Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Perifosine inhibits biofilm formation of Pseudomonas aeruginosa by interacting with PqsE protein / 中华预防医学杂志

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 μg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.

Acute uveitis: A rare adverse effect of miltefosine in the treatment of post-kala-azar dermal leishmaniasis

Abstract Post-kala-azar dermal leishmaniasis is a skin disorder occurring in 5-10% of visceral leishmaniasis patients after treatment with miltefosine,the first-line drug for this skin disorder. We reported a case of acute anterior uveitis,a rare adverse effect, experienced by a patient treated with miltefosine for post-kala-azar dermal leishmaniasis. This adverse effect developed after 15 days of miltefosine consumption, and the patient himself discontinued the treatment. The ophthalmic complication was completely resolved with antibiotics and steroid eye drops. After recovery from the ophthalmic complication, the patient was successfully treated with liposomal amphotericin B for the skin lesions.

A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

Akt Inhibitor Perifosine Prevents Epileptogenesis in a Rat Model of Temporal Lobe Epilepsy / 神经科学通报·英文版

Accumulating data have revealed that abnormal activity of the mTOR (mammalian target of rapamycin) pathway plays an important role in epileptogenesis triggered by various factors. We previously reported that pretreatment with perifosine, an inhibitor of Akt (also called protein kinase B), abolishes the rapamycin-induced paradoxical increase of S6 phosphorylation in a rat model induced by kainic acid (KA). Since Akt is an upstream target in the mTOR signaling pathway, we set out to determine whether perifosine has a preventive effect on epileptogenesis. Here, we explored the effect of perifosine on the model of temporal epilepsy induced by KA in rats and found that pretreatment with perifosine had no effect on the severity or duration of the KA-induced status epilepticus. However, perifosine almost completely inhibited the activation of p-Akt and p-S6 both acutely and chronically following the KA-induced status epilepticus. Perifosine pretreatment suppressed the KA-induced neuronal death and mossy fiber sprouting. The frequency of spontaneous seizures was markedly decreased in rats pretreated with perifosine. Accordingly, rats pretreated with perifosine showed mild impairment in cognitive functions. Collectively, this study provides novel evidence in a KA seizure model that perifosine may be a potential drug for use in anti-epileptogenic therapy.

Effects of water-aging for 6 months on the durability of a novel antimicrobial and protein-repellent dental bonding agent / 国际口腔科学杂志·英文版

Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate (DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent (MPC) and antibacterial agent (DMAHDM) were added to a Scotchbond multi-purpose (SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days (d). At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control (P  0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.

Adamantylidene-substituted alkylphosphocholine TCAN26 is more active against Sporothrix schenckii than miltefosine

Sporotrichosis is the most frequent subcutaneous mycosis in the world and its increasing incidence has led to the search for new therapeutic options for its treatment. In this study, we demonstrated that three structural analogues of miltefosine (TCAN26, TC19, and TC70) showed inhibitory activity against Sporothrix schenckii sensu stricto and that TCAN26 was more active in vitro than miltefosine against several isolates. Scanning electron microscopy showed that S. schenckii exposure to TCAN26 resulted in cells that were slightly more elongated than untreated cells. Transmission electron microscopy showed that TCAN26 treatment induced loss of the regular cytoplasmic electron-density and altered the cell envelope (disruption of the cell membrane and cell wall, and increased cell wall thickness). Additionally, TCAN26 concentrations required to kill S. schenckii cells were lower than concentrations that were cytotoxic in mammalian cells, and TCAN26 was more selective than miltefosine. Thus, the adamantylidene-substituted alkylphosphocholine TCAN26 is a promising molecule for the development of novel antifungal compounds, although further investigations are required to elucidate the mode of action of TCAN26 in S. schenckii cells.

Effect of 2-methacryloyloxyethyl phosphorylcholine on the protein-repellent property of dental adhesive / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) and nanoparticles of amorphous calcium phosphate (NACP) on the protein-repellent property of dental adhesive.</p><p><b>METHODS</b>MPC and NACP were incorporated into SBMP as the test group. Scotchbond Multi-Purpose (SBMP) was used as control group. Human dentin shear bond strengths were measured. Protein adsorption onto samples was determined by micro bicinchoninic acid (BCA) method. A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm viability.</p><p><b>RESULTS</b>The dentin bond strength of modified group was (28.7±2.2) MPa, which was not significantly different from that of the SBMP control group. The amount of protein adsorption in the modified group and the SBMP control group were (0.21±0.02) µg/cm(2) and (4.17±0.45) µg/cm(2) respectively. Lactic acid production of biofilms in modified group and SBMP control were (7.71 ± 1.01) mmol/L and (19.18 ± 2.34) mmol/L repectively.</p><p><b>CONCLUSIONS</b>MPC-NACP based dental adhesive greatly reduce the protein adsorption and bacterial adhesion, without compromising dentin shear bond strength. This novel bonding agent may have wide application.</p>

Surface Modification of Intraocular Lenses / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs).</p><p><b>DATA SOURCES</b>All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect.</p><p><b>STUDY SELECTION</b>The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded.</p><p><b>RESULTS</b>Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments.</p><p><b>CONCLUSION</b>The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.</p>

Bacterial colonization due to increased nurse workload in an intensive care unit / Colonização bacteriana por causa do aumento da carga de trabalho da equipe de enfermagem em unidade de terapia intensiva / Colonización bacteriana debido al aumento de la carga de trabajo del equipo de enfermería en una unidad de cuidados intensivos

INTRODUCTION: The rates of multiresistant bacteria colonization or infection (MRB+) development in intensive care units are very high. The aim of this study was to determine the possible association between the risk of development of nosocomial infections and increased daily nurse workload due to understaffing in intensive care unit. METHODS: We included 168 patients. Intensity of workload and applied procedures to patients were scored with the Project de Recherché en Nursing and the Omega scores, respectively. The criteria used for infections were those defined by the Centers for Disease Control. RESULTS: Of the 168 patients, 91 (54.2%) were female and 77 (45.8%) were male patients. The mean age of female and male was 64.9 ± 6.2 years and 63.1 ± 11.9 years, respectively. The mean duration of hospitalization in intensive care unit was 18.4 ± 6.1 days. Multiresistant bacteria were isolated from cultures of 39 (23.2%) patients. The development of MRB+ infection was correlated with length of stay, Omega 1, Omega 2, Omega 3, Total Omega, daily PRN, and Total PRN (p < 0.05). There was no correlation between development of MRB+ infection with gender, age and APACHE-II scores (p > 0.05). CONCLUSION: The risk of nosocomial infection development in an intensive care unit is directly correlated with increased nurse workload, applied intervention, and length of stay. Understaffing in the intensive care unit is an important health problem that especially affects care-needing patients. Nosocomial infection development has laid a heavy burden on the economy of many countries. To control nosocomial infection development in the intensive care unit, nurse workload, staffing level, and working conditions must be arranged. .

INTRODUÇÃO: As taxas de desenvolvimento de infecção ou colonização por bactérias multirresistentes (BMR+) em unidades de terapia intensiva são muito elevadas. O objetivo deste estudo foi determinar a possível associação entre o risco de desenvolvimento de infecções hospitalares e o aumento da carga de trabalho diária da equipe de enfermagem devido à insuficiência de pessoal em unidade de terapia intensiva. MÉTODOS: Cento e sessenta e oito pacientes foram incluídos. O volume da carga de trabalho e os procedimentos realizados em pacientes foram avaliados com o uso de instrumentos de medidas como o Projeto de Pesquisa em Enfermagem (Project de Recherché en Nursing) e o Omega, respectivamente. Os critérios usados para definir infecções foram os definidos pelos Centros de Controle de Doenças. RESULTADOS: Dos 168 pacientes, 91 (54,2%) eram do sexo feminino e 77 (45,8%) do sexo masculino. As médias das idades de mulheres e homens foram 64,9 ± 6,2 e 63,1 ± 11,9 anos, respectivamente. A média do tempo de internação em unidade de terapia intensiva foi de 18,4 ± 6,1 dias. As bactérias multirresistentes foram isoladas a partir de culturas de 39 (23,2%) pacientes. O desenvolvimento de infecção por BMR+ foi correlacionado com tempo de internação, Omega 1, Omega 2, Omega 3, Omega total, PPE diário e PPE total (p < 0,05). Não houve correlação entre desenvolvimento de infecção por BMR+ e gênero, idade e escores no APACHE-II (p > 0,05). CONCLUSÃO: O risco de desenvolvimento de infecção hospitalar em unidade de terapia intensiva está diretamente relacionado com o aumento da carga de trabalho de enfermagem, as intervenções praticadas e o tempo de internação. A falta de pessoal em unidade de terapia intensiva é um problema de saúde importante que afeta principalmente os pacientes que requerem cuidados. A infecção hospitalar colocou um fardo pesado sobre a economia de muitos países. Para controlar o desenvolvimento de infecção hospitalar em UTI, a carga ...

INTRODUÇÃO: as taxas de desenvolvimento de infecção ou colonização por bactérias multirresistentes [BMR (+)] em unidades de terapia intensiva são muito elevadas. O objetivo deste estudo foi determinar a possível associação entre o risco de desenvolvimento de infecções hospitalares e o aumento da carga de trabalho diária da equipe de enfermagem por causa da insuficiência de pessoal em unidade de terapia intensiva. MÉTODOS: foram incluídos 168 pacientes. O volume da carga de trabalho e os procedimentos feitos em pacientes foram avaliados com o uso de instrumentos de medidas como o Projeto de Pesquisa em Enfermagem (Project de Recherché en Nursing) e o Omega, respectivamente. Os critérios usados para definir infecções foram os estabelecidos pelos Centros de Controle de Doenças. RESULTADOS: dos 168 pacientes, 91 (54,2%) eram do sexo feminino e 77 (45,8%) do masculino. As médias das idades de mulheres e homens foram 64,9 ± 6,2 e 63,1 ± 11,9 anos, respectivamente. A média do tempo de internação em unidade de terapia intensiva foi de 18,4 ± 6,1 dias. As bactérias multirresistentes foram isoladas a partir de culturas de 39 (23,2%) pacientes. O desenvolvimento de infecção por BMR (+) foi correlacionado com tempo de internação, Omega 1, Omega 2, Omega 3, Omega total, PPE diário e PPE total (p < 0,05). Não houve correlação entre desenvolvimento de infecção por BMR (+) e gênero, idade e escores no Apache-II (p > 0,05). CONCLUSÃO: o risco de desenvolvimento de infecção hospitalar em unidade de terapia intensiva está diretamente relacionado com o aumento da carga de trabalho de enfermagem, as intervenções praticadas e o tempo de internação. A falta de pessoal em unidade de terapia intensiva é um problema de saúde importante que afeta principalmente os pacientes que requerem cuidados. A infecção hospitalar colocou um fardo pesado sobre a economia de muitos países. Para controlar o desenvolvimento de infecção hospitalar em UTI, a carga de trabalho ...

INTRODUCCIÓN: Las tasas de desarrollo de infección o colonización por bacterias multirresistentes en unidades de cuidados intensivos son muy elevadas. El objetivo de este estudio fue determinar la posible asociación entre el riesgo de desarrollo de infecciones hospitalarias y el aumento de la carga de trabajo diaria del equipo de enfermería debido a la falta de personal en la unidad de cuidados intensivos. MÉTODOS: Ciento sesenta y ocho pacientes fueron incluidos. El volumen de la carga de trabajo y los procedimientos realizados en pacientes fueron evaluados con el uso de instrumentos de medidas como el Proyecto de Investigación en Enfermería (Project de Recherché en Nursing) y el Omega, respectivamente. Los criterios usados para definir infecciones fueron los definidos por los Centros de Control de Enfermedades. RESULTADOS: De los 168 pacientes, 91 (54,2%) eran del sexo femenino y 77 (45,8%) del sexo masculino. La edad media de las mujeres y de los hombres fueron 64,9 ± 6,2 y 63,1 ± 11,9 años, respectivamente. El tiempo medio de ingreso en la unidad de cuidados intensivos fue de 18,4 ± 6,1 días. Las bacterias multirresistentes fueron aisladas a partir de cultivos de 39 (23,2%) pacientes. El desarrollo de infección por bacterias multirresistentes fue correlacionado con el tiempo de ingreso, Omega 1, Omega 2, Omega 3, Omega total, PPE diario y PPE total (p < 0,05). No hubo correlación entre el desarrollo de la infección por bacterias multirresistentes y el sexo, la edad y las puntuaciones en el APACHE-II (p > 0,05). CONCLUSIÓN: El riesgo de desarrollo de infección hospitalaria en una unidad de cuidados intensivos está directamente relacionado con el aumento de la carga de trabajo de enfermería, las intervenciones practicadas y el tiempo de ingreso. La falta de personal en la unidad de cuidados intensivos es un problema de sanidad importante que afecta principalmente a los pacientes que necesitan esos cuidados. La infección hospitalaria ...

A novel protein-repellent dental composite containing 2-methacryloyloxyethyl phosphorylcholine / 国际口腔科学杂志·英文版

Secondary caries due to biofilm acids is a primary cause of dental composite restoration failure. To date, there have been no reports of dental composites that can repel protein adsorption and inhibit bacteria attachment. The objectives of this study were to develop a protein-repellent dental composite by incorporating 2-methacryloyloxyethyl phosphorylcholine (MPC) and to investigate for the first time the effects of MPC mass fraction on protein adsorption, bacteria attachment, biofilm growth, and mechanical properties. Composites were synthesized with 0 (control), 0.75%, 1.5%, 2.25%, 3%, 4.5% and 6% of MPC by mass. A commercial composite was also tested as a control. Mechanical properties were measured in three-point flexure. Protein adsorption onto the composite was determined by the microbicinchoninic acid method. A human saliva microcosm biofilm model was used. Early attachment at 4 h, biofilm at 2 days, live/dead staining and colony-forming units (CFUs) of biofilms grown on the composites were investigated. Composites with MPC of up to 3% had mechanical properties similar to those without MPC and those of the commercial control, whereas 4.5% and 6% MPC decreased the mechanical properties (P<0.05). Increasing MPC from 0 to 3% reduced the protein adsorption on composites (P<0.05). The composite with 3% MPC had protein adsorption that was 1/12 that of the control (P<0.05). Oral bacteria early attachment and biofilm growth were also greatly reduced on the composite with 3% MPC, compared to the control (P<0.05). In conclusion, incorporation of MPC into composites at 3% greatly reduced protein adsorption, bacteria attachment and biofilm CFUs, without compromising mechanical properties. Protein-repellent composites could help to repel bacteria attachment and plaque build-up to reduce secondary caries. The protein-repellent method might be applicable to other dental materials.

Miltefosina versus antimoniato de meglumina en el tratamiento de la leishmaniasis mucosa

El tratamiento convencional para la leishmaniasis tegumentaria es el antimoniato de meglumina, el cual presenta falla terapéutica creciente, producción de efectos adversos graves, y necesidad de administración parenteral, justificando la búsqueda de alternativas terapéuticas. Presentamos aquí los resultados preliminares de un ensayo clínico de fase II en pacientes con leishmaniasis mucosa, en el que se comparó la eficacia de miltefosina por vía oral con respecto a la del compuesto antimonial. La evaluación de la respuesta a los tratamientos se realizó mediante un seguimiento con videofibroscopia nasofaríngea, utilizándose un score de gravedad de lesiones mucosas para aplicar en cada momento del seguimiento de los pacientes. No se encontraron hasta ahora diferencias significativas entre el número de pacientes curados con miltefosina o con la quimioterapia convencional. Los resultados favorables de este trabajo sugieren que miltefosina podría constituir una alternativa terapéutica efectiva y segura en la región.

The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia / Termoterapia efectiva y más segura que la miltefosina en el tratamiento de la leishmaniasis cutánea en Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

En Colombia antimoniales pentavalentes y miltefosina son los medicamentos de primera elección para el tratamiento de la leishmaniosis cutánea; sin embargo, su toxicidad, duración (que lleva a problemas de adherencia), costo y la disminución de la sensibilidad de los parásitos a los mismos, hacen necesaria la búsqueda de nuevas alternativas de tratamiento para la leishmaniosis cutánea americana. A partir de resultados derivados de un ensayo clínico controlado abierto, aleatorizado, fase III, se comparó la eficacia y seguridad de la miltefosina con la de la termoterapia, para el tratamiento de la leishmaniosis cutánea en Colombia. Adultos pertenecientes al Ejército de Colombia participaron el estudio. Miltefosina, una cápsula de 50 mg tres veces día durante 28 días, vía oral (n = 145). Termoterapia (Thermomed®) aplicación de 50 °C/30" sobre la lesión y el área circundante (n = 149). Ambos grupos fueron comparables en características sociodemográficas, clínicas y parasitológicas. Eficacia de la miltefosina por protocolo 70% (85/122 pacientes) y 69% (85/145 pacientes) por intención a tratar. Termoterapia eficacia por protocolo 64% (86/134 pacientes) y 58% (86/149 pacientes) por intención a tratar. En miltefosina los eventos adversos fueron principalmente de tipo gastrointestinal y en termoterapia se encontró dolor en el sitio de la lesión luego del tratamiento. En el análisis de eficacia (intención a tratar y protocolo) no se encontró diferencia estadísticamente significativa entre los tratamientos evaluados. ClinicalTrials.gov: NCT00471705.