Sleep and quality of life of patients with glycogen storage disease on standard and modified uncooked cornstarch

Background

Glycemic control in hepatic glycogen storage diseases (GSDs) relies on specific nutritional recommendations, including strict avoidance of a fasting period. Uncooked cornstarch (UCCS) is an important therapeutic component. A new modified UCCS, Glycosade?, was created with the objective of prolonging euglycemia. We aimed to determine the length of euglycemia on Glycosade? using a continuous glucose monitor (CGM) and to evaluate whether longer euglycemia and thus less nighttime interruptions would improve sleep and quality of life (QoL) after the introduction of the modified cornstarch.

The effect of low-load exercise on joint pain,function, and activities of daily living in patients with knee osteoarthritis

Background

Knee osteoarthritis has a lifetime risk of nearly one in two, with obese individuals being most susceptible. While exercise is universally recognized as a critical component for management, unsafe or ineffective exercise frequently leads to exacerbation of joint symptoms.

Non-exercising muscle metabolism during exercise

Glycogen decrements have been observed in non-exercising muscles during exercise. We therefore investigated whether the degraded glycogen was retained within the muscle in the form of glycolytic intermediates, or whether it was effluxed from the non-exercising muscles. For these studies a suspension harness was used to unload the hindlimb muscles at rest and during exercise [McDermott et al. (1987) J Appl Physiol 63:1275–1283]. Concentrations of glycogen and glycolytic intermediates glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, glycerol 3-phosphate, and lactate) were measured in non-exercising and exercising muscles (soleus, plantaris, red and white gastrocnemius) during a 90-min exercise bout 15 m/min, 8% grade). On-line electromyographic analysis showed that the contractile activity in the non-exercising muscles was markedly lower than in the exercising muscles. Similar decrements in muscle glycogen levels were observed in both the non-exercising and exercising muscles at the end of the 90-min, exercise bout (P<0.05), despite significantly different activity profiles. An increase in tissue lactate concentrations occurred in both non-exercising and exercising muscle (P<0.05), although only slight changes in the glycolytic intermediates occurred. The sum total of all the accumulated glycolytic intermediates and lactate (converted to glucosyl units) in the non-exercising muscles only accounted for a small fraction of the glycogen degraded ( 15%–28%). We conclude that the metabolism of glycogen is enhanced in non-exercising muscle, and that glycogen utilization is uncoupled from the energetic demands of the muscle. Furthermore, the glycogen mobilized in non-exercising muscle is not retained within the muscle in other metabolite pools. We speculate that the carbon units derived from glycogen may be effluxed into the circulation to join the oxidizable/gluconeogenic carbon pool.     

Glycogen metabolism and the function of fast and slow muscles of the rat

Changes in glycogen metabolism with function have been explored in a fast (the extensor digitorum longus, EDL) and in a slow (the soleus, S) muscle of rat. The rate of glucose incorporation is not related to the glycogen levels. In the S glycogen levels are lower and glucose incorporation is higher than in EDL and differences almost disappear after denervation and increase with exercise. In the S, synthetic activities may be higher and glycogenolytic activities are lower than in the EDL. The levels are given of many substrates and cofactors which can affect glycogen enzymes in vivo.On the whole, the data indicate that the rate of glycogen turnover can change dramatically with muscle function even at very light work load and may be higher in the so called oxidative than in the glycolytic muscles.     

Muscle energy metabolism: structural and functional features in different types of porcine striated muscles

Striated muscles exhibit a wide range of metabolic activity levels. Heart and diaphragm are muscles with continuous contractile performance, which requires life-long function. In contrast, skeletal muscles like longissimus muscle can adapt metabolism from resting to different stages of exercise. The aim of this study was to compare the morphological features of these three muscles and the expression of genes that are important for energy metabolism. Therefore, histochemical studies were performed for determination of muscle fibre type composition. Oxidative and glycolytic capacity was assessed by measuring isocitrate dehydrogenase (ICDH) and lactate dehydrogenase (LDH) activities. The mRNA expression of glucose transporter 4 (GLUT 4), growth hormone receptor (GHR) and AMP-activated kinase (AMPK) α₁ and α₂ subunits was studied by semiquantitative Northern blotting. Heart, and to a slightly lesser extent diaphragm were highly oxidative muscles characterised by high expression of oxidative muscle fibres and ICDH activity. Longissimus muscle exhibited the highest percentage of glycolytic fibres and LDH activity. GLUT 4 mRNA was lowest in heart reflecting the dependency of heart muscle on fatty acids as major energy source. Higher expression of GLUT 4 in diaphragm indicated that glucose is an important energy substrate in this oxidative muscle. Highest GLUT 4 expression in longissimus should be essential for the refilling of glycogen stores after exercise. AMPK subunits, which are important stimulators of GLUT 4 protein insertion into the sarcolemma, are also highest expressed in longissimus muscle indicating the strong capacity to adapt energy metabolism to large changes in energy demand. Interestingly, AMPK α₁ subunit expression on protein level is strongly restricted to muscle fibres containing type I myosin in this muscle. GHR mRNA expression was also highest in longissimus muscle indicating that an enhanced effect of growth hormone, which is described to be diabetogenic, could be involved in the lower insulin sensitivity of glycolytic muscles.     

Topographical relationships of intramuscular nerves and vessels of the motor endplates in the thigh and gluteal regions of human fetuses: an immunohistochemical study

Purpose

The aim of this study was to describe topography of vessels and nerves in striated muscles to understand individual muscle function.

Materials and methods

Immunohistochemistry for nerve and artery was used to examine the thigh and gluteal muscles of six human midterm fetuses.

Results

The supplying nerves often accompanied arteries along epimysium bundling muscle fibers as well as in the covering fascia surrounding the entire muscle mass. However, courses of nerve twigs were usually independent of those of vessels in muscle bundles. Notably, irrespective of whether or not the vascular bundle accompanied the nerves at the muscle surface or hilus, most of the motor endplate bands did not accompany the vessels.

Conclusion

Since the motor endplates were low vascularised, a chemical induction of vessels for nerve terminal development (or the reversed induction) seemed unlikely in striated muscles. In contrast to proprioceptive neuromuscular facilitation, manual stimulation of the endplate bands may stimulate muscle activity without sympathetic reflexes through vessel-accompanying nerves.

     

Neuromuscular adaptations in older males and females with knee osteoarthritis during weight-bearing force control

Background

Females exhibit significantly greater incidence, prevalence, and severity of osteoarthritis (OA) compared to males. Despite known biological, morphological, and functional differences between males and females, there has been little sex-related investigation into sex-specific biomechanical and neuromuscular responses to OA.

Sustained high glucose exposure sensitizes macrophage responses to cytokine stimuli but reduces their phagocytic activity

Background

Macrophages are tissue resident immune cells important for host defence and homeostasis. During diabetes, macrophages and other innate immune cells are known to have a pro-inflammatory phenotype, which is believed to contribute to the pathogenesis of various diabetic complications. However, diabetic patients are highly susceptible to bacterial infections, and often have impaired wound healing. The molecular mechanism underlying the paradox of macrophage function in diabetes is not fully understood. Recent evidence suggests that macrophage functions are governed by metabolic reprograming. Diabetes is a disorder that affects glucose metabolism; dysregulated macrophage function in diabetes may be related to alterations in their metabolic pathways. In this study, we seek to understand the effect of high glucose exposure on macrophage phenotype and functions.

Results

Bone marrow cells were cultured in short or long term high glucose and normal glucose medium; the number and phenotype of bone marrow derived macrophages were not affected by long-term high glucose treatment. Short-term high glucose increased the expression of IL-1β. Long-term high glucose increased the expression of IL-1β and TNFα but reduced the expression of IL-12p40 and nitric oxide production in M1 macrophage. The treatment also increased Arg-1 and IL-10 expression in M2 macrophages. Phagocytosis and bactericidal activity was reduced in long-term high glucose treated macrophages and peritoneal macrophages from diabetic mice. Long-term high glucose treatment reduced macrophage glycolytic capacity and glycolytic reserve without affecting mitochondrial ATP production and oxidative respiration.

Conclusion

Long-term high glucose sensitizes macrophages to cytokine stimulation and reduces phagocytosis and nitric oxide production, which may be related to impaired glycolytic capacity.

     

Glycogen reduction in non-exercising muscle depends on blood lactate concentration

The purpose of this study was to determine for the first time by repeated non-invasive ¹³C-NMR spectrometry whether blood lactate concentration affects glycogen reduction in non-exercising muscle during prolonged (6 h) physical exercise in healthy adult males. Such an effect would indirectly show that glycogenolysis independent of nervous activation occurs in non-exercising muscle. After an overnight fast, 12 subjects performed alternating one-leg cycle exercise and arm cranking exercise at an average work load of 106 (SD 26) W [63 (9)% maximum oxygen consumption for one-leg exercise] and 69 (13) W [61 (10)% maximum oxygen consumption for arm cranking exercise], respectively. During the 6-h exercise test, glycogen concentration of the non-exercising calf muscle decreased by 17 (7)% while the glycogen concentration in the exercising calf muscle decreased by 45 (8)%. In a resting control group (n=6), the glycogen concentration did not decrease significantly. The higher the exercise intensity and therefore blood lactate concentration, the smaller was the glycogen reduction in the non-exercising calf muscles. We conclude that during prolonged physical exercise glycogenolysis in non-exercising human muscles decreases as exercise intensity increase contrary to exercising muscles. This observation might be an indirect evidence for a non-exercise induced glycogenolysis in inactive muscles.     

Coordination of intrinsic and extrinsic foot muscles during walking

Purpose

The human foot undergoes complex deformations during walking due to passive tissues and active muscles. However, based on prior recordings it is unclear if muscles that contribute to flexion/extension of the metatarsophalangeal (MTP) joints are activated synchronously to modulate joint impedance, or sequentially to perform distinct biomechanical functions. We investigated the coordination of MTP flexors and extensors with respect to each other, and to other ankle–foot muscles.

Methods

We analyzed surface electromyographic (EMG) recordings of intrinsic and extrinsic foot muscles for healthy individuals during level treadmill walking, and also during sideways and tiptoe gaits. We computed stride-averaged EMG envelopes and used the timing of peak muscle activity to assess synchronous vs. sequential coordination.

Results

We found that peak MTP flexor activity occurred significantly before peak MTP extensor activity during walking (P < 0.001). The period around stance-to-swing transition could be roughly characterized by sequential peak muscle activity from the ankle plantarflexors, MTP flexors, MTP extensors, and then ankle dorsiflexors. We found that foot muscles that activated synchronously during forward walking tended to dissociate during other locomotor tasks. For instance, extensor hallucis brevis and extensor digitorum brevis muscle activation peaks decoupled during sideways gait.

Conclusions

The sequential peak activity of MTP flexors followed by MTP extensors suggests that their biomechanical contributions may be largely separable from each other and from other extrinsic foot muscles during walking. Meanwhile, the task-specific coordination of the foot muscles during other modes of locomotion indicates a high-level of specificity in their function and control.

     

An anatomic study of the attachments on the condylar process of the mandible: muscle bundles from the temporalis

Purpose

The aim of this study was to evaluate anatomically the relationship between bone and muscles by detailed observation of the bone shape and the structure of muscles to facilitate an understanding of the function of the muscles involved in jaw movement.

Methods

36 specimens of 24 Japanese cadavers were examined. The insertion areas were marked using a radiopaque marker and examined by micro-computed tomography. For morphological observation, we used 101 condylar processes. In addition, we made histological sections in some specimens to observe the detailed attachments of the muscle.

Results

Based on the micro-CT images and dissection findings, the lateral pterygoid muscle was found to be most frequently inserted into the anterior impression and attached to the medial impression of the process. According to the histological observations, the lateral pterygoid muscle mainly inserted to the condylar process. The micro-CT images indicated that the obvious bony ridge was lateral to the pterygoid fovea on the condylar process in all specimens. The midmedial muscle bundle of the temporalis was attached to the ridge. Based on the morphological observations, the ridge was situated on the lateral area of the condylar process.

Conclusions

Since dysfunction of the temporomandibular joint is likely closely related to both the lateral pterygoid muscle and also the temporalis, further studies are necessary to evaluate the function of these muscles and consider jaw movement.

     

Cardiac function and exercise adaptation in 8 children with LPIN1 mutations

Introduction

Lipin-1 deficiency is a major cause of rhabdomyolysis that are precipitated by febrile illness. The prognosis is poor, with one-third of patients dying from cardiac arrest during a crisis episode. Apart from acute rhabdomyolysis, most patients are healthy, showing normal clinical and cardiac ultrasound parameters.

The styloauricular muscle: clinical relevance and literature review of this rare muscle

Purpose

In humans, the styloauricularis is a rare muscle extending from the tragal cartilage of the auricle to the styloid process. When it contracts, by bearing on the styloid process, it increases the cephalo-auricular angle. It can be a landmark for the facial nerve. We report a case with bilateral presence of the styloauricularis.

Methods

Bilateral presence of the styloauricularis was discovered during routine dissection of the head and neck.

Results

In the presented case, styloauricularis muscles arose from the cartilage of the external acoustic meatus on both sides of the head, crossing halfway along the facial nerve trunk and inserting the styloid process. Both muscles were vascularized by a branch of the posterior auricular artery, and innervated by the facial nerve.

Conclusions

The ventral auricular muscle, formed by the auricular parotid and the styloauricular muscles, is a muscle that lowers and abducts the auricle in animals. There is generally considered to be no equivalent for these muscles in humans, however, this bilateral case reveals evidence to the contrary. There is a dearth of scientific literature about the styloauricularis. The study of this muscle demonstrated the usefulness of comparative anatomy in understanding its action in increasing the cephalo-auricular angle.

     

High expression of GRK3 is associated with favorable prognosis in pancreatic ductal adenocarcinoma

Background

It was found that G-protein-coupled receptor kinase 3 (GRK3) played key biological roles in some cancers. However, its associations with clinicopathologic features and prognosis in pancreatic ductal adenocarcinoma (PDAC) remain unknown.

Reference data on muscle volumes of healthy human pelvis and lower extremity muscles: an in vivo magnetic resonance imaging feasibility study

Purpose

Muscle volumes are of crucial interest when attempting to analyze individual physical performance and disease- or age-related alterations in muscle morphology. However, very little reference data are available in the literature on pelvis and lower extremity muscle volumes originating from healthy and young individuals. Furthermore, it is of interest if representative muscle volumes, covering large anatomical regions, can be obtained using magnetic resonance imaging (MRI) in a setting similar to the clinical routine. Our objective was therefore to provide encompassing, bilateral, 3-T MRI-based datasets on muscle volumes of the pelvis and the lower limb muscles.

Methods

T1-weighted 3-T MRI records were obtained bilaterally from six young and healthy participants. Three-dimensional volumes were compiled from 28 muscles and muscle groups of each participant before the muscle volumes were computed.

Results

Muscle volumes were obtained from 28 muscles and muscle groups of the pelvis and lower extremity. Volumes were larger in male than in female participants. Volumes of the dominant and non-dominant sides were similar in both genders. The obtained results were in line with volumetric data obtained from smaller anatomical areas, thus extending the available datasets.

Conclusions

This study provides an encompassing and feasible approach to obtain data on the muscle volumes of pelvic and limb muscles of healthy, young, and physically active individuals. The respective data form a basis to determine effects of therapeutic approaches, progression of diseases, or technical applications like automated segmentation algorithms applied to different populations.

     

Cytokine-targeting biologics for allergic diseases

Objective

Asthma and allergic diseases continue to increase in prevalence, creating a financial burden on the health care system and affecting the quality of life for those who have these diseases. Many intrinsic and extrinsic factors are involved in the initiation and maintenance of the allergic response. Cytokines are proteins with growth, differentiation, and activation functions that regulate and direct the nature of immune responses.

Effects of eccentric overload training on patellar tendon and vastus lateralis in three days of consecutive running

Background

The analysis of structural changes in patellar tendon and muscle of healthy subjects in response to mechanical loads provides useful insight into the mechanism underlying overuse injuries.

The relationship between performance on the modified star excursion balance test and the knee muscle strength before and after anterior cruciate ligament reconstruction

Objectives

The objective of this study was to evaluate the dynamic balance of the injured and uninjured limb before and after the anterior cruciate ligament (ACL) reconstruction and compare with the control group.

Abnormal lung function at preschool age asthma in adolescence?

Background

Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate.

Tourniquet time in total knee arthroplasty

Background

Whether the arterial tourniquet in total knee arthroplasty (TKA) is a friend or a foe is still debated.Longer ischemia causes hypoxic damage; yet short duration of a tourniquet may influence outcome. Understanding the time-dependent influence of the tourniquet in TKA patients could improve the overall outcome and safety. The purpose of the study was to measure the tourniquet-induced time-dependent alterations in skeletal muscle metabolism in TKA to establish a ‘safe tourniquet time.’