A practice guide for continuous opioid therapy for refractory daily headache: patient selection, physician requirements, and treatment monitoring.

Objectives: To provide a guide to the use and limitations of continuous opioid therapy (COT, or daily scheduled opioids) for refractory daily headache, based on the best available evidence and expert clinical experience.

Background: There has been a dramatic increase in opioid administration over the past 25 years, with limited evidence of efficacy for either pain reduction or increased function, and increasing evidence of adverse effects, including headache chronification. To date, there has been no consensus on headache-specific guidelines for selecting patients for COT, physician requirements, and treatment monitoring.

An ATP and oxalate generating variant tricarboxylic acid cycle counters aluminum toxicity in Pseudomonas fluorescens.

Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al).

Comprehensive inpatient treatment of refractory chronic daily headache.

Objective: (1) To assess outcome at discharge for a consecutive series of admissions to a comprehensive, multidisciplinary inpatient headache unit; (2) To identify outcome predictors.

Background: An evidence-based assessment (2004) concluded that many refractory headache patients appear to benefit from inpatient treatment, underscoring the need for more research, including outcome predictors.

Methods: The authors completed a retrospective chart review of 283 consecutive admissions over 6 months.

Trendelenburg position: a tool to screen for the presence of a low CSF pressure syndrome in daily headache patients.

Objective: To test the hypothesis that the Trendelenburg position is an accurate screening investigation for the presence of a low cerebrospinal fluid (CSF) pressure syndrome in patients with daily headache.

Background: The Trendelenburg position causes a rapid increase in intracranial CSF pressure. In a patient with a known CSF leak who overtime had less improvement in the supine position, being placed in Trendelenburg rapidly alleviated her daily headache.

The tricarboxylic acid cycle, an ancient metabolic network with a novel twist.

The tricarboxylic acid (TCA) cycle is an essential metabolic network in all oxidative organisms and provides precursors for anabolic processes and reducing factors (NADH and FADH(2)) that drive the generation of energy. Here, we show that this metabolic network is also an integral part of the oxidative defence machinery in living organisms and alpha-ketoglutarate (KG) is a key participant in the detoxification of reactive oxygen species (ROS). Its utilization as an anti-oxidant can effectively diminish ROS and curtail the formation of NADH, a situation that further impedes the release of ROS via oxidative phosphorylation.

Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes.

Aluminum (Al), a known environmental toxicant, has been linked to a variety of pathological conditions such as dialysis dementia, osteomalacia, Alzheimer's disease, and Parkinson's disease. However, its precise role in the pathogenesis of these disorders is not fully understood. Using hepatocytes as a model system, we have probed the impact of this trivalent metal on the aerobic energy-generating machinery.

Aluminum-tolerant Pseudomonas fluorescens: ROS toxicity and enhanced NADPH production.

Aluminum (Al) triggered a marked increase in reactive oxygen species (ROS) such as O(2) (-) and H(2)O(2) in Pseudomonas fluorescens. Although the Al-stressed cells were characterized with higher amounts of oxidized lipids and proteins than controls, NADPH production was markedly increased in these cells. Blue native polyacrylamide gel electrophoresis (BN-PAGE) analyses coupled with activity and Coomassie staining revealed that NADP(+) -dependent isocitrate dehydrogenase (ICDH, E.

Aluminum triggers decreased aconitase activity via Fe-S cluster disruption and the overexpression of isocitrate dehydrogenase and isocitrate lyase: a metabolic network mediating cellular survival.

Although aluminum is known to be toxic to most organisms, its precise biochemical interactions are not fully understood. In the present study, we demonstrate that aluminum promotes the inhibition of aconitase (Acn) activity via the perturbation of the Fe-S cluster in Pseudomonas fluorescens. Despite the significant decrease in citrate isomerization activity, cellular survival is assured by the overexpression of isocitrate lyase and isocitrate dehydrogenase (IDH)-NADP+.

Overexpression of isocitrate lyase is an important strategy in the survival of Pseudomonas fluorescens exposed to aluminum.

Isocitrate lyase, ICL (EC 4.1.3.

Adaptation of Pseudomonas fluorescens to Al-citrate: involvement of tricarboxylic acid and glyoxylate cycle enzymes and the influence of phosphate.

The degradation of Aluminum-citrate by Pseudomonas fluorescens necessitated a major restructuring of the various enzymatic activities involved in the TCA and glyoxylate cycles. While a six-fold increase in fumarase (FUM EC 4.2.

The metabolism of aluminum citrate and biosynthesis of oxalic acid in Pseudomonas fluorescens.

(13)CNMR and (1)HNMR studies revealed that aluminum citrate (Al-citrate) was metabolized intracellularly and that oxalic acid was an important product in the Al-stressed cells. This dicarboxylic acid was produced via the oxidation of glyoxylate, a precursor generated through the cleavage of isocitrate. In the control cells, citrate was biotransformed essentially with the aid of regular tricarboxylic cycle (TCA) enzymes.

Aluminum detoxification in Pseudomonas fluorescens is mediated by oxalate and phosphatidylethanolamine.

13C NMR studies with aluminum (Al)-stressed Pseudomonas fluorescens revealed that the trivalent metal was secreted in association with oxalate and phosphatidylethanolamine (PE). These moieties were observed in the insoluble pellet obtained upon incubation of these resting cells in the presence of either Al-citrate or citrate. This extrusion process was concomitant with the utilization of either of these tricarboxylic acids as a substrate.