Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcrvpdate=20110329inogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

Efficacy of geraniol but not of ß-ionone or their combination for the chemoprevention of rat colon carcinogenesis.

ß-ionone (ßI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of ßI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with ßI (16 mg/100 g body weight), GO (25 mg/100 g body weight), ßI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the ßI (91 ± 11 and 14 ± 3) and ßI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of ßI and GO (gas chromatography/mass spectrometry) were higher in the ßI and GO groups, respectively, compared to the control and ßI+GO groups. Therefore, GO, but not ßI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

Abnormal neuronal network in anorexia nervosa studied with I-123-IMP SPECT.

Single photon emission computed tomography was used to study 14 female patients with anorexia nervosa and 8 female normal comparison subjects. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Statistics across the entire brain were displayed as Z scores (threshold: P<0.05). Compared with the normal comparison subjects, the anorectic patients were characterized by hypoperfusion in the medial prefrontal cortex and the anterior cingulate gyrus, and hyperperfusion in the thalamus and the amygdala-hippocampus complex. These results suggest that a dysfunction in neuronal circuitry may be related to anorexia nervosa.

Electrophysiological characteristic of a patient exhibiting the short-coupled variant of torsade de pointes.

A 41-year-old man was admitted because of syncope. The electrocardiogram showed torsade de pointes (Tdp) with no long QT interval and the coupling interval of the initial beat of Tdp was 240 ms. Heterogeneity of ventricular refractoriness was observed together with shortness of the effective refractory period measured at the right ventricular inflow site where the paced QRS morphology was the same as that of the initial beat of Tdp. Verapamil could suppress frequent ventricular premature complexes with a short coupling interval, which lead to Tdp. Polymorphic ventricular tachycardia was induced by triple ventricular extrastimuli. A pure potassium channel blocker was successful in inhibiting polymorphic ventricular tachycardia inducibility by prolongation of refractoriness. These results suggested that triggered ventricular premature complexes may be represent the initiating mechanism, whereas the shortness of local refractory period and heterogeneity of ventricular refractoriness may play a role in the development and the maintenance of the Tdp.

Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in diagnosis of recurrent or metastatic thyroid carcinoma.

UNLABELLED: There are several reports about the usefulness of (18)F-FDG PET in thyroid cancer. However, few studies have compared FDG PET with (131)I and (201)Tl scintigraphy. The aim of this study was to evaluate the clinical significance of whole-body FDG PET in differentiated thyroid cancer and to compare the results with those obtained from (131)I and (201)Tl scintigraphy. METHODS: Whole-body FDG PET was performed on 32 patients (10 men, 22 women; age range, 30-77 y; mean age, 54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of papillary cancer) after total thyroidectomy. An overall clinical evaluation was performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to allow a comparison with functional imaging results for each patient. Metastatic regions were divided into five areas: neck, lung, mediastinum, bone, and other. Multiple lesions in one area were defined as one lesion. The tumor-to-background ratio (TBR) was measured for the lesions that were positive for both (201)Tl uptake and FDG PET uptake. RESULTS: The number of lesions totaled 47. Forty-one (87%) were detected by all scintigraphic methods. FDG uptake was concordant with (131)I uptake in only 18 lesions (38%). FDG uptake was concordant with (201)Tl uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and positive for (201)Tl uptake, and two lesions were positive for FDG uptake and negative for (201)Tl uptake. A significant correlation was seen between the TBR of (201)Tl and that of FDG (r = 0.69; P<0.05). CONCLUSION: These data indicate that for detecting metastatic lesions, FDG PET and (131)I scintigraphy may provide complementary information, whereas FDG PET may provide results similar to those of (201)Tl scintigraphy. Thus, the combination of (131)I scintigraphy and FDG PET (or (201)Tl scintigraphy) is the method of choice for detecting metastatic thyroid cancer after total thyroidectomy.

Thalamic asymmetry on interictal SPECT in patients with frontal lobe epilepsy.

BACKGROUND: Interictal brain single photon emission computed tomography (SPECT) is useful for the detection of seizure focus. Recent reports indicate a hypoperfusion in the ipsilateral thalamus as a seizure focus on interictal SPECT in temporal lobe epilepsy. In frontal lobe epilepsy (FLE), however, the alteration of perfusion in the thalamus has not been well documented. This study aimed to assess whether perfusion analysis on the thalamus may add useful information for the detection of epileptic foci in patients with FLE. METHODS: Interictal brain SPECT was performed in 11 patients with FLE. The asymmetry index for the thalamus and frontal area in the SPECT image was calculated in order to compare the laterality of the seizure foci. RESULTS: Thalamic asymmetry was seen in seven patients (64%), while cortial asymmetry was seen in six patients (55%). The concordance with the lateralization of the seizure foci was 6/7 (86%) in the thalamus, and 4/6 (67%) in the frontal area. Four patients showed only thalamic asymmetry. Concordance with the lateralization of the seizure focus was found in all of them. CONCLUSION: These preliminary results suggest that hypoperfusion in the thalamus may have a complementary role to lateralize the epileptic foci in patients with FLE.

Experimental use of a transportable hyperbaric chamber durable for 15 psi at 3700 meters above sea level.

A transportable hyperbaric chamber durable for 15 psi of pressure was used to treat a patient suffering from moderate acute mountain sickness at 3700 m above sea level. The symptoms were ameliorated a few minutes after pressurization in the chamber. After a 20-minute stay in the chamber, the patient was completely free of symptoms. Since the chamber can be inflated by using compressed air from a cylinder, no strenuous work was required of the operators. This transportable chamber seems to be useful for the treatment of high-altitude disorders at around 3000 m above sea level.

Dynamic computed tomography predicts tumor temperature and response to thermoradiotherapy in superficial and subsurface tumors.

BACKGROUND: Dynamic computed tomography (CT) was performed on patients undergoing thermoradiotherapy for superficial or subsurface tumors, and the correlation between tumor enhancement and tumor temperature during hyperthermia was evaluated. The authors further investigated whether tumor enhancement by dynamic CT is predictive of tumor response to thermoradiotherapy. METHODS: Thermoradiotherapy was given to 26 patients. Radiotherapy consisted of 40-70 gray. Hyperthermia was conducted over 3-5 sessions, and tumor temperature was measured at each session. Dynamic CT was performed prehyperthermia (within 1 week before the initiation of hyperthermia) and midtherapy (within 1 week after 2 sessions of hyperthermia). RESULTS: A complete response (CR) was obtained in 11 patients (42%) and either a partial response or no response (non-CR) in 15 (58%). There was no correlation between tumor enhancement obtained by prehyperthermia CT and tumor temperature parameters or response. However, the deltaCTmax (maximum increased enhancement) by prehyperthermia and midtherapy CT was 39.0 +/- 18.9 HU and 26.1 +/- 14.2 HU, respectively, in CR patients, and 46.4 +/- 21.1 HU and 49.6 +/- 19.1 HU, respectively, in non-CR patients. This change in deltaCTmax at midtherapy was significantly different between groups (P < 0.01). The deltaCTmax ratio for prehyperthermia and midtherapy CT studies correlated with the average tumor temperature (P < 0.05). CONCLUSIONS: Tumor enhancement by prehyperthermia and midtherapy dynamic CT predicted tumor temperature during hyperthermia and response to thermoradiotherapy for superficial or subsurface malignancies.

Relevance of a new impedance matching, or subtrap, method for the reduction of pain during hyperthermia.

Capacitive heating is widely used in hyperthermic treatment of human malignancies. However, the pain on the body surface or thermoesthesia in the subcutaneous fatty layer may prevent an elevation of temperature in the tumors. Impedance matching is improved by a subtrap method entailing the application of two copper plates (10 x 850 x 0.06 mm) as a subtrap circuit to each of two capacitive electrodes. In a clinical trial the Tmax, Tave, Tmin for the subtrap method were all higher in comparison with those for the conventional technique (42.5 +/- 0.7 degrees C, 41.9 +/- 1.0 degrees C, 41.3 +/- 1.1 degrees C vs. 41.1 +/- 1.5 degrees C, 40.6 +/- 1.3 degrees C, 40.0 +/- 1.3 degrees C). Although the maximal radiofrequency (RF) power applied to patients was higher with the subtrap method (875 +/- 189 W vs. 763 +/- 200 W), the incidence of surface pain was reduced dramatically. It is concluded that the subtrap method substantially improves the RF capacitive heating of deep-seated tumors.

Enhancement of thermoradiotherapy by glucose administration for superficial malignant tumours.

The effect of hyperglycemia on the thermoradiotherapy of superficial malignant tumours was investigated. Glucose administration alone (500 ml of 10% glucose by intravenous drip infusion) reduced the tumour blood flow, when measured by laser Doppler flowmetry, to 66.1% of the baseline level at 30 minutes after the beginning of glucose infusion. Forty patients received glucose in tandem during the hyperthermia and radiotherapy (group A), and 38 patients received thermoradiotherapy alone (group B). The mean Tave (the average temperature of all intratumoural sensors) in group A was 43.4 +/- 1.1 degrees C while that in group B was 42.5 +/- 1.2 degrees C, i.e., glucose administrations significantly increased the tumour temperature (p < 0.01). In group A, complete tumour response (CR) was observed in 12 patients (30.0%), partial response (PR) in 25 patients (62.5%) and no response (NR) in three patients (7.5%). In group B, seven (18.4%), 20 (52.7%) and 11 (28.9%) patients showed CR, PR and NR, respectively. The tumour response rates were significantly different between two treatment groups (p < 0.05). The frequency of side effects of hyperthermia in groups A and B were 22.5 and 21.1%, respectively. This study suggests that hyperglycemia enhances the effectiveness of thermoradiotherapy.

Normal human fibroblasts immortalized by introduction of human papillomavirus type 16 (HPV-16) E6-E7 genes.

This report demonstrates that normal human fibroblasts can be immortalized by the introduction of HPV-16 E6-E7 genes. We designed zinc-inducible expression plasmids with HPV-16 E6, E7 or both. Each plasmid was introduced into normal human fibroblasts (TIG-3 cells) using lipofection methods. Only transfectants with the HPV-16 E6-E7 zinc-inducible expression plasmid, which were cultured in medium supplemented with 100 microM ZnSO4, overcame crisis and could be cultured over 200 population doubling levels (PDLs). These cell lines showed the reactivation of telomerase after crisis, and morphological alterations were also observed.

[Treatment of prostatic carcinoma with UFT and leucovorin--basic study using SRCA].

Combination effect of UFT and leucovorin against the rat prostatic carcinoma (R-3327) was evaluated by the subrenal capsular assay (SRCA) using nude mice. Anticancer effect of UFT was augmented by co-administration of both low and high dose leucovorin. These results suggest a clinical usefulness of UFT administration with leucovorin for the patients with hormonally refractory advanced prostatic carcinoma.

Effects of high alpha-linolenate and linoleate diets on erythrocyte deformability and hematological indices in rats.

Rats were fed either a high alpha-linolenate diet or a high linoleate diet from weaning to 4 mon of age. Soybean oil was used as a control. Phospholipid compositions of erythrocytes from the three dietary groups were not significantly different. However, the difference in the alpha-linolenate (18:3n-3)/linoleate (18:2n-6) ratio of the diets was reflected in the n-3/n-6 ratios of the 20 and 22 carbon highly unsaturated fatty acids except for docosahexaenoic acid (22:6n-3) in the phospholipids. Despite the significant differences in the fatty acid compositions of phospholipids, no measurable differences were detectable in erythrocyte deformability, whole blood viscosity and hematological indices of the three dietary groups. These results indicate that the beneficial effects of the high alpha-linolenate diet, as compared with the high linoleate diet, are exerted without significant changes in these parameters.