changes in expression of platelet derived growth factor [PDGF] and PDGF receptor in rat corpus cavernosum after exposure to in vivo hypoxia and cigarette smoking

Platelet derived growth factor [PDGF] over activity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension [hypoxia] and cigarette smoking is a known stimulus for transcriptional induction of [PDGF] ligand and receptor gene. We studied the expression of [PDGF-A] and [PDGFR-beta] in adult male rat isolated corpus cavernosum under hypoxic and cigarette smoking conditions being associated with induction of fibrosis which may lead to erectile dysfunction. Fifty adult male albino rats were used in this experiment. They were divided into 5 groups. Group I [n=10], served as control group. Group II [n=10] rats exposed to acute hypoxia. Group III [n=10] rats exposed to chronic hypoxia. Group IV [n=10] rats exposed to acute cigarette smoking. Group V [n=10] rats exposed to chronic cigarette smoking. In all groups at the end of each experiment corpora cavernosa of all rats were carefully dissected and freed from surrounding tunica albuginia then frozen in -80°C for subsequent reverse transcriptase polymerase chain reaction [RT-PCR]. In all groups of rats PDGF-A and PDGR-m RNA were measured. There was significant increase in PDGF-A mRNA and PDGF- beta receptor in acute hypoxic group, chronic hypoxic group, and chronic cigarette smoking groups of rats compared to control group. It was found that hypoxia, whether, acute or chronic have similar effect of increasing PDGF-A mRNA and PDGF-beta receptor as well as chronic cigarette smoking group of rats. This may lead to erectile dysfunction

Angiogenic factors in Egyptian bladder cancer patients

Bladder cancer is the second most common urological cancer with an estimated 53,200 diagnosed cases and 12,100 resultant deaths in the year 2000. The incidence of bladder cancer has increased over the past two decades due to improved detection rate of the early stages of the disease i.e. superficial bladder cancer, while the decreasing mortality rate results from a decrease in the incidence of invasive and metastatic form of the disease and improvement in the therapy. Angiogenesis is a prerequisite for normal growth and development and abnormal angiogenesis is a critical feature of many diseases including cancers. The molecules that stimulate angiogenesis are called antigenic factors and are released by tumour cells or leukocytes within the turnour. This submitted work has been performed to fulfill the following objectives: 1- Determination of the angiogenic stimulators, Platelet derived growth factor [PDGF] and nitric oxide [NO] in sera as well as basic fibroblast growth factor [bFGF], hyaluronic acid [HA] and hyauronidase [HAase] in urine of patients with bladder cancer as well as reference healthy persons and patients with benign bladder lesions for comparison. 2- Matching of the assayed measures to be correlated with clinicopathological criteria of patients. The current study included 60 patients divided into two groups: I] Group 1: included 30 patients who were already diagnosed as bladder cancer by cystoscopy and biopsy, and further subdivided into 2 subgroups according to the histopathological picture of their cancer tissues into: A] Squamous cell carcinoma [76.7%] included 22 patients B] Transitional cell carcinoma [23.3%] included 8 patients II] Croup II: included 30 patients with benign bladder lesions subjected to: 1] Thorough clinical examination. 2] Urine analysis 3] complete blood picture. 4] Cystoscopy. 5] Biopsy and histopathological examination of the tissue sample. The study also included 14 reference healthy subjects. The work has concluded that serum levels of PDGF were significantly higher [p<0.0001] in patients with bladder cancer compared with both of benign -bladder diseases and the -healthy subjects. Meanwhile, serum levels of PDGF were also significantly higher in-patients with benign bladder diseases compared to healthy persons. Measured bFGF in the urine of patients with bladder cancer was significantly higher with respect to those with benign lesions as well as the reference healthy cases. [P<0.0001]. Urinary HA of bladder cancer patients was also significant higher than those with benign bladder lesion or health persons [p<0.0001]. Urinary HA ase activity was found to be significantly higher in the patients with bladder cancer compared to those with benign bladder lesions and the health pet [P<0.0001]. The serum concentrations of nitric oxide were significantly higher in-patients bladder cancer compared to those with benign with bladder diseases and the healthy group [P< 0001]. This work obviates that measured angiogenic factors [PDGF and bFGF] have a domain role in development of bladder cancer. Hence, angiogenic inhibitors and as beneficial components as adjuvant therapy with surgery, chemotherapy radiotherapy

Effect of P53 antibodies, interleukin-10, platelet derived growth factor and nitric oxide on apoptosis in discoid and systemic lupus erythematosus and systemic sclerosis

This study included seventy patients with systemic lupus erythematosus [SLE, twenty-five patients], systemic sclerosis [SSc, twenty-five patients] and discoid lupus erythematosus [DLE, twenty patients]. The study also included fifteen healthy subjects of comparable age as controls. P53 antibodies were detected in 32% of SLE, 20% SSc and 10% of DLE patients, while they were undetectable in sera of the controls. Serum IL-10, PDGF and NO were significantly higher in SLE, SSc and DLE compared with controls [except for PDGF in DLE]. NO and PDGF were significantly higher in SLE than either SSc or DLE patients. Circulating P53 antibodies were significantly correlated with IL-10, PDGF and NO in all studied groups of patients. Only in SLE patients, disease activity score significantly correlated with the studied bioindices except IL-10. From the revealed results, patients with SLE, SSc and DLE had changes in the aforementioned biochemical factors which might had a role in the defective apoptotic process which occurs in these autoimmune diseases

Stress and atherogenesis: smooth muscle cell mitogenic activity and other biochemical changes associated with sera of stressed subjects

The proliferation of smooth muscle cells in the arterial wall [VSMC] is considered to play a key role in the development of atherosclerosis. To investigate the possible contribution of "stress" [experimentally induced] to this process, blood from healthy volunteers, ages 21 to 65, screened to exclude major risk factors for coronary heart disease, was assayed for mitogenic activity after the subjects were exposed to one of 2 "stress" conditions. These consisted of a cognitive task with superimposed verbal harassment [group 1], and the cognitive task without harassment [group 2]. Mitogenic activity was determined by studying the growth stimulatory effects of PDGF-depleted plasma derived serum [PDS] from "stressed" subjects added to cultured VSMC, as measured by incorporation of radioactive thymidine into DNA or increase in cell number. In addition, changes in the steady state of the mRNA for the c-myc protooncogene were also assayed in VSMC by Northern blot analysis, using sera showing the greatest differential "pre/post stress" mitogenic activity. Blood pressure [BP], heart rate [HR], cortisol, and serum total and HDL cholesterol were also evaluated. All measurements were made immediately before [baseline] and after a 30 min interval. Analysis of the data revealed that there were 33% of subjects in group 1 with an increase of thymidine incorporation 15% or greater than baseline, versus 21% in group 2. The average increases were 45% and 30%. A higher percentage [35-42%] of subjects in group 1 responded with increases in systolic and diastolic blood pressure, compared to subjects in group 2 [15-20%]; the average in blood pressure was 10-15%. Similarly, more subjects [52%] in group 1 had an elevated [average 10-15%] serum cortisol, compared to the 42% in group 2 subjects. HR, total HDL cholesterol showed slight changes only. These results suggest that psychoactive factors may affect cardiovascular systems via rapid elicited rises in serum mitogenic activity for VSMC