ABSTRACT
Photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad (Pd-bacteriopheophorbide) was investigated as an alternative modality for treating prostate cancer. Photodynamic effects on the prostate gland and its adjacent tissues were evaluated in a canine model. Interstitial prostate PDT was performed by irradiating individual lobes with a cylindrical diffuser fiber at various drug/light doses. The sensitivity of the adjacent tissues to Tookad PDT was determined by directly irradiating the surface of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathological examination. PDT-induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus appeared to be sensitive to PDT although the Tookad PDT-induced responses in these tissues were minimal compared to that of the prostate gland at the same dose levels. Nevertheless, the protection of the adjacent tissues should be taken into consideration during the total prostate ablation process due to their sensitivity to PDT. The sensitivity of the prostatic urethra is worth further investigation. Direct intraurethral irradiation might provide an ideal means to determine the sensitivity of the prostatic urethra and might lead to transurethral PDT protocols for the management of benign prostatic hyperplasia (BHP).
Subject(s)
Bacteriochlorophylls/pharmacology , Photochemotherapy , Photosensitizing Agents/pharmacology , Prostate/drug effects , Prostate/radiation effects , Abdomen/radiation effects , Animals , Colon/drug effects , Colon/radiation effects , Dogs , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Male , Neurons/drug effects , Neurons/radiation effects , Urinary Bladder/drug effects , Urinary Bladder/radiation effectsABSTRACT
OBJECTIVE: Our aim is to investigate the effects of photodynamic therapy (PDT) on peripheral nerve conductivity. BACKGROUND DATA: Interstitial PDT has been demonstrated as a promising treatment modality for prostate cancer. However, the sensitivity of nerves, in the immediate vicinity of the prostate gland, to PDT procedures has not been studied. This study attempts to establish an in situ canine model to evaluate direct PDT effect on peripheral nerves. METHODS: PDT was performed by irradiating the cutaneous branches of the saphenous nerve at 763 nm with light doses of 50-200 J/cm2 after i.v. infusion of the photosensitizer Tookad (0-2 mg/kg). Evoked compound-action potentials (CAP) were recorded directly from the surface of the saphenous nerve. The latencies to onset and conduction velocities were determined during PDT and 1-week post-PDT. RESULTS: Nerve and surrounding tissue damage corresponded well with drug/light doses. With Tookad doses of 2 mg/kg, treatment with 50 J/cm2 induced little change in saphenous nerve conduction properties. However, treatment with 100 J/cm2 resulted in localized nerve injury and decreases in nerve conduction velocities, and treatment with 200 J/cm2 severely damaged the nerve. CONCLUSIONS: This canine model adequately demonstrates effects of Tookad PDT on peripheral nerves. Direct irradiation of 100-200 J/cm2 can alter nerve conduction and induce nerve damage. Therefore, possible side effects of interstitial PDT on the pelvic plexus need to be investigated in future studies.
Subject(s)
Action Potentials/drug effects , Action Potentials/radiation effects , Peripheral Nerves/drug effects , Peripheral Nerves/radiation effects , Photochemotherapy , Animals , Bacteriochlorophylls/pharmacology , Dogs , Dose-Response Relationship, Drug , Male , Models, Animal , Neural Conduction/drug effects , Neural Conduction/radiation effects , Photosensitizing Agents/pharmacologyABSTRACT
BACKGROUND: the neuropeptides most consistently reported to be altered in Alzheimer's disease are corticotropin-releasing factor and somatostatin (somatotropin-release inhibiting factor), although this has been previously assessed in a limited number of brain regions. METHODS: in order to comprehensively characterize the involvement of these two anatomically distinct neuropeptide systems in Alzheimer's disease and to determine if they are equally involved in the associated pathology, we measured the concentration of corticotropin-releasing factor and somatostatin in post-mortem brain tissue. Radioimmunoassay of 24 cortical and 13 sub-cortical brain regions from 16 cases of neuropathologically confirmed AD and 9 non-Alzheimer's disease controls were performed and significant differences in group regional neuropeptide concentrations were sought using the Student Newman-Keuls test after ANOVA. RESULTS: comparison of group mean regional neuropeptide concentrations revealed several brain regions where both peptides were decreased in Alzheimer's disease and some regions where only one of the two peptides were decreased, while still other regions exhibited no changes in either peptide. These changes were principally found in frontal and temporal cortex, with few subcortical regions exhibiting pathologic changes in peptide concentration. Regional peptide content was correlated among peptides and with duration of dementia in several brain regions. CONCLUSIONS: these data support the hypothesis that the somatostatin- and corticotropin-releasing factor containing neurons are pathologically involved in AD and that the involved neurons are limited to specific areas of the brain.
