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A general limitation of ecological investigations based on nematodes is related to the difficult and time-consuming taxonomic identification of species. Therefore, nematologists are investing many efforts to develop alternative approaches as proxies applicable in biomonitoring assessment. Recently, an alternative method that combines morpho-functional traits was proposed for detecting assemblage changes of marine nematodes. In view of the promising results, it was tested the same approach to document taxonomic structure changes of soil free-living and plant parasitic nematodes. Specifically, this attempt was carried out using three data sets that include studies from various European regions and different types of ecosystems: forests, grasslands and maize crops. Multivariate statistical analysis revealed that the simple combination of the four traits (i.e., buccal cavity cuticularization occurrence, amphideal fovea size and shape, morphology of the cuticle and pharynx) in a single code number perfectly mirrors the taxonomic structure trends of the nematode assemblage at genus level. Therefore, we predict that similar results can be also obtained by directly encoding nematode specimens with the selected traits and we point to new important advances if this procedure can be coupled with advanced machine learning.
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PURPOSE: The elevated frequency of discordance for congenital hypothyroidism (CH) phenotype between monozygotic twins suggests the involvement of non-mendelian mechanisms. The aim of the study was to investigate the role of epigenetics in CH pathogenesis. METHODS: A genome-wide DNA methylation analysis was performed on the peripheral blood of 23 twin pairs (10 monozygotic and 13 dizygotic), 4 concordant and 19 discordant pairs for CH at birth. RESULTS: Differential methylation analysis did not show significant differences in methylation levels between CH cases and controls, but a different methylation status of several genes may explain the CH discordance of a monozygotic twin couple carrying a monoallelic nonsense mutation of DUOX2. In addition, the median number of hypo-methylated Stochastic Epigenetic Mutations (SEMs) resulted significantly increased in cases compared to controls. The prioritization analysis for CH performed on the genes epimutated exclusively in the cases identified SLC26A4, FOXI1, NKX2-5 and TSHB as the genes with the highest score. The analysis of significantly SEMs-enriched regions led to the identification of two genes (FAM50B and MEG8) that resulted epigenetically dysregulated in cases. CONCLUSION: Epigenetic modifications may potentially account for CH pathogenesis and explain discordance among monozygotic twins.
Subject(s)
Congenital Hypothyroidism , Epigenesis, Genetic , Humans , Congenital Hypothyroidism/genetics , DNA Methylation , Mutation , Phenotype , Twins, Monozygotic/geneticsABSTRACT
INTRODUCTION: Deep margin elevation (DME) is an emerging technique attempting to minimize the need for surgical procedures (i.e., crown lengthening [CL]), deliver indirect restorations in one clinical session and reduce overall treatment time. The present study evaluated the impact of DME upon periodontal measurements based exclusively on human studies. METHODS: A literature search was performed by two independent reviewers in several databases including PubMed, EMBASE, and Cochrane Central up to March 2022. This review searched for randomized human trials, cohort (prospective/ retrospective) and/or case series studies using DME, reporting periodontal (i.e. marginal bone levels [MBL], probing depths [PD], bleeding on probing [BoP], recession [REC], clinical attachment level [CAL]), and the type of approach (non-surgical or surgical) with at least ⟩3 months of post-operative outcomes. RESULTS: None of the included studies reported MBL, REC or CAL, and thus, results were limited to PD and BoP. BoP was increased when the distance between restorative margin and alveolar bone was approximately ⟨2mm. Non-surgical and surgical DME approaches led to different outcomes in PD (0.26±0.77mm vs -0.39±0.85mm) and BoP (31.50% vs -22.33%). CONCLUSIONS: Limited findings of the present systematic review can be drawn and thus, the impact of DME upon the periodontium remains inconclusive.
Subject(s)
Prospective Studies , Humans , Retrospective StudiesABSTRACT
BACKGROUND: Metastatic pancreatic cancer has a median overall survival of less than 12 months, even if treated with chemotherapy. Selected patients with oligometastatic disease could benefit from multimodal treatments connecting chemotherapy and surgical treatment or radiofrequency ablation (RFA) of metastases. CASE PRESENTATION: We present a patient with oligometastatic pancreatic cancer recurrence who was successfully treated with a multimodal therapeutic approach. A 57-year-old male initially presenting with resectable pancreatic cancer underwent pancreatoduodenectomy. The histopathological diagnosis revealed ductal pancreatic adenocarcinoma with positive surgical resection margins and negative lymph nodes. He completed six cycles of adjuvant therapy with gemcitabine (1000 mg/mq 1,8,15q 28), followed by external radiotherapy (54 Gy in 25 fractions) associated with gemcitabine 50 mg/mq twice weekly. Three years later, the patient developed multiple liver metastases, and he started FOLFIRINOX (oxaliplatin 85 mg/mq, irinotecan 180 mg/mq, leucovorin 400 mg/mq and fluorouracil 400 mg/mq given as a bolus followed by 2400 mg/mq as a 46 h continuous infusion,1q 14) as a first-line treatment. The CT scan showed a partial response after 6 cycles. After multidisciplinary discussion, the patient underwent a laparotomic metastasectomy of the three hepatic lesions. After additional postsurgical chemotherapy with 4 cycles of the FOLFIRINOX schedule, the patient remained free of recurrence for 12 months. A CT scan showed a new single liver metastasis, which was treated with radiofrequency ablation (RFA). A second radiofrequency ablation was performed when the patient developed another single liver lesion 12 months after the first RFA; currently, the patient is free from recurrence with an overall survival of 6 years from the diagnosis. CONCLUSIONS: Our case has benefited from successful multimodal treatment, including surgical and local ablative techniques and systemic chemotherapy. A multimodal approach may be warranted in selected patients with oligometastatic pancreatic cancer and could improve overall survival. Further research is needed to investigate this approach.
Subject(s)
Adenocarcinoma/therapy , Liver Neoplasms/therapy , Pancreatic Neoplasms/therapy , Adenocarcinoma/secondary , Chemoradiotherapy , Combined Modality Therapy , Disease-Free Survival , Hepatectomy , Humans , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy , Radiofrequency AblationABSTRACT
PURPOSE: Type I interferons (IFN-α and IFN-ß) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-ß showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-ß products, such as IFN-ß1a and IFN-ß1b, have been produced in order to improve the stability and bioavailability of natural IFN-ß. In this report, we analyzed the effects of recombinant IFN-ß1a on the cell proliferation of two human androgen-resistant prostate cancer cell lines with neuroendocrine differentiation (DU-145, PC-3) and related mechanisms of action. METHODS: The effects of IFN-ß1a on the cell growth proliferation, cell cycle, and apoptosis have been evaluated in DU-145 and PC-3 cells through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. Moreover, the expression of neuron-specific enolase (NSE), cleaved caspase-3, caspase-8, and PARP was evaluated through Western blotting. RESULTS: IFN-ß1a showed a significant anti-proliferative activity in both androgen-resistant cell lines. This effect was related to cell cycle perturbation and induction in apoptosis, as shown by flow cytometric analysis, the activation of caspase-3 and caspase-8 and PARP cleavage during incubation with IFN-ß1a. Moreover, this cytokine reduced the expression of NSE in both cell lines. CONCLUSIONS: Recombinant IFN-ß1a (Rebif) showed a potent in vitro anti-proliferative activity in androgen-resistant prostate cancer cells, and it could represent a promising tool for the treatment of this tumor.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Differentiation/drug effects , Interferon beta-1a/pharmacology , Neuroendocrine Tumors/drug therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Male , Neuroendocrine Tumors/pathology , Prostatic Neoplasms, Castration-Resistant/pathology , Tumor Cells, CulturedABSTRACT
Trigeneric hybrids in Triticeae may help to establish evolutionary relationships among different genomes present in the same cellular genetic background and to transfer different alien characters into cultivated wheat. In the present study, a trigeneric hybrid involving species of Triticum, Secale, and Thinopyrum was synthesized by crossing hexaploid triticale with hexaploid trigopiro. The meiotic behaviour of chromosomes belonging to different genomes was analyzed, using routine and in situ hybridization techniques in F1, F2, and F3 generations of the trigeneric hybrid. The purpose of this study was to determine the chromosome number and genomic constitution and to discuss the mechanisms involved in the stabilization of the artificial tricepiro hybrids. The chromosome number of the trigeneric F1 hybrid was 2n = 42. Between 12 and 16 bivalents were observed in the central zone of the equatorial meiotic plate and between 9 and 18 univalents were found in the periphery of the MI equatorial plate. Seven of these univalents showed hybridization signals with rye DNA. Lagging rye and non-rye chromosomes and separation of sister chromatids were found in anaphase I. Tetrads with a maximum of six micronuclei, with and without hybridization signals of rye DNA, were observed. After three generations, meiotic cells revealed the presence of 42 chromosomes and 21 bivalents in diakinesis cells. The presence of 14 rye (Secale cereale) chromosomes and the complete pairing of chromosomes in F3 hybrids suggest that rye chromosomes would be preferentially transmitted to the progeny and that an elimination mechanism would act on chromosomes of Thinopyrum and wheat D genome.
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BACKGROUND: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer. PATIENTS AND METHODS: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (α = 0.05, power = 0.80). The proposed treatment could be considered promising if ≥13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365). RESULTS: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation). CONCLUSION: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Capecitabine/pharmacology , Capecitabine/therapeutic use , Prospective Studies , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Chemoradiotherapy/adverse effects , Diarrhea/chemically induced , Transaminases/therapeutic useABSTRACT
Background and Purpose: The accurate prediction of prognosis and pattern of failure is crucial for optimizing treatment strategies for patients with cancer, and early evidence suggests that image texture analysis has great potential in predicting outcome both in terms of local control and treatment toxicity. The aim of this study was to assess the value of pretreatment 18F-FDG PET texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiation therapy. Methods: We performed a retrospective analysis of 90 patients diagnosed with primary HNSCC treated between January 2010 and June 2017 with concurrent chemo-radiotherapy. All patients underwent 18F-FDG PET/CT before treatment. 18F-FDG PET/CT texture features of the whole primary tumor were measured using an open-source texture analysis package. Least absolute shrinkage and selection operator (LASSO) was employed to select the features that are associated the most with clinical outcome, as progression-free survival and overall survival. We performed a univariate and multivariate analysis between all the relevant texture parameters and local failure, adjusting for age, sex, smoking, primary tumor site, and primary tumor stage. Harrell c-index was employed to score the predictive power of the multivariate cox regression models. Results: Twenty patients (22.2%) developed local failure, whereas the remaining 70 (77.8%) achieved durable local control. Multivariate analysis revealed that one feature, defined as low-intensity long-run emphasis (LILRE), was a significant predictor of outcome regardless of clinical variables (hazard ratio < 0.001, P=0.001).The multivariate model based on imaging biomarkers resulted superior in predicting local failure with a c-index of 0.76 against 0.65 of the model based on clinical variables alone. Conclusion: LILRE, evaluated on pretreatment 18F-FDG PET/CT, is associated with higher local failure in patients with HNSCC treated with chemoradiotherapy. Using texture analysis in addition to clinical variables may be useful in predicting local control.
Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Positron-Emission Tomography/methods , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/therapy , Humans , Image Interpretation, Computer-Assisted , Male , Middle Aged , Prognosis , Radionuclide Imaging/methods , Retrospective Studies , Survival Analysis , Young AdultABSTRACT
The high cost of virgin (18)O-enriched water has forced many researchers to study methods to purify and recycle enriched water after the first irradiation for the production of radiopharmaceuticals. In our study, [(18)O]H(2)O was purified by ozonolysis and distillation. Analyses showed a large decrease in impurities after this treatment. The purification procedure was carried out after the production of 94 batches of [18F]-FDG, which were manufactured using a GE Minitrace cyclotron and a GE Mx TracerLab synthesizer. Saturation yields after bombardment, using virgin and re-purified water were, respectively, 2864+/-204MBq/muA and 2727+/-167MBq/muA, a decrease of 5.5%. The decrease in [18F]-FDG yield, from 67.2+/-0.7% to 65.5+/-0.9%, can be ascribed to the irradiation step only.
Subject(s)
Fluorodeoxyglucose F18/chemistry , Oxygen Isotopes/chemistry , Radiopharmaceuticals/chemistry , Water/chemistry , CyclotronsABSTRACT
AIM: It is important to assess aphasics' quality of life in order to plan a rehabilitation treatment. To date such a tool is still missing for Italian patients. This paper reports normative data of the Italian version of SAQOL-39, a British questionnaire aimed to assess aphasics' quality of life. It consists of 39 items, divided into 4 subdomains (Physical, Communication, Psychosocial and Energy). METHODS: Forty-two patients coming from 3 different Speech Therapy Services were enrolled. All patients completed speech therapy before examination. They were submitted to the Italian SAQOL-39 and 2 screening tests for aphasia: 1) Communication Assessment Scale according Goodglass and Kaplan; 2) Franchay Aphasia Screening Test (FAST). A receptive FAST score of 7 out of 15 was used as a cut-off score for SAQOL-39 administration. RESULTS: The Italian SAQOL-39 showed good internal consistency (full scale Cronbach's alpha 0.939). Cronbach's alpha for every subdomains ranged from 0.950 (Communication) to 0.720 (Energy). Fluent aphasics gave significantly higher scores than nonfluent ones on full scale, and all out of Energy subdomains. Furthermore gravity of aphasia correlated with both full scale and Communication subdomain scores. CONCLUSIONS: In authors' opinion, the Italian SAQOL-39 shares many psychometric features with the English one. This questionnaire seems to be suitable for clinical practice.
Subject(s)
Aphasia/rehabilitation , Quality of Life , Surveys and Questionnaires/standards , Aged , Aphasia/physiopathology , Female , Humans , Male , Middle Aged , Psychometrics , Regression Analysis , Reproducibility of Results , Treatment OutcomeABSTRACT
BACKGROUND: Targeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning systems are entering the market. However, some in-house systems are currently developed for a more flexible and customized dosimetry calculation at voxel-level. For this purpose, we developed a novel software, VoxelMed, and performed a comparison with the software STRATOS. METHODS: The validation of both of them was undertaken using radioactive phantoms with different volume inserts. A cohort of 10 patients was also studied after a therapeutic administration of (177)Lu-labelled radiopeptides. The activity, number of disintegrations, absorbed dose and dose-volume histogram (DVH) were calculated for the phantoms and the kidneys in patients, which were the main critical organs at risk in this study. RESULTS: In phantoms the absorbed doses computed with VoxelMed and STRATOS agree within 5%. In patients at the voxel-level the absorbed dose to kidneys (VoxelMed: mean 0.66 Gy/GBq) showed a limited difference of 5%, but with a remarkable range (-40%, +60%) between the two software packages. Voxel-dosimetry allows to estimate the dose non-homogeneities in volumes, which may be evaluated through DVHs. CONCLUSION: This study demonstrates that a fully 3D voxel-dosimetry with multiple SPECT images is feasible by using home-made or commercial software package and absorbed dose results obtained are similar. The main difference between the studied tools was observed in the activity integration method (effective vs physical half-time to time activity curve tail). We believe that an effective half-time integration method produces a more accurate approximation of clinical uptake and resultant dosimetry.
Subject(s)
Octreotide/analogs & derivatives , Organometallic Compounds/therapeutic use , Radiometry/methods , Software , Aged , Female , Humans , Male , Middle Aged , Octreotide/therapeutic use , Phantoms, Imaging , Radiotherapy DosageABSTRACT
OBJECTIVE: The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. METHOD: In a multicenter study, a phantom with spheres of different diameters (6.5-57.4 mm) was filled with (18)F-FDG at different target-to-background ratios (TBR: 2.5-70) and scanned for different acquisition periods (2-5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. RESULTS: The goodness of the model fit was high (R(2): 0.74-0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. CONCLUSIONS: Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration.
Subject(s)
Positron-Emission Tomography/statistics & numerical data , Algorithms , Computational Biology , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Linear Models , Models, Statistical , Phantoms, Imaging , Radiopharmaceuticals , Reproducibility of Results , Tomography, X-Ray ComputedABSTRACT
We investigated the number of echinocytes, the serum hemopexin level, and spectrin band II phosphorylation in the blood of normal subjects, patients, and carriers of Duchenne dystrophy. The patients and carriers exhibited quantitatively significant differences with respect to controls.
Subject(s)
Genetic Carrier Screening/methods , Muscular Dystrophies/genetics , Erythrocytes, Abnormal/pathology , Hemopexin/analysis , Humans , Muscular Dystrophies/blood , Muscular Dystrophies/diagnosis , Phosphorylation , Spectrin/analysisABSTRACT
Because of previous reports of a possible correlation between echinocytogenesis and muscular dystrophies, we investigated the time-dependent development of echinocytes in the blood of normal subjects, patients, and healthy carries of Duchenne dystrophy. There was a quantitatively significant increase of echinocytes in patients and carriers.
Subject(s)
Erythrocytes, Abnormal , Muscular Dystrophies/blood , Adolescent , Adult , Aged , Child , Child, Preschool , Erythrocyte Count , Humans , Middle AgedABSTRACT
OBJECTIVES: To determine whether conventional as well as high-frequency somatosensory evoked potentials (SEPs) to upper limb stimulation are influenced by GABAergic intracortical circuitry. METHODS: We recorded SEPs from 6 healthy volunteers before and after a single-oral administration of tiagabine. Conventional low-frequency SEPs have been obtained after stimulation of the median nerve, as well as after stimulation of the first phalanx of the thumb, which selectively involves cutaneous finger inputs. Median nerve SEPs have been further analyzed after digital narrow-bandpass filtering, to selectively examine high-frequency responses. Lastly, in order to explain scalp SEP distribution before and after tiagabine administration, we performed the brain electrical source analysis (BESA) of raw data. RESULTS: After tiagabine administration, conventional scalp SEPs showed a significant amplitude increase of parietal P24, frontal N24 and central P22 components. Similarly, BESA showed a significant strength increase of the second peak of activation of the first two perirolandic dipoles, which are likely to correspond to the N24/P24 and P22 generators. By contrast, no significant changes of high-frequency SEPs were induced by drug intake. CONCLUSIONS: Our findings support the view that both N24/P24 and P22 SEP components are probably generated by deep spiny cell hyperpolarization, which is strongly increased by inhibitory inputs from GABAergic interneurons. By considering the clear influence of inhibitory circuitry in shaping these SEP components, conventional scalp SEP recording could be useful in the functional assessment of the somatosensory cortex in different physiological and pathological conditions. By contrast, intrinsic firing properties of the cell population generating high-frequency SEP responses are unaffected by the increase of recurrent GABAergic inhibition.
Subject(s)
Evoked Potentials, Somatosensory/drug effects , GABA Agonists/administration & dosage , Nipecotic Acids/administration & dosage , Somatosensory Cortex/physiology , gamma-Aminobutyric Acid/physiology , Adult , Evoked Potentials, Somatosensory/physiology , GABA Agonists/adverse effects , Humans , Male , Muscle, Skeletal/innervation , Neurons, Afferent/physiology , Nipecotic Acids/adverse effects , Proprioception/drug effects , Proprioception/physiology , TiagabineABSTRACT
Amyotrophic lateral sclerosis (ALS) is a progressive fatal disorder, which results from the degeneration of motor neurons in the brain and spinal cord. Approximately 20% of the inherited autosomal dominant cases are due to mutations within the gene coding for Cu/Zn superoxide dismutase 1 (SOD1), a cytosolic homodimeric enzyme that catalyzes the dismutation of toxic superoxide anion. We investigated the presence of SOD1 gene mutations and activity alterations in two unrelated families of ALS patients from Elba, an island of central Italy. No mutation in SOD1 exon 1 to 5 and no activity alteration were observed in all members of the two analyzed ALS families (FALS). These data show an apparent heterogeneous distribution of ALS patients with SOD1 gene mutations among different populations and suggest that another genetic locus could be involved in the disease.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Mutation/genetics , Superoxide Dismutase/genetics , DNA Mutational Analysis/statistics & numerical data , Exons/genetics , Female , Humans , Italy , Male , Middle Aged , Pedigree , Superoxide Dismutase-1ABSTRACT
Our purpose was to test the dopamine D2 receptor gene (DRD2), the tyrosine hydroxylase (TH) gene and the monoamino oxydase A (MAO-A) gene for linkage to schizophrenia and bipolar disorders. We have analyzed seven Italian families with schizophrenia and four families with bipolar disorders for a total of 68 individuals; 32 individuals were affected. Diagnoses were made using the structured clinical interview Schedule for Affective Disorders and Schizophrenia, Lifetime version (SADS-L). The results of our study provide no evidence of linkage between alleles at D2 dopamine receptor loci and schizophrenia or bipolar disorders. The markers TH gene and MAO-A gene give slightly positive or negative results suggesting the utility of further analysis on more informative families.
Subject(s)
Bipolar Disorder/genetics , Genetic Linkage , Monoamine Oxidase/genetics , Receptors, Dopamine D2/genetics , Schizophrenia/genetics , Tyrosine 3-Monooxygenase/genetics , Chromosome Mapping , Humans , ItalyABSTRACT
Formation of 7 alpha-hydroxycholesterol by rat liver microsomes was quantitated using a gas chromatograph-mass spectrometer (GC/MS) operated in selected ion monitoring (SIM) mode. Microsomes from normal rat livers incubated for different periods were found to yield increased 7 alpha-hydroxycholesterol with time. This was also true when incubations contained Tween-80, but in this instance, the rate of 7 alpha-hydroxycholesterol production was lower and dependent on the concentration of Tween used. Similarly, Triton X-100, Renex-30, Kyro EOB, Cutscum, and Emulgen 911 all lowered the formation of 7 alpha-hydroxycholesterol by rat liver microsomes, whereas Triton WR-1339 stimulated its production. Analysis of data obtained from following the enzyme reaction over an extended period using an integrated Michaelis-Menten equation indicated the enzyme possesses a very significant affinity for the product (Ks greater than Kp). Similar analysis shows that Tween-80 is a noncompetitive inhibitor of the enzyme.
Subject(s)
Detergents/pharmacology , Hydroxycholesterols/metabolism , Microsomes, Liver/metabolism , Surface-Active Agents/pharmacology , Animals , Gas Chromatography-Mass Spectrometry , Male , Mathematics , Microsomes, Liver/drug effects , Rats , Time FactorsABSTRACT
Previous studies performed by positron emission tomography and Transcranial Doppler (TCD) found a different cerebral activation during musical stimuli in musicians compared to non-musicians. The aim of our study is to evaluate by means of TCD, possible different pattern of cerebral activation during the performance of different musical tasks in musicians, non-musicians and lyrical singers. Our findings show a left hemispheric activation in musicians and a right one in non-musicians. Preliminary data on lyrical singers' activation patterns need further confirmation with a larger population. These data could be related to a different approach to music listening in musicians (analytical) and non-musicians who are supposed to have an emotional approach to music.
Subject(s)
Cerebrovascular Circulation/physiology , Functional Laterality/physiology , Music , Perception/physiology , Recognition, Psychology/physiology , Adult , Blood Flow Velocity/physiology , Female , Humans , Male , Middle Aged , Middle Cerebral Artery/physiology , Ultrasonography, Doppler, Transcranial/methodsABSTRACT
The purpose of the present work is to evaluate the action of a benzofuran derivative, Amiodarone, on an experimental acute infarction model. Six pigs were intravenously administered 1 mg/kg Amiodarone (A) 20 minutes before inducing ischemia (I) by occlusion of the anterior descending coronary artery, which was maintained for 90 minutes. A similar dose level was repeated 20 minutes before ligation release (R). Similarly, another six animals received a placebo and formed the Control Group (C). The extent of myocardial injury was assessed by summations of ST segments (Sigma ST) and R (Sigma R) and Q (Sigma Q) waves of electrocardiographic epicardial mappings, as well as by serum levels for SGOT and LDH. Systemic blood pressure, pulmonary pressure, right atrial pressure, systemic resistance and cardiac output were also controlled. Two hundred and ten minutes after R, the animal was sacrificed for the purpose of carrying out morphological and histochemical studies. No significant differences were observed in the blood pressure of either group. During I, systemic resistance values suffered a drop in the Amiodarone Group A, whereas they increased in both groups after reperfusion. Pulmonary pressure was higher in Group A. Cardiac output showed a similar behavior in both groups up to R, when it significantly decreased in animals receiving Amiodarone. The Sigma ST and the Sigma Q were higher in the Control Group C, whereas the Sigma R was higher in Group A. The SGOT and LDH levels were higher during R in Group C. Histochemistry showed a higher activity for SDH and LDH in treated animals. Due to its action on afterload, its contractility and its direct myocardial action, Amiodarone limited the extent of necrosis and increased the recoverable amount of myocardium.