Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.     

How can we predict ureteral obstruction after gynecological surgery? The changes in Doppler resistive index and plasma creatinine and magnesium concentrations after surgical, unilateral ureteral obstruction in a rabbit model

The aim of this study is to evaluate the changes in Doppler resistive index (RI) and plasma creatinine and magnesium concentrations after unilateral ureteral obstruction in a rabbit model. Fourteen adult female rabbits were used in this study. In seven rabbits, the left ureter was ligated with silk suture, and the control group was sham operated. Before surgery and on the second and seventh days after surgery, blood samples were obtained to measure plasma creatinine and magnesium concentrations. Doppler RIs of both kidneys were also measured before surgery and on the second and seventh days after the surgical procedure. With regard to magnesium levels, there was a significant within-subjects sessions difference [F(2, 20) = 15.21, P= 0.001] indicating a decrease through sessions. Magnesium concentrations decreased significantly at the postoperative second and seventh days compared to preoperative baseline levels (P= 0.003 and P= 0.001, respectively). Multifactorial analysis of variance was applied for each session separately with laterality, and groups as factors. The Doppler RI and the creatinine level did not show any significant differences or interactions for all sessions (P > 0.05). The decreasing plasma magnesium concentration after surgery may indicate ureteral injury; however, Doppler studies and creatinine levels may not be useful as well.     

Short-term subjective efficacy of doxazosin in predicting probability of prostatectomy in the management of benign prostatic hyperplasia in patients with severe symptoms

BACKGROUND: The severity of symptoms still constitutes the major indication for transurethral prostatectomy, despite the extensive utilization of medical treatments. The aim of the study presented here was to investigate the impact of doxazosin on symptoms in relation to the probability of consequent surgery in severely symptomatic patients. METHODS: Patients with an International Prostate Symptom Score (IPSS) between 18 and 35 were included in the study. The patients received 4 mg/day doxazosin, and subjective efficacy was assessed by IPSS at the first and third months. In addition, the patients were classified at the third month according to a single question regarding satisfaction with medical treatment in terms of symptom relief as 'ineffective, no change, and effective'. RESULTS: A total of 178 patients constituted the study group. Mean total symptom scores were 24, 19 and 17 at baseline, first and third months, respectively (P < 0.05). According to results of the questionnaire, 23% of the patients claimed the treatment was ineffective, and subsequently, the majority of this group (93%) underwent prostatectomy in a year. In addition, 33% of the patients reported no change in their symptoms, while 44% reported that the medication was effective. However, after 1 year, 59% and 15% of these cases underwent surgical treatment, respectively. The probability of surgery in the 'ineffective' group was significantly higher compared to the remaining groups (P < 0.05). CONCLUSION: The majority of patients with severe symptoms who were not satisfied with the medication at the 3rd month underwent surgery. This observation may provide a predictor for subsequent probability of prostatectomy. Therefore, reassessment of patients would be a cost-effective approach for the treatment of BPH in severely symptomatic patients.     

PENILE ANATOMY UNDER THE PUBIC ARCH: RECONSTRUCTIVE IMPLICATIONS

PURPOSE: We have previously defined the anatomy of the neurovascular bundle in the normal and hypospadiac penis. These studies were based on analysis of the fetal penis distal to the pubic arch without total inclusion of the crural bodies. To our knowledge the neuroanatomy beneath the pubic arch has not been well described. We defined the nerve distribution under the pubic arch and the relationship of the nerves to the crural bodies, corporeal bodies and urethra of the penis. MATERIALS AND METHODS: Eight normal human fetal penile specimens (at 17.5 to 29 weeks of gestation and 1 hypospadiac specimen at 32 weeks were serially sectioned and stained with Masson's trichrome, and the neuronal markers protein gene product 9.5 and S-100. These specimens were unique in that they contained the whole penis from the glans to the crural bodies beneath the pubic arch. Older specimens were decalcified before fixation. Computer reconstruction with commercially available graphics software allowed 3-dimensional analysis of the nerves and crural bodies in relation to the pubic arch and surrounding structures. RESULTS: The nerves of the penile shaft and glans surrounded the corporeal bodies, extending from the junction of the urethral spongiosum to the classic 11 and 1 o'clock positions with a paucity of nerves at the 12 o'clock position in the dorsal midline. Beneath the pubic arch the nerves to the penis were an extension of the dorsal neurovascular bundle of the prostate. The nerves formed 2 bundles following a path just under the pubic arch in close proximity to the bone, superior to the urethra and medial to the origin of the crural bodies. The nerve bundles joined the corporeal bodies at the proximal origin, where the 2 crural bodies fused together. At this point perforating branches into the corporeal bodies from the cavernous nerves were documented. As the dorsal nerves joined the dorsal aspect of the corporeal bodies, they immediately began to fan out along the surface of the corporeal tissue to the junction of the urethral spongiosum. Three-dimensional reconstruction showed the relationship of the nerves to the pubic arch and urethra in multiple views. CONCLUSIONS: A precise understanding of penile anatomy beneath the pubic arch and at the origin of the crural bodies is important for preserving neuronal structures. This anatomy is especially germane in children undergoing posterior urethral reconstruction secondary to trauma, intersex requiring feminizing genitoplasty and severe hypospadias.     

Protective effects of trapidil in ischemia–reperfusion injury due to testicular torsion and detorsion: An experimental study

OBJECTIVE: We aimed to detect the preventive effects of trapidil in ischemia-reperfusion (IR) injury due to testicular torsion and detorsion. METHODS: Forty prepubertal albino rats were used. In the IR group, torsion was created by rotating the left testis over 2 h, and detorsion was done by untwisting the testis. Bilateral orchiectomies were performed after 4 h. In study group, 2-h torsion was performed and trapidil was administered as a single dose 1 h before detorsion. Bilateral orchiectomies were performed after 4 h. In the sham group, a sham operation was done. In the sham plus trapidil group, a sham operation was done and trapidil was administered as a single dose. Testicular tissue malondialdehyde (MDA), nitric oxide (NO) and total sulfhydryl (T-SH) levels were determined for each group. The grades of interstitial injury were determined in histopathologic examination. RESULTS: The NO and MDA levels in the IR group were significantly higher than the study, sham and sham plus trapidil groups in the left testis (P<0.05, P<0.001 and P<0.001, respectively). A statistical difference was not found among study, sham and sham plus trapidil groups in the left testis in NO and MDA levels (P>0.05). The T-SH level in the study group was significantly higher than in the IR, sham and sham plus trapidil groups in left testis P<0.05). In the IR group (left testis), grade 1 interstitial injury was 30% (3/10), grade 2 injury was 60% (6/10) and grade 3 injury was 10% (1/10). In the study group (left testis), grade 1 interstitial injury was 30% (3/10) and there was no injury in 70% (7/10). CONCLUSION: Trapidil decreased free oxygen radical formation in testicular torsion and detorsion, and attenuated histopathological damage in the ipsilateral twisted testis.     

Extensive cutaneous metastasis of transitional cell carcinoma of the bladder

Cutaneous metastasis of bladder carcinoma is extremely rare. Iatrogenic implantations have been the main cause in the majority of cases of transitional cell carcinoma with cutaneous metastasis. Otherwise, primary cutaneous metastasis is accepted as the late manifestation of systemic spread. The present paper describes a case of relatively early and extensive skin metastasis of transitional cell carcinoma in a 78-year-old man. The patient had a histopathological diagnosis of poorly differentiated (grade III) muscle invasive transitional cell carcinoma with a staging of T2NOMO 6 months prior to presenting. He presented to our outpatient clinic with a 3-month history of skin lesions as multiple, rubbery subcutaneous nodules. Radiological reinvestigation revealed no other metastatic site (including bone and lung), except for a metastatic nodule in the liver. The present paper reports an interesting and rare case of extensive skin metastasis of transitional cell carcinoma as the primary complaint.     

Therapeutic efficacy of sequential and simultaneous treatments with interferon-α and lamivudine in children with chronic hepatitis B

BACKGROUND: Interferon (IFN)-alpha and lamivudine (LAM), a nucleoside analog, are frequently used drugs for the treatment of chronic hepatitis B (CHB), and their combined therapy has been shown to be effective. The purpose of the present study was to examine the therapeutic efficacy of sequential and simultaneous combination therapies of IFN-alpha and LAM in children with CHB. METHODS: A total of 45 children with CHB, whose antibody status was positive for hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and HBV-DNA at least for 6 months; who had alanine aminotransferase (ALT) levels 1.5-fold higher than normal and hepatic activity index scores higher than 6, were allocated to two groups. The first group included 24 children who were given standard dose IFN-alpha (5 MU/m(2) s.c., thrice weekly) for 6 months, followed by LAM (4 mg/kg per day per oral, maximum 100 mg/day) for an additional 6 months (sequential therapy group). The second group included 21 children who were given IFN-alpha and LAM therapy simultaneously for 6 months and who continued with LAM alone for another 6 months (simultaneous therapy group). Partial response was defined as normalization of ALT and eradication of HBV-DNA. Complete response was defined as normalization of ALT, eradication of HBV-DNA and e seroconversion. Non-responders were defined as having positive HBV-DNA and abnormal ALT levels. Sustained response was defined as absence of HBsAg and presence of hepatitis B surface antibody (anti-HBs). RESULTS: The mean age of the sequential therapy group was 12.7 +/- 4.1 years, and 16 (66.7%) of the patients were male. The mean age of the simultaneous therapy group was 14.8 +/- 4.6 years, and 15 (71.4%) were male. In the first group, 13 patients (54.2%) were non-responders; partial response was observed in five patients (20.8%), and complete response was seen in six patients (25%). Despite the occurrence of e seroconversion, normalization of ALT was not achieved in one case. In the second group, which consisted of 21 patients, 11 subjects (52.4%) were non-responders; partial response was observed in one case (4.8%), and complete response was seen in seven (33.3%). Sustained response was found in two patients (9.5%). There were no significant differences between the groups (P > 0.05). CONCLUSION: When the therapeutic efficiency of two different treatment regimens applied for 1 year was evaluated in childhood CHB therapy, it was remarkable that there was a sustained response and a higher complete response in group 2, although there was no considerable difference between the therapy results of both groups.     

Adjuvant effect of vitamin A on recurrent lower urinary tract infections

BACKGROUND: The purpose of the present paper was to investigate the effects of vitamin A supplementation on recurrent lower urinary tract infections (RUTI). METHODS: Twenty-four patients with non-complicated RUTI were included in a placebo-controlled, double-blinded study. Twelve patients received a single dose of 200,000 IU vitamin A in addition to antimicrobial therapy. Patient and control groups (each containing 12 patients) were followed for up to 1 year and were evaluated for eradication and frequency of lower urinary tract infections (UTI). Serum levels of vitamin A and beta-carotene were determined periodically. RESULTS: During the first 6 months follow-up period the infection rate of the vitamin A-supplemented group reduced from 3.58 to 0.75 per 6 months, and in the subsequent 6 months the infection rate was 1.75 per 6 months. These values were calculated as 2.75, 2.83 and 2.66, respectively, in the placebo group. CONCLUSION: Vitamin A supplementation may have an adjuvant effect on the treatment of RUTI.