Effect of prebiotic fiber on physical function and gut microbiota in adults, mostly women, with knee osteoarthritis and obesity: a randomized controlled trial.

PURPOSE: Obesity is a primary risk factor for knee osteoarthritis (OA). Prebiotics enhance beneficial gut microbes and can reduce body fat and inflammation. Our objective was to examine if a 6-month prebiotic intervention improved physical function in adults with knee osteoarthritis and obesity. We also measured knee pain, body composition, quality of life, gut microbiota, inflammatory markers, and serum metabolomics. METHODS: Adults (n = 54, mostly women) with co-morbid obesity (BMI > 30 kg/m2) and unilateral/bilateral knee OA were randomly assigned to prebiotic (oligofructose-enriched inulin; 16 g/day; n = 31) or isocaloric placebo (maltodextrin; n = 21) for 6 months. Performance based-tests, knee pain, quality of life, serum metabolomics and inflammatory markers, and fecal microbiota and short-chain fatty acids were assessed. RESULTS: Significant between group differences were detected for the change in timed-up-and-go test, 40 m fast paced walk test, and hand grip strength test from baseline that favored prebiotic over placebo. Prebiotic also reduced trunk fat mass (kg) at 6 months and trunk fat (%) at 3 months compared to placebo. There was a trend (p = 0.059) for reduced knee pain at 6 months with prebiotic versus placebo. In gut microbiota analysis, a total of 37 amplicon sequence variants differed between groups. Bifidobacterium abundance was positively correlated with distance walked in the 6-min walk test and hand grip strength. At 6 months, there was a significant separation of serum metabolites between groups with upregulation of phenylalanine and tyrosine metabolism with prebiotic. CONCLUSION: Prebiotics may hold promise for conservative management of knee osteoarthritis in adults with obesity and larger trials are warranted. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov/study/NCT04172688.

Effects of ß-hydroxy-ß-methylbutyrate supplementation on muscle mass and strength in onabotulinumtoxin type-A-injected and contralateral quadriceps femoris in rabbits.

OBJECTIVE: To determine the effects of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits. METHODS: A total of 21, female rabbits were divided into 3 groups (n=7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs. RESULTS: Injected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p<0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p<0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively. CONCLUSION: While HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.

Effect of a prebiotic supplement on knee joint function, gut microbiota, and inflammation in adults with co-morbid obesity and knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Osteoarthritis (OA) is a chronic and painful condition where the articular cartilage surfaces progressively degenerate, resulting in loss of function and progressive disability. Obesity is a primary risk factor for the development and progression of knee OA, defined as the "metabolic OA" phenotype. Metabolic OA is associated with increased fat deposits that release inflammatory cytokines/adipokines, thereby resulting in systemic inflammation which can contribute to cartilage degeneration. There is currently no cure for OA. Prebiotics are a type of dietary fiber that can positively influence gut microbiota thereby reducing systemic inflammation and offering protection of joint integrity in rodents. However, no human clinical trials have tested the effects of prebiotics in adults with obesity suffering from knee OA. Therefore, the purpose of this double-blind, placebo-controlled, randomized trial is to determine if prebiotic supplementation can, through positive changes in the gut microbiota, improve knee function and physical performance in adults with obesity and knee OA. METHODS: Adults (n = 60) with co-morbid obesity (BMI > 30 kg/m2) and knee OA (Kellgren-Lawrence grade II-III) will be recruited from the Alberta Hip and Knee Clinic and the Rocky Mountain Health Clinic and surrounding community of Calgary, Canada, and randomized (stratified by sex, BMI, and age) to prebiotic (oligofructose-enriched inulin; 16 g/day) or a calorie-matched placebo (maltodextrin) for 6 months. Anthropometrics, performance-based tests, knee pain, serum inflammatory markers and metabolomics, quality of life, and gut microbiota will be assessed at baseline, 3 months, 6 months (end of prebiotic supplementation), and 3 months following the end of the prebiotic supplementation. CLINICAL SIGNIFICANCE: There is growing pressure on health care systems for aggressive OA treatment such as total joint replacement. Less aggressive, yet effective, conservative treatment options have the potential to address the growing prevalence of co-morbid obesity and knee OA by delaying the need for joint replacement or ideally preventing its need altogether. The results of this clinical trial will provide the first evidence regarding the efficacy of prebiotic supplementation on knee joint function and pain in adults with obesity and knee OA. If successful, the results may provide a simple, safe, and easy to adhere to intervention to reduce knee joint pain and improve the quality of life of adults with co-morbid knee OA and obesity. TRIAL REGISTRATION: Clinical Trials.gov NCT04172688 . Registered on 21 November 2019.

Force depression following a stretch-shortening cycle depends on the amount of residual force enhancement established in the initial stretch phase.

Studies on residual force enhancement (rFE) and residual force depression (rFD) of the muscle-tendon unit (MTU) have typically been conducted independent of each other, with little information available on how stretch-induced rFE affects the shortening phase and the steady-state MTU isometric force at the end of stretch-shortening cycles (SSCs). We showed previously that when rFE is kept constant, but the force at the end of the stretch is varied by changing the stretch speed, the steady-state forces at the end of SSCs were the same. These results led to the hypothesis that the amount of rFE of the MTU established in the initial stretch phase of SSCs determines the steady-state force following the shortening phase of SSCs. This study was aimed at testing this hypothesis. Steady-state MTU isometric thumb adduction forces were measured for pure isometric contractions, following pure shortening contractions, following pure stretch contractions, and following SSCs with constant shortening speed and magnitude. However, two stretch magnitudes (30° and 10° thumb abduction) and stretch speeds (15°/sec and ~ 60°/sec, respectively) were chosen such that forces at the end of the stretch phase of the SSCs were the same, while rFE differed substantially. As hypothesized, the steady-state isometric MTU forces following SSCs were positively related to the stretch-magnitude dependent amount of rFE established in the stretch phase and were independent of the force reached at the end of the stretch phase in SSCs. Among many competing theories, these results can potentially be explained with the idea that there is a length-specific engagement of a passive structural element at the initial length of muscle activation.

Force depression following a stretch-shortening cycle is independent of stretch peak force and work performed during shortening.

The steady-state isometric force following active muscle shortening or lengthening is smaller (force depression; FD) or greater (residual force enhancement; RFE) than a purely isometric contraction at the corresponding length. The mechanisms behind these phenomena remain not fully understood, with few studies investigating the effects of FD and RFE in stretch-shortening cycles (SSC). The purpose of this study was to investigate the influence of RFE and peak force at the end of the stretch phase on the steady-state isometric force following shortening. Isometric thumb adduction force measurements were preceded by an isometric, a shortening contraction to induce FD, and SSCs at different stretch speeds (15°/s, 60°/s, and 120°/s). The different peak force values at the end of stretch and the different amounts of work performed during shortening did not influence the steady-state isometric force at the end of the SSC. We conclude that the FD following SSC depends exclusively on the amount of RFE established in the initial stretch phase in situations where the timing and contractile conditions of the shortening phase are kept constant .

Messenger RNA profiling of rabbit quadriceps femoris after repeat injections of botulinum toxin: Evidence for a dynamic pattern without further structural alterations.

INTRODUCTION: Onabotulinum toxin type A (BoNT-A) is widely used clinically, but it may cause adverse effects. Earlier studies showed repeat BoNT-A injections did not cause progressive atrophy or function loss. The purpose of this study was to assess the influence of repeat BoNT-A injections into rabbit muscle on subsequent molecular alterations. METHODS: Twenty-two rabbits received 0, 1, 2, or 3 BoNT-A injections in the quadriceps femoris muscle at 3-month intervals and were euthanized 6 months after the last injection. Aliquots of both injected and contralateral muscle were frozen, and the total RNA quantified. RESULTS: Total RNA per illigram wet weight tissue was significantly elevated compared with control after 1, 2, or 3 BoNT-A injections. Analysis of mRNA levels for inflammatory molecules, proteinases, adipokines, and mesenchymal stem cells were elevated with increasing BoNT-A injections in injected leg and contralateral leg. DISCUSSION: Future studies should focus on the safety and possible complications of repeat BoNT-A treatments. Muscle Nerve 57: 487-493, 2018.

Shortening-induced force depression is modulated in a time- and speed-dependent manner following a stretch-shortening cycle.

The steady-state isometric force following active muscle shortening or lengthening is smaller (force depression, FD) or greater (residual force enhancement, RFE) than a purely isometric contraction at the corresponding length. The mechanism underlying these phenomena is not explained within the context of the cross-bridge theory, with few studies investigating the effects of FD and RFE in stretching-shortening cycle (SSC). The purpose of this study was to perform SSC, where the time between the end of stretch and the end of shortening was manipulated by (1) adding a pause between stretch and shortening (protocol 1) or (2) performing the shortening contraction at different speeds (protocol 2). The results show that, in protocol 1, FD was reduced for SSC with a 0-sec and 0.5-sec interval between stretching and shortening, but was the same for SSC with a 1-sec interval compared to the pure FD condition. In protocol 2, FD was reduced for SSC with shortening speeds of 30 and 60°/sec, but was the same for shortening speeds of 15 and 20°/sec compared to the pure FD condition. These findings provide evidence that stretch preceding shortening affects FD in a time- and speed-dependent manner, providing new information on the potential mechanism of FD and RFE.

In vivo Sarcomere Lengths and Sarcomere Elongations Are Not Uniform across an Intact Muscle.

Sarcomere lengths have been a crucial outcome measure for understanding and explaining basic muscle properties and muscle function. Sarcomere lengths for a given muscle are typically measured at a single spot, often in the mid-belly of the muscle, and at a given muscle length. It is then assumed implicitly that the sarcomere length measured at this single spot represents the sarcomere lengths at other locations within the muscle, and force-length, force-velocity, and power-velocity properties of muscles are often implied based on these single sarcomere length measurements. Although, intuitively appealing, this assumption is yet to be supported by systematic evidence. The objective of this study was to measure sarcomere lengths at defined locations along and across an intact muscle, at different muscle lengths. Using second harmonic generation (SHG) imaging technique, sarcomere patterns in passive mouse tibialis anterior (TA) were imaged in a non-contact manner at five selected locations ("proximal," "distal," "middle," "medial," and "lateral" TA sites) and at three different lengths encompassing the anatomical range of motion of the TA. We showed that sarcomere lengths varied substantially within small regions of the muscle and also for different sites across the entire TA. Also, sarcomere elongations with muscle lengthening were non-uniform across the muscle, with the highest sarcomere stretches occurring near the myotendinous junction. We conclude that muscle mechanics derived from sarcomere length measured from a small region of a muscle may not well-represent the sarcomere length and associated functional properties of the entire muscle.

Residual force enhancement following shortening is speed-dependent.

The steady-state isometric force following active muscle shortening or lengthening is smaller (force depression; FD) or greater (residual force enhancement; RFE) than a purely isometric contraction at the corresponding length. The mechanisms underlying these phenomena are not explained within the context of the cross-bridge theory and are rarely studied in concert. Previous studies have shown RFE to be speed-independent. In the present study, we investigated if RFE preceded by active shortening is time-dependent by electrically evoking RFE in the human adductor pollicis muscle. The results shown that a slow stretch following FD fully re-established RFE compared to higher speeds of stretch. The mechanism(s) responsible for the recovery of RFE following a preceding shortening contraction (FD) might be associated with the recovery of cross-bridge based force and/or the re-engagement of a passive structural element (titin). Voluntary interaction with one's environment involves highly coordinated shortening and lengthening muscle contractions. Therefore comprehending these history-dependent muscle properties in the context of movement control is paramount in understanding the behavior of in vivo motor control.

A clinically relevant BTX-A injection protocol leads to persistent weakness, contractile material loss, and an altered mRNA expression phenotype in rabbit quadriceps muscles.

Botulinum toxin type-A (BTX-A) injections have become a common treatment modality for patients suffering from muscle spasticity. Despite its benefits, BTX-A treatments have been associated with adverse effects on target muscles. Currently, application of BTX-A is largely based on clinical experience, and research quantifying muscle structure following BTX-A treatment has not been performed systematically. The purpose of this study was to evaluate strength, muscle mass, and contractile material six months following a single or repeated (2 and 3) BTX-A injections into the quadriceps femoris of New Zealand white rabbits. Twenty three skeletally mature rabbits were divided into four groups: experimental group rabbits received 1, 2, or 3 injections at intervals of 3 months (1-BTX-A, 2-BTX-A, 3-BTX-A, respectively) while control group rabbits received volume-matched saline injections. Knee extensor strength, quadriceps muscle mass, and quadriceps contractile material of the experimental group rabbits were expressed as a percentage change relative to the control group rabbits. One-way ANOVA was used to determine group differences in outcome measures (α=0.05). Muscle strength and contractile material were significantly reduced in experimental compared to control group rabbits but did not differ between experimental groups. Muscle mass was the same in experimental BTX-A and control group rabbits. We concluded from these results that muscle strength and contractile material do not fully recover within six months of BTX-A treatment.

Tibiofemoral loss of contact area but no changes in peak pressures after meniscectomy in a Lapine in vivo quadriceps force transfer model.

PURPOSE: The menisci are thought to modulate load transfer and to absorb shocks in the knee joint. No study has experimentally measured the meniscal functions in the intact, in vivo joint loaded by physiologically relevant muscular contractions. METHODS: Right knee joints of seven New Zealand white rabbits were loaded using isometric contractions of the quadriceps femoris muscles controlled by femoral nerve stimulation. Isometric knee extensor torques at the maximal and two submaximal force levels were performed at knee angles of 70°, 90°, 110°, and 130°. Patellofemoral and tibiofemoral contact areas and pressure distributions were measured using Fuji Presensor film inserted above and below the menisci and also with the menisci removed. RESULTS: Meniscectomy was associated with a decrease in tibiofemoral contact area ranging from 30 to 70% and a corresponding increase in average contact pressures. Contact areas measured below the menisci were consistently larger than those measured on top of the menisci. Contact areas in the patellofemoral joint (PFJ), and peak pressures in tibiofemoral and PFJs, were not affected by meniscectomy. Contact areas and peak pressures in all joints depended crucially on knee joint angle and quadriceps force: The more flexed the knee joint was, the larger were the contact areas and the higher were the peak pressures. CONCLUSIONS: In agreement with the literature, removal of the menisci was associated with significant decreases in tibiofemoral contact area and corresponding increases in average contact pressures, but surprisingly, peak pressures remained unaffected, indicating that the function of the menisci is to distribute loads across a greater contact area.

Do skeletal muscle properties recover following repeat onabotulinum toxin A injections?

Onabotulinum toxin A (BTX-A) is a frequently used treatment modality to relax spastic muscles by preventing acetylcholine release at the motor nerve endings. Although considered safe, previous studies have shown that BTX-A injections cause muscle atrophy and deterioration in target and non-target muscles. Ideally, muscles should fully recover following BTX-A treatments, so that muscle strength and performance are not affected in the long-term. However, systematic, long-term data on the recovery of muscles exposed to BTX-A treatments are not available, thus practice guidelines on the frequency and duration of BTX-A injections, and associated recovery protocols, are based on clinical experience with little evidence-based information. Therefore, the purpose of this study was to investigate muscle recovery following a six months, monthly BTX-A injection (3.5 U/kg) protocol. Twenty seven skeletally mature NZW rabbits were divided into 5 groups: Control (n=5), zero month recovery - BTX-A+0M (n=5), one month recovery - BTX-A+1M (n=5), three months recovery - BTX-A+3M (n=5), and six months recovery - BTX-A+6M (n=7). Knee extensor strength, muscle mass and percent contractile material in injected and contralateral non-injected muscles was measured at each point of recovery. Strength and muscle mass were partially and completely recovered in injected and contralateral non-injected muscles for BTX-A+6M group animals, respectively. The percent of contractile material partially recovered in the injected, but did not recover in the contralateral non-injected muscles. We conclude from these results that neither target nor non-target muscles fully recover within six months of a BTX-A treatment protocol and that clinical studies on muscle recovery should be pursued.

Long-term repetitive mechanical loading of the knee joint by in vivo muscle stimulation accelerates cartilage degeneration and increases chondrocyte death in a rabbit model.

BACKGROUND: Excessive chronic loading is thought to be one factor responsible for the onset of osteoarthritis. For example, studies using treadmill running have shown an increased risk for osteoarthritis, thereby suggesting that muscle-induced joint loading may play a role in osteoarthritis onset and progression. However, in these studies, muscle-induced loading was not carefully quantified. Here, we present a model of controlled muscular loading which allows for the accurate quantification of joint loading. The aim of this study was to evaluate the effects of long-term, cyclic, isometric and dynamic, muscle-induced joint loading of physiologic magnitude but excessive intensity on cartilage integrity and cell viability in the rabbit knee. METHODS: 24 rabbits were divided into an (i) eccentric, (ii) concentric, or (iii) isometric knee extensor contraction group (50 min of cyclic, submaximal stimulation 3 times/week for four weeks=19,500 cycles) controlled by the stimulation of a femoral nerve cuff electrode on the right hind limb. The contralateral knee was used as a non-loaded control. The knee articular cartilages were analysed by confocal microscopy for chondrocyte death, and histologically for Mankin Score, cartilage thickness and cell density. FINDINGS: All loaded knees had significantly increased cell death rates and Mankin Scores compared to the non-loaded joints. Cartilage thicknesses did not systematically differ between loaded and control joints. INTERPRETATION: Chondrocyte death and Mankin Scores were significantly increased in the loaded joints, thereby linking muscular exercise of physiologic magnitude but excessive intensity to cartilage degeneration and cell death in the rabbit knee.

Dynamic in-vivo force transfer in the lapine knee loaded by quadriceps muscle contraction.

BACKGROUND: The rabbit knee is a frequently used model for experimental osteoarthritis (OA). Despite the acknowledged importance of joint loading in the onset and progression of OA, the load transfer in the three compartments of the intact rabbit knee remains unknown. Therefore, this study was aimed at determining load transfer in the three compartments for isometric, concentric, and eccentric knee extensor contractions. METHODS: Maximal and sub-maximal isometric, concentric, and eccentric knee extensor contractions were produced by electrical stimulation of the femoral nerve in 13 rabbits. Knee extensor forces were measured using a custom-built servomotor. Contact areas and pressure distributions were measured in the patello-femoral, and the medial and lateral tibio-femoral joints using Fuji Presensor film. FINDINGS: Contact areas and peak pressures increased with increasing quadriceps forces for all compartments. Maximal knee extensor forces, joint moments, and contact pressures reached values of 504 N, 5.5 Nm and 60 MPa, respectively. Force transfer in the patello-femoral joint was about twice that observed in the individual tibio-femoral joints. During isometric contractions, force transfer was higher in the medial compared to the lateral tibio-femoral joint, while this trend was reversed for dynamic contractions. INTERPRETATION: The results of this study suggest that the increasing muscular forces are transferred through an increased contact area, thereby limiting the increase in average contact pressure. These results may be used as reference data for contact pressures in the intact rabbit knee and may form the foundation for studies using the lapine knee as an experimental model of osteoarthritis.

The effects of electrical stimulation exercise on muscles injected with botulinum toxin type-A (botox).

Botulinum toxin type A (BTX-A) is a frequently used treatment modality for a variety of neuromuscular disorders. It acts by preventing acetylcholine release at the motor nerve endings, inducing muscle paralysis. Although considered safe, studies suggest that BTX-A injections create adverse effects on target and non-target muscles. We speculate that these adverse effects are reduced by direct electrical stimulation (ES) exercising of muscles. The aims were to determine the effects of ES exercise on strength, mass, and contractile material in BTX-A injected muscles, and to investigate if BTX-A injections affect non-target muscles. Seventeen New Zealand White (NZW) rabbits were divided into three groups: (1) Control group received saline injections; (2) BTX-A group received monthly BTX-A (3.5 U/kg) injections into the quadriceps for six months and (3) BTX-A+ES group received monthly BTX-A injections and ES exercise three times a week for six months. Outcome measures included knee extensor torque, muscle mass, and contractile material percentage area in injected and contralateral, non-injected quadriceps. Glycogen depletion and direct muscle stimulation were used to assess possible muscle inhibition in non-injected quadriceps. ES exercise partially prevented muscle weakness, atrophy, and contractile material loss in injected muscles, and mostly prevented muscle degeneration in contralateral, non-injected muscles. Non-injected muscles of BTX-A+ES group showed higher force with direct muscle compared to nerve stimulation, and retained glycogen following the depletion protocol, suggesting that BTX-A inhibited activation in non-target muscles. We conclude that ES exercise provides some protection from degeneration to target and non-target muscles during BTX-A treatments.

Effects of Russian current and low-frequency pulsed current on discomfort level and current amplitude at 10% maximal knee extensor torque.

BACKGROUND: Low-frequency pulsed current (LFPC) and Russian current (RC), a type of kilohertz-frequency alternating current, have been frequently used for muscle strengthening in rehabilitation programs. Despite the popularity of these current types, it is unclear which is most effectively able to generate a similar submaximal torque with minimal discomfort and current amplitude. OBJECTIVE: To compare discomfort and current amplitude between LFPC and RC to achieve a knee extensor torque of 10% of the maximal isometric voluntary contraction (MIVC). METHODS: Twenty-two healthy subjects were subjected to three electrically elicited knee extensor submaximal contractions (10% MIVC) that were sustained for 10 seconds. The current amplitude required to achieve 10% MIVC and subjective discomfort were assessed directly by the electrical stimulator and with the Visual Analogue Pain Scale, respectively. A paired t-test was used to determine differences between the electrical currents (α = 0.05). RESULTS: LFPC required significantly lower current amplitude (15%) and a lower discomfort level (50%) to achieve 10% of MIVC compared to RC. CONCLUSION: LFPC current seems to be more effective than RC with respect to discomfort level and current amplitude to produce 10% of MIVC.

The influence of cyclic concentric and eccentric submaximal muscle loading on cell viability in the rabbit knee joint.

BACKGROUND: Cartilage loading is associated with the onset and progression of osteoarthritis and cell death may play an important role in these processes. Although much is known about cell death in joint impact loading, there is no information on joints loaded by muscular contractions. The aim of this study was to evaluate the influence of muscle generated eccentric and concentric submaximal joint loading on chondrocyte viability. We hypothesised that eccentric muscle activation leads to increased cell death rates compared to concentric loading and to controls. METHODS: 16 rabbits received either 50 min of uni-lateral, cyclic eccentric (n=8) or concentric (n=8) knee loading. Muscle activation for these dynamic conditions was equivalent to an activation level that produced 20% of maximum isometric force. Contralateral joints served as unloaded controls. Cell viability was assessed using confocal microscopy. FINDINGS: Eccentric contractions produced greater knee loading than concentric contractions. Sub-maximal contractions caused a significant increase in cell death in the loaded knees compared to the unloaded controls, and eccentric loading caused significantly more cell death than concentric loading. INTERPRETATION: Cyclic sub-maximal muscle loading of the knee caused increased chondrocyte death in rabbits. These findings suggest that low levels of joint loading for prolonged periods, as occurs in endurance exercise or physical labour, may cause chondrocyte death, thereby predisposing joints to degeneration.

Catchlike property in human adductor pollicis muscle.

The "catchlike" property is defined as the dramatic force increase in skeletal muscles when a single pulse is added at the onset of a sub-tetanic low-frequency stimulation train. This property has been observed in single motor units, whole animal and human muscles. It is an inherent property of muscle fibres and is not related to an increase in motor unit recruitment. Despite an abundance of observations, its origin remains unclear. The aim of this study was to induce the catchlike property in human adductor pollicis and identify its possible origin. Thumb adduction forces were measured using ulnar nerve electrical stimulation at 10Hz for reference trains (RTs) with one extra pulse 8ms after the first stimulation pulse for the experimental trains (ETs). Tests were performed at two muscle length and three stimulation levels and muscle stiffness and potentiation were quantified for all test conditions. The ETs showed higher forces and greater rates of force increase than the RTs. In addition, force increase was more pronounced at short compared to long muscle length, but no differences were found in force increase for the three stimulation levels. Furthermore, potentiation and stiffness were similar across all experimental conditions. Together, these results suggest that the increase in force associated with the catchlike property is neither caused by an increased proportion of attached cross-bridges nor potentiation of the muscle, but appears to be muscle length dependent and present in both slow and fast motor units.

Complicações neonatais do diabetes mellitus gestacional ­ DMG / Neonatal complications of gestacional diabetes mellitus ­ GDM

O diabetes mellitus gestacional (DMG) está associado a um risco aumentado de complicações fetais, neonatais e no desenvolvimento a longo prazo. As taxas de aborto espontâneo, natimorto, mal formações congênitas e morbidade e mortalidade perinatal são maiores em filhos de mães diabéticas. As principais complicações neonatais são: macrossomia, hipoglicemia neonatal, deficiência de ferro, alterações da função cardiorrespiratória, hiperbilirrubinemia, anormalidades neurológicas, hipocalcemia, hipomagnesemia e policitemia. A macrossomia predispõe a lesões do parto, especialmente distócia de ombro, maior risco de lesão do plexo braquial, fraturas de clavícula ou do úmero, asfixia perinatal, e, menos frequentemente, hemorragia subdural e paralisia facial. O controle glicêmico rigoroso pré-concepção e durante a gestação associa-se com menor morbimortalidade perinatal. Assim, o controle do DMG representa tarefa de fundamental importância para impedir sequelas em neonatais. (AU)

The gestational diabetes mellitus (GDM) is associated with an increased risk of fetal, neonatal, and possibly long-term complications. The rates of spontaneous abortion, stillbirth, congenital malformations, and perinatal morbidity and mortality are higher in infants of a diabetic mother than in pregnancies with normal glycemic control. The main neonatal complications are: macrosomia, neonatal hypoglycemia, iron deficiency, changes in cardiac and respiratory function, hyperbilirubinemia, neurological abnormalities, hypocalcemia, hypomagnesemia and polycythemia. Macrosomia predisposes to birth injury, especially shoulder dystocia, increased risk of brachial plexus injury, clavicular or humeral fractures, perinatal asphyxia, and, less often, subdural hemorrhage and facial palsy. Strict glycemic control preconception and during pregnancy is associated with lower perinatal morbidity and mortality. Thus, GDM control is of paramount importance to prevent neonatal harm. (AU)

Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox).

Botulinum toxin type A (BTX-A) is a frequently used therapeutic tool to denervate muscles in the treatment of neuromuscular disorders. Although considered safe by the US Food and Drug Administration, BTX-A can produce adverse effects in target and non-target muscles. With an increased use of BTX-A for neuromuscular disorders, the effects of repeat injections of BTX-A on strength, muscle mass and structure need to be known. Therefore, the purpose of this study was to investigate the changes in strength, muscle mass and contractile material in New Zealand White (NZW) rabbits. Twenty NZW rabbits were divided into 4 groups: control and 1, 3 and 6 months of unilateral, repeat injections of BTX-A into the quadriceps femoris. Outcome measures included knee extensor torque, muscle mass and the percentage of contractile material in the quadriceps muscles of the target and non-injected contralateral hindlimbs. Strength in the injected muscles was reduced by 88%, 89% and 95% in the 1, 3 and 6 months BTX-A injected hindlimbs compared to controls. Muscle mass was reduced by 50%, 42% and 31% for the vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM), respectively, at 1 month, by 68%, 51% and 50% at 3 months and by 76%, 44% and 13% at 6 months. The percentage of contractile material was reduced for the 3 and 6 months animals to 80-64%, respectively, and was replaced primarily by fat. Similar, but less pronounced results were also observed for the quadriceps muscles of the contralateral hindlimbs, suggesting that repeat BTX-A injections cause muscle atrophy and loss of contractile tissue in target muscles and also in non-target muscles that are far removed from the injection site.