Drops of Lactiplantibacillus plantarum CRL 759 culture supernatant attenuates eyes inflammation induced by lipopolysaccharide.

Anti-inflammatory effect of soluble secreted compounds of probiotic bacteria was widely demonstrated as therapy for different inflammatory diseases, but was not investigated in inflammatory eye disorders. The aim of this study was to determine whether Lactiplantibacillus plantarum CRL759 cell-free supernatant reduced inflammatory parameters and clinical signs in ocular inflammations. First, we evaluated the effect of L. plantarum CRL759 supernatant in vitro on human retinal cell line, ARPE-19 cells, stimulated with lipopolysaccharide (LPS). Then, we investigated in vivo its capacity to decrease inflammation by local administration on the eyes of mice with endotoxin induced inflammation. In vitro assays demonstrated that L. plantarum CRL759 supernatant reduced the production of interleukin (IL)-6, IL-8, nitric oxide and thiobarbituric acid reactive substances in LPS-stimulated ARPE-19 cells. Our in vivo data proved that L. plantarum supernatant significantly reduced the clinical score of endotoxin treated mice and diminished levels of tumour necrosis factor alpha, interferon gamma and protein concentration in aqueous humour. Histological examination showed reduction of infiltrating inflammatory cells in the posterior segment of the eyes. As far as we know, this is the first report showing that Lactobacillus spp. supernatant administered as drops reduces some parameters of ocular inflammation. This promising strategy is safe and could alleviate symptoms and signs of ocular inflammation in people that are refractories to the conventional therapies.

Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma. / Insulina tópica en queratopatía neurotrófica tras resección de neurinoma del acústico.

CASE REPORT: A patient with a history of surgical resection of an acoustic neuroma presented with involvement of both the left facial nerve and the left trigeminal nerve. She initially consulted for exposure keratitis, but two weeks later presented with an infectious keratitis. After taking the corneal sample, she presented with persistent epithelial defect, which did not respond to medical management. Topical insulin was indicated, and a decrease in the area of the lesion was seen in the following 5 days. A therapeutic contact lens was also placed at that time and finally, two weeks after the initiation of insulin, the epithelial defect completely closed. DISCUSSION: This was a complex case due to the confluence of facial paralysis, neurotrophic keratitis, and infectious keratitis, which finally had a successful outcome. Topical insulin can be an effective adjuvant therapy in cases of neurotrophic ulcers that do not respond to standard therapy.

Effects of a respiratory functional training program on pain and sleep quality in patients with fibromyalgia: A pilot study.

OBJECTIVE: To evaluate the effect of 8-week respiratory functional training program on pain tolerance, sleep, and urinary antioxidant and cortisol levels in 18 patients with fibromyalgia. METHODS: Participants underwent a 12-week intervention: 4 weeks as control and 8 weeks of breathing exercises. Pain tolerance assay was done by using an algometer, whereas sleep quality was evaluated by actigraphy and by the Pittsburgh Sleep Quality Index. Cortisol and antioxidant levels were determined using commercial assay kits. RESULTS: Increases in the pain tolerance threshold were detected in the occiput point after one month of intervention as well as in the low cervical and second rib points after one and two months. Actigraphy revealed a decrease in sleep latency, whereas sleep questionnaire showed improvements in sleep quality, sleep duration and sleep efficiency. No changes in cortisol and antioxidant levels were detected. CONCLUSION: The 8-week breathing exercise intervention reduced pain and improved sleep quality.

Application of theoretical methods to increase succinate production in engineered strains.

Computational methods have enabled the discovery of non-intuitive strategies to enhance the production of a variety of target molecules. In the case of succinate production, reviews covering the topic have not yet analyzed the impact and future potential that such methods may have. In this work, we review the application of computational methods to the production of succinic acid. We found that while a total of 26 theoretical studies were published between 2002 and 2016, only 10 studies reported the successful experimental implementation of any kind of theoretical knowledge. None of the experimental studies reported an exact application of the computational predictions. However, the combination of computational analysis with complementary strategies, such as directed evolution and comparative genome analysis, serves as a proof of concept and demonstrates that successful metabolic engineering can be guided by rational computational methods.

Sacral nerve stimulation in the treatment of severe faecal incontinence: long-term clinical, manometric and quality of life results.

BACKGROUND: Faecal incontinence (FI) is a complex and multifactorial health problem. Treatment has to be individualised, analysing the aetiology and gravity in every case. Sacral nerve stimulation (SNS) has been shown to effectively improve treatment of FI. METHODS: Fifty patients with severe FI treated with SNS between March 2002 and December 2010 were analysed. Preoperative assessment included physical examination, anorectal manometry and anal endosonography. Anal continence was evaluated using the Wexner continence grading system. Quality of life was evaluated using the Fecal Incontinence Quality of life Scale (FIQLS). Follow-up appointments were scheduled at 1, 6 and 12 months and annually thereafter. Wexner score, FIQLS and the ability to defer defecation were assessed at each visit. RESULTS: Fifty patients underwent a permanent implant. The overall mean follow-up period was 55.52 ± 31.84 months. After 6 months, SNS significantly improved FI and positively impacted quality of life, as evidence by significant improvements in all 4 scales of the FIQLS. Anorectal manometry showed a trend towards an increase in maximum resting pressure and maximum pressure. After the first assessment at 6 months, Wexner score and FIQLS remained stable. Ability to defer defecation was also maintained. During follow-up, 3 patients (6 %) experienced implant site pain and episodes of extremity pain and paresthesias that were refractory to medical management and required device explantation. The implant site infection rate was 2 %. CONCLUSIONS: Analysis of our long-term results confirms the safety and effectiveness of SNS in the management of patients with FI.

Effects of parenteral nutrition formulas on plasma lipid profile in children with bone marrow transplantation.

BACKGROUND/AIMS: Children undergoing bone marrow transplantation (BMT) often require parenteral nutrition (PN). This is a comparative study of plasma lipid profiles in BMT children after fish oil or soybean PN. METHODS: A total of 14 children with BMT requiring PN for at least 10 days were recruited during 24 months. They were randomized to receive a lipid emulsion enriched with ω3 polyunsaturated fatty acid, or soybean oil. Clinical monitoring was performed. Blood samples were collected before and after administration of PN to analyze the lipid profile. RESULTS: There were no complications associated with PN. The increase in TG levels was more pronounced after administration of an enriched ω3 emulsion and the decrease in cHDL and apo A was greater after administration of soybean. The ω3 group showed an increase in eicosapentaenoic and a decrease in arachidonic acids compared to the soybean group. Both groups showed similar levels of linolenic acid. CONCLUSION: PN with soybean or ω3 emulsions for 10 days is safe in children. However, research in children are necessary in order to examine the impact of the duration of PN and the type of lipid formula used, and determine their health benefits in relation to the fatty acid profile.

Mineralogical controls on aluminum and magnesium in uranium mill tailings: Key Lake, Saskatchewan, Canada.

The mineralogy and evolution of Al and Mg in U mill tailings are poorly understood. Elemental analyses (ICP-MS) of both solid and aqueous phases show that precipitation of large masses of secondary Al and Mg mineral phases occurs throughout the raffinate neutralization process (pH 1-11) at the Key Lake U mill, Saskatchewan, Canada. Data from a suite of analytical methods (ICP-MS, EMPA, laboratory- and synchrotron-based XRD, ATR-IR, Raman, TEM, EDX, ED) and equilibrium thermodynamic modeling showed that nanoparticle-sized, spongy, porous, Mg-Al hydrotalcite is the dominant mineralogical control on Al and Mg in the neutralized raffinate (pH ≥ 6.7). The presence of this secondary Mg-Al hydrotalcite in mineral samples of both fresh and 15-year-old tailings indicates that the Mg-Al hydrotalcite is geochemically stable, even after >16 years in the oxic tailings body. Data shows an association between the Mg-Al hydrotalcite and both As and Ni and point to this Mg-Al hydrotalcite exerting a mineralogical control on the solubility of these contaminants.

[Budget impact of growth hormone treatment during the transition phase between childhood and adulthood]. / Impacto presupuestario de la utilización de hormona de crecimiento de la edad pediátrica a la adulta.

OBJECTIVE: To estimate the budget impact of somatrophin (Genotonorm) use in growth hormone deficiency (GHD) patients during the transition between childhood and adulthood. METHOD: A budget impact model was designed under the Spanish National Health System with a 5-year time horizon. Calculations of susceptible patients were based on disease prevalence (0.02%) applied to Spanish population. From total GHD cases, 60% was considered persistent and treatment candidates. An expert panel assumed that 20% of candidates would reject the treatment and 8% would withdraw therapy annually. Considered costs included: therapy costs, diagnosis (test and medical visit) and follow-up cost. RESULTS: There would be 49, 93, 132, 186 and 199 patients undergoing treatment each year (2010-2014). The total impact of Genotonorm use during the transition phase would be €367,691, €655,430, €1044,874, €1334,059, and €1594,670 for years 1 to 5. The average annual cost per patient would be €7506, €7059, €7903, €7960, €7995. CONCLUSIONS: GHD treatment during the transition phase in Spain poses an annual average layout of €7684/patient.

[Comparative study of the effectiveness two of hyperoxygenated fatty acids in the treatment of grade I ulcers in geriatric hospitalized patients]. / Estudio comparativo de efectividad de dos ácidos grasos hiperoxigenados en el tratamiento de úlceras de grado I en pacientes geriátricos hospitalizados.

OBJECTIVE: To evaluate whether there is equivalence between two treatments for grade I ulcers with a base of hyperoxygenated fatty acids, AGHO and Mepentol: AGHO and phytotherapy. METHOD: A randomized, controlled, triple blind clinical trial was conducted with patients admitted at the Elderly Ward at San Carlos Hospital in Madrid between November 2006 and January 2008. There were two treatment groups: Experimental and control. A theoretical limit of 15% was determined between both groups. We took a random sample of patients admitted to the Elderly Ward, which produced a sample of 151 sores. The control group received treatment with Mepentol and the experimental group received AGHO. The assignment to the group was at random. The output variable was healing of erythema within the first 72h. We calculated the absolute difference in the incidence of healing between both treatments with a level of confidence of 95%. RESULTS: The sample at the end of the study was 148 (72 control and 76 experimental). There was a healing incidence of 55.6% in the control group and 69.7% in the experimental group (p=0.074). The difference in the incidence of healing between both treatments was 14% (95% CI: 29% to -1%). The upper limit of the confidence interval of the difference is outside the margin of equivalence. CONCLUSIONS: We cannot conclude that the treatment with AGHO fatty acids is equivalent to Mepentol treatment. With both treatments the healing is clinically significant.

Phase I/II trial of irinotecan plus high-dose 5-fluorouracil (TTD regimen) as first-line chemotherapy in advanced colorectal cancer.

BACKGROUND: We conducted a phase I/II study of weekly irinotecan [30 min intravenous (i.v.) infusion] combined with 5-fluorouracil (5-FU 3 g/m(2) weekly 48 h i.v. infusion, TTD regimen) as first-line chemotherapy for patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: The maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in the treatment of gastrointestinal solid tumors (in phase I), and the antitumor activity and toxicity of the recommended phase I dose (in phase II) were determined. RESULTS: Diarrhea was the DLT, and irinotecan 80 mg/m(2) plus 5-FU 3 g/m(2) was the recommended phase I dose. In phase II, the confirmed response rate was 44% [95% confidence interval (CI) 29% to 59%] and the median overall survival was 23.8 months. However, grade 3/4 diarrhea affected 59% of patients and led to withdrawal of three patients. A second cohort of patients studied using the same schedule but with a reduced 5-FU starting dose of 2.25 g/m(2) showed improved tolerance (the incidence of grade 4 diarrhea decreased from 28% to 11% and overall grade 3/4 diarrhea to 56%, with no patient withdrawals) but the confirmed response rate was 28% (95% CI 14% to 45%) and median overall survival was 17.2 months. CONCLUSIONS: We found weekly irinotecan 80 mg/m(2) plus TTD regimen (5-FU 2.25 g/m(2) given as 48-h i.v. infusion) to be a feasible and active combined chemotherapy for the first-line treatment of advanced colorectal cancer.

Cytostatic activity of Achillea ageratum L.

The cytostatic activity of a chloroform extract and two isolated compounds from Achillea ageratum L. (Asteraceae) was determined in vitro against Hep-2 and McCoy cells. The chloroform extract exhibited a high degree of growth inhibition compared with the values obtained with the 6-mercaptopurine (positive control) against both cultures. Stigmasterol and beta-sitosterol, isolated from the chloroform extract, showed a high degree of growth inhibition.

Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models.

Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant, used in folk medicine for the treatment of several antiinflammatory disorders. A preliminary phytochemical study showed that the hexane extract is rich in terpenic compounds. Chromatographic fractionation of this extract yielded: alpha-cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95%) clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5)24-stigmastadienol and delta 7-avenasterol. The topical antiinflammatory activity of the hexane extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0-tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple applications of the phlogistic agent. Both reduced the oedema in a similar proportion in the two model assays (acute and chronic). Meloperoxidase activity was strongly reduced by both the extract and the compound, in the acute but not the chronic model. These results indicate that the leaves of Eryngium foetidum L may be effective against topical inflammation processes. Stigmasterol also exerts a significant topical antiinflammatory activity although it cannot be considered to be a major antiinflammatory agent, therefore other bioactive components are probably involved in the activity of the hexane extract.

Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models

Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant used in folk medicine for the treatment of several antiinflammatory disorders. A preliminary phytochemical study showed that the hexane extract is rich in terpenic compounds. Chromatographic fractionation of this extract yielded: alpha-cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95 percent) clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5) 24-stigmastadienol and delta 7-avenasterol. The topical antiinflammatory activity of the hexane extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0-tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple applications of the phlogistic agent. Both reduced the oedema in a similar proportion in the two model assays (acute and chronic). Meloperoxidase activity was strongly reduced by both the extract and the compound, in the acute but not the chronic model. These results indicate that the leaves of Eryngium foetidum L may be effective against topical inflammation processes. Stigmasterol also exerts a significant topical antiinflammatory activity although it cannot be considered to be a major antiinflammatory agent, therefore other bioactive components are probably involved in the activity of the hexane extract.(AU)

Study of the topical anti-inflammatory activity of Achillea ageratum on chronic and acute inflammation models.

We have produced a chloroform extract from Achillea which includes stigmasterol and sitosterol. By comparing it with the pure compounds an anti-inflammatory effect (with mouse ears) is assumed. The topical anti-inflammatory effect of the chloroform extract from Achillea ageratum (Asteraceae) and of stigmasterol and beta-sitosterol, isolated of this extract has been evaluated, against to 12-0-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema, using simple (acute model) and multiple applications (chronic model) of the phlogistic agent. Myeloperoxydase activity also was studied in the inflamed ears. In the acute model the extract exerted a dose-dependent effect. All the doses assayed (1, 3 and 5 mg/ear) significantly reduced the edema (50%, 66% and 82%, respectively). The isolated sterols stigmasterol and beta-sitosterol (with doses of 0.5 mg/ear) had similar effect as the extract with doses of 1 and 3 mg (59% and 65% respectively). In the chronic model the anti-inflammatory effect generally was a more moderate one. The highest dose of the extract decreased the edema reduction to 26% with the highest dose of the extract applied. With the compounds the effect decreased to 36% with stigmasterol, and 40.6% with beta-sitosterol. Myeloperoxydase activity (MPO) was reduced by the extract and the compounds in the acute model, however, in the chronic edema, the enzyme inhibition was very weak with all treatments even with the standard substance. These results indicate that the chloroform extract of Achillea ageratum and some of the its components stigmasterol and beta-sitosterol are more effective as topical anti-inflammatory agents in acute than in the chronic process and their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue.

Angiodysplasia of the colon in children.

Angiodysplasia of the colon as a cause of lower intestinal bleeding is diagnosed frequently in the elderly, with defined clinical characteristics. In the pediatric population there is little experience; only six cases have been reported. The present study evaluates the clinical, radiological, and surgical aspects of nine children with angiodysplasia of the colon who were treated at the National Institute of Pediatrics in Mexico City between 1970 and 1993. The mean age of clinical onset was 2.3 years. In six patients, symptoms appeared before the first year of life. Lower intestinal bleeding and severe anemia were present in all cases. The diagnosis and localization of the lesions were established by selective visceral angiography. Six patients were treated by operative resection of the affected colonic segments. For four patients with lesions in the rectum and sigmoid, a Swenson pull-through was performed. In one patient the lesion was recurrent because of incomplete resection. Follow-up ranges from 8 months to 4 years; all patients have had normal hemoglobin levels and negative stool results. Unlike in the elderly and the cases reported in the literature, the left hemicolon was the most frequently involved area.

Endorectal pull-through with conservation of the rectal mucosa: experimental study.

The present experimental work was designed to study an abdominoanal pull-through technique, with conservation of rectal mucosa. Continence was evaluated from clinical, radiologic, and histopathologic standpoints. The animals defecated normally. A good retention of barium was seen in the radiologic enema. On the reexploration of the animals, we found a distal dehiscence with elevation of the intussuscepted stump towards the rectum in all. A reepithelization process of serosa of the intussuscepted segment was noted.