Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain

Abstract Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration

Quantitative assessments of static and dynamic balance performance in patients with chronic ankle instability.

Patients with chronic ankle instability (CAI) have postural-control deficits during center-of-pressure excursions than do healthy individuals. While an external analysis of center-of-pressure excursions in CAI has been performed, a quantitative analysis of center-of-gravity movements, to detect the balance deficits associated with CAI, has yet to be performed. Therefore, the aim of the study is to quantify the balance deficits in patients with unilateral CAI.Forty-four patients with unilateral CAI (24 men; age, 31.7 ±â€Š5.5 years) and 26 uninjured volunteers (12 men; age, 28.6 ±â€Š5.9 years) underwent Neurocom Balance Manager assessments of dynamic and static balance responses in limits of stability, unilateral stance, and forward lunge tests.In the limits of stability test, there were no significant group differences in the forward direction; however, reaction times were longer in the CAI group than in the control group in the backward (P = .037, effect size [ES] = 0.49) and rightward directions (P = .032, ES  = 0.47). Furthermore, the CAI group showed more excursions in the rightward (P = .046, ES = 0.50) and leftward directions (P = .002, ES = 0.80), and less directional control in the leftward direction (P = .036, ES = 0.59). In the unilateral stance test, the center of gravity sway velocity was faster in the CAI group than in the control group, whether eyes were opened or closed (P < .05). There were no significant group differences in forward lunge-test outcomes.Patients with CAI have poor static and dynamic balance performance compared to that in healthy counterparts. Thus, balance retraining should be an essential component of rehabilitation programs for patients with CAI.

Focus on echocardiographic right ventricular strain analysis in cystic fibrosis adults without cardiovascular risk factors: a case-control study.

Strain echocardiography is able to detect subclinical ventricular systolic and diastolic dysfunction. Prolonged survival to cystic fibrosis favors heart and vessel involvement. The purpose of the present study was to compare clinically stable adult patients affected by cystic fibrosis without overt pulmonary hypertension with controls to evaluate right ventricular (RV) systolic and diastolic function by means of strain and tissue Doppler imaging (TDI), respectively. 22 adults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors or overt pulmonary hypertension. All people underwent blood pressure measurement and transthoracic echocardiography. Cystic fibrosis patients showed higher sPAP [median 25 (IQR 21-30) vs 22 (22-22) mmHg; p = 0.02] and more frequent RV diastolic dysfunction (p < 0.001). Among cases, some RV systolic parameters were significantly altered than controls, such as TAPSE [20 (18-24) vs. 23 (21-28) mm; p = 0.001], FAC [34 (26-44) vs. 49 (48-50)%; p < 0.001], midwall tissue strain [- 25.0 (- 31.3 to - 22.8) vs. - 30.5 (- 31.8 to - 29.3)%; p = 0.03], apical tissue strain [- 22 (- 29.3 to - 19.0) vs. - 30.5 (- 32.8 to - 28.3)%; p = 0.001] and 2D strain [- 22.0 (- 25.1 to - 19.0) vs. - 29.5 (- 31.8 to - 27.3)%; p < 0.001]. Finally, 2D strain correlated with spirometric FEV1 (ρ = - 0.463, p = 0.03) and nearly with FEF25-75% (ρ = - 0.393, p = 0.07). Our study confirmed a RV subclinical systo-diastolic dysfunction in clinically stable patients affected by cystic fibrosis without overt pulmonary hypertension nor cardiovascular risk factors. This may be due to systemic inflammation and temporary recurrent pulmonary hypertension. We retain that RV 2D strain and TDI echocardiography could become an important tool in the follow-up of these patients.

Noninvasive Interactive Neurostimulation Therapy for the Treatment of Low-Grade Lateral Ankle Sprain in the Professional Contact Sport Athlete Improves the Short-Term Recovery and Return to Sport: A Randomized Controlled Trial.

Ankle injuries are very common between professional athletes and recreational sports. Lateral stable ligaments injury can be treated conservatively. Noninvasive interactive neurostimulation (NIN) is a form of electric therapy that works by locating areas of lower skin impedance. The objective of this prospective, double-blinded, randomized controlled trial was to compare the results in terms of improvement of a foot functional score, lower level of reported pain, and return to sports in 2 groups of contact sport athlete affected by a grade I or II lateral ankle sprain. Patients were randomized using random blocks to the NIN program (group I) or a sham device (group II). The outcome measurements were the use of a self-reported Inability Walking Scale, patient-reported subjective assessment of the level of pain using a standard visual analogue scale, and daily intake of nonsteroidal antiinflammatory drugs (etoricoxib 60 mg). Patients were also reached by telephone at 2 and 4 months of follow-up to register their return to sport activity. Beyond baseline evaluation, follow-ups were done after 5 (1 week) and 10 sessions (2 weeks) of treatment, and then at 30 days after the end of therapy. Of the 70 athletes admitted to the study, 61 eligible patients were randomized using random blocks to group I (n = 32) and group II (n = 29). Group I patients showed better improvement in terms of functional impairment (Inability Walking Scale), reported pain (visual analogue scale), and daily intake of etoricoxib 60 mg. Athletes of group I registered a faster resuming of sport activities. This prospective, randomized trial showed NIN can improve short-term outcomes in athletes with acute grade I or II ankle sprain and that it can hasten resuming of sport activities.

[Sprain of the thumb metacarpal-phalangeal with lesion of the ulnar collateral ligament]. / Entorse de l'articulation métacarpo-phalangienne du pouce avec lésion du ligament collatéral ulnaire.

The sprain of the thumb metacarpal-phalangeal joint must be treated in an adapted way in order to avoid chronic laxity. The comparative and bilateral clinical exam is the main element that will allow to detect laxity. In the case of non laxity, a conservative treatment with a splint makes sense. In the case of laxity with Stener effect, a surgical procedure is recommended in order to reintegrate the collateral ligament. In the case of laxity without Stener effect, the choice of treatment is contentious. A US or MRI would be useful if the Stener effect could be underlying. For whichever treatment opted, rehabilitation is to be started as soon as at week 4, in order to reduce risks of stiffness. The return to any sport or training will depend on the sprain stage and on the possibility to wear a rigid splint or not.

L'entorse de l'articulation métacarpo-phalangienne du pouce doit être traitée de manière adaptée pour éviter une laxité chronique. L'examen clinique bilatéral et comparatif est l'élément central pour dépister une laxité. Il doit être précédé d'une radiographie. En cas d'absence de laxité, un traitement conservateur par attelle se justifie. En cas de laxité avec effet Stener, un traitement chirurgical est indispensable pour réinsérer le ligament collatéral. En cas de laxité sans effet Stener, le traitement est controversé. Un US ou une IRM sont utiles en cas de suspicion d'effet Stener pour statuer sur l'état du ligament. Quel que soit le traitement, la rééducation est débutée dès la 4e semaine pour limiter l'enraidissement. Le retour à la pratique sportive dépend du stade de l'entorse et de la possibilité de porter une attelle rigide.

Contrast Therapy and Heat Therapy in Subacute Stage of Grade I and II Lateral Ankle Sprains.

UNLABELLED: Objective This study was conducted to determine the most effective thermal modality; heat or contrast therapy-in reducing pain, reducing swelling, and increasing range of movement (ROM) of the grade I and II lateral ankle sprain in the prechronic stage of the subacute phase. Design Randomized control trail. Methods One hundred and fifteen participants of both genders who were diagnosed as having grade I or II lateral ankle sprain were randomly assigned to the study on the fifth day of injury. Pain, volume, and ROM were recorded before and after treatment continuously for 3 days. Results Effects were evaluated as "Immediately after application" and "3 days after continuous application." Immediately after application, there was no difference between the 2 modalities on ankle ROM; heat reduced pain over contrast therapy, and both modalities increased swelling. When considering the effects after continuous application for 3 days, no difference was found between the 2 modalities on ROM and the reduction of pain. Contrast therapy reduced swelling while heat caused increased swelling even after 3 days. Conclusion The use of different thermal modalities during the transition from the acute to chronic phase of injury can be suggested as effective treatment options according to the objectives of injury management: pain reduction, improve ROM, and swelling management. LEVELS OF EVIDENCE: Therapeutic, Level II: Randomized clinical trial.

Finger joint injuries.

Finger joint dislocations and collateral ligament tears are common athletic hand injuries. Treatment of the athlete requires a focus on safe return to play and maximizing function. Certain dislocations, such as proximal interphalangeal and distal interphalangeal volar dislocations, may be associated with tendon injuries and must be treated accordingly. Treatment of other dislocations is ultimately determined by postreduction stability, with many dislocations amenable to nonoperative treatment (ie, immobilization followed by rehabilitation). Protective splinting does not necessarily preclude athletic participation. Minor bone involvement typically does not affect the treatment plan, but significant articular surface involvement may necessitate surgical repair or stabilization. Percutaneous and internal fixation are the mainstays of surgical treatment. Treatment options that do not minimize recovery or allow the patient to return to protected play, such as external fixation, are generally avoided during the season of play. Undertreated joint injuries and unrecognized ligament injuries can result in long term disability.

Terminology and classification of muscle injuries in sport: the Munich consensus statement.

OBJECTIVE: To provide a clear terminology and classification of muscle injuries in order to facilitate effective communication among medical practitioners and development of systematic treatment strategies. METHODS: Thirty native English-speaking scientists and team doctors of national and first division professional sports teams were asked to complete a questionnaire on muscle injuries to evaluate the currently used terminology of athletic muscle injury. In addition, a consensus meeting of international sports medicine experts was established to develop practical and scientific definitions of muscle injuries as well as a new and comprehensive classification system. RESULTS: The response rate of the survey was 63%. The responses confirmed the marked variability in the use of the terminology relating to muscle injury, with the most obvious inconsistencies for the term strain. In the consensus meeting, practical and systematic terms were defined and established. In addition, a new comprehensive classification system was developed, which differentiates between four types: functional muscle disorders (type 1: overexertion-related and type 2: neuromuscular muscle disorders) describing disorders without macroscopic evidence of fibre tear and structural muscle injuries (type 3: partial tears and type 4: (sub)total tears/tendinous avulsions) with macroscopic evidence of fibre tear, that is, structural damage. Subclassifications are presented for each type. CONCLUSIONS: A consistent English terminology as well as a comprehensive classification system for athletic muscle injuries which is proven in the daily practice are presented. This will help to improve clarity of communication for diagnostic and therapeutic purposes and can serve as the basis for future comparative studies to address the continued lack of systematic information on muscle injuries in the literature. WHAT ARE THE NEW THINGS: Consensus definitions of the terminology which is used in the field of muscle injuries as well as a new comprehensive classification system which clearly defines types of athletic muscle injuries. LEVEL OF EVIDENCE: Expert opinion, Level V.

Acute muscle strain injuries: a proposed new classification system.

PURPOSE: To better define and classify acute muscle strain injuries. METHODS: Historically, acute muscle strains have been classified as grade I, II and III. This system does not accurately reflect the anatomy of the injury and has not been shown to reliably predict prognosis and time for return to sport. RESULTS: We describe an imaging (magnetic resonance or ultrasound) nomenclature, which considers the anatomical site, pattern and severity of the lesion in the acute stage. By site of injury, we define muscular injuries as proximal, middle and distal. Anatomically, based on the various muscular structures involved, we distinguish intramuscular, myofascial, myofascial/perifascial and musculotendinous injuries. CONCLUSIONS: This classification system must be applied to a variety of muscle architectures and locations to determine its utility; additional studies are therefore needed prior to its general acceptance. LEVEL OF EVIDENCE: V.

Acromioclavicular joint injuries and reconstructions: a review of expected imaging findings and potential complications.

Shoulder injuries, including acromioclavicular (AC) joint separations, remain a common reason for presentation to the emergency room. Although the diagnosis can be made apparent through proper history and physical examination by the emergency medicine physician, ascertaining the degree of injury can be difficult on the basis of clinical evaluation alone. While there is consensus in the literature that low-grade AC joint injuries can be treated with conservative management, high-grade injuries will generally require surgical intervention. Furthermore, the treatment of grade 3 injuries remains controversial, making it incumbent upon the radiologist to become comfortable with distinguishing this diagnosis from lower or higher grade injuries. Imaging of AC joint injuries after clinical evaluation is generally initiated in the emergency room setting with plain film radiography; however, on occasion, an alternative modality may be presented to the emergency room radiologist for interpretation. As such, it remains important to be familiar with the appearance of AC joint separations on a variety of modalities. Another possible patient presentation in both the emergent and nonemergent setting includes new onset of pain or instability in the postsurgical shoulder. In this scenario, the onus is often placed on the radiologist to determine whether the pain or instability represents the sequelae of reinjury versus a complication of surgery. The purpose of this review is to present an anatomically based discussion of imaging findings associated with AC joint separations as seen on multiple modalities, as well as to describe and elucidate a variety of potential complications which may present to the emergency room radiologist.

[Supination external rotation lesions of the ankle joint in osteoporotic lower leg specimens. Experimental induction and review of the literature]. / Die Supinations-Eversions-Verletzung des OSG in osteoporotischen Unterschenkelpräparaten. Experimentelle Induktion und Literaturübersicht.

BACKGROUND: Knowledge of the pathomechanism and the detailed extent of ankle joint lesions determines adequate therapy and success of treatment. MATERIAL AND METHODS: Supination external rotation lesions were induced in 29 human cadavera with a testing apparatus; 27 of these specimens were from elderly women. Bone mineral density was measured. The literature review includes experimental studies of this fracture entity. RESULTS: We induced stage II in 42%; applying an additional lateral force on the fibula raised the incidence. The syndesmosis stayed intact in 50% although the fibula fractured at the level of the tibial plafond. Stage IV lesions were registered in 25%. The overall low bone mineral density showed a positive correlation to the angle at which the fibula fracture occurred. CONCLUSIONS: We reproduced supination external rotation lesions according to Lauge-Hansen in osteoporotic ankles. There is a certain discrepancy between the obligatory lesion of the inferior anterior tibiofibular syndesmosis at stage II according to Lauge-Hansen, as we observed an intact syndesmosis in 50% at stage II. Stage IV defining medial malleolar fractures were reproduced after Lauge-Hansen and Michelson et al.

Comparison of magnetic resonance imaging to physical examination for syndesmotic injury after lateral ankle sprain.

BACKGROUND: Clinical assessment of syndesmotic injury usually consists of two tests: the ankle external rotation test and squeeze test. This study sought to determine the sensitivity and specificity of both for syndesmotic injury secondary to lateral ankle sprain. METHODS: Fifty-six patients with sprained ankles underwent clinical examination for syndesmotic injury with the aforementioned tests. Clinical findings were compared against magnetic resonance imaging (MRI) of the ankle. Sprains were graded on anatomical and functional classification scales, and correlation and agreement between both scales were assessed. RESULTS: The MRI prevalence of syndesmotic injury in patients with lateral ankle sprains was 17.8%. Sensitivity and specificity were 30% and 93.5% for the squeeze test, and 20% and 84.8% for the external rotation test, respectively. Using the anatomical scale for sprain grading, 40% of syndesmotic injuries occurred in Grade I, 40% in Grade II, and 20% in Grade III sprains. Ten percent of patients with syndesmotic injury had no lateral ligament injury on MRI, 70% had injury of the anterior talofibular (ATFL) ligament, and 20% had injury to the ATFL and calcaneofibular (CFL). CONCLUSION: The sensitivity of the squeeze test and external rotation test was low, suggesting that physical examination often fails to diagnose syndesmotic injury. Conversely, specificity was very high; nearly all patients with a positive test actually had syndesmotic injury. Severity of ankle sprain was not associated with prevalence of syndesmotic injury.

Effect of high-voltage pulsed current on recovery after grades I and II lateral ankle sprains.

CONTEXT: High-voltage pulsed current (HVPC), a form of electrical stimulation, is known to curb edema formation in laboratory animals and is commonly applied for ankle sprains, but the clinical effects remain undocumented. OBJECTIVE: To determine whether, as an adjunct to routine acute and subacute care, subsensory HVPC applied nearly continuously for the first 72 h after lateral ankle sprains affected time lost to injury. DESIGN: Multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Data were collected at 9 colleges and universities and 1 professional training site. PARTICIPANTS: 50 intercollegiate and professional athletes. INTERVENTIONS: Near-continuous live or placebo HVPC for 72 h postinjury in addition to routine acute and subacute care. MAIN OUTCOME MEASURE: Time lost to injury measured from time of injury until declared fit to play. RESULTS: Overall, time lost to injury was not different between treated and control groups (P = .55). However, grade of injury was a significant factor. Time lost to injury after grade I lateral ankle sprains was greater for athletes receiving live HVPC than for those receiving placebo HVPC (P = .049), but no differences were found between groups for grade II sprains (P = .079). CONCLUSIONS: Application of subsensory HVPC had no clinically meaningful effect on return to play after lateral ankle sprain.

Outcome of the functional treatment of first-time ankle inversion injury.

BACKGROUND: Avulsion fractures of the lateral malleoli in ankle inversion injuries are often undetected on routine radiographs. Undetected avulsion fractures have been managed as ankle sprain, which may affect the outcome of the treatment of the ankle sprain. The purposes of this study are to compare the outcomes of functional treatment between the first-time severe ligament injury and avulsion fracture of the lateral ankle, and to investigate how the anterior talofibular ligament (ATFL) view or the calcaneofibular ligament (CFL) view affects the diagnosis of the avulsion fracture and outcome of functional treatment of the ankle inversion injury. METHODS: A total of 276 consecutive patients with a first-time severe ankle inversion injury were classified into a ligament injury group (group I) or an avulsion fracture group (group II) on the basis of physical examination and radiographs. The patients with a negative finding on routine radiographs and a positive finding on the ATFL or CFL view derived from group II (group IIA). Age, sex, and activity level were analyzed. Patients were treated by stirrup splint. RESULTS: A total of 202 (73.2%) patients were in group I and 74 (26.8%) were in group II. In all, 50 patients in group II showed negative standard radiographs and a positive ATFL or CFL view. Altogether, 240 patients were followed up for at least 1 year and assessed clinically and radiographically. Differences in age, sex, and activity level before injury between groups were not statistically significant. Clinical and radiographic results of group II were inferior to those of group I. The outcome of group IIA was comparable to that of group I. CONCLUSIONS: The outcome of functional treatment of avulsion fracture was inferior to that of ligament injury. The ATFL and CFL views provide a more precise diagnosis but do not affect the outcome of the functional treatment.

Reinjury after acute lateral ankle sprains in elite track and field athletes.

BACKGROUND: Lateral ankle sprains can lead to persistent disability in athletes. The authors studied the effect of a lateral ankle sprain on reinjury occurrence in the same region. HYPOTHESIS: There will be no difference in reinjury rate between low-grade (grades I and II) and high-grade (IIIA and IIIB) acute lateral ankle sprains. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 1. METHODS: From 1996 to 2004, the authors managed 202 elite Greek track and field athletes for an acute lateral ankle sprain. Sprains were classified into 4 degrees (I, II, IIIA, and IIIB). The same rehabilitation protocol was prescribed for all the athletes. The rate of a lateral ankle reinjury was recorded in the 24 months following injury. RESULTS: At a follow-up of 24 months, 36 of 202 athletes (17.8%) experienced a second lateral ankle sprain. Of the 79 athletes with a grade I injury, 11 (14%) experienced a recurrence during the study period. Of the 81 athletes with a grade II injury, 23 (29%) experienced a recurrence during the study period. Of the 36 athletes with a grade IIIA injury, 2 (5.6%) experienced a recurrence during the study period. Of the 6 athletes with a grade IIIB injury, none experienced a recurrence during the study period. CONCLUSION: Athletes with a grade I or II lateral ankle sprain are at higher risk of experiencing a reinjury. Low-grade acute lateral ankle sprains result in a higher risk of reinjury than high-grade acute lateral ankle sprains.

Lisfranc injuries in sport.

Injuries to the Lisfranc ligament complex have traditionally been associated with high energy trauma such as motor vehicle collisions and industrial accidents. Recently, there has been a greater appreciation of mid-foot sprains that represent a spectrum of injury to the Lisfranc ligament complex. As a result, there has been an increased incidence of such injury resulting from low-energy trauma in activities ranging from recreational activity to elite athletic activity. This article discusses issues related to anatomy, clinical presentation, mechanism of injury, and diagnosis that are necessary to provide appropriate treatment for these injuries. There should be a high index of suspicion of this injury, and prompt diagnosis is important to allow athletes to return to sport with the best possible outcome.

Factors that distinguish serious versus less severe strain and sprain injuries: an analysis of electric utility workers.

BACKGROUND: Occupational sprain and strain injuries are one of the most common types of nonfatal occupational injuries and a significant source of lost workdays. This study examines factors associated with severe work-related sprain/strain injuries to the back, shoulder, and knees. METHODS: A synthetic case-control study was performed (controls were selected from the same pool of utility workers as cases). Cases included all electric utility workers who had experienced a severe work-related sprain/strain injury to the back, knee, or shoulder. Primary controls were selected from all workers who had sustained a minor injury. Secondary controls were selected from employees with a minor sprain/strain injury to the back, knee, or shoulder. Multivariate logistic regression models were used to estimate odds ratios and 95% confidence intervals. RESULTS: Workers 41 years and older were more likely to have experienced severe shoulder sprain/strain injuries [Age 41-50: OR = 3.62, 95% CI: 1.71-7.65; age 51 and older: OR = 4.49, 95% CI: 1.89-10.67] and severe back sprain/strain injuries [Age 41-50: OR = 1.70, 95% CI: 1.06-2.33; age 51 and older: OR = 1.5, 95% CI: 0.90-2.52]. Line workers and maintenance workers had an increased risk of serious sprain/strain injuries. Gender and day of week were not significantly associated with sprain/strain injuries. DISCUSSION: Though this study is limited by available data, future studies may benefit from this preliminary examination of occupational and demographic characteristics associated with serious sprain/strain injuries among electric utility workers.