Effects of the GingivalStat approach on early gingival margin remodeling following esthetic clinical crown lengthening: A case series.

OBJECTIVES: The aim of this case series is to present the potential applications of the GingivalStat approach, that is, the use of temporary gingival stabilizers, to favor early gingival margin remodeling and prevent the occurrence of gingival rebound following esthetic clinical crown lengthening. CLINICAL CONSIDERATIONS: Four patients requiring clinical crown lengthening were treated for esthetical and functional reasons. The surgical approach included: (a) gingival margin recontouring; (b) full-thickness flap elevation; (c) osteotomy (to achieve an adequate dimension between the alveolar bone crest and the CEJ) and osteoplasty (to reduce the bone thickness and improve the buccal bone anatomic profile, where indicated); (d) temporary gingival stabilizer placement using a block-out resin or a composite (the GingivalStat approach); and (e) flap repositioning, adaptation, and suture. One- to five-year follow-ups, reported in the different case scenarios, show evidence of clinically stable gingival margins around the treated teeth. CONCLUSIONS: Within the limits of this case series, it can be concluded that the GingivalStat approach appears as a further maneuver to cope with clinical crown lengthening procedures at esthetic sites. GingivalStat seems to favor gingival margin contour remodeling during the early phase of healing as well as prevent the occurrence of gingival rebound. CLINICAL SIGNIFICANCE: GingivalStat approach may guide gingival margin remodeling and prevent gingival rebound after wound healing of sites submitted to esthetic clinical crown lengthening.

Osmotic Demyelination Syndrome in a Normonatremic Patient Under Treatment With Proton Pump Inhibitors.

A 66-year-old woman was admitted to the emergency department with diarrhea, nausea, and vomiting as well as low-grade fever. She was initially treated with ciprofloxacin and metronidazole with symptomatic improvement and was discharged. One week later, she returned to the emergency department for gait instability, dizziness, and vomiting and had a witnessed generalized tonic-clonic seizure in the hospital. During both admissions, the presence of ionic alterations such as severe hypomagnesemia, hypophosphatemia, and hypokalemia stood out, while sodium levels remained normal. Among her antecedents, she had a hiatal hernia and had been receiving treatment with omeprazole for years.

Active alcohol consumption is associated with acute-on-chronic liver failure in Hispanic patients.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America. METHODS: Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models. RESULTS: We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001). CONCLUSIONS: Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF.

Probing the Binding Mechanism of Acylated Peptides to Human Serum Albumin.

Peptides represent an increasingly important class of pharmaceutical products. During the last decade or so, acylation with fatty acids has demonstrated considerable success in prolonging the circulating half-life of therapeutic peptides by exploiting the ability of fatty acids to reversibly bind to human serum albumin (HSA), thus significantly impacting their pharmacological profiles. Employing methyl-13C-labeled oleic acid or palmitic acid as probe molecules and exploiting HSA mutants designed to probe fatty acid binding, the signals in two-dimensional (2D) nuclear magnetic resonance (NMR) spectra corresponding to high-affinity fatty acid binding sites in HSA were assigned. Subsequently, using a set of selected acylated peptides, competitive displacement experiments by 2D NMR identified a primary fatty acid binding site in HSA utilized in acylated peptide binding. These results represent an important first step toward understanding the structural basis for acylated peptides binding to HSA.

Errors and complications in clinical periodontal practice due to methodologic bias and bad interpretation of the evidence.

Different types of errors and complications may arise during and after the execution of periodontal or implant-related procedures. Some of the most relevant, although also controversial, and less commented, causative agents of errors and complications are methodological biases and bad interpretation of the evidence. Proper assessment of the literature requires of solid clinical knowledge combined with a systematic approach built on the recognition of common methodological biases and the avoidance of interpretive errors to critically retrieve, dissect, and judiciously apply available information for the promotion of periodontal and peri-implant health. This review addresses common types of methodological bias and interpretive errors that can alter the reader's perceptions on the real effect and potential ramifications of the reported outcomes of a given therapeutic approach due to bad interpretation of the available evidence: (1) types of methodological biases; (2) spin and interpretive bias; (3) interpretation pitfalls when assessing the evidence (4) choice of relevant endpoints to answer the question(s) of interest; and (5) balance between statistical significance and clinical relevance.

Periodontal phenotype modification of complexes periodontal-orthodontic case scenarios: A clinical review on the applications of allogenous dermal matrix as an alternative to subepithelial connective tissue graft.

OBJECTIVES: The aim of this review is to address the potential applications of allogenous dermal matrix (ADM), as an alternative to subepithelial connective tissue graft (SCTG), in promoting periodontal phenotype modification (PPM) of challenging periodontal-orthodontic clinical scenarios. OVERVIEW: The rationale behind the need of changing thin to thick gingival tissues is associated to the superior and more stable treatment outcomes promoted by PPM therapy. PPM, via soft tissue grafting, leads to clinical and histological changes of the pre-established original genetic conditions of the gingiva. Although SCTG-based procedures are recognized as the "gold standard" for the treatment of sites requiring root coverage and gingival augmentation, ADM has been recognized as the most suitable alternative to SCTG, particularly in clinical scenarios where the use of autogenous grafts is not possible. Thus, ADM is considered an optimal option for the treatment of patients with a history (or in need) of orthodontic tooth movement, due its two-fold potential indication: (1) the promotion of periodontal soft tissue phenotype modification; and (2) its use, as a barrier membrane, in hard tissues augmentation procedures. CONCLUSIONS: ADM is a viable option for soft tissue augmentation, as well as for treatment approaches involving buccal bone gain. CLINICAL SIGNIFICANCE: Periodontal phenotype modification therapy, when applied in challenging periodontal-orthodontic clinical scenarios, promotes root coverage and prevents the onset and development clinical attachment loss.

Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site.

OBJECTIVE: Ultra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog® and Lyumjev® formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model. METHODS: We employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy. RESULTS: Through experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step. CONCLUSIONS: This study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future.

Plant responses to heterogeneous salinity: agronomic relevance and research priorities.

BACKGROUND: Soil salinity, in both natural and managed environments, is highly heterogeneous, and understanding how plants respond to this spatiotemporal heterogeneity is increasingly important for sustainable agriculture in the era of global climate change. While the vast majority of research on crop response to salinity utilizes homogeneous saline conditions, a much smaller, but important, effort has been made in the past decade to understand plant molecular and physiological responses to heterogeneous salinity mainly by using split-root studies. These studies have begun to unravel how plants compensate for water/nutrient deprivation and limit salt stress by optimizing root-foraging in the most favourable parts of the soil. SCOPE: This paper provides an overview of the patterns of salinity heterogeneity in rain-fed and irrigated systems. We then discuss results from split-root studies and the recent progress in understanding the physiological and molecular mechanisms regulating plant responses to heterogeneous root-zone salinity and nutrient conditions. We focus on mechanisms by which plants (salt/nutrient sensing, root-shoot signalling and water uptake) could optimize the use of less-saline patches within the root-zone, thereby enhancing growth under heterogeneous soil salinity conditions. Finally, we place these findings in the context of defining future research priorities, possible irrigation management and crop breeding opportunities to improve productivity from salt-affected lands.

Sintomatología depresiva y trastornos neurocognitivos en pacientes con VIH adherentes y no adherentes a TARAA: estudio transversal analítico / Depressive symptomatology and neurocognitive disorders in haart-adherent and non-adherent hiv patients: a cross-sectional analytical study

Introducción: Las personas portadoras del virus de inmunodeficiencia humana (VIH) presentan mayor comorbilidad de trastornos neurocognitivos y del ánimo que la población general. La introducción de los antirretrovirales ha disminuido significativamente la demencia asociada a VIH, relacionado a la adherencia a la terapia antirretroviral altamente activa (TARAA). Diversos estudios han demostrado la coexistencia de otros factores para explicar dicho trastorno cognitivo, tales como enfermedad neurológica previa, enfermedad psiquiátrica, consumo de drogas, nivel educativo, reserva cognitiva, entre otras. Objetivo: Determinar el grado de sintomatología depresiva, deterioro cognitivo y su relación con la adherencia a TARAA y otros factores de curso clínico en pacientes portadores de VIH en control ambulatorio. Métodos: Estudio transversal. Se incluyeron pacientes que viven con VIH adscritos al programa de infectología del Hospital Dr. Gustavo Fricke, Viña del mar, Chile. Se utilizaron datos sociodemográficos, clínicos y se aplicaron las escalas Depression in the Medicaly III Questionary, Montreal Cognitive Assesment y Morysky Green Levin Test. Resultados: Se incluyeron 29 participantes, en su mayoría hombres (86,2%) y con escolaridad técnica o profesional (86.2%). No hubo diferencias entre variables biodemográficas, depresivas ni subdimensiones cognitivos. Entre pacientes adherentes y no adherentes se encontró diferencias significativas respecto a la presencia de algún deterioro cognitivo. Conclusiones: Los resultados deben ser interpretados con cautela, dado su alcance limitado. Futuros estudios traslacionales debieran incorporar mediciones más certeras del nivel de adherencia al TARAA.

Introduction: Human immunodeficiency virus (HIV) carriers present more neurocognitive and mood disorders than the general population. The introduction of antiretrovirals has significantly lowered the incidence of HIV associated dementia, and this is related to adherence to highly active antiretroviral therapy (HAART). Several studies have shown the coexistence of other factors that could explain the cognitive disorder, such as a pre-existing neurological disease, psychiatric disease, drug consumption, level of education, cognitive reserve, and others. Objective: To determine the degree of depressive symptomatology and cognitive impairment and their relation to adherence to HAART and other factors of the clinical course of HIV carriers in outpatient supervision. Methods: Cross-sectional study. We included HIV patients in the infectious diseases program, Dr Gustavo Fricke Hospital, Viña del Mar, Chile. We used sociodemographic and clinical data and we applied the Depression in the Medically Ill questionnaire, Montreal Cognitive Assessment, and the Morysky Green Levin Test. Results: 29 patients participated, mainly men (86.2%) with technical or professional education (86.2%). There were no significant differences in sociodemographic, depressive, or cognitive subdomain variables. There were significant differences in cognitive impairment between adherents and non-adherents. Conclusions: Care should be taken with interpreting the results, given their limited scope. Future cross-sectional studies should incorporate more accurate measurements of HAART adherence.

Characterization of viral insulins reveals white adipose tissue-specific effects in mice.

OBJECTIVE: Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e., more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 (LCDV-1) for the first time. METHODS: The dcVILPs were chemically synthesized. Using murine fibroblast cell lines overexpressing insulin receptor (IR-A or IR-B) or IGF1R, we first determined the binding affinity of dcVILPs to the receptors and characterized post-receptor signaling. Further, we used C57BL/6J mice to study the effect of dcVILPs on lowering blood glucose. We designed a 3-h dcVILP in vivo infusion experiment to determine the glucose uptake in different tissues. RESULTS: GIV and SGIV dcVILPs bind to both isoforms of human insulin receptor (IR-A and IR-B) and to the IGF1R, and for the latter, show higher affinity than human insulin. These dcVILPs stimulate IR and IGF1R phosphorylation and post-receptor signaling in vitro and in vivo. Both GIV and SGIV dcVILPs stimulate glucose uptake in mice. In vivo infusion experiments revealed that while insulin (0.015 nmol/kg/min) and GIV dcVILP (0.75 nmol/kg/min) stimulated a comparable glucose uptake in heart and skeletal muscle and brown adipose tissue, GIV dcVILP stimulated 2-fold higher glucose uptake in white adipose tissue (WAT) compared to insulin. This was associated with increased Akt phosphorylation and glucose transporter type 4 (GLUT4) gene expression compared to insulin in WAT. CONCLUSIONS: Our results show that GIV and SGIV dcVILPs are active members of the insulin superfamily with unique characteristics. Elucidating the mechanism of tissue specificity for GIV dcVILP will help us to better understand insulin action, design new analogs that specifically target the tissues and provide new insights into their potential role in disease.

Optimized Production of a Redox Metabolite (pyocyanin) by Pseudomonas aeruginosa NEJ01R Using a Maize By-Product.

Pseudomonas aeruginosa metabolizes pyocyanin, a redox molecule related to diverse biological activities. Culture conditions for the production of pyocyanin in a defined medium were optimized using a statistical design and response surface methodology. The obtained conditions were replicated using as substrate an alkaline residual liquid of cooked maize and its by-products. The untreated effluent (raw nejayote, RN) was processed to obtain a fraction without insoluble solids (clarified fraction, CL), then separated by a 30 kDa membrane where two fractions, namely, retentate (RE) and filtered (FI), were obtained. Optimal conditions in the defined medium were 29.6 °C, 223.7 rpm and pH = 6.92, which produced 2.21 µg mL-1 of pyocyanin, and by using the wastewater, it was possible to obtain 3.25 µg mL-1 of pyocyanin in the retentate fraction at 40 h. The retentate fraction presented the highest concentration of total solids related to the maximum concentration of pyocyanin (PYO) obtained. The pyocyanin redox behavior was analyzed using electrochemical techniques. In this way, valorization of lime-cooked maize wastewater (nejayote) used as a substrate was demonstrated in the production of a value-added compound, such as pyocyanin, a redox metabolite of Pseudomonas aeruginosa NEJ01R.

Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice.

OBJECTIVE: The continuous endothelium of skeletal muscle (SkM) capillaries regulates insulin's access to skeletal myocytes. Whether impaired transendothelial insulin transport (EIT) contributes to SkM insulin resistance (IR), however, is unknown. METHODS: Male and female C57/Bl6 mice were fed either chow or a high-fat diet for 16 weeks. Intravital microscopy was used to measure EIT in SkM capillaries, electron microscopy to assess endothelial ultrastructure, and glucose tracers to measure indices of glucose metabolism. RESULTS: Diet-induced obesity (DIO) male mice were found to have a ~15% reduction in EIT compared with lean mice. Impaired EIT was associated with a 45% reduction in endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with sustained interstitial insulin delivery, DIO male mice still showed SkM IR indicating severe myocellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure, or SkM insulin sensitivity between lean female mice and female mice fed a high-fat diet. CONCLUSIONS: These results suggest that, in male mice, obesity results in ultrastructural alterations to the capillary endothelium that delay EIT. Nonetheless, the myocyte appears to exceed the endothelium as a contributor to SkM IR in DIO male mice.

Acute Nitric Oxide Synthase Inhibition Accelerates Transendothelial Insulin Efflux In Vivo.

Before insulin can stimulate glucose uptake in muscle, it must be delivered to skeletal muscle (SkM) through the microvasculature. Insulin delivery is determined by SkM perfusion and the rate of movement of insulin across the capillary endothelium. The endothelium therefore plays a central role in regulating insulin access to SkM. Nitric oxide (NO) is a key regulator of endothelial function and stimulates arterial vasodilation, which increases SkM perfusion and the capillary surface area available for insulin exchange. The effects of NO on transendothelial insulin efflux (TIE), however, are unknown. We hypothesized that acute reduction of endothelial NO would reduce TIE. However, intravital imaging of TIE in mice revealed that reduction of NO by l-NG-nitro-l-arginine methyl ester (l-NAME) enhanced the rate of TIE by ∼30% and increased total extravascular insulin delivery. This accelerated TIE was associated with more rapid insulin-stimulated glucose lowering. Sodium nitroprusside, an NO donor, had no effect on TIE in mice. The effects of l-NAME on TIE were not due to changes in blood pressure alone, as a direct-acting vasoconstrictor (phenylephrine) did not affect TIE. These results demonstrate that acute NO synthase inhibition increases the permeability of capillaries to insulin, leading to an increase in delivery of insulin to SkM.

Insulin exits skeletal muscle capillaries by fluid-phase transport.

Before insulin can stimulate myocytes to take up glucose, it must first move from the circulation to the interstitial space. The continuous endothelium of skeletal muscle (SkM) capillaries restricts insulin's access to myocytes. The mechanism by which insulin crosses this continuous endothelium is critical to understand insulin action and insulin resistance; however, methodological obstacles have limited understanding of endothelial insulin transport in vivo. Here, we present an intravital microscopy technique to measure the rate of insulin efflux across the endothelium of SkM capillaries. This method involves development of a fully bioactive, fluorescent insulin probe, a gastrocnemius preparation for intravital microscopy, an automated vascular segmentation algorithm, and the use of mathematical models to estimate endothelial transport parameters. We combined direct visualization of insulin efflux from SkM capillaries with modeling of insulin efflux kinetics to identify fluid-phase transport as the major mode of transendothelial insulin efflux in mice. Model-independent experiments demonstrating that insulin movement is neither saturable nor affected by insulin receptor antagonism supported this result. Our finding that insulin enters the SkM interstitium by fluid-phase transport may have implications in the pathophysiology of SkM insulin resistance as well as in the treatment of diabetes with various insulin analogs.

Short-Term Effects of Kinesio Taping on Muscle Recruitment Order During a Vertical Jump: A Pilot Study.

CONTEXT: Kinesio taping is commonly used in sports and rehabilitation settings with the aim of prevention and treatment of musculoskeletal injuries. However, limited evidence exists regarding the effects of 24 and 72 hours of kinesio taping on trunk and lower limb neuromuscular and kinetic performance during a vertical jump. OBJECTIVE: The purpose of this study was to analyze the short-term effects of kinesio taping on height and ground reaction force during a vertical jump, in addition to trunk and lower limb muscle latency and recruitment order. DESIGN: Single-group pretest-posttest. SETTING: University laboratory. PARTICIPANTS: Twelve male athletes from different sports (track and field, basketball, and soccer). INTERVENTIONS: They completed a single squat and countermovement jump at basal time (no kinesio taping), 24, and 72 hours of kinesio taping application on the gluteus maximus, biceps femoris, rectus femoris, gastrocnemius medialis, and longissimus. MAIN OUTCOME MEASURES: Muscle onset latencies were assessed by electromyography during a squat and countermovement jump, in addition to measurements of the jump height and normalized ground reaction force. RESULTS: The kinesio taping had no effect after 24 hours on either the countermovement or squat jump. However, at 72 hours, the kinesio taping increased the jump height (P = .02; d = 0.36) and normalized ground reaction force (P = .001; d = 0.45) during the countermovement jump. In addition, 72-hour kinesio taping reduced longissimus onset latency (P = .03; d = 1.34) and improved muscle recruitment order during a countermovement jump. CONCLUSIONS: These findings suggest that kinesio taping may improve neuromuscular and kinetic performance during a countermovement jump only after 72 hours of application on healthy and uninjured male athletes. However, no changes were observed on a squat jump. Future studies should incorporate a control group to verify kinesio taping's effects and its influence on injured athletes.

Portación de Staphylococcus aureus enterotoxigénico tipo A, en frotis nasofaríngeos en manipuladores de alimentos / Carriage of Staphylococcus aureus among food service workers

Background Staphylococcus aureus produces 11 serotypes of endotoxins that may cause food poisoning. Aim To determine the prevalence of type A enterotoxigenic Staphylococcus aureus carriage among food service workers in Chillan, Chile. Material and Methods Pharyngeal swabs were obtained from 100 food service workers and were cultured in Agar plates. After identifying the presence of Staphylococcus aureus, DNA was extracted to identify type A toxin by conventional PCR. Results Thirty eight percent of samples were colonized with Staphylococcus aureus. Among these, 26% were toxin A producers. Conclusions Half of the sampled workers carried Staphylococcus aureus and a quarter of these produced type A enterotoxin.

Deciphering the Function of the Blunt Circadian Rhythm of Melatonin in the Newborn Lamb: Impact on Adrenal and Heart.

Neonatal lambs, as with human and other neonates, have low arrhythmic endogenous levels of melatonin for several weeks until they start their own pineal rhythm of melatonin production at approximately 2 weeks of life. During pregnancy, daily rhythmic transfer of maternal melatonin to the fetus has important physiological roles in sheep, nonhuman primates, and rats. This melatonin rhythm provides a circadian signal and also participates in adjusting the physiology of several organs in preparation for extrauterine life. We propose that the ensuing absence of a melatonin rhythm plays a role in neonatal adaptation. To test this hypothesis, we studied the effects of imposing a high-amplitude melatonin rhythm in the newborn lamb on (1) clock time-related changes in cortisol and plasma variables and (2) clock time-related changes of gene expression of clock genes and selected functional genes in the adrenal gland and heart. We treated newborn lambs with a daily oral dose of melatonin (0.25 mg/kg) from birth to 5 days of age, recreating a high-amplitude melatonin rhythm. This treatment suppressed clock time-related changes of plasma adrenocorticotropic hormone, cortisol, clock gene expression, and functional genes in the newborn adrenal gland. In the heart, it decreased heart/body weight ratio, increased expression of Anp and Bnp, and resulted in different heart gene expression from control newborns. The interference of this postnatal melatonin treatment with the normal postnatal pattern of adrenocortical function and heart development support a physiological role for the window of flat postnatal melatonin levels during the neonatal transition.

Mechanistic characterization and inhibition of sphingomyelinase C over substituted Iron Schiff bases of chitosan adsorbed on glassy carbon electrode.

The medical treatment of laxoscelisms is based solely on supportive measures. Although equine antiserum for Sphingomyelinase C (SMASE) and D isomers are available, it is not used due to the risk of an anaphylactic reaction and its unproven efficacy. As potential enzyme inhibitors, derivatives of Iron chitosan complexes were studied (Shiff base having -R = -H, -Cl, -Br, -F, -OCH3, -CH3, -NO2). These chitosan complexes were chosen because they have revealed good results in medicine and catalysis due to their biodegradable characteristics and bioavailability. Besides considering that these complexes have not been studied in relation to this toxin. The mechanisms underlying the catalytic and catcher effects of Iron chitosan complexes were studied using electrochemistry, UV-Vis spectroscopy and microscopic assay at physiological pH. The electrochemical studies showed that one of seven Schiff bases of chitosan adsorbed on glassy carbon electrode was electrocatalytically active for the oxidation of sphingomyelinase at 1.27 V, and that allowed proposing a reaction scheme for SMASE oxidation by adsorbed Iron complexes. On the other hand, even though the spectroscopic studies indicated that there was no chemical bond formation between the complex and SMASE in solution, the microscopic studies showed that this complex proved to be a remarkable cellular protector in presence of the enzyme. In conclusion, Shiff base of chitosan with R = -CH3 was the only active complex in front of sphingomyelinase C, protecting red blood cells, according to our electrochemical and microscopic studies.

[Carriage of Staphylococcus aureus among food service workers]. / Portación de Staphylococcus aureus enterotoxigénico tipo A, en frotis nasofaríngeos en manipuladores de alimentos.

Background Staphylococcus aureus produces 11 serotypes of endotoxins that may cause food poisoning. Aim To determine the prevalence of type A enterotoxigenic Staphylococcus aureus carriage among food service workers in Chillan, Chile. Material and Methods Pharyngeal swabs were obtained from 100 food service workers and were cultured in Agar plates. After identifying the presence of Staphylococcus aureus, DNA was extracted to identify type A toxin by conventional PCR. Results Thirty eight percent of samples were colonized with Staphylococcus aureus. Among these, 26% were toxin A producers. Conclusions Half of the sampled workers carried Staphylococcus aureus and a quarter of these produced type A enterotoxin.

Evaluation of two novel 64Cu-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin αvß3.

PURPOSE: Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin αvß3, may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues. METHODS: Two cyclic RGDfK derivatives, (PEG)2-c(RGDfK) and PEG4-SAA4-c(RGDfK), were constructed and conjugated to NOTA for (64)Cu labeling. Their integrin αvß3-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the (64)Cu-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers. RESULTS: The IC50 values of NOTA-(PEG)2-c(RGDfK) and NOTA-PEG4-SAA4-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of (64)Cu-NOTA-(PEG)2-c(RGDfK) and (64)Cu-NOTA-PEG4-SAA4-c(RGDfK) showed similar circulation t 1/2 and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, (64)Cu-NOTA-PEG4-SAA4-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin αvß3-specificity of the peptides. CONCLUSION: Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin αvß3. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake.