ABSTRACT
INTRODUCTION: While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. METHODS: COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. RESULTS: Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. CONCLUSION: IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.
Subject(s)
COVID-19 , Olfaction Disorders , Humans , Prospective Studies , Smell , Cytokines , BiomarkersABSTRACT
Antecedentes: La preferencia de los ortodoncistas en Colombia en el uso de aparatos funcionales y los factores diagnósticos que pueden influenciar la indicación del clínico de una determinada aparatología no es bien conocidos. Objetivo: Comparar las preferencias en el uso de aparatos funcionales para tratamiento de maloclusiones clases II y III entre un posgrado de ortodoncia y una población de ortodoncistas y evaluar la asociación entre el aparato indicado y las características demográficas y diagnósticas de los pacientes del postgrado de ortodoncia. Métodos: Estudio de corte transversal. Se revisaron 565 historias clínicas, de un programa de posgrado de ortodoncia y 180 encuestas a miembros de la Sociedad Colombiana de Ortodoncia (SCO). Para evaluar asociación se utilizó la prueba Chi2 y prueba t. La significancia estadística fue establecida en P < 0,05. Resultados: En el posgrado de ortodoncia el aparato funcional más utilizado para tratar la maloclusión Clase II fue el Simoes Network (55,42 %) y para Clase III fue el Lázaro (28,95 %). La mayoría de los miembros de la SCO prefiere tratar la maloclusión de Clase II con las Pistas Indirectas Planas (32,78 %) y la Clase III con la Máscara Facial (62,22 %). Se encontraron diferencias estadísticamente significativas (P < 0,05) entre las preferencias de uso de aparatos funcionales por los ortodoncistas de SCO y el postgrado de ortodoncia evaluado. Conclusiones: Los resultados sugieren que la indicación de los aparatos funcionales para el manejo de maloclusiones Clase II y Clase III no solamente está guiada por la maloclusión, sino que también por la formación académica y preferencias individuales de los ortodoncistas.
Background: The preference for the functional appliances to treat Class II and Class III malocclusions by orthodontists in Colombia and their reasons to select them is not well established, yet. Purpose: To compare the preferences in the use of functional appliances to treat Class II and Class III malocclusions between an orthodontic graduate program and the orthodontist members of the Colombian Society of Orthodontists (CSO) and to evaluate the association between the indicated functional appliance and the diagnostic and demographic characteristics of the patients in the orthodontic program. Methods: In this cross-sectional study were reviewed 565 clinical records of the orthodontic graduate program and the survey of 180 members of the CSO. Chi square and t test at a level of significance P < 0.05 were used to compare both groups. Results: the most frequently functional appliance used to treat Class II malocclusion in the orthodontic graduate program was Simoes Network (55, 42 %) and to treat Class III was the Lazaro (28, 95 %). CSO members preferred Planas indirect tracks (32,78 %) to treat Class II and Facial Mask (62,22 %) to treat Class III. Statistically significant differences (P < 0, 05) in the use preference of functional appliances between the orthodontic graduate program and the orthodontist from the CSO were found. Conclusions: The results suggest that the selection of functional appliances to treat Class II and Class III malocclusions is not only guided by the malocclusion but by the orthodontist´s academic background and individual preferences as well.
Antecedentes: A preferência pelos aparelhos funcionais para tratar as más oclusões de Classe II e Classe III por ortodontistas na Colômbia e seus motivos para selecioná-los ainda não está bem estabelecida. Objetivo: Comparar as preferências no uso de aparelhos funcionais para tratamento de más oclusões Classe II e Classe III entre um programa de pós-graduação ortodôntica e os membros ortodontistas da Sociedade Colombiana de Ortodontistas (CSO) e avaliar a associação entre o aparelho funcional indicado e o características diagnósticas e demográficas dos pacientes no programa ortodôntico. Métodos: Neste estudo transversal foram revisados 565 prontuários clínicos do programa de pós-graduação ortodôntica e a pesquisa de 180 membros da OSC. Qui-quadrado e teste t ao nível de significância P <0,05 foram usados para comparar ambos os grupos. Resultados: o aparelho funcional mais frequentemente utilizado para tratar a má oclusão de Classe II no programa de pós-graduação ortodôntica foi a Rede Simões (55, 42%) e para tratar a Classe III foi o Lazaro (28, 95%). Os membros da OSC preferiram as pistas indiretas Planas (32,78%) para tratar a Classe II e a Máscara Facial (62,22%) para tratar a Classe III. Diferenças estatisticamente significantes (P <0,05) na preferência de uso de aparelhos funcionais entre o programa de pós-graduação ortodôntica e o ortodontista da OSC foram encontradas. Conclusões: Os resultados sugerem que a seleção de aparelhos funcionais para tratar as más oclusões de Classe II e Classe III não é guiada apenas pela má oclusão, mas também pela formação acadêmica do ortodontista e preferências individuais.
Subject(s)
Humans , Malocclusion , Orthodontic Appliances/statistics & numerical data , Dental Occlusion , Malocclusion, Angle Class IIABSTRACT
A 23-year-old male with one month of intractable vomiting, subsequent cholecystitis status post cholecystectomy, and overall 40-pound weight loss over the last few months presented with altered mental status and seizures. MRI showed signal abnormalities involving the hypothalamus, periaqueductal gray matter, 4th ventricle, and bilateral thalami, indicative of Wernicke's encephalopathy. The patient was started on empiric IV thiamine and methylprednisolone; thiamine levels were subsequently found to be low. Infectious disease workup was negative. Within a few days of this therapy, the patient's neurological status steadily improved with increased responsiveness and communication. Repeat MRI 7 days after admission showed significant resolution of the signal abnormalities. Over the next several weeks the patient became fully conversational, cognitively intact, and increasingly ambulatory. Nonalcoholic Wernicke's encephalopathy is rare; there have been reports relating it separately to vomiting and invasive surgery. In this case report, we associate it with both recurrent vomiting and minimally invasive cholecystectomy. We also discuss combinatorial therapy of thiamine and corticosteroids, which is poorly defined in the literature. Though there is no consensus-based optimal treatment of Wernicke's encephalopathy, this adds to the discussion of using dual therapy and supports that the use of empiric corticosteroids does not harm the patient.
ABSTRACT
Existen diversos criterios sobre la utilidad del electrocardiograma (ECG) preoperatorio. Evaluar su utilidad en pacientes programados para cirugía no cardiaca. Se realizó un estudio descriptivo, prospectivo y transversal en 150 pacientes adultos y de uno u otro sexo, programados para cirugía bajo anestesia general, regional o combinada, en el Hospital Dr Carlos J Finlay, en el periodo enero-abril 2007. Se estudiaron los hallazgos electrocardiográficos y su influencia en la conducta preoperatoria y predicción de complicaciones. 71,3 por ciento de los electrocardiogramas realizados resultaron normales, 67,4 por ciento de las alteraciones del electrocardiograma fueron esperadas y 55,8 por ciento menores. El electrocardiograma influyó en la conducta preoperatoria del 1,3 por ciento de los pacientes. Las complicaciones perioperatorias se presentaron en 3,7 por ciento de los pacientes y todos con electrocardiograma normal. Las alteraciones electrocardiográficas fueron pocas, predominantemente menores y no esperadas e influyeron escasamente en la conducta preoperatoria. El ECG preoperatorio no permitió predecir complicaciones(AU)
Subject(s)
Humans , Male , Female , Adult , Electrocardiography/methods , Preoperative Care/instrumentationABSTRACT
Existen diversos criterios sobre la utilidad del electrocardiograma (ECG) preoperatorio. Evaluar su utilidad en pacientes programados para cirugía no cardiaca. Se realizó un estudio descriptivo, prospectivo y transversal en 150 pacientes adultos y de uno u otro sexo, programados para cirugía bajo anestesia general, regional o combinada, en el Hospital Dr Carlos J Finlay, en el periodo enero-abril 2007. Se estudiaron los hallazgos electrocardiográficos y su influencia en la conducta preoperatoria y predicción de complicaciones. 71,3 por ciento de los ECG realizados resultaron normales, 67,4 por ciento de las alteraciones del ECG fueron esperadas y 55,8 por ciento menores. El ECG influyó en la conducta preoperatoria del 1,3 porciento de los pacientes. Las complicaciones perioperatorias se presentaron en 3,7 por ciento de los pacientes y todos con ECG normal. Las alteraciones electrocardiográficas fueron pocas, predominantemente menores y no esperadas e influyeron escasamente en la conducta preoperatoria. El ECG preoperatorio no permitió predecir complicaciones(AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Blood Pressure , Heart Rate , AnestheticsABSTRACT
A series of novel and potent 6-heteroaryl-pyrrolidino-tetrahydroisoquinolines with dual histamine H(3) antagonist/serotonin transporter inhibitor activity is described. In vitro and in vivo data are discussed.
Subject(s)
Histamine H1 Antagonists/pharmacology , Pyrrolidines/pharmacology , Receptors, Histamine H3/drug effects , Serotonin Plasma Membrane Transport Proteins/drug effects , Tetrahydroisoquinolines/pharmacology , Animals , Blood-Brain Barrier , Histamine H1 Antagonists/chemistry , Mice , Pyrrolidines/chemistry , Structure-Activity Relationship , Tetrahydroisoquinolines/chemistryABSTRACT
A series of novel and potent pyrrolidino-tetrahydroisoquinolines with dual histamine H(3) antagonist/serotonin transporter inhibitor activity is described. A highly regio- and diastereoselective synthesis of the pyrrolidino-tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH(3) was developed. In vitro and in vivo data are discussed.
Subject(s)
Chemistry, Pharmaceutical/methods , Histamine Antagonists/chemical synthesis , Histamine Antagonists/pharmacology , Receptors, Histamine H3/chemistry , Selective Serotonin Reuptake Inhibitors/chemical synthesis , Selective Serotonin Reuptake Inhibitors/pharmacology , Serotonin/chemistry , Tetrahydroisoquinolines/chemical synthesis , Tetrahydroisoquinolines/pharmacology , Animals , Depression/drug therapy , Drug Design , Humans , Kinetics , Models, Chemical , Molecular Conformation , RatsABSTRACT
A series of tetrahydroisoquinolines acting as dual histamine H3/serotonin transporter ligands is described. A highly regio-selective synthesis of the tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH3 was developed. In vitro and in vivo data are discussed.
Subject(s)
Receptors, Histamine H3/chemistry , Receptors, Histamine H3/drug effects , Serotonin Plasma Membrane Transport Proteins/drug effects , 5-Hydroxytryptophan/pharmacology , Animals , Behavior, Animal/drug effects , Humans , Isoquinolines/chemical synthesis , Isoquinolines/pharmacology , Ligands , Mice , Piperazines/chemical synthesis , Piperazines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
A series of novel 4-aryl-1,2,3,4-tetrahydroisoquinoline-based histamine H(3) ligands that also have serotonin reuptake transporter inhibitor activity is described. The synthesis, in vitro biological data, and select pharmacokinetic data for these novel compounds are discussed.
Subject(s)
Histamine Antagonists/chemical synthesis , Histamine Antagonists/pharmacology , Receptors, Histamine H3/drug effects , Selective Serotonin Reuptake Inhibitors/chemical synthesis , Selective Serotonin Reuptake Inhibitors/pharmacology , Tetrahydroisoquinolines/chemical synthesis , Tetrahydroisoquinolines/pharmacology , Animals , Crystallography, X-Ray , Dopamine Plasma Membrane Transport Proteins/drug effects , Dopamine Plasma Membrane Transport Proteins/metabolism , Half-Life , Humans , Indicators and Reagents , Models, Molecular , Molecular Conformation , Norepinephrine/metabolism , Rats , Serotonin Plasma Membrane Transport Proteins/drug effects , Serotonin Plasma Membrane Transport Proteins/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Structure-Activity Relationship , Tetrahydroisoquinolines/pharmacokineticsABSTRACT
Tosyl- and Boc-hydrazones were found to be effective nucleophiles in the Mitsunobu reaction. Tosyl hydrazones reacted cleanly with primary and secondary alcohols when co-administered to a cooled DBAD/PPh3 or DEAD/PPh3 complex. Boc-hydrazones required electron-withdrawing substituents to participate in the reaction.
Subject(s)
Chemistry, Organic/methods , Hydrazones/chemistry , Alcohols/chemistryABSTRACT
A class of inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2) was discovered. These compounds have demonstrated activity against the enzyme with IC50 values as low as 130 nM and suppress the expression of TNFalpha in U937 cells. These represent the first small molecule inhibitors of MK-2 to be reported.
Subject(s)
MAP Kinase Kinase 2/antagonists & inhibitors , Pyridines/chemistry , Pyridines/pharmacology , Animals , Gene Expression , Humans , Models, Chemical , Molecular Structure , Rats , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism , U937 CellsABSTRACT
Bacterial elongation factor Tu (EF-Tu) and EF-Ts are interacting proteins involved in polypeptide chain elongation in protein biosynthesis. A novel scintillation proximity assay for the detection of inhibitors of EF-Tu and EF-Ts, as well as the interaction between them, was developed and used in a high-throughput screen of a chemical library. Several compounds from a variety of chemical series with inhibitory properties were identified, including certain indole dipeptides, benzimidazole amidines, 2-arylbenzimidazoles, N-substituted imidazoles, and N-substituted guanidines. The in vitro activities of these compounds were confirmed in a coupled bacterial transcription-translation assay. Several indole dipeptides were identified as inhibitors of bacterial translation, with compound 2 exhibiting a 50% inhibitory concentration of 14 microM and an MIC for S. aureus ATCC 29213 of 5.6 microg/ml. Structure-activity relationship studies around the dipeptidic indoles generated additional analogs with low micromolar MICs for both gram-negative and gram-positive bacteria. To assess the specificity of antibacterial action, these compounds were evaluated in a metabolic labeling assay with Staphylococcus aureus. Inhibition of translation, as well as limited effects on other macromolecular pathways for some of the analogs studied, indicated a possible contribution from a non-target-based antibacterial mechanism of action.
