Understanding the molecular mechanisms of post-exercise muscle inflammation and repair

This study explored the relationship between exercise-induced inflammation and post-exercise muscle recovery. The findings show for the first time that events occurring early in acute inflammation engage an active resolution programme that is essential in optimising recovery from intense exercise

Inflammation and resolution in exercise-induced skeletal muscle injury: The effect of NSAID treatment on pro-inflammatory and anti-inflammatory/pro-resolving lipid mediators.

Current approaches in the treatment of exercise-induced muscle injury rely on the inhibition of pro-inflammatory pathways to alleviate cardinal signs of inflammation; redness, swelling, heat and pain. However, recent research suggests that the cellular events which occur early in acute inflammation engage an active and coordinated inflammatory resolution program characterised by a switch from pro-inflammatory mediators to production of active pro-resolution factors that govern the withdrawal of inflammation whilst facilitating tissue healing. This led to the identification of novel classes of anti-inflammatory/pro-resolving lipid mediators, including the lipoxins (LX), resolvins (Rv), and protectins (P), which may provide new targets in the treatment of inflammation. METHODS: Sixteen untrained male subjects (age 23±0.7yr, mass 88±3.1kg) were assigned to a placebo (PLA) (n=8) or ibuprofen (IBU) (n=8) group. Subjects completed a single bout of resistance exercise consisting of 3 sets of 8-12 repetitions of a squat, leg press and leg extensions at 80% 1RM. Intravenous blood samples were obtained at rest, at 30 min intervals between 0 and 3 h and again at 24 h post exercise. The IBU group orally consumed 400mg of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen pre-exercise, and again at 5 and 10 h post exercise (1200 mg/day). Serum lipid mediator profiles were analysed via LC-MS targeted lipidomics. RESULTS: Acute exercise increased serum levels of pro-inflammatory eicosanoid species derived from both the COX-1 and 2 (prostaglandins: e.g. PGF2α, PGE2, PGD2, TXB2) and 5-LOX (leukotrienes: e.g. LTB4, LTB5) pathways. Additionally, heightened circulating levels of novel pro-resolving lipid mediators derived from arachidonic acid (LXA4 and LXB4), EPA (RvE1) and DHA (RvD1 andPD1 isomer) were detected post-exercise. Both the pro-inflammatory COX-1 & 2/5-LOX responses, as well as pro-resolving lipid mediator biosynthesis were blunted by the administration of the COX-1 and 2 inhibiting NSAID ibuprofen. CONCLUSION: Pro-inflammatory eicosanoids as well as novel pro-resolving bioactive lipid mediators are acutely up regulated following unaccustomed resistance exercise; a response which is diminished by IBU treatment. We hypothesize that the active resolution of exercise-induced inflammation may be important in effective post-exercise recovery and that a shift from anti-inflammatory interventions towards those which promote active resolution may hasten natural withdrawal of inflammation whilst facilitating the successful repair and regeneration of damaged muscle tissue

Inhibition of purple acid phosphatase with a-alkoxynaphthylmethylphosphonic acids

Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyse the hydrolysis of a range of phosphorylated substrates. Human PAP is a major histochemical marker for the diagnosis of osteoporosis. In patients suffering from this disorder, PAP activity contributes to increased bone resorption and, therefore, human PAP is a key target for the development of anti-osteoporotic drugs. This manuscript describes the design and synthesis of derivatives of 1-naphthylmethylphosphonic acids as inhibitors of PAP. The Ki values of these compounds are as low as 4 lM, the lowest reported to date for a PAP inhibitor

Intramuscular inflammatory and resolving lipid profile responses to an acute bout of resistance exercise in men

Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. Lipid mediators including classical arachidonic acid-derived eicosanoids (e.g. prostaglandins and leukotrienes) and more recently identified specialized pro-resolving-mediator metabolites of the omega-3 fatty acids play essential roles in initiation, self-limitation, and active resolution of acute inflammatory responses. In this study, we examined the bioactive lipid mediator profile of human skeletal muscle at rest and following acute resistance exercise. Twelve male subjects completed a single bout of maximal isokinetic unilateral knee extension exercise and muscle biopsies were taken from the m.vastus lateralis before and at 2, 4, and 24 h of recovery. Muscle tissue lipid mediator profile was analyzed via liquid chromatography–mass spectrometry (LC-MS)-based targeted lipidomics. At 2 h postexercise, there was an increased intramuscular abundance of cyclooxygenase (COX)-derived thromboxanes (TXB2: 3.33 fold) and prostaglandins (PGE2: 2.52 fold and PGF2α: 1.77 fold). Resistance exercise also transiently increased muscle concentrations of lipoxygenase (LOX) pathway-derived leukotrienes (12-Oxo LTB4: 1.49 fold and 20-COOH LTB4: 2.91 fold), monohydroxy-eicosatetraenoic acids (5-HETE: 2.66 fold, 12-HETE: 2.83 fold, and 15-HETE: 1.69 fold) and monohydroxy-docosahexaenoic acids (4-HDoHE: 1.69 fold, 7-HDoHE: 1.58 fold and 14-HDoHE: 2.35 fold). Furthermore, the abundance of CYP pathway-derived epoxy- and dihydroxy-eicosatrienoic acids was increased in 2 h postexercise biopsies (5,6-EpETrE: 2.48 fold, 11,12-DiHETrE: 1.66 fold and 14,15-DiHETrE: 2.23 fold). These data reveal a range of bioactive lipid mediators as present within human skeletal muscle tissue and demonstrate that acute resistance exercise transiently stimulates the local production of both proinflammatory eicosanoids and pathway markers in specialized proresolving mediator biosynthesis circuits

Ibuprofen ingestion does not affect markers of post-exercise muscle inflammation

PURPOSE: We investigated if oral ingestion of ibuprofen influenced leucocyte recruitment and infiltration following an acute bout of traditional resistance exercise Methods: Sixteen male subjects were divided into two groups that received the maximum over-the-counter dose of ibuprofen (1200mg d(-1)) or a similarly administered placebo following lower body resistance exercise. Muscle biopsies were taken from m.vastus lateralis and blood serum samples were obtained before and immediately after exercise, and at 3 and 24 h after exercise. Muscle cross-sections were stained with antibodies against neutrophils (CD66b and MPO) and macrophages (CD68). Muscle damage was assessed via creatine kinase and myoglobin in blood serum samples, and muscle soreness was rated on a ten-point pain scale. RESULTS: The resistance exercise protocol stimulated a significant increase in the number of CD66b(+) and MPO(+) cells when measured 3 h post exercise. Serum creatine kinase, myoglobin and subjective muscle soreness all increased post-exercise. Muscle leucocyte infiltration, creatine kinase, myoglobin and subjective muscle soreness were unaffected by ibuprofen treatment when compared to placebo. There was also no association between increases in inflammatory leucocytes and any other marker of cellular muscle damage. CONCLUSION: Ibuprofen administration had no effect on the accumulation of neutrophils, markers of muscle damage or muscle soreness during the first 24 h of post-exercise muscle recovery

The languages of Malta

The purpose of this volume is to present a snapshot of the state of the art of research on the languages of the Maltese islands, which include spoken Maltese, Maltese English and Maltese Sign Language. Malta is a tiny, but densely populated country, with over 422,000 inhabitants spread over only 316 square kilometers. It is a bilingual country, with Maltese and English enjoying the status of official languages. Maltese is a descendant of Arabic, but due to the history of the island, it has borrowed extensively from Sicilian, Italian and English. Furthermore, local dialects still coexist alongside the official standard language. The status of English as a second language dates back to British colonial rule, and just as in other former British colonies, a characteristic Maltese variety of English has developed. To these languages must be added Maltese Sign Language, which is the language of the Maltese Deaf community. This was recently recognised as Malta’s third official language by an act of Parliament in 2016. While a volume such as the present one can hardly do justice to all aspects of a diverse and complex linguistic situation, even in a small community like that of Malta, our aim in editing this book was to shed light on the main strands of research being undertaken in the Maltese linguistic context. Six of the contributions in this book focus on Maltese and explore a broad range of topics including: historical changes in the Maltese sound system; syllabification strategies; the interaction of prosody and gesture; the constraints regulating /t/-insertion; the productivity of derivational suffixes; and raising phenomena. The study of Maltese English, especially with the purpose of establishing the defining characteristics of this variety of English, is a relatively new area of research. Three of the papers in this volume deal with Maltese English, which is explored from the different perspectives of rhythm, the syntax of nominal phrases, and lexical choice. The last contribution discusses the way in which Maltese Sign Language (LSM) has evolved alongside developments in LSM research. In summary, we believe the present volume has the potential to present a unique snapshot of a complex linguistic situation in a geographically restricted area. Given the nature and range of topics proposed, the volume will likely be of interest to researchers in both theoretical and comparative linguistics, as well as those working with experimental and corpus-based methodologies. Our hope is that the studies presented here will also serve to pave the way for further research on the languages of Malta, encouraging researchers to also take new directions, including the exploration of variation and sociolinguistic factors which, while often raised as explanatory constructs in the papers presented here, remain under-researched

The languages of Malta

The purpose of this volume is to present a snapshot of the state of the art of research on the languages of the Maltese islands, which include spoken Maltese, Maltese English and Maltese Sign Language. Malta is a tiny, but densely populated country, with over 422,000 inhabitants spread over only 316 square kilometers. It is a bilingual country, with Maltese and English enjoying the status of official languages. Maltese is a descendant of Arabic, but due to the history of the island, it has borrowed extensively from Sicilian, Italian and English. Furthermore, local dialects still coexist alongside the official standard language. The status of English as a second language dates back to British colonial rule, and just as in other former British colonies, a characteristic Maltese variety of English has developed. To these languages must be added Maltese Sign Language, which is the language of the Maltese Deaf community. This was recently recognised as Malta’s third official language by an act of Parliament in 2016. While a volume such as the present one can hardly do justice to all aspects of a diverse and complex linguistic situation, even in a small community like that of Malta, our aim in editing this book was to shed light on the main strands of research being undertaken in the Maltese linguistic context. Six of the contributions in this book focus on Maltese and explore a broad range of topics including: historical changes in the Maltese sound system; syllabification strategies; the interaction of prosody and gesture; the constraints regulating /t/-insertion; the productivity of derivational suffixes; and raising phenomena. The study of Maltese English, especially with the purpose of establishing the defining characteristics of this variety of English, is a relatively new area of research. Three of the papers in this volume deal with Maltese English, which is explored from the different perspectives of rhythm, the syntax of nominal phrases, and lexical choice. The last contribution discusses the way in which Maltese Sign Language (LSM) has evolved alongside developments in LSM research. In summary, we believe the present volume has the potential to present a unique snapshot of a complex linguistic situation in a geographically restricted area. Given the nature and range of topics proposed, the volume will likely be of interest to researchers in both theoretical and comparative linguistics, as well as those working with experimental and corpus-based methodologies. Our hope is that the studies presented here will also serve to pave the way for further research on the languages of Malta, encouraging researchers to also take new directions, including the exploration of variation and sociolinguistic factors which, while often raised as explanatory constructs in the papers presented here, remain under-researched

The languages of Malta

The purpose of this volume is to present a snapshot of the state of the art of research on the languages of the Maltese islands, which include spoken Maltese, Maltese English and Maltese Sign Language. Malta is a tiny, but densely populated country, with over 422,000 inhabitants spread over only 316 square kilometers. It is a bilingual country, with Maltese and English enjoying the status of official languages. Maltese is a descendant of Arabic, but due to the history of the island, it has borrowed extensively from Sicilian, Italian and English. Furthermore, local dialects still coexist alongside the official standard language. The status of English as a second language dates back to British colonial rule, and just as in other former British colonies, a characteristic Maltese variety of English has developed. To these languages must be added Maltese Sign Language, which is the language of the Maltese Deaf community. This was recently recognised as Malta’s third official language by an act of Parliament in 2016. While a volume such as the present one can hardly do justice to all aspects of a diverse and complex linguistic situation, even in a small community like that of Malta, our aim in editing this book was to shed light on the main strands of research being undertaken in the Maltese linguistic context. Six of the contributions in this book focus on Maltese and explore a broad range of topics including: historical changes in the Maltese sound system; syllabification strategies; the interaction of prosody and gesture; the constraints regulating /t/-insertion; the productivity of derivational suffixes; and raising phenomena. The study of Maltese English, especially with the purpose of establishing the defining characteristics of this variety of English, is a relatively new area of research. Three of the papers in this volume deal with Maltese English, which is explored from the different perspectives of rhythm, the syntax of nominal phrases, and lexical choice. The last contribution discusses the way in which Maltese Sign Language (LSM) has evolved alongside developments in LSM research. In summary, we believe the present volume has the potential to present a unique snapshot of a complex linguistic situation in a geographically restricted area. Given the nature and range of topics proposed, the volume will likely be of interest to researchers in both theoretical and comparative linguistics, as well as those working with experimental and corpus-based methodologies. Our hope is that the studies presented here will also serve to pave the way for further research on the languages of Malta, encouraging researchers to also take new directions, including the exploration of variation and sociolinguistic factors which, while often raised as explanatory constructs in the papers presented here, remain under-researched

The languages of Malta

The purpose of this volume is to present a snapshot of the state of the art of research on the languages of the Maltese islands, which include spoken Maltese, Maltese English and Maltese Sign Language. Malta is a tiny, but densely populated country, with over 422,000 inhabitants spread over only 316 square kilometers. It is a bilingual country, with Maltese and English enjoying the status of official languages. Maltese is a descendant of Arabic, but due to the history of the island, it has borrowed extensively from Sicilian, Italian and English. Furthermore, local dialects still coexist alongside the official standard language. The status of English as a second language dates back to British colonial rule, and just as in other former British colonies, a characteristic Maltese variety of English has developed. To these languages must be added Maltese Sign Language, which is the language of the Maltese Deaf community. This was recently recognised as Malta’s third official language by an act of Parliament in 2016. While a volume such as the present one can hardly do justice to all aspects of a diverse and complex linguistic situation, even in a small community like that of Malta, our aim in editing this book was to shed light on the main strands of research being undertaken in the Maltese linguistic context. Six of the contributions in this book focus on Maltese and explore a broad range of topics including: historical changes in the Maltese sound system; syllabification strategies; the interaction of prosody and gesture; the constraints regulating /t/-insertion; the productivity of derivational suffixes; and raising phenomena. The study of Maltese English, especially with the purpose of establishing the defining characteristics of this variety of English, is a relatively new area of research. Three of the papers in this volume deal with Maltese English, which is explored from the different perspectives of rhythm, the syntax of nominal phrases, and lexical choice. The last contribution discusses the way in which Maltese Sign Language (LSM) has evolved alongside developments in LSM research. In summary, we believe the present volume has the potential to present a unique snapshot of a complex linguistic situation in a geographically restricted area. Given the nature and range of topics proposed, the volume will likely be of interest to researchers in both theoretical and comparative linguistics, as well as those working with experimental and corpus-based methodologies. Our hope is that the studies presented here will also serve to pave the way for further research on the languages of Malta, encouraging researchers to also take new directions, including the exploration of variation and sociolinguistic factors which, while often raised as explanatory constructs in the papers presented here, remain under-researched

The languages of Malta

The purpose of this volume is to present a snapshot of the state of the art of research on the languages of the Maltese islands, which include spoken Maltese, Maltese English and Maltese Sign Language. Malta is a tiny, but densely populated country, with over 422,000 inhabitants spread over only 316 square kilometers. It is a bilingual country, with Maltese and English enjoying the status of official languages. Maltese is a descendant of Arabic, but due to the history of the island, it has borrowed extensively from Sicilian, Italian and English. Furthermore, local dialects still coexist alongside the official standard language. The status of English as a second language dates back to British colonial rule, and just as in other former British colonies, a characteristic Maltese variety of English has developed. To these languages must be added Maltese Sign Language, which is the language of the Maltese Deaf community. This was recently recognised as Malta’s third official language by an act of Parliament in 2016. While a volume such as the present one can hardly do justice to all aspects of a diverse and complex linguistic situation, even in a small community like that of Malta, our aim in editing this book was to shed light on the main strands of research being undertaken in the Maltese linguistic context. Six of the contributions in this book focus on Maltese and explore a broad range of topics including: historical changes in the Maltese sound system; syllabification strategies; the interaction of prosody and gesture; the constraints regulating /t/-insertion; the productivity of derivational suffixes; and raising phenomena. The study of Maltese English, especially with the purpose of establishing the defining characteristics of this variety of English, is a relatively new area of research. Three of the papers in this volume deal with Maltese English, which is explored from the different perspectives of rhythm, the syntax of nominal phrases, and lexical choice. The last contribution discusses the way in which Maltese Sign Language (LSM) has evolved alongside developments in LSM research. In summary, we believe the present volume has the potential to present a unique snapshot of a complex linguistic situation in a geographically restricted area. Given the nature and range of topics proposed, the volume will likely be of interest to researchers in both theoretical and comparative linguistics, as well as those working with experimental and corpus-based methodologies. Our hope is that the studies presented here will also serve to pave the way for further research on the languages of Malta, encouraging researchers to also take new directions, including the exploration of variation and sociolinguistic factors which, while often raised as explanatory constructs in the papers presented here, remain under-researched