Comparison of the Effects of Ice and 3.5% Menthol Gel on Blood Flow and Muscle Strength of the Lower Arm

Context: Soft-tissue injuries are commonly treated with ice or menthol gels. Few studies have compared the effects of these treatments on blood flow and muscle strength. Objective: To compare blood flow and muscle strength in the forearm after an application of ice or menthol gel or no treatment. Design: Repeated measures design in which blood-flow and muscle-strength data were collected from subjects under 3 treatment conditions. Setting: Exercise physiology laboratory. Participants: 17 healthy adults with no impediment to the blood flow or strength in their right arm, recruited through word of mouth. Intervention: Three separate treatment conditions were randomly applied topically to the right forearm: no treatment, 0.5 kg of ice, or 3.5 mL of 3.5% menthol gel. To avoid injury ice was only applied for 20 min. Main Outcome Measures: At each data-collection session blood flow (mL/min) of the right radial artery was determined at baseline before any treatment and then at 5, 10, 15, and 20 min after treatment using Doppler ultrasound. Muscle strength was assessed as maximum isokinetic flexion and extension of the wrist at 30°/s 20, 25, and 30 min after treatment. Results: The menthol gel reduced (–42%, P \u3c .05) blood flow in the radial artery 5 min after application but not at 10, 15, or 20 min after application. Ice reduced (–48%, P \u3c .05) blood flow in the radial artery only after 20 min of application. After 15 min of the control condition blood flow increased (83%, P \u3c .05) from baseline measures. After the removal of ice, wrist-extension strength did not increase per repeated strength assessment as it did during the control condition (9–11%, P \u3c .05) and menthol-gel intervention (8%, P \u3c .05). Conclusions: Menthol has a fast-acting, short-lived effect of reducing blood flow. Ice reduces blood flow after a prolonged duration. Muscle strength appears to be inhibited after ice application

Host-Directed Therapies for tackling Multi-Drug Resistant TB – learning from the Pasteur-Bechamp debates

Tuberculosis (TB) remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of TB treatment has been on antibiotic development targeting Mycobacterium tuberculosis (M.tb). The lengthy TB treatment duration and poor treatment outcomes associated with multi-drug resistant TB (MDR-TB) are of major concern. The sparse new TB drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the ‘microbe’ versus the ‘host internal milieu’ in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of TB therapy and improving treatment outcomes for drug-susceptible TB and MDR-TB. Funder initiatives that may enable further research into HDTs are described

Towards host-directed therapies for tuberculosis

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. Despite the availability of effective antibiotics for tuberculosis (TB) for the past half century, it remains an important global health problem; there are ~9 million active TB cases and ~1.5 million TB-induced deaths per year (see the World Health Organization (WHO) Global Tuberculosis Report in Further information). Health services around the world face major barriers to achieving optimal outcomes from current TB treatment regimens. These barriers include: the spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB); complex and toxic treatment regimens for MDR-TB; HIV co-infection; pharmacokinetic interactions between TB drugs and antiretroviral drugs; relapse; permanent damage to lung and other tissues; long-term functional disability; immune reconstitution inflammatory syndrome (IRIS); and co-morbidity with non-communicable diseases such as diabetes and chronic obstructive airway diseases. Another fundamental problem is the long duration of TB drug treatment (6 months for drug-sensitive TB and at least 18 months for drug-resistant TB) to achieve a cure, owing to the presence of dormant Mycobacterium tuberculosis bacilli that are phenotypically resistant to current classes of anti-TB drugs, which can only target bacterial replication. There is therefore an urgent need for new TB treatments. However, the TB drug pipeline is thin1, 2. For the past 60 years, efforts to develop new treatments have focused on compounds and regimens that target M. tuberculosis directly. Recently, however, attention has focused on investigating a range of adjunct treatment interventions known as host-directed therapies (HDTs) that instead target the host response to infection. Here, we highlight the rationale for HDTs, the current portfolio of HDTs and their mechanisms of action, and a consortium-based approach to drive forward their evaluation in clinical trials