Physical compatibility of sulbactam/durlobactam with select intravenous drugs during simulated Y-site administration.

PURPOSE: Sulbactam/durlobactam is a combination antibiotic designed to target Acinetobacter baumannii, including carbapenem-resistant and multidrug-resistant strains. The objective of this study was to determine the physical compatibility of sulbactam/durlobactam solution during simulated Y-site administration with 95 intravenous (IV) drugs. METHODS: Vials of sulbactam/durlobactam solution were diluted in 0.9% sodium chloride injection to a volume of 100 mL (the final concentration of both drugs was 15 mg/mL). All other IV drugs were reconstituted according to the manufacturer's recommendations and diluted with 0.9% sodium chloride injection to the upper range of concentrations used clinically or tested undiluted as intended for administration. Y-site conditions were simulated by mixing 5 mL of sulbactam/durlobactam with 5 mL of the tested drug solutions in a 1:1 ratio. Solutions were inspected for physical characteristics (clarity, color, and Tyndall effect), turbidity, and pH changes before admixture, immediately post admixture, and over 4 hours. Incompatibility was defined as any observed precipitation, significant color change, positive Tyndall test, or turbidity change of ≥0.5 nephelometric turbidity unit during the observation period. RESULTS: Sulbactam/durlobactam was physically compatible with 38 out of 42 antimicrobials tested (90.5%) and compatible overall with 86 of 95 drugs tested (90.5%). Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium, and propofol. CONCLUSION: The Y-site compatibility of sulbactam/durlobactam with 95 IV drugs was described. These compatibility data will assist pharmacists and nurses to safely coordinate administration of IV medications with sulbactam/durlobactam.

Expression of SATB1 and SATB2 in the brain of bony fishes: what fish reveal about evolution.

Satb1 and Satb2 belong to a family of homeodomain proteins with highly conserved functional and regulatory mechanisms and posttranslational modifications in evolution. However, although their distribution in the mouse brain has been analyzed, few data exist in other non-mammalian vertebrates. In the present study, we have analyzed in detail the sequence of SATB1 and SATB2 proteins and the immunolocalization of both, in combination with additional neuronal markers of highly conserved populations, in the brain of adult specimens of different bony fish models at key evolutionary points of vertebrate diversification, in particular including representative species of sarcopterygian and actinopterygian fishes. We observed a striking absence of both proteins in the pallial region of actinopterygians, only detected in lungfish, the only sarcopterygian fish. In the subpallium, including the amygdaloid complex, or comparable structures, we identified that the detected expressions of SATB1 and SATB2 have similar topologies in the studied models. In the caudal telencephalon, all models showed significant expression of SATB1 and SATB2 in the preoptic area, including the acroterminal domain of this region, where the cells were also dopaminergic. In the alar hypothalamus, all models showed SATB2 but not SATB1 in the subparaventricular area, whereas in the basal hypothalamus the cladistian species and the lungfish presented a SATB1 immunoreactive population in the tuberal hypothalamus, also labeled with SATB2 in the latter and colocalizing with the gen Orthopedia. In the diencephalon, all models, except the teleost fish, showed SATB1 in the prethalamus, thalamus and pretectum, whereas only lungfish showed also SATB2 in prethalamus and thalamus. At the midbrain level of actinopterygian fish, the optic tectum, the torus semicircularis and the tegmentum harbored populations of SATB1 cells, whereas lungfish housed SATB2 only in the torus and tegmentum. Similarly, the SATB1 expression in the rhombencephalic central gray and reticular formation was a common feature. The presence of SATB1 in the solitary tract nucleus is a peculiar feature only observed in non-teleost actinopterygian fishes. At these levels, none of the detected populations were catecholaminergic or serotonergic. In conclusion, the protein sequence analysis revealed a high degree of conservation of both proteins, especially in the functional domains, whereas the neuroanatomical pattern of SATB1 and SATB2 revealed significant differences between sarcopterygians and actinopterygians, and these divergences may be related to the different functional involvement of both in the acquisition of various neural phenotypes.

Biological properties and therapeutic applications of garlic and its components.

Garlic is one of the most widely employed condiments in cooking. It has also been used since ancient times in traditional plant-based medicine, largely based on its organosulfur compounds. The objective of this study was to provide updated information on the biological and therapeutic garlic properties. Garlic has been found to possess important biological properties with high therapeutic potential, which is influenced by the mode of its utilization, preparation, and extraction. It has been attributed with antioxidant, anti-inflammatory, and immunomodulatory capacities. Garlic, in particular its organosulfur compounds, can maintain immune system homeostasis through positive effects on immune cells, especially by regulating cytokine proliferation and expression. This may underlie their usefulness in the treatment of infectious and tumor processes. These compounds can also offer vascular benefits by regulating lipid metabolism or by exerting antihypertensive and antiaggregant effects. However, further clinical trials are warranted to confirm the therapeutic potential of garlic and its derivatives.

Separation and determination of cysteine enantiomers in plasma after derivatization with 4-fluoro-7-nitrobenzofurazan.

The importance of D-amino acids in mammals associated with enantio-dependent biological functions has been increasingly highlighted. In addition to naturally occurring, D-amino acid supplementation could have a positive biological impact, including cytoprotective implications. In this context, supplementation with D-cysteine has revealed beneficial effects. Quantification of cysteine enantiomers in rodent plasma has been achieved by using 4-fluoro-7-nitrobenzofurazan derivatization of the target analytes. Cystine, the main form of cysteine in the plasma, was initially reduced to cysteine using DL-dithiothreitol. Baseline enantioseparation was then achieved in less than 3 min using a (R,R)-Whelk-O 1 stationary phase and isocratic elution using CH3OH-H2O 90:10 (v/v) with 15 mM ammonium formate (apparent pH 6.0) at 0.5 mL/min. The derivatives were then detected using negative ESI-MS in SRM mode. An external calibration was employed for D-cysteine, while L-cysteine quantification, as an endogenous analyte, was addressed using a background subtraction strategy. The method was validated. Response functions were obtained from 0 to 300 µM and from 0 to 125 µM for D-cysteine and L-cysteine, respectively. The trueness ranged from 96% to 105% for both enantiomers with repeatability and intermediate precision lower than 8% and 15% for the D-form and the endogenous L-form, respectively. The method was successfully applied for determining D- and L-cysteine in mouse plasma after D-cysteine administration.

Wood Smoke Extract Promotes Extracellular Matrix Remodeling in Normal Human Lung Fibroblasts.

Wood smoke (WS) contains many harmful compounds, including polycyclic aromatic hydrocarbons (PAHs). WS induces inflammation in the airways and lungs and can lead to the development of various acute and chronic respiratory diseases. Pulmonary fibroblasts are the main cells involved in the remodeling of the extracellular matrix (ECM) during the WS-induced inflammatory response. Although fibroblasts remain in a low proliferation state under physiological conditions, they actively participate in ECM remodeling during the inflammatory response in pathophysiological states. Consequently, we used normal human lung fibroblasts (NHLFs) to assess the potential effects of the PAHs-containing wood smoke extract (WSE) on the growth rate, total collagen synthesis, and the expression levels of collagen I and III, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, and the transforming growth factor (TGF)-ß1. We also assessed MMPs activity. The results showed that WSE induced a trimodal behavior in the growth rate curves in NHLFs; the growth rate increased with 0.5-1 % WSE and decreased with 2.5% WSE, without causing cell damage; 5-20% WSE inhibited the growth and induced cell damage. After 3 hours of exposure, 2.5% WSE induced an increase in total collagen synthesis and upregulation of TGF-ß1, collagen I and III, MMP-1, TIMP-1, and TIMP-2 expression. However, MMP-2 expression was downregulated and MMP-9 was not expressed. The gelatinase activity of MMP-2 was also increased. These results suggest that WSE affects the ECM remodeling in NHLFs and indicate the potential involvement of PAHs in this process.

Role of Vitamin D in the Metabolic Syndrome.

The prevalence of hypovitaminosis D has risen in developed countries over the past few years in association with lifestyle changes and an increase in unhealthy habits. Vitamin D deficiency has been implicated in various diseases, including metabolic syndrome (MetS), which is clinically defined by a set of metabolic and vascular disorders. The objective of this study was to review scientific evidence on the relationship between MetS and vitamin D deficiency to support the development of prevention strategies and health education programs. An inverse relationship has been reported between plasma vitamin D concentrations and the features that define MetS, i.e., elevated serum concentrations of glucose, total cholesterol, low-density lipoproteins, triglycerides, glycosylated hemoglobin, and a high body mass index. Numerous studies have described the benefits of vitamin D supplementation to improve outcomes in individuals with MetS. Interventions to maintain optimal vitamin D concentrations are proposed as a preventive strategy against MetS.

Vitamin D and autoimmune diseases.

The prevalence of autoimmune diseases (ADs) has increased over the past few decades. Vitamin D deficiency is a common factor in many of these diseases, whose etiology remains poorly understood. The objective of this study was to review published data on the role of vitamin D in ADs. Vitamin D insufficiency has been described as an important factor in the development of some ADs, generally attributed to the key role of this vitamin in the immune system. Most studies show that adequate supplementation can prevent and improve the development of some of these diseases, although the optimal vitamin D dose remains controversial. We highlight the importance of measuring serum vitamin D levels of the population and developing strategies to improve and maintain levels with no health risks.

Novel allosteric covalent inhibitors of bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa identified by virtual screening.

Protozoans of the genus Cryptosporidium are the causative agent of the gastrointestinal disease, cryptosporidiosis, which can be fatal in immunocompromised individuals. Cryptosporidium hominis (C. hominis) bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in the folate biosynthesis pathway and a molecular target for inhibitor design. Previous studies have demonstrated the importance of the ChTS-DHFR linker region "crossover helix" to the enzymatic activity and stability of the ChDHFR domain. We conducted a virtual screen of a novel non-active site pocket located at the interface of the ChDHFR domain and crossover helix. From this screen we have identified and characterized a noncompetitive inhibitor, compound 15, a substituted diphenyl thiourea. Through subsequent structure activity relationship studies, we have identified a time-dependent inhibitor lead, compound 15D17, a thiol-substituted 2-hydroxy-N-phenylbenzamide, which is selective for ChTS-DHFR, and whose effects appear to be mediated by covalent bond formation with a non-catalytic cysteine residue adjacent to the non-active site pocket.

Participación materna en prevención y control de anemia con micronutrientes en lactantes. Distrito de Independencia, Lima - 2015 / Maternal engagement in infant's prevention and control of anemia with micronutrients. District of Independencia, Lima - 2015

Objetivo: Identificar el nivel de participación materna en el cumplimiento del esquema de suplementación con micronutrientes (MN) para la prevención y control de anemia en niños menores de 24 meses en el distrito de Independencia en Lima entre el 2015 y 2016. Materiales y métodos: Estudio descriptivo, observacional, longitudinal, retrospectivo realizado en el centro de salud Ermitaño Bajo. Participaron madres cuyos niños iniciaron suplementación con micronutrientes. Los datos se recolectaron de 40 historias clínicas seleccionadas. El análisis de datos se realizó mediante estadísticas descriptivas. Principales medidas de resultados: I) Participación alta: recibió ≥181 sobres (MN) y realizó ≥2 dosajes de hemoglobina al niño. II) Participación intermedia alta: recibió ≥181 sobres (MN) y realizó ≤1 dosaje de hemoglobina. III) Participación intermedia baja: recibió ≤180 sobres (MN) y realizó ≥2 dosajes de hemoglobina. IV) Participación baja: recibió ≤180 sobres (MN) y realizó ≤1 dosaje de hemoglobina. Resultados: I) Participación alta: 9 (22,5 %), II) Participación intermedia alta: 3 (7,5 %), III) Participación intermedia baja: 5 (12 5 %) y IV) Participación baja: 23 (57,5 %). Conclusiones: Solo 9 madres (22,5 %) tuvieron una participación alta en el cumplimiento del esquema de suplementación con micronutrientes para prevenir y controlar la anemia en niños menores de 24 meses en el Centro de Salud Ermitaño Bajo del distrito de Independencia

Objective: To identify the level of maternal engagement in complying with the micronutrient (MN) supplementation guidelines for the prevention and control of anemia in children under 24 months of age "in the district of Independencia, Lima, between the years 2015 and 2016". Materials and methods: A descriptive, observational, longitudinal and retrospective study was performed at the Centro de Salud Ermitaño Bajo, district of Independencia, Lima, between the years 2015 and 2016. Participants were mothers whose children started micronutrient supplementation. Data was collected from 40 selected medical records. Data analysis was performed using descriptive statistics. Main outcome measures were: I) High level of engagement: the infant received ≥ 181 MN sachets and ≥ 2 hemoglobin doses. II) Intermediate-high level of engagement: the infant received ≥ 181 MN sachets and ≤ 1 hemoglobin dose. III) Intermediate-low level of engagement: the infant received ≤ 180 MN sachets and ≥ 2 hemoglobin doses. IV) Low level of engagement: the infant received ≤ 180 MN sachets and ≤ 1 hemoglobin dose. Results: I) High level of engagement: 9 mothers (22.5 %). II) Intermediate-high level of engagement: 3 mothers (7.5 %). III) Intermediate-low level of engagement: 5 mothers (12.5 %). IV) Low level of engagement: 23 mothers (57.5 %). Conclusions: Only 9 (22.5 %) mothers had a high level of engagement in complying with the micronutrient supplementation guidelinesfor the prevention and control of anemia in children under 24 months of age at the Centro de Salud Ermitaño Bajo, district of Independencia

Adherencia a terapia médica nutricional en pacientes con diabetes mellitus tipo 2, de un hospital nacional de nivel III en Lima, Perú / Adherence to nutritional therapy in patients with type 2 diabetes mellitus in a level III national hospital in Lima, Peru

Objetivos: Determinar la adherencia a la terapia médica nutricional (TMN) en pacientes con Diabetes Mellitus tipo 2 (DM2) en un hospital nacional de nivel III de Lima-Perú y explorar factores asociados. Material y métodos: Estudio descriptivo transversal, realizado en 163 pacientes con diagnóstico de DM2 del servicio de Endocrinología del Hospital Cayetano Heredia. Se utilizó un Cuestionario de Frecuencia de Alimentos (CFA). La valoración calórica y de macronutrientes fue realizada con valores de referencia del Centro Nacional de Alimentación y Nutrición (CENAN). Se definió adherencia al cumplimiento de recomendación de carbohidratos, fibra, lípidos y proteínas según la American Diabetes Association (ADA). Resultados: El promedio de edad fue 61,1 ± 10,3 años, con predominancia del sexo femenino (61,9%). El 40,5% tenía instrucción primaria. El 38% de los participantes tenía sobrepeso. El 35,6% de los encuestados fueron adherentes a TMN. El tiempo de enfermedad fue mayor en el grupo adherente (9,8 años vs 7,5 años; p=0,035); la frecuencia de pie diabético del grupo adherente fue tres veces mayor que en los no adherentes (12,1% vs 3,8%; p=0,04). Conclusiones: Los resultados muestran una baja adherencia a la TMN. Este estudio da acceso a una de las primeras aproximaciones de la adherencia a TMN en el Perú. (AU)

Objectives: To ascertain the adherence to nutritional therapy (NT) among type 2 diabetes mellitus (DM2) in a level III national hospital in Lima, Peru and to explore factors associated with it. Methods: Cross-sectional study performed in 163 patients with DM2 at the Endocrinology service of Hospital Cayetano Heredia. A food frequency questionnaire was applied; caloric and macronutrient evaluation was performed with reference values from the Centro Nacional de Alimentación y Nutrición (CENAN). Adherence to recommendation for consumption of carbohydrates, proteins and lipids was evaluated based on recommendations by the American Diabetes Association (ADA). Results: Mean age was 61.1 ± 10.3 years; 61.9% were females; 40.5% had elementary education; 38% had obesity. Only 35.6% adhered to NT. Time with DM2 was higher in the adherent group (9.8 vs. 7.5 years; p=0.035); frequency of diabetic foot was three times higher than that of non-adherent patients (12.1% vs 3.8%; p=0.04). Conclusions: This is the first attempt to evaluate adherence to NT in Peru showing low adherence rates. (AU)

Bleomycin-induced pulmonary fibrosis is attenuated in gamma-glutamyl transpeptidase-deficient mice.

To investigate repair mechanisms in bleomycin-induced pulmonary fibrosis, we used mice deficient in gamma-glutamyl transpeptidase (GGT-/-), a key enzyme in glutathione (GSH) and cysteine metabolism. Seventy-two hours after bleomycin (0.03 U/g), GGT-/- mice displayed a different inflammatory response to wild-type mice as judged by a near absence of neutrophils in lung tissue and bronchoalveolar lavage and a less pronounced rise in matrix metalloproteinase-9. Inflammation in GGT-/- mice consisted mainly of lymphocytes and macrophages. At 1 month, lungs from bleomycin-treated GGT-/- mice exhibited minimal areas of fibrosis compared with wild-type mice(light microscopy fibrosis index: 510 +/- 756 versus 1975 +/- 817, p < 0.01). Lung collagen content revealed a significant increase in bleomycin-treated wild-type (15.1 +/- 3.8 versus 8.5 +/- 0.7 microg hydroxy(OH)-proline/mg dry weight, p < 0.01) but not in GGT-/- (10.4 +/- 1.7 versus 8.8 +/- 0.8). Control lungs from GGT-/- showed a significant reduction of cysteine (0.03 +/- 0.005 versus 0.055 +/- 0.001, p < 0.02) and GSH levels (1.24 +/- 0.055 versus 1.79 +/- 0.065, p < 0.002). These values decreased after 72 hours of bleomycin in both GGT-/- and wild-type but reached their respective control values after 1 month. Supplementation with N-acetyl cysteine partially ameliorated the effects of GGT deficiency. These findings suggest that increased neutrophils and matrix metalloproteinase-9 during the early inflammatory response and adequate thiol reserves are key elements in the fibrotic response after bleomycin-induced pulmonary injury.