[Severe acute pancreatitis secondary to hypertriglyceridemia as the onset of Type 1 Diabetes Mellitus in the pediatric age]. / Pancreatitis aguda grave secundaria a hipertrigliceridemia como debut de Diabetes Mellitus Tipo 1 en edad pediátrica.

Hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) secondary to insulin deficiency following the onset of type 1 diabetes mellitus (T1DM) is a rare but serious complication in children. OBJECTIVE: To describe the diagnosis and treatment of severe HTG and to emphasize the need for timely diagnosis of T1DM. CLINICAL CASE: A 15-year-old female adolescent with a history of overweight presented with a two-weeks history of fever, anorexia, and diffuse abdominal pain. Laboratory tests revealed triglycerides of 17,580 mg/dL, lipase of 723 U/L, and blood glucose of 200 mg/dL. An abdominal CT scan showed an enlarged and edematous pancreas. She was hospitalized with a diagnosis of AP and severe HTG, which progressed to acute necro-hemorrhagic pancreatitis. Treatment included continuous intravenous insulin infusion until triglyceride levels decreased. Upon discontinuation of insulin, fasting hyperglycemia (206 mg/dL) and metabolic acidosis recurred, therefore DM was suspected. Upon targeted questioning, a history of polydipsia, polyuria, and weight loss during the last 3 months stood out. Glycated hemoglobin was markedly elevated (14.7%). Insulin therapy was optimized, achieving stabilization of laboratory parameters after 15 days of treatment and complete anatomical resolution of pancreatic involvement at one year of follow-up. CONCLUSIONS: The presence of severe HTG in pediatrics compels us to consider its secondary causes, such as the onset of T1DM. It is crucial to improve the ability to diagnose T1DM early, as it may present with infrequent and high-risk presentations for the patient.

Effects of type of substrate and dilution rate on fermentation in serial rumen mixed cultures.

Forages and concentrates have consistently distinct patterns of fermentation in the rumen, with forages producing more methane (CH4) per unit of digested organic matter (OM) and higher acetate to propionate ratio than concentrates. A mechanism based on the Monod function of microbial growth has been proposed to explain the distinct fermentation pattern of forages and concentrates, where greater dilution rates and lower pH associated with concentrate feeding increase dihydrogen (H2) concentration through increasing methanogens growth rate and decreasing methanogens theoretically maximal growth rate, respectively. Increased H2 concentration would in turn inhibit H2 production, decreasing methanogenesis, inhibit H2-producing pathways such as acetate production via pyruvate oxidative decarboxylation, and stimulate H2-incorporating pathways such as propionate production. We examined the hypothesis that equalizing dilution rates in serial rumen cultures would result in a similar fermentation profile of a high forage and a high concentrate substrate. Under a 2 × 3 factorial arrangement, a high forage and a high concentrate substrate were incubated at dilution rates of 0.14, 0.28, or 0.56 h-1 in eight transfers of serial rumen cultures. Each treatment was replicated thrice, and the experiment repeated in two different months. The high concentrate substrate accumulated considerably more H2 and formate and produced less CH4 than the high forage substrate. Methanogens were nearly washed-out with high concentrate and increased their initial numbers with high forage. The effect of dilution rate was minor in comparison to the effect of the type of substrate. Accumulation of H2 and formate with high concentrate inhibited acetate and probably H2 and formate production, and stimulated butyrate, rather than propionate, as an electron sink alternative to CH4. All three dilution rates are considered high and selected for rapidly growing bacteria. The archaeal community composition varied widely and inconsistently. Lactate accumulated with both substrates, likely favored by microbial growth kinetics rather than by H2 accumulation thermodynamically stimulating electron disposal from NADH into pyruvate reduction. In this study, the type of substrate had a major effect on rumen fermentation largely independent of dilution rate and pH.

Subclinical hearing loss associated with aging.

Objective: Contribute to clarifying the existence of subclinical hearing deficits associated with aging. Design: In this work, we study and compare the auditory perceptual and electrophysiological performance of normal-hearing young and adult subjects (tonal audiometry, high-frequency tone threshold, a triplet of digits in noise, and click-evoked auditory brainstem response). Study sample: 45 normal hearing volunteers were evaluated and divided into two groups according to age. 27 subjects were included in the "young group" (mean 22.1 years), and 18 subjects (mean 42.22 years) were included in the "adult group." Results: In the perceptual tests, the adult group presented significantly worse tonal thresholds in the high frequencies (12 and 16 kHz) and worse performance in the digit triplet tests in noise. In the electrophysiological test using the auditory brainstem response technique, the adult group presented significantly lower I and V wave amplitudes and higher V wave latencies at the supra-threshold level. At the threshold level, we observed a significantly higher latency in wave V in the adult group. In addition, in the partial correlation analysis, controlling for the hearing level, we observed a relationship (negative) between age and speech in noise performance and high-frequency thresholds. No significant association was observed between age and the auditory brainstem response. Conclusion: The results are compatible with subclinical hearing loss associated with aging.

Seaweeds in Food: Current Trends.

Edible seaweeds are an excellent source of macronutrients, micronutrients, and bioactive compounds, and they can be consumed raw or used as ingredients in food products. However, seaweeds may also bioaccumulate potentially hazardous compounds for human health and animals, namely, heavy metals. Hence, the purpose of this review is to analyze the recent trends of edible seaweeds research: (i) nutritional composition and bioactive compounds, (ii) the use and acceptability of seaweeds in foodstuffs, (iii) the bioaccumulation of heavy metals and microbial pathogens, and (iv) current trends in Chile for using seaweeds in food. In summary, while it is evident that seaweeds are consumed widely worldwide, more research is needed to characterize new types of edible seaweeds as well as their use as ingredients in the development of new food products. Additionally, more research is needed to maintain control of the presence of heavy metals to assure a safe product for consumers. Finally, the need to keep promoting the benefits of seaweed consumption is emphasized, adding value in the algae-based production chain, and promoting a social algal culture.

Expression of Macrophage Polarization Markers against the Most Prevalent Serotypes of Aggregatibacter actinomycetemomitans.

Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium with seven serotypes (a-g) according to the structure of its LPS, has been defined as one of the most important pathogens in the development of a dysbiotic periodontal biofilm and the onset of periodontitis (an inflammatory chronic disease of the tissues around the teeth), where the serotype b is characterized as the most virulent compared with the other serotypes. The aim of this study was to evaluate the expression of the macrophage polarization markers M0, M1, and M2 against A. actinomycetemcomitans. METHODS: THP-1 cells were infected with A. actinomycetemcomitans serotypes a, b, and c. The expression of CD11b, CD4, CD14, and CD68 for M0; IL-6, HLA/DRA, and CXCL10 for M21, and IL-10, CD163, fibronectin-1 or FN1, and CCL17 was evaluated by qPCR at 2 and 24 h after infection. RESULTS: An increase in the expression of these molecules was induced by all serotypes at both times of infection, showing higher levels of expression to the M1 panel at 2 and 24 h compared to other markers. CONCLUSIONS: A. actinomycetemcomitans has a role in the macrophage polarization to the M1 phenotype in a non-serotype-dependent manner.

3-Nitrooxypropanol substantially decreased enteric methane emissions of dairy cows fed true protein- or urea-containing diets.

Methane is a potent but short-lived greenhouse gas targeted for short-term amelioration of climate change, with enteric methane emitted by ruminants being the most important anthropogenic source of methane. Ruminant production also releases nitrogen to the environment, resulting in groundwater pollution and emissions of greenhouse gas nitrous oxide. We hypothesized that inhibiting rumen methanogenesis in dairy cows with chemical inhibitor 3-nitrooxypropanol (3-NOP) would redirect metabolic hydrogen towards synthesis of microbial amino acids. Our objective was to investigate the effects of 3-NOP on methane emissions, rumen fermentation and nitrogen metabolism of dairy cows fed true protein or urea as nitrogen sources. Eight ruminally-cannulated cows were fed a plant protein or a urea-containing diet during a Control experimental period followed by a methanogenesis inhibition period with 3-NOP supplementation. All diets were unintentionally deficient in nitrogen, and diets supplemented with 3-NOP had higher fiber than diets fed in the Control period. Higher dietary fiber content in the 3-NOP period would be expected to cause higher methane emissions; however, methane emissions adjusted by dry matter and digested organic matter intake were 54% lower with 3-NOP supplementation. Also, despite of the more fibrous diet, 3-NOP shifted rumen fermentation from acetate to propionate. The post-feeding rumen ammonium peak was substantially lower in the 3-NOP period, although that did not translate into greater rumen microbial protein production nor lesser nitrogen excretion in urine. Presumably, because all diets resulted in low rumen ammonium, and intake of digestible organic matter was lower in the 3-NOP period compared to the Control period, the synthesis of microbial amino acids was limited by nitrogen and energy, precluding the evaluation of our hypothesis. Supplementation with 3-NOP was highly effective at decreasing methane emissions with a lower quality diet, both with true protein and urea as nitrogen sources.

Long-Term and Carryover Effects of Supplementation with Whole Oilseeds on Methane Emission, Milk Production and Milk Fatty Acid Profile of Grazing Dairy Cows.

Research is ongoing to find nutritional methane (CH4) mitigation strategies with persistent effects that can be applied to grazing ruminants. Lipid addition to dairy cow diets has shown potential as means to decrease CH4 emissions. This study evaluated the effects of oilseeds on CH4 emission and production performance of grazing lactating dairy cows. Sixty Holstein Friesian cows grazing pasture were randomly allocated to 1 of 4 treatments (n = 15): supplemented with concentrate without oilseeds (CON), with whole cottonseed (CTS), rapeseed (RPS) or linseed (LNS). Oilseeds were supplemented during weeks 1-16 (spring period) and 17-22 (summer period), and the autumn period (wk 23-27) was used to evaluate treatment carryover effects. Cows fed CTS decreased CH4 yield by 14% compared to CON in spring, but these effects did not persist after 19 weeks of supplementation (summer). Compared to CON, RPS decreased milk yield and CTS increased milk fat concentration in both spring and summer. In summer, CTS also increased milk protein concentration but decreased milk yield, compared to CON. In spring, compared to CON, CTS decreased most milk medium-chain fatty acids (FA; 8:0, 12:0, 14:0 and 15:0) and increased stearic, linoleic and rumenic FA, and LNS increased CLA FA. There were no carry-over effects into the autumn period. In conclusion, supplementation of grazing dairy cows with whole oilseeds resulted in mild effects on methane emissions and animal performance. In particular, supplementing with CTS can decrease CH4 yield without affecting milk production, albeit with a mild and transient CH4 decrease effect. Long term studies conducted under grazing conditions are important to provide a comprehensive overview of how proposed nutritional CH4 mitigation strategies affect productivity, sustainability and consumer health aspects.

Assessment protocol and reference values of vestibulo-ocular reflex (VOR) gain in the horizontal plane recorded with video-Head Impulse Test (vHIT) in a pediatric population. / Protocolo de evaluación y valores de referencia de la ganancia del reflejo vestíbulo-ocular (RVO) en el plano horizontal registrado mediante el video-Head Impulse Test (v-HIT) en población pediátrica.

PURPOSE: To develop an assessment protocol and establish reference values of vestibulo-ocular reflex gain of the horizontal semicircular canal obtained with vHIT in a pediatric population without vestibular changes. METHODS: Quantitative, non-experimental, analytical study with a non-probabilistic convenience sample. A total of 39 subjects aged 5 to 17 years were selected based on the inclusion and exclusion criteria. RESULTS: The mean gain obtained of the horizontal right semicircular canal was 0.93 and of the left one, 1.08, with statistically significant differences between the ears. There were no statistically significant differences between the 5-to-10-year and 11-to-17-year subgroups. CONCLUSION: The vestibulo-ocular reflex gain in children neared the values found in the international scientific literature and the adult population. The protocol developed can guide beginning professionals in the otoneurological evaluation of children.

OBJETIVO: Elaborar un protocolo de evaluación y establecer valores de referencia de las ganancias del reflejo vestíbulo-ocular del canal semicircular horizontal obtenidas con el v-HIT en población pediátrica sin alteraciones vestibulares. MÉTODO: Estudio cuantitativo, analítico, no experimental con muestreo no probabilístico por conveniencia. Se seleccionaron 39 sujetos entre 5 a 17 años, los cuales cumplieron los criterios de inclusión y exclusión. RESULTADOS: El promedio de la ganancia obtenida para el conducto semicircular horizontal derecho fue de 0,93 y para el conducto semicircular izquierdo fue de 1,08. Existen diferencias estadísticamente significativas entre oídos. No existen diferencias estadísticamente significativas entre los subgrupos de 5 a 10 años y 11 a 17 años. CONCLUSIÓN: La ganancia del reflejo vestíbulo-ocular en población pediátrica se acerca a los valores encontrados en la literatura científica internacional y de la población adulta. El protocolo confeccionado puede orientar a profesionales que están comenzando en la evaluación otoneurológica de esta población.

Protocolo de evaluación y valores de referencia de la ganancia del reflejo vestíbulo-ocular (RVO) en el plano horizontal registrado mediante el video-Head Impulse Test (v-HIT) en población pediátrica / Assessment protocol and reference values of vestibulo-ocular reflex (VOR) gain in the horizontal plane recorded with video-Head Impulse Test (vHIT) in a pediatric population

RESUMEN Objetivo Elaborar un protocolo de evaluación y establecer valores de referencia de las ganancias del reflejo vestíbulo-ocular del canal semicircular horizontal obtenidas con el v-HIT en población pediátrica sin alteraciones vestibulares. Método Estudio cuantitativo, analítico, no experimental con muestreo no probabilístico por conveniencia. Se seleccionaron 39 sujetos entre 5 a 17 años, los cuales cumplieron los criterios de inclusión y exclusión. Resultados El promedio de la ganancia obtenida para el conducto semicircular horizontal derecho fue de 0,93 y para el conducto semicircular izquierdo fue de 1,08. Existen diferencias estadísticamente significativas entre oídos. No existen diferencias estadísticamente significativas entre los subgrupos de 5 a 10 años y 11 a 17 años. Conclusión La ganancia del reflejo vestíbulo-ocular en población pediátrica se acerca a los valores encontrados en la literatura científica internacional y de la población adulta. El protocolo confeccionado puede orientar a profesionales que están comenzando en la evaluación otoneurológica de esta población.

ABSTRACT Purpose To develop an assessment protocol and establish reference values of vestibulo-ocular reflex gain of the horizontal semicircular canal obtained with vHIT in a pediatric population without vestibular changes. Methods Quantitative, non-experimental, analytical study with a non-probabilistic convenience sample. A total of 39 subjects aged 5 to 17 years were selected based on the inclusion and exclusion criteria. Results The mean gain obtained of the horizontal right semicircular canal was 0.93 and of the left one, 1.08, with statistically significant differences between the ears. There were no statistically significant differences between the 5-to-10-year and 11-to-17-year subgroups. Conclusion The vestibulo-ocular reflex gain in children neared the values found in the international scientific literature and the adult population. The protocol developed can guide beginning professionals in the otoneurological evaluation of children.

Penicillin desensitization in allergic pregnant women with syphilis. Report of two cases.

Syphilis during pregnancy has a high risk of congenital transmission with disastrous fetal consequences. Penicillin (PNC) is the only effective antimicrobial for the treatment of pregnant women with syphilis. Chilean guidelines do not consider desensitization to PNC in these women. We report two cases of pregnant women aged 32 and 23 years, with immediate allergy to PNC and syphilis who were safely and successfully desensitized using a four-hour intravenous protocol in the critical care unit and who subsequently received benzathine G PNC. An electronic survey was conducted among approximately 100 Clinical Pharmacists (CP) in the country. Of these, 16 answered and 13 reported having experience in drug desensitization, in at least five cases with PNC and none reported deaths or cardiorespiratory arrest. Desensitization to PNC can be carried out safely and in Chile, this alternative should be incorporated to the management of pregnant women with syphilis and immediate allergy to PNC, instead of using erythromycin.

Actualización general de inmunoterapia en cáncer / Cancer immunotherapy: an update

Cancer is one of the leading causes of death worldwide. The success rate of conventional anticancer therapeutic approaches such as chemotherapy is limited by the non-specific toxicity and low specificity towards specific tumors, which are highly dependent on the mutational burden present on each patient. Similarly, targeted therapies have proven to induce resistance in numerous malignancies. Therefore, immunotherapy has emerged as a better approach to discriminate between "the own" and "the non-own", which occurs through two types of mechanisms, innate and acquired immunity. Acquired immunity is one of the targets for new immunotherapeutic treatments, unleashing the power of antigen-specific T cells as a potential therapeutic weapon for cancer treatment. Thus, immunotherapy modifies the own immune system to increase the recognition and elimination of cancer cells by identifying these cancer antigens. One of the advantages of immunotherapy, when compared to conventional anticancer approaches, is the generation of long-term immunity (immunological memory). Currently, there are different potential types of immunotherapy in cancer to promote the modulation of the immune response. Among them, the use of cytokines, vaccines, viruses, monoclonal antibodies, and the generation of adaptive immune response cells have achieved successful results in some types of cancer.

Inhibiting Methanogenesis Stimulated de novo Synthesis of Microbial Amino Acids in Mixed Rumen Batch Cultures Growing on Starch but Not on Cellulose.

Ameliorating methane (CH4) emissions from ruminants would have environmental benefits, but it is necessary to redirect metabolic hydrogen ([H]) toward useful sinks to also benefit animal productivity. We hypothesized that inhibiting rumen methanogenesis would increase de novo synthesis of microbial amino acids (AA) as an alternative [H] sink if sufficient energy and carbon are provided. We examined the effects of inhibiting methanogenesis with 9, 10-anthraquione (AQ) on mixed rumen batch cultures growing on cellulose or starch as sources of energy and carbon contrasting in fermentability, with ammonium (NH4+) or trypticase (Try) as nitrogen (N) sources. Inhibiting methanogenesis with AQ inhibited digestion with cellulose but not with starch, and decreased propionate and increased butyrate molar percentages with both substrates. Inhibiting methanogenesis with 9, 10-anthraquinone increased de novo synthesis of microbial AA with starch but not with cellulose. The decrease in the recovery of [H] caused by the inhibition of methanogenesis was more moderate with starch due to an enhancement of butyrate and AA as [H] sinks. There may be an opportunity to simultaneously decrease the emissions of CH4 and N with some ruminant diets and replace plant protein supplements with less expensive non-protein nitrogen sources such as urea.

Academically Oriented Activity Breaks for First-Grade Chilean Students: Development and Pilot Testing Effectiveness.

We developed and pilot tested the effectiveness of a physically active academic program, Active Breaks (AB), whose objective is to increase school time moderate/vigorous physical activity (MVPA) among first graders, through daily 15-minute bouts of MVPA, at the beginning of the first lesson. Initially, 240 cards including one game each were developed and tested in first-grade students from 16 schools in Santiago. Trained observers and school teachers assessed the time, ease, and feasibility of implementation for each card. Barriers and facilitators to implementation were obtained from semistructured interviews to 14 teachers (out of 16). In eight schools (n = 556 students), we compared school time MVPA (with accelerometers) at baseline and follow-up, using test of proportions. One-hundred and twenty cards (games) complied with all aspects. AB were implemented 50% of the time with a duration of 14 minutes (SD = 5). More than 90% of the time, teachers felt competent to conduct AB, and children understood the instructions and enjoyed the activity. The main facilitators included teachers liking physical activity and considering it important, support of principal and school staff, and conducting AB inside the classroom. Barriers included teacher's workload and having to conduct AB during the first lesson. During the 4-month period of implementation, MVPA increased by 1.5 and 1.2 percentage points in boys and girls, respectively. The set of 120 cards is easy and feasible to implement. Moreover, preliminary results suggest they could be effective in increasing MVPA during school time, although studies with longer follow-ups are needed to assess the validity of these findings.

Penicillin desensitization in allergic pregnant women with syphilis. Report of two cases / Desensibilización a penicilina en mujeres embarazadas alérgicas. Informe de dos casos

ABSTRACT Syphilis during pregnancy has a high risk of congenital transmission with disastrous fetal consequences. Penicillin (PNC) is the only effective antimicrobial for the treatment of pregnant women with syphilis. Chilean guidelines do not consider desensitization to PNC in these women. We report two cases of pregnant women aged 32 and 23 years, with immediate allergy to PNC and syphilis who were safely and successfully desensitized using a four-hour intravenous protocol in the critical care unit and who subsequently received benzathine G PNC. An electronic survey was conducted among approximately 100 Clinical Pharmacists (CP) in the country. Of these, 16 answered and 13 reported having experience in drug desensitization, in at least five cases with PNC and none reported deaths or cardiorespiratory arrest. Desensitization to PNC can be carried out safely and in Chile, this alternative should be incorporated to the management of pregnant women with syphilis and immediate allergy to PNC, instead of using erythromycin.

La sífilis durante el embarazo tiene un alto riesgo de transmisión congénita con consecuencias desastrosas para el feto. La penicilina (PNC) es el único compuesto efectivo para el tratamiento de sífilis en una mujer embarazada.. En Chile, ante alergias de tipo inmediata, no se considera la desensibilización a la PNC en mujeres embarazadas por norma ministerial. Se comunican dos casos de mujeres embarazadas con alergia tipo inmediata y sífilis durante la gestación que fueron desensibilizadas a este compuesto con un protocolo endovenoso de 4 horas en la unidad de pacientes críticos, sin observar complicaciones, recibiendo posteriormente PNC G Benzatina. Se efectuó una encuesta electrónica a farmacéuticos clínicos del país que incluyó más de 100 profesionales. De ellos, 16 contestaron y 13 declararon poseer experiencia en desensibilización de fármacos, en al menos cinco casos con PNC y ninguno reportó muertes o paro cardiorrespiratorio. La desensibilización a PNC puede ser efectuada en forma segura en embarazadas con alergia de tipo inmediata a PNC que cursan con sífilis. En Chile se debería incorporar esta alternativa en el manejo de mujeres embarazadas con sífilis y alergia inmediata a PNC en lugar de solo considerar por norma el uso de eritromicina.

[Cancer immunotherapy: an update]. / Actualización general de inmunoterapia en cáncer.

Cancer is one of the leading causes of death worldwide. The success rate of conventional anticancer therapeutic approaches such as chemotherapy is limited by the non-specific toxicity and low specificity towards specific tumors, which are highly dependent on the mutational burden present on each patient. Similarly, targeted therapies have proven to induce resistance in numerous malignancies. Therefore, immunotherapy has emerged as a better approach to discriminate between "the own" and "the non-own", which occurs through two types of mechanisms, innate and acquired immunity. Acquired immunity is one of the targets for new immunotherapeutic treatments, unleashing the power of antigen-specific T cells as a potential therapeutic weapon for cancer treatment. Thus, immunotherapy modifies the own immune system to increase the recognition and elimination of cancer cells by identifying these cancer antigens. One of the advantages of immunotherapy, when compared to conventional anticancer approaches, is the generation of long-term immunity (immunological memory). Currently, there are different potential types of immunotherapy in cancer to promote the modulation of the immune response. Among them, the use of cytokines, vaccines, viruses, monoclonal antibodies, and the generation of adaptive immune response cells have achieved successful results in some types of cancer.

Antimicrobial Activity of Piper marginatum Jacq and Ilex guayusa Loes on Microorganisms Associated with Periodontal Disease.

BACKGROUND: Chronic periodontitis is a multifactorial infectious disease, where multiple bacteria, such as Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum are implicated. The main purpose of researching natural products is to find substances or compounds with antimicrobial activity. AIM: The objective of this work was to determine antimicrobial activity from extracts and obtained fractions from Piper marginatum Jacq and Ilex guayusa Loes on P. gingivalis ATCC 33277, F. nucleatum ATCC 25586, and P. intermedia ATCC 25611. METHODS: Total ethanol extracts were obtained from both plants. Fractions were obtained from total ethanol extracts with amberlite as a stationary phase employing hexane, acetone, and ethanol-water as solvents. Qualitative and quantitative phytochemical characterization was performed on total ethanol extracts from both plants. Antimicrobial activity from total ethanol extracts and fractions from both plants were evaluated on P. gingivalis ATCC 33277, F. nucleatum ATCC 25586, and P. intermedia ATCC by the well diffusion method with Wilkins-Chalgren agar. RESULTS: Piper marginatum Jacq total ethanol extract presented antimicrobial activity against all three bacteria, whereas Ilex guayusa Loes was only efficient against P. gingivalis ATCC 33277 and P. intermedia ATCC 25611, with inhibition halos from 9.3 to 30 mm. Ilex guayusa Loes obtained fractions presented antimicrobial activity against all three microorganisms evaluated, with inhibition halos ranging from 9.7 to 18.7 mm. In regards to Piper marginatum Jacq fractions, inhibition halos were between 8.3 and 19 mm, against all three microorganisms evaluated; only hexane fraction did not present antimicrobial activity against F. nucleatum ATCC 25586. CONCLUSION: Piper marginatum Jacq and Ilex guayusa Loes total ethanol extracts and fractions presented outstanding antimicrobial activity against P. gingivalis ATCC 33277, P. intermedia ATCC 25611, and F. nucleatum ATCC 25586.

In Situ Visualization of the Local Photothermal Effect Produced on α-Cyclodextrin Inclusion Compound Associated with Gold Nanoparticles.

Evidence of guest migration in α-cyclodextrin-octylamine (α-CD-OA) inclusion compound (IC) generated via plasmonic heating of gold nanoparticles (AuNPs) has been studied. In this report, we demonstrate local effects generated by laser-mediated irradiation of a sample of AuNPs covered with inclusion compounds on surface-derivatized glass under liquid conditions by atomic force microscopy (AFM). Functionalized AuNPs on the glass and covered by the ICs were monitored by recording images by AFM during 5 h of irradiation, and images showed that after irradiation, a drastic decrease in the height of the AuNPs occurred. The absorption spectrum of the irradiated sample showed a hypsochromic shift from 542 to 536 nm, evidence suggesting that much of the population of nanoparticles lost all of the parts of the overlay of ICs due to the plasmonic heat generated by the irradiation. Mass spectrometry matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) performed on a sample containing a collection of drops obtained from the surface of the functionalized glass provided evidence that the irradiation lead to disintegration of the ICs and therefore exit of the octylamine molecule (the guest) from the cyclodextrin cavity (the matrix). Graphical Abstract Atomic Force Microscopy observation of the disintegration of a cyclodextrin inclusion compound by gold nanoparticles photothermal effect.

Synthesis, in silico, in vitro, and in vivo investigation of 5-[¹¹C]methoxy-substituted sunitinib, a tyrosine kinase inhibitor of VEGFR-2.

Sunitinib (SU11248) is a highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of receptor tyrosine kinases (RTKs) might be useful tools for monitoring RTKs levels in tumor tissue giving valuable information for anti-angiogenic therapy. Herein we report the synthesis of 5-methoxy-sunitinib 5 and its (11)C-radiolabeled analog [(11)C]-5. The non-radioactive reference compound 5 was prepared by Knoevenagel condensation of 5-methoxy-2-oxindole with the corresponding substituted 5-formyl-1H-pyrrole. A binding constant (K(d)) of 20 nM for 5 was determined by competition binding assay against VEGFR-2. In addition, the binding mode of sunitinib and its 5-methoxy substituted derivative was studied by flexible docking simulations. These studies revealed that the substitution of the fluorine at position 5 of the oxindole scaffold by a methoxy group did not affect the inhibitor orientation, but affected the electrostatic and van der Waals interactions of the ligand with residues near the DFG motif of VEGFR-2. 5-[(11)C]methoxy-sunitinib ([(11)C]-5) was synthesized by reaction of the desmethyl precursor with [(11)C]CH(3)I in the presence of DMF and NaOH in 17 ± 3% decay-corrected radiochemical yield at a specific activity of 162-205 GBq/µmol (EOS). In vivo stability studies of [(11)C]-5 in rat blood showed that more than 70% of the injected compound was in blood stream, 60 min after administration.

Study of differences in the VEGFR2 inhibitory activities between semaxanib and SU5205 using 3D-QSAR, docking, and molecular dynamics simulations.

Semaxanib (SU5416) and 3-[4'-fluorobenzylidene]indolin-2-one (SU5205) are structurally similar drugs that are able to inhibit vascular endothelial growth factor receptor-2 (VEGFR2), but the former is 87 times more effective than the latter. Previously, SU5205 was used as a radiolabelled inhibitor (as surrogate for SU5416) and a radiotracer for positron emission tomography (PET) imaging, but the compound exhibited poor stability and only a moderate IC(50) toward VEGFR2. In the current work, the relationship between the structure and activity of these drugs as VEGFR2 inhibitors was studied using 3D-QSAR, docking and molecular dynamics (MD) simulations. First, comparative molecular field analysis (CoMFA) was performed using 48 2-indolinone derivatives and their VEGFR2 inhibitory activities. The best CoMFA model was carried out over a training set including 40 compounds, and it included steric and electrostatic fields. In addition, this model gave satisfactory cross-validation results and adequately predicted 8 compounds contained in the test set. The plots of the CoMFA fields could explain the structural differences between semaxanib and SU5205. Docking and molecular dynamics simulations showed that both molecules have the same orientation and dynamics inside the VEGFR2 active site. However, the hydrophobic pocket of VEGFR2 was more exposed to the solvent media when it was complexed with SU5205. An energetic analysis, including Embrace and MM-GBSA calculations, revealed that the potency of ligand binding is governed by van der Waals contacts.

Determination of cellular debris in endodontically treated teeth: a pilot study / Determinación de restos celulares en dientes endodonciados: estudio piloto

Previous studies indicate that dental tissues are a source of mitochondrial DNA that could be useful for human identification. The main cell in the pulpo-dentin complex is the odontoblast, whose cellular body is located on the border between the pulp and dentin and continues through cell processes. In endodontically treated teeth, pulp tissue is removed, assuming the complete elimination of cellular content and the inner third of dentin. Facing the possibility of finding teeth that were treated endodontically as the only source available for a forensic analysis, is that the objective of this study is to determine the presence of cellular debris in the dentin of teeth with root canal treatment. Twenty teeth roots obtained from 8 single and multi-rooted teeth were treated endodontically, with conventional manual technique. The samples were processed by conventional histological analysis (H&E). In root canals endodontic cement remnants and cylinder-cubic structures resembled odontoblastic bodies were observed, but without certainty to establish its presence. This research concludes that it is not possible to determine presence of cellular debris in endodontically treated teeth using the described technique...

Estudios previos indican que los tejidos dentales son fuente de DNA mitocondrial útiles para la identificación humana. La principal célula del complejo pulpo-dentinario es el odontoblasto, cuyo cuerpo celular ubicado en el límite entre la pulpa y la dentina se continúa por prolongaciones celulares. En dientes tratados endodónticamente se extrae el tejido pulpar, presumiendo la completa eliminación del contenido celular y el tercio interno de la dentina. Frente a la posibilidad de encontrar dientes que fueron tratados endodónticamente como única fuente disponible para análisis forense, es que el objetivo de este estudio es determinar la presencia de restos celulares en la dentina de dientes con tratamiento de canales radiculares. 20 raíces dentarias obtenidas de 8 dientes uni y multirradiculares, fueron tratadas endodónticamente con terapia manual convencional. Las muestras fueron procesadas mediante análisis histológico convencional (H&E). En los canales radiculares se observaron restos de cemento endodóntico y estructuras cilindro-cúbicas que asemejaron a cuerpos de odontoblastos, sin poder establecer con certeza su presencia. En esta investigación se concluye que no es posible determinar mediante la técnica utilizada la presencia de restos celulares en dientes tratados endodónticamente...