Profiling the physicochemical and solid state properties of edible Tetracarpidium conophorum oil and its admixtures for drug delivery

Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.

Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp

Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.

Comparison of the High Cycle Fatigue Behavior of the Orthodontic NiTi Wires: An in Vitro Study

Abstract Objective: To compare the high-cycle fatigue behavior of four commercially available NiTi orthodontic wires. Material and Methods: Twelve NiTi orthodontic wires, round, 0.016-in, three per brand, were selected and divided into four groups: G1 - Heat-activated NiTi, G2 - Superelastic NiTi, G3 - Therma-Ti, and G4 - CopperNiTi. The atomic absorption spectrometry method was used to determine the chemical composition of investigated NiTi wires. We also performed a fatigue test at three-point bending using a universal testing machine for 1000 cycles in a 35 °C water bath. For the first and thousandth cycle, the average plateau load and the plateau length were determined in the unloading area of the force versus displacement diagram. In addition, we calculated the difference between the average plateau load of the first and thousandth cycle (∆F), as well as the difference between the plateau length of both cases (∆L). Results: According to our results, there were no significant differences between the average plateau load of the first and thousandth cycles of each group (p>0.05) and in the plateau length of the first and thousandth cycles of the groups (p>0.05). Conclusion: There were no significant differences between the groups changing the superelasticity property after high-cycle fatigue.

Modelagem celular in vitro da Doença de Huntington com ácido 3-nitropropiônico e ácido quinolínico & Avaliação das funções neuroprotetoras da adenosina / In vitro cell modeling of Huntington's Disease with 3-nitropropionic acid and quinolinic acid and evaluation of the neuroprotective functions of adenosine

A Doença de Huntington (Huntington's disease - HD) trata-se de uma patologia neurodegenerativa hereditária caracteriza por meio da expressão das proteínas huntingtinas mutantes (mHtt), das mortes dos neurônios espinhais médios (medium spiny neurons MSNs) GABAérgicos D2-positivos do striatum e da hipercinesia. Uma hipótese se refere à função das mHtts de potencializarem os efeitos excitotóxicos das estimulações dos receptores de NMDA (NMDAR) por meio da inibição da succinato desidrogenase, resultando em desequilibrio das [Ca2+]i, estresse oxidativo e apoptose. A adenosina agonista dos receptores purinérgicos P1 tem sido descrita por conta das suas funções neuroprotetoras e neuromodulatórias. Assim, estabelecemos dois modelos in vitro da HD fundamentados nas neurodiferenciações das linhagens murinas de célula-tronco embrionárias E14-TG2a e progenitoras neurais do hipocampo HT-22; seguidas pelos tratamentos com ácido quinolínico (QA) agonista seletivo dos NMDARs , na ausência e na presença do ácido 3-nitropropiônico (3-NP) inibidor irreversível da succinato desidrogenase. Estes modelos foram utilizados nas avaliações das funções neuroprotetoras da adenosina. Os neurônios pós-mitóticos das culturas de E14-TG2a diferenciadas foram caracterizados conforme os MSNs GABAérgicos do striatum; enquanto os neurônios HT-22 diferenciados foram caracterizados de modo inespecífico. Metodologia: imunofluorescência (microscopia e citometria); PCR em tempo real; análise das variações dos potenciais das membranas plasmáticas e das variações transientes das [Ca2+]i por microfluorimetria; e quantificações das reduções do AlamarBlue® (% de sobrevida celular) e das atividades extracelulares de LDH (U/L) (necrose) por espectrometria. Avaliamos a capacidade do 3-NP de potencializar os efeitos excitotóxicos do QA comparando dois grupos de neurônios HT-22 diferenciados: QA 8mM (EC50) (controle); e 3-NP 5mM/QA 8mM. Avaliarmos o potencial neuroprotetor da adenosina comparando quatro grupos de neurônios HT-22 diferenciados: QA 8mM; adenosina 250µM/QA 8mM; 3-NP 5mM/QA 8mM; 3-NP 5mM/adenosina 250µM/QA 8mM. Os neurônios pós-mitóticos derivados das E14TG2a foram classificados como MSNsGABAérgicos do striatum integrantes de uma cultura neuronal heterogênea semelhante às conexões nigroestriatais, corticoestriatais, striatonigral e striatopallidal. Os neurônios HT-22 diferenciados perfaziam uma cultura neuronal heterogênea, não totalmente madura, composta por neurônios glutamatérgicos, dopaminérgicos, colinérgicos e GABAérgicos. Os neurônios HT-22 diferenciados 3-NP 5mM apresentaram menores % de sobrevida celular após os tratamentos com QA 8mM por 24h (p<0.05); e maiores amplitudes das variações das [Ca2+]i dependentes do QA 8mM (p<0.05) (cinética 6 minutos). Por outro lado, os neurônios HT-22 diferenciados pré- tratados com 3-NP 5mM apresentaram menores atividades extracelulares de LDH após o tratamento com QA 8mM por 24h menor proporção de necrose. Os pré-tratamentos com adenosina 250µM indicaram uma tendência dos efeitos neuroprotetores (p>0.05) maiores % de sobrevida celular; menores atividades extracelulares de LDH; e menores amplitudes das variações transientes das [Ca2+]i. Em conjunto, nossos resultados indicam que a inibição da succinato desidrogenase potencializa os efeitos excitotóxicos dos NMDARs por meio da alteração das [Ca2+]i e, provavelmente, dos mecanismos de morte celular; enquanto a adenosina apenas tendeu à neuroproteção

Huntington's disease (HD) is a hereditary neurodegenerative pathology characterized by mutant huntingtin proteins (mHtt) expression, striatum D2-positive GABAergic medium spiny neurons (MSNs) cell death and hyperkinetic motor symptoms development. One hypothesis refers to the principle that mHtt potentiates the excitotoxic effects of NMDA receptor (NMDAR) stimulation by the inhibition of mitochondrial succinate dehydrogenase, resulting in [Ca2+]i imbalance, oxidative stress and apoptosis. Adenosine P1 purinergic receptor agonist is related to neuroprotective and neuromodulatory functions. Thus, we established two in vitro HD models based on the neurodifferentiation of murine embryonic stem cell lines E14-TG2a and hippocampal neuroprogenitor cell line HT-22 followed by treatment with quinolinic acid (QA) selective agonist of NMDARs , in the absence and in the presence of 3-nitropropionic acid (3-NP) irreversible inhibitor of succinate dehydrogenase. These models were used to assess the neuroprotective functions of adenosine. Post-mitotic neurons from differentiated E14-TG2a cultures were characterized according to striatum's GABAergic MSNs; while the differentiated HT-22 neurons were characterized in a non-specific way. Methodology included immunofluorescence (microscopy and cytometry); real-time PCR; analysis of variations in the plasma membrane potentials and of transient variations in the [Ca2+]i by microfluorimetry; and quantification of AlamarBlue® reductions (% cell survival) and of extracellular LDH activity (U/L) (necrosis) by spectrometry. We evaluated the ability of 3-NP to potentiate the excitotoxic effects of QA by comparing two groups of differentiated HT-22 neurons: 8mM QA (control); and 5mM 3-NP/8mM QA. We evaluated the neuroprotective potential of adenosine comparing four groups of differentiated HT-22 neurons: QA 8mM; 250µM adenosine/8mM QA; 5mM 3-NP/8mM QA; 5mM 3-NP/250µM adenosine/8mM QA. Postmitotic neurons derived from E14TG2a were classified as striatums GABAergic MSNs that are part of a heterogeneous neuronal culture similar to nigrostriatal, corticostriatal, striatonigral, and striatopallidal connections. Differentiated HT-22 neurons consisted of a heterogeneous neuronal culture and not fully mature glutamatergic,dopaminergic, cholinergic and GABAergic neurons. Differentiated HT-22 neurons following 5mM 3-NP treatment showed lower % cell survival after treatments with 8mM QA for 24h (p<0.05); and higher amplitudes of the variations of [Ca2+]i induced by 8mM QA (p<0.05) (kinetics 6 minutes). On the other hand, differentiated HT-22 neurons 5mM 3-NP showed lower extracellular LDH activities after treatment with 8mM QA for 24h indicating a lower proportion of necrotic cells. Pretreatments with 250µM adenosine indicated a trend towards neuroprotective effects, such as higher percentages of cell survival; lower extracellular LDH activities; and lower amplitudes of transient variations of [Ca2+]i. Taken together, our results indicate that succinate dehydrogenase inhibition potentiated the excitotoxic effects of NMDARs by altering [Ca2+]i and, probably, cell death mechanisms, while adenosine only to neuroprotection

Estudio de envejecimiento de poliamida de alto impacto marca Deflex® en saliva artificial comercial / Deflex® brand high impact polyamide aging study in commercial artificial saliva

Este trabajo presenta los resultados de un estudio de envejecimiento natural y acelerado en saliva artificial, de un material para uso odontológico de la marca Deflex® a base de poliamida de alto impacto, según lo establece la norma UNE EN IS0 10993-13 (2009) (AU)

is work presents the results of the study of natural and accelerated aging in artificial saliva, of a material for dental use of the brand Deflex® based on high impact polyamide, as established by the standard UNE EN IS0 10993-13 (2009) (AU)

Desenvolvimento e otimização de sistemas conservantes empregando os conceitos de Qualidade por Design (QbD) e Tecnologia Analítica de Processos (PAT) / Development and optimization of preservative systems using Quality by Design (QbD) and Process Analytical Technology (PAT) concepts

Recentemente, produtos farmacêuticos e cosméticos com concentrações mínimas de parabenos e outros conservantes ganharam e apelo comercial e de segurança, devido à controvérsia sobre a segurança dos conservantes. No entanto, o uso de conservantes é essencial para garantir a conservação microbiana de produtos cosméticos e farmacêuticos durante o seu uso. Neste trabalho, desenvolveu-se um método quimiométrico de espectroscopia no infravermelho com Fourier transform near-infrared (FTIR) para prever a eficácia de sistemas conservantes em produtos farmacêuticos e cosméticos tópicos usando os conceitos de Quality by design (QbD) e Process Analytical Technology (PAT). A abordagem de QbD foi usada para determinar a eficácia antimicrobiana frente aos microrganismos: Candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) e Staphylococcus aureus (ATCC 6538), em funções das concentrações de parabenos, e determinar a região de Design Space, empregando o delineamento de compóstio central (CCD) Todas as 15 formulações preparadas foram analisadas utilizando um espectrofotômetro (FTIR) equipado com aparato de Attenuated Total Reflectance (ATR). Os modelos de regressão por Partial Least Squares (PLS) para predição dos "slopes" das curvas de morte microbiana em função dos espectros ATR/FTIR foram bem ajustados, com R2 e R2-predição de 0,9937 e 0,8921, 0,9947 e 0,8783, e 0,9957 e 0,9222 para Candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) e Staphylococcus aureus (ATCC 6538), respectivamente. O método FTIR proposto aplicado em uma abordagem de PAT foi capaz de prever a eficácia do sistema conservante em tempo reduzido. Este método de predição de silício permitirá um controle lote-a-lote da eficácia do sistema conservante de produtos farmacêuticos e cosméticos

Recently, pharmaceuticals and cosmetics with minimal concentrations of parabens and other preservatives have gained and commercial and safety appeal due to controversy over the safety of preservatives. However, the use of preservatives is essential to ensure the microbial conservation of cosmetic and pharmaceutical products during use. In this work, a chemometric method of infrared spectroscopy with Fourier transform (FTIR) was developed to predict the effectiveness of preservative systems in pharmaceutical products and topical cosmetics using the concepts of Quality by design (QbD) and Process Analytical Technology (PAT). The QbD approach was used to determine antimicrobial efficacy against candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC) microorganisms 6538), in functions of paraben concentrations, and determine the Design Space region, employing the design of central composite (CCD). All 15 prepared formulations were analyzed using a spectrophotometer (FTIR) equipped with Attenuated Total Reflectance (ATR). The Partial Least Squares (PLS) regression models for the prediction of the slopes of microbial death curves as a function of ATR /FTIR spectra were well adjusted, with R2 and R2-prediction 0.9937 and 0.8921, 0.9947 and 0.8783, and 0.9957 and 0.9222 for Candida albicans (ATCC 10231), Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC 6538)respectively. The proposed FTIR method applied in a PAT approach was able to predict the effectiveness of the preservative system in reduced time. This method in silico prediction will allow a batch-to-lot control of the effectiveness of the preservative system of pharmaceuticals and cosmetics

Structural Assessment of Chemical Constituent of Sidaguri (Sida rhombifolia Linn) and Its Ability to Inhibit Cyclooxygenase

Objective: To elicit the structure of isolated compounds from roots of sidaguri (Sida rhombifolia Linn). Material and Methods: Several organic standard protocols were involved, including extraction, fractionation, and phytochemical testing. Further spectroscopy methods, FTIR and 1HNMR, were used to determine the predicted structure of molecules, while their ability to inhibit cyclooxygenase (COX 1 and 2) were tested using in vitro method. Results: Overall assessments showed that the structure of the sidaguri is a long chain aliphatic carboxylic acid and identified as Z-3, 6, 6 trimethylhept-2-en-1-ol (T12) and nonanoic (T13). Both isolates significantly inhibit COX-1 and COX-2 non-selectively (the COX-1/COX-2 ratio for T12 was 0.91 and 0.82; while COX-1/COX-2 ratio for T13 was 0.89 and 0.87 at concentrations of 0.05 and 0.025 µg/mL respectively). Conclusion: The active compounds of Sidaguri have antiinflammatory effect by inhibiting COX non-selectively.

Corrosion Resistance of Stainless Steel Brackets After Thermal Recycling by Direct Flaming

Objective: To determine and compare the corrosion resistance (based on the release of nickel and chromium in artificial saliva) of various brands of stainless steel brackets after thermal recycling by direct flaming. Material and Methods: This research study employed 40 stainlesssteel maxillary premolar brackets from different brands (Ormco, GAC, Versadent, S-Ortho, and Protect), which were divided into 5 groups consisting of 8 brackets. The nickel and chromium content of the metal brackets were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), conducted before immersion. For the first treatment, each group was immersed in artificial saliva without direct flaming (recycling); for the second treatment, each group was immersed in artificial saliva with direct flaming (recycling) for 30 days in a pH-neutral (pH=7) solution. ICP-MS was employed to analyze the nickel and chromium released in saliva. The mean differences were measured with Wilcoxon, Kruskal Wallis test, and Post-Hoc Mann Whitney test. Differences were considered statistically significant when p-value<0.05. Results: The mean corrosion resistance based on the nickel content released by the new brackets was 99.95%, 99.87%, 87.09%, 90.58%, and 90.26% for groups A, B, C, D, and E, respectively. The mean corrosion resistance based on the nickel content released by the recycled brackets was 99.90%, 99.80%, 98.19%, 89.76%, and 72.82%, respectively. There was a significant difference in corrosion resistance among the 5 groups after recycling by direct flaming and between new and recycled brackets in each group. Conclusion: The corrosion resistance of the brackets in groups A (Ormco), B (GAC), D (S-Ortho), and E (Protect) decreased after thermal recycling by direct flaming. The Ormco brackets had the highest corrosion resistance after thermal recycling by direct faming.

Energy Dispersive Spectroscopy (EDS) Analysis of Calcium and Phosphor Minerals Elements on Bone After Insertion Immediate Implant on Socket Filled with Extract Aloe vera

Objective: To examine the effect of aloe vera that containing bioactive materials on the levels of calcium (Ca) and phosphorus (P) minerals and their ratios around the immediate implanted in alveolar bone. Material and Methods: Research method by conducting experimental test on experimental animals: 9 male mongrel dogs are divided into 3 groups each 3 tails. In each animal was pulled the second premolar teeth on right side and left side, and immediately inserted titanium implant (3mm x 10mm diameter) after the socket filled with 10% aloevera extract on the right side and control on the left side. Analysis of calcium and phosphorus minerals content formed by examination of Energy Dispersive Spectroscopy (EDS) on Scanning Electron Microscope on implant and around bone tissue was done on days 14, 28 and 56. The result of statistical analysis using repeated ANOVA with independent t test. The level of significance was set at 5%. Results: There was a significant difference on calcium level between control and treatment groups on days 14, 28 and 56 (p<0.05). There was no significant difference on phosphorus level between control and treatment groups (p>0.05). The ratio of Ca / P in both control and treatment groups was also significantly different in every observation day (p<0.05). Conclusion: The addition of aloe vera extract that containing bioactive materials has an effect on increasing levels of mineral elements calcium and calciumphosphorus ratio after immediate implant insertion.

Herramientas invasivas y no invasivas para el diagnóstico de cáncer oral: revisión de la literatura / Invasive and non-invasive tools for the diagnosis of oral cancer: review of the literature

El cáncer oral es una neoplasia frecuente a nivel mundial; su diagnóstico se realiza de forma tardía por lo menos en un 50-60 por ciento de los casos, lo que empeora el pronóstico de los pacientes, ya que a mayor estadio, mayor es la tasa de mortalidad. Por lo tanto, es fundamental contar con herramientas que permitan realizar un diagnóstico temprano y tratamiento oportuno, sobre todo cuando existen lesiones premalignas clínicamente identificables. En el presente estudio se revisan las herramientas invasivas y no invasivas (modernas y antiguas) que han demostrado utilidad para el diagnóstico de cáncer oral; se basan tanto en técnicas ampliamente disponibles en la práctica clínica como en otras aún no disponibles, pero que podrían implementarse con una apropiada coordinación entre el profesional dedicado a la clínica y los investigadores.

Oral cancer is a neoplasm that is frequent on a worldwide level andis diagnosed late in at least 50-60% of the cases. Its late detection worsens the prognosis of patients because it is associated with a greater mortality. Therefore, it is essential to have tools that allow a timely diagnosis when premalignant lesions present and when there are noclinically identifi able premalignant lesions. In the present study, wereview the invasive and non-invasive tools (modern and old) that haveproven useful for the diagnosis of oral cancer; they are based bothon techniques widely available in clinical practice and on techniques not yet available, but that could be implemented with appropriate coordination between the clinic professional and the researchers.

A comparative study of two separate analytical techniques for the simultaneous determination of diclofenac sodium and diacerein from combined dosage form

ABSTRACT Diclofenac sodium (DS) and diacerein (DC) have emerged as a potential combination therapy for the treatment of knee osteoarthritis. Therefore a validated analytical method is essential for the simultaneous estimation of both from combined dosage form. A ratio derivative spectrophotometric and a chromatographic technique have been developed for the simultaneous determination of DS and DC. The quantification was done at 263.00 nm for DC and 304.50 nm for DS in the first method, whereas 257 nm for DC and at 274 nm for DS for LC-DAD analysis in chromatographic method using acetate buffer and methanol as the mobile phase at a flow-rate 0.50 mL/min. Both of these methods are found to be linear in the concentration range under study with r2 value 0.999 and 0.996 for DS and DC respectively in ratio derivative spectroscopy and 0.998 and 0.999 for DS and DC respectively in LC-DAD study. Both of these methods are found to be accurate and precise, though greater robustness and precision is observed with chromatographic analysis over the ratio derivative spectroscopy. Statistically there was no significant difference between proposed ratio derivative spectrophotometric and LC-DAD methods.

Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins

Background: Synthesized aminocoumarins are heterocyclic compounds possessing potential for the treatment of insulin-dependent diabetes mellitus with unexplored anti-glycative action. Results: In this study 4-aminocoumarin derivatives (4-ACDs) were evaluated in vitro for antiglycation (AG) activities by using the human serum albumin (HSA)/glucose system, for 8 weeks of incubation. The glycation and conformational alteration of HSA in the presence of the tested compounds were evaluated by Congo red assay, fluorescence and circular dichroism spectroscopy. The antioxidant (AO) capacity were also tested by four different assays including: DPPH (2,2'-diphenyl-1-picrylhydrazyl radical), ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulphonate) diammonium salt), FRAP (ferric reducing antioxidant power) and β-carotene-linoleic acid assay. The tested compounds showed AG and AO effects. The intensity of the accomplished AO potential is related to the type of the used assay. Significant alterations in the secondary (monitored by CD spectropolarimetry) and tertiary structure (assessed by spectrofluorimetry) of HSA upon glycation were mitigated by the 4-ACDs, suggesting their suppressive role in the late stage (post-Amadori) of the HSA glycation. Conclusions: By the analogues, in vitro ascertained AO and AG properties of 4-ACD may be recognized as rationale for their protective role against oxidative changes of proteins, thereby precluding diabetic complications in humans.

Strontium Ranelate Effect on the Repair of Bone Defects and Molecular Components of the Cortical Bone of Rats

Abstract This study was conducted to evaluate the effects of treatment with strontium ranelate (SR) on the repair of bone defects and molecular components of bones in femurs. Adult female rats (n=27) were subjected to ovariectomy (OVX) or Sham surgery. Thirty days after surgery, a defect was made in the femur and the animals were then divided into three groups: OVX, SHAM and OVX+SR. Euthanasia was performed four weeks after the bone defect surgery. Repair in bone defect was assessed by computed microtomography (μCT) and chemical composition of cortical bone was analyzed by Fourier transform infrared (FTIR) spectroscopy and energy dispersive X-ray spectroscopy (EDS). The trabecular thickness (Tb.Th) of the newly formed bone in the OVX+SR group was significantly higher than that for the OVX group. The collagen maturity in the OVX+SR group was smaller than in the other two groups. In this group, a significant increase in the amount of strontium (Sr) and a decrease in the amount of calcium (Ca) embedded to bone tissue were also observed. Systemic treatment with SR improved microarchitecture of the newly formed bone inside the defect, but decreased cross-linking of mature collagen in cortical bone.

Resumo Este estudo foi conduzido para avaliar os efeitos do tratamento com ranelato de estrôncio (RE) na reparação de defeitos ósseos e componentes moleculares de ossos nos fêmures. Ratas adultas (n = 27) foram submetidas a ovariectomia (OVX) ou cirurgia Sham. Trinta dias após a cirurgia, um defeito foi feito no fêmur e os animais foram então divididos em três grupos: OVX, SHAM e OVX+RE. A eutanásia foi realizada quatro semanas após a cirurgia de preparo do defeito ósseo. A reparação do defeito ósseo foi avaliada por microtomografia computorizada (μCT) e a composição química do osso cortical foi analisada por espectroscopia de infravermelho de transformada de Fourier (FTIR) e espectroscopia por energia dispersiva de raios X (EDS). A espessura do osso trabecular (Tb.Th) recém formado no grupo OVX+SR foi significativamente maior que a do grupo OVX. A maturidade do colágeno no grupo OVX+SR foi menor do que nos outros dois grupos. Neste grupo, observou-se também um aumento significativo na quantidade de estrôncio (Sr) e uma diminuição na quantidade de cálcio (Ca) no tecido ósseo. O tratamento sistêmico com RE melhorou a microarquitetura do osso recém formado dentro do defeito, mas diminuiu a reticulação do colágeno maduro no osso cortical.

Moderada concordancia espectroscópica e histopatológica en pacientes con lesiones cerebrales no traumáticas, Hospital Escuela Universitario, 2012-2015 / Spectroscopic and histopathologic moderate concordance in patients with non-traumatic brain injuries, Hospital Escuela Universitario, 2012 - 2015

Antecedentes:La comparación entre diagnóstico espectroscópico e histopatológico se fundamenta en variaciones de los metabolitos encontrados en las lesiones cerebrales. En Honduras no se cuenta con datos de correlación diagnostica entre estos métodos. Objetivo: Determinar la concordancia diagnóstica entre espectroscopía por resonancia magnética e histopatología en pacientes con lesiones cerebrales no traumáticas, Sala de Neurocirugía de Adultos, Hospital Escuela Universitario, Tegucigalpa, 2012-2015. Metodología: Estudio de valoración de concordancia entre pruebas diagnósticas en pacientes mayores de 18 años, con lesión cerebral no traumática. Se registró información sociodemográfica, antecedentes, presentación clínica y resultados diagnósticos. Los datos fueron procesados en programa SPSS Statistics versión 22. La concordancia se estableció estimando índice Kappa. Resultados: De 150 casos registrados, se evaluaron 42 pacientes con criterios de inclusión; 57.1% (24) hombres, edad promedio 44.8 años (18­79), 17 (40.5%) procedentes de Francisco Morazán. Al ingreso presentaron hipertensión endocraneana 38.1% (16), hemiparesia 33.3% (14) y parálisis facial periférica 4.8% (2). Los metabolitos Colina y N-Acetil Aspartato presentaron elevación 76.2% (32) y disminución 71.4% (30), respectivamente. Astrocitomas de bajo grado 9 (21.4%) y de alto grado 8 (19.0%) fueron los diagnósticos espectroscópicos más frecuentes. Astrocitomas de bajo grado y de alto grado, 10 (23.8%) cada uno, fueron los diagnósticos histopatológicos más frecuentes. Se estimó Índice diagnósticos espectroscópicos e histopatológicos sugiere que la combinación de ambos mejora la precisión del diagnóstico pero no la diferenciación entre tipos de lesiones...(AU)

Biofilm Formation on Different Materials Used in Oral Rehabilitation

Abstract The aim of this study was to evaluate the density and the morphological aspects of biofilms adhered to different materials applied in oral rehabilitation supported by dental implants. Sixty samples were divided into four groups: feldspar-based porcelain, CoCr alloy, commercially pure titanium grade IV and yttria-stabilized zirconia. Human saliva was diluted into BHI supplemented with sucrose to grow biofilms for 24 or 48 h. After this period, biofilm was removed by 1% protease treatment and then analyzed by spectrophotometry (absorbance), colony forming unit method (CFU.cm-2) and field-emission guns scanning electron microscopy (FEG-SEM). The highest values of absorbance and CFU.cm-2 were recorded on biofilms grown on CoCr alloys when compared to the other test materials for 24 or 48 h. Also, FEG-SEM images showed a high biofilm density on CoCr. There were no significant differences in absorbance and CFU.cm-2 between biofilms grown on zirconia, porcelain and titanium (p<0.05). Microbiological assays associated with microscopic analyses detected a higher accumulation of oral biofilms on CoCr-based materials than that on titanium or zirconia that are used for prosthetic structures.

Resumo O objetivo deste estudo foi avaliar a densidade e os aspectos morfológicos dos biofilmes aderidos a diferentes materiais aplicados em reabilitação oral sobre implantes dentários. Sessenta amostras foram divididas em quatro grupos: porcelana à base de feldspato, liga de CoCr, titânio grau IV comercialmente puro e zircônia estabilizada com ítrio. Saliva humana diluída em BHI foi suplementada com sacarose para possibilitar a formação de biofilme por 24 e 48 h. Após este período, o biofilme foi removido utilizando protease a 1% e, em seguida, analisada por espectrofotometria (absorbância), unidades formadoras de colônia (CFU.cm-2) e microscopia eletrônica de varredura (MEV). Os valores mais elevados de absorbância e CFU.cm-2 foram encontrados em ligas de CoCr quando comparado com os outros materiais testados. Os resultados obtidos foram semelhantes nos biofilmes formados sobre titânio e zircônia durante 24 e 48 h (p<0,05). As análises microbiológicas e microscópicas demostraram uma maior tendência ao acúmulo de biofilmes orais sobre estruturas protéticas baseadas em CoCr quando comparadas com porcelana feldspática, titânio ou zircônia.

Estudos biofísicos e de atividade de peptídeos correspondentes ao N-terminal das toxinas esticolisinais I e II - contribuição para a elucidação do mecanismo de ação / Biophysical and activity studies of peptides corresponding to the N-termini of sticholysins I and II - a contribution to the elucidation of the toxins' mechanism of action

Esticolisinas I e II, citolisinas purificadas da anêmona marinha Stichodactyla helianthus, agem lisando membranas biológicas e modelo. O mecanismo de ação proposto consiste na formação de um poro toroidal com o envolvimento do domínio N-terminal. Diferentes aspectos da interação entre peptídeos derivados do N-terminal das toxinas (StI1-31 and StI12-31 SELAGTIIDGASLTFEVLDKVLGELGKVSRK, e StII1-30 and StII11-30 ALAGTIIAGASLTFQVLDKVLEELGKVSRK) com membranas modelo - micelas e bicamadas - foram estudados com o objetivo de contribuir para a elucidação do mecanismo de ação das toxinas em nível molecular. O emprego dos peptídeos teve como base a hipótese de que fragmentos proteicos podem ser capazes de mimetizar a estrutura e atividade das proteínas inteiras. O análogo contendo o aminoácido paramagnético TOAC (N-TOAC-StII11-30) também foi estudado. Estudos conformacionais foram realizados empregando-se as técnicas espectroscópicas de dicroísmo circular (CD), ressonância paramagnética eletrônica (EPR) e fluorescência. Foram ainda realizados estudos de predição de estrutura e modelagem molecular. Espectros de CD mostraram que os peptídeos adquirem conformação em α-hélice ao interagir com membranas modelo, de acordo com a conformação observada nessa região para as toxinas. Variando a composição lipídica das membranas modelo estudadas, foi possível investigar a contribuição de forças eletrostáticas de de interações hidrofóbicas para a ligação do peptídeo. Ensaios de supressão de fluorescência de lípidos contendo grupamentos fluorescentes em diferentes posições pelo resíduo paramagnético TOAC e espectros de ressonância paramagnética eletrônica (EPR) permitiram localizar o resíduo TOAC na interface membrana-água, corroborando o modelo proposto do poro toroidal. A análise dos espectros de CD e EPR também permitiu obter as constantes de ligação dos peptídeos com micelas e bicamadas. Os peptídeos também foram capazes de mimetizar as toxinas do ponto de vista funcional, como mostrado por testes de vazamento de carboxifluoresceína e atividade hemolítica. Peptídeos curtos, contendo partes da sequência de StII1-30, sintetizados com o objetivo de examinar uma eventual atividade antimicrobiana, demonstraram baixa atividade, bem como ausência de atividade hemolítica e de toxicidade para células humanas

Sticholysins I and II, cytolysins purified from the sea anemone Stichodactyla helianthus, act by lysing biological and model membranes. The proposed mechanism of action consists in the formation of a toroidal pore with the involvement of the N-terminal domain [1]. Different aspects of the interaction between peptides from the toxins' N-termini (StI1-31 and StI12-31 SELAGTIIDGASLTFEVLDKVLGELGKVSRK, and StII1-30 and StII11-30 ALAGTIIAGASLTFQVLDKVLEELGKVSRK) and model membranes - micelles and bilayers - have been studied to contribute to the elucidation of the toxins mechanism of action at the molecular level. The use of peptides was based on the hypothesis that potein fragments can eventually mimic the structure and activity of the whole protein. An analogue containing the paramagnetic amino acid TOAC (N-TOAC-StII11-30) was also studied. Conformational studies were performed making use of the spectroscopic techniques circular dichroism (CD), electron paramagnetic resonance (EPR), and fluorescence. Studies of structure prediction and molecular modeling were also performed. CD spectra showed that the peptides acquired α-helical conformation upon interaction with model lipid membranes, in agreement with the conformation found for these segments in the whole proteins. Making use of membranes of variable lipid composition, it was possible to assess the contribution of electrostatic and hydrophobic interactions for peptide binding. Fluorescence quenching of labeled lipids by paramagnetic TOAC and EPR spectra allowed us to locate the TOAC residue at the membrane-water interface, corroborating the proposed model of the toroidal pore. The CD and EPR studies also allowed us to obtain the binding constants for the peptide-micelle and peptide-bilayer interaction. The peptides were also capable of mimicking the toxins function, as shown by assays of carboxyfluorescein leakage and hemolytic activity. Short peptides containing parts of StII1-30's sequence were synthesized with the aim of testing their antimicrobial activity. The peptides displayed low antimicrobial activity, as well as lack of hemolytic activity and toxicity against human cells

Composición de las urolitiasis en pacientes cubanos por sexo / Composition of urolithiasis in Cuban patients by sex

INTRODUCCIÓN: las urolitiasis implican morbilidad y costos económicos sustanciales. Para su manejo resulta fundamental una evaluación clínica y de laboratorio, que incluya el estudio de la composición química. OBJETIVO: determinar la frecuencia de presentación de los diferentes tipos de urolitiasis según su composición y su relación con el sexo de los sujetos. MÉTODOS: estudio descriptivo, transversal. Se incluyeron las urolitiasis de adultos cubanos, enviadas al Laboratorio de Fisiopatología Renal del Instituto de Nefrología para estudio de composición química, en el período 2001-2011. Las litiasis fueron analizadas con un espectroscopio infrarrojo modelo Philips PU9516. Los diferentes compuestos se identificaron mediante comparación con espectros de referencia. Toda la información fue procesada automatizada (SPSS 15.0.). Se utilizó análisis de distribución de frecuencias. Para probar la existencia de diferencias entre los sexos, en cuanto al tipo de litiasis, se emplearon los tests: de independencia y exacto de Fisher. RESULTADOS: de las 1851 litiasis analizadas, 1316 (71,1 %) eran litiasis simples. Las litiasis simples de oxalato de calcio constituyeron el 46,8 % del total. Dentro de las compuestas, las más frecuentes fueron las de oxalato de calcio más fosfato de calcio (24,7 %). La frecuencia de las litiasis de oxalato de calcio y ácido úrico resultó mayor entre los hombres (p= 0,00), y las de fosfato de calcio y de estruvita (p= 0,00), entre las mujeres. CONCLUSIONES: los cálculos cálcicos, fundamentalmente de oxalato de calcio monohidratado, son los más comunes en la población litiásica estudiada. Las litiasis de oxalato de calcio y ácido úrico son más comunes entre los hombres, mientras las de estruvita y fosfato de calcio lo son, entre las mujeres.

INTRODUCTION: urolithiasis imply significant morbidity and economic costs. For its management, it is fundamental to make clinical and lab evaluation including the study of the chemical composition. OBJECTIVE: to determine the frequency of occurrence of several types of urolithiasis according to their composition and relationship with the individual's sex. METHODS: descriptive and cross-sectional study that included urolithiasis of Cuban adults sent to the Renal Physiopathology Lab of the Institute of Nephrology for the study of chemical composition in the 2001-2011 period. A Philips PU9516 infrared spectroscope served to analyze lithiasis. The various compounds were identified by comparing them with the reference spectra. All the data were collected and processed with SPSS 15.0; the frequency distribution analysis. Independence test and Fisher's exact test were used to confirm the differences between sexes in terms of type of lithiasis. RESULTS: of 1815 analyzed lithiasis, 1316 (71.1 %) were simple. Simple calcium oxalate lithiasis represented 46.8 % of the total number. In the combinations, the most frequent were calcium oxalate plus calcium phosphate (24.7 %). The frequency of calcium oxalate and uric acid lithiasis was higher in men (p= 0.00 and those of calcium phosphate and struvite (p= 0.00) in women. CONCLUSIONS: calcium stones, mainly monohydrated calcium oxalate, are the most common in the studied lithiatic population. Calcium oxalate and uric acid are the commonest in men whereas struvite and calcium phosphate are more frequent in women.

Globally chaotic analysis of Heart Rate Variability during acute auditory stimulus by heavy metal music / Medidas globalmente caóticas de variabilidade de frequência cardíaca durante estímulo auditivo agudo por música heavy metal

OBJECTIVE: Auditory stimulation with relaxing style music can improve cardiac autonomic regulation in subjects treated with a cardio-toxic medication. We assess the acute effect of heavy metal music on cardiac autonomic regulation, through novel high spectral chaotic global analysis techniques: (a) high spectral detrended fluctuation, (b) high spectral entropy (c) spectral multi-taper method. METHOD: We investigated young adult women between 18 and 30 years old exposed to heavy metal (75-84 dB) music for 20 min. Normality tests were applied: (i) Anderson-Darling, (ii) Ryan-Joiner (similar to Shapiro-Wilk); (iii) Lilliefors for low number of subjects. They all indicated a non-normal data distribution. Consequently we applied the Kruskal-Wallis non-parametric test. Also because of the small population, we used a broader than usual level of significance (critical p = 0.1). RESULTS: The application of the three tests for normality and the non-parametric test of significance by the Kruskal-Wallis technique showed that acute musical auditory stimulation with heavy metal music lead to a significant increase (p < 0.07) in one of the seven combinations of chaotic globals. The most significant combination of chaotic globals is the Chaos Forward Parameter One (CFP1), which includes all three studied chaotic globals (high spectral detrended fluctuation, high spectral entropy, spectral multi-taper method). We found significantly increased values during musical auditory stimulation for this specific CFP1. CONCLUSION: It is suggested that acute musical stimulation with heavy metal influences cardiac autonomic regulation at a more complex level than previously reported and that this may be beneficial to heart function.

OBJETIVO: A estimulação auditiva com música relaxante pode melhorar a regulação autonômica cardíaca em indivíduos tratados com um medicamento cardiotóxica. Avaliamos o efeito agudo de música heavy metal sobre a regulação autonômica cardíaca, por meio de novas técnicas de análise, ditas globalmente caóticas de espectrais altos: (a) high spectral detrended fluctuation, (b) high spectral entropy (c) spectral multi-taper method. MÉTODO: Estudamos mulheres jovens entre 18 e 30 anos de idade expostas a música heavy metal (75-84 dB) durante 20 min. Foram aplicados os seguintes testes de normalidade: (i) Anderson-Darling, (ii) Ryan-Joiner (similhante ao de Shapiro-Wilk); (iii) Lilliefors para baixo número de indivíduos. Todos indicaram que os dados obtidos apresentavam distribuição não-normal. Consequentemente foi aplicado o teste não-paramétrico de Kruskal-Wallis. Por causa da pequena população, utilizou-se um nível de significância mais amplo do que o habitual (p crítico = 0,1). RESULTADOS: A aplicação dos três testes para normalidade e o teste não-paramétrico de significância pela técnica de Kruskal-Wallis mostrou que a estimulação auditiva musical aguda com metais pesados produziu um aumento significativo (p < 0,07) em uma das sete combinações de globais caóticos. A combinação de globais caóticos que é mais importante é a "Chaos Forward Paremeter one" (VFP1) na qual se manifestam todos os três globais caóticos aplicados (high spectral detrended fluctuation, high spectral entropy, spectral multi-taper method). Encontramos um aumento significativo durante a estimulação auditiva musical para este parâmetro específico. CONCLUSÃO: Sugere-se que a estimulação musical aguda com heavy metal influencia a regulação autonômica cardíaca em um nível mais complexo e pode ser benéfica para a função cardíaca.

Development of alternative methods for the determination of raloxifene hydrochloride in tablet dosage form / O desenvolvimento de métodos alternativos para a determinação do cloridrato de raloxifeno na forma de dosagem em comprimidos

Three methods are proposed for the quantitative determination of raloxifene hydrochloride in pharmaceutical dosage form: ultraviolet method (UV) high performance liquid chromatography (HPLC) and micellar capillary electrophoresis (MEKC). These methods were developed and validated and showed good linearity, precision and accuracy. Also they demonstrated to be specific and robust. The HPLC and MEKC methods were tested in regards to be stability indicating methods and they showed to have this attribute. The UV method used methanol as solvent and optimal wavelength at 284 nm, obeying Lambert-Beer law in these conditions. The chromatographic conditions for the HPLC method included: NST column C18 (250 x 4.6 mm x 5 µm), mobile phase water:acetonitrile:triethylamine (67:33:0,3 v/v), pH 3.5, flow rate 1.0 mL min^-1, injection volume 20.0 µl, UV detection 287 nm and analysis temperature 30 °C. The MEKC method was performed on a fused-silica capillary (40 cm effective length x 50 µm i.d.) using as background electrolyte 35.0 mmol L^-1 borate buffer and 50.0 mmol L^-1 anionic detergent sodium dodecyl sulfate (SDS) at pH 8.8. The capillary temperature was 32°C, applied voltage 25 kV, UV detection at 280 nm and injection was perfomed at 45 mBar for 4 s, hydrodimanic mode. In this MEKC method, potassium diclofenac (200.0 µg mL^-1) was used as internal standard. All these methods were statistically analyzed and demonstrated to be equivalent for quantitative analysis of RLX in tablets and were successfully applied for the determination of the drug...

Três métodos são propostos para a quantificação de cloridrato de raloxifeno em sua forma farmacêutica de comprimidos: espectrofotometria no ultravioleta (UV), cromatografia líquida de alta eficiência (HPLC) e eletroforese capilar micelar (MEKC). Estes métodos desenvolvidos e validados demonstraram linearidade, precisão e exatidão. Também foram específicos e robustos. Os métodos HPLC e MEKC foram desenvolvidos para indicar a estabilidade do fármaco e demonstraram ter este atributo. O método UV usou metanol como solvente e comprimento de onda de 284nm, obedecendo a Lei de Lambert-Beer nestas condições. Os parâmetros cromatográficos para o método HPLC foram: coluna NST C18 (250 x 4,6 mm x 5 µm), fase móvel composta de água:acetonitrila:trietilamina (67:33:0,3 v/v), pH 3,5, vazão da fase móvel de 1,0 mL min^-1, volume de injeção de 20 µl, detecção no comprimento de onda de 287 nm e temperatura de análise de 30°C. O método MEKC foi realizado utilizando capilar de sílica fundida (40 cm de comprimento efetivo x 50 µm de diâmetro interno) usando como fase móvel solução tampão borato 35.0 mmol L^-1 e solução de dodecil sulfato de sódio (SDS) 50.0 mmol L^-1 pH 8,8. A temperatura de análise foi de 32 °C, com voltagem aplicada de 25 kV, detecção no comprimento de onda de 280 nm e injeção da amostra realizada a 45 mBar por 4 s em modo hidrodinâmico. Para este método MEKC, foi utilizado diclofenaco de potássio (200.0 µg mL^-1) como padrão interno. Todos os métodos foram analisados estatisticamente e demostraram ser equivalentes para a análise quantitativa de raloxifeno em comprimidos e foram aplicados com sucesso na determinação do fármaco...

A novel 96-microwell-based high-throughput spectrophotometric assay for pharmaceutical quality control of crizotinib, a novel potent drug for the treatment of non-small cell lung cancer / Um ensaio espectrofotométrico de alto rendimento à base de novo de 96 micropoços para o controlo de qualidade farmacêutica crizotinibe, um novo potente fármaco para o tratamento de cancro do pulmão de células não-pequenas

This study describes the development and validation of a novel 96-microwell-based high throughput spectrophotometric assay for pharmaceutical quality control of crizotinib (CZT), a novel drug for the treatment of non-small cell lung cancer. We examined the reaction between CZT and 1,2-naphthoquinone-4-sulphonate, a chromogenic reagent. A red-colored product showing a maximum absorption peak (λ_max) at 490 nm was produced in an alkaline medium (pH 9). We examined stoichiometry of the reaction and postulated the reaction mechanism. To our knowledge, this is the first study to describe a color-developing reaction for the proposed assay. The reaction was performed in a 96-microwell plate, and the absorbance of the colored product was measured using an absorbance reader at 490 nm. Under optimized reaction conditions, Beer's law, which shows a correlation between absorbance and CZT concentration, was obeyed in the range of 4-50 µg/well with an appropriate correlation coefficient (0.999). The limits of detection and quantification were 1.73 and 5.23 µg/well, respectively. The assay showed high precision and accuracy. The proposed assay was applied successfully for the determination of CZT in capsules. Thus, the assay proposed in this study is practical and valuable for routine application in pharmaceutical quality control laboratories...

Este estudo descreve o desenvolvimento e a validação de um novo ensaio espectrofotométrico em larga escala em 96 micropoços para o controle farmacêutico de crizotinibe (CZT), novo fármaco para o tratamento de câncer de pulmão de células não pequenas. Examinamos a reação entre o CZT e o 4-sulfonato de 1,2-naftoquinona, um reagente cromogênico. Obteve-se, em meio alcalino (pH 9), produto vermelho, com absorção máxima (λ_max) em 490 nm. Examinamos a estequiometria da reação e propusemos mecanismo de reação. Este, segundo nosso conhecimento, é o primeiro estudo para descrever reação de desenvolvimento de cor para o ensaio proposto. A reação foi realizada em placas de 96 micropoços e mediu-se a absorbância do produto colorido utilizando-se leitor de absorbância a 490 nm. Sob condições otimizadas de reação, a lei de Beer, que mostra a correlação entre a absorbância e a concentração de CZT, foi obedecida na faixa de 4-50 µg/poço, com coeficiente de correlação apropriado (0,999). Os limites de detecção e de quantificação foram, respectivamente, 1,73 e 5,23 µg/poço. O ensaio mostrou alta precisão e exatidão. O ensaio proposto foi aplicado com sucesso para a determinação de CZT em cápsulas e é prático e válido para a aplicação de rotina em laboratórios de controle farmacêutico...