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1.
Rev. neurol. (Ed. impr.) ; 78(9)1-15 may 2024. tab, graf
Article in Spanish | IBECS | ID: ibc-CR-367

ABSTRACT

Introducción El ictus isquémico agudo es una de las principales causas globales de morbimortalidad. La trombectomía mecánica ha mejorado el pronóstico funcional de esta patología; sin embargo, la transformación hemorrágica es una complicación frecuente. La tomografía computarizada (TC) de tecnología espectral, como prueba de neuroimagen de control, diferencia la extravasación de contraste de la transformación hemorrágica gracias al diferente comportamiento de los materiales a la energía dual, y esta distinción es de utilidad en su manejo clinicoterapéutico. Material y métodos. Estudio unicéntrico, observacional y retrospectivo, en el cual se investigó, mediante el acceso a una base de datos disociada y a la historia clínica, la presencia de una serie de variables clínicas, radiológicas y terapéuticas en los pacientes con ictus isquémico agudo que fueron tratados con trombectomía mecánica en nuestro hospital entre julio de 2022 y marzo de 2023.ResultadosDe los 155 pacientes incluidos, se realizó una TC craneal espectral en 63 y convencional en 75. En el grupo de TC espectral se detectaron 21 imágenes hiperdensas y en el grupo de TC convencional fueron 28. En el 42,8% de los casos en los que se detectó una hiperdensidad en el grupo de TC convencional no se pudo distinguir entre extravasación de contraste y transformación hemorrágica, en comparación con el 4,8% del grupo de TC espectral (p < 0,001).ConclusionesLa TC espectral confiere una gran confianza diagnóstica al radiólogo para establecer el tipo de hiperdensidad detectada y, por ello, proporciona también una gran confianza terapéutica al neurólogo para reiniciar precozmente la anticoagulación. (AU)


Introduction. Acute ischemic stroke is one of the leading global causes of morbidity and mortality. Mechanical thrombectomy has improved the functional prognosis of this condition; however, hemorrhagic transformation is a common complication. Spectral computed tomography (CT) imaging, as a neuroimaging control test, distinguishes contrast extravasation from hemorrhagic transformation due to the differential behavior of materials at dual energy levels. This distinction is valuable in its clinical therapeutic management.Material and methods. A single-center, observational, retrospective study was conducted in which the presence of various clinical, radiological, and therapeutic variables in patients with acute ischemic stroke treated with mechanical thrombectomy at our hospital between July 2022 and March 2023 was investigated using access to a dissociated database and medical records.Results. Out of 155 included patients, spectral cranial CT was performed in 63, and conventional cranial CT in 75. In the spectral CT group, 21 hyperdense images were detected, compared to 28 in the conventional CT group. In 42.8% of cases where hyperdensity was detected in the conventional CT group, it was not possible to distinguish between contrast extravasation and hemorrhagic transformation, in contrast to the 4.8% in the spectral CT group (p < 0.001).Conclusions. Spectral CT provides high diagnostic confidence to the radiologist in identifying the type of detected hyperdensity, thereby offering significant therapeutic confidence to the neurologist in early resuming anticoagulation therapy. (AU)


Subject(s)
Humans , Tomography, X-Ray Computed , Thrombectomy , Atrial Fibrillation
2.
Rev Neurol ; 78(9): 247-252, 2024 May 01.
Article in Spanish, English | MEDLINE | ID: mdl-38682762

ABSTRACT

INTRODUCTION: Acute ischemic stroke is one of the leading global causes of morbidity and mortality. Mechanical thrombectomy has improved the functional prognosis of this condition; however, hemorrhagic transformation is a common complication. Spectral computed tomography (CT) imaging, as a neuroimaging control test, distinguishes contrast extravasation from hemorrhagic transformation due to the differential behavior of materials at dual energy levels. This distinction is valuable in its clinical therapeutic management. MATERIAL AND METHODS: A single-center, observational, retrospective study was conducted in which the presence of various clinical, radiological, and therapeutic variables in patients with acute ischemic stroke treated with mechanical thrombectomy at our hospital between July 2022 and March 2023 was investigated using access to a dissociated database and medical records. RESULTS: Out of 155 included patients, spectral cranial CT was performed in 63, and conventional cranial CT in 75. In the spectral CT group, 21 hyperdense images were detected, compared to 28 in the conventional CT group. In 42.8% of cases where hyperdensity was detected in the conventional CT group, it was not possible to distinguish between contrast extravasation and hemorrhagic transformation, in contrast to the 4.8% in the spectral CT group (p < 0.001). CONCLUSIONS: Spectral CT provides high diagnostic confidence to the radiologist in identifying the type of detected hyperdensity, thereby offering significant therapeutic confidence to the neurologist in early resuming anticoagulation therapy.


TITLE: Aplicación clinicorradiológica del uso de la tomografía computarizada craneal de tecnología espectral en el manejo del ictus isquémico agudo tras trombectomía mecánica.Introducción. El ictus isquémico agudo es una de las principales causas globales de morbimortalidad. La trombectomía mecánica ha mejorado el pronóstico funcional de esta patología; sin embargo, la transformación hemorrágica es una complicación frecuente. La tomografía computarizada (TC) de tecnología espectral, como prueba de neuroimagen de control, diferencia la extravasación de contraste de la transformación hemorrágica gracias al diferente comportamiento de los materiales a la energía dual, y esta distinción es de utilidad en su manejo clinicoterapéutico. Material y métodos. Estudio unicéntrico, observacional y retrospectivo, en el cual se investigó, mediante el acceso a una base de datos disociada y a la historia clínica, la presencia de una serie de variables clínicas, radiológicas y terapéuticas en los pacientes con ictus isquémico agudo que fueron tratados con trombectomía mecánica en nuestro hospital entre julio de 2022 y marzo de 2023. Resultados. De los 155 pacientes incluidos, se realizó una TC craneal espectral en 63 y convencional en 75. En el grupo de TC espectral se detectaron 21 imágenes hiperdensas y en el grupo de TC convencional fueron 28. En el 42,8% de los casos en los que se detectó una hiperdensidad en el grupo de TC convencional no se pudo distinguir entre extravasación de contraste y transformación hemorrágica, en comparación con el 4,8% del grupo de TC espectral (p < 0,001). Conclusiones. La TC espectral confiere una gran confianza diagnóstica al radiólogo para establecer el tipo de hiperdensidad detectada y, por ello, proporciona también una gran confianza terapéutica al neurólogo para reiniciar precozmente la anticoagulación.


Subject(s)
Ischemic Stroke , Thrombectomy , Tomography, X-Ray Computed , Humans , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/surgery , Male , Retrospective Studies , Female , Aged , Middle Aged , Aged, 80 and over , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology
3.
IEEE Trans Neural Syst Rehabil Eng ; 26(6): 1264-1271, 2018 06.
Article in English | MEDLINE | ID: mdl-29877851

ABSTRACT

Partial hand amputation is by far the most common type of amputation worldwide. Nevertheless, regardless of their potential clinical and socioeconomic impact, battery-powered partial hand prostheses, namely, powered digits, have modestly progressed so far, and very few clinical solutions are available today. Here, we present a mechanical architecture, an alternative to state-of-the-art solutions, which exploits a high efficiency, non-back drivable mechanical transmission based on a face-gear pair and a miniaturized clutch. We took inspiration from the synergetic prehension approach proposed by Childress for whole hand amputation. The finger was equipped with a myoelectric controller and a tactile sensor able to provide users with discrete event sensory feedback. Measured speed (90°/s) and force (6.5 N) of the newly dubbed S-Finger proved comparable with those of clinically available prostheses. The design demonstrated to be compact and rugged enough to undergo a clinical viability test with two partial hand amputees, fitted with custom three-fingered research prostheses using the S-Finger. The subjects successfully completed several dexterity tests and gave relevant feedback for the development of a second-generation device. These results contribute to the increasing research endeavors in the field of partial hand amputation.


Subject(s)
Feedback, Sensory , Fingers , Prostheses and Implants , Touch , Amputees , Biomechanical Phenomena , Electromyography , Hand , Hand Strength , Humans , Prosthesis Design
4.
Knee Surg Sports Traumatol Arthrosc ; 26(1): 182-187, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28707116

ABSTRACT

PURPOSE: In order to evaluate whether overuse has a significant role in rotator cuff tear (RCT) aetiology, we evaluated both shoulders of patients with old unilateral arm amputation expecting a higher rate of RC degeneration in the healthy side. METHODS: Nineteen males and six females (mean age: 57.3 ± 10.1) with an old (>20 years) unilateral arm amputation were submitted to an MRI of both shoulders. Tendon status and muscle tropism were evaluated according to Sugaya and Fuchs classifications, respectively; the acromion humeral distance was measured. Statistical analysis was performed to verify the prevalence of Sugaya and Fuchs categories in each sides. RESULTS: A significant prevalence of Sugaya type II in the amputated side (p = 0.02) and of type I in the healthy side (p < 0.001) was found. Rotator cuff was healthy in 28 and 52% of amputated and non-amputated side, respectively. The mean acromio-humeral distances of the amputated and healthy side were 0.8 cm (SD: 0.1) and 0.9 cm (SD: 0.1), respectively, (p = 0.02). A significant prevalence of Fuchs type II category in the healthy side (p < 0.001) was found. Fuchs III/IV were observed in 40 and 12% of amputated and healthy side, respectively. CONCLUSIONS: The present study resizes the role of overuse on the aetiology of RCT. Cuff tear prevalence in not amputated shoulders, inevitably submitted to functional overload, was not higher than that of coetaneous subjects with two functional upper limbs. Shoulder non-use is a risk factor for rotator cuff tear. As the prevalence of rotator cuff degeneration/tear is higher in the amputee side, non-use is a more relevant risk factor than overuse. In the daily clinical practice, patients with rotator cuff tear should be encouraged to shoulder movement because rotator cuff tendon status could be worsened by disuse. LEVEL OF EVIDENCE: III.


Subject(s)
Amputation, Surgical , Cumulative Trauma Disorders/etiology , Postoperative Complications/etiology , Rotator Cuff Injuries/etiology , Adult , Aged , Cross-Sectional Studies , Cumulative Trauma Disorders/diagnosis , Cumulative Trauma Disorders/epidemiology , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Prevalence , Risk Factors , Rotator Cuff Injuries/diagnosis , Rotator Cuff Injuries/epidemiology
5.
Vet Comp Oncol ; 15(1): 215-225, 2017 Mar.
Article in English | MEDLINE | ID: mdl-26109175

ABSTRACT

The frequency of normoblastemia in dogs receiving chemotherapy is unknown. To provide this information, we calculated the percentage and number of nucleated erythrocytes (nRBCs) in blood of dogs treated for lymphoma (n = 284), mast cell tumour (n = 40) or carcinoma (n = 46). Relative normoblastemia (>1 or >5%) and absolute normoblastemia (>0.1 or >0.4 × 103 µL-1 ) were found after administration of vincristine (49.3, 20.5, 42.5, 19.2%, respectively), carboplatin (37.0, 2.2, 34.8, 13.0%), cyclophosphamide (30.8, 7.7, 23.1, 7.7%), doxorubicin (25.0, 8.3, 21.7, 6.7%), vinblastine and prednisone (25.0; 5.0; 22.5; 7.5%). Absolute normoblastemia was very severe (>1.0 × 103 nRBC µL-1 ) after administration of vincristine (9.6%), doxorubicin (3.3%), vinblastine and prednisone (2.5%). Absolute normoblastemia negatively correlated with RBC counts (P < 0.001) and positively (P < 0.001) with reticulocyte and WBC counts, but correlation coefficients were low (-0.19, 0.37, 0.15). Vincristine, doxorubicin or vinblastine and prednisone may induce severe normoblastemia. This may increase WBC counts and mask neutropenia associated with chemotherapy.


Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma/veterinary , Dog Diseases/blood , Erythroblasts/drug effects , Lymphoma/veterinary , Mastocytosis/veterinary , Analysis of Variance , Animals , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma/blood , Dogs , Erythrocyte Count , Erythrocytes/drug effects , Erythrocytes/pathology , Italy , Lymphoma/blood , Mastocytosis/blood , Retrospective Studies
6.
Physiol Res ; 64(5): 769-82, 2015.
Article in English | MEDLINE | ID: mdl-26047373

ABSTRACT

CARM1 interacts with numerous transcription factors to mediate cellular processes, especially gene expression. This is important for the maintenance of ESC pluripotency or intervention to tumorigenesis. Here, we studied epigenomic effects of two potential CARM1 modulators: an activator (EML159) and an inhibitor (ellagic acid dihydrate, EA). We examined nuclear morphology in human and mouse embryonic stem cells (hESCs, mESCs), as well as in iPS cells. The CARM1 modulators did not function similarly in all cell types. EA decreased the levels of the pluripotency markers, OCT4 and NANOG, particularly in iPSCs, whereas the levels of these proteins increased after EML159 treatment. EML159 treatment of mouse ESCs led to decreased levels of OCT4 and NANOG, which was accompanied by an increased level of Endo-A. The same trend was observed for NANOG and Endo-A in hESCs affected by EML159. Interestingly, EA mainly changed epigenetic features of nucleoli because a high level of arginine asymmetric di-methylation in the nucleoli of hESCs was reduced after EA treatment. ChIP-PCR of ribosomal genes confirmed significantly reduced levels of H3R17me2a, in both the promoter region of ribosomal genes and rDNA encoding 28S rRNA, after EA addition. Moreover, EA treatment changed the nuclear pattern of AgNORs (silver-stained nucleolus organizer regions) in all cell types studied. In EA-treated ESCs, AgNOR pattern was similar to the pattern of AgNORs after inhibition of RNA pol I by actinomycin D. Together, inhibitory effect of EA on arginine methylation and effect on related morphological parameters was especially observed in compartment of nucleoli.


Subject(s)
Cell Nucleolus/physiology , Cell Nucleolus/ultrastructure , Embryonic Stem Cells/physiology , Embryonic Stem Cells/ultrastructure , Epigenesis, Genetic/physiology , Protein-Arginine N-Methyltransferases/physiology , Animals , Cell Line , Cell Nucleolus/drug effects , Ellagic Acid/pharmacology , Embryonic Stem Cells/drug effects , Epigenesis, Genetic/drug effects , Humans , Mice , Protein-Arginine N-Methyltransferases/antagonists & inhibitors
7.
J Biosci ; 32(4): 763-8, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17762149

ABSTRACT

A chromosome study was carried out on a number of European and Central Asiatic diploid green toad populations by means of standard and various other chromosome banding and staining methods (Ag-NOR-, Q-, CMA3-, late replicating [LR] banding pattern, C-and sequential C-banding + CMA3 + DAPI). This study revealed the remarkable karyological uniformity of specimens from all populations, with the only exception being specimens from a Moldavian population, where one chromosome pair was heteromorphic. Though similar in shape, size and with an identical heterochromatin distribution,the difference in the heteromorphic pair was due to a large inverted segment on its long arms. This heteromorphism was restricted to females, suggesting a female heterogametic sex chromosome system of ZZ/ZW type at a very early step of differentiation.


Subject(s)
Anura/genetics , Sex Chromosomes , Animals , Female , Karyotyping , Male
8.
Am J Hum Biol ; 19(4): 589-92, 2007.
Article in English | MEDLINE | ID: mdl-17546608

ABSTRACT

We analyzed the frequencies of eight human polymorphic Alu insertion loci in population samples from five towns in North-West Italy: Postua, Cavaglià, Biella, Torino, and Genova. All loci under scrutiny were found to be polymorphic in all samples, with the two exceptions of locus A25 in Postua, which was fixed for the absence of the Alu element, and APO in Genova, where the Alu insertion was fixed. Heterozigosity values were highly variable in all loci. F(ST) values for all loci indicate that most of the variability is found within populations, while between population variability is lower. In the multidimensional scaling (MDS) analysis plot, the studied populations are separated from the main group represented by European populations. The Postua sample is set apart also from neighboring towns as Cavaglià and Biella, confirming previous observations of the demographic isolation of this population.


Subject(s)
Alu Elements/genetics , Gene Frequency , Genetics, Population , Polymorphism, Genetic/genetics , Humans , Italy , Population Groups/genetics
9.
Pharmazie ; 61(6): 505-10, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16826968

ABSTRACT

Four series of 5-aryl-imidazo[2,-c][1,4]benzodiazepine derivatives 1a-f, 2a-f, 3a-f, and 4a-f were synthesized and tested for their affinity at both the peripheral and central benzodiazepine receptors. Among the four series, only N-10 and C-11 sites were changed, mainly [N(CH3)-CO], [N=CH], [NH-CO], [NH-CH2], and in each series the halogen site was varied at the positions C-7, C-2', and C-4'. In particular, 10-methyl-benzodiazepinones 1a and 1b were designed as tricyclic constrained analogues of diazepam and Ro5-4864. All the tested compounds did not show significant binding activity at central benzodiazepine receptors, but relatively good PBzR binding affinities were found for 10-methyl-benzodiazepinone 1c and benzodiazepines 2b, c. Benzodiazepinones 3a-f were prepared by cyclization with 1,1'-carbonyldiimidazole of the corresponding 2-(aryl-imidazol-1-yl-methyl)-arylamines, obtained from the suitable (2-amino-aryl)-aryl-methanols with 1,1'-carbonyldiimidazole in different conditions. N-Alkylation of 3a-f to 1a-f was achieved using dimethylformamide-dimethylacetal. Reduction of 3a-f to 4a-f was accomplished with lithium aluminum hydride or borane and oxidation of 4a-f to 2a-f was performed with manganese (IV) oxide.


Subject(s)
Benzodiazepines/chemical synthesis , Benzodiazepines/pharmacokinetics , Benzodiazepinones/pharmacokinetics , Central Nervous System/metabolism , Diazepam/analogs & derivatives , Diazepam/pharmacokinetics , Hypnotics and Sedatives/pharmacokinetics , Imidazoles/chemical synthesis , Imidazoles/pharmacokinetics , Peripheral Nervous System/metabolism , Receptors, GABA-A/metabolism , Adrenal Cortex/drug effects , Adrenal Cortex/metabolism , Animals , Binding, Competitive/drug effects , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Isoquinolines/pharmacokinetics , Rats
10.
J Oral Pathol Med ; 32(6): 323-9, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12787038

ABSTRACT

BACKGROUND: Topical corticosteroids are the mainstay treatment for oral lichen planus (OLP), but some authors suggest that systemic corticosteroid therapy is the only way to control acute presentation of OLP. METHODS: Forty-nine patients with histologically proven atrophic-erosive OLP were divided into two groups matched for age and sex. The test group (26 patients) was treated systemically with prednisone (50 mg/day), and afterwards with clobetasol ointment in an adhesive medium plus antimicotics, whereas the control group (23 patients) was only treated topically with clobetasol plus antimycotics. RESULTS: Complete remission of signs was obtained in 68.2% of the test group and 69.6% of the control group, respectively (P = 0.94). Similar results were obtained for symptoms. Follow-up showed no significant differences between the two groups. One-third of the patients of the test group versus none in the control group experienced systemic side-effects (P = 0.003). CONCLUSIONS: The most suitable corticosteroid therapy in the management of OLP is the topical therapy, which is easier and more cost-effective than the systemic therapy followed by topical therapy.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Clobetasol/analogs & derivatives , Clobetasol/administration & dosage , Lichen Planus, Oral/drug therapy , Prednisone/administration & dosage , Administration, Oral , Administration, Topical , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Glucocorticoids , Humans , Lichen Planus, Oral/pathology , Male , Middle Aged
12.
Farmaco ; 56(10): 771-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11718270

ABSTRACT

In the context of a research program aimed at elucidating the properties of the 5H-imidazo[2,1-c][1.4]benzodiazepine system, a series of 11-aryl-5H-imidazo[2,1-c][1,4]benzodiazepines (3a-i) and their 10,11-dihydro-derivatives (4a-i) has been synthesized. The synthetic strategy includes the preparation of the aryl-[1-(2-nitrobenzyl)-1H-imidazol-2-yl]methanones (5a-i) followed by their reduction and subsequent cyclization. Affinities of compounds 3a-i and 4a-i for central benzodiazepine as well as for adenosine A1-receptors were determined by radioligand binding assays. Among the unsaturated analogues, the highest activity at both receptors is displayed by 1H-(2-thienyl) derivative 3e. The hydrogenated analogues 4a-i do not exhibit considerable binding affinity either for central benzodiazepine or for adenosine A1-receptors.


Subject(s)
Anti-Anxiety Agents/chemical synthesis , Benzodiazepines/chemical synthesis , Receptors, Purinergic P1/metabolism , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/metabolism , Benzodiazepines/chemistry , Benzodiazepines/metabolism , Binding Sites/drug effects , Male , Mice , Mice, Inbred CBA , Rats , Rats, Sprague-Dawley
13.
Dentomaxillofac Radiol ; 30(6): 346-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11641735

ABSTRACT

A unique case of fatty replacement of the masticatory muscles, causing progressive limitation of mouth opening, is presented. Both CT and MRI revealed an almost total substitution of the masticatory muscles with fatty tissue, confirmed by the histopathology at surgery. Myotomy of masseter and internal pterygoid muscles and coronoidotomy improved his symptoms. There is no known cause of fibroadipose replacement of muscle fibres.


Subject(s)
Adipose Tissue/diagnostic imaging , Masticatory Muscles/diagnostic imaging , Masticatory Muscles/pathology , Muscular Disorders, Atrophic/diagnostic imaging , Adult , Humans , Magnetic Resonance Imaging , Male , Muscular Disorders, Atrophic/pathology , Range of Motion, Articular , Tomography, X-Ray Computed
14.
Clín. salud ; 12(3): 391-404, sept. 2001. tab, graf
Article in Es | IBECS | ID: ibc-8237

ABSTRACT

La tecnología de la Realidad Virtual (RV) está teniendo un gran impacto en diferentes ámbitos de la salud, especialmente en el de los tratamientos psicológicos. Este trabajo se centra en su utilidad para el tratamiento de la fobia a volar. Las intervenciones psicológicas para este problema basadas en la terapia de la exposición han demostrado ser eficaces, pero dada la naturaleza de este trastorno tienen importantes limitaciones, pues resultan caras en términos de tiempo, dinero y esfuerzos. La RV ayuda a superar estas dificultades, ya que permite recrear diferentes ambientes en los que la persona puede interactuar con sus miedos mientras está en un medio seguro y protegido (la consulta del terapeuta). El presente trabajo tiene dos objetivos: mostrar los escenarios virtuales que nuestro equipo ha diseñado para el tratamiento del miedo a volar mediante RV y presentar los resultados de un estudio de caso que apoyan su eficacia (AU)


Subject(s)
Humans , Phobic Disorders/therapy , User-Computer Interface
15.
EMBO Rep ; 2(8): 697-702, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11493597

ABSTRACT

In selenoproteins, incorporation of the amino acid selenocysteine is specified by the UGA codon, usually a stop signal. The alternative decoding of UGA is conferred by an mRNA structure, the SECIS element, located in the 3'-untranslated region of the selenoprotein mRNA. Because of the non-standard use of the UGA codon, current computational gene prediction methods are unable to identify selenoproteins in the sequence of the eukaryotic genomes. Here we describe a method to predict selenoproteins in genomic sequences, which relies on the prediction of SECIS elements in coordination with the prediction of genes in which the strong codon bias characteristic of protein coding regions extends beyond a TGA codon interrupting the open reading frame. We applied the method to the Drosophila melanogaster genome, and predicted four potential selenoprotein genes. One of them belongs to a known family of selenoproteins, and we have tested experimentally two other predictions with positive results. Finally, we have characterized the expression pattern of these two novel selenoprotein genes.


Subject(s)
Codon, Terminator/genetics , Drosophila melanogaster/genetics , Genome , Insect Proteins/genetics , Proteins/genetics , Selenocysteine/metabolism , Amino Acid Sequence , Animals , Cell Line , Drosophila melanogaster/embryology , Gene Expression Profiling , Humans , In Situ Hybridization , Insect Proteins/chemistry , Molecular Sequence Data , Nucleic Acid Conformation , Proteins/chemistry , Regulatory Sequences, Nucleic Acid/genetics , Selenium Radioisotopes/metabolism , Selenoproteins , Sequence Alignment
16.
Org Lett ; 2(25): 3955-8, 2000 Dec 14.
Article in English | MEDLINE | ID: mdl-11112616

ABSTRACT

[structure] Two water-soluble fullerene derivatives have been computer-designed and synthesized. They may exhibit interesting anti-HIV activity owing to the presence of two ammonium groups strategically located on the spheroid surface.


Subject(s)
Carbon/chemistry , Fullerenes , HIV Protease Inhibitors/chemical synthesis , Drug Design , Magnetic Resonance Spectroscopy , Models, Molecular
17.
Arch Pharm (Weinheim) ; 333(11): 373-80, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11129979

ABSTRACT

The synthesis and the biological activity of (+/-)-cis- and (+/-)-trans-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methylthio]phenyl]carbamic acid ethyl esters (2a and 2b) are discussed. They were designed as structural analogues of Tubulozole, a synthetic tubulin polymerisation inhibitor with antimitotic properties. Biological tests were carried out on PC12, a neuronal-like cell line derived from rat pheochromocytoma, and on GL15, a cell line derived from human glioblastoma. The exposure (from 5 to 20 h) of GL15 and PC12 cells to different concentrations (0.1-1000 microM; IC50 approximately 1 microM) of 2a or 2b resulted in a drastic decrease in the number of viable cells without an apparent effect on the cell distribution in the various phases of the cell cycle. Compound 2a or 2b (10 microM) induced cell death by activating apoptosis. This was correlated with the activation of an oscillating Ca(2+)-dependent mechanism which increased the intracellular calcium concentration ([Ca2+]i) via Ca(2+)-release from internal stores. Moreover, 2a (10 microM) also induced severe damage of cytoskeletal F-actin filaments after a 5 h incubation in GL15 cells. This was also observed but to a smaller extent, for 2b. Under the same experimental conditions, PC12 cells showed similar actin deregulation.


Subject(s)
Apoptosis/drug effects , Cytoskeleton/drug effects , Dioxolanes/chemical synthesis , Dioxolanes/pharmacology , Neuroglia/drug effects , Neurons/drug effects , Adrenal Gland Neoplasms , Animals , Cytoskeleton/ultrastructure , Dioxolanes/chemistry , Molecular Structure , Neuroglia/cytology , Neuroglia/ultrastructure , Neurons/cytology , Neurons/ultrastructure , PC12 Cells , Pheochromocytoma , Rats , Structure-Activity Relationship
18.
FEMS Microbiol Lett ; 192(1): 9-14, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11040421

ABSTRACT

The poly(ADP-ribose) polymerase-like thermozyme purified from Sulfolobus solfataricus was characterised with respect to some physico-chemical properties. The archaeal protein exhibited a scarce electrophoretic mobility at both pH 2.9 and pH 7.5. Determination of the isoelectric point (pI=7.0-7.2) allowed us to understand the reason for the limited migration at pH 7.5, while amino acid composition analysis showed a moderate content of basic residues, which reduced mobility at pH 2.9. With respect to the charge, the archaeal enzyme behaved differently from the eukaryotic thermolabile poly(ADP-ribose) polymerase, described as a basic protein (pI=9.5). Well known inhibitors of the mesophilic polymerase like Zn(2+), nicotinamide and 3-aminobenzamide exerted a smaller effect on the enzyme from S. solfataricus, reducing the activity by at most 50%. Mg(2+) was a positive effector, although in a dose-dependent manner. It influenced the fluorescence spectrum of the archaeal protein, whereas NaCl had no effect.


Subject(s)
Poly(ADP-ribose) Polymerases/chemistry , Poly(ADP-ribose) Polymerases/metabolism , Sulfolobus/enzymology , Amino Acids/analysis , Cations, Divalent/pharmacology , Electrophoresis, Polyacrylamide Gel , Isoelectric Focusing , Molecular Weight , Spectrometry, Fluorescence
19.
Arch Pharm (Weinheim) ; 333(9): 299-304, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11039186

ABSTRACT

In this study we extended our exploration of the N-azolylamine moiety for its antifungal activity. We prepared a number of N-azolylamino derivatives. The synthetic sequence includes the preparation of aminoazole Schiff bases, and the reduction and the alkylation of the corresponding secondary amines. The title compounds were evaluated in vitro against several pathogenic fungi responsible for human disease. The most potent antimicrobial compound was the N-(biphenyl-4-yl)methyl-N-(2,4-dichlorophenyl)methyl-1H-imidazol-l-yl amine (21), which was found to be active against yeasts and dermatophytes; its potency and selectivity were comparable to those of miconazole.


Subject(s)
Amines/chemical synthesis , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Azoles/chemical synthesis , Fungi/drug effects , Amines/chemistry , Amines/pharmacology , Antifungal Agents/chemistry , Azoles/chemistry , Azoles/pharmacology , Humans , Microbial Sensitivity Tests , Molecular Structure , Mycoses/microbiology , Structure-Activity Relationship , Yeasts/drug effects
20.
Arch Pharm (Weinheim) ; 333(6): 162-6, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10909187

ABSTRACT

The methyl group of naftifine (1) and butenafine (2) was replaced by an azolic nucleus to obtain the new compounds 3-8 which exhibit the characteristics of both allylamine (or benzylamine) and azole antifungals. The title compounds were evaluated in vitro against several pathogenic fungi responsible for human disease. Among these, compounds 5, 6, and 8 were found to inhibit the growth of dermatophytes with a potency comparable to that of naftifine. The synthetic sequence includes the preparation of aminoazole Schiff bases, reduction, and alkylation of the corresponding secondary amines.


Subject(s)
Allylamine/analogs & derivatives , Antifungal Agents/chemical synthesis , Benzylamines/chemical synthesis , Naphthalenes/chemical synthesis , Allylamine/chemical synthesis , Allylamine/pharmacology , Antifungal Agents/pharmacology , Benzylamines/pharmacology , Cell Line , Fungi/drug effects , Humans , Naphthalenes/pharmacology , Structure-Activity Relationship
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