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1.
Metabolism ; 102: 153996, 2020 01.
Article in English | MEDLINE | ID: mdl-31678069

ABSTRACT

BACKGROUND: We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS: We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS: Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ±â€¯0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ±â€¯0.17], 10 overweight (BMI: 27.1 ±â€¯0.5; HOMAIR: 1.25 ±â€¯0.11), and 10 obese (BMI: 35.9 ±â€¯1.3; HOMAIR: 5.82 ±â€¯0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS: Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS: These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.


Subject(s)
Blood Proteins/metabolism , Eating/physiology , Meat , Muscle, Skeletal/metabolism , Obesity/metabolism , Phosphotransferases (Phosphate Group Acceptor)/metabolism , Proteome/metabolism , Adult , Age Factors , Blood Proteins/analysis , Body Mass Index , Dietary Fats/pharmacology , Energy Metabolism/physiology , Female , Glucose/metabolism , Humans , Insulin Resistance/physiology , Male , Middle Aged , Muscle Proteins/analysis , Muscle Proteins/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Obesity/blood , Obesity/pathology , Phosphotransferases (Phosphate Group Acceptor)/analysis , Postprandial Period/physiology , Proteome/analysis , Thinness/blood , Thinness/metabolism , Thinness/pathology , Young Adult
2.
Front Nutr ; 6: 146, 2019.
Article in English | MEDLINE | ID: mdl-31552262

ABSTRACT

Sarcopenia is defined as the combined loss of skeletal muscle strength, function, and/or mass with aging. This degenerative loss of muscle mass is associated with poor quality of life and early mortality humans. The loss of muscle mass occurs due to acute changes in daily muscle net protein balance (NPB). It is generally believed a poor NPB occurs due to reduced muscle protein synthetic responses to exercise, dietary amino acid availability, or an insensitivity of insulin to suppress breakdown. Hence, aging muscles appear to be resistant to the anabolic action of exercise and protein (amino acids or hormonal) when compared to their younger counterparts. The mechanisms that underpin anabolic resistance to anabolic stimuli (protein and resistance exercise) are multifactorial and may be partly driven by poor lifestyle choices (increased sedentary time and reduced dietary protein intake) as well as an inherent dysregulated mechanism in old muscles irrespective of the environmental stimuli. The insulin like growth factor 1 (IGF-1), Akt /Protein Kinase B and mechanistic target of rapamycin (mTOR) pathway is the primary driver between mechanical contraction and protein synthesis and may be a site of dysregulation between old and younger people. Therefore, our review aims to describe and summarize the differences seen in older muscle in this pathway in response to resistance exercise (RE) and describe approaches that researchers have sought out to maximize the response in muscle. Furthermore, this review will present the hypothesis that inositol hexakisphosphate kinase 1 (IP6K1) may be implicated in IGF-1 signaling and thus sarcopenia, based on recent evidence that IGF-1 and insulin share some intracellular bound signaling events and that IP6K1 has been implicated in skeletal muscle insulin resistance.

3.
Appl Spectrosc ; 70(12): 1974-1980, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27364365

ABSTRACT

We report new instrumentation for rapidly and reliably measuring the temperature-dependent photoluminescence response from porous silicon as a function of analyte vapor concentration. The new system maintains the porous silicon under inert conditions and it allows on-the-fly steady-state and time-resolved photoluminescence intensity and hyper-spectral measurements between 293 K and 450 K. The new system yields reliable data at least 100-fold faster in comparison to previous instrument platforms.

4.
Antimicrob Agents Chemother ; 56(7): 3963-4, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22508314

ABSTRACT

Mycograb C28Y is a recombinant human antibody fragment thought to target HSP-90 and potentiate amphotericin B (AMB). Absence of in vivo efficacy led us to reevaluate its in vitro activity. Interactions between AMB and Mycograb were investigated using a checkerboard design. Addition of Mycograb or various unrelated proteins, including human serum, resulted in similar decreases in the MIC of AMB. Potentiation of AMB by Mycograb appears to be a nonspecific protein effect.


Subject(s)
Amphotericin B/pharmacology , Antibodies, Monoclonal/pharmacology , Antifungal Agents/pharmacology , Antibodies, Monoclonal, Humanized , Candida albicans/drug effects , Caspofungin , Drug Interactions , Echinocandins/pharmacology , Fluconazole/pharmacology , Humans , Lipopeptides , Microbial Sensitivity Tests
5.
Phys Rev Lett ; 92(4): 045501, 2004 Jan 30.
Article in English | MEDLINE | ID: mdl-14995383

ABSTRACT

The combination of long-time, tight-binding molecular dynamics and real-time multiresolution analysis techniques reveals the complexity of small silicon interstitial defects. The stability of identified structures is confirmed by ab initio relaxations. The majority of structures were previously unknown, demonstrating the effectiveness of the approach. A new, spatially extended tri-interstitial ground state structure is identified as a probable nucleation site for larger extended defects and may be key for the compact-to-extended transition.

6.
J Foot Ankle Surg ; 40(4): 240-51, 2001.
Article in English | MEDLINE | ID: mdl-11924686

ABSTRACT

A review of current knowledge of the clinical syndrome of functional ankle instability is presented. Recent evidence has demonstrated that the majority of patients with functional instability of the ankle do not have mechanical hypermobility of the ankle joint. Functional instability of the ankle results from a loss of neuromuscular control. Components of neuromuscular control include proprioception, muscle strength, muscle reaction time, and postural control. Proprioceptive deficits lead to a delay in peroneal reaction time, which appears to be a peripheral reflex. Proprioception and eversion muscle strength improve with the use of passive supportive devices. Balance and postural control of the ankle appear to be diminished after a lateral ankle sprain and can be restored through training that is mediated through central nervous mechanisms. Methods of detecting deficits in neuromuscular control are presented along with rehabilitation techniques to treat functional instability of the ankle.


Subject(s)
Ankle Injuries/physiopathology , Joint Instability/physiopathology , Proprioception/physiology , Sprains and Strains/physiopathology , Ankle Injuries/rehabilitation , Humans , Joint Instability/diagnosis , Orthotic Devices , Reaction Time/physiology , Sprains and Strains/rehabilitation
7.
Neuroreport ; 10(4): 723-9, 1999 Mar 17.
Article in English | MEDLINE | ID: mdl-10208538

ABSTRACT

The scrapie isoform of the prion protein (PrPres) induces neurodegeneration and gliosis in the central nervous system. These features may be reproduced in vitro on exposure of neuronal and glial cultures to PrPres and the peptide HuPr P106-126. In the present study, we investigated the role of microglial cells and astrocytes in the pathological process by studying their molecular response to PrP 106-126 exposure. PrP 106-126 elicited a specific overproduction of pro-inflammatory cytokines IL1beta and IL6 in microglial cells (but not increased expression of TNFalpha, IL10, and TGFbeta1) and over-expression of GFAP in astrocytes. These effects were strictly dependent on the ability of the peptide to form amyloid fibrils. These data strongly suggest that microglial cells contribute to prion-related neurodegenerative processes by producing proinflammatory cytokines in the brain areas of amyloid PrP deposition.


Subject(s)
Cytokines/biosynthesis , Microglia/metabolism , Peptide Fragments/pharmacology , Prions/pharmacology , Animals , Cells, Cultured , Electrophoresis, Polyacrylamide Gel , Humans , Inflammation/metabolism , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Lipopolysaccharides/pharmacology , Mice , Mice, Inbred C57BL , Microglia/drug effects , Nerve Degeneration/pathology , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/biosynthesis
8.
J Am Podiatr Med Assoc ; 83(9): 515-22, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8289142

ABSTRACT

A longitudinal single-blind study was conducted to test the friction blister prevention properties of synthetic acrylic socks in a generic construction. This study serves as a comparison with the authors' previous work comparing acrylic and cotton socks in a patented padded construction. Twenty-seven long-distance runners provided data regarding dampness, temperature, friction blister incidence, severity, and size. Two different socks were tested; each was identical in every aspect of construction except the fiber content. One test sock was composed of 100% synthetic acrylic fibers, and the other was composed of 100% natural cotton fibers. These results were unsuccessful at demonstrating any superiority of cotton or acrylic fibers when knitting produced a generic "cushion sole" sock. The superiority of acrylic fibers has thus far been demonstrated only when sock knitting provides adequate anatomical padding [corrected].


Subject(s)
Blister/prevention & control , Clothing , Foot Dermatoses/prevention & control , Running/injuries , Acrylates , Adult , Female , Gossypium , Humans , Longitudinal Studies , Male , Single-Blind Method , Textiles
9.
J Am Podiatr Med Assoc ; 83(9): 492-8, 1993 Sep.
Article in English | MEDLINE | ID: mdl-7904642

ABSTRACT

Forty recreational and professional athletes were followed in this prospective study comparing the acceptability and effectiveness of two orthotic component materials commonly used in sports medicine. TL-2100 SF (semiflexible) was compared to 4.0-mm thick polypropylene in six different subjective categories. The subjects were able to perceive a significant difference in favor of TL-2100 SF in the categories of weight, resilience and springiness, and overall comfort of the orthosis. The subjects were also able to perceive physical differences between these two component materials, which had previously been confirmed in laboratory studies.


Subject(s)
Athletic Injuries/therapy , Cumulative Trauma Disorders/therapy , Orthotic Devices , Equipment Design , Female , Foot Injuries , Graphite , Humans , Male , Patient Satisfaction , Plastics , Polypropylenes , Prospective Studies
10.
Diabetes Care ; 16(8): 1190-2, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8375250

ABSTRACT

OBJECTIVE: To assess the acceptability of specially designed socks to provide satisfactory pressure relief in the insensitive, high-risk, diabetic foot. We have conducted a longitudinal multicenter patient evaluation study to assess the acceptability of such hosiery in neuropathic diabetic patients. RESEARCH DESIGN AND METHODS: A group of 86 neuropathic diabetic patients (69 males, 14 with type I diabetes) with a mean age of 63 yr (range 34-85 yr), and a diabetes duration of 16 yr (range 1-45 yr) participated in the study. Peripheral vascular disease was present in 28 (33%) patients, previous foot ulceration in 39 (44%) patients, and active ulceration was present in 11 (13%) patients. All patients were provided with three pairs of specially designed socks and 80 patients with extra-depth shoes. Evaluation and foot examination were performed at 3 and 6 mo. RESULTS: Socks were worn for a mean of 6 days/wk (range 1-7 days/wk). Patient satisfaction evaluated at both visits was good or very good in 85%, average in 12%, and poor in 3% of patients. Ten ulcers healed during this period, and seven new ulcers occurred. Intention to continue wearing the socks, most or all of the time, was expressed by 84% of patients. CONCLUSIONS: We conclude that the experimental socks have a high level of patient satisfaction when worn with suitable shoes, and may be an acceptable and inexpensive addition to existing methods of protecting the high-risk insensitive diabetic foot.


Subject(s)
Bandages , Clothing , Diabetes Mellitus, Type 1/therapy , Foot Diseases/therapy , Foot Ulcer/therapy , Adult , Aged , Aged, 80 and over , Diabetes Mellitus, Type 1/physiopathology , Female , Foot Ulcer/physiopathology , Humans , Longitudinal Studies , Male , Middle Aged , Patient Satisfaction , Shoes
11.
J Am Podiatr Med Assoc ; 83(4): 181-90, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8473989

ABSTRACT

Twelve human subjects were studied to determine the effect of three different floor surfaces on the medial shin musculature during stationary running. Electromyographic equipment, gated by an accelerometer affixed to the subject's shin, was used to separate the impact (eccentric) phase from the propulsive (concentric) phase of each running step. Excessive eccentric muscle activity has been associated with increased muscle damage, and recent investigations have linked medial tibial shin pain with actual structural damage to the muscle-fascial attachments to the posteromedial aspect of the tibia. Therefore, this study tends to verify the previous assumption that running on hard, noncompliant sport surfaces would predispose running and dancing athletes to shin muscle damage and resultant pain.


Subject(s)
Exercise/physiology , Floors and Floorcoverings , Muscles/physiopathology , Pain/physiopathology , Running/physiology , Absorption , Electromyography , Humans , Leg
12.
J Am Podiatr Med Assoc ; 80(2): 63-71, 1990 Feb.
Article in English | MEDLINE | ID: mdl-2304016

ABSTRACT

A longitudinal double-blind study was conducted to determine the effect of sock fiber composition on the frequency and size of blistering events in long-distance runners. Thirty-five long-distance runners participated in this study. Two different socks were tested, which were identical in every aspect of construction except fiber composition. One test sock was composed of 100% acrylic fibers, and the other test sock was composed of 100% natural cotton fibers. The results showed that acrylic fiber socks were associated with fewer blistering events and smaller blisters (mm2), when compared directly to cotton fiber socks.


Subject(s)
Blister/prevention & control , Clothing , Foot Dermatoses/prevention & control , Running/injuries , Acrylates , Adult , Double-Blind Method , Female , Gossypium , Humans , Longitudinal Studies , Male
14.
Phys Sportsmed ; 13(2): 130-40, 1985 Feb.
Article in English | MEDLINE | ID: mdl-27421328

ABSTRACT

In brief: In this study shoes, floor types, and individual physical differences were evaluated for their effects on aerobic dance injuries. The injury frequency was 75.9% for instructors and 43.3% for students. The shin was the most common site of injury in both groups. Overall, 60% of the injuries in the student group and 52% of injuries in the instructor group occurred below the knee. Most injuries were not debilitating, and few required medical treatment. The authors concluded that resilient but stable floor surfaces, proper shoes, and moderating the frequency of participation can prevent injuries in aerobic dance.

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