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Biomedical subjects

F Melo

Publications and source records attributed to F Melo.

At least 19 recordsLinked to original sources
PubMed1999

Therapeutic effects of different doses of botulinum toxin in chronic anal fissure.

PURPOSE: The aim of this study was to evaluate the clinical and manometric results of three different doses of botulinum toxin and two methods of injection for the treatment of chronic idiopathic anal fissure. METHODS: Sixty-nine patients with chronic anal fissure were included in a non-randomized, prospective trial of intrasphincteric injection of botulinum toxin. All patients reported postdefecatory anal pain lasting more than two months. Scoring systems were developed for anal pain, bleeding, and defecatory difficulty. Maximum resting and squeeze anal pressures were determined before and one month after treatment. Twenty-three patients undergoing a 5-U injection of diluted botulinum toxin A (BOTOX) on each side of the anal sphincter (total dose, 10 U) constituted the first group. In a second group 27 patients were injected as previously described, with an additional 5-U injection below the fissure (total dose, 15 U). The 19 patients constituting the third group received a 7-U injection on each side of the anus and below the fissure (total dose, 21 U). All patients were followed up for at least six months. RESULTS: Pain relief one month after treatment was more evident in the second and the third group (48 percent of patients in the first group, 74 percent in the second group, and 100 percent in the third group). A significant reduction of the mean resting pressure was demonstrated only in Groups II and III (P < 0.05), whereas the mean squeeze pressure significantly decreased in the three groups (P < 0.01 in Group I and P < 0.001 in Groups II and III). Fifty-two percent of the patients in the first group, 30 percent in the second group, and 37 percent in the third group were reinjected during the follow-up period, because of persistence of symptomatology or early relapse. The need for surgery was similar in the first and the second group (17 and 19 percent, respectively) and clearly lower in the last group (5 percent). No serious complications or incontinence attributable to this therapeutic modality developed in any patient. CONCLUSIONS: Intrasphincteric injection of botulinum toxin is a reliable new option in the treatment of uncomplicated chronic anal fissure. The healing rate is related to the dose and probably to the number of puncture sites. No permanent damage to the continence mechanism was detected in these patients.

Adult↗
PubMed1998

Assessing protein structures with a non-local atomic interaction energy.

We describe a new approach, based on the energy of non-local interactions, to assess protein structures. The method uses a very sensitive and accurate atomic mean force potential (AMFP) to calculate the non-local energy profile (NL-profile) of a proteins structure. Several protein models, built using the comparative modeling technique and containing several errors, were evaluated. These models exhibit a good stereochemistry and have been previously checked with different, widely used, methods that failed to detect the errors. The AMFP-derived energy profiles are able to correlate high scores with point errors and misalignments in the models. The point errors are frequently found in loops or regions of structural differences between the template and the target protein. The misalignments are clearly detected with very high scores. The performance of the method was also tested for the assessment of X-ray solved protein structures. In a data set of 143 well solved and non-redundant protein structures, we find that the average energy Z-scores, obtained from AMFP, increase as the resolution decreases. In the case of structures that have already been described as having an unusual stereochemistry, very high Z-scores are obtained. Moreover, energy calculations for some pairs of obsolete and replacement proteins always show higher Z-scores for the obsolete proteins. Finally, two particular cases show the usefulness of the profiles in the assessment of X-ray solved protein structures. First, the NL-profile of a protein structure refined in the incorrect space group has very high scores in several regions. One region has already been described to be out-of-register with the density map of the structure. The NL-profile of the re-refined structure with the correct space group is vastly improved. In the second case, the method is able to accurately point out disordered residues, even if the atoms of these residues do not violate the sum of the van der Waals radii. ANOLEA, the program used to calculate the NL-profile of a protein structure containing one or more chains is accessible through the World Wide Web at: http://www.fundp.ac.be/pub/ANOLEA.html.

Crystallography, X-Ray↗
PubMed1998

[Agenesis of the vagina].

In the last 10 years we treated ten patients with the diagnosis of vaginal agenesia. The reconstruction was performed according to the McIndoe procedure. The medical records of these patients were retrospectively reviewed in what concerns the diagnosis (Mayer-Rokitansky S.-7, Androgenital S.-1, Testicular feminization S.-1), classification, treatment, complications, and outcome. It is the authors' opinion that the McIndoe method is the most appropriate for the treatment of vaginal agenesia, because of its simplicity, low morbidity and absence of mortality.

Adolescent↗
PubMed1998

[Importance of J. Brazy's neurobiological index. Prediction of the number and severity of complications in very low birth weight infants].

The objective of this study was to evaluate the neurodevelopment outcome of Very-Low-Birth-Weight Infants (VLBW), between 1987 and 1993, and correlate these findings with J.Brazy's Neurobiologic Risk Score (NBRS). The minimum corrected age at follow-up was 12 months. The neurodevelopmental assessment was performed using Mary Sheridan and Ruth Griffiths scales, Auditory and Visual Brainstem Evoked Responses and Stycar test. The NBRS was applied to 77 children. According to the score, three groups of risk were defined: Low < or = 4; Intermediate 5-7; High > or = 8. We obtained the following results: children with NBRS < 4, 20% had handicaps (5% of which major); children with NBRS 5-7, 41% had handicaps (23% of which major); in children with NBRS > 8, 95% had handicaps (80% of which major). The incidence of handicaps, (all grades included) was 71.4% for those weighing less than 1000 gr at birth, and 39.2% for those weighing 1000-1499 gr at birth. Major handicaps, mainly motor deficits, occurred in 26.8% of VLBW infants and minor to moderate handicaps were observed in 18.3% of patients in this group. These results were compared to J.Brazy's originals. We concluded that the NBRS, which is simple and objective to perform, is a good predictor of subsquent abnormal development in VLBW infants, allowing the infant's integration as soon as possible in high-risk follow-up programs, to place as soon as possible.

Developmental Disabilities↗
PubMed1997

Novel knowledge-based mean force potential at atomic level.

We present a new approach at the atomic level for the development of knowledge-based mean force potentials (MFPs) that can be used in fold recognition, ab initio structure prediction, comparative modelling and molecular recognition. Our method is based on atom-type definitions, raising the total frequency of the pairwise distributions and leading to very accurate and specific distance-dependent energy functions. Forty different heavy atom types were defined depending on their bond connectivity, chemical nature and location level (side-chain or backbone). Using this approach it has been possible to obtain average frequencies of pairwise contacts about 15 times higher than the ones obtained using the classic way of one heavy atom definition for each amino acid (i.e. alpha-carbon, beta-carbon, virtual centroid or virtual beta-carbon co-ordinates). In this paper we use this approach to develop a MFP that can be used in fold recognition and we compare it with a classic MFP at the amino acid level compiled from the alpha-carbon distances between the different amino acid pairs. Both potentials involve all the pairwise contacts extracted from a non-redundant folds database of 180 protein chains with a sequence identity threshold of 25%. The pairwise energy functions of the MFP at the atomic level have a deep and very well defined minimum for each pairwise interaction, in contrast to the same curves obtained from the MFP developed at the amino acid level, which generally have multiple minima with similar depth. Our results also show that this MFP is able to produce very similar energy profiles for couples of proteins that share a very low sequence identity but are closely related at the structural level. When these profiles are plotted considering the structure-structure alignment, they are mostly superimposed, showing a correlation with the structure-structure similarity. In the same test, the MFP at the amino acid level fails to produce similar profiles. We suggest that using this MFP at the atomic level in the last stages of fold recognition or threading, when some candidates are available, can improve the sequence-structure alignments and, therefore, the final models. We also discuss the possibility of using this approach in the development of new MFPs to be used in ab initio structure prediction, comparative modelling and molecular recognition procedures.

Amino Acids↗
PubMed1997

ANOLEA: a www server to assess protein structures.

ANOLEA (Atomic Non-Local Environment Assessment) is a www server that performs energy calculations at the atomic level in protein structures. The calculations involve the non-local interactions between all the heavy atoms of the twenty standard amino acids in the molecule. The input of the server is a PDB file containing one or more protein chains. The output is an energy profile, which gives an energy value for each amino acid of the protein. High energy zones (HEZs) in the profile correlate with errors or with potential interacting zones of proteins. The output of the server also displays the structure in three dimensions, pointing out the high energy amino acids in the protein. This option requires the CHIME plug-in, which is freely available on Internet and makes possible, in real time, to rotate, translate and change the point of view and presentation of the molecule in three dimensions. Thus, a fast analysis of a protein structure can be done using a personal computer connected to Internet. The server is available at: http:@www.fundp.ac.be/pub/ANOLEA.html.

Amino Acids↗
PubMed1996

Extracellular matrix is required for skeletal muscle differentiation but not myogenin expression.

Skeletal muscle cells are a useful model for studying cell differentiation. Muscle cell differentiation is marked by myoblast proliferation followed by progressive fusion to form large multinucleated myotubes that synthesize muscle-specific proteins and contract spontaneously. The molecular analysis of myogenesis has advanced with the identification of several myogenic regulatory factors, including myod1, myd, and myogenin. These factors regulate each other's expression and that of muscle-specific proteins such as the acetylcholine receptor and acetylcholinesterase (AChE). In order to investigate the role of extracellular matrix (ECM) in myogenesis we have cultured myoblasts (C2C12) in the presence or absence of an exogenous ECM (Matrigel). In addition, we have induced differentiation of myoblasts in the presence or absence of Matrigel and/or chlorate, a specific inhibitor of proteoglycan sulfation. Our results indicated that the formation of fused myotubes and expression of AChE was stimulated by Matrigel. Treatment of myoblasts induced to differentiate with chlorate resulted in an inhibition of cell fusion and AChE activity. Chlorate treatment was also found to inhibit the deposition and assembly of ECM components such fibronectin and laminin. The expression of myogenin mRNA was observed when myoblasts were induced to differentiate, but was unaffected by the presence of Matrigel or by culture of the cells in the presence of chlorate. These results suggest that the expression of myogenin is independent of the presence of ECM, but that the presence of ECM is essential for the formation of myotubes and the expression of later muscle-specific gene products.

Acetylcholinesterase↗
PubMed1996

Synthesis and processing of glypican during differentiation of skeletal muscle cells.

We identified previously a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan (HSPG) releasable by phosphatidylinositol-specific phospholipase C (PI-PLC) on the surface of differentiated skeletal muscle cells (Campos et al., Eur. J. Biochem. 216, 587-595 (1993)) which is homologous to the HSPG synthesized by fibroblasts and Schwann cells called glypican. In this study we have evaluated the processing, location and amount of this HSPG in skeletal muscle cells during differentiation. Immunoprecipitation of incubation medium obtained from differentiated cells incubated with [35S]sulfate by specific antibodies against glypican isolated from Schwann cells demonstrated that the antisera precipitated an intact HSPG. Immunoblot analysis of the proteins released by PI-PLC after heparitinase treatment revealed the presence of a main band of 64 and a faint band of 62 kDa, whereas the sizes of the core proteins for glypican present in the incubation media were 62 and 59 kDa. Pulse-chase experiments indicated that glypican present in the membrane was spontaneously released into the culture medium with a t1/2 of 12 h. The level of expression of glypican was analyzed during in vitro differentiation. The specific amount of the PI-PLC releasable HSPG increased about fourfold during cell differentiation. No changes were detected in the level of the mRNA for glypican. Indirect analysis revealed that in myotubes glypican is present on the cell surface as well as associated with the extracellular matrix (ECM). These results indicate that glypican is present, at least, in two different compartments on the surface of skeletal muscle cells.

Animals↗
PubMed1995

[Auricular fibrillation. Antiarrhythmic treatment revisited].

Atrial fibrillation is one of the most common symptomatic sustained arrhythmias seen in clinical practice. Long-term control of heart rate and maintenance of sinus rhythm often require chronic antiarrhythmic therapy. For patients with disabling symptoms of atrial fibrillation that cannot be controlled with pharmacologic therapy, catheter ablation techniques of the atrioventricular junction and surgical procedures aimed at maintaining sinus rhythm have now been effectively used. The efficacy, risks and limitations of pharmacologic and non-pharmacologic therapies are presented in this review article.

Anti-Arrhythmia Agents↗
PubMed1993

Decorin is specifically solubilized by heparin from the extracellular matrix of rat skeletal muscles.

We have previously communicated that heparin co-solubilizes the asymmetric form of acetylcholinesterase (AChE) and a dermatan sulfate proteoglycan from the extracellular matrix (ECM) of rat skeletal muscles. In this report we unequivocally demonstrate by biochemical and immunological analyses that the proteoglycan that is solubilized by heparin from rat skeletal muscle ECM corresponds to decorin. These results support the concept for the role of decorin in the ECM organization.

Acetylcholinesterase↗