Singlet molecular oxygen quenching by the antioxidant dimethylmethoxy chromanol in solution and in ex vivo porcine skin.

Singlet-oxygen is a non-radical reactive oxygen species believed to play a major role in many photooxidation processes in connection with diverse photo-biological processes such as skin ageing or photocarcinogenesis. Dimethylmethoxy chromanol (3,4-dihydro-6-hydroxy-2,2-dimethyl-7-methoxy-1(2H)-benzopyran) is a potent antioxidant used in cosmetic and pharmaceutical formulations. We have assessed the singlet oxygen quenching ability of dimethylmethoxy chromanol, by monitoring the near-IR phosphorescence of singlet-oxygen in solution and in ex vivo porcine skin samples. Dimethylmethoxy chromanol quenches singlet oxygen with a rate constant of (1.3 ± 0.1) × 108 M⁻¹ s⁻¹ in solution. Consistent with this, a clear reduction in the singlet oxygen lifetime and emission intensity was observed when ex vivo porcine skin samples were treated with dimethylmethoxy chromanol.

[Leiomyosarcoma of the larynx. Based on one case]. / Leiomiosarcoma de laringe. A propósito de un nuevo caso.

Leiomyosarcoma is a malignant tumour of smooth muscle cells. Usually is found in the gastrointestinal and female genital tracts, but is extremely rare in the larynx. Diagnosis is based in immunohistochemical studies. From the related literature is concluded that this tumour has a very aggressive behavior, with a very bad prognosis in spite of a radical surgery. A case of glottic Laryngeal Leiomyosarcoma (LL) treated with partial surgery is presented, There isn't any evidence of recurrent or metastases after a two years follow-up.

Leiomiosarcoma de laringe. A propósito de un nuevo caso / Leiomyosarcoma of the larynx. Based on one case

El Leiomiosarcoma es un tumor maligno de células musculares lisas. Se localiza habitualmente a nivel gastrointestinal y genital femenino, pero es excepcional en la laringe. El diagnóstico se fundamenta en técnicas inmunohistoquímicas. De la literatura existente se concluye que se trata de un tumor con un comportamiento muy agresivo, lo cual le confiere un mal pronóstico pese a efectuar cirugías radicales. Se presenta un caso de Leiomiosarcoma de Laringe (LL) de localización glótica, tratado mediante cirugía parcial. No hay signos de recidiva ni mestástasis tras dos años de seguimiento (AU)

Leiomyosarcoma is a malignant tumour of smooth muscle cells. Usually is found in the gastrointestinal and female genital tracts, but is extremely rare in the larynx. Diagnosis is based in immunohistochemical studies. From the related literature is concluded that this tumour has a very aggressive behavior, with a very bad prognosis in spite of a radical surgery. A case of glottic Laryngeal Leiomyosarcoma (LL) treated with partial surgery is presented, There isn't any evidence of recurrent or metastases after a two years follow-up (AU)

Long-lived glycosyl-enzyme intermediate mimic produced by formate re-activation of a mutant endoglucanase lacking its catalytic nucleophile.

The mutant E134A 1,3-1,4-beta-glucanase from Bacillus licheniformis, in which the catalytic nucleophilic residue has been removed by mutation to alanine, has its hydrolytic activity rescued by exogenous formate in a concentration-dependent manner. A long-lived alpha-glycosyl formate is detected and identified by (1)H-NMR and matrix-assisted laser desorption ionization-time-of-flight-MS. The intermediate is kinetically competent, since it is, at least partially, enzymically hydrolysed, and able to act as a glycosyl donor in transglycosylation reactions. This transient compound represents a true covalent glycosyl-enzyme intermediate mimic of the proposed covalent intermediate in the reaction mechanism of retaining glycosidases.

Expeditious synthesis of a new hexasaccharide using transglycosylation reaction catalyzed by Bacillus (1-->3),(1-->4)-Beta-D-glucan 4-glucanohydrolase.

Enzymatic hydrolysis of barley (1-->3),(1-->4)-beta-D-glucan using a recombinant (1-->3),(1-->4)-beta-glucanase from Bacillus licheniformis gives Glc beta 4Glc beta 3Glc isolated after acetylation in 49% yield. Conventional treatment produced the corresponding beta-fluoride which was carefully de-O-acetylated. A transglycosylation reaction with this substrate, catalyzed by the title enzyme, gave Glc beta 4Glc beta 3Glc beta 4Glc beta 4Glc beta 3Glc in 20% yield.

Synthesis of aryl 3-O-beta-cellobiosyl-beta-D-glucopyranosides for reactivity studies of 1,3-1,4-beta-glucanases.

A series of substituted aryl beta-glycosides derived from 3-O-beta-cellobiosyl-D-glucopyranose with different phenol-leaving group abilities as measured by the pKa of the free phenol group upon enzymatic hydrolysis has been synthesised. Aryl beta-glycosides with a pKa of the free phenol leaving group > 5 were prepared by phase-transfer glycosidation of the per-O-acetylated alpha-glycosyl bromide with the corresponding phenol, whereas the 2,4-dinitrophenyl beta-glycoside was obtained by condensation of 1-fluoro-2,4-dinitrobenzene with the partially acetylated trisaccharide followed by acid de-O-acetylation. The aryl beta-glycosides have been used for reactivity studies of the wild-type Bacillus licheniformis 1,3-1,4-beta-D-glucan 4-glucanohydrolase. The Hammett plot log kcat versus pKa is biphasic with an upward curvature at low pKa values suggesting a change in transition-state structure depending on the aglycon.

Probing the mechanism of Bacillus 1,3-1,4-beta-D-glucan 4-glucanohydrolases by chemical rescue of inactive mutants at catalytically essential residues.

The role of the key catalytic residues Glu134 and Glu138 in the retaining 1,3-1,4-beta-glucanase from Bacillus licheniformis is probed by a chemical rescue methodology based on enzyme activation of inactive mutants by the action of added nucleophiles. While Glu134 was proposed as the catalytic nucleophile on the basis of affinity labeling experiments, no functional proof supported the assignment of Glu138 as the general acid-base catalyst. Alanine replacements are prepared by site-directed mutagenesis to produce the inactive E138A and E134A mutants. Addition of azide reactivates the mutants in a concentration-dependent manner using an activated 2, 4-dinitrophenyl glycoside substrate. The chemical rescue operates by a different mechanism depending on the mutant as deduced from 1H NMR monitoring and kinetic analysis of enzyme reactivation. E138A yields the beta-glycosyl azide product arising from nucleophilic attack of azide on the glycosyl-enzyme intermediate, thus proving that Glu138 is the general acid-base residue. Azide activates the deglycosylation step (increasing kcat), but it also has a large effect on a previous step (as seen by the large decrease in KM, the increase in kcat/KM, and the pH dependence of activation), probably increasing the rate of glycosylation through Bronsted acid catalysis by enzyme-bound HN3. By contrast, azide reactivates the E134A mutant through a single inverting displacement to give the alpha-glycosyl azide product, consistent with Glu134 being the catalytic nucleophile. Formate as an exogenous nucleophile has no effect on the E138A mutant, whereas it is a better activator of E134A than azide. Although the reaction yields the normal hydrolysis product, a transient compound was detected by 1H NMR, tentatively assigned to the alpha-glycosyl formate adduct. This is the first case where a nonmodified sugar gives a long-lived covalent intermediate that mimics the proposed glycosyl-enzyme intermediate of retaining glycosidases.

Design and chemoenzymatic synthesis of thiooligosaccharide inhibitors of 1,3:1,4-beta-D-glucanases.

A successful chemoenzymatic synthesis of oligosaccharides with an interglucosidic sulfur atom as inhibitors of 1,3:1,4-D-glucanases is described. The key compound 3a was synthesized from acetylated 1-thio-beta-laminaribiose 4 and the methyl 4'-O-triflyl-lactoside 5. After de-O-acylation, the tetrasaccharide 3b was used as an acceptor and glucose-1-P as a donor in a phosphorolytic elongation catalysed by cellodextrin phosphorylase from Clostridium thermocellum. The expected pentasaccharide 2a and hexasaccharide 1 were isolated in 56% and 13% yield, respectively. As expected, the thiooligosaccharides 1, 2a, and 3b were resistant to enzymatic cleavage by 1,3:1,4-beta-D-glucanase isolated from Bacillus licheniformis. Furthermore, they have been shown to act as competitive inhibitors of the hydrolysis of the chromophoric trisaccharide substrate 11 by this enzyme.

[Adenolymphoma or Warthin's tumor: review of 30 cases]. / Adenolinfoma o tumor de Warthin: revisión de 30 casos.

Perusal of Warthin's tumors treated during the past 20 years (1969-1989) in our Hospital department. As a whole 229 tumors of salivary glands were operated upon, 30 of them being adenolymphomata. The parameters of our series were confronted with those given by the cases of the literature. In the paper are also reminded the several theories concerning the origin of this tumor.

[Myringoplasty. A prospective study of 238 cases]. / Miringoplastia. Estudio prospectivo de 238 casos.

It has been made a review of 238 myringoplasties done in the last three years (1988-90) at the Santa Creu i Sant Pau Hospital. In this work are only contemplated the plain myringoplasties. Tympanoplasties because cholesteatoma and ossiculoplasties are excluded. Some characteristics are studied: age, sex, ear state, kind of perforation, ossicular chain state and others. Anatomical and functional results are analyzed as also the relationship between the type of perforation with the audiometric loose and anatomic success.

[Adenocarcinoma of the nose and paranasal sinuses. Presentation of 3 cases]. / Adenocarcinoma de nariz y senos paranasales. Presentación de tres casos.

Three cases of intestinal type adenocarcinomas of the nose and sinuses are described. In two of them the tumors were associated with an extended exposure to wood dust, while no association with any known exposure factor was detected in the third. Clinical history, pathology, treatment and follow-up of each case are reviewed.

[Nasopharyngeal carcinoma. An epidemiological and clinical study]. / Carcinoma de nasofaringe. Estudio epidemiológico y clínico.

Clinical and epidemiological data from 46 cases of nasopharyngeal carcinoma retrieved from our E.N.T. department data base are analysed. These tumors represent about 5% of all head and neck carcinomas seen at our department between 1984 and 1989. Neither geographic origin nor occupation of patients have proved significant to the epidemiological analysis. Patients are most frequently in their sixth decade of life at presentation, with a clear male predominance, but not as marked as in other locations of head and neck tumours. As in other series, a significant relationship between nasopharyngeal tumours and alcohol and tobacco consumption has been discarded. Most patients were in good condition at diagnosis. Sublocation (usually on the lateral and/or posterior walls of the nasopharynx), predominance of undifferentiated carcinomas and isolated neck adenopathy as presenting symptom, are all features found in our series as well as in other reports. In contrast, the time between first symptom and diagnosis has been moderately longer in our patients. Cranial nerve and base of skull involvement have been found in 20% and 37% of cases, respectively. A great proportion of patients present with advanced disease: T3-T4 tumours in 67%; clinically detectable adenopathy in 69.5%; and distant metastasis in 4.3% of cases. Almost 75% of our patients showed stage IV disease at diagnosis.