The fractal lightning burn results from a positively charged strike

Non peer reviewe

Clinical use of lactate monitoring in critically ill patients

Increased blood lactate levels (hyperlactataemia) are common in critically ill patients. Although frequently used to diagnose inadequate tissue oxygenation, other processes not related to tissue oxygenation may increase lactate levels. Especially in critically ill patients, increased glycolysis may be an important cause of hyperlactataemia. Nevertheless, the presence of increased lactate levels has important implications for the morbidity and mortality of the hyperlactataemic patients. Although the term lactic acidosis is frequently used, a significant relationship between lactate and pH only exists at higher lactate levels. The term lactate associated acidosis is therefore more appropriate. Two recent studies have underscored the importance of monitoring lactate levels and adjust treatment to the change in lactate levels in early resuscitation. As lactate levels can be measured rapidly at the bedside from various sources, structured lactate measurements should be incorporated in resuscitation protocols

Lactate-Protected Hypoglycemia (LPH)

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of these experimental methods rely on a significant elevation in lactate in the tumor microenvironment. To date it remains unclear how various tumors behavein vivo, and how they might respond to perturbations in lactate and glucose concentrations or transport inhibition. By exploiting and targeting lactate transport and metabolism in tumors (with a combination of changes in lactate and glucose concentrations, transport inhibitors, etc.), we can begin developing novel methods for targeting otherwise difficult to treat pathologies in the brain and spinal cord. Here we discuss evidence both experimental and observational, and provide direction for next steps in developing therapies based on these concepts

Hyperglycaemic index as a tool to assess glucose control: a retrospective study

INTRODUCTION: Critically ill patients may benefit from strict glucose control. An objective measure of hyperglycaemia for assessing glucose control in acutely ill patients should reflect the magnitude and duration of hyperglycaemia, should be independent of the number of measurements, and should not be falsely lowered by hypoglycaemic values. The time average of glucose values above the normal range meets these requirements. METHODS: A retrospective, single-centre study was performed at a 12-bed surgical intensive care unit. From 1990 through 2001 all patients over 15 years, staying at least 4 days, were included. Admission type, sex, age, Acute Physiology and Chronic Health Evaluation II score and outcome were recorded. The hyperglycaemic index (HGI) was defined as the area under the curve above the upper limit of normal (glucose level 6.0 mmol/l) divided by the total length of stay. HGI, admission glucose, mean morning glucose, mean glucose and maximal glucose were calculated for each patient. The relations between these measures and 30-day mortality were determined. RESULTS: In 1779 patients with a median stay in the intensive care unit of 10 days, the 30-day mortality was 17%. A total of 65,528 glucose values were analyzed. Median HGI was 0.9 mmol/l (interquartile range 0.3–2.1 mmol/l) in survivors versus 1.8 mmol/l (interquartile range 0.7–3.4 mmol/l) in nonsurvivors (P < 0.001). The area under the receiver operator characteristic curve was 0.64 for HGI, as compared with 0.61 and 0.62 for mean morning glucose and mean glucose. HGI was the only significant glucose measure in binary logistic regression. CONCLUSION: HGI exhibited a better relation with outcome than other glucose indices. HGI is a useful measure of glucose control in critically ill patients

Lactate-protechypoglycemia (LPH)

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ( LPH ), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit the Warburg effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a reverse-Warburg, where some tumors may preferentially consume lactate, many of these experimental methods rely on a significant elevation in lactate in the tumor microenvironment. To date it remains unclear how various tumors behav

Quantitative assessment of required separator fluid volume in multi-infusion settings

Background: Administering a separator fluid between incompatible solutions can optimize the use of intravenous lumens. Factors affecting the required separator fluid volume to safely separate incompatible solutions are unknown. Methods: An intravenous tube (2-m, 2-mL, 6-French) containing methylene blue dye was flushed with separator fluid until a methylene blue concentration ⩽2% from initial was reached. Independent variables were administration rate, dye solvent (glucose 5% and NaCl 0.9%), and separator fluid. In the second part of the study, methylene blue, separator fluid, and eosin yellow were administered in various administration profiles using 2- and 4-mL (2 × 2 m, 4-mL, 6-French) intravenous tubes. Results: Neither administration rate nor solvent affected the separator fluid volume (p = 0.24 and p = 0.12, respectively). Glucose 5% as separator fluid required a marginally smaller mean ± SD separator fluid volume than NaCl 0.9% (3.64 ± 0.13 mL vs 3.82 ± 0.11 mL, p < 0.001). Using 2-mL tubing required less separator fluid volume than 4-mL tubing for methylene blue (3.89 ± 0.57 mL vs 4.91 ± 0.88 mL, p = 0.01) and eosin yellow (4.41 ± 0.56 mL vs 5.63 ± 0.15 mL, p < 0.001). Extended tubing required less separator fluid volume/mL of tubing than smaller tubing for both methylene blue (2 vs 4 mL, 1.54 ± 0.22 vs 1.10 ± 0.19, p < 0.001) and eosin yellow (2 vs 4 mL, 1.75 ± 0.22 vs 1.25 ± 0.03, p < 0.001). Conclusion: The separator fluid volume was neither affected by the administration rate nor by solvent. Glucose 5% required a marginally smaller separator fluid volume than NaCl 0.9%, however its clinical impact is debatable. A larger intravenous tubing volume requires a larger separator fluid volume. However, the ratio of separator fluid volume to the tubing’s volume decreases as the tubing volume increases

Low cancer incidence in naked mole-rats may be related to their inability to express the Warburg effect

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have a remarkably low cancer incidence. Most advanced cancers in mammals display increased production of lactic acid from glucose, irrespective of oxygen availability. This hallmark of cancer is known as the Warburg effect (WE). Most malignancies acquire this metabolic phenotype during their somatic evolution, as the WE benefits tumor growth in several ways. We propose that the peculiar metabolism of the NMR makes development of the WE inherently difficult, which might contribute to the extraordinarily low cancer rate in NMRs. Such an adaptation of NMRs to their subterranean environment may have been facilitated by modified biochemical responses with a stronger inhibition of the production of C

Low Cancer Incidence in Naked Mole-Rats May Be Related to Their Inability to Express the Warburg Effect

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have a remarkably low cancer incidence. Most advanced cancers in mammals display increased production of lactic acid from glucose, irrespective of oxygen availability. This hallmark of cancer is known as the Warburg effect (WE). Most malignancies acquire this metabolic phenotype during their somatic evolution, as the WE benefits tumor growth in several ways. We propose that the peculiar metabolism of the NMR makes development of the WE inherently difficult, which might contribute to the extraordinarily low cancer rate in NMRs. Such an adaptation of NMRs to their subterranean environment may have been facilitated by modified biochemical responses with a stronger inhibition of the production of CO2 and lactic acid by a decreased extracellular pH. Since this pH-inhibition could be deeply hard-wired in their metabolic make-up, it may be difficult for malignant cells in NMRs to acquire the WE-phenotype that facilitates cancer growth in other mammals. In the present commentary, we discuss this idea and propose experimental tests of our hypothesis