Inhibition of renin and the (pro)renin receptor system.

Renin is the rate-limiting step of the renin-angiotensin system (RAS) and can induce hypertension and cardiovascular diseases (CVDs) through the over-activated renin-angiotensin-converting enzyme (ACE)-angiotensin (Ang) II-Ang II type 1 receptor (AT(1)R) axis. Prorenin and renin bound to the (pro)renin receptor [(P)RR] not only increase the catalytic conversion of angiotensinogen (AGT) to Ang I, but also upregulate the expression of profibrotic genes. This review will discuss the inhibition of renin and the (P)RR system pharmacologically and nutritionally.

Three key proteases--angiotensin-I-converting enzyme (ACE), ACE2 and renin--within and beyond the renin-angiotensin system.

The discovery of angiotensin-I-converting enzyme 2 (ACE2) and a (pro)renin receptor has renewed interest in the physiology of the renin-angiotensin system (RAS). Through the ACE2/angiotensin-(1-7)/Mas counter-regulatory axis, ACE2 balances the vasoconstrictive, proliferative, fibrotic and proinflammatory effects of the ACE/angiotensin II/AT1 axis. The (pro)renin receptor system shows an angiotensin-dependent function related to increased generation of angiotensin I, and an angiotensin-independent aspect related to intracellular signalling. Activation of ACE2 and inhibition of ACE and renin have been at the core of the RAS regulation. The aim of this review is to discuss the biochemistry and biological functions of ACE, ACE2 and renin within and beyond the RAS, and thus provide a perspective for future bioactives from natural plant and/or food resources related to the three proteases.

Assessment of carotid artery dose in the treatment of nasopharyngeal cancer with IMRT versus conventional radiotherapy.

PURPOSE: To determine the radiation dose to the carotid artery in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT) and to compare it to the dose delivered by a conventional three-field (3F) technique. MATERIALS AND METHODS: Sixteen patients with nasopharyngeal cancer who were treated at UCSF with IMRT were selected for this analysis. 3F plans were reconstructed for comparison. The carotid arteries were retrospectively contoured, and the dose received by each of the 32 carotid arteries was determined for both IMRT and 3F plans. A subset of 8 patients with N0/N1 nodal disease was selected for IMRT replanning using additional constraints to reduce the dose to the arteries. RESULTS: Using the standard prescription doses for IMRT and 3F plans, the dose delivered to 95% of the tumor volume was significantly higher in the IMRT plans, reflecting the greater conformality of this technique. The median mean dose to the carotid arteries was 65.7Gy with IMRT vs. 58.4Gy with 3F (p<0.001). After the application of dose constraints to the carotid arteries, it was possible to reduce the mean carotid dose to 54Gy in the IMRT replans. CONCLUSIONS: IMRT achieves a higher tumoricidal dose and superior clinical target volume coverage, but results in an increase in the carotid artery dose as compared to conventional 3F technique. With careful IMRT planning, it is possible to constrain the carotid dose for a subset of patients with low-risk neck disease. Further study is necessary to quantify the long-term clinical impact of this intervention.

Evaluation of different counting methods for use in radiochemical purity testing procedures for 99mTc-labelled radiopharmaceuticals.

The efficiency and accuracy of different methods for quality control of radiopharmaceutical preparations for diagnostic purpose were studied. The radiochemical purity of (99m)Tc Tetrafosmin, (99m)Tc Exametazime, (99m)Tc Sestamibi and (99m)Tc Oxidronate was evaluated by different thin layer chromatography systems, followed by cutting of the strips into two or three sections and by the measurement of radioactivity distribution by dose calibrator or gamma counter. In addition, to confirm the accuracy of these routine procedures, the strips were cut into a number of micro-sections (14-25) and each of them evaluated by the gamma counter. The three tested procedures gave similar results and revealed a good and comparable accuracy. The radioactivity measurement with the dose calibrator remains the most practicable because of the rapidity of execution.

Resveratrol sensitization of DU145 prostate cancer cells to ionizing radiation is associated to ceramide increase.

Radiotherapy is an established therapeutic modality for prostate cancer. Since it is well known that radiotherapy is limited due to its severe toxicity towards normal cells at high dose and minimal effect at low dose, the search for biological compounds that increase the sensitivity of tumors cells to radiation may improve the efficacy of therapy. Resveratrol, a natural antioxidant, was shown to inhibit carcinogenesis in animal models, and to block the process of tumor initiation and progression. The purpose of this study was to examine whether or not resveratrol can sensitize DU145, an androgen-independent human prostate cancer cell line, to ionizing radiation. We report here that DU145 cells are resistant to ionizing radiation-induced cell death, but pretreatment with resveratrol significantly enhances cell death. Resveratrol acts synergistically with ionizing radiation to inhibit cell survival in vitro. Resveratrol also potentiates ionizing radiation-induced ceramide accumulation, by promoting its de novo biosynthesis. This confirms ceramide as an effective mediator of the anticancer potential induced by resveratrol.

Abomasal nematode community in an alpine chamois (Rupicapra r. rupicapra) population before and after a die-off.

Abomasa of 185 chamois shot during 5 consecutive hunting seasons were collected as part of a health monitoring program in an alpine area of Italy and examined for nematodes. The data were obtained during both the preceding period and that following a severe die-off caused by a pneumonia outbreak. Prevalence, mean abundance, mean intensity, and Thul Importance index were consistently high, in particular for Haemonchus contortus, having a low host specificity and high pathogenic potential. Species typical of cervids were also consistently detected. The abomasal nematode community showed an isolationist structure, suggesting its composition was primarily determined by external factors such as interspecific interaction among host species and environmental conditions. The effect of different factors (host sex, sampling site, and time) on nematode counts and aggregation were analyzed and discussed considering the peculiarities of the study site and the chamois population crash. In the light of parallel results for health monitoring, abomasal parasitism could represent a predisposing factor for the observed die-off.

Radiotherapy-induced ear toxicity.

Despite their particular functional consequences, radiotherapy-induced ear injuries remain under-evaluated and under-reported. These reactions may have acute or late character, may affect all structures of the hearing organ, and result in conductive, sensorineural or mixed hearing loss. Up to 40% of patients have acute middle ear side effects during radical irradiation including acoustic structures and about one-third of patients develop late sensorineural hearing loss (SNHL). Total radiotherapy dose and tumour site seem to be among the most important factors associated with the risk of hearing impairment. Thus, reduction in radiation dose to the auditory structures should be attempted whenever possible. New radiotherapy techniques (3-dimensional conformal irradiation, intensity modulated radiotherapy, proton therapy) allow better dose distribution with lower dose to the non-target organs. Treatment of acute and late external otitis is mainly conservative and includes the anti-inflammatory agents (applied topically and systematically). Post-radiation chronic otitis media and the eustachian tube pathology may be managed with tympanic membrane incision with insertion of a tympanostomy tube (grommet), although the benefit of such approach is controversial and some authors advocate a more conservative approach. In these patients the functional deficit can be alleviated by application of bone conduction hearing aids such as, e.g., the bone anchored hearing aid (BAHA). There is no standard therapy for post-irradiation sudden or progressive SNHL yet corticosteroid therapy, rheologic medications, hyperbaric oxygen or carbogen therapy are usually employed (as for idiopathic SNHL), although controversial data on the efficacy of these treatment modalities have been published. In selected cases with bilateral profound hearing loss or total deafness, cochlear implants may prove effective. Further improvements in radiotherapy techniques and progress in otologic diagnostics and therapy may allow better prevention and management of radiation-related acoustic injury.