Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery.

Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by the World Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutant-type (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs.

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis.

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models-S. cerevisiae, five cancer cell lines, and the parasite L. mexicana-were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

Preclinical evidences of safety of a new synthetic adjuvant to formulate with the influenza human vaccine: absence of subchronic toxicity and mutagenicity.

Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5 years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations. GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice. Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted. Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines. Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally. Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.

Further evidence on the favorable role of the anomeric effect on the cleavage of HepDirect and cyclophosphamide prodrugs.

On the basis of previous conformational and configurational studies of 4-aryl-substituted cyclophosph(on)ates derived from d-xylofuranose derivatives, wherein it was proposed that the anomeric effect is involved in the spontaneous isomerization of the P atom and the C4 carbon, and consequently, this unusual behavior was associated with the cleavage of the HepDirect prodrugs. We synthesized an analogous series of 2-amino-2-oxo-1,3,2-dioxaphosphorinanes and performed a conformational and configurational analysis in solution and the solid state followed by an examination of their mutagenic activity. The results showed that the 2-amino-2-oxo-1,3,2-dioxaphosphorinanes with the largest mutagenic activity contain either a 4-methoxyphenyl or 4-fluorophenyl group at C4 carbon and presented a major chair conformation, which is prone to weaken the C4-O3 bond via the anomeric effect and facilitates the cleavage for the release of the biologically active metabolite.

Functional outcomes and quality of life in patients treated with laparoscopic total colectomy for colonic inertia.

PURPOSE: To assess the functional outcomes and quality of life in patients with laparoscopic total colectomy for slow-transit constipation (STC). METHODS: All patients undergoing laparoscopic colectomy with ileorectal anastomosis for colonic inertia at two referral centers were analyzed. Their preoperative, intraoperative and postoperative details were recorded with a one-year follow-up. Their quality of life was assessed using the SF-36 questionnaire. RESULTS: Between 2004 and 2007, 710 patients were evaluated. Eight female patients (1.1 %) fulfilled the criteria for STC without obstructive defecation syndrome. Their mean age was 38 years ± 15 (range from 22 to 62). The conversion rate was 12.5 %. The morbidity rate was 37.5 %, and mortality was nil. The preoperative abdominal pain was 6.6 ± 0.3 and had decreased to 3.6 ± 2.3 postoperatively (P = 0.008). At 1 year, the defecation frequency per week had increased from 0.84 ± 0.24 to 6.75 ± 3.4 (P = 0.001). Three patients developed nocturnal leakage (37.5 %). Eighty-eight percent of the patients recommend the procedure. All parameters of the SF-36 questionnaire had improved at the one-year follow-up examination. CONCLUSION: Laparoscopic colectomy for slow-transit constipation is safe and increased the number of evacuations per week. Although nocturnal leakage may occur, these patients experience improvements in their quality of life.

CYP1A1 and Cnr nitroreductase bioactivated niclosamide in vitro.

Niclosamide produces genotoxic effects, such as point mutations in Salmonella sp., sperm-head abnormalities in mice and clastogenic effects in human lymphocytes in vitro and in vivo. As cytochrome P450 could be involved in the bioactivation of niclosamide, we investigated which subfamily was involved. We used liver microsomal fractions from rats treated with phenobarbital/ß-naphthoflavone (PB/ß-NF), benzo[a]pyrene (BaP) or cyclohexanol, which are known to induce different cytochrome P450 subfamilies, such as CYP2B, CYP1A1, CYP1A2 and CYP2E1. We also inhibited CYP1A and CYP2E using α-NF and diethyldithiocarbamate to identify the cytochrome P450 involved. Liver-S9 fractions obtained from PB/ß-NF- and BaP-treated rats significantly increased the number of revertants induced by niclosamide, while the CYP1A1 inhibitor α-NF decreased the number of revertants. The incubation of niclosamide with CYP1A1 Supersomes™ increased the number of revertants, suggesting that CYP1A1 is responsible for the bioactivation of niclosamide. Nitroreduction is also involved in niclosamide bioactivation, as the nitroreductase-deficient strain YG7132 did not respond to the niclosamide treatment. Our findings indicated that a metabolite, derived from the action of CYP1A1 and a nitroreduction-reaction process, has a key role in the bioactivation of niclosamide.

Lower Gastrointestinal Bleeding Associated With Variceal Hemorrhoidal Disease in a Patient With Pan-Colonic Varices.

Colonic varices are a rare condition primarily caused by portal hypertension associated with conditions such as cirrhosis or hepatocellular carcinoma. Idiopathic cases are even rarer, with less than 50 cases with a pan-colonic affection reported in the literature. Males are more commonly affected, with an average age of 41 years. Colonic varices can involve the entire colon in idiopathic cases and are often familial. Gastrointestinal bleeding is the main symptom, ranging from mild to life-threatening. Diagnosis is typically made through colonoscopy, which reveals dilated bluish vascular tracts. Treatment involves fluid IV resuscitation and controlling hemorrhage through various methods such as endoscopic procedures. Correction of the underlying cause is essential in cases of portal hypertension. Recurrent or unstable cases may require colon resection. On this occasion, we present the case of a female patient who experienced profuse lower gastrointestinal bleeding. The patient's colonoscopy revealed the presence of varices throughout the entire length of the colon, with the only recent bleeding site being in the hemorrhoidal tissue. Therefore, a hemorrhoidectomy was performed to carry out an effective and less invasive therapeutic procedure than a colectomy with an excellent postoperative evolution.

Solid Lipid Nanoparticles Enhancing the Leishmanicidal Activity of Delamanid.

Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.

Analysis of the air flow generated by an air-assisted sprayer equipped with two axial fans using a 3D sonic anemometer.

The flow of air generated by a new design of air assisted sprayer equipped with two axial fans of reversed rotation was analyzed. For this goal, a 3D sonic anemometer has been used (accuracy: 1.5%; measurement range: 0 to 45 m/s). The study was divided into a static test and a dynamic test. During the static test, the air velocity in the working vicinity of the sprayer was measured considering the following machine configurations: (1) one activated fan regulated at three air flows (machine working as a traditional sprayer); (2) two activated fans regulated at three air flows for each fan. In the static test 72 measurement points were considered. The location of the measurement points was as follow: left and right sides of the sprayer; three sections of measurement (A, B and C); three measurement distances from the shaft of the machine (1.5 m, 2.5 m and 3.5 m); and four measurement heights (1 m, 2 m, 3 m and 4 m). The static test results have shown significant differences in the module and the vertical angle of the air velocity vector in function of the regulations of the sprayer. In the dynamic test, the air velocity was measured at 2.5 m from the axis of the sprayer considering four measurement heights (1 m, 2 m, 3 m and 4 m). In this test, the sprayer regulations were: one or two activated fans; one air flow for each fan; forward speed of 2.8 km/h. The use of one fan (back) or two fans (back and front) produced significant differences on the duration of the presence of wind in the measurement point and on the direction of the air velocity vector. The module of the air velocity vector was not affected by the number of activated fans.

Evaluation of the microbiological quality of natural processed products for medicinal use marketed in Quito, Ecuador. / Evaluación de la calidad microbiológica de productos naturales procesados de uso medicinal comercializados en Quito, Ecuador.

OBJECTIVES: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. MATERIALS AND METHODS: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. RESULTS: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. CONCLUSIONS: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.

OBJETIVOS: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. MATERIALES Y MÉTODOS: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. RESULTADOS: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. CONCLUSIONES: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.

Microcrystalline Cellulose Extracted from Native Plants as an Excipient for Solid Dosage Formulations in Drug Delivery.

Excipients represent the complement of the active principle in any pharmaceutical form. Their function is to provide stability, protection, and to ensure absorption of the drug and acceptability in patients. Cellulose is a conventional excipient in many pharmaceutical solid dosage products. Most of the sources used to extract microcrystalline cellulose come from cotton or wood, which are expensive and in high demand from other industries. As plants are considered the main source of excipient production, we have taken advantage of the biodiversity of Ecuador to evaluate microcrystalline cellulose extracted from borojó (Alibertia patinoi), a native plant, as an excipient for solid dosage formulations. The method of choice for tablet manufacturing was direct compression since it is a conventional fabrication method in the pharmaceutical industry. First, we performed scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) in order to compare the structure and characteristics of the extracted cellulose with two reference commercial cellulose materials. Second, we performed quality tests to evaluate the use of the isolate as an excipient including fluidity, hardness, friability, and disintegration. Compared with commercial and microcrystalline cellulose, the extracted cellulose from the native plant showed comparable characteristics and is consequently a potential excipient that could be used in the pharmaceutical industry. Last, we performed a dissolution test in which we concluded that all tablets have a short release time of active principle.

RecBCD and RecFOR dependent induction of chromosomal deletions by sodium selenite in Salmonella.

RecBCD and RecFOR homologous recombination pathways induced bacterial chromosomal duplication-segregation by sodium selenite (SSe) at sub-inhibitory concentrations. This evidence suggests that SSe induces both, double and single DNA strand damage with a concomitant DNA repair response, however the strong dependence for recombinogenic activity of RecB product suggests that the main DNA repair pathway copes with dsDNA breaks. A role for SSe recombinogenic induction is proposed to explain its effect on DNA instability.

Cytotoxicity of the beta-carboline alkaloids harmine and harmaline in human cell assays in vitro.

beta-Carboline alkaloids are natural products widely distributed in plants and also found in alcoholic beverages, well-cooked foods and tobacco smoke. Various authors have reported genotoxic activities of several carboline in prokaryotic and eukaryotic cells that have been attributed to their abilities to intercalate into DNA. But studies on the genotoxic and on the cytotoxic potencies in human cells in vitro are not found in the literature. In the present study the toxicities of one full aromatic beta-carboline alkaloid (harmine) and one dihydro-beta-carboline alkaloid (harmaline) were evaluated by means of two in vitro human cell assays: the cytochalasin-B blocked micronucleus (CBMN) assay and the viability/colony formation assay with four different human cultured non-transformed (CCD18Lu) and transformed (HeLa, C33A and SW480) cells. Neither alkaloid was able to induce micronuclei levels above that of control levels in a wide range of doses tested; although, harmine at the highest concentrations assayed induced apoptotic as well as necrotic cells. Harmine produced a good viability of all cell lines assayed (control and tumor) while harmaline significantly reduced the viability of transformed and non-transformed cell lines in a dose-dependent manner. Harmine displayed a dose-dependent inhibitory effect on cell proliferation against all human carcinoma cells, but the SW480 transformed cell line showed a higher sensitivity. These results suggested that harmine was identified as a useful inhibitor of tumor development.

[Hemorroidal disease in a specialty medical center]. / Enfermedad hemorroidal en unidad médica de alta especialidad.

BACKGROUND DATA: Haemorrhoids and the symptoms they produce have been recorded throughout history. This disease affects 4-10% of the population. The treatment is based on the degree of haemorrhoidal prolapse and the severity of symptoms. OBJECTIVES: The aim of this study is to show our experience in the treatment of haemorrhoidal disease in the colorectal surgery department from the Centro Médico Nacional Siglo XXI, (IMSS, México, D.F). METHODS: Clinical files were reviewed of patients treated by surgical procedures in a period from March 1996 to March 2004. RESULTS: 3,304 medical consultations were given to first time patients; 443 patients were diagnosed with haemorrhoidal disease representing 13.4% of the anorectal pathology: 358 patients underwent an anorectal operation, 225 males (62.8%) and 133females (37.2%), mean age of 48 years (range 18-78 years). The principal symptoms were bleeding and pain. We found another associated pathology in 20% of the cases. 46 patients were affected by second degree haemorrhoids (12.8%), 244 third degree (68.3%) and 68 patients by fourth degree (19%). The Ferguson technique was the most used (84%). At the same time as the haemorrhoidectomy we did other anorrectal procedures in 20% of patients. The mean operation time was 53 minutes (range 19-150). Acute urinary retention occurred in 28 patients (8%) leak sutures in seven (2%), and bleeding in six (1.7%). The mean hospital stays were two days with follow up of 42 days. The total morbility was 4.7%. CONCLUSIONS: The incidence of haemorrhoidal disease in this study was 13.4%. 80% ofpatients were treated by surgery. This pathology is more common in the fifth decade of life with male-female relation of 1. 7:1. The acute urinary retention was the most common complication. During the performing of a haemorrhoidectomy it was possible to resolve other anorectal pathologies. The Ferguson technique was the most used with a total morbility of 4.7%.

Effect of [Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)]NO3, Casiopeína III-Ea, on the activity of cytochrome P450.

Casiopeína III-Ea (Cas III-Ea(1)) is a copper complex with antiproliferative and antitumor activities, designed to act via alternative mechanisms of action different from Cisplatin. This compound has also been well characterized in preclinical test and pharmacokinetic analysis, being a good candidate for clinical phases. Since very little is known about the processes of biotransformation of therapeutic metal based drugs, this paper report the first approach to the study of the interaction between metal complex Cas III-Ea and cytochromes P450 with the aim to find out possible biotransformation pathways for this complexes and feasible drug-drug interactions. Results showed that Cas III-Ea is a strong irreversible competitive inhibitor of CYP1A1 (IC50 = 7.5 ± 1.0 µM; Ki = 240 nM). The magnitude of values indicate that it is necessary to be taken into account such effect when analyzing possible drug interactions with these new drugs in order to prevent adverse reactions derived from this inhibition.

[Hereditary mixed polyposis syndrome. First report in Mexico]. / Síndrome de poliposis mixta hereditaria. Primer reporte en México.

OBJECTIVE: Report for first time in Mexico a case of hereditary mixed polyposis and review the literature. BACKGROUND: The hereditary mixed polyposis syndrome (HMPS) is an uncommon condition, distinguished by presence of a different histological pattern of polyps in digestive tract, clinically manifested by diarrhea, anemia and weight loss. CASE REPORT: Male patient, 38 years old, with familiar antecedent (dead sister) with polyps and gastric cancer. With history of a 1 year with bleeding and mucous diarrhea, and weight loss of a 28.6 pounds. Pale at physical examination, without abdominal signs. At blood test with hemoglobin of 9.7 g/dL, and colonoscopy with multiple polyps within colon and rectum, upper endoscopy with a big esophageal polyp and multiple polyps in gastric and duodenal lining smaller than 1 cm. Contrast study of intestine was normal. Histopathologic study of the polyps report mixed pattern of polyps: (hyperplasic-adenomatous, juvenile-adenomatous, adenoma-inflammatory-hyperplasic, hyperplasic-adenomatous with a high degree dysplasia); juvenile in esophagus, and hyperplasic in stomach and duodenum. Patient was undergone to totalproctocolectomy and reconstruction by "J" ileoanal pouch with good outcome, and endoscopic esophageal polypectomy, with actual surveillance.

Formación médica para afrontar emergencias y desastres: experiencia de enseñanza-aprendizaje con trabajo colaborativo, uso de tecnologías de información y comunicación, y simulación / Medical education to manage emergencies and disasters: teaching-learning experience with collaborative work, use of information and communication technologies, and simulation spaces

INTRODUCCIÓN: El contexto actual demanda incorporar el manejo de situaciones de catástrofes en la formación médica. Se presenta una experiencia original en la enseñanza de emergencias y desastres, en la carrera de medicina, con uso de metodologías didácticas activas. SUJETOS Y MÉTODOS: El plan didáctico del curso se diseñó incorporando el uso de metodologías de trabajo colaborativo (desarrollo de casos, team based learning, juego de roles), uso de tecnologías de información y comunicación, visitas sobre el terreno y simulaciones. Para cada actividad docente, se elaboró material y pautas de evaluación correspondientes. El curso se evaluó con las calificaciones de los estudiantes, su grado de satisfacción y sus comentarios. Adicionalmente, se realizó un análisis de fortalezas y debilidades por parte del equipo docente, planteándose un plan de mejoras. RESULTADOS: Las calificaciones del curso (escala de 1 a 7; n = 58) fueron altas (media: 6,1; rango: 5,7-6,5). Se observó un alto grado de satisfacción con las estrategias docentes utilizadas (valoraciones del 85-95%). Según el parecer de los estudiantes, se lograron los objetivos de aprendizaje en un 88% (trabajo en equipo) y 93% (conceptualización y aplicación). CONCLUSIÓN: El uso de metodologías activas motiva y favorece el aprendizaje, lo que se traduce en altas calificaciones y grado de satisfacción de los estudiantes, así como una buena percepción de utilidad respecto de su futuro desarrollo profesional

INTRODUCTION: The current context demands to incorporate the management of catastrophe situations in medical education. The original experience utilizing active teaching methodologies in a new course of emergencies and disasters in the medical undergraduate formation is presented. SUBJECTS AND METHODS: The course's didactic plan was designed incorporating the use of collaborative work methodologies (case development, team based learning, role play), use of information and communication technologies, field visit and simulations. For each teaching activity, material and corresponding evaluation guidelines were developed. The course was evaluated with the students' qualifications, their degree of satisfaction and their comments. Additionally, an analysis of strengths and weaknesses was carried out by the teaching team; considering an improvement plan. RESULTS: The course qualifications (scale 1 to 7; n = 58) were highly acceptable (average: 6.1; range: 5.7-6.5). A high degree of satisfaction was observed with the teaching strategies used (valuations between 85-95%). In the opinion of the students, the learning objectives were achieved between 88% (teamwork) and 93% (conceptualization and application). CONCLUSION: The use of active methodologies motivates and favors learning, resulting in high qualifications and student's satisfaction, as well as a good perception of usefulness regarding their future professional development

Evaluación de la calidad microbiológica de productos naturales procesados de uso medicinal comercializados en Quito, Ecuador / Evaluation of the microbiological quality of natural processed products for medicinal use marketed in Quito, Ecuador

RESUMEN Objetivos: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. Materiales y métodos: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. Resultados: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. Conclusiones: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.

ABSTRACT Objectives: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. Materials and methods: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. Results: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. Conclusions: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.

Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. METHODS: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications. TRIAL REGISTRATION: Registered on 5 June 2014 with identification no. NCT02158923 .

Glucagonoma and pseudoglucagonoma syndrome.

CONTEXT: Glucagonoma syndrome may present either associated with a pancreatic neoplasm which secretes glucagon or as a pseudo-glucagonoma associated with other diseases. It is extremely infrequent but well-known with a current prevalence estimated at 1/20,000,000. DESIGN: A retrospective review of glucagonoma and pseudoglucagonoma cases observed between January 1998 and December 2003 in three hospitals. PATIENTS: Five cases: 3 with a demonstrable glucagon-secreting tumor and 2 cases without an associated neoplasm. MAIN OUTCOME MEASURES: Age, sex, initial diagnosis, associated symptoms, and pathology were analyzed as were procedures employed in diagnosis, imaging studies, laboratory data, surgery and follow-up. RESULTS: Hyperglycemia and elevated plasma glucagon levels were found in all cases. In 3 cases, hypo-aminoacidemia and a descrease in fatty acids were found. No changes of zinc levels were observed. Abdominal ultrasound studies were of no value except in evaluating pancreatitis. A CT-scan was conclusive when a pancreatic neoplasm existed and 3 patients were operated on a curative basis. DISCUSSION: Necrolytic migratory erythema was the key diagnosis in all cases. Surgery was intended to be curative. The follow-up was of 8, 37 and 57 months in the cases of true glucagonoma syndrome. CONCLUSIONS: A real prevalence of glucagonoma syndrome could be greater than currently estimated. In our series, it was 13.5/20,000,000. Pseudoglucagonoma syndrome remains a rarity.