Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually, more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on certain snake venom components and their applications in health and disease.

SUBMARY1. The effects of altered tissue temperature on muscle metabolism during successive isometric contractions, sustained to fatigue, have been studied in the quadriceps muscle of man by combining biochemical analyses of metabolites in needle biopsy samples with measurements of endurance time with a force of 2/3 maximum voluntary contraction. Fatigue and recovery were observed repeatedly in a series of seven contractions at intervals of 20 sec, following immersion of the test leg in water at 12, 26 or 440 C for 45 min. Muscle temperatures corresponding to these water temperatures were 22-5, 32-6 and 38 6°C respectively.2. Increased levels of several glycolytic intermediates at rest in the heated muscle suggested an increased rate of glycolysis. ATP and phosphoryl creatine were lower at the end of the first contraction and the calculated rate of ATP utilization (including the contribution from anaerobic glycolysis) was highest in the heated nuscle.3. Significantly shorter endurance times were found for the heated muscle. These could not be attributed to depletion of local energy resources in muscle. Fatigue may be due to a reduction in the rate of regeneration of ATP from anaerobic glycolysis below that needed to maintain the contraction force. Lower values for the ratio of fructose 1,6-diphosphate: fructose 6-phosphate at the end of contractions, particularly at the highest temperature, are compatible with the hypothesis that there is partial inhibition of the rate controlling enzyme phosphofructokinase, possibly due to the accumulation of hydrogen ions in muscle.

During sepsis, activation of phagocytes leads to the overproduction of proinflammatory cytokines, causing systemic inflammation. Despite substantial information regarding the underlying molecular mechanisms that lead to sepsis, several elements in the pathway remain to be elucidated. We found that the enzyme sphingosine kinase 1 (SphK1) is up-regulated in stimulated human phagocytes and in peritoneal phagocytes of patients with severe sepsis. Blockade of SphK1 inhibited phagocyte production of endotoxin-induced proinflammatory cytokines. We observed protection against sepsis in mice treated with a specific SphK1 inhibitor that was enhanced by treatment with a broad-spectrum antibiotic. These results demonstrated a critical role for SphK1 in endotoxin signaling and sepsis-induced inflammatory responses and suggest that inhibition of SphK1 is a potential therapy for septic shock.

The Maslach Burnout Inventory for healthcare professionals (MBI-HSS) and its abbreviated version (aMBI), are the most common tools to detect burnout in clinicians. A wide range in burnout prevalence is reported in anesthesiology, so this study aimed to ascertain which of these two tools most accurately detected burnout in our anesthesiology residents. The MBI-HSS and aMBI were distributed amongst 86 residents across three hospitals, with a total of 58 residents completing the survey (67.4% response rate; 17 male and 41 female). Maslach-recommended cut-offs for the MBI-HSS and the aMBI with standard cut-offs were used to estimate burnout prevalence, and actual prevalence was established clinically by a thorough review of multiple data sources. Burnout proportions reported by the MBI-HSS and aMBI were found to be significantly different; 22.4% vs. 62.1% respectively (p < 0.0001). Compared to the actual prevalence of burnout in our cohort, the MBI-HSS detected burnout most accurately; area under receiver operating characteristic of 0.99 (95% confidence interval (CI): 0.92–1.0). Although there was a good correlation between the MBI-HSS and aMBI subscale scores, the positive predictive value of the aMBI was poor; 33.3% (95% CI:27.5–39.8%), therefore caution and clinical correlation are advised when using the aMBI tool because of the high rates of false-positives.

Botulinum neurotoxins (BoNTs) inhibit cholinergic synaptic transmission by specifically cleaving proteins that are crucial for neurotransmitter exocytosis. Due to the lethality of these toxins, there are elevated concerns regarding their possible use as bioterrorism agents. Moreover, their widespread use for cosmetic purposes, and as medical treatments, has increased the potential risk of accidental overdosing and environmental exposure. Hence, there is an urgent need to develop novel modalities to counter BoNT intoxication. Mammalian motoneurons are the main target of BoNTs, however, due to the difficulty and poor efficiency of the procedures required to isolate the cells, they are not suitable for high-throughput drug screening assays. Here, we explored the suitability of embryonic stem (ES) cell-derived motoneurons as a renewable, reproducible, and physiologically relevant system for BoNT studies. We found that the sensitivity of ES-derived motoneurons to BoNT/A intoxication is comparable to that of primary mouse spinal motoneurons. Additionally, we demonstrated that several BoNT/A inhibitors protected SNAP-25, the BoNT/A substrate, in the ES-derived motoneuron system. Furthermore, this system is compatible with immunofluorescence-based high-throughput studies. These data suggest that ES-derived motoneurons provide a highly sensitive system that is amenable to large-scale screenings to rapidly identify and evaluate the biological efficacies of novel therapeutics.