In vivo efficiency of antimicrobial inorganic bone grafts in osteomyelitis treatments.

The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 µm vs. macroporosity, i.e. >5 µm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy.

Axillary brachial plexus block duration with mepivacaine in patients with chronic renal failure. Case-control study. / Duración de bloqueo axilar con mepivacaína 1,5% en pacientes con insuficiencia renal crónica programados para fístula arteriovenosa. Estudio casos-controles.

INTRODUCTION: Regional anaesthesia is commonly preferred for arteriovenous fistula (AVF) creation. Previous studies suggest a shorter block duration in patients with chronic renal failure, maybe because of the changes in regional blood flow. The aim of our study was to evaluate the duration of the axillary block with 1.5% mepivacaine in patients with chronic renal failure scheduled for AVF compared with healthy controls. METHODS: Patients scheduled for AVF creation for the first time (GIRC) were included. They were compared with patients without renal failure (GC), with similar anthropometric characteristics. Ultrasound-guided axillary blocks with 20mL of 1.5% mepivacaine were performed on all patients. We evaluated onset time, humeral artery diameter and blood flow before and after the block, as well as the block duration. RESULTS: Twenty-three patients (GIRC: 12 and GC: 11) were included. No differences between groups were observed in block duration (GIRC: 227±43min vs GC: 229±27min; P=.781), or in onset time (GIRC: 13±5min vs GC: 12.2±3min; P=.477). The humeral blood flow before and after block was significantly lower in the GIRC (pre-block: GIRC: 52±21ml/min GC: 100±62ml/min; P=.034 and p ost block: GIRC: 130±57ml/min and GC: 274±182ml/min; P=.010). There was no significant correlation between the duration of the block and the preblock humeral blood flow (Spearman Rho: 0.106; P=.657) or the postblock humeral blood flow (Spearman Rho: 0.267; P=.254). CONCLUSION: The duration of the axillary block with 1.5% mepivacaine in patients with chronic renal failure was similar to that of the control patients. The duration of axillary brachial plexus block seems not to be related to changes in regional blood flow.

Secondary procedures in thoracic aorta.

Secondary procedures for thoracic aorta are very demanding to the patient, with significantly high perioperative mortality and morbidity. The aim of this paper was to review the most remarkable secondary procedures following open and endorepairs of thoracic aorta. The PubMed database was searched without any year limits. Search terms used %were "thoracic", "aorta" and "reintervention". Two authors independently reviewed abstracts identified by the search and subsequently the reference lists of eligible series were scrutinized in order to detect any additional relevant articles. Different early and late complications following open an endovascular repair of thoracic aorta were described adding their incidence and their potential solutions with secondary interventions. Secondary interventions after open repair (OR) are more related to bleeding and progression of the aortic disease issues and open surgery is again the most common solution. However, in more fragile patients with favorable anatomy, endovascular repair can be offered as a secondary procedure. Reinterventions after endovascular treatment of thoracic aorta diseases (TEVAR) are mostly related to endoleaks and also to the aortic disease progression. Hopefully, the oncoming technological improvements together with the optimized operator expertise can reduce the incidence of secondary procedures following TEVAR for all the aortic pathologies.

Aneurysmal degeneration of the inflow artery after arteriovenous access for hemodialysis.

OBJECTIVES: After arteriovenous fistula creation, the arterial flow increase can lead to aneurysmal degeneration, even increased after fistula ligation or renal transplant immunosuppression. The aim of this study is to describe the therapeutic options and outcomes of true aneurysms of the inflow artery after arteriovenous fistula for hemodialysis. METHODS: Prospectively collected data of patients with true aneurysmal degeneration of the inflow artery after fistula creation (excluding pseudoaneuryms, anastomotic or infected aneurysms, or surgical complications), surgically repaired between January 2010 and February 2014 (cohort study) have been included. Patient demographics and access characteristics, symptoms, treatment, and follow-up have been reviewed. RESULTS: 12 patients (75% men, median age 63 years) were treated for aneurysmal degeneration of the axillary (1), brachial (6), or radial (5) artery. They had had a previous distal arteriovenous fistula (7 radiocephalic, 3 brachiocephalic, 2 brachiobasilic) created 15.6 years before (range 9.9-28.5) and the majority of them were currently ligated or thrombosed. Most patients were symptomatic (pain [6], distal embolization [1]). They were treated by means of a bypass (using the cephalic [3], basilic [4], or saphenous vein [2]), direct ligature (2), or excision with end-to-end reconstruction (1). No major complications or ischemic symptoms occurred before discharge. After a median follow-up of 8.6 months (3.1-36.5), one patient needed re-operation for new proximal brachial aneurysmal degeneration, and another presented with an asymptomatic post-traumatic thrombosis of the proximal axillary artery and brachial bypass. No other complications, bypass dilatation or ischemic symptoms occurred during follow-up. CONCLUSIONS: Inflow artery aneurysmal degeneration can occur after long-term arteriovenous access. Surgical treatment by autogenous bypass exclusion in most cases (or ligation or end-to-end reconstructions in selected cases) is a safe and effective option.

Current technology for the treatment of infection following abdominal aortic aneurysm (AAA) fixation by endovascular repair (EVAR).

In recent years, in parallel with the increase of endovascular aortic repair (EVAR) procedures performances, a rise of late open surgical removal of EVAR implants has been observed, due to non-endovascularly correctable graft complications. Among them endograft infection is a rare but devastating occurrence, accounting for an incidence ranging from 0.2% to 0.7% in major series, and almost 1% of all causes of endograft explantations. However, a real estimation of the incidence of the problem respect to the number of EVAR implantations is difficult to obtain. Time to infection is usually defined as the period between EVAR and presentation of symptoms that leads to the infection diagnosis. It can be extremely variable, depending on bacterial virulence and host conditions. The diagnosis of an endograft infection is usually based on a combination of clinical symptoms, imaging studies and microbial cultures whenever possible. If computed tomography (CT) scan is employed in almost 100% of infection diagnosis, a combination of fluorodeoxyglucose-positron emission tomography (FDG-PET) and CT scan is nowadays used with increasing frequency in order to rise the likelihood of detecting a graft infection, since even cultures of blood or samples collected from the infected field can sometimes be negative. Complete graft excision seems the best approach whenever a surgical reconstruction could be attempted. In situ reconstruction can be performed by the interposition of an autologous vein, a cryopreserved allograft or a rifampin-soaked Dacron graft. The so-called conventional treatment contemplates the re-establishment of vascularization through extranatomical routes, thus preserving the new graft material from possible contamination by the surgical field just cleaned. When severe comorbid conditions did not allow graft excision, a conservative treatment should be taken into account. It is mainly based on broad-spectrum or culture-specific antibiotic therapy combined, whenever possible, with percutaneous drainage of the infectious cavity or aneurismal sac followed by irrigation with saline and antibiotic solutions. New techniques of percutaneous drainage under CT scan guidance can allow expedite collection of fluid material for microbial culture or fluid drainage, catheter positioning to collect infectious material from the cavity and perform irrigation of the infected field or injection of iodine contrast when the suspicion of aortoenteric fistula exists.

Magnesium phosphate cements for endodontic applications with improved long-term sealing ability.

AIM: To characterize three radiopaque Magnesium Phosphate Cements (MPCs) developed for endodontic purposes. METHODOLOGY: Three experimental MPCs containing Bi2 O3 were formulated. The experimental cements, which consisted of mixtures of magnesium oxide with different phosphate salts, were characterized for setting time, injectability, porosity, compressive strength and phase composition. The long-term sealing ability of the experimental MPCs applied in single-rooted teeth as root canal filling material or as sealer in combination with gutta-percha was also assessed using a highly sensitive fluid filtration system. A mineral trioxide aggregate (MTA) cement was used as control. Statistical analysis was performed with two- or three-way analysis of variance (anova) and Tukey's test was used for comparisons. RESULTS: The addition of 10 wt% Bi2 O3 within the composition of the MPCs provided an adequate radiopacity for endodontic applications according to ISO 6876 standard. The reaction products resulting from the MPCs were either struvite (MgNH4 PO4 ·6H2 O) or an amorphous sodium magnesium phosphate. The porosity of the three MPCs ranged between 4% and 11%. The initial setting time of the experimental cements was between 6 and 9 min, attaining high early compressive strength values (17-34 MPa within 2 h). All MPC formulations achieved greater sealing ability than MTA (P < 0.05) after 3 months, which was maintained after 6 months for two of the experimental cements (P < 0.05). CONCLUSIONS: These MPCs had adequate handling and mechanical properties and low degradation rates. Furthermore, a stable sealing ability was demonstrated up to 6 months when using the cement both as root filling material and as sealer in conjunction with gutta-percha.

Antimicrobial properties and dentin bonding strength of magnesium phosphate cements.

The main objective of this work was to assess the antimicrobial properties and the dentin-bonding strength of novel magnesium phosphate cements (MPC). Three formulations of MPC, consisting of magnesium oxide and a phosphate salt, NH4H2PO4, NaH2PO4 or a mixture of both, were evaluated. As a result of the setting reaction, MPC transformed into either struvite (MgNH4PO4·6H2O) when NH4H2PO4 was used or an amorphous magnesium sodium phosphate when NaH2PO4 was used. The MPC had appropriate setting times for hard tissue applications, high early compressive strengths and higher strength of bonding to dentin than commercial mineral trioxide aggregate cement. Bacteriological studies were performed with fresh and aged cements against three bacterial strains, Escherichia coli, Pseudomonas aeruginosa (planktonic and in biofilm) and Aggregatibacter actinomycetemcomitans. These bacteria have been associated with infected implants, as well as other frequent hard tissue related infections. Extracts of different compositions of MPC had bactericidal or bacteriostatic properties against the three bacterial strains tested. This was associated mainly with a synergistic effect between the high osmolarity and alkaline pH of the MPC. These intrinsic antimicrobial properties make MPC preferential candidates for applications in dentistry, such as root fillers, pulp capping agents and cavity liners.

The best conditions for parallel stenting during EVAR: an in vitro study.

OBJECTIVES: The aim of this study is to identify which endograft, and to what degree of oversizing, in combination with what type of parallel stent, may result in the most adequate fit in a juxtarenal abdominal aneurysmal neck when using a parallel-stent technique. MATERIALS/METHODS: In-vitro silicon aneurysmal neck models of different diameters, with one side-branch, were constructed. Two different endografts (Medtronic-Endurant Abdominal Stent Graft and Gore-Excluder abdominal aortic aneurysm Endoprosthesis; three diameters each), and two stents (self-expanding Gore Viabahn Endoprosthesis and balloon-expandable Atrium Advanta V12; 6-mm diameter) were tested, applying three endograft-oversizing degrees (15%, 30% and 40%). After remodelling using the kissing-balloon technique at 37 °C, the 36 endograft-stent-oversizing combinations were scanned by computed tomography (CT). The size of the results in gutters, parallel-stent compression and main stent-graft infolding were recorded. RESULTS: Increasing oversizing (15%, 30% and 40%) significantly decreased gutter areas (11.5, 6.2, 4.3 mm(2), P < 0.001); nevertheless, main endograft infolding of most 40%-oversized stent grafts was detected, particularly with Excluder devices. Lower stent compression, but wider gutters, were observed with the Excluder when compared to Endurant stent grafts, and with V12 when compared to Viabahn parallel stents. The Endurant-Viabahn combination resulted in maximum stent compression (35%). CONCLUSIONS: Better endograft-stent apposition was achieved when using 30% endograft oversizing. Lower stent compression, but wider gutters, were observed with the Excluder stent-graft and V12 parallel stent, achieving maximum stent compression with the Endurant-Viabahn combination.

Assessment of in vitro dermal absorption of the kaurenic acid from Coespeletia moriziana extracts.

Espeletiinae are plants which grow above 3000 m of altitude in the Northern Andes and kaurenic acid was extracted from the leaves of Coespeletia moritziana. This compound has shown a wide range of biological activities, including cytotoxicity which is efficient in cancer therapy. The percutaneous penetration of this compound was measured in vitro using Franz cells. At appropriate intervals for up to 24h, diffusion samples were analyzed using HPLC. At the end of the test period, the amount of kaurenic acid was determined in each compartment and approximately 10% of kaurenic acid had been absorbed and was found in the skin layers.

Early abdominal aortic endografts: a decade follow-up results.

OBJECTIVES: To report the results of long-term follow-up of abdominal aortic aneurysms (AAAs) treated with endografts more than a decade ago. DESIGN: Retrospective analysis of estimated long-term follow-up, mortality and morbidity in terms of complications and re-interventions, using the Kaplan-Meier survival analysis. MATERIALS/METHODS: Between March 1997 and January 2000, 61 patients with AAA (53 asymptomatic, four symptomatic and three ruptured) were treated with aortic endografts. All preoperative, operative and follow-up data were recorded according to the EUROpean collaborators on Stent graft Techniques for abdominal aortic Aneurysm (EUROSTAR) criteria. RESULTS: The primary technical success rate was 98.4%. The majority of used devices were Vanguard (65.0%), and in a bifurcated configuration (86.7%). At 10-year follow-up, the estimated cumulative follow-up rate was 82.0%; complications occurred in 74.6% of the patients and re-interventions were required in 56.9%. The Vanguard endograft was related to a higher incidence of re-interventions (P=0.012). The combined in-hospital or AAA-related mortality rate was 5.0% at 30 days and 8.2% at a 10-year follow-up (1.8% and 5.0% in elective cases, respectively). CONCLUSIONS: Early abdominal endografts are associated with high incidence of complications (74.6%) and re-interventions (56.9%) at a 10-year follow-up; however, the mortality rate related to the procedure or aneurysm is low (5.0% in elective cases). Early endografts need lifelong strict surveillance.

Benzophenone-3 entrapped in solid lipid microspheres: formulation and in vitro skin evaluation.

Solid lipid microspheres (SLM), lipid-in-water formulations made from oil-and-wax mixtures, were studied concerning feasibility. SLMs were then loaded with a benzophenone-3, water insoluble UVAB-filter intended for dermal application. Microspheres were prepared by dispersion with homogenisers and investigated by polarizing micrography and scanning electron micrography. For the selected formulations, investigations on percutaneous penetration of B-3 capacity were performed "in vitro" using Franz cells. Microspheres, 5-50 µm in size, and a spherical shape were obtained from several mixtures. B-3 was added and the loading capacity of this drug in the SLM was obtained for a maximum of 5% when the lipophilic phase was 18%. The lipophilic mixture with non-ionic surfactants in the selected formulation of lipid microspheres has a favorable effect on size. The selected formulation is also cosmetically adapted and it is composed of physiological and biodegradable lipids. B-3 was released and penetrated into skin more quickly and in greater quantity than in SLM form, from vehicles containing free B-3. This work has shown that SLM is an excellent carrier for lipophilic sunscreens like B-3 in order to decrease the release and penetration rate of this UV absorber compared with B-3 in oily solution.

New processing approaches in calcium phosphate cements and their applications in regenerative medicine.

The key feature of calcium phosphate cements (CPCs) lies in the setting reaction triggered by mixing one or more solid calcium phosphate salts with an aqueous solution. Upon mixture, the reaction takes place through a dissolution-precipitation process which is macroscopically observed by a gradual hardening of the cement paste. The precipitation of hydroxyapatite nanocrystals at body or room temperature, and the fact that those materials can be used as self-setting pastes, have for many years been the most attractive features of CPCs. However, the need to develop materials able to sustain bone tissue ingrowth and be capable of delivering drugs and bioactive molecules, together with the continuous requirement from surgeons to develop more easily handling cements, has pushed the development of new processing routes that can accommodate all these requirements, taking advantage of the possibility of manipulating the self-setting CPC paste. It is the goal of this paper to provide a brief overview of the new processing developments in the area of CPCs and to identify the most significant achievements.

The "in vitro" percutaneous penetration of three antioxidant compounds.

Caffeic acid, chlorogenic acid and oraposide, a natural glycoside, are phenyl-propanoid compounds. These natural products have been reported to have antioxidant activities such as the scavenging of superoxide anions and hydroxyl radicals. These compounds could be used in the dermocosmetic field to protect the skin from oxidative stress induced by UV radiation. To this end, the permeation of caffeic acid, chlorogenic acid, and oraposide, through pig-ear skin was evaluated in vitro. The percutaneous permeation of these three compounds through pig skin was measured and compared using Franz diffusion cells. At appropriate intervals, up to 72 h, diffusion samples were analyzed using an HPLC assay. After 48 h of drug contact the permeation was also evaluated with a fluorescent microscope on vertical microtomed pig skin sections. In this study on excised pig skin, the flux value was found to be equal to 0.32 and 0.48 microgcm(-2)h(-1) for caffeic and chlorogenic acids, respectively; for oraposide the levels were below the limit of detection and the flux was not evaluated. These results were corroborated by fluorescent microscopy. Caffeic and chlorogenic acids were found in all skin sections, and these might represent a systemic activity, whereas oraposide remained in the upper superficial layer of the skin. This latter phenomenon seems to be interesting for dermocosmetic applications.

Benzophenone-3: rapid prediction and evaluation using non-invasive methods of in vivo human penetration.

The study described in this paper constitutes a practical assay system to evaluate in vivo drug penetration using two complementary non-invasive methods. An electrical capacitance test was first applied to the skin on the forearm to evaluate the hydration of the skin, and check the integrity of the stratum corneum. In the first step, the percentage absorption was measured using an occlusive and difference method; following benzophenone-3 application any residual formulation was washed off and the amount removed analyzed. In the second step, the tape stripping method-a useful procedure for selectively removing the skin's outermost layer, the stratum corneum, and measuring the stratum corneum adsorption-was performed. Under these conditions the human skin permeation of this UV-filter over four hours was near to 35% of the applied dose with the occlusive method. The amount of topically applied benzophenone-3 found in the stratum corneum after 30 min exposure using the stripping procedure was evaluated at 4% to the applied dose.

LC analysis of benzophenone-3: II application to determination of 'in vitro' and 'in vivo' skin penetration from solvents, coarse and submicron emulsions.

The aim of this study was to determine the skin penetration of benzophenone-3 in vitro and in vivo in order to investigate a possible influence of formulation. Six different vehicles, three solvents and three different emulsion types were evaluated in vitro and in vivo. Each vehicle was applied to the skin model at 2 mg cm(-2). First, histological studies on ear pigskin and human skin were evaluated. In vitro measurements were performed with static diffusion cells using pigskin at 1, 2, 4, and 8-h. In vivo, benzophenone-3 concentration in stratum corneum was evaluated by the stripping method after 30-min application on forearm of volunteers. It was shown that ear pigskin and human skin appear similar and in both experiments significant differences between vehicles were noticed. The six vehicles could be ranked in the same order of benzophenone-3 skin concentration. At 8-h, the highest concentration of benzophenone-3 in skin was obtained with propylene glycol, and O/W submicron emulsion. On the contrary. the two oily solvents. W/O emulsion and O/W coarse emulsion restrain the concentration of this UV-filter in the skin. At each time, permeability in vitro and in vivo were well correlated. Low concentrations were measured in the receptor fluid suggesting that percutaneous absorption of this UV-filter across the skin would be minimal. The in vitro and in vivo skin penetration capacity of benzophenone-3 from six vehicles was confirmed and quantified. A satisfactory relationship between binary in vitro and in vivo was established.

Bilateral effect of a unilateral occlusal splint on the expression of myosin heavy-chain isoforms in rat deep masseter muscle.

Many studies have shown that various myosin isoforms are involved in muscle contraction. A search for specific antibodies directed against the myosin heavy chain (MHC) resulted in the identification of at least two main classes, referred to as MHC type I and type II. In this study, immunohistology and gel electrophoresis were used to determine the proportion of MHC isoforms in rat deep masseter muscle at different times after the insertion of an unilateral occlusal splint. An increasing proportion of MHC type I isoforms was found in both deep masseters soon after splinting, and this trend continued until 7 days after splint insertion. The type I fibres were clearly distributed on either side of the central axis of the muscle. At 15 days, a significant decrease in the percentage of the type IIb MHC isoform was observed on the occlusal splint side compared to the contralateral side. After 30 days of unilateral splinting, the proportion of type IIb fibres on the splint side returned to baseline whereas on the contralateral side there was an increase in the proportion of this type. The results suggest an initial adaptation after the unilateral occlusal disturbance in which muscles of both sides react in the same way; later, the muscles of each side adapt their expression of MHC isoforms according to altered functional demand.

Effect of the addition of oxybenzone or octyl-methoxycinnamate on particle size of submicron emulsions.

The formulation of sunscreen products requires understanding of the solubilization of these products in different vehicles to obtain aesthetic preparations and to evaluate long-term stability. For this study, two different ultraviolet (UV) filters were selected: oxybenzone (powder) and octyl-methoxycinnamate (liquid). First, the solubility of these UV filters was tested using a three-component simplex-centroid design strategy. The mixtures were prepared with three oily phases used in this field of cosmetics: liquid paraffin, isopropyl myristate, and coconut oil. A phase diagram method was used to carry out a systematic study of submicron oil-in-water emulsions. Phase diagrams were produced by diluting fixed binary mixtures with water. The surfactant consisted of polyoxyethylene-20-sorbitan monostearate/sorbitan monostearate (50/50, w/w). The oily phase contained equal quantities of each oil studied. From this water/surfactant/oil ternary system, we selected two reference emulsions with receptively 75/5/20 and 68/7/25 proportions. Photon correlation spectroscopy (PCS) was used to investigate the influence of these two UV filters at several concentrations on droplet size and distribution of the oil droplets in the material. All emulsions were stored and checked every month for 6 months.

Solubilisation de filtres-UV dans des melanges ternaires de phases apolaires, optimisation par l'utilisation de reseaux centres.

This paper is concerned with the solubility of UV filters. Emulsions are perfect formulations used for sunscreens, but to give the skin silky feel without being greasy, the oily phase content is low. Considerations of sunscreen solubility can help to solve specific problems of stability in formulations. It is important to determine what solvent dissolves them and what mixture of solvent improves their solubility. Two water insoluble sunscreens were tested at several concentrations in various non-polar solvents. A strategy with simplex centroid design was used to optimize this work. The graphical interpretation of the data assists our understanding of the solubility of UV filters.