alter cell-matrix and cell-cell interactions involved in gene expression, genomic stability, cellular differentiation, and cell proliferation. 相似文献
997.
Kowalski W Przytocka-Jusiak M Błaszczyk M Hołub W Wolicka D Wesołowska I 《Acta microbiologica Polonica》2002,51(1):47-56
The effect of nitrates on the biotransformation of phosphogypsum at 30 degrees C in stationary cultures of anaerobic, heterogeneous microflora growing in medium with phenol (250-1,000 mg/L) as sole carbon source was studied. The microorganisms used in this study were isolated from sludge in biological petroleum-refining wastewater treatment plant. Phosphogypsum (a waste product in the chemical industry that contains approximately 95% CaSO4) was added in amount of 5 g/L, the source of nitrates was KNO3 in concentration equivalent to that of phenol (250-1,000 mg N-NO3/L). The presence of nitrates in heterogeneous cultures has an inhibitory effect on the process of phosphogypsum biotransformation and stimulates the uptake of phenol. We have found that in cultures in medium containing phenol, phosphogypsum and nitrates at least three physiological groups of microorganisms were present. These were phenol-biodegrading microorganisms not requiring an external electron acceptor, sulfate-reducing bacteria biodegrading phenol or intermediate products of its breakdown and denitrifying bacteria not utilising phenol as a carbon source. On solid medium these bacteria together formed heterogeneous single colonies. In spite of repeated attempts we were unable to isolate pure strains and the only result of these measures was loss of denitrification ability in medium with phenol. 相似文献
998.
999.
Szak ST Pickeral OK Makalowski W Boguski MS Landsman D Boeke JD 《Genome biology》2002,3(10):research0052.1-research005218
Background
As the rough draft of the human genome sequence nears a finished product and other genome-sequencing projects accumulate sequence data exponentially, bioinformatics is emerging as an important tool for studies of transposon biology. In particular, L1 elements exhibit a variety of sequence structures after insertion into the human genome that are amenable to computational analysis. We carried out a detailed analysis of the anatomy and distribution of L1 elements in the human genome using a new computer program, TSDfinder, designed to identify transposon boundaries precisely. 相似文献1000.
Pawełczak K Makowski M Kempny M Dzik JM Gołos B Rode W Rzeszotarska B 《Acta biochimica Polonica》2002,49(2):407-420
Synthesis and biological evaluation are described of seven new analogues (3-9) of two potent thymidylate synthase inhibitors, 10-propargyl-5,8-dideazafolate (1) and its 2-methyl-2-deamino congener ICI 198583 (2). While the new compunds 3 and 4 were analogues of 1 and 2, respectively, containing a p-aminobenzenesulfonyl residue in place of the p-aminobenzoic acid residue, the remaining 5 new compounds were analogues of 4 with the L-glutamic acid residue replaced by glycine (5), L-valine (6), L-alanine (7), L-phenylglycine (8) or L-norvaline (9). The new analogues were tested as inhibitors of thymidylate synthases isolated from tumour (Ehrlich carcinoma), parasite (Hymenolepis diminuta) and normal tissue (regenerating rat liver) and found to be weaker inhibitors than the parent 10-propargyl-5,8-dideazafolic acid. Selected new analogues, tested as inhibitors of growth of mouse leukemia L 5178Y cells, were less potent than the parent 10-propargyl-5,8-dideazafolic acid. Substitution of the glutamyl residue in compound 4 with L-norvaline (9) resulted in only a 5-fold stronger thymidylate synthase inhibitor, but a 40-fold weaker cell growth inhibitor. 相似文献