High efficacy and economical procedure of oral vaccination against Lactococcus garvieae/Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

The present study was aimed to examine the efficacy of chitosan-alginate coated vaccines against pathogenicity of Lactococcus garvieae and Streptococcus iniae in rainbow trout. Fish were divided into four groups including: Group A: fish immunized by chitosan-alginate coated vaccine, Group B: fish immunized by non-coated vaccine, Group C: fish feed by chitosan-alginate coated pellets without vaccine and Group D: fish feed by basic diet (non-coated and without vaccine). In groups A and B, the vaccination was carried out for 14 days and after that supplemented with fundamental diet (control diet). Comparable to groups A and B, fish of group C were also fed 14 days with test diets and after that fed control food. On day 0, 20, 40 and 60 of the experiment, serum samples were given. Fish have been challenged with live L. garvieae and S. iniae after 60 days. The levels of bactericidal activity and complement activity among innate immunity components extended on day 20 of the research and after that decreased in group A and B (P < 0.05) all through the examination. The relative expression of IL-6 and IgM in groups A and B extended on examination day 20. The expression of these genes illustrated no advancements in different groups in during the examination (P > 0.05). In group A, the serum antibody titer against L. garvieae and S. iniae broadly raised on day 40 and 60 of examination, whereas in group B, the immune response titer against S. iniae and L. garvieae illustrated a significant elevation on day 60 of the trial (P < 0.05). After challenge with live bacteria, survival rate of 83 ± 9.1%(challenged with S. iniae) and 72.18 ± 9.8% (challenged with L. garvieae) were gotten independently in group A, which were higher than survival of other exploratory groups (P < 0.05). In conclusion, the results of the present examination appear that the orally vaccination of rainbow trout with chitosan-alginate covered vaccine stimulates immunity system and also efficiently protects rainbow trout against Lactococcus garvieae and Streptococcus iniae.

In vitro and in vivo toxicity assessment of alginate/eudragit S 100-enclosed chitosan-calcium phosphate-loaded iron saturated bovine lactoferrin nanocapsules (Fe-bLf NCs).

Lactoferrin has been known to have antimicrobial properties. This research was conducted to investigate the toxicity of Alginate/EUDRAGIT® S 100-enclosed chitosan-calcium phosphate-loaded Fe-bLf nanocapsules (NCs) by in vitro and in vivo assays. Brine shrimp lethality assay showed that the LC50 value of NCs was more than 1mg/mL which indicated that NCs was not toxic to Brine shrimp. However, the LC50 values for the positive control potassium dichromate at 24h is 64.15µg/mL, which was demostrated the toxic effect against the brine shrimp. MTT cytotoxicity assay also revealed that NCs was not toxic against non-cancerous Vero cell line with IC50 values of 536µg/mL. Genotoxicity studies by comet assay on Vero cells revealed that NCs exerted no significant genotoxic at 100µg/mL without tail or shorter comet tail. Allium cepa root assay carried out at 125, 250, 500 and 1000µg/mL for 24h revealed that the NCs was destitute of significant genotoxic effect under experimental conditions. The results show that there is no significant difference (p>0.05) in mitotic index between the deionized water and NCs treated Allium cepa root tip cells. In conclusion, no toxicity was observed in NCs in this study. Therefore, nontoxic NCs has the good potential to develop as a therapeutic agent.

Reactogenicity and safety assessment of an attenuated nanovaccine against scorpion envenomation: Preclinical study.

An attenuated nanovaccine (Nps - V∗) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps - V∗ nanovaccine developed against Androctonus australis hector (Aah) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100µg of irradiated Aah venom (V∗) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c) route. The local reactogenicity was evaluated by dermal Draize observations and skin tissue analysis at the injection site of vaccinated rabbits with 250 or 500µg of V∗-loaded into Nps. All animals gained weight and had normal food consumption during the study. Additionally, results showed that the nanoformulation Nps - V∗ did not cause clinical evidence of systemic toxicity in mice or rabbits, a transient edema/erythema at the injection site was only recorded as treatment-related reactogenicity. These results indicated a favorable safety profile for Nps - V∗ and supported its use in superior animal tests, then in a Phase 1 clinical trial.

A Randomized Controlled Trial on the Outcome in Comparing an Alginate Silver Dressing With a Conventional Treatment of a Necrotizing Fasciitis Wound.

Necrotizing fasciitis (NF) is a high morbidity and mortality disease and also demands high economic resources. The standard treatment of NF is surgical debridement and proper dressing for wound bed preparation. The efficacy of silver alginate dressing can inhibit the growth of microorganisms and keep the environment clean for wound bed preparation. However an optimal dressing to manage such wounds has yet to emerge. NF patients who were admitted between April 2013 and May 2016 were randomized to have wound dressing using either silver dressing (Ag group) or normal saline solution gauze (NSS group). The 4 main outcomes for comparison between the 2 groups were the duration of wound bed preparation, total cost during hospital stay, the duration of hospital stay, and the pain score. Thirty-nine patients were included in the study: 19 patients in the NSS group and 20 patients in the Ag group. The mean duration of wound bed preparation in the NSS group was 31.87 days, and in Ag group it was 21.39 days, but this trend was not statistically significant ( P = .057). The mean cost of treatment in the NSS and Ag groups was not significantly different ( P = .434; US$3308.83 and US$2647.82, respectively). The duration of hospital days in the 2 groups was not significantly different either (29.19 days [NSS group] and 20.99 days [Ag group]; P = .222). The pain score was significantly lower in the Ag group than those in the NSS group. Although silver dressing seems to be expensive, the cost of total treatment during hospital stay and the duration of hospital stay were not significantly different between groups. However, the mean duration of wound bed preparation seems to trend favoring toward the silver dressing group.

Medical and Economic Evaluation of FOREseal Bioabsorbable Reinforcement Sleeves Compared With Current Standard of Care for Reducing Air Leakage Duration After Lung Resection for Malignancy: A Randomized Trial.

OBJECTIVE: The objective of this study was to determine the efficacy of alginate staple-line reinforcement of fissure openings as compared with stapling alone, with or without tissue sealant or glue, in reducing the incidence and duration of air leakage after pulmonary lobectomy for malignancy. SUMMARY BACKGROUND DATA: No randomized trial evaluating alginate staple-line reinforcement has been performed to date. METHODS: The Staple-line Reinforcement for Prevention of Pulmonary Air Leakage study was a multicenter randomized trial, with blinded evaluation of endpoints. Patients over 18 years of age scheduled for elective open lobectomy or bilobectomy for malignancy were eligible for enrollment. At thoracotomy, patients were deemed ineligible if an unanticipated pneumonectomy was indicated, or if air leakage occurred after the liberation of pleural adhesions. Otherwise, if the fissure was incomplete or the lung had an emphysematous appearance, patients were randomized to either standard management or interventional procedure consisting of fissure opening with linear cutting staplers buttressed with paired alginate sleeves (FOREseal). The number of eligible patients necessary in each randomization arm was estimated to be 190, and an outcomes analysis was performed on an intention-to-treat basis. RESULTS: Of the 611 patients consented to study enrollment, 380 met the inclusion criteria and were randomized. Based on an intention-to-treat analysis, the primary endpoint of air leak duration was not different between the 2 groups: 1 day (range: 0-2 d) in the FOREseal group and 1 day (range: 0-3 d) in the control group (P = 0.8357). In addition, the 2 groups were similar in terms of the proportion of patients presenting with prolonged air leakage (7.8% in the FOREseal group vs 11.3% in the control group, P = 0.264) and the average duration of chest drainage (P = 0.107). Procedure costs were comparable for both groups. CONCLUSIONS: FOREseal did not demonstrate a significant advantage over standard treatment alone.

Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment.

INTRODUCTION: Periodontal disease broadly defines group of conditions in which the supportive structure of the tooth (periodontium) is destroyed. Recent studies suggested that the anti-diabetic drug metformin hydrochloride (MF) has an osteogenic effect and is beneficial for the management of periodontitis. OBJECTIVE: Development of strong mucoadhesive multiple layer film loading small dose of MF for intra-pocket application. METHODOLOGY: Multiple layer film was developed by double casting followed by compression method. Either 6% carboxy methyl cellulose sodium (CMC) or sodium alginate (ALG) constituted the inner drug (0.6%) loaded layer. Thiolated sodium alginate (TSA; 2 or 4%) constituted the outer drug free layers to enhance mucoadhesion and achieve controlled drug release. Optimized formulation was assessed clinically on 20 subjects. RESULTS: Films were uniform, thin and hard enough for easy insertion into periodontal pockets. Based on water uptake and in vitro drug release, CMC based film with 4% TSA as an outer layer was the optimized formulation with enhanced mucoadhesion and controlled drug release (83.73% over 12 h). SEM showed the effective fabrication of the triple layer film in which connective lines between the layers could be observed. FTIR examination suggests possibility of hydrogen bonding between the -NH groups of metformin and -OH groups of CMC. DSC revealed the presence of MF mainly in the amorphous form. Clinical results indicated improvement of all clinical parameters six months post treatment. CONCLUSION: The results suggested that local application of the mucoadhesive multiple layer films loaded with metformin hydrochloride was able to manage moderate chronic periodontitis.

Evaluación del gel antiadherencial post quirúrgico: hialuronato de sodio más carboximetilcelulosa y alginato / Evaluation of post-surgical antiadherence gel: sodium hyaluronate plus carboxymethylcellulose and alginate

INTRODUCCIÓN: Antecedentes: Las adherencias son bandas de tejido similar el tejido cicatricial que se forman entre superfícies dentro del organismo y hacen que estas se unan. Se forman más frecuentemente en el abdomen y pelvis después de cirugias intestinales o de los órganos femeninos, estas producen diversar molestias como distención o hinchazón abdominal, estreñimiento, náuseas y vomitos, incluso dolor pélvico intenso y crónico. Las adherencias son parte de un proceso fisiopatológico desencadenado o en respuesta al corte, isquemia, abrasión del peritoneo durante la cirugia. Las zonas alteradas sufren de regeneración mesotelial y fibrosis resultando en la formación de adherencias entre los tejidos serosos dañados. Las adherencias pueden tener un efecto beneficioso, ya que permite neovscularización de zonas isquémicas del intestino, tales como en las anastomosis, pero generalmente ocasionan probelmas cuando se vuelven excesivas. Las adherencias son la principal causa de obstrucción intestinal que causa el 70% de readmisiones hospitalarias. El hialuronato de sodio más carboximetilcelulosa, es descrito como un agente antiadherente no tóxico, no inmunogénico y biocompatible que reduce la incidencia y extensión de las adherencias postoperatorias. Compuesto de hialuronato de sodio y carboximetilcelulosa está modificado químicamente para retardar su tasa de degradación y deputación después de entrar en contato con el organismo. METODOLOGÍA: Se realizó una búsqueda bibliográfica de la literatura con respecto a la eficacia y seguridad del uso del Gel Antiadherencial Post quirúrgico. Se seleccionaron artículos científicos: evaluación de tecnologías santiarias, revisiones sistemáticas, met-análisis y ensayos clínicos. Se realizó una búsqueda dentro de la información generada por grupos que realizan revisiones sistemáticas, evaluación de tencologías sanitarias y guías de práctica clínica, tales como The Cochrane Library y The National Institute for Health and Care Excelence (NICE). Además, se hizo una búsqueda en www.clinicaltrials.gov, para poder identificar ensayos aún en elaboración o que no hayan sido publicados. CONCLUSIONES: Las investigaciones publicadas hasta marzo del 2016 son insuficientes para poder determinar la eficacia y seguridad del gel antiadherencial postquirúrgico (hialuronato de sodio más carboximetilcelulosa). Los resultados de los estudios preclínicos son discordantes con los ensayos clínicos realizados posteriomente. El Instituto de Tecnologías en Salud e Investigación-IETSI, no aprueba el uso del gel antiadherencial en sus presentaciones: (hialuronato de sodio más carboximetilcelulosa, alginato o la combinación de hialuronato de sodio más carboximetilcelulosa y alginato; para la reducción de adherencias abdominlaes y pélvicas.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

OBJECTIVES: Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. METHODS: Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. RESULTS: Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05). CONCLUSIONS: Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

MR-guided portal vein delivery and monitoring of magnetocapsules: assessment of physiologic effects on the liver.

PURPOSE: The authors previously developed magnetic resonance (MR)-trackable magnetocapsules (MCs) that can simultaneously immunoprotect human islet cells and noninvasively monitor portal delivery and engraftment in real time with MR imaging. This study was designed to assess the physiologic effects of the delivery of a clinical dose of MCs (140,000 capsules) into the portal vein (PV) in swine over a 1-month period. MATERIALS AND METHODS: MCs were formed by using clinical-grade alginate mixed with a clinically applicable dosage of ferumoxide. Percutaneous access into the PV was obtained by using a custom-built, MR-trackable needle, and 140,000 MCs were delivered under MR guidance in five swine. Portal pressures and liver function data were obtained over a 4-week period. RESULTS: A transient increase in portal pressure occurred immediately after MC delivery that returned to normal levels by 4 weeks after MC delivery. Liver function test results were normal during the entire period, and the appearance of the MCs on MR imaging did not change. CONCLUSIONS: A clinically applicable dose of 140,000 MCs has no adverse effects on portal pressures or liver function in this normal swine model during the first month after delivery.

Randomized controlled trial of pelvic calcium alginate following rectal cancer surgery.

BACKGROUND: The aim of this randomized controlled trial was to assess the possible benefit of using a new haemostatic agent (Hémoionic) in the pelvic cavity in sphincter-saving surgery for rectal cancer. METHODS: Eighty-five patients undergoing elective sphincter-saving rectal resection for cancer were randomized into Hémoionic (41 patients) and control (44) groups. In both groups, a pelvic suction drain was left in place for as long as the daily output exceeded 20 ml. The primary endpoint was volume of fluid collected by the suction drain; secondary endpoints were duration of drainage, and postoperative mortality and morbidity rates. RESULTS: The mean total drainage volume was significantly lower in the Hémoionic group (453 ml versus 758 ml in control group; P = 0.031). There was no significant difference between groups in duration of drainage and morbidity. The mortality rate was four of 41 in the Hémoioni group and one of 44 in the control group (P = 0.192). CONCLUSION: Hémoionic may reduce the drainage volume after sphincter-saving surgery for rectal cancer, but offers no clinical advantage. REGISTRATION NUMBER: ISRCTN79721331 (http://www.isrctn.org).

Assessment of the antimicrobial effectiveness of a new silver alginate wound dressing: a RCT.

OBJECTIVE: To compare the efficacy and tolerability of a new ionic silver alginate matrix (Askina Calgitrol Ag) with that of a standard silver-free alginate dressing (Algosteril). METHOD: Patients with locally infected chronic wounds (pressure ulcers, venous or mixed aetiology leg ulcers, diabetic foot ulcers) or acute wounds were eligible for this prospective, open-label, controlled and randomised trial. Patients were randomised to receive one of the two dressings for a two-week period. Criteria of efficacy were based on the evolution, from day 1 to day 15, of local signs of infection using a clinical score ranging from 0 to 18, and the evolution of the bacteriological status for each wound. The latter was determined by (blind) bacteriological examinations of results obtained from two biopsies performed at days 1 and 15. A three-point scale (deterioration, unchanged, improvement) was also used. Acceptability, usefulness and tolerance were also assessed. RESULTS: Forty-two patients (20 women and 22 men, 68.9 +/- 18.8 and 66.5 +/- 15.7 years old respectively) were randomly assigned to receive either Askina Calgitrol Ag (n=20) or Algosteril (n=22). Most had chronic wounds such as pressure ulcers (57%) or venous or mixed aetiology leg ulcers and diabetic foot ulcers (29%); few had acute wounds (14%). Clinical scores of infection were comparable in both groups at inclusion, 8.9 +/- 2.4 and 8.6 +/- 3.2 in the Askina Calgitrol Ag group and the Algosteril group respectively (not significant), but decreased significantly in both groups at day 15, 3.8 +/- 2.9 in the Askina Calgitrol Ag group (p=0.001) and 3.8 +/- 3.4 in the Algosteril group (p=0.007). There was no significant difference between the two groups at day 15. Although there was also no significant difference in bacteriological status between the treatment groups, a trend in favour of Askina Calgitrol Ag was found for the relative risk of improvement, especially in patients who were not treated with antibiotics either at the beginning of the study or during it. No differences between groups were observed regarding local tolerance, acceptability and usefulness of the dressings. CONCLUSION: The regression of local signs of infection, local tolerance, acceptability and usefulness were similar for the two dressings. However, Askina Calgitrol Ag improved the bacteriological status of the wounds. Further trials are required to show that it has a positive impact on the healing process.

Targeted delivery of chemotherapeutic agents using improved radiosensitive liquid core microcapsules and assessment of their antitumor effect.

PURPOSE: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. METHODS AND MATERIALS: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 microg) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl(2) solution supplemented with 0-0.01% yttrium. These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy (60)Co gamma-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. RESULTS: Microcapsules that had been polymerized using a 4.34% CaCl(2) solution supplemented with 5.0 x 10(-3)% (10(-3)% meant or 10%(-3)) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. CONCLUSION: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.

Assessment and management of fungating wounds: a review.

Fingating wounds always present a management challenge. Not only is it often difficult to manage the physical aspects of the wound - pain, bleeding, exudate and odour - but also the psychological impact of a fungating wound on the patient and their family or carers is often considerable. This review examines current practice in relation to fungating wounds, and emphasizes the central important of assessment, communication and sensitivity in nursing management.

Economic evaluation of the treatment of chronic wounds: hydroactive wound dressings in combination with enzymatic ointment versus gauze dressings in patients with pressure ulcer and venous leg ulcer in Germany.

OBJECTIVE: The treatment costs for pressure ulcers and venous leg ulcers were estimated based on the hospital administrator's perspective in Germany. DESIGN: A spreadsheet model using input data from various hospitals in Germany was developed. INTERVENTIONS: Five currently used treatment strategies were analysed: gauze, impregnated gauze, calcium alginate and hydroactive wound dressing with enzymatic ointment. PARTICIPANTS: All cases used for and in the analysis were treated in the inpatient setting (4 hospitals and 120 patients were included). MAIN OUTCOME MEASURES AND RESULTS: The outcome distributions were calculated using the Monte Carlo method. For the whole treatment process, the attributable costs for the hospital were calculated for different cases (severity) and all treatment strategies (1997 values). The costs for treatment with gauze were the highest, whereas the costs for treatment with hydroactive wound dressings and enzymatic ointment were the lowest. The relation between personnel and material costs for gauze is approximately 95 to 5% and for hydroactive wound dressings 67 to 33%, respectively. The cost savings per case were between 1196 deutschmark (DM) and DM9826 using hydroactive wound dressings instead of gauze dressings (depending on the severity of the pressure ulcer), and between DM135 and DM677 for venous leg ulcers. The results were robust and did not change in any performed sensitivity analysis (parameter: 'personnel costs per minute', 'time required for changing a wound dressing', 'total number of wound dressing changes'). CONCLUSIONS: Despite the higher material costs of the hydroactive wound dressings in combination with enzymatic wound cleaning compared with other wound dressings, they should be recommended for the treatment of pressure ulcers and venous leg ulcers. This therapy alternative brings about significant reductions in total costs for hospitals because of significant reductions in personnel costs and the duration of treatment.