Anti-tumor therapy with macroencapsulated endostatin producer cells

Background: Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Results: Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 10(7) recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. Conclusions: This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors. Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.

A comparison of lower limb EMG and ground reaction forces between barefoot and shod gait in participants with diabetic neuropathic and healthy controls

Background: It is known that when barefoot, gait biomechanics of diabetic neuropathic patients differ from nondiabetic individuals. However, it is still unknown whether these biomechanical changes are also present during shod gait which is clinically advised for these patients. This study investigated the effect of the participants own shoes on gait biomechanics in diabetic neuropathic individuals compared to barefoot gait patterns and healthy controls. Methods: Ground reaction forces and lower limb EMG activities were analyzed in 21 non-diabetic adults (50.9 +/- 7.3 yr, 24.3 +/- 2.6 kg/m(2)) and 24 diabetic neuropathic participants (55.2 +/- 7.9 yr, 27.0 +/- 4.4 kg/m(2)). EMG patterns of vastus lateralis, lateral gastrocnemius and tibialis anterior, along with the vertical and antero-posterior ground reaction forces were studied during shod and barefoot gait. Results: Regardless of the disease, walking with shoes promoted an increase in the first peak vertical force and the peak horizontal propulsive force. Diabetic individuals had a delay in the lateral gastrocnemius EMG activity with no delay in the vastus lateralis. They also demonstrated a higher peak horizontal braking force walking with shoes compared to barefoot. Diabetic participants also had a smaller second peak vertical force in shod gait and a delay in the vastus lateralis EMG activity in barefoot gait compared to controls. Conclusions: The change in plantar sensory information that occurs when wearing shoes revealed a different motor strategy in diabetic individuals. Walking with shoes did not attenuate vertical forces in either group. Though changes in motor strategy were apparent, the biomechanical did not support the argument that the use of shoes contributes to altered motor responses during gait.

Plantar Pressures During Shod Gait in Diabetic Neuropathic Patients with and without a History of Plantar Ulceration

Background: Diabetic neuropathy leads to progressive loss of sensation, lower-limb distal muscle atrophy, autonomic impairment, and gait alterations that overload feet. This overload has been associated with plantar ulcers even with consistent daily use of shoes. We sought to investigate and compare the influence of diabetic neuropathy and plantar ulcers in the clinical history of diabetic neuropathic patients on plantar sensitivity, symptoms, and plantar pressure distribution during gait while patients wore their everyday shoes. Methods: Patients were categorized into three groups: a control group (CG; n = 15), diabetic patients with a history of neuropathic ulceration (DUG; n = 8), and diabetic patients without a history of ulceration (DG; n = 10). Plantar pressure variables were measured by Pedar System shoe insoles in five plantar regions during gait while patients wore their own shoes. Results: No statistical difference between neuropathic patients with and without a history of plantar ulcers was found in relation to symptoms, tactile sensitivity, and duration of diabetes. Diabetic patients without ulceration presented the lowest pressure-time integral under the heel (72.1 +/- 16.1 kPa x sec; P=.0456). Diabetic patients with a history of ulceration presented a higher pressure-time integral at the midfoot compared to patients in the control group (59.6 +/- 23.6 kPa x sec x 45.8 +/- 10.4 kPa x sec; P = .099), and at the lateral forefoot compared to diabetic patients without ulceration (70.9 +/- 17.7 kPa sec x 113.2 +/- 61.1 kPa x sec, P = .0193). Diabetic patients with ulceration also presented the lowest weight load under the hallux (0.06 +/- 0.02%, P = .0042). Conclusions: Although presenting a larger midfoot area, diabetic neuropathic patients presented greater pressure-time integrals and relative loads over this region. Diabetic patients with ulceration presented an altered dynamic plantar pressure pattern characterized by overload even when wearing daily shoes. Overload associated with a clinical history of plantar ulcers indicates future appearance of plantar ulcers. (J Am Podiatr Med Assoc 99(4): 285-294, 2009)

Phototherapy Improves Healing of Chronic Venous Ulcers

Objective: We tested the hypothesis that LED phototherapy with combined 660-nm and 890-nm light will promote healing of venous ulcers that failed to respond to other forms of treatment. Background Data: A variety of dressings, growth factors, and adjunct therapies are used to treat venous ulcers, but none seems to yield satisfactory results. Materials and Methods: We used a randomized placebo-controlled double-blind study to compare a total of 20 patients divided with 32 chronic ulcers into three groups. In group 1 the ulcers were cleaned, dressed with 1% silver sulfadiazine (SDZ) cream, and treated with placebo phototherapy (<.03 J/cm(-3)) using a Dynatron Solaris 705 phototherapy research device. In group 2 the ulcers were treated similarly but received real phototherapy (3 J/cm(-2)) instead of placebo. In group 3 (controls), the ulcers were simply cleaned and dressed with SDZ without phototherapy. The ulcers were evaluated with digital photography and computer image analysis over 90 d or until full healing was attained. Results: Ulcers treated with phototherapy healed significantly faster than controls when compared at day 30 (p < 0.01), day 60 (p < 0.05), and day 90 (p < 0.001), and similarly healed faster than the placebo-treated ulcers at days 30 and 90 (p < 0.01), but not at day 60. The beneficial effect of phototherapy was more pronounced when the confounding effect of small-sized ulcers was removed from the analysis. Medium- and large-sized ulcers healed significantly faster with treatment (>= 40% rate of healing per month) than placebo or control ulcers (p < 0.05). Conclusion: Phototherapy promotes healing of chronic venous ulcers, particularly large recalcitrant ulcers that do not respond to conventional treatment.

Fat and fiber consumption are associated with peripheral arterial disease in a cross-sectional study of a Japanese-Brazilian population

Background The Western diet plays a role for the epidemics of obesity and related diseases. This study examined a possible association between peripheral arterial disease (PAD) and the dietary components of Japanese immigrants living in Brazil. Methods and Results In this cross-sectional study, 1,267 subjects (aged 30 years) with complete dietary, clinical and laboratory data were studied according to a standardized protocol. Ankle-to-brachial index was used to identify subjects with PAD. The overall prevalence of PAD was 14.6%. Subjects with PAD were older, had lower education and higher mean values of blood pressure, triglycerides, and fasting and 2-h plasma glucose levels compared with those without the disease. Among the subjects with PAD, the consumption of fiber from whole grains (3.0 vs 3.4g, p=0.001) and linoleic acids (11.0 vs 11.7g, p=0.017) were lower and intake of total (72.8 vs 69.1 a, p=0.016) and saturated fatty acids (17.4 vs 16.3g, p=0.012) were higher than those without PAD. Results of multiple logistic regression analysis showed a significant association between PAD with high total fat intake, low intake of fiber from fruit and oleic acid, independently of other variables. Conclusions Despite limitations in examining the cause-effect relationship, the data support the notion that diet could be important in reducing the occurrence of PAD.

Silica-based cationic bilayers as immunoadjuvants

Background: Silica particles cationized by dioctadecyldimethylammonium bromide (DODAB) bilayer were previously described. This work shows the efficiency of these particulates for antigen adsorption and presentation to the immune system and proves the concept that silica-based cationic bilayers exhibit better performance than alum regarding colloid stability and cellular immune responses for vaccine design. Results: Firstly, the silica/DODAB assembly was characterized at 1 mM NaCl, pH 6.3 or 5 mM Tris. HCl, pH 7.4 and 0.1 mg/ml silica over a range of DODAB concentrations (0.001-1 mM) by means of dynamic light scattering for particle sizing and zeta-potential analysis. 0.05 mM DODAB is enough to produce cationic bilayer-covered particles with good colloid stability. Secondly, conditions for maximal adsorption of bovine serum albumin (BSA) or a recombinant, heat-shock protein from Mycobacterium leprae (18 kDa-hsp) onto DODAB-covered or onto bare silica were determined. At maximal antigen adsorption, cellular immune responses in vivo from delayed-type hypersensitivity reactions determined by foot-pad swelling tests (DTH) and cytokines analysis evidenced the superior performance of the silica/DODAB adjuvant as compared to alum or antigens alone whereas humoral response from IgG in serum was equal to the one elicited by alum as adjuvant. Conclusion: Cationized silica is a biocompatible, inexpensive, easily prepared and possibly general immunoadjuvant for antigen presentation which displays higher colloid stability than alum, better performance regarding cellular immune responses and employs very low, micromolar doses of cationic and toxic synthetic lipid.

Treatment of Osteomyelitis in the Feet of Diabetic Patients by Photodynamic Antimicrobial Chemotherapy

Objective: This article describes two inexpensive photodynamic antimicrobial chemotherapy (PACT) protocols to provide intensive local care on ulcerated feet of diabetic patients with osteomyelitis. Background Data: Patients with this condition generally have poor quality of life. The usual treatment consists of the administration of a cocktail of drugs including anti-inflammatories, promoters of blood circulation, and systemic antibiotics. However, depending on the conditions of the tissues, amputation may be required. Consequently, it is important to develop PACT protocols that can help avoid amputation. Materials and Methods: Two PACT protocols were applied to two diabetic patients with osteomyelitis. These protocols were based on several PACT sessions that consisted of: (1) local injection of mixtures of phenothiazines (2% in water) and Hypericum perforatum extract (10% in propylene glycol), and (2) illumination, lasting 10 min, applied to the lesion's interior and exterior using, respectively, an optical fiber and a non-coherent light source. The frequency of PACT was daily or every other day in the beginning, and weekly after tissue recovery begun. The patients were followed clinically and by radiographic testing. Results: Both PACT protocols helped cure these patients who were about to have amputation of their feet. Radiograms showed that bone had healed and that the bone's texture had improved. Conclusion: Here we have described efficient and affordable PACT protocols to treat osteomyelitis in the feet of diabetic patients. This treatment modality should be considered by vascular surgeons and by orthopedists to treat osteomyelitis that is resistant to conventional treatments.

Dual-task interference: Attentional and neurophysiological influences

Performing two tasks simultaneously often degrades performance of one or both tasks. While this dual-task interference is classically interpreted in terms of shared attentional resources, where two motor tasks are performed simultaneously interactions within primary motor cortex (i.e., activity-dependent coupling) may also be a contributing factor. In the present study TMS (transcranial magnetic stimulation) was used to examine the contribution of activity-dependent coupling to dual-task interference during concurrent performance of a bimanual coordination task and a discrete probe reaction time (RT) task involving the foot. Experiments 1 and 2 revealed that activity-dependent coupling within the leg corticomotor pathway was greater during dual-task performance than single-task performance, and this was associated with interference on the probe RT task (i.e., increased RT). Experiment 3 revealed that dual-task interference occurred regardless of whether the dual-task involved two motor tasks or a motor and cognitive task, however activity-dependent coupling was present only when a dual motor task was performed. This suggests that activity-dependent coupling is less detrimental to performance than attentional processes operating upstream of the corticomotor system. Finally, while prioritising the RT task reduced, but did not eliminate, dual-task interference the contribution of activity-dependent coupling to dual-task interference was not affected by task prioritisation. This suggests that although activity-dependent coupling may contribute to dual motor-task interference, attentional processes appear to be more important. It also suggests that activity-dependent coupling may not be subject to modulation by attentional processes. (C) 2009 Elsevier B.V. All rights reserved.

THE SUMMATION OF VOLUNTARY AND ELECTRICAL ELICITED STIMULUS INCREASES JOINT TORQUE?

The aim of this study is to analyze the effect of neuromuscular electrical stimulation (NMES) on myoelectrical activity and on joint torque during isometric plantar flexion contraction. Ten healthy young adult subjects participate in this study. The electrodes for NMES are placed along posterior thigh along ciatic nerve trajectory. It is measured the myoelectrical activity and the isometric torque generated by ankle plantar flexion with an isokinetic dynamometer. The conditions of isometric contractions are maximum isometric voluntary contraction (MIVC), NMES, and association of both (MIVC+NMES). The results show lower torque during NMES and larger SOL activity compare to the others. Besides, in order to keep the same objective task (to produce the same level of torque), neuromuscular adaptations are necessary on the common drive.

IS ORDINARY ELECTRIC DRILLS` VENTING PORT A POTENTIAL SOURCE OF SURGICAL INFECTION?

Objective: To evaluate the potential risk of surgical contamination by the venting port of ordinary electric drills (ED) employed in orthopaedic surgeries. Materials and Methods: an experimental laboratory, randomized study was developed to analyze EDs in surgical practice and new cleaned and sterilized equipment, which were contaminated with Bacillus atrophaeus spores at a concentration of 84 X 10(6) UFC. The air generated by the engine of each drill was collected and cultivated on sterile agar plates. Results: Positive culture was identified in two ED in surgical practice, as well as a positive culture to Bacillus atrophaeus with 1 CFU growth (1, 19 X 10(-8)). Conclusion: In the conditions of the experiment, the air generated by the venting port of the ED`s engine does not consist of a source of contamination for the surgical site.

Age-related difference on weight transfer during unconstrained standing

The ability to transfer weight from one lower limb to the other is essential for the execution of daily life activities and little is known about how weight transfer during unconstrained natural standing is affected by age. This study examined the weight transfer ability of elderly individuals during unconstrained standing (for 30 mill) in comparison to young adults. The subjects (19 healthy elderly adults, range 65-80 years, and 19 healthy young adults, range 18-30 years) stood with each foot on a separate force plate and were allowed to change their posture freely at any time. The limits of stability and base of support width during standing, measures of mobility (using the timed up and go and the preferred walking speed tests), and fear of falling were also measured. In comparison to the young adults, during unconstrained standing the elderly adults produced four times fewer weight transfers of large amplitude (greater than,half of their body weight). The limits of stability and base of support width were significantly smaller for the elderly adults but there were no significant differences in the measures of mobility and in the fear of falling score compared to young adults. The observed significant age-related decrease in the use of weight transfer during unconstrained standing, despite any difference in the measured mobility of the subjects, suggests that this task reveals unnoticed and subtle differences in postural control, which may help to better understand age related impairments in balance that the elderly population experiences. (C) 2010 Elsevier B.V. All rights reserved.

Effects of joint immobilization on standing balance

We investigated the effect of joint immobilization on the postural sway during quiet standing. We hypothesized that the center of pressure (COP), rambling, and trembling trajectories would be affected by joint immobilization. Ten young adults stood on a force plate during 60 s without and with immobilized joints (only knees constrained, CK; knees and hips, CH; and knees, hips, and trunk, CT). with their eyes open (OE) or closed (CE). The root mean square deviation (RMS, the standard deviation from the mean) and mean speed of COP, rambling, and trembling trajectories in the anterior-posterior and medial-lateral directions were analyzed. Similar effects of vision were observed for both directions: larger amplitudes for all variables were observed in the CE condition. In the anterior-posterior direction, postural sway increased only when the knees, hips, and trunk were immobilized. For the medial-lateral direction, the RMS and the mean speed of the COP, rambling, and trembling displacements decreased after immobilization of knees and hips and knees, hips, and trunk. These findings indicate that the single inverted pendulum model is unable to completely explain the processes involved in the control of the quiet upright stance in the anterior-posterior and medial-lateral directions. (C) 2009 Elsevier B.V. All rights reserved.

Leg preference and interlateral performance asymmetry in soccer player children

Strength of leg peference and interlateral asymmetry in kinematics of kicking a ball for power were assessed in 6- to 10-year-old right-footed soccer player children. Leg preference was evaluated separately for three task categories: balance stabilization, soccer related mobilization, and general mobilization. The results showed that while both categories of mobilization tasks were featured by a consistent preference for the right leg, in stabilization tasks we observed lower scores and greater interindividual variability of leg preference. No effect of age was detected on leg preference. Analysis of peak foot velocity revealed similar increment of performance of the right and left legs from the ages 6-8 to 10 years. This finding supports the notion of stable Magnitude of interlateral asymmetries of performance during motor development. (C) 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 799-806, 2008.

Biomechanical characteristics of elderly individuals walking on land and in water

In this study, we examined Spatial-temporal gait stride parameters, lower extremity joint angles, ground reaction forces (GRF) components, and electromyographic activation patterns of 10 healthy elderly individuals (70 +/- 6 years) walking in water and on land and compared them to a reference group of 10 younger adults (29 +/- 16 years). They all walked at self-selected comfortable speeds both on land and while immersed in water at the Xiphoid process level. Concerning the elderly individuals, the main significant differences observed were that they presented shorter stride length, slower speed, lower GRF values, higher horizontal impulses, smaller knee range of motion, lower ankle dorsiflexion, and more knee flexion at the stride`s initial contact in water than on land. Concerning the comparison between elderly individuals and adults, elderly individuals walked significantly slower on land than adults but both groups presented the same speed walking in water. In water, elderly individuals presented significantly shorter stride length, lower stride duration, and higher stance period duration than younger adults. That is, elderly individuals` adaptations to walking in water differ from those in the younger age group. This fact should be considered when prescribing rehabilitation or fitness programs for these populations. (C) 2006 Elsevier Ltd. All rights reserved.

Kinematic, kinetic and EMG patterns during downward squatting

The aim of this study was to investigate the kinematic, kinetic, and electromyographic pattern before, during and after downward squatting when the trunk movement is restricted in the sagittal plane. Eight healthy subjects performed downward squatting at two different positions, semisquatting (40 degrees knee flexion) and half squatting (70 degrees knee flexion). Electromyographic responses of the vastus medialis oblique, vastus medialis longus, rectus femoris, vastus lateralis, biceps femoris, semitendineous, gastrocnemius lateralis, and tibialis anterior were recorded. The kinematics of the major joints were reconstructed using an optoelectronic system. The center of pressure (COP) was obtained using data collected from one force plate, and the ankle and knee joint torques were calculated using inverse dynamics. In the upright position there were small changes in the COP and in the knee and ankle joint torques. The tibialis anterior provoked the disruption of this upright position initiating the squat. During the acceleration phase of the squat the COP moved posteriorly, the knee joint torque remained in flexion and there was no measurable muscle activation. As the body went into the deceleration phase, the knee joint torque increased towards extension with major muscle activities being observed in the four heads of the quadriceps. Understanding these kinematic, kinetic and EMG strategies before, during and after the squat is expected to be beneficial to practitioners for utilizing squatting as a task for improving motor function. (C) 2006 Elsevier Ltd. All rights reserved.