Oxidative stress and neurodegeneration in penile ischaemia

OBJECTIVE

To seek markers of oxidative stress and examine neural structural integrity in chronic penile ischaemia using a rabbit model of arteriogenic erectile dysfunction (ED), as the role of ischaemia in penile neuropathy and the oxidative mechanism of neurodegeneration in ED remains unknown.

MATERIALS AND METHODS

A rabbit model of atherosclerosis‐induced ED was developed by partial balloon de‐endothelialization of the iliac arteries. After 10 weeks, intracavernosal blood flow and erectile function in the arteriogenic ED group were compared with age‐matched controls. Erectile tissues were processed for analysis of oxidative stress markers and nerve fibre density using enzyme immunoassay and immunohistochemical staining, respectively. Oxidative stress‐sensitive genes were determined with quantitative real‐time polymerase chain reaction. Tissue ultrastructure was examined by transmission electron microscopy.

RESULTS

Significant erectile tissue ischaemia, erectile dysfunction, increased levels of oxidative products, and marked nitrotyrosine immunoreactivity was evident in the ED group. Oxidative stress‐sensitive genes encoding hypoxia inducible factor‐1α (HIF‐1α), superoxide dismutase (SOD), aldose reductase (AR) and nerve growth factor (NGF) were up‐regulated in the ischaemic erectile tissue. These changes were associated with collapsed axonal and Schwann cell profiles, neurodegeneration, mitochondrial structural damage, increased caveolae, loss of endothelium, and sporadic vacuolization.

CONCLUSIONS

Neuropathy appears to follow the vascular insult in arteriogenic ED. Neural injury in penile ischaemia involves a neurovascular phenomenon mediated by oxidative free radicals. Mitochondrial structural damage and increased HIF‐1α gene expression may be early signals of oxidative stress and neurodegeneration in ED. Up‐regulation of SOD, AR and NGF may be a coordinated defensive reaction to oxidative radicals that seems to fail to prevent neural injury in the ischaemic penis. Our study introduces the concept of oxidative neurodegeneration in the pathophysiology of arteriogenic ED. Therapeutic strategies to protect penile nerves from free radical incursion may enhance the efficacy of surgical and pharmacological interventions in arteriogenic ED.     

Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy

The aim of this study was to evaluate the ferric-reducing ability of serum (FRAS), paraoxonase 1 (PON1), ceruloplasmin serum oxidase activity and hsCRP level in patients with type1 diabetes mellitus without and with diabetic retinopathy. The study was performed in 76 patients with type 1 diabetes mellitus, 35 without diabetic retinopathy (group 1) and 41 with preproliferative and proliferative retinopathy (group 2). Control group consisted of 35 nondiabetic, age-, gender-, body mass-matched healthy volunteers who came to the outpatient clinic for a routine health check-up. We evaluated FRAS using the method described by Benzie and Strain; PON1 by kinetic spectrophotometric assay with paraoxon as substrate and ceruloplasmin using its oxidative activity with 3-phenylenodiamine as substrate. CRP was measured with a high sensitive enzyme immunoassay. PON1 activity was significantly decreased in patients with diabetic retinopathy (227.66 ± 123.57 U/l) when compared with control (312.04 ± 129.77 U/l). FRAS was significantly decreased in group 2 (439.33 ± 79.87 μmol/l) when compared with group 1 (522.79 ± 167.56 μmol/l) and control (529.80 ± 81.99 μmol/l). Ceruloplasmin activity was significantly elevated in group 1 (58.36 ± 22.56 U/g protein) when compared with control (45.22 ± 14.96 U/g protein). We have found significant increase in hsCRP level in group 2 (3.71 ± 2.47 mg/l) when compared with group 1 (1.75 ± 1.01 mg/l) and control (0.57 ± 0.46 mg/l). The PON1/CRP ratio in control group was significantly increased when compared with diabetic patients and was significantly decreased in group 2 compared with group 1. We have not found gender-dependent difference in studied parameters in both control and in study groups. We have found tendency to decrease the serum activity of FRAS and hsCRP in elder patients but the difference was significant only in group 2. FRAS and PON 1 activity is decreased in patients with type 1 diabetes mellitus with presence of diabetic retinopathy which confirms that oxidative stress could play a role in pathogenesis of diabetic retinopathy. Significantly elevated levels of hsCRP in diabetic patients with the presence of diabetic retinopathy compared with patients without diabetic retinopathy providing a link between inflammation and the development of microvascular complication of diabetes. Because of the significant difference in PON1/CRP ratio between patients without and with the presence of diabetic retinopathy, it seems that PON1:CRP ratio may be used as a biochemical marker for progression of retinopathy. The link between the antioxidant concentration, inflammation and the development of diabetes complications needs further longitudinal studies in order to confirm our findings.     

The course of actinomycosis of female reproductive organs mimicking ovarian cancer--the diagnostic limits and difficulties

A case of actinomycosis presenting as tubo-ovarian abscess, misdiagnosed as ovarian malignancy in 54-year old woman with IUD is reported. Author presents the diagnostic problems due to uncommon location, no reliable clinical manifestation and nonspecific CT imaging findings, based on current literature. Knowledge of the characteristic features may help one consider the possibility of actinomycetic infection in the differential diagnosis, in patients with a previous history of predisposing factors and treat them appropriately.     

The comparison of the angles of doppler wave spectrum of blood flow in tumor vessels in case of adnexal masses

OBJECTIVES: To evaluate the usefulness of the measurement of angles of doppler wave spectrum in systolic phase in tumor vessels in adnexal masses and potential usefulness of this parameter in differential diagnosis of these lesions. MATERIAL AND METHODS: The study covers 173 patients with adnexal masses found on the examination. RESULTS AND CONCLUSIONS: The mean value of the measured angles in benign lesions amounted to 65.68 degrees and in malignant lesions 87.79 degrees. Additionally the readings of pulsatility index PI and flow speed: minimal -min, maximal -max and maximal mean -Ta ?r max. in examined vessels were taken into consideration. The statistically significant differences in the angle values of the two groups were noticed, although the usefulness of this single parameter in differential diagnosis of the lesions is not as helpful as usefulness of RI and PI but it is more useful than Ta min, Ta max and Ta ?r max.     

Collagen deposition around polypropylene tapes implanted in the rectus fascia of female rats

OBJECTIVE: Implantation of the mesh induces a foreign-body reaction followed by the development of connective tissue that may alter tape property. The aim of our study was to evaluate the deposition of collagen in the vicinity of monofilament tension-free vaginal tape (TVT; Ethicon Inc., Johnson & Johnson) and multifilament intravaginal slingplasty (IVS; Tyco Healthcare) polypropylene tapes implanted in female rats. METHODS: The samples of the meshes (10 mg each) were implanted in the rectus fascia of 14 Wistar female rats and removed after 42 days. Collagen was extracted with 0.5 M acetic acid and subsequently with pepsin (1 mg/ml in 0.5 M acetic acid). Collagen concentration was measured using Sircol Collagen Assay (Biocolor Ltd.) and normalised for milligrams of tape weight. For histological examination, tape samples were stained with haematoxylin and eosin or with silver for type III collagen. RESULTS: The total amount of collagen extracted did not differ significantly between TVT and IVS samples. For both tapes, extraction with acetic acid yielded a higher amount of collagen (about 70%) than extraction with pepsin. On histological examination, less densely packed bundles of collagen fibres and a slightly more intense inflammatory reaction were observed with TVT compared with IVS mesh. CONCLUSION: The total amount of collagen deposited around the polypropylene mesh implanted in female rats was similar for TVT and IVS meshes, but differences were noted in the arrangement of the collagen fibres and the intensity of the inflammatory reaction.     

The presence of facial nerve weakness on diagnosis of a parotid gland malignant process

The objectives of this article are to assess the frequency and significance of facial paralysis and undiagnosed nerve infiltration in patients with parotid malignancies. 103 patients with parotid gland malignancies were treated in a single institution, the tertiary center for ENT at the University Department in Poznan between 1996 and 2006. Facial palsy at the initial presentation was found in 32 patients. The stage of the primary tumor in the examined group of 103 patients is as follows: 20—T1, 31—T2, 20—T3, 32—T4. The correlation between facial nerve function before treatment and patients’ characteristics, including the treatment methods, were analyzed. Intact facial nerve function at patient presentation was a very strong prognostic factor determining the treatment and final outcome for malignant neoplasms of parotid gland. Similarly, T stage and a high-grade malignant histology had a direct influence on the duration of patients’ survival.     

Association of rash with outcomes in a randomized phase II trial evaluating cetuximab in combination with mitoxantrone plus prednisone after docetaxel for metastatic castration-resistant prostate cancer

Purpose

Cetuximab (C), a chimeric monoclonal antibody that binds epidermal growth factor receptor (EGFR), is active against androgen-independent prostate cancer cell lines and might enhance the activity of chemotherapy. The efficacy of combining cetuximab with mitoxantrone (M) plus prednisone (MP) was evaluated in progressive metastatic castrate-resistant prostate cancer (CRPC) after receiving docetaxel.

Materials and Methods

Patients with progression after receiving docetaxel were eligible and randomized 2:1 to CMP or MP. Therapy was mitoxantrone 12 mg/m² intravenously (I.V.) on day 1, oral prednisone 10 mg daily in both arms, and cetuximab 250 mg/m² I.V. (400 mg/m² day 1, cycle 1) on days 1, 8, and 15 in the CMP arm. Cycles were repeated every 21 days. Radiologic assessments of disease and PSA (prostate-specific antigen) occurred every 4 cycles. The primary endpoint was time to progression (TTP).

Results

A total of 115 patients were enrolled, 75 in the CMP and 40 in the MP arm: the median TTP was 4.9 and 6.6 months, respectively; the measurable disease response rate was 2% and 4%, the PSA response rate 7.7% and 17.6%, and median survival 11.9 and 15.7 months, respectively. Key grade 3-4 toxicities were neutropenia 44% and 25.6%, anemia 6.7% and 7.7%, thrombocytopenia 6.7% and 2.6%, and fatigue 8% in both arms. In an unplanned exploratory analysis, median TTP with (n = 24) and without rash (n = 51) in the CMP arm was 10.3 months vs. 2.8 months (P = .004). On multivariable analysis,rash was significantly associated with TTP (hazard ratio [HR] = 0.43; P = .01).

Conclusions

The treatment with CMP is not recommended in unselected men with docetaxel-treated CRPC, although rash might help develop tailored therapy.     

Changes in expression of human serine protease HtrA1, HtrA2 and HtrA3 genes in benign and malignant thyroid tumors

Human HtrA proteins are serine proteases involved in essential physiological processes. HtrA1 and HtrA3 function as tumor suppressors and inhibitors of the TGF-β signaling pathway. HtrA2 regulates mitochondrial homeostasis and plays a pivotal role in the induction of apoptosis. The aim of the study was to determine whether the HtrA proteins are involved in thyroid carcinogenesis. We used the immunoblotting technique to estimate protein levels of HtrA1, HtrA2, long and short variants of HtrA3 (HtrA3-L and HtrA3-S) and TGF-β1 in tissues of benign and malignant thyroid lesions, and control groups. We found that the levels of HtrA2 and HtrA3-S were higher in thyroid malignant tumors compared to normal tissues and benign tumors. The HtrA3-L level was increased in malignant tumor tissues compared to benign tumor tissues and control tissues from patients with benign lesions, and elevated in normal tissues from patients with thyroid carcinoma compared to normal tissues from patients with benign lesions. We also compared levels of HtrA proteins in follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) and found that these types of carcinoma differed in the expression of HtrA3-S and HtrA1. These results indicate the implication of HtrA proteins in thyroid carcinogenesis suggest that HtrA3 variants may play different roles in cancer development, and that the increased HtrA3-L levels in thyroid tissue could be correlated with the development of malignant lesions. The TGF-β1 levels in tumor tissues were not significantly altered compared to control tissues.