Stevia rebaudiana germplasm characterization using microsatellite markers and steviol glycosides quantification by HPLC.

Stevia rebaudiana Bertoni, Asteraceae, is an herbaceous perennial plant native to Paraguay. This species is considered since ancient times a medicinal plant with important bioactive compounds and pharmacologic and food properties, namely diterpenes glycosides. The high natural sweetener potential stevioside and rebaudioside A produced by S. rebaudiana plants are suitable sucrose substitutes, and their obtention is influenced by environmental, phytosociological, and genetic factors. The plants' genetic profile and sweet potential depiction are needed for suitable plant selection for improvement and deployment. Thirty-one S. rebaudiana accessions grown in the same plot where leaves samples were collected in early 2019, were genotyped using six microsatellite markers, including two steviol glycosides biosynthesis functionally involved markers. Additionally, an aqueous extract of each sample was obtained in a water bath and purified by SPE for stevioside and rebaudioside A quantification by normal phase HPLC. Stevioside and rebaudioside A contents varied between 0.53-7.36% (w w-1) and 0.37-3.60% (w w-1), respectively. Two genotypes displayed interesting ratios of rebaudioside A/stevioside (number 3 and 33). The level of genetic similarity between genotypes was tested through a pairwise similarity coefficient, and two groups of individuals had the same fingerprinting. Strong relatedness was found within genotypes, possibly due to cloning, thus, influx of new germplasm ought to be made to prevent mating between relatives, and for further selection and genetic improvement.

Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in HIV-positive pregnant women.

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 µg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 µg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.).

Humulus lupulus aqueous extract and hydrolate as a potential ingredient for cosmetics: chemical characterization and in vitro antimicrobial, cytotoxicity, antioxidant and anti-inflammatory assessment.

Humulus lupulus extracts have in their composition different molecules, such as polyphenols, α-acids, ß-acids, and hydrocarbons, which contribute to the plant's medicinal properties. These molecules are associated with antimicrobial, antioxidant and anti-inflammatory activities. OBJECTIVE: This work focuses on the evaluation of H. lupulus biological activities, with the aim of evaluating its potential for inclusion in cosmetic formulations. METHODS: Two distinct aqueous extracts and two hydrolates obtained via hydrodistillation were evaluated. These include the flower parts (FE, FH) and the mix of aboveground parts (ME, MH). The chemical profiles for both aqueous extracts and hydrolates were identified by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Antimicrobial, antioxidant, cytotoxicity, and anti-inflammatory activity were tested in vitro using standard methods. RESULTS: Rutin was the major compound found in FE (40.041 µg mg-1 of extract) and ME (2.909 µg mg-1 of extract), while humulenol II was the most abundant compound in hydrolates (FH: 20.83%; MH: 46.80%). Furthermore, FE was able to inhibit the growth of Staphylococcus aureus and Staphylococcus epidermis with MIC values of 50% and 25% (v/v), respectively. FH showed the same effect in Staphylococcus aureus (50% v/v). FH evidenced poor antioxidant potential in DPPH scavenging test and demonstrated significant antioxidant and anti-inflammatory effects by reducing (***p < 0.001) intracellular reactive oxygen species (ROS), NO (nitric oxide) levels (***p < 0.001) and cyclooxygenase-2 (COX-2) protein expression (***p < 0.001) in lipopolysaccharide (LPS)-stimulated macrophages. Nevertheless, it is important to note that FH exhibited cytotoxicity at high concentrations in 3T3 fibroblasts and RAW 264.7 macrophages. CONCLUSION: The studied H. lupulus aqueous extracts and hydrolates revealed that FH stands out as the most promising bioactive source for cosmetic formulations. However, future research addressing antimicrobial activity is necessary to confirm its potential incorporation into dermatological and cosmetic formulations.

Mediterranean Lavenders from Section Stoechas: An Undervalued Source of Secondary Metabolites with Pharmacological Potential.

Globally, climate change and wildfires are disrupting natural ecosystems, thus setting several endemic species at risk. The genus Lavandula is widely present in the Mediterranean region and its species, namely, those included in the section Stoechas, are valuable resources of active compounds with several biological assets. Since ancient times lavenders have been used in traditional medicine and for domestic purposes. These species are melliferous, decorative, and essential oil-producing plants with a high economic interest in the pharmaceutical, flavor, fragrance, and food industries. The essential oils of Lavandula section Stoechas are characterized by high amounts of 1,8-cineole, camphor, fenchone, and specifically for L. stoechas subsp. luisieri one of the major compounds is trans-α-necrodyl acetate. On the other hand, the diversity of non-volatile components like phenolic compounds, such as phenolic acids and flavonoids, make these species an important source of phytochemicals with pharmacological interest. Rosmarinic, caffeic, and salvianolic B acids are the major phenolic acids, and luteolin and eriodictyol-O-glucuronide are the main reported flavonoids. However, the concentration of these secondary metabolites is strongly affected by the plant's phenological phase and varies in Lavandula sp. from different areas of origin. Indeed, lavender extracts have shown promising antioxidant, antimicrobial, anti-inflammatory, and anticancer properties as well as several other beneficial actions with potential for commercial applications. Despite several studies on the bioactive potential of lavenders from the section Stoechas, a systematized and updated review of their chemical profile is lacking. Therefore, we carried out the present review that gathers relevant information on the different types of secondary metabolites found in these species as well as their bioactive potential.

A curative cryosurgical technique for advanced cancer of sacrococcygeal pilonidal sinuses.

BACKGROUND AND OBJECTIVE: Malignant degeneration of pilonidal sinuses of the sacrococcygeal region is rare but quite serious, as the tumor soon perforates the sacral fascia and becomes adherent to the irregular posterior aspect of the sacrum, making it very difficult, if not impossible, to remove all neoplastic tissue by conventional surgery, hence the high recurrence rate and poor prognosis. A new cryosurgical technique to treat advanced sacrococcygeal pilonidal cancer is herein presented. MATERIALS AND METHODS: Seven men aged 30-75 (mean: 54.4 years) with advanced squamous-cell carcinomas (four primary, three recurrent) arising in sacrococcygeal pilonidal sinuses were treated with open and thick liquid nitrogen spray-two freeze-thaw cycles. Temperature monitoring was made by thermocouples. RESULTS: Local eradication was achieved in all cases; one patient, however, died of metastatic disease 10 months after treatment, without local recurrence. One patient had a recurrence, or a new tumor, 8 years after treatment and was again submitted to aggressive cryosurgery followed by plastic surgery. He was followed for 14 years without recurrence. The follow-up of the remaining six patients ranges between 7 and 18 years. CONCLUSION: To the author's knowledge, this is the first series of carcinomas of sacrococcygeal pilonidal sinuses successfully treated by cryosurgery.

Prediction scenarios of past, present, and future environmental suitability for the Mediterranean species Arbutus unedo L.

Climate change is a challenge for forests in the coming decades, with a major impact on species adaptation and distribution. The Mediterranean Basin is one of the most vulnerable hotspots for biodiversity conservation under climate change in the world. This research aimed at studying a Mediterranean species well adapted to the region: the Arbutus unedo L. (strawberry tree). The MaxEnt, a presence-only species-distribution software, was used to model A. unedo's environmental suitability. The current species potential distribution was accessed based on actual occurrences and selected environmental variables and subsequently projected for the Last Glacial Maximum (LGM), the Mid-Holocene (MH), and the years 2050 and 2070, considering the two Representative Concentration Pathways: RCP4.5 and RCP8.5. Results from the LGM projection suggest the presence of refugia in the core of the Mediterranean Basin, in particular the Iberian Peninsula (IP). The projections for the MH indicate increasing climatic suitability for the species and an eastward expansion, relatively to LGM. The predicted future environmental changes will most likely act as a catalyst for suitable habitat loss and a range shift towards the North is likely to occur.

Assessing the contribution of UGT isoforms on raltegravir drug disposition through PBPK modeling.

This work aimed to develop a physiologically based pharmacokinetic (PBPK) model for raltegravir accounting for UDP-glucuronosyltransferase (UGT) metabolism to assess the effect of UGT gene polymorphisms. Raltegravir elimination was evaluated using Km and Vmax values from human recombinant systems and UGT tissue scalar considering liver, kidney, and intestine. The predicted/observed ratios for raltegravir PK parameters were within a 2-fold error range in UGT1A1 poor and normal metabolizers, except in Asian UGT1A1 poor metabolizers. This PBPK modeling approach suggests that UGT1A3 is the main contributor to raltegravir's metabolism. UGT1A3 and UGT1A1 gene polymorphisms might have an additive effect on raltegravir's drug disposition and response. The final model accounting for hepatic, renal, and intestinal UGT metabolism, biliary clearance, and renal excretion improved model predictions compared with the previously published models. This PBPK model with the quantitative characterization of raltegravir elimination pathways can support dose adjustments in different clinical scenarios.

Pretreatment and non-specific binding in ultrafiltration device: Impact on protease inhibitor quantification.

INTRODUCTION: Ultrafiltration (UF) is used to separate unbound drugs; however, non-specific binding (NSB) may be a limiting factor of this technique. Pretreatment of UF devices has been suggested to reduce NSB. Therefore, the pretreatment methodologies for UF devices were evaluated in order to test their effectiveness in reducing NSB of protease inhibitors (PIs). METHODOLOGY: Two PIs (lopinavir-LPV and ritonavir-RTV) were tested. UF devices were pretreated with ultrapure water, Tween-20 or Tween-80. To evaluate the NSB, after UF devices being pretreated, ultrafiltrate solutions containing the analytes at two concentrations (low and high) were used. Samples were quantified by LC-MS/MS. RESULTS: UF devices pretreated with Tween-5% had the lowest NSB for both analytes. NSB values varied between 7 and 11% at low concentration 16-34% at high LPV concentration, respectively. For RTV, NSB was approximately 6% for low concentration and 18% for high concentration. Failure to completely remove Tween in UF devices could results in an overestimation of NSB. CONCLUSION: Pretreatment of UF device with Tween and subsequent removal proved to be effective in reducing NSB of PI.

Pharmacokinetic/pharmacodynamic modeling of psychomotor impairment induced by oral clonazepam in healthy volunteers.

This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacodynamic (PK/PD) study is important to interpret properly the consequences of determined levels of plasma concentrations of psychoactive therapeutic drugs reported to be involved in road-traffic accidents. Twenty-three male subjects received a single oral dose of 4 mg clonazepam. Plasma concentration, determined by on-line solid phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry, and psychomotor performance, quantified through the Digit Symbol Substitution Test, were monitored for 72 hours. A 2-compartment open model with first order absorption and lag-time better fitted the plasma clonazepam concentrations. Clonazepam decreased the psychomotor performance by 72 +/- 3.7% (observed maximum effect), 1.5 to 4 hours (25th-75th percentile) after drug administration. A simultaneous population PK/PD model based on a sigmoid Emax model with time-dependent tolerance described well the time course of effect. Such acute tolerance could minimize the risk of accident as a result of impairment of motor skill after a single dose of clonazepam. However, an individual analysis of the data revealed a great interindividual variation in the relationship between clonazepam effect and plasma concentration, indicating that the phenomenon of acute tolerance can be predicted at a population, but not individual, level.

Fractional cryosurgery for skin cancer.

BACKGROUND: Cryosurgical treatment of facial skin cancers 10 mm or larger in diameter can originate retractile scars that may alter physiognomic features. OBJECTIVES: To treat skin cancers 10 mm or larger in diameter on the face with a cryosurgical method that prevents retractile scars. Also, to clarify the differences between this method and Zacarian's segmental cryosurgery. METHODS AND MATERIALS: Fractional cryosurgery is performed in stages. First, the center of the lesion is frozen, reducing its size, then this procedure is repeated as necessary until the tumor diameter is smaller than 10 mm, at which point the standard cryosurgical procedure is performed. Eighty-seven basal cell carcinomas (BCCs) and nine squamous cell carcinomas (SCCs) of the face (65 of which were orbital or periocular) measuring between 9 and 45 mm were treated. RESULTS: The cure rate of BCCs was related to tumor size. All SCCs were cured without recurrence. Global mean follow-up was 4.5 years. CONCLUSION: Fractional cryosurgery does not cause deformity, and the final scar has no relation to the mass of the original tumor but instead corresponds to the size of the lesion preceding the last cryosurgical procedure.

A novel and simple LC-MS/MS quantitative method for dextromethorphan and dextrorphan in oral fluid.

Aim: To develop and validate a simple method using LC-MS/MS for determination of dextromethorphan (DXM) and dextrorphan (DT) in human oral fluid. Results: Following protein precipitation, chromatographic separation used a phenyl column with isocratic elution (1 ml/min) of 10 mM ammonium-formate buffer and acetonitrile (65:35; v/v) with 0.1% formic acid. Retention times were 2.6 min for DT and 5 min for DXM. Total run time was 7 min. The intra- and inter-assay deviations (accuracy) for DT (1-100 ng/ml) and DXM (5-1000 ng/ml) ranged from -13.6 to 8.8% and -9.6 to 5.7%, respectively. Precision variations were ≤7.5%. Matrix effect was ≤11.8%. Conclusion: This method may prove helpful for quantification of DT and DXM in oral fluid for either clinical or toxicological purposes.

Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST.

SETTING: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH). DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. OBJECTIVE: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. DESIGN: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. RESULTS: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. CONCLUSION: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p=0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.

A Rapid and Simple HPLC Method for Therapeutic Monitoring of Vancomycin.

Therapeutic monitoring of the antibiotic vancomycin is important to achieve specific plasma concentration and prevent toxic effects. Several assays have been described for vancomycin determination in clinical practice, but high-performance liquid chromatography is still considered the gold standard for the quantification of vancomycin. In this study, we developed a new and rapid high-performance liquid chromatography method requiring 50 µL of plasma for the quantification of vancomycin. Acetonitrile was used for processing plasma by protein precipitation (1:2.5). Isocratic chromatographic analysis was carried out on a C18 silica-based (2.7 µm) column with the mobile phase containing 20 mM ammonium acetate/formic acid buffer (pH 4.0):methanol 88:12 (v/v). A diode array detector was used for UV detection at 240 nm. This method was validated according to the Brazilian Health Surveillance Agency legislation and International Conference on Harmonization guidelines. The measurement range was 1-100 µg/mL, analysis time was 8 min, and intermediate precision was <12%, supporting the present method as a fast, simple, and effective alternative for therapeutic monitoring of vancomycin.

Development and validation of liquid chromatography-tandem mass spectrometry method to quantify dasatinib in plasma and its application to a pharmacokinetic study

Abstract Dasatinib, a potent oral multi-targeted kinase inhibitor against Src and Bcr-Abl, can decrease inflammatory response in sepsis. A simple and cost-effective method for determination of an effective dose dasatinib was established. This method was validated in human plasma, with the aim of reducing the number of animals used, thus, avoiding ethical problems. Dasatinib and internal standard lopinavir were extracted from 180 uL of plasma using liquid-liquid extraction with methyl tert-butil ether, followed by liquid chromatography coupled to triple quadrupole mass spectrometry in multiple reaction monitoring mode. For the pharmacokinetic study, 1 mg/kg of dasatinib was administered to mice with and without sepsis. The method was linear over the concentration range of 1-98 ng/mL for DAS in mice and human plasma, with r2>0.99 and presented intra- and interday precision within the range of 2.3 - 6.2 and 4.3 - 7.0%, respectively. Further intra- and interday accuracy was within the range of 88.2 - 105.8 and 90.6 - 101.7%, respectively. The mice with sepsis showed AUC0-t = 2076.06 h*ng/mL and Cmax =102.73 ng/mL and mice without sepsis presented AUC0-t = 2128.46 h*ng/mL. Cmax = 164.5 ng/mL. The described analytical method was successfully employed in pharmacokinetic study of DAS in mice.

Extended stability study of an extemporaneously analgesic solution of clonidine, ropivacaine and fentanyl

Abstract The aim of this work was to perform an extended stability study for the analgesic containing fentanyl, clonidine and ropivacaine in physiological saline solution 0.9% at different infusion sites, such as infusion bags, epidural infusion sets and syringes. The extended stability was assessed by an HPLC system equipped with a photodiode array detector set at 210 nm. The separation was conducted on a C18 column maintained at 40˚C and using an isocratic mobile phase consisted of buffer solution-methanol-acetonitrile (45:45:10, v/v/v). The presence of particulate matter and the pH of each solution were also investigated. Twenty-four hours after the preparation, the formation of one suspected product was observed and for all drugs, in 24 hours it was observed the concentration decrease in different sets (PVC infusion bags, syringes and epidural infusion administration sets). The pH values of each solution varied no more than 5% during the study and no particle was observed. Conclusion: The extended stability study was applied to the analgesic solution and promoted the detection of an unexpected peak in 24 hours. Based on it, further stability studies are necessary to determine the extended stability data.

Vertebroplasty in bone fragility fractures and tumor fractures: risks and benefits / Vertebroplastia em fraturas por fragilidade óssea e tumorais: riscos e benefícios / Vertebroplastia en fracturas por fragilidad ósea y tumorales: riesgos y beneficios

ABSTRACT Objective: To evaluate the results of percutaneous vertebroplasty (PV) in spinal fragility fractures (osteoporosis/tumor), analyzing possible complications. Method: We evaluated 33 patients with spinal fractures (FXV) due to osteoporosis or tumor who underwent PV between January and November 2021. A physical examination was performed, obtaining the history and risk factors for bone fragility/tumor and a radiological evaluation of the spine to verify FXV. Genant's semiquantitative method was used for postoperative classification, the VAS score, and a disability questionnaire (ODI). A radiologist evaluated tomographic control to quantify vertebral filling and extravasation, determining where they occurred. Results: 46 vertebrae of 33 patients were operated on, with a mean age of 71 years, and 11 patients with more than one level of surgery. Of the total, 13 patients had tumor fractures, and 20 had fractures due to insufficiency. PMMA extravasation was observed in 31 vertebrae, most frequently in the External Vertebral Venous Plexus (23), Discal Body (9), Anterior Epidural Recess (4), Pulmonary Vessels (4), Internal Vertebral Venous Plexus (3), Inferior Cava (2), Adipose Plane (2) and Azygos Vein (1). No patient had clinical complications. Furthermore, the mean preoperative VAS was eight, the postoperative one was 3, the mean preoperative ODI was 56, and the postoperative one was 30. Conclusion: PMMA extravasation was frequent in several locations and levels without any clinical complications. VP proved to be effective in improving pain and function. Level III; Longitudinal Retrospective Cohort Study.

RESUMO Objetivo: Avaliar os resultados da vertebroplastia percutânea (VP) em fraturas por fragilidade da coluna (osteoporose/tumoral), analisando possíveis complicações. Método: Foram avaliados 33 pacientes com fratura da coluna vertebral (FXV) por osteoporose ou tumor, entre janeiro e novembro de 2021, submetidos à VP. Foi realizado exame físico junto à obtenção da história e fatores de risco para fragilidade óssea / tumor, além de avaliação radiológica da coluna para constatação de FXV. O método semiquantitativo de Genant foi empregado para a classificação no pós-operatório, além do score EVA e do questionário de incapacidade (ODI). O controle tomográfico foi avaliado por médico radiologista para quantificação do preenchimento vertebral e extravasamento, determinando para onde ocorreram. Resultados: Foram operadas 46 vértebras de 33 pacientes, como média de idade de 71 anos, sendo 11 pacientes com mais de um nível operado. Do total, 13 pacientes apresentavam fraturas tumorais e 20 possuíam fraturas por insuficiência. Observou-se extravasamento do PMMA em 31 vértebras, mais frequentemente para Plexo Venoso Vertebral Externo (23), Corpo Discal (9), Recesso Epidural Anterior (4) Vasos Pulmonares (4), Plexo Venoso Vertebral Interno (3), Cava Inferior (2), Plano Adiposo (2) e Veia Ázigos (1). Nenhum paciente apresentou complicações clínicas. Ainda, o EVA pré-operatório médio foi 8 e o pós-operatório de 3, enquanto o ODI pré-operatório médio foi de 56 e o pós-operatório de 30. Conclusão: O extravasamento de PMMA foi frequente em diversos locais e níveis, sem nenhuma complicação clínica. A VP mostrou-se eficaz na melhora de dor e função. Nível III; Estudo Longitudinal Coorte Retrospectivo.

RESUMEN Objetivo: Evaluar los resultados de la vertebroplastia percutánea (PV) en fracturas por fragilidad de columna (osteoporosis/tumor), analizando posibles complicaciones. Método: Se evaluaron 33 pacientes con fractura de columna (FXV) por osteoporosis o tumor, entre enero y noviembre de 2021, que fueron sometidos a PV. Se realizó examen físico junto con obtención de antecedentes y factores de riesgo de fragilidad ósea/tumor, además de evaluación radiológica de columna para verificar FXV. Para la clasificación postoperatoria se utilizó el método semicuantitativo de Genant, además de utilizar la escala EVA y un cuestionario de discapacidad (ODI). El control tomográfico fue evaluado por un radiólogo para cuantificar el llenado vertebral y la extravasación, determinando dónde se producían. Resultados: Se operaron 46 vértebras de 33 pacientes, con una edad promedio de 71 años, 11 pacientes con más de un nivel de cirugía. Del total, 13 pacientes presentaron fracturas tumorales y 20 fracturas por insuficiencia. Se observó extravasación de PMMA en 31 vértebras, con mayor frecuencia en el Plexo Venoso Vertebral Externo (23), Cuerpo Discal (9), Receso Epidural Anterior (4), Vasos Pulmonares (4), Plexo Venoso Vertebral Interno (3), Cava Inferior (2), Plano Adiposo (2) y Vena Azygos (1). Ningún paciente presentó complicaciones clínicas. Además, la EVA preoperatoria media fue de 8 y la postoperatoria de 3, mientras que la ODI preoperatoria media fue de 56 y la postoperatoria de 30. Conclusión: La extravasación de PMMA fue frecuente en varias localizaciones y niveles, sin complicaciones clínicas. VP demostró ser eficaz para mejorar el dolor y la función. Nivel III; Estudio de cohorte retrospectivo longitudinal.

Usefulness of serotoninergic challenge with oral citalopram.

OBJECTIVE: Challenge tests designed to evaluate serotoninergic pathways have widely used intravenous citalopram. Oral citalopram has also been used, but unsatisfactory results were obtained with a dose of 20 mg. The objective of this study was to determine whether a higher oral dose would reproduce similar to those described for intravenous administration. To that end, we evaluated cortisol, growth hormone and prolactin levels. METHOD: Eight healthy male volunteers were evaluated in a randomized crossover challenge test with 40 mg of oral citalopram or placebo. RESULTS: Cortisol levels increased at 2-4h after the oral citalopram intake, with a small amplitude peak occurring in two-thirds of the subjects. Levels of prolactin and growth hormone remained unchanged throughout the study. CONCLUSION: The use of oral citalopram might present an alternative in serotoninergic challenge tests, but higher doses are required.

A new sunscreen of the cinnamate class: synthesis and enzymatic hydrolysis evaluation of glyceryl esters of p-methoxycinnamic acid.

Glyceryl esters of p-methoxycinnamic acid, 1,3-dipalmitoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol and 1,3-dioctanoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol were synthesised in an attempt to increase substantivity and decrease eventual undesirable effects of sunscreens of this class. To assess if the glyceryl esters could present a higher stability towards hydrolysis by lipases in the stratum corneum, hydrolysis rates were determined in vitro using a commercial fungal lipase from Rhizomucor miehei. Results presented herein show that the glyceryl esters have similar lambda(max) and epsilon values to sunscreens of the cinnamate class. The ester 1,3-dipalmitoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol presented a 2.8 times lower hydrolysis rate by lipase, in vitro, than the commercial sunscreen 2-ethylhexyl-p-methoxycinnamate (alkyl ester). This finding suggests that this triacylglycerol can possibly have a longer retention time in the skin and consequently promote a more intense and effective antisolar action than the commercial sunscreen.

Vitamin A and retinol-binding protein deficiency among chronic liver disease patients.

OBJECTIVE: Vitamin A deficiency (VAD) is associated with the progression of chronic liver disease (CLD). The aim in this study was to assess levels of serum retinol and retinol-binding protein (RBP) as well as liver vitamin A stores in the presence of liver cirrhosis and hepatocellular carcinoma. METHODS: We ascertained the serum retinol and RBP levels of randomly selected CLD patients divided into two groups, one given 1500 UI (n = 89) and the other receiving 2500 UI (n = 89) doses of retinyl palmitate for the relative dose response test. Blood samples were collected in a fasting state and 5 and 7 h after supplementation. RESULTS: The prevalence of VAD was 62.4%. There was a progressive drop in serum retinol (P < 0.001) and RBP (P = 0.002) according to the severity of the liver disease, and a greater prevalence of severe VAD was noted in cirrhosis Child & Pugh C (52.8%). Fifty percent of the patients presented a low availability of RBP relative to retinol concentration, and there was no peak in RBP levels regardless of the dose of retinyl palmitate administered. CONCLUSIONS: Our findings suggest serum retinol and RBP are relevant as indicators of vitamin A nutritional status in the presence of CLD. Liver vitamin A store cannot be evaluated using the RDR test because CLD causes a reduction in RBP synthesis and interferes with the mobilization of endogenous vitamin A. Considering how the patients already showed a drop in RBP relative to retinol concentrations, it is reasonable to assume vitamin A supplementation may trigger harmful effects in CLD patients.

Does decubitus affect neural elements positioning? a mri study comparing dorsal and lateral position / O decúbito afeta a posição dos elementos neurais? estudo de ressonância magnética comparando a posição dorsal e lateral / ¿la posición afecta el posicionamiento de los elementos neurales? un estudio de rm que compara la posición dorsal y lateral

ABSTRACT Objective To evaluate the displacement of nerve structures according to the decubitus position of the patient in a magnetic resonance imaging (MRI) study. Methods MRI was performed at a radiology clinic in 20 patients in dorsal and right lateral decubitus. The measurement considered was the shortest distance between the dura mater and the medial wall of the pedicle. Results The largest measurement was 11.6 mm in left lateral decubitus, 12.2 mm in right lateral decubitus, 10.5 mm in right dorsal decubitus, and 9.2 mm in left dorsal decubitus. In some patients the space between the medial wall of the pedicle and the dura mater was larger when in lateral decubitus, while in others when in dorsal decubitus. The mean displacement of the measurements on the left was 1.14 mm and on the right 1.355 mm. Conclusions The structures moved on average little more than 1 mm in the positions studied. The positioning of the patient for surgery does not change the space to be approached, being the surgeon's choice according to his learning curve. Level of evidence II; Prospective study of lower quality.

RESUMO Objetivo Avaliar o deslocamento das estruturas nervosas conforme o decúbito do paciente em um estudo de Ressonância Nuclear Magnética (RNM). Métodos Foram realizadas RNM em 20 pacientes em uma clínica de radiologia em decúbito dorsal e lateral direito. A medida considerada será a menor distância entre a dura-máter e a parede medial do pedículo. Resultados A maior medida em decúbito lateral esquerdo foi 11,6 mm, em decúbito lateral direito foi 12,2 mm, em decúbito dorsal direito foi 10,5 mm e no esquerdo, 9,2 mm. O espaço entre a parede medial do pedículo é maior em decúbito lateral em alguns pacientes e, em outros, em decúbito dorsal. O deslocamento médio das medidas à esquerda foi 1,14 mm e à direita 1,355 mm. Conclusões As estruturas se deslocaram, em média, pouco mais de 1 mm nas posições estudadas. O posicionamento do paciente na cirurgia não muda o espaço a ser abordado, sendo de escolha do cirurgião, conforme a sua curva de aprendizado. Nível de evidência II; Estudo prospectivo de menor qualidade .

RESUMEN Objetivo Evaluar el desplazamiento de las estructuras nerviosas conforme al decúbito del paciente en un estudio de Resonancia Nuclear Magnética (RNM). Métodos Fueron realizadas RNM en 20 pacientes en una clínica de radiología en decúbito dorsal y lateral derecho. La medida considerada será la menor distancia entre la duramadre y la pared medial del pedículo. Resultados La mayor medida en decúbito lateral izquierdo fue 11,6 mm, en decúbito lateral derecho fue 12,2 mm, en decúbito dorsal derecho fue 10,5 mm y en el izquierdo, 9,2 mm. El espacio entre la pared medial del pedículo es mayor en decúbito lateral en algunos pacientes y, en otros, en decúbito dorsal. El desplazamiento promedio de las medidas a la izquierda fue 1,14 mm y a la derecha de 1,355 mm. Conclusiones Las estructuras se desplazaron, en promedio, poco más de 1 mm en las posiciones estudiadas. El posicionamiento del paciente en la cirugía no cambia el espacio a ser abordado, siendo la elección del cirujano conforme a su curva de aprendizaje. Nivel de evidencia II; Estudio prospectivo de menor calidad.