A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.

The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances from the tissue.

Appearance of intracranial meningioma in FDG and 68Ga-DOTATOC PET/CT / PET/TAC con FDG y 68Ga-DOTATOC en un meningioma intracraneal

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Thalidomide attenuates learning and memory deficits induced by intracerebroventricular administration of streptozotocin in rats.

Neuroinflammatory responses caused by amyloid ß (Aß) peptide deposits are involved in the pathogenesis of Alzheimer's disease (AD). Thalidomide has a significant anti-inflammatory effect by inhibiting TNF-α, which plays role in Aß neurotoxicity. We investigated the effect of thalidomide on AD-like cognitive deficits caused by intracerebroventricular injection of streptozotocin (STZ). Intraperitoneal thalidomide was administered 1 h before the first dose of STZ and continued for 21 days. Learning and memory behavior was evaluated on days 17, 18 and 19, and the rats were sacrificed on day 21 to examine histopathological changes. STZ injection caused a significant decrease in the mean escape latency in passive avoidance and decreased improvement of performance in Morris water maze tests. Histopathological changes were examined using hematoxylin-eosin and Bielschowsky staining. Brain sections of STZ treated rats showed increased neurodegeneration and disturbed linear arrangement of cells in the cortical area compared to controls. Thalidomide treatment attenuated significantly STZ induced cognitive impairment and histopathological changes. Thalidomide appears to provide neuroprotection from the memory deficits and neuronal damage induced by STZ.

The effect of prepubertal ovariohysterectomy on spine 1 mineral density and mineral content in puppies: a preliminary study.

This pilot study investigated early effects of prepubertal ovariohysterectomy on bone mineral density (BMD) and bone mineral content (BMC) of lumbar vertebraes (L2-L5 and L Total) and on serum biochemistry. Both prepubertal ovariohysterectomy (Group Po: n=3) and sham surgery (Group Lp: n=3) were performed at 10 weeks of age. Blood samplings, BMD and BMC measurements of L2, L3, L4, L5 and L Total were performed at 12, 16, 20 and 24 weeks of age. No significant difference (P>0.05) in BMD and BMC was observed between the groups during the experimental period. The difference in serum calcium and phosphorus concentrations was found to be statistically unsignificant (P>0.05). These results fail to demonstrate a difference in BMD and BMC of lumbar vertebraes (L2-L5) as well as serum calcium and phosphorus levels after prepubertal ovariohysterectomy until six months of age in mixed breed puppies, but they should be considered only descriptive because of the very low sample number and of the low power of the statistical analyses.

Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats.

The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation. Sprague-Dawley rats were pre-treated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to irradiation, while another group was followed for 72 h after irradiation, during which saline or PTU injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde (MDA; an index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels, myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH), an indicator of tissue damage, and tumour necrosis factor-alpha (TNFalpha) were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the tissues studied (P<0.05-0.001). Similarly, serum TNFalpha and LDH were elevated in the irradiated rats as compared with the control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggested that PTU-induced hypothyroidism reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.

Synthesis of some novel azo derivatives of 3,5-dimethyl-1-(2-hydroxyethyl)pyrazole as potent analgesic agents.

A series of 1-(2-hydroxyethyl)-3,5-dimethylpyrazolylazo derivatives, incorporating thiosemicarbazide 2a-c, 1,3,4-thiadiazole 3a-c, and 1,2,4-triazole-3-thione 4a-c were synthesized. The structure of these novel synthesized compounds 2a-c, 3a-c, and 4a-c was confirmed by spectral analysis. All these compounds were screened for their analgesic activity. Hot-plate and tail-immersion tests were used for the determination of the analgesic activity. Morphine, an analgesic through both spinal and supraspinal pathways, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg i.p. Among the compounds, 2-(butylamino)-5-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-1,3,4-thiadiazole 3a and 4-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-4-(2-phenethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 4c showed analgesic effects in both tests. Especially 4c exerted strong analgesia starting at 30 min after injection.

Effect of prepubertal ovariohysterectomy on bone mineral density and bone mineral content in puppies.

In this study, dual energy X-ray absorptiometry (DXA) was performed on the calcaneus (CAL) and accessory carpal bone (ACB) of early-age neutered (n = 11) and sham-operated puppies (n = 10) to investigate changes in bone mineral density (BMD) and bone mineral content (BMC) over time. Prepubertal ovariohysterectomy and sham surgery were performed at 10 weeks, while BMD and BMC were measured at 12, 16, 20 and 24 weeks of age. BMD and BMC of CAL and ACB of ovariohysterectomised puppies were found to be higher. The differences between the groups were statistically unimportant; however, the fourth measurement of the ACB showed a significant (P < 0.05) difference. Sexually intact puppies weighed less than gonadectomised puppies in all measurements. Because of the positive correlations between body weight and bone mineral density, BMD and BMC of early-age neutered puppies were found to be higher. These results suggest that BMD and BMC are not affected by prepubertal ovariohysterectomy until six months of age in mixed-breed puppies.

The in vivo metabolism of 5-(4-nitrophenyl)-4-(2-phenylethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in rats.

The purpose of this study was to investigate the in vivo metabolism of 5-(4-nitrophenyl)-4-(2-phenylethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione. First its potential metabolites were synthesized and then the structures of the original compound were elucidated by UV, 1H-NMR and elemantary analysis. 40 mg dose was given intraperitoneally to rats. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 12, 24, 48 and 72 hours after administration of substrate and blood was centrifuged to obtain plasma. The plasma were passed through a Sep-Pak C18 cartridge. The samples were separated using HPLC on a reverse phase system. This study revealed reduction, N-acetylation and N-dealkylation as pathway of 5-(4-nitrophenyl)-4-(2-phenylethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione metabolism.

Is (99m)Tc-sestamibi scintimammography complementary to conventional mammography for detecting breast cancer in patients with palpable masses?

UNLABELLED: The aim of this trial was to evaluate in developing countries from different regions the diagnostic performance of (99m)Tc-sestamibi scintimammography (SM) in palpable breast lesions and to verify the clinical usefulness of a joint evaluation with mammography and SM. METHODS: From 10 countries, a total of 238 patients with palpable breast masses (n = 245) were included in this prospective multicenter trial. Prone SM was performed 10 min and 60-90 min (157 patients) after injection using an isotime acquisition of 10 min. Mammography was assessed by the same dedicated imaging radiologist according to breast imaging reporting and data system (BI-RADS) categories for malignancy and breast density. Masked SM findings and mammography findings were checked for a correlation with histopathology findings for excisional biopsy samples. Diagnostic values for breast cancer detection were calculated per lesion. RESULTS: Histopathology revealed 189 cancerous lesions and 56 benign lesions. The sensitivity and specificity of SM were 0.83 and 0.77, respectively. SM diagnostic values did not depend on the incidence of breast cancer in the country of origin or on the timing of imaging (early vs. delayed scans). On mammography, the technique yielded a sensitivity and specificity of 0.85 and 0.66, with 27 mammograms classified as BI-RADS category 1, 33 as category 2, 5 as category 3, 56 as category 4, and 124 as category 5. Thirty-seven lesions were considered to show increased radiologic density. No significant difference was found in SM diagnostic values among different BI-RADS categories or between the groups with low and high breast density. A sensitivity of 96% was calculated when SM and mammography results were combined, with 75% of all false-negative mammography findings classified as true-positive results by SM. CONCLUSION: SM complements mammography in patients with palpable masses and negative mammography findings.

A comparison of Tl-201 stress-reinjection-prone SPECT and Tc-99m-sestamibi gated SPECT in the differentiation of inferior wall defects from artifacts.

The frequency of false positive results obtained from the inferior myocardial region using single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy is significantly higher than that obtained from other regions. Several methods, such as prone-position imaging, have been proposed to overcome this diagnostic problem. The aim of the present study was to compare the results of Tc-99m-sestamibi gated SPECT and Tl-201 prone SPECT in the differentiation of inferior wall artifacts from true defects. For this purpose, 38 subjects, whose coronary anatomies were documented on angiography, underwent same-day stress-rest Tc-99m-sestamibi gated SPECT and Tl-201 stress-reinjection-prone (whose standard supine images demonstrated fixed defects on the inferior wall) SPECT. Gated SPECT was performed by 8 frames per cycle acquisition over a 180 degree rotation on 30 projections. Four gated SPECT slices were obtained on mid-ventricular vertical long axis, horizontal long axis and apical and basal short axis planes, and displayed in cine-format. Both Tl-201 prone imaging and Tc-99m-sestamibi gated analysis increased the specificity of inferior wall disease detection remarkably from 54% to 85% and 46% to 82%, respectively (P<0.05). The difference between diagnostic accuracies was not significant (80% and 82%, respectively) (P > 0.05). The positive predictive values for true defects were 96% for Tl-201 prone imaging and 94% for Tc-99m-sestamibi gated imaging. Based on segmental analysis, the two modalities showed fair agreement (kappa = 0.44 for standard supine protocols, kappa = 0.46 for Tl-201 prone and Tc-99m-sestamibi gated SPECT). It can be concluded that Tc-99m-sestamibi gated SPECT, requiring only two-step acquisition, may potentially increase the test specificity for coronary artery disease (CAD) of the inferior wall as well as does Tl-201 stress-reinjection-prone SPECT. By giving functional information, it seems the most practical method in daily use for supplying the most extensive information about patients with suspected or known CAD.

Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology.

A comparative prospective study of technetium-99m methoxyisobutylisonitrile (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for 201Tl) imaging in the differentiation of thyroid lesions is presented. Forty patients with cold thyroid nodules visualised on 99mTc-pertechnetate scan and with dyskaryotic or atypical epithelial cells verified by fine needle aspiration biopsy underwent MIBI and 201Tl scintigraphy at 3-day intervals. Subsequent thyroidectomies were carried out in all patients. Semiquantitative analysis was performed using a lesion to non-lesion ratio on early (ER) and delayed images (DR). Additionally, a retention index (RI) was calculated using the formula RI=(DR-ER) x 100/ER. The reproducibility of the method for the early and delayed measurements was tested by analysing intra- and inter-observer variability and repeatability coefficients. Histopathologically, the nodules were found to be well-differentiated thyroid cancer in 21 patients and benign in 19 patients. There was no significant difference in the ER between malignant and benign lesions for either 201Tl or MIBI (P>0.05). However, for both agents significant differences were found between malignant and benign lesions with regard to DR (P<0.01 for 201Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents). Statistical comparison of the two agents showed no significant differences (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A receiver operating characteristic analysis was performed to determine threshold levels for the differentiation of malignant from benign nodules. Following this analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and < or =1.42, 1.24 and 5 for 201Tl were selected. Using these threshold levels, the sensitivity, specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI, 61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%, 47.3% and 67.5% for ER 201Tl, 80.9%, 73.6% and 77.5% for DR 201Tl, and 90.5%, 94.7% and 92.5% for RI 201Tl. In conclusion, the DR for MIBI and 201Tl is superior to the ER in detecting malignant nodules, and the RI for both MIBI and 201Tl is more valuable than the DR in differentiating malignant from benign thyroid nodules.

Comparison of 99mTc-methoxyisobutyl isonitrile and 201T1 scintigraphy in visualization of suppressed thyroid tissue.

UNLABELLED: Both (201)TI and (99m)Tc-methoxyisobutyl isonitrile (MIBI) have been used in the visualization of suppressed thyroid tissue in patients with autonomously functioning thyroid nodules (AFTNs). It has been suggested that thyroid-stimulating hormone (TSH) control is not a major determinant of both tracers. However, the mechanism of thyroid uptake of these agents is controversial. In this study, we compared (201)TI and MIBI in the visualization of suppressed thyroid tissue in patients with a solitary toxic AFTN. METHODS: Thirty-two patients (13 triiodothyronine [T3] and 19 T3 + levorotatory thyroxine [T4] hyperthyroid patients) with toxic AFTNs visualized on (99m)Tc-pertechnetate scanning were included in the study. All patients underwent MIBI and (201)TI thyroid scintigraphy within a 3-d interval. The scintigrams were analyzed both visually and semiquantitatively. For the semiquantitative analysis, regions of interest (ROIs) were generated over the nodule (N) and contralateral normal lobe (E), and the mean counts in each ROI were calculated. RESULTS: The N/E uptakes (mean +/- SD) for pertechnetate, MIBI, and (201)TI were 11.37 +/- 4.53, 4.76 +/- 1.38, and 1.63 +/- 0.15, respectively, in T3 + T4 hyperthyroid patients and 9.46 +/- 3.64, 2.73 +/- 0.63, and 1.57 +/- 0.23, respectively, in T3 hyperthyroid patients. Our results showed that (201)TI uptake of suppressed thyroid tissue compared with AFTN was more prominent and significantly higher than that of MIBI for both groups of patients (P = 1.08E-05 for T3 and 6.15E-09 for T3 + T4 hyperthyroidism). There was no significant difference for either pertechnetate or (201)TI (P > 0.05) when the N/E uptakes of both groups of patients were compared. However, the N/E uptake of MIBI in T3 + T4 hyperthyroid patients was significantly higher than that in T3 hyperthyroid patients (P = 6.69E-06). CONCLUSION: Clear visualization of suppressed thyroid tissue with both (201)TI and MIBI in patients with low serum concentrations of TSH suggests that TSH is not a major factor in the thyroid uptake of either agent. (201)TI is superior to MIBI in the visualization of suppressed thyroid tissue in patients with a toxic thyroid nodule. An increased rate of metabolism in the follicular cells of AFTNs in T3 + T4 hyperthyroid patients compared with that in T3 hyperthyroid patients might be responsible for the higher N/E for MIBI compared with that for (201)TI.

Ictal and interictal SPECT findings in childhood absence epilepsy.

The purpose of this study was to investigate the informative value of single photon emission tomography (SPECT) in relation to the pathophysiological functioning of the brain during absence seizures and the origin of ictal discharges in idiopathic generalized epilepsies (IGEs). Six patients with childhood absence epilepsy (CAE) were selected for the study and two consecutive SPECT sessions were performed concomitant with EEG recordings revealing normal results and during hyperventilation (HV) studies where the ictal discharges were induced either alone or accompanied by clinical absence seizures. All six patients had ictal discharges in their EEGs during HV and two of them also had clinical absences. SPECT findings during HV revealed an overall increase in the cerebral blood flow (CBF) with significantly higher values as compared to the baseline data. There was no indication for any focal origin in either the interictal or the ictal SPECT findings. Results of the study were supportive for the concept of subcortical origin for the absence seizures and they were also promising for the diagnostic value of ictal SPECT in epileptic cases with undetermined origin as to whether they were localization-related or generalized.

The role of 99Tcm-tetrofosmin in the evaluation of thyroid nodules.

Various radionuclides, including 67Ga, 201Tl and 99Tcm-sestamibi, have been used to differentiate benign from malignant thyroid nodules. 99Tcm-tetrofosmin, a lipophilic cationic radiotracer, and 99Tcm-sestamibi have also been reported to accumulate in thyroid tumours. In this study, we evaluated the role of 99Tcm-tetrofosmin in the differentiation of malignant from benign thyroid nodules. Seventy-nine patients with solitary non-functioning thyroid nodules were included in the study. Fine-needle aspiration biopsy was performed in all patients. Sixty patients were subsequently operated on and 19 patients refused surgery. After the injection of 370 MBq 99Tcm-tetrofosmin, static images at 5, 30, 60, 120 and 180 min were acquired. Both visual and semi-quantitative analysis was performed. On visual interpretation, the nodules with late retention were classified as positive for malignancy and nodules without late retention were classified as negative for malignancy. In the semi-quantitative analysis, regions of interests were drawn over the nodule and contralateral normal thyroid tissue. The average number of counts was recorded and tumour-to-normal thyroid tissue ratios calculated. Post-operative histology revealed 19 malignant and 41 benign nodules. Of the benign nodules, adenomas behaved similarly to the malignant nodules with late retention of tracer, while adenomatous nodules revealed no late retention on delayed images and could be differentiated from malignant tumours. In the semi-quantitative analysis, there was a significant difference in tumour-to-normal tissue ratios for adenomatous nodules and malignant tumours as well as adenomas. We conclude that it is not possible to differentiate between malignant and benign thyroid nodules with 99Tcm-tetrofosmin. However, 99Tcm-tetrofosmin scintigraphy is helpful in selecting nodules that can be cured by surgical intervention.