Three-dimensional lip morphometry in adults operated on for cleft lip and palate

Measurements were taken from 18 patients operated on for cleft lip and palate, aged 19 to 27 years, and 162 control subjects matched for sex, age, and ethnic group. Nine soft-tissue landmarks on the lips were digitized by a three-dimensional electromagnetic instrument. From the landmarks, several linear distances (mouth width, philtrum width, vermilion height of upper and lower lip, total vermilion height, total lip height), the interlabial angle, and some areas (vermilion of upper lip, vermilion of lower lip, total vermilion) and volumes (upper lip volume, lower lip volume, total lip volume) were calculated. Patient and reference data were compared by t tests and Watson-Williams tests. In the men, significant differences (p < 0.05) were found in width of the philtrum, height and area of the vermilion part of the upper lip, and total vermilion height and area (all larger in male patients than in controls). In the women, significant differences were found in the height and area of the vermilion part of the upper lip (larger in female patients than in controls), and in the height and area of the vermilion part of the lower lip (smaller in patients than in controls). In both sexes, the interlabial angle was smaller than in the reference population. In conclusion, the upper lip of adult patients operated on for cleft lip and palate differed from that of healthy controls of the same age, sex, and ethnic group. Surgical correction of cleft lip and palate failed to provide a completely normal appearance. The analysis pointed out those parts of the lips and mouth (in particular, the vermilion part of the upper lip) that differed the most from the norm. The method may be used to indicate to the surgeon and patient where additional procedures might be performed to approximate the morphologic characteristics of a reference population.     

Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent

Midodrine hydrochloride is a peripheral alpha(1)-adrenoreceptor agonist that induces venous and arterial vasoconstriction. Midodrine, after oral or intravenous administration, undergoes enzymatic hydrolysis and releases deglymidodrine, a pharmacologically active metabolite. Midodrine and deglymidodrine have a chiral carbon in the 2-position. To investigate the bioactivity of racemates and enantiomers of the drug and metabolite, three chromatographic chiral stationary phases, Chiralcel OD-H, Chiralcel OD-R, and alpha(1)-AGP, were evaluated for enantiomeric resolution. Good enantioseparation of midodrine racemate was obtained using the Chiralcel OD-H column. This stationary phase was then used to collect separately the midodrine enantiomers. By alkaline hydrolysis of rac-midodrine and each separated enantiomer, rac-deglymidodrine and its enantiomers were prepared. The control of the enantiomeric purity was carried out by alpha(1)-AGP stationary phase, while the hydrolysis of rac-midodrine and its enantiomers was controlled by capillary electrophoresis using trimethyl-beta-cyclodextrin as chiral selector. The pharmacological activity of the two racemates and the two enantiomeric pairs was tested in vitro on a strip of rabbit descending thoracic aorta. The tests continued that the activity of the drug and metabolite is due only to the (-)-enantiomer because neither of the (+)-enantiomers is active.     

Purification and characterization of a small (7.3 kDa) putative lipid transfer protein from maize seeds

The present study reports, for the first time in literature, the purification and biochemical characterization of a small basic protein from maize seeds similar to plant lipid transfer proteins-2, named mLTP2. The mLTP2 consists of 70 amino acid residues and has an M(r) of 7303.83, determined by electrospray ionization mass spectrometry. The primary structure of mLTP2 was determined by automated Edman degradation of the intact protein and peptides obtained from digestions with trypsin and by C-terminal sequencing using carboxypeptidase Y. The mLTP2 exhibits high sequence similarity (51-44% identical positions) with other plant LTP2s previously described.     

Assessment of post extraction complications in Indians

Extraction is one of the commonest procedures in dentistry. Therefore, it is of interest to evaluate the post extraction complications in patients undergoing extractions of permanent teeth. A total of 70 adult patients who had undergone dental extractions and presented with post -operative complications were included in the study and evaluated. Data collected was statistically analyzed using SPSS software and results obtained. Most of the patients with post extraction complications were in the age group of 31-40 years (21.6%), followed by 21-30 (20.2%) and 61-70 years (20.2%). Dry socket (39.19%) was the common post extraction complication in our study especially in the age group of 31-40 years. There was a statistically significant association between age of the patients and the post extraction complications (p<0.001). In our study, post extraction complications were commonly observed in age group of 31-40 years with a predilection for males. Dry socket was the most common post extraction complication. Age of the patient has a significant effect on post extraction complications. However, gender, smoking habits and systemic diseases have no influence on post extraction complications.     

Vanadium(V) complexes with salicylaldehyde semicarbazone derivatives bearing in vitro anti-tumor activity toward kidney tumor cells (TK-10): crystal structure of [VVO2(5-bromosalicylaldehyde semicarbazone)

As a contribution to the development of novel vanadium complexes with pharmacologically interesting moieties, new dioxovanadium(V) semicarbazone complexes with the formula cis-VO(2)L, where L=5-bromosalicylaldehyde semicarbazone and 2-hydroxynaphtalen-1-carboxaldehyde semicarbazone have been synthesized and characterized by (1)H and (13)C NMR, Raman and FTIR spectroscopies. Results were compared with those previously reported for other three analogous complexes of this series. The five complexes were tested in three different human tumor cell lines for bioactivity as potential anti-tumor agents, showing selective cytotoxicity on TK-10 cell line. Results showed that structural modifications on the semicarbazone moiety could have a significant effect on the anti-tumor activity of the vanadium complexes. In addition, the electrochemical behavior of all the complexes was studied. No apparent correlation could be demonstrated between reduction potentials of the complexes and their anti-tumor activities. The molecular structure of the novel [V(V)O(2)(5-bromosalicylaldehyde semicarbazone)] complex was solved by X-ray diffraction methods. The vanadium atom shows a distorted square pyramidal coordination sphere. The (VO(2))(+) cation is coordinated to a nearly planar (L)(-) anion acting as a tridentate ligand through both oxygen and one nitrogen atoms.     

Synthesis and biological properties of new 5-nitroindazole derivatives

A series of new 3-alkoxy- or 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5-nitroindazoles have been synthesized and their trichomonacidal, antichagasic and antineoplastic properties studied. Five derivatives (5, 6, 8, 9 and 17) showed remarkable trichomonacidal activity against Trichomonas vaginalis at 10 microg/mL concentration. Three compounds (8, 10, 11) exhibited interesting antichagasic activity and these same compounds moderate antineoplastic activity against TK-10 and HT-29 cell lines. Unspecific cytotoxicity against macrophages has also been evaluated and only compounds 9, 10 and 11 resulted cytotoxic at the higher dose evaluated (100 microg/mL), loosing cytotoxicity at lower doses. QSAR studies have been carried out. X-ray crystallographic study of compound 8 has been performed.     

Refinement of unbound protein docking studies using biological knowledge

In this work we present two methods for the reranking of protein-protein docking studies. One scoring method searches the InterDom database for domains that are available in the proteins to be docked and evaluates the interaction of these domains in other complexes of known structure. The second one analyzes the interface of each proposed conformation with regard to the conservation of Phe, Met, and Trp and their polar neighbor residues. The special relevance of these residues is based on a publication by Ma et al. (Proc Natl Acad Sci USA 2003;100:5772-5777), who compared the conservation of all residues in the interface region to the conservation on the rest of the protein's surface. The scoring functions were tested on 30 unbound docking test cases. The evaluation of the methods is based on the ability to rerank the output of a Fast Fourier Transformation (FFT) docking. Both were able to improve the ranking of the docking output. The best improvement was achieved for enzyme-inhibitor examples. Especially the domain-based scoring function was successful and able to place a near-native solution on one of the first six ranks for 13 of 17 (76%) enzyme-inhibitor complexes [in 53% (nine complexes) even on the first rank]. The method evaluating residue conservation allowed us to increase the number of good solutions within the first 100 ranks out of approximately 9000 in 82% of the 17 enzyme-inhibitor test cases, and for seven (41%) out of 17 enzyme-inhibitor complexes, a near native solution was placed within the first seven ranks.     

Characterization of the hepatitis C virus NS2/3 processing reaction by using a purified precursor protein

The NS2-NS3 region of the hepatitis C virus polyprotein encodes a proteolytic activity that is required for processing of the NS2/3 junction. Membrane association of NS2 and the autocatalytic nature of the NS2/3 processing event have so far constituted hurdles to the detailed investigation of this reaction. We now report the first biochemical characterization of the self-processing activity of a purified NS2/3 precursor. Using multiple sequence alignments, we were able to define a minimal domain, devoid of membrane-anchoring sequences, which was still capable of performing the processing reaction. This truncated protein was efficiently expressed and processed in Escherichia coli. The processing reaction could be significantly suppressed by growth in minimal medium in the absence of added zinc ions, leading to the accumulation of an unprocessed precursor protein in inclusion bodies. This protein was purified to homogeneity, refolded, and shown to undergo processing at the authentic NS2/NS3 cleavage site with rates comparable to those observed using an in vitro-translated full-length NS2/3 precursor. Size-exclusion chromatography and a dependence of the processing rate on the concentration of truncated NS2/3 suggested a functional multimerization of the precursor protein. However, we were unable to observe trans cleavage activity between cleavage-site mutants and active-site mutants. Furthermore, the cleavage reaction of the wild-type protein was not inhibited by addition of a mutant that was unable to undergo self-processing. Site-directed mutagenesis data and the independence of the processing rate from the nature of the added metal ion argue in favor of NS2/3 being a cysteine protease having Cys993 and His952 as a catalytic dyad. We conclude that a purified protein can efficiently reproduce processing at the NS2/3 site in the absence of additional cofactors.