Silicea terra200cH evaluated by two different spectroscopy methods: a pilot study

Spectroscopy has been shown to bea useful method to study the physicochemical properties of homeopathic preparations. Aim: In this pilot study, we comparedtwo methods (photon scattering and visible-light spectroscopy) in the physicalevaluation of Silicea terra200cH. Methodology: Italian test: Two sampleshave been examinedand compared: Silicea terra200cH and Sac lac200cH, both preparedin water solution, diluted and succussed according to German Homeopathic Pharmacopoeia(Cemon Lab, Italy).Lactose was includedbecause the first 3 potencies of Silicea terraaremadeby trituration in lactosepowder.Measurements were made using an innovative Charge-Coupled Device (CCD) camera developedby Daniele Gullà, called MIRA/CORA(proprietary name). Slight variations in chrominance and luminance due to micro-vibrational 3D phenomenawere analyzed.Allmeasurements have been performed in a dark room at a constant temperature of 22°C +/-0,2°C usingafilter with very narrow spectral bands (10 nm).The measurements have been repeated three times on both Silicea terra200cH and Sac lac200cHwithin a few minutes aftereach other.Brazilian test: In the second test, performed in Brazil, variations in absorbance were used to identify Silicea terra200cH compared with Sac lac200cH andcompared withanother control solution of non-succussed 30% alcohol, using six solvatochromic dyes, following the method developed by Cartwright [1,2]. Both homeopathic samples were imported from Italy(the same sample bottles used in the Italian test),in Brazil they have beendiluted 1:100 in 30% hydro-alcoholic solution, and submitted to 100 succussions using an automatic mechanical arm (Denise, AUTIC, Brazil) prior to being tested. Samples were inserted into dyes solutions and evaluated by visible spectroscopy (FEMTO Spectrophotometer, Brazil). Dyes were prepared in ethanol P.A., according to previous established methods [3]. Three series in triplicate were performed and the results were analyzed by ANOVA / Tukey, comparing both samples and the unsuccussed 30% hydroalcoholic control solution.Results: Italian test: Measurements of the mean entropy of the signals, statistically elaborated with T Student test,yielded a two tailed p value < 0.05, where the entropy of the signal recorded from the Silicea terra200cHsample was statistically lower than the 200cH Sac lacsample.Brazilian test: Among all tested dyes, only BDN(4-(Bis-(4-(dimethylamino)-phenyl)methylene)-1(4H)-naphthalenone) showed aninteraction with Silicea terra200cH, reproducing the conclusions obtained in [3].Conclusions: Two different spectroscopic methods were able to show signal differences betweenSilicea terra200cH andSac lac200cH, suggesting that changes in solvent organization could be involved in the homeopathic signaling process, along withchanges in dipole moments of solvent and dyes. The results are potentially in line witha recent publishedpaper [4], that supportsthe propositionthatthe lower entropy of the verum signal compared with controls could beexplained by increased coherent vibrations of the verum sample, as theoretically explained in previous literature [5].

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

Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

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.

Inclusion complexes of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin with 2-hydroxypropyl-(-cyclodextrin: solubility and antimicrobial activity

The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-ß-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-ß-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.

Intra and Extra-granular Disintegrant Properties of Modified Underutilised Red Lima Bean Starch in Paracetamol Tablet Formulation

Abstract Red lima bean (Phaseolus lunatus Linn) Family Fabaceae, has been modified by succinylation and annealing, and used as intra- and extra-granular disintegrants at concentrations of 5 and 10 %w/w in paracetamol tablet formulation in comparison with corn starch BP. The starches were characterised using FT-IR spectroscopy, SEM, proximate analysis, physicochemical and functional properties. FT-IR spectrometry revealed characteristic peaks at 1575.53 and 1713.99 cm-1 for the succinylated starch while the annealed showed no significant difference from the native starch. Modifications did not alter the ovoid shape of the native starch but reduced the particle size. Succinylation improved water absorption capacity, solubility and swelling of lima bean starch but annealing reduced the parameters. Tablets with disintegrants of lima bean starches generally had higher crushing strengths and lower friability than tablets with corn starch. Modifications reduced the disintegration time of the tablets when the starches were incorporated intra-granularly, which suggested particle-particle bond interruption and destruction of hydrogen bonds as mechanism of disintegration. Tablets containing 10 %w/w succinylated red lima bean starch incorporated intra-granularly had the highest disintegration efficiency ratio, DER, indicating a great balance between mechanical and disintegration properties. Modified red lima bean starches incorporated intra-granularly into paracetamol tablets led to faster disintegration and could efficiently substitute corn starch as disintegrant.

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.

Design and evaluation of ocular hydrogel containing combination of ofloxacin and dexamethasone for the treatment of conjunctivitis

Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.

The chemical composition and antibacterial activity of a methanolic extract of Satureja khuzistanica

Abstract In the present study, the metabolite profiling of methanolic extract from aerial parts of Satureja khuzistanica Jamzad, as an endemic medicinal plant from Iran, was evaluated using HPLC-PDA-ESI. Then, the main compound from the extract was isolated and purified by using extensive chromatographic techniques. In addition, the structure of the isolated compounds was elucidated using 1D, 2D NMR, and MS spectrometry, upon which 22 compounds were identified. The antibacterial activity of diosmetin 7-rutinoside (6) and linarin (13) in combination with carvacrol as a major compound of the essential oil was tested against Pseudomonas aeruginosa and Staphylococcus aureus through disc diffusion and minimum inhibitory concentration methods. The results indicated that the linarin, when mixed with carvacrol as the main compounds in the essential oil of the plant, has a satisfactory activity against both Pseudomonas aeruginosa and Staphylococcus aureus with MIC values of 0.16 and 0.18 µg/mL, respectively. Further, the fractional inhibitory concentration (FIC) index indicated that this compound had synergism with carvacrol.

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.

Content and distribution of inorganic elements in Laminaria japonica based on ICP-MS and Micro-XRF / 中国中药杂志

In order to evaluate the composition and distribution characteristics of inorganic elements in Laminaria japonica, this study employed inductively coupled plasma mass spectrometry(ICP-MS) to detect the inorganic elements and used high performance liquid chromatography tandem ICP-MS(HPLC-ICP-MS) to determine the content of different arsenic species in L. japonica from diffe-rent origins. Micro X-ray fluorescence(Micro-XRF) was used to determine micro-area distribution of inorganic elements in L. japonica. The results showed that the average content of Mn, Fe, Sr, and Al was high, and that of As and Cr exceeded the limits of the national food safety standard. According to the results of HPLC-ICP-MS, arsenobetaine(AsB) was the main species of As contained in L. japonica. The more toxic inorganic arsenic accounts for a small proportion, whereas its content was 1-4 times of the limit in the national food safety standard. The results of Micro-XRF showed that As, Pb, Fe, Cu, Mn, and Ni were mainly distributed on the surface of L. japonica. Among them, As and Pb had a clear tendency to diffuse from the surface to the inside. The results of the study can provide a basis for the processing as well as the medicinal and edible safety evaluation of L. japonica.

Distinguishing trans women in men who have sex with men populations and their health access in East Africa: A Tanzanian study

Background: Few data are available on the presence and characteristics of transgender populations in sub-Saharan Africa (SSA), which makes the provision of health services for key populations difficult. Aim: This study aimed to ascertain the presence and characteristics of trans women in seven cities in Tanzania, East Africa.Setting: Tanzania, East Africa. Methods: Outreach to men who have sex with men (MSM) in seven large cities in Tanzania was carried out by non-governmental organisation (NGO) staff familiar with this community. Survey questions administered via interviews were used to identify participants who self-identify as trans. From the self-identification data, an estimate of the relative size of the trans women population in this sample was calculated. Results: In the sample of 300 participants, 17.0% of participants were identified as 'transsexual or transgender' (survey wording); 70.1% of these trans participants indicated that they identify themselves as a woman. Of those identifying themselves as transsexual or transgender, 43.1% reported living part- or full-time as a woman and eight (15.0%) reported hormone use. The highest percentage of hormone use (40.0%) was found in those living as a woman full-time. Notably, there was significant ignorance amongst the sample of the terms 'transsexual and transgender' or their explanation in Swahili, reported by interviewers. Conclusion: In this study, it is clear that trans women populations exist in Tanzania, with high levels of stigmatisation and threats to their lives. They should be included in health outreach and services to key populations. One in six self-identified as trans women, although the lack of knowledge of this concept in Swahili or English may have inaccurately represented numbers.

Neuromonitoreo no invasivo en unidades de cuidados intensivos en Colombia / Non-invasive neuromonitoring in intensive care units in Colombia

Resumen | El monitoreo electroencefalográfico no invasivo continuo es una técnica indispensable en los pacientes neurológicos críticos, ya que muestra de forma directa e indirecta su actividad cerebral y permite relacionar los hallazgos con su estado clínico. Es muy sensible, aunque su especificidad es menor, por lo que puede demostrar la alteración del estado de conciencia sin aclarar su etiología. El uso del registro electroencefalográfico continuo en pacientes con alteraciones del estado de conciencia, convulsiones, o estado epiléptico convulsivo y no convulsivo, se ha incrementado en los últimos años porque permite obtener información en tiempo real de la función cerebral y de los cambios en el tiempo; además, facilita la detección de crisis epilépticas subclínicas y electrográficas, estas últimas de gran importancia, ya que no presentan correlación clínica. Los hallazgos del monitoreo permiten modificar el tratamiento farmacológico y anticonvulsivo, y constituyen una gran ventaja para el médico tratante en la toma de decisiones oportunas que redunden en la mejoría del pronóstico del paciente.

Abstract | Continuous non-invasive electroencephalographic monitoring is an essential technique for critical care patients as it shows directly and indirectly the patient's brain activity and makes it possible to relate it with findings in the clinical status. It is highly sensitive, although its specificity is lower, so they can show alterations of the state of consciousness without clarifying the etiology. Continuous electroencephalographic recording in patients with altered levels of consciousness, seizures, and convulsive and non-convulsive status epilepticus has been increasing in recent years as real-time feedback of the cerebral function shows evolution changes and allows for the identification of electric and subclinical epileptic seizures that are highly important since they do not have clinical correlations. These findings in electroencephalographic monitoring also help to modify pharmacological and antiseizure treatments. For practitioners, they are advantageous when making timely decisions that impact the prognosis of the patient.

High dilutions of a drug of COVID-19 origin show difference in ranks

High dilutions (HDs) of drugs, used in Homeopathy, are prepared in aqueous EtOH (ethanol) through serial dilution accompanying mechanical agitation or succussion, and are called potencies. The potencies from the rank 12 onwards are too dilute to contain any original drug molecules. Do the potency ranks show any difference from each other? Do serial dilution and succussion contribute to the difference in potency ranks? This study aims to address these two questions. The throat swab of a Covid-19 patient was preserved and diluted with aqueous EtOH 90% to prepare the mother tincture (MT) and five different potencies of Covid named Covidinum. These potencies and their solvent media were analysed by electronic and vibrational spectroscopy. Charge transfer (CT) and proton transfer interactions occur during preparation of the potencies. The FT-IR spectra of all the test samples after normalization show difference from each other with respect to O-H stretching and bending (v2) bands. Serial dilution and succussion contribute to the observed difference in ranks and CT interactions.

Determinación niveles de glucosa por medio de espectroscopía como método no invasivo / Determination of glucose levels by means of spectroscopy as a non-invasive method

Introducción: la diabetes mellitus es uno de los problemas más graves de salud pública que enfrenta México. El factor más preocupante es la falta de control de la misma, lo que incide de manera directa, causando daños severos a la salud y la calidad de vida del paciente y familiares, así como una carga económica al país. Por lo tanto, el desarrollo de un método no invasivo para la medición de la glucemia proporcionaría a los pacientes una forma sencilla e indolora de monitoreo y, en consecuencia, un mejor control de la diabetes. Objetivo: investigar, desarrollar y validar un sensor no invasivo por medio de la espectroscopía para la estimación del nivel de glucosa en sangre. Material y métodos: se realizó un análisis de estudio transversal analítico de correlación realizado en las instalaciones del laboratorio de la UMAE No 1, Bajío. Se incluyeron pacientes adultos voluntarios que acudieron al laboratorio de dicha unidad para la toma de niveles de glucosa sérica y de manera simultánea se realizó la medición a través de método no invasivo por espectroscopía y, posteriormente, se compararon ambos resultados para demostrar la validez del dispositivo. Resultados: mediante el análisis de la diferencia de medias de Bland-Altman, se identificó que solamente un paciente tuvo un valor extremo, y que el método para medir la glucosa de manera no invasiva sobreestima hasta un 10.2% del valor de glucosa central. Conclusión: comparando dichos resultados con las normas para glucómetros digitales se concluye que nuestro dispositivo es capaz de proporcionar niveles de glucosa certeros.

Background: Diabetes mellitus is one of the most serious public health problems in Mexico. The most worrying factor is the lack of control of it, which has a direct impact, causing severe damage to the health and quality of life of the patient and its family, as well as an economic burden to the health system. Therefore, the development of a non-invasive method for measuring blood glucose would provide to patients a simple and painless way of monitoring and consequently better control of diabetes. Objective: Research, development and validation of a non-invasive sensor by means of spectroscopy for the estimation of the blood glucose level. Material and methods: An analysis of a cross-sectional analytical correlation study was carried out in the facilities of the laboratory at the UMAE No. 1, Bajío. Voluntary adult patients who attended the laboratory of the UMAE to take serum glucose levels were included, and simultaneously the measurement was carried out through a non-invasive method by spectroscopy and, later, both results were compared to demonstrate the validity of the device. Results: By the Bland-Altman mean difference analysis, it was identified that only one patient had an extreme value, and that the method to measure glucose non-invasively overestimates up to 10.2% of the central glucose value. Conclusion: Comparing these results with the standards for digital glucometers, it is concluded that our device is capable of providing accurate glucose levels.

Assessment of total mercury content in tissues of Mullus argentinae in Rio de Janeiro, Brazil / Avaliação de mercúrio total em tecido comestível de Mullus argetinae coletados no Rio de Janeiro, Brasil

This study has as objective to determine total mercury (Total Hg) levels by atomic absorption spectrophotometry in 134 individuals edible part of Mullus argentinae, in two different fishing areas and two seasons in Rio de Janeiro State. Also, proximate composition was performed. Total Hg results in wet weight basis ranged from 0.0867 to 0.7476 µg.g-1 in muscle; 0.0023 to 0,1034 µg.g-1 in flippers; and 0.0177 to 0.1849 µg.g-1 in skin. Mean evaluated moisture was 73.39%; protein was 18.76%; lipid concentration of 5.36%; carbohydrates of 2.35%; and ashes were 0.85%.Results showed that Total Hg contents was lower than accepted limits established by regulatory organization. Higher averages were observed in muscle (0.2441 µg.g-1) when compared with skin (0.2386 µg.g-1) and flippers (0.0195 µg.g-1). In general, samples collected on summer showed higher values of total Hg when comparing to winter. Regarding beach areas there was no significant difference (p>0.05). We can conclude that this specie should be cautious consumed because of total Hg bioaccumulation characteristics, although neither levels were above limits established.

O objetivo deste estudo foi determinar o teor de mercúrio no tecido comestível de Mullus argentinae, conhecido como peixe trilha, espécie amplamente consumida no Rio de Janeiro, Brasil. Foi determinado o teor de mercúrio total (Hg total) por espectrofotometria de absorção atômica em 134 amostras, coletados em duas áreas e estações climáticas diferentes. Além disso, foi avaliada a composição centesimal das amostras. Os resultados de Hg total em peso úmido variaram de 0,0867 a 0,7476 µg.g-1 no músculo; 0,0023 a 0,1034 µg.g-1 nas nadadeiras; e 0,0177 a 0,1849 µg.g-1 na pele. Os valores médios da composição centesimal foram de 73,30% de umidade, 18,76% de proteína, 5,36% de lipídios, 2,35% de carboidratos e 0,85% de matéria mineral. Os resultados das 134 amostras analisadas demostraram que os teores de Hg Total apresentam concentração inferior aos limites aceitos pelos órgãos reguladores. As maiores médias foram observadas no músculo (0,2441 µg.g-1) quando comparadas à pele (0,2386 µg.g-1) e nadadeiras (0,0195 µg.g-1). Em geral, as amostras coletadas no verão apresentaram maiores valores de Hg total em relação ao inverno. Em relação aos locais de coleta não houve diferença significativa (p> 0,05). Podemos concluir que esta espécie deve ser consumida com cautela devido às características de bioacumulação do Hg total, apesar das médias apresentadas estarem abaixo dos limites estabelecidos pela legislação.

Hormônio do crescimento versus treinamento de força: alterações nas estruturas colágenas, lipídicas e glicídicas / Growth hormone (gh) versus strength training: changes in collagen, lipid and glucidic structures

O objetivo deste estudo foi avaliar o efeito da aplicação de hormônio do crescimento (Growth Hormone - GH) e treinamento de força (TF) na composição do tecido ósseo de ratos Wistar a partir da Espectroscopia Raman. 40 ratos machos foram distribuídos de forma aleatória em quatro grupos: controle (C [n=10]), controle a aplicação de GH (GHC [n=10]), treinamento de força (T [n=10]) e treinamento de força e aplicação de GH (GHT [n=10]). O treinamento foi composto por quatro séries de 10 saltos aquáticos, realizados três vezes por semana, com sobrecarga correspondente a 50% do peso corpóreo e duração de quatro semanas. O GH foi aplicado na dose de 0,2 UI/Kg em cada animal, três vezes por semana e em dias alternados. Ao final do experimento, os animais foram eutanasiados e coletados os fêmures direitos para realização da análise da composição óssea. A espectroscopia Raman (ER) foi utilizada para observar os seguintes compostos a partir de suas respectivas bandas: colágeno e fosfolipídio (1445 cm-1), colesterol (548 cm-1), glicerol (607 cm-1), glicose (913 cm-1), Pico de carboidrato (931 cm-1 ) e prolina (918 cm-1 ). Para a análise estatística, foram realizados os testes de normalidade de Shapiro-Wilk e análise de variâncias ANOVA one-way, seguida pelo pós-teste de Tukey. Os resultados revelaram aumento nas concentrações de colágeno e fosfolipidio, colesterol, glicerol, glicose, pico de carboidrato e prolina em todos os grupos experimentais, associados ou não à realização do ST e/ou aplicação de GH. Porém, somente o grupo T diferiu significativamente do grupo C (p<0,05). Conclui-se que todas intervenções puderam promover ganho no tecido ósseo, porém, somente o grupo T demonstrou diferença significativa nos compostos minerais analisados. (AU)

The objective of this study was to evaluate the effect of the application of growth hormone (GH) and strength training (TF) on the bone tissue composition of Wistar rats using Raman Spectroscopy. 40 male rats were randomly assigned to four groups: control (C [n = 10]), control the application of GH (GHC [n = 10]), strength training (T [n = 10]) and training of strength and application of GH (GHT [n = 10]). The training consisted of four series of 10 water jumps, performed three times a week, with an overload corresponding to 50% of body weight and lasting four weeks. GH was applied at a dose of 0.2 IU / kg to each animal, three times a week and on alternate days. After four weeks, the animals were euthanized and the right femurs were collected to carry out the analysis of the bone composition. Raman spectroscopy (ER) was used to observe the following compounds from their respective bands: collagen and phospholipid (1445 cm-1), cholesterol (548 cm-1), glycerol (607 cm-1), glucose (913 cm-1), Peak carbohydrate (931 cm-1), proline (918 cm-1). For statistical analysis, the Shapiro-Wilk normality tests and ANOVA One-Way analysis of variances were performed, followed by the Tukey post-test. The results revealed an increase in the concentrations of collagen and phospholipid, cholesterol, glycerol, glucose, peak carbohydrate and proline in all experimental groups, associated or not with the performance of ST and / or application of GH. However, only group T differed significantly from group C (p <0.05). It was concluded that all intervention could promote gain in bone tissue, however, only the T group showed a significant difference in the analyzed mineral compounds. (AU)

Assessment of changes in the electrical activity of the brain during general anesthesia using portable electroencephalography / Evaluación de los cambios de la actividad eléctrica cerebral durante anestesia general usando electroencefalografía portable

Abstract Introduction The analysis of the electrical activity of the brain using scalp electrodes with electroencephalography (EEG) could reveal the depth of anesthesia of a patient during surgery. However, conventional EEG equipment, due to its price and size, are not a practical option for the operating room and the commercial units used in surgery do not provide access to the electrical activity. The availability of low-cost portable technologies could provide for further research on the brain activity under general anesthesia and facilitate our quest for new markers of depth of anesthesia. Objective To assess the capabilities of a portable EEG technology to capture brain rhythms associated with the state of consciousness and the general anesthesia status of surgical patients anesthetized with propofol. Methods Observational, cross-sectional study that reviewed 10 EEG recordings captured using OpenBCI portable low-cost technology, in female patients undergoing general anesthesia with propofol. The signal from the frontal electrodes was analyzed with spectral analysis and the results were compared against the reports in the literature. Results The signal captured with frontal electrodes, particularly α rhythm, enabled the distinction between resting with eyes closed and with eyes opened in a conscious state, and sustained anesthesia during surgery. Conclusions It is possible to differentiate a resting state from sustained anesthesia, replicating previous findings with conventional technologies. These results pave the way to the use of portable technologies such as the OpenBCI tool, to explore the brain dynamics during anesthesia.

Resumen Introducción El análisis de la actividad eléctrica cerebral mediante electrodos ubicados sobre el cuero cabelludo con electroencefalografía (EEG) podría permitir conocer la profundidad anestésica de un paciente durante cirugía. Sin embargo, los equipos de EEG convencionales, por su precio y tamaño, no son una alternativa práctica en quirófanos y los equipos comerciales usados en cirugía no permiten acceder a la actividad eléctrica. Disponer de tecnologías portables y de bajo costo aumentaría el número de investigaciones sobre la actividad cerebral bajo anestesia general y facilitaría la búsqueda de nuevos marcadores para la profundidad anestésica. Objetivo Evaluar la capacidad de una tecnología EEG portable de adquirir ritmos cerebrales relacionados con el estado consciente y el estado de anestesia general de pacientes en cirugía anestesiados con propofol. Métodos Estudio observacional de corte transversal en el que se analizaron datos de 10 registros EEG obtenidos mediante tecnología portable y de bajo costo OpenBCI, de pacientes de sexo femenino que fueron sometidas a anestesia general con propofol. La señal obtenida de los electrodos frontales se analizó mediante análisis espectral y se contrastaron los resultados con lo descrito en la literatura. Resultados La señal obtenida con electrodos frontales, especialmente el ritmo α, permitió diferenciar el reposo con ojos cerrados y ojos abiertos en estado consciente, del estado de mantenimiento de la anestesia durante cirugía. Conclusiones Se logra la diferenciación de estado de reposo y de mantenimiento de la anestesia replicando hallazgos previos de tecnologías convencionales. Estos resultados abren la posibilidad de utilizar las tecnologías portables como el OpenBCI para investigar la dinámica cerebral durante la anestesia.

Association between pain, anxiety, and alpha2 frontal activity in women with fibromyalgia

Fibromyalgia is a disorder of the central nervous system, with the presence of chronic generalized pain, fatigue, morning stiffness, anxiety and depression symptoms. Higher amplitudes of the frequency band alpha2 have been associated with higher relaxationin this population. In the present study, we analysed the association between pain, anxiety, and the spectral power of alpha2 frontal in women with fibromyalgia. Thirty-one women diagnosed with fibromyalgia, for at least three months, took part in the study. Results revealed a statistically significant positive relationship between pain and anxiety levels. However, we found no association between the spectral power of alpha2 in the frontal cortex and the measures between anxiety and pain in the patients. Present findings emphasize the importance of understanding the cortical activity and the central control mechanisms in fibromyalgia.

Inibidores de Desmetilase Lisina-Específica 1 (LSD1) como candidatos a agentes antineoplásicos / Lysine-Specif Demethylase 1 (LSD1) inhibitors as candidates for antineoplastic agents

O câncer é uma das principais causas de morte no mundo sendo, atualmente, a segunda principal causa de morte, perdendo apenas para as doenças cardiovasculares, tornando-se um grande desafio para as autoridades de saúde pública. No Brasil são estimados 625000 novos casos desta enfermidade para o triênio de 2020-2022. Nesse cenário, vários alvos epigenéticos são considerados alternativas no desenvolvimento de inibidores para a terapia do câncer devido serem identificados e relacionados com a carcinogênese, incluindo modificações no perfil de metilação do DNA e modificações de histonas como a metilação, acetilação e fosforilação. Dentre estas modificações, a metilação de histonas é regulada reversivelmente por histonas metiltransferases e desmetilases. A enzima desmetilase lisina-específica 1 (LSD1) foi a primeira histona desmetilase caracterizada e catalisa a remoção de grupos metila das lisinas 4 e 9 da histona H3 (H3K4 e H3K9), utilizando o FAD como cofator. Superexpressa em vários tumores de alto risco e tendo seus níveis correlacionados com a reincidência do tumor durante o tratamento, a LSD1 apresenta papel fundamental na tumorgênese. Portanto, tem sido considerado um alvo biológico promissor no desenvolvimento de novos fármacos para terapêutica contra o câncer. Sendo assim, neste trabalho, a partir de dados de triagem virtual baseado neste alvo biológico, selecionou-se um hit, o qual foi utilizado como protótipo para o planejamento de análogos visando melhorar as características farmacológicas, pois possuem grupos químicos passíveis das mesmas interações com o alvo. Foram sintetizadas 16 moléculas, sendo 7 compostos finais inéditos derivados carboxamídicos e 9 derivados sulfonamídicos. Todos os compostos foram caracterizados por RMN (1H e 13C), espectrometria de massas de alta resolução, espectroscopia de infravermelho, ponto de fusão, polarímetro e a pureza dos compostos foi avaliada por CLAE. Os compostos finais foram submetidos ao ensaio enzimático frente à LSD1, acoplado a Enzima Horseradish Peroxidase (EHP), mostrando que apenas o composto 4g apresentou atividade inibitória de 64% e 57% em 50 µM e 500 µM respectivamente. No ensaio de viabilidade celular na linhagem HEL (linhagem leucêmica) os 16 compostos (4a- 4g, 5a-5d e 6a-6d) apresentaram-se ativos com valores de CI50 na faixa de 5,3 µM a 20,25 µM. Os compostos mais potentes foram os 4e (CI50 = 6,9 µM), 5d (CI50 =5,30 µM) e 6ª (CI50 =6,61 µM), evidenciando que os compostos possuem elevada potência, tornando-se moléculas promissoras em linhagens leucêmicas. Os estudos de ancoramento molecular com a LSD1 sugeriram que a mudança de orientação do composto 4g, permitiu que o grupo benzila da porção benzilamida faça interação com os resíduos PHE560 e TYR807 no bolso hidrofóbico, o que possivelmente acarretou um bloqueio na entrada da cavidade, permitindo a inibição pelo composto

Cancer is one of the leading causes of death in the world and is currently the second leading cause of death, second only to cardiovascular disease, making it a major challenge for public health authorities. In Brazil, approximately, 625000 new cases of this disease are estimated for the 2020-2022 period. In this scenario, several epigentic targets are considered alternatives in the development of inhibitors in cancer therapy, since they are identified and related to carcinogenesis, including changes in the DNA methylation profile and changes in histones such as methylation, acetylation and phosphorylation. Among these modifications, histone methylation is reversibly regulated by histones methyltransferases and demethylases. Lysine-specific demethylase1 (LSD1) was the first histone demethylase characterized and catalyzes the removal of methyl groups from lysines 4 and 9 of histone H3 (H3K4 and H3K9), using FAD as a cofactor. LSD1 has been found to be overexpressed in several high-risk tumors and these levels are correlated with tumor recurrence during treatment. Therefore, it has been considered a promising biological target in the development of new drugs with therapeutic potential against cancer. Thus, in this work, the virtual screening technique based on the biological target was used to discover LSD1 interactions, and then based on the hit found, we propose to synthesize compounds that have chemical groups susceptible to such interactions, seeking to evaluate the enzymatic activity in LSD1 enzyme. Were synthesized 16 molecules, 7 of which are unpublished final compound derived from carboxamides and 9 sulfonamide derivatives. All compounds were characterized by NMR (1H and 13C), high resolution mass spectrometry, infrared spectroscopy, melting point, polarimeter and the purity of the compounds was assessed by CLAE. The final compounds were subjected to enzymatic assays Against LSD1, coupled with enzime Horseradish Peroxidase (HRP), showing that only the 4g compound showed 64% and 57% inhibitory activity in 50 µM and 500 µM respectively. In the cell viability assay in the HEL line (Leukemic line) the 16 compounds (4a-4g, 5a-5d and 6a-6d) were active with IC 50 values in the range of 5.3 µM to 20.25 µM. The most potent compounds were 4e (CI50 = 6.9 µM), 5d (CI50 = 5.30 µM) and 6a (CI50 = 6.61 µM), showing that the compounds have high potency, becoming promising molecules in leukemic lines. Docking studies with LSD1 suggested, that the change in orientation of the 4g compound allows the benzyl group of the benzylamide portion to interact with the PHE560 and TYR807 residues in the hydrophobic pocket, which possibly cause a block in the entrance of the cavity, allowing the inhibition by the compound. Thus, the results obtained indicate that the class of compounds described is likely to continue to be investigated, both in the search for new LSD1 inhibitory hits based on the structure of the 4g compound, how to deepen the studies with 16 compounds of the present work in the performance of more specific tests in leukemic cells, in order to unravel the mechanism of action and possible targets