Expression of estrogen receptor alpha and progesterone receptor in children with undescended testicle previously treated with human chorionic gonadotropin

PURPOSE: The aim of this study was to investigate expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) in paratesticular tissues obtained from boys with undescended testes. MATERIALS AND METHODS: A total of 65 boys with unilateral cryptorchidism and failed human chorionic gonadotropion treatment underwent orchiopexy. A small sample of gubernaculum, cremasteric muscle and processus vaginalis was obtained. A total of 57 boys who underwent inguinal hernia repair served as the control group. All boys in the control group had testes in the scrotum. The expression of estrogen receptor alpha and progesterone receptor was measured by counting the number of ERalpha or PR positive cells detected by immunohistochemical analysis. RESULTS: ERalpha and PR density was higher in cremasteric muscle and processus vaginalis obtained from boys with undescended testes than in the control group. Density of progesterone receptor in the examined groups was lower than the density of estrogen receptor. CONCLUSIONS: ERalpha and PR are expressed in paratesticular tissues important for normal testicular descent. ERalpha was over expressed in cremasteric muscle and processus vaginalis in boys with undescended testes previously treated with human chorionic gonadotropin.     

Ozonated autohemotherapy in patients on maintenance hemodialysis: influence on lipid profile and endothelium

Ozonated autohemotherapy (O3-AHT) is used in the treatment of atherosclerotic ischemia of lower limbs (AILL). The impact of ozone on serum lipids and endothelium injury is of particular interest since these factors are important in the development of atherosclerotic lesions. To evaluate this issue, a prospective, placebo-controlled study was designed. Twelve hemodialyzed subjects with AILL received autohemotherapy with oxygen as a control followed by O3-AHT with ozone concentration of 50 micro g/ml. Serum lipids and plasma activity of von Willebrand factor (vWF) were measured. After O3-AHT, total cholesterol significantly decreased compared to the baseline (-8.34%) [P < 0.01]. LDL cholesterol was also significantly lower than the initial value (-17.71%) [P < 0.001]. No significant changes in the activity of vWF were found after the first session of O3-AHT and after all nine sessions of O3-AHT. The study demonstrated that O3-AHT did not affect deleteriously the endothelium in patients with chronic renal failure on maintenance hemodialysis. It may stimulate beneficial changes in serum lipid profile manifesting as a decrease in the total- and LDL-cholesterol levels.     

Fistula function and dialysis adequacy during ozonotherapy in chronically hemodialyzed patients

There are a variety of complications related to chronic hemodialysis treatment, including thrombosis in hemodialysis access leading to blood recirculation, and in turn to the deterioration in hemodialysis effectiveness. Given that ozone decreases blood viscosity, increases erythrocyte deformability, and inhibits coagulation, the periodic blood ozonation may be of benefit in the attenuation of these disturbances. To gain insight into this issue,we originally evaluated the impact of ozonated autohemotherapy on recirculation in arteriovenous fistula, hemodialysis adequacy, and the frequency of dialyzer reuse. Twelve chronically hemodialyzed patients with peripheral arterial disease were enrolled in the prospective, placebo-controlled study. Nine sessions of autohemotherapy with the exposure of blood to oxygen, as a control, and nine sessions of autohemotherapy where the blood is exposed to ozone in a concentration of 50 microg/mL are administered in a single-blind manner. Access recirculation is measured by means of spectral technology(Crit Line Monitor, HemaMetrics, Kaysville, UT, U.S.A.), and hemodialysis adequacy is calculated using the Daugirdas formula and expressed as the Kt/V index. The Kt/V index and the frequency of dialyzer reuse do not change after ozonated autohemotherapy. Recirculation decreases after ozonotherapy in the majority of patients.on average by 35.3%, but the change does not reach the level of statistical significance (P = 0.064). We demonstrate that ozonated autohemotherapy does not influence dialysis adequacy and the frequency of dialyzer reuse. The improvement of fistula function, expressed as a decrease in recirculation, is not significant, although seen in the majority of patients.     

Vascular endothelial growth factor and soluble FLT-1 receptor interactions and biological implications

Vascular endothelial growth factor (VEGF), binding to an appropriate receptor like FLT, is the main mitogen for endothelial cells and a strong inducer of angiogenesis. A soluble form of VEGF receptor, sFLT-1, specifically binds VEGF and inhibits its activity. The following expression plasmids were used in the experiments: pVEGF plasmid encoding VEGF165, pFGF-2 encoding FGF-2 and psFLT-1 plasmid encoding the soluble form of VEGF receptor, sFLT-1. The interaction between VEGF and sFLT-1 was evaluated using a migration test and ERK1/2 activity utilizing mouse sarcoma cells (L-1). Implication of the VEGF/sFLT-1 action was also visualized using in vivo angiogenesis assay. The conditioned medium (CM) from L-1 phVEGF-165 transfectants stimulated L-1 cell migration more than medium from non-transfected L-1 cells. Media collected from phVEGF-165 transfectants or original L-1 cells only slightly stimulated the migration of cells transfected with psFLT-1. The L-1 cells also showed intensive phospho-ERK1/2 activity when treated with the CM from VEGF transfectants. In vivo tests showed that sFLT-1 effectively suppressed VEGF-mediated angiogenesis without affecting FGF-2-driven angiogenesis. To summarize, this study documented that sFLT-1 released from transfected cells might inhibit cell functions induced by VEGF, but not by FGF. The results obtained from in vivo angiogenesis tests also confirm the antiangiogenic potency of cloned sFLT-1, which can be useful for planning cancer experimental therapy studies.     

Neuregulin signaling through a PI3K/Akt/Bad pathway in Schwann cell survival

beta-Neuregulin (betaNRG) is a potent Schwann cell survival factor that binds to and activates a heterodimeric ErbB2/ErbB3 receptor complex. We found that NRG receptor signaling rapidly activated phosphoinositide 3-kinase (PI3K) in serum-starved Schwann cells, while PI3K inhibitors markedly exacerbated apoptosis and completely blocked NRG-mediated rescue. NRG also rapidly signaled the phosphorylation of mitogen-activated protein kinase (MAPK) and the serine/threonine kinase Akt. The activation of Akt and MAPK in parallel pathways downstream from PI3K resulted in the phosphorylation of Bad at different serine residues. PI3K inhibitors that blocked NRG-mediated rescue also blocked the phosphorylation of Akt, MAPK, and Bad. However, selective inhibition of MEK-dependent Bad phosphorylation downstream from PI3K had no effect on NRG-mediated survival. Conversely, ectopic expression of wild-type Akt not only enhanced Bad phosphorylation but also enhanced autocrine- and NRG-mediated Schwann cell survival. Taken together, these results demonstrate that NRG receptor signaling through a PI3K/Akt/Bad pathway functions in Schwann cell survival.     

Phase-locked responses to pure tones in guinea pig auditory cortex

Phase-locked responses to pure tones are a characteristic of most auditory cells at the level of the brain stem and allow sophisticated analyses based on coincidence detection. Phase-locking to tones has not previously been shown at the level of the auditory cortex in single unit studies. We have now identified phase-locked responses in 10% of low-frequency (< 1 kHz) units in the ventrorostral belt, a strip of cortex immediately ventral to the primary auditory area. All of these units showed phase-locking in their response to binaural tone pips of 60-200 Hz and showed narrow band pass characteristics within this range.     

Randomized placebo-controlled study on the effects of losartan and carvedilol on albuminuria in renal transplant recipients

BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg. RESULTS: The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected. CONCLUSION: Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.     

Effect of different hemodialysis regimens on genomic damage in end-stage renal failure

Patients with end-stage renal disease display enhanced genomic damage that may have pathophysiologic relevance for cancer development and cardiovascular complications. We investigated to what extent the genomic damage in peripheral blood lymphocytes can be modulated #1: by initiation of standard hemodialysis (SHD) in formerly conservatively treated end-stage renal disease patients, #2: by a switch from SHD to hemodiafiltration, and #3: daily dialysis (DHD). Genomic damage was evaluated by the micronuclei (MN) frequency test and the comet assay (CA). In a prospective study we found that initiation of SHD did not induce significant changes of genomic damage in peripheral blood lymphocytes whereas the change to hemodiafiltration improved the percentage of DNA in the tail as measured by CA without modulating the MN frequency. In a cross-sectional investigation the degree of genomic damage as evaluated by MN frequency was significantly lower in a patient group treated by DHD as compared with a group treated by SHD. In the DHD patients there also was a significant decrease of the plasma concentrations of urea and the advanced glycation end products imidazolone A, carboxymethyllysine, and of advanced glycation end product-associated fluorescence.     

Blood coagulation unaffected by ozonated autohemotherapy in patients on maintenance hemodialysis

BACKGROUND: Ozonated autohemotherapy (O(3)-AHT) is a clinically useful therapeutic procedure in hemodialyzed patients with peripheral arterial occlusive disease (PAOD). The majority of patients on dialysis are in a hypercoagulable state. Thrombotic complications are the major cause of morbidity and mortality in hemodialyzed patients. Effects of O(3)-AHT on blood coagulation were evaluated in 11 hemodialyzed patients affected by PAOD. METHODS: We performed an oxygen-controlled, crossover study in which nine sessions of autohemotherapy with oxygen administration (AHT) as a control were followed by nine sessions of O(3)-AHT. Blood coagulation was assessed by antithrombin III, activated partial thromboplastin time, prothrombin time, D-dimer and fibrinogen plasma concentrations. RESULTS: The extents of all the measured parameters after nine sessions of O(3)-AHT did not differ statistically from the values after nine sessions of AHT. Similarly, there were no differences in the measured variables after the first session of O(3)-AHT as compared to the values before therapy. We did not observe any thrombotic accidents during the study. CONCLUSIONS: O(3)-AHT with ozone concentration of 50 microg/mL and citrate as an anticoagulant does not influence blood coagualation parameters in hemodialyzed patients with PAOD.     

Quality-of-life evaluation in an interferon therapy after radical surgery in cutaneous melanoma patients

Melanoma is the fastest growing solid tumor in men and women, and despite accounting for only 4% of skin cancer cases, it accounts for more than 79% of skin cancer-related deaths. The present study was designed to evaluate the impact of interferon (IFN) treatment on patients' quality of life (QOL) after radical surgery of cutaneous melanoma. The tests were carried out in a group of patients treated in the Department of Soft Tissue and Bone Cancer, Institute of Oncology, in Warsaw. The present study included 2 groups of the patients, 110 persons each. One group consisted of patients who had been subjected to radical surgery of cutaneous melanoma, and the other one consisted of 110 patients treated with a supplementary interferon alfa-2b (IFN-alpha-2b) therapy. Data were collected by means of an anonymous QLQ-C30 (version 2.0.) questionnaire elaborated and provided by the European Organisation for Research and Treatment of Cancer. The QLQ-C30 questionnaire consisted of 43 questions. The IFN-alpha-2b treatment significantly affected patients' physical condition, mental health, and social life. The emotional state of the patients was more affected during IFN-alpha-2b treatment. Somatic symptoms were also increased in those patients. The IFN-alpha-2b therapy also significantly affected family and social life. In spite of several adverse effects, the patients assessed their QOL as good. The IFN-alpha-2b treatment is troublesome for the melanoma patients. It is important that the treating physician and nurse should be aware of the 4 major categories of IFN-alpha-2b toxicity: constitutional, neuropsychiatric, hepatic, and hematologic. A number of steps can be taken to minimize the morbidity associated with IFN-alpha-2b therapy, resulting in an improvement in both QOL and patient compliance.