High efficacy of photodynamic therapy on rat endometrium after systemic administration of benzoporphyrin derivative monoacid ring A

BACKGROUND: The aim of this study was to evaluate the effect of the benzoporphyrin derivative monoacid ring A (verteporfin)‐mediated photodynamic therapy (PDT) on rat endometrium and to determine the optimal drug concentration for endometrial ablation. METHODS: Five minutes after i.v. injection of different concentrations of verteporfin into 24 female Sprague-Dawley rats, 630nm light treatment was delivered for 500 s (120J/cm2) to the left horn of the uterus. The 24 rats were divided into six groups according to the drug dose injected, four rats per group: group I (2 mg/kg), group II (1 mg/kg), and groups III, IV, V and VI with 0.5, 0.25, 0.125 and 0.0625mg/kg respectively. Four days later, the rat uteri were analysed by light microscopy. RESULTS: Endometrial destruction was seen in all six groups, with the most significant result in group I (P < 0.008). Conservation of the myometrium was most significant in groups III, IV, V and VI. Acute inflammatory cells in the stromal endometrium were recorded mainly in groups I and II. However, the drug dosage that was most significant in destroying the glands with conservation of the myometrium and not causing severe inflammation was between 0.5 and 0.125mg/kg. CONCLUSIONS: Verteporfin was effective in endometrial ablation in all our animal groups, and the dose range of 0.5-0.125mg/kg appeared to be adequate. This observation will have to be scaled for clinical applicatio

Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and their value in predicting tumor progression

BACKGROUND: Cell cycle proteins are important markers in predicting tumor behavior in urothelial carcinoma of the bladder. The objectives of this study were 1) to determine the expression levels of some of those markers in a series of patients with bladder carcinoma, 2) to define their value in distinguishing T1a (minimally invasive) from T1b (invasive) tumors, and 3) to evaluate their use as predictive factors in the progression of T1a and T1b tumors. METHODS: Tumor specimens from 101 patients were included (22 Ta specimens, 34 T1a specimens, 15 T1b specimens, and 30 T2 specimens). A tissue microarray from the 101 paraffin embedded tissue blocks was constructed. Immunohistochemistry for p16, p27, p21, p53, cyclin D1, and Ki-67 were performed. To evaluate T1a and T1b tumor progression, clinical and follow-up data were available for all 49 patients. RESULTS: Cyclin D1 and p27 were the only markers that showed a significant association with tumor stage and tumor grade (cyclin D1: P = 0.002 and P > 0.00, respectively; p27: P = 0.024 and P = 0.031, respectively). The results indicated that a combination of p21 (odds ratio, 5.7; 95% confidence interval [95% CI], 1.3-24.8 [P = 0.022]) and p16 (odds ratio, 3.7; 95% CI, 0.8-16.5 [P = 0.081]) may have potential use in distinguishing T1b tumors from T1a tumors. Finally, none of the markers examined were found to have predictive value for T1a and T1b tumor progression. CONCLUSIONS: The expression of cyclin D1 and p27 was associated with the most important prognostic factors (tumor stage and grade). The combination of p21 and p16 may have value in distinguishing T1b tumors from T1a tumors, although this finding must be evaluated in much larger series. Finally, none of the markers studied appeared to have predictive value for disease progression in patients with T1a and T1b urothelial bladder tumors

High efficacy of photodynamic therapy on rat endometrium after systemic administration of benzoporphyrin derivative monoacid ring A

BACKGROUND: The aim of this study was to evaluate the effect of the benzoporphyrin derivative monoacid ring A (verteporfin)-mediated photodynamic therapy (PDT) on rat endometrium and to determine the optimal drug concentration for endometrial ablation. METHODS: Five minutes after i.v. injection of different concentrations of verteporfin into 24 female Sprague-Dawley rats, 630 nm light treatment was delivered for 500 s (120 J/cm(2)) to the left horn of the uterus. The 24 rats were divided into six groups according to the drug dose injected, four rats per group: group I (2 mg/kg), group II (1 mg/kg), and groups III, IV, V and VI with 0.5, 0.25, 0.125 and 0.0625 mg/kg respectively. Four days later, the rat uteri were analysed by light microscopy. RESULTS: Endometrial destruction was seen in all six groups, with the most significant result in group I (P < 0.008). Conservation of the myometrium was most significant in groups III, IV, V and VI. Acute inflammatory cells in the stromal endometrium were recorded mainly in groups I and II. However, the drug dosage that was most significant in destroying the glands with conservation of the myometrium and not causing severe inflammation was between 0.5 and 0.125 mg/kg. CONCLUSIONS: Verteporfin was effective in endometrial ablation in all our animal groups, and the dose range of 0.5-0.125 mg/kg appeared to be adequate. This observation will have to be scaled for clinical application

Implication of dipeptidylpeptidase IV activity in human bronchial inflammation and in bronchoconstriction evaluated in anesthetized rabbits.

BACKGROUND: Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis. OBJECTIVE: To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation. METHODS: DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits. RESULTS AND CONCLUSIONS: DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor