Hexyltrimethylammonium ion enhances potential copper-chelating properties of ammonium thiomolybdate in an in vivo zebrafish model.

Ammonium and hexyltrimethylammonium thiomolybdates (ATM and ATM-C6) and thiotungstates (ATT and ATT-C6) were synthesized. Their toxicity was evaluated using both in vitro and in vivo approaches via the zebrafish embryo acute toxicity assay (ZFET), while the copper-thiometallate interaction was studied using cyclic voltammetry, as well as in an in vivo assay. Cyclic voltammetry suggests that all thiometallates form complexes with copper in a 2:1 Cu:thiometallate ratio. Both in vitro and in vivo assays demonstrated low toxicity in BALB/3T3 cells and in zebrafish embryos, with high IC50 and LC50 values. Furthermore, the hexyltrimethylammonium ion played a crucial role in enhancing viability and reducing toxicity during prolonged treatments for ATM and ATT. In particular, the ZEFT assay uncovered the accumulation of ATM in zebrafish yolk, averted by the incorporation of the hexyltrimethylammonium ion. Notably, the copper-thiometallate interaction assay highlighted the improved viability of embryos when cultured in CuCl2 and ATM-C6, even at high CuCl2 concentrations. The hatching assay further confirmed that copper-ATM-C6 interaction mitigates inhibitory effects induced by thiomolybdates and CuCl2 when administered individually. These results suggest that the incorporation of the hexyltrimethylammonium ion in ATM increase its ability to interact with copper and its potential application as a copper chelator.

Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends. / Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias.

BACKGROUND: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. OBJECTIVES: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. METHODS: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). RESULTS: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. CONCLUSIONS: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

Epidemiological, Clinical, and Allergic Profile of Psoriatic Patients. Evaluation of the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC). / Perfil epidemiológico, clínico y alérgico en pacientes con psoriasis. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis whose clinical and topographic distribution requires differential diagnosis, or the possible association with allergic contact dermatitis (ACD), requiring patch testing (PT) as part of the diagnostic procedure. OBJECTIVES: To describe the epidemiological, clinical, and allergic profile of patients with a primary or secondary diagnosis of psoriasis undergoing PT and compare them with patients with a diagnosis of ACD at the end of the diagnostic process. METHODS: Cross-sectional study with data from REIDAC from 2018 through 2023 of selected patients with a diagnosis of psoriasis and/or ACD. RESULTS: A total of 11 502 patients were included, 513 of whom had been diagnosed with primary or secondary psoriasis, 3640 with ACD, and 108 with both diseases. Men were more predominant in the groups of patients with psoriasis, psoriasis+ACD, and lesions were more predominantly seen in the hands with little association with atopic factors vs the ACD group. The rate of positivity in PT to the 2022 Spanish battery of allergens was lower in the group with psoriasis only in 27% of the patients. The most common allergens found in the psoriasis group were also the most common ones found in the overall ACD population. CONCLUSIONS: Overall, 36.2% of psoriatic patients tested positive in PT to the 2022 Spanish battery of allergens, which proved that this association is not uncommon. Overall, psoriatic patients had a higher mean age, were more predominantly men, and showed more hand involvement.

Standard and Expanded Series Patch Testing Update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Actualización de la batería estándar y batería ampliada de pruebas alérgicas de contacto por el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC).

After the meeting held by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) back in October 2021, changes were suggested to the Spanish standard series patch testing. Hydroxyethyl methacrylate (2% pet.), textile dye mixt (6.6% pet.), linalool hydroperoxide (1% pet.), and limonene hydroperoxide (0.3% pet.) were, then, added to the series that agreed upon in 2016. Ethyldiamine and phenoxyethanol were excluded. Methyldibromoglutaronitrile, the mixture of sesquiterpene lactones, and hydroxyisohexyl 3-cyclohexene (Lyral) were alo added to the extended Spanish series of 2022.

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

AIM: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of ß cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. PATIENTS AND METHODOLOGY: 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). RESULTS: A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). CONCLUSION: TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

AIM: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of ß cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. PATIENTS AND METHODOLOGY: 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). RESULTS: A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). CONCLUSION: TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

Barley ß-glucan accelerates wound healing by favoring migration versus proliferation of human dermal fibroblasts.

ß-Glucans are considered candidates for the medication in different human pathologies. In this work, we have purified ß-glucan from a selected barley line and tested their effects in primary human dermal fibroblasts. Unexpectedly, we have observed that this compound promoted a short-transitory proliferation arrest at 24 h after its addition on the medium. We have determined that this transitory arrest was dependent on the cell-cycle regulator protein Retinoblastoma. Moreover, dermal fibroblasts increase their migration capacities at 24 h after barley ß-glucan addition. Also, we have described that barley ß-glucan strongly reduced the ability of fibroblasts to attach and to spread on cell plates. Our data indicates that barley ß-glucan signal induces an early response in HDF cells favoring migration versus proliferation. This feature is consistent with our observation that the topical addition of our barley ß-glucan in vivo accelerates the wound closure in mouse skin.

Prevalence of esophageal inlet patch and clinical characteristics of the patients. / Prevalencia y características clínicas de pacientes con parche de mucosa gástrica ectópica en esófago.

INTRODUCTION AND AIMS: An inlet patch (IP) is the presence of gastric columnar epithelium outside of the stomach. No studies have been conducted in Mexico on that pathology. The aim of the present study was to determine the prevalence of esophageal IP and the clinical characteristics of the patients that present it. MATERIALS AND METHODS: A cross-sectional study was conducted that included consecutive patients referred for endoscopy within the time frame of September 2015 to May 2016. The patients answered a questionnaire, and high-definition endoscopy with digital chromoendoscopy was performed. The prevalence of IP was identified. The chi-square test was used to compare the clinical characteristics between patients that presented with esophageal IP and those without it. RESULTS: A total of 239 patients were included in the study. Their mean age was 53 years, and 130 (54.4%) were women. IP was found in 26 patients (10.9%), 15 of whom were men (57.7%). The main reason for referral to endoscopy was gastroesophageal reflux disease, present in 69.2% of the patients with IP and in 55.9% without IP (p=.19). The most common symptoms were heartburn and regurgitation. The former was present in 69.2% of the patients with IP and in 59.1% without IP (p=.32), and the latter was present in 65.4% of the patients with IP and 69.1% without IP (p=.7). Extraesophageal manifestation distribution was: cough in 46.2% of the patients with IP and 38% without IP (p=.45) and dysphonia in 54% with IP and 47% without IP (p=.53). Twenty-three percent of the patients with IP had Barrett's esophagus, as did 23% without IP (p=.99). CONCLUSIONS: The prevalence of IP was high. The primary referral diagnosis was gastroesophageal reflux disease. No differences were found in relation to symptoms or the presence of Barrett's esophagus between the patients with and without IP.

New variants of polar glycopeptidolipids detected in Mycobacterium simiae, including 'habana' strains, as evidenced by electrospray ionization-ion trap-mass spectrometry.

AIMS: To determine the composition of polar glycopeptidolipids (pGPLs) of Mycobacterium simiae and, particularly, those of 'habana' strains, in a search for specific markers given the immunogenic potential of 'habana' TMC 5135 in experimental tuberculosis. METHODS AND RESULTS: pGPLs were determined in free lipid extracts using electrospray ionization-ion trap-mass spectrometry (ESI-IT-MS), working in both negative- and positive-ion mode. In the case of TMC 5135, the presence of the previously characterized GPL-II (containing 2,4-di-O-CH(3) glucuronic acid as distal sugar in the oligosaccharide antigenic moiety) and GPL-III (containing 4-O-CH(3) glucuronic acid as distal sugar) was confirmed using MS/MS and MS/MS/MS approaches. Interestingly, some 'habana' strains presented variants of GPL-II, designated GPL-II'-A and GPL-II'-B. A di-O-CH(3)-deoxy-hexose (tentatively, 2,3-di-O-CH(3)-fucose) was identified as the penultimate sugar in the oligosaccharide moiety of GPL-II'-A, whereas in GPL-II'-B the penultimate sugar was fucose (tentative identification). On the contrary, the distal sugar of the oligosaccharide chain of pGPLs of Myco. simiae ATCC 25275(T) was identified as tri-O-CH(3)-glucuronic acid (designated GPL-sim(T)-I, with two variants: GPL-sim(T)-I-A and GPL-sim(T)-I-B), O-CH(3)-glucuronic acid (designated GPL-sim(T)-II) and di-O-CH(3)-glucuronic acid (GPL-II'-A and GPL-II'-B). The penultimate sugar of the oligosaccharide chain of GPL-sim(T)-I-A and GPL-sim(T)-II was identified as di-O-CH(3)-deoxy-hexose (tentatively, 2,3-di-O-CH(3) fucose), and that of GPL-sim(T)-I-B as deoxy-hexose (tentatively, fucose). In all strains studied, each [M-H](-) and [M+Na](+) ion was revealed as a mixture of homologous compounds varying in the number of -O-CH(3) groups present in the oligosaccharide moiety and in the length of the fatty acyl linked to the peptide. CONCLUSIONS: The present work indicates that, within a similar general pattern of pGPLs, different strains of Myco. simiae present some variations, so that new compounds (GPL-II'-A, GPL-II'-B, GPL-sim(T)-I-A, GPL-sim(T)-I-B and GPL-sim(T)-II) were defined. Noteworthy was the fact that the 'habana' strains clearly differed from the type strain of Myco. simiae. SIGNIFICANCE AND IMPACT OF THE STUDY: The data obtained can be used in the delineation of the 'habana' group of Myco. simiae, including the quality control of the immunogenic strain 'habana' TMC 5135.

Papulopustular Rosacea: Response to Treatment with Oral Azithromycin. / Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral.

INTRODUCTION: Oral tetracyclines and topical antibiotics have been used to treat papulopustular rosacea (PPR) for years, but it is not uncommon to find patients who do not respond to this standard treatment. In such refractory cases, oral azithromycin has proven to be an effective option. MATERIAL AND METHOD: We conducted a prospective pilot study of 16 patients with PPR who were treated with oral azithromycin after a lack of response to oral doxycycline and metronidazole gel. At the first visit, the patients were assessed for baseline severity of PPR on a 4-point clinical scale and started on oral azithromycin. At the second visit, response to treatment in terms of improvement from baseline was evaluated on a 3-point scale. Patients were then scheduled for follow-up visits every 12 weeks to assess long-term effectiveness. RESULTS: All 16 patients experienced an improvement in their PPR following treatment with oral azithromycin. Eight weeks after completion of treatment, 14 patients (87.5%) showed complete or almost complete recovery (slight or no residual redness and complete clearance of papules and pustules). Only 2 patients experienced a new episode of inflammatory PPR lesions during follow-up. CONCLUSIONS: The findings of this pilot study suggest that oral azithromycin could be a very effective short-term and long-term treatment for RPP resistant to conventional treatment.

Decrease in the cattle tick Rhipicephalus microplus biological parameters using anti-subolesin peptide antibodies by artificial capillary feeding.

Ticks represent a threat to animal health worldwide and are considered the second most important vectors of human diseases. The main method of control of ticks has been the usage of chemical products; however, the use of acaricides has resulted in some serious drawbacks such as acaricide-resistant ticks and environmental pollution. As a result the use of immunological control using tick proteins is suggested as an alternative to control tick populations. The protocols used to test the ticks to antigens, needs a complementary method that would allow control to be carried out in external conditions. In this context, the use of the in vitro capillary feeding represents a low cost alternative to test candidate antigens allowing to get important data on the protective effect during interactions between antigenantibody. In order to evaluate the effect in biological parameters of female R. microplus ticks by artificial feeding with bovine blood containing anti-subolesin peptide IgG's obtained at different times after immunization. Results of this study showed the effect on weight of ticks and oviposition due to antibodies obtained at weeks 3, 5 and 7 after immunization. The results proved that anti-subolesin peptide IgG´s at week 7 demonstrated better effect reducing tick weight by 45% and oviposition by 71% (P<0.05) with respect to tick fed on blood with preimmune serum. These results strongly suggested that the negative effects in cattle tick biological parameters were the result of the protective antibodies against subolesin peptide. Finally, the artificial feeding of ticks should be used to evaluate antigen-specific antibodies avoiding external factors.

Lipids of 'Mycobacterium habana', a synonym of Mycobacterium simiae with vaccine potential.

'Mycobacterium habana' was proposed as a distinct species within the genus Mycobacterium; however, it is actually a synonym of Mycobacterium simiae and included in the serotype I of this species. The potential use of 'M. habana' as a vaccine in both leprosy and tuberculosis has led to the analysis of its lipid composition in an attempt to define distinctive markers that could be used in the quality control of true strains of this bacterium. Lipids of taxonomic value (fatty and mycolic acids) are similar in 'M. habana' and M. simiae; nevertheless, they clearly differ on the basis of glycopeptidolipid (GPL) composition. Thus, contrary to M. simiae, most strains of 'M. habana' can be defined by the presence of three polar compounds, designated GPL-I, GPL-II and GPL-III, easily determined by thin-layer chromatography, and characterized, respectively, by the content of l-fucose, 2,4-di-O-Me-d-glucuronic acid, and 4-O-Me-d-glucuronic acid, as epitopes.

[Implication of ermX genes in macrolide- and telithromycin-resistance in Corynebacterium jeikeium and Corynebacterium amycolatum]. / Implicacion de los genes ermX en la resistencia a los macrolidos y la telitromicina de Corynebacterium jeikeium y Corynebacterium amycolatum.

The activity of seven macrolides, clindamycin and telithromycin against clinical isolates of Corynebacterium spp. was studied. Of these, 36 isolates were identified as C. jeikeium and 57 as C. amycolatum. The frequency of resistance to erythromycin and other macrolides as well as clindamycin was high, with CMI(90) >256 microg/ml. Telithromycin showed the best activity, with 52.3% of C. amycolatum and 70% of C. jeikeium erythromycin-resistant strains susceptible to this ketolide. All strains had the MLSb constitutive phenotype. The ermX gene was present in all erythromycin-resistant strains, and in C. amycolatum was 100% homologous with that of C. striatum and C. diphtheriae.

Comparison of the safety and efficacy of lomefloxacin and trimethoprim/sulfamethoxazole in the treatment of uncomplicated urinary tract infections: results from a multicenter study.

Lomefloxacin, a new difluorinated quinolone, and trimethoprim/sulfamethoxazole (TMP/SMX) were compared in the treatment of adults with uncomplicated urinary tract infections. The study was conducted as a multicenter, controlled, prospectively randomized, single-blind study in five countries (Argentina, Belgium, Brazil, Mexico, and Venezuela). A total of 254 patients were enrolled: 129 in the lomefloxacin group and 125 in the TMP/SMX group. Patients received either 400 mg lomefloxacin orally once daily or 160 mg/800 mg TMP/SMX orally twice daily for 7-10 days. Escherichia coli and Proteus mirabilis were the pathogens most frequently isolated. At 5-9 days post-therapy, satisfactory bacteriologic results were noted in 98.4% of patients treated with lomefloxacin and in 95.8% of patients in the TMP/SMX group (p = 0.2153). Clinical success 5-9 days post-therapy was noted in 99.2% of patients in the lomefloxacin group and in 98.3% of patients in the TMP/SMX group (p = 0.5138). Adverse events probably related to treatment occurred in 6% of those treated with lomefloxacin and in 7% of patients treated with TMP/SMX. Once-daily oral lomefloxacin is a well-tolerated and effective treatment of uncomplicated urinary tract infections caused by susceptible pathogens.

The molecular epidemiology of HIV type 1 of men in Mexico.

Genotypic characteristics of human immunodeficiency virus type 1 (HIV-1) in Mexico were investigated in a multicenter study that involved centers in five geographic regions of the country. Study samples (n = 65) collected from male patients in 1998-1999 were sequenced within the C2-V5 region of the gp120 env gene. Phylogenetic analysis revealed that subtype B predominates in Mexico. The level of interpatient nucleotide diversity (mean value of 8.9%) was congruent with multiple introductions of the virus and the "aging" epidemic in Mexico. One-third of samples (30.8% of cases) showed polymorphism within the crown of the V3 loop demonstrating non-GPGR motifs. Two new motifs in the V3 loop crown - HPGG and GPEG - were observed. The evolution of the AIDS epidemic in Mexico should be closely monitored since non-B HIV-1 subtypes might be introduced. The nucleotide sequences were deposited in the GenBank under accession numbers AF200855-AF200869, AF200871-AF200892, and AF200894-AF200921.

Delineation of molecular species of a family of diacyltrehaloses from Mycobacterium fortuitum by mass spectrometry.

A family of 2,3-di-O-acyl trehaloses (DAT), previously identified in Mycobacterium fortuitum, was studied by fast-atom bombardment mass spectrometry to establish the combinations of fatty acyl substituents and, hence, to delineate the molecular species there comprised. The mass spectra indicated the possible existence of 41 molecular species, with a total of 35-40 carbon atoms and 0-4 double bonds in the lipid moiety. The principal components were situated a m/z (M+ +23) 919 (formulated as 2-methyloctadec-2-enoyl,2-methyloctadecadienoyl trehalose and as 2-methylhexadec-2-enoyl,2-methyleicosadienoyl trehalose) and m/z (M+ +23) 921 (formulated as di-2-methyloctadec-2-enoyl trehalose and as 2-methylhexadec-2-enoyl,2-methyleicos-2-enoyl trehalose). The data obtained revealed that DAT was composed of three types of combinations of fatty acyl groups; (i) linear plus linear; (ii) linear plus 2-methyl branched; and (iii) 2-methyl branched plus 2-methyl branched.

Acyl phosphatidylglycerol: a major phospholipid of Corynebacterium amycolatum.

The type strain and several clinical isolates of Corynebacterium amycolatum were examined for lipid composition as a chemotaxonomic character for routine identification. The phospholipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides, together with various unidentified compounds. One of them, accounting for 20-29% of total phospholipids, was purified and characterized as acyl phosphatidylglycerol by chromatographic and spectrometric techniques. The acyl substituents on the phosphatidyl moiety were characterized as tetradecanoyl, pentadecanoyl, hexadecenoyl, hexadecanoyl, heptadecenoyl, heptadecanoyl, octadecenoyl (the major one), and octadecanoyl. The acyl group on the polar head (glycerol) was only octadecenoyl. Phospholipid analysis by thin-layer chromatography of a collection of Corynebacterium strains proved that this compound is widely distributed, although it only represents a minor (2-9%) component among mycolic acid-containing species. Acyl phosphatidylglycerol can be considered as a useful chemical marker for the identification of C. amycolatum in addition to the absence of mycolic acids.

Taxonomic implications of the chemical analysis of the D2 group of corynebacteria.

Whole cell acid methanolysates from corynebacteria of the D2 group were found to contain meso-diaminopimelic acid, arabinose and galactose. Among lipids of taxonomic value, saturated and unsaturated straight chain fatty acids (14 to 18 carbon atoms), tuberculostearic acid (10-methyl octadecanoic acid) and mycolic acids were present. The last compounds ranged from 26 to 36 carbon atoms, the predominant types being 28.2, 28.1, 30.3, 30.2, 32.3 and 32.2. By reverse phase thin-layer chromatography the major menaquinone was identified as MK-9(H2)-containing nine isoprene units with two additional hydrogens. Moreover, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides were detected among the phospholipids of these bacteria. Thus, on these bases, the D2 group appears to be closely related to the true corynebacteria.