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Biomedical subjects

A Morello

Publications and source records attributed to A Morello.

At least 19 recordsLinked to original sources
PubMed2004

Nuclear spin dynamics in the quantum regime of a single-molecule magnet.

We show that the nuclear spin dynamics in the single-molecule magnet Mn12-ac below 1 K is governed by quantum tunneling fluctuations of the cluster spins, combined with intercluster nuclear spin diffusion. We also obtain the first experimental proof that-surprisingly-even deep in the quantum regime the nuclear spins remain in good thermal contact with the lattice phonons. We propose a simple model for how T-independent tunneling fluctuations can relax the nuclear polarization to the lattice that may serve as a framework for more sophisticated theories.

Journal Article↗
PubMed2004

Laser-assisted uvulopalatoplasty for snoring: does it meet the expectations?

The high prevalence of habitual snoring (35% of the general population) and the increasing demand for an effective treatment have led, in the last decade, to the generalisation of laser-assisted uvulopalatoplasty (LAUP). However, acceptable studies on its effectiveness are lacking. The present randomised, placebo-controlled study included 25 nonapnoeic and mild obstructive sleep apnoea snorers to evaluate LAUP effectiveness for snoring. Group I received a one-stage LAUP treatment and group II a placebo (simulated snore surgery followed by an oral placebo). Before each treatment and 3 months after, the variables and procedures assessed were: body weight; sleepiness (Epworth sleepiness scale); quality of life (SF-36); subjective snoring intensity (0-10 analogue scale); objective snoring intensity (average decibel intensity); snoring index (number of snores per hour); and apnoea/hypopnea index. No differences were observed in body weight, sleepiness, quality of life, subjective and objective intensity, and frequency of snoring, and apnoea/hypopnea index between the groups before and 3 months after treatment. In conclusion, this study provides evidence of the lack of effectiveness of one-stage laser-assisted uvulopalatoplasty for snoring in nonapnoeic and mild obstructive sleep apnoea patients, with the result that it does not meet the expectations generated by the procedure.

Adult↗
PubMed2003

Long-range ferromagnetic dipolar ordering of high-spin molecular clusters.

We report the first example of a transition to long-range magnetic order in a purely dipolarly interacting molecular magnet. For the magnetic cluster compound Mn6O4Br4(Et2dbm)6, the anisotropy experienced by the total spin S = 12 of each cluster is so small that spin-lattice relaxation remains fast down to the lowest temperatures, thus enabling dipolar order to occur within experimental times at T(c) = 0.16 K. In high magnetic fields, the relaxation rate becomes drastically reduced and the interplay between nuclear- and electron-spin lattice relaxation is revealed.

Journal Article↗
PubMed2001

Trypanosoma cruzi: inhibition of parasite growth and respiration by oxazolo(thiazolo)pyridine derivatives and its relationship to redox potential and lipophilicity.

Chagas' disease constitutes a therapeutic challenge because presently available drugs have wide toxicity to the host and are generally ineffective in the chronic stages of the disease. A series of oxazolo(thiazolo)pyridene derivatives were studied on Trypanosoma cruzi epimastigote growth and oxygen consumption and their electrochemical (redox) potentials and lipophilicity. The derivatives produced different degrees of parasite growth and respiration inhibition on CL Brener, LQ, and Tulahuen strains of T. cruzi epimastigotes. Respiratory chain inhibition appears to be a determinant of the trypanosomicidal activity of these compounds, since a significant correlation between respiration and culture growth inhibition was found. A similar correlation was found, within the different structural subfamilies, between toxic effects and the ability of the compounds to be oxidized in aqueous media. The inhibition of respiration and of parasite growth in culture increases with the lipophilicity of the substituents on the oxazolopyridine nucleus. No difference in the action of these derivatives was found among the different parasite strains. It is concluded that these compounds may have a potential usefulness in the treatment of Chagas' disease.

Animals↗
PubMed2001

Late sequelae of pontine lesions by acute uncal herniation.

The authors report the late macro- and microscopic aspects of the brainstem lesions found in two patients who survived an acute uncal herniation, respectively, 176 and 62 days. They also describe the evolution of the clinical picture characterized by the complete disappearance of initially present neurological signs but by a persistent comatose state.

Acute Disease↗
PubMed2000

Trypanosoma cruzi: H2 complex and genetic background influence on the humoral immune response against epimastigotes.

Using A.SW, A.CA, B10.S and B10.M congenic mouse strains, we measured the IgG specific humoral immune responses against sonicated and live Trypanosoma cruzi epimastigotes. Genes located in the A background (A.SW and A.CA strains) mediate higher IgG responses against the parasite antigenic complexes than those located in the B background (strains B10.S and B10.M), regardless of the H2 haplotypes. Thus, non H2 genetic elements seem to be more important in determining differences in the total IgG immune response against T. cruzi. Whether a detectable H2 effect, in favor of the H2(s) haplotype, occurred in the A or B background, was contingent on the immunisation protocol used. Thus, the H2(s) haplotype mediates a higher IgG response in the A background, if immunised with live epimastigotes, and in the B background against sonicated epimastigotes. Most likely this represents a complex sequence of events, controlled by non-MHC genes, involving antigen handling and processing and depending on the physical form of antigen delivery.

Animals↗
PubMed2000

Effects of 3-chloro-phenyl-1,4-dihydropyridine derivatives on Trypanosome cruzi epimastigotes.

A series of 3-chloro-phenyl-1,4-dihydropyridine derivatives produced different degrees of inhibition of parasite growth and respiration on clone Brener, LQ and Tulahuen strains of Trypanosome cruzi epimastigotes. Respiratory chain inhibition appears to be a posible determinant of the trypanosomicidal activity of this compounds. No difference in the action of these derivatives was found among the different parasite strains. For comparative purposes, the inhibitory effects of felodipine and nicardipine are also reported. A good correlation between toxic effects and the easiness of oxidation of the dihydripyridine ring was found. The presence of a fused ring on the dihydropyridine moiety significantly diminished the inhibitory effects.

Animals↗
PubMed1999

Effects of some beta-carboline alkaloids on intact Trypanosoma cruzi epimastigotes.

Several beta-carboline (9H-pyrido-[3,4-b]-indole) alkaloids were evaluated for in vitro trypanosomicidal activity against Trypanosoma cruzi epimastigotes belonging to two different strains (Tulahuén and LQ) showing different sensitivity to nifurtimox. Important differences were observed in the susceptibility of the parasites to these natural substances, with the relatively nifurtimox-resistant LQ strain showing greater sensitivity to the beta-carbolines. Respiratory chain inhibition appears to be a possible determinant of the trypanosomicidal activity of these compounds.

Animals↗
PubMed1999

Stretching (?) of the spinal cord as a cause of paraplegia in a patient with Cushing's syndrome.

Paraplegia with a total anesthesia level was found in a patient who had Cushing's syndrome. There was marked osteoporosis of the spine and a moderate wedge shaped compression fracture of the T4 vertebral body but no stenosis of the canal could be observed. On the grounds of the CT findings stretching of the spinal cord caused by the rapidly evolving kyphosis of the thoracic tract has been thought to be the responsible factor of the clinical deficits.

Adult↗
PubMed1998

Involvement of thiol metabolism in resistance to glucantime in Leishmania tropica.

Clinical resistance to pentavalent antimonials, in the form of pentostam (sodium stibogluconate) or glucantime (N-methylglucamine antimoniate), has long been recognized as a problem in Leishmaniasis. However, the mechanisms of resistance are unclear. We selected in vitro a Leishmania tropica line resistant to 1.2 mg/mL of Sb(V) of glucantime (GLU-R10). The cell line has a stable phenotype for at least 6 months and a resistance index of 1400-fold. The resistant line has no cross-resistance to pentostam or to SbCl3 and SbCl5. The resistance to glucantime was reverted by buthionine sulfoximine (BSO) and chlorambucil (CLB); however, thiol analyses by HPLC of wild-type and GLU-R10 cell lines, in the presence or absence of the drug, showed no differences between these two cell lines. The resistant line had a DNA amplification shown as a circular extrachromosomal element (G-circle) of approximately 22 kb. However, the specific probes for gamma-glutamyl cysteine synthetase, ornithine decarboxylase and trypanothione reductase did not recognize the G-circle amplified in the GLU-R10. The G-circle did not arise from the H region and was not related with P-glycoprotein Pgp-MDR- or Pgp-MRP-like genes. Northern blot analysis of the G-circle showed that a single transcript of approximately 6 kb was overexpressed in the resistant line. Molecular characterization of the G-circle would lead to the determination of the gene(s) involved in resistance to glucantime in Leishmania.

Animals↗
PubMed1997

Nitro aryl 1,4-dihydropyridine derivatives: effects on Trypanosoma cruzi.

A series of nitro aryl 1,4-dihydropyridine derivatives produced inhibition of both cell growth and oxygen consumption on Tulahuen and LQ strains, and clone Dm 28c of epimastigotes of Trypanosoma cruzi. Nicardipine was found to be the most potent derivative in both growth cell (I50 = 70 microM) and oxygen uptake (I50 = 26 microM in intact parasites, I50 = 325 microM in situ mitochondria). A correlation between the inhibitory effects on the growth cell and the apparent first order kinetic for the uptake of the 1,4-dihypyridine derivatives by T. cruzi epimastigotes was found. Thus, nicardipine, the most potent derivative, exhibited the highest apparent rate constant, ku, (0.043 min-1). On the other hand, no susceptibility differences by strains and clone Dm 28c to the action of these drugs were found.

Animals↗
PubMed1997

[Discitis in childhood: integrated neuroradiological imaging in diagnosis and follow-up study of one case].

Discitis is an inflammatory disease of the intervertebral disc which has usually a benign evolution in childhood. It often recognizes an infectious etiology. Still discussed however is the possibility of a primitive discal involvement (not secondary to a vertebral inflammation) or of a non infectious etiology and the subsequent more correct diagnostic-therapeutic procedures. We report a case of a girl with discitis diagnosed early and treated with antibiotics and orthopedic corset, whose follow-up shows a benign evolution. We underline the importance of modern neuroradiological imaging: in particular, MR plays a major role in the inflammatory diseases of the column, both in diagnosis and in follow-up. MR scans of the involved disc allow frequent controls without radiogenic risks and with a good resolution because of the multiplanarity typical of the method.

Anti-Infective Agents↗
PubMed1996

Glutathione and trypanothione in several strains of Trypanosoma cruzi: effect of drugs.

Glutathione (GSH), trypanothione (T(SH)2) and glutathionyl spermidine (GSH-SP) concentrations were determined in the Tulahuén and LQ strains and the DM 28c clone of Trypanosoma cruzi. The concentrations of GSH, T(SH)2 and GSH-SP, expressed as nmol of GSH per g of parasite fresh weight, were 60.1, 397.8 and 103.9, respectively, for the Tulahuén strain. For the DM 28c clone, the values were 113.9, 677.9 and 164.1, respectively, and for the LQ strain they were 199.1, 1100.5 and 55.3, respectively. When the parasites were treated with 10 microM nifurtimox or 50 microM benznidazole for 2 h, the concentrations of all three reduced thiols decreased strongly. The total amount of T(SH)2 decreased by more than 50%. Treatment of the parasites with 5 mM buthionine sulfoximine, an inhibitor of GSH synthesis, for 6 h diminished the concentrations of the reduced thiols by between 27% and 53% with respect to the controls. Cyclohexylamine, an inhibitor of spermidine synthesis, decreased the concentrations of T(SH)2 and GSH-SP but not that of GSH. It is possible to conclude from this study that trypanothione is the most important thiol involved in the detoxication of nifurtimox and benznidazole in T. cruzi and that electrophilic reduced metabolites of both drugs are most probably conjugated with GSH, T(SH)2 and GSH-SP, thus decreasing their concentrations. GSH biosynthesis is an important drug target.

Animals↗
PubMed1995

Effects and mode of action of 1,4-naphthoquinones isolated from Calceolaria sessilis on tumoral cells and Trypanosoma parasites.

The naphthoquinones 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (CS-1), (-)-2,3,3-trimethyl-2-3-dihydronaphtho[2,3-b]furan-4,9-quinone (CS-3), and 2-acetoxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (CS-5) isolated from Calceolaria sessilis were tested against Trypanosoma cruzi epimastigotes, the TA3 tumor cell line and the methotrexate-resistant subline TA3-MTX-R. Naphthoquinone CS-3 was the most active; the 50% culture growth inhibition (I50) on T. cruzi (Tulahuén and LQ strain and DM28c clone) was at concentrations ranging from 2.1 to 5.2 mumolar. Also CS-3 inhibited TA3 and TA3-MTX-R culture growth with an I50 of 2.1 and 3.8 mumolar, respectively. Naphthoquinone CS-3 inhibited the respiration of the tumor cells by interfering with the electron transport at some point between NADH and ubiquinone. The respiration of T. cruzi was not inhibited by naphthoquinone CS-3. Naphthoquinone CS-3 produced a temporary increase of oxygen consumption in T. cruzi and tumor cells, suggesting the generation and participation of free radicals.

Animals↗
PubMed1995

Time-course of stepwise CPAP titration. Behavior of respiratory and neurological variables.

Because successful medical treatment of obstructive sleep apnea/hypopnea syndrome (SAHS) depends on adequate CPAP treatment, we have analyzed in nine SAHS patients the behavior of respiratory and neurological parameters during a stepwise, polysomnography-controlled CPAP titration to achieve an optimal CPAP. Particularly, we have focused on which simple variable could predict the optimal CPAP pressure and could better define a distinctive optimal-suboptimal pattern. Main parameters analyzed through the CPAP titration procedure were respiratory events (apnea, hypopnea), the contour of inspiratory flow, the pleural pressure behavior, the thoraco-abdominal motion, oximetry, arousals, and sleep stage. During the CPAP titration we observed: (1) a rounded shape in the inspiratory flow contour was associated with the lowest esophageal pressure; (2) during stepwise increases in CPAP, almost all apnea events changed to hypopnea periods, followed by prolonged periods of limited inspiratory flow with still high esophageal pressure but without arousals (probably suboptimal CPAP); and (3) as CPAP reached suboptimal levels, sleep stage moved to deeper stages without arousals. We conclude that if during CPAP titration the end point is the disappearance of arousals, most patients with SAHS will still exhibit periods of high intrathoracic pressures with limited inspiratory flow. Alternatively, if the end point to be reached is the lowest esophageal pressure, higher CPAP levels will be needed. The contour of inspiratory flow appears as the simplest variable that best correlates with lowest esophageal pressure during CPAP titration.

Adult↗