Drug-induced hyperuricaemia and gout.

Hyperuricaemia is a common clinical condition that can be defined as a serum uric acid level >6.8 mg/dl (404 µmol/l). Gout, a recognized complication of hyperuricaemia, is the most common inflammatory arthritis in adults. Drug-induced hyperuricaemia and gout present an emergent and increasingly prevalent problem in clinical practice. Diuretics are one of the most important causes of secondary hyperuricaemia. Drugs raise serum uric acid level by an increase of uric acid reabsorption and/or decrease in uric acid secretion. Several drugs may also increase uric acid production. In this review, drugs leading to hyperuricaemia are summarized with regard to their mechanism of action and clinical significance. Increased awareness of drugs that can induce hyperuricaemia and gout, and monitoring and prevention are key elements for reducing the morbidity related to drug-induced hyperuricaemia and gout.

Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise.

Intramuscular acidosis is a contributing factor to fatigue during high-intensity exercise. Many nutritional strategies aiming to increase intra- and extracellular buffering capacity have been investigated. Among these, supplementation of beta-alanine (~3-6.4 g/day for 4 weeks or longer), the rate-limiting factor to the intramuscular synthesis of carnosine (i.e. an intracellular buffer), has been shown to result in positive effects on exercise performance in which acidosis is a contributing factor to fatigue. Furthermore, sodium bicarbonate, sodium citrate and sodium/calcium lactate supplementation have been employed in an attempt to increase the extracellular buffering capacity. Although all attempts have increased blood bicarbonate concentrations, evidence indicates that sodium bicarbonate (0.3 g/kg body mass) is the most effective in improving high-intensity exercise performance. The evidence supporting the ergogenic effects of sodium citrate and lactate remain weak. These nutritional strategies are not without side effects, as gastrointestinal distress is often associated with the effective doses of sodium bicarbonate, sodium citrate and calcium lactate. Similarly, paresthesia (i.e. tingling sensation of the skin) is currently the only known side effect associated with beta-alanine supplementation, and it is caused by the acute elevation in plasma beta-alanine concentration after a single dose of beta-alanine. Finally, the co-supplementation of beta-alanine and sodium bicarbonate may result in additive ergogenic gains during high-intensity exercise, although studies are required to investigate this combination in a wide range of sports.

Sodium lactate for fluid resuscitation: the preferred solution for the coming decades?

In a recent issue of Critical Care, 0.5 M sodium lactate infusion for 24 hours was reported to increase cardiac output in patients with acute heart failure. This effect was associated with a concomitant metabolic alkalosis and a negative water balance. Growing data strongly support the role of lactate as a preferential oxidizable substrate to supply energy metabolism leading to improved organ function (heart and brain especially) in ischemic conditions. Due to its sodium/chloride imbalance, this solution prevents hyperchloremic acidosis and limits fluid overload despite the obligatory high sodium load. Sodium lactate solution therefore shows many advantages and appears a very promising means for resuscitation of critically ill patients. Further studies are needed to establish the most appropriate dose and indications for sodium lactate infusion in order to prevent the occurrence of severe hypernatremia and metabolic alkalosis.

Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats.

Rats with chronic inhibition of GABA synthesis by infusion of l-allyglycine, a glutamic acid decarboxylase inhibitor, into their dorsomedial/perifornical hypothalamus are anxious and exhibit panic-like cardio-respiratory responses to treatment with intravenous (i.v.) sodium lactate (NaLac) infusions, in a manner similar to what occurs in patients with panic disorder. We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2/3 receptor agonists can block such a NaLac response, suggesting that a glutamate mechanism is contributing to this panic-like state. Using this animal model of panic, we tested the efficacy of CBiPES and THIIC, which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators (at 10-30 mg/kg i.p.), in preventing NaLac-induced panic-like behavioral and cardiovascular responses. The positive control was alprazolam (3mg/kg i.p.), a clinically effective anti-panic benzodiazepine. As predicted, panic-prone rats given a NaLac challenge displayed NaLac-induced panic-like cardiovascular (i.e. tachycardia and hypertensive) responses and "anxiety" (i.e. decreased social interaction time) and "flight" (i.e. increased locomotion) -associated behaviors; however, systemic injection of the panic-prone rats with CBiPES, THIIC or alprazolam prior to the NaLac dose blocked all NaLac-induced panic-like behaviors and cardiovascular responses. These data suggested that in a rat animal model, selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti-panic efficacy similar to alprazolam.

The lactate provocation test to investigate the relationships between panic attacks and psychosis: a report of two cases.

It was suspected that the delusional convictions of bewitchment and devil persecution of two female patients (41 and 40-years-old) could be the consequence of an erroneous interpretation of the sensations induced by panic attacks, as several authors have previously suggested. The interest of this case report stems from the manner in which we tested our clinical hypothesis. The patients agreed to the use of a lactate provocation test in double-blind, placebo-controlled conditions during four randomized sessions on consecutive days (two with lactate and two with placebo). The results for patient A strongly supported our hypothesis: patient A developed two full-blown panic attacks during the active lactate sessions, whereas patient B developed one subthreshold and one moderate panic attack during the active lactate sessions. The results of these investigations led to a more specific psychotherapeutic approach for patient A.

Disruption of GABAergic tone in the dorsomedial hypothalamus attenuates responses in a subset of serotonergic neurons in the dorsal raphe nucleus following lactate-induced panic.

Panic patients are vulnerable to induction of panic attacks by sub-threshold interoceptive stimuli such as intravenous (i.v.) sodium lactate infusions. Facilitation of serotonergic signaling with selective serotonin reuptake inhibitors can suppress anxiety and panic-like responses, but the mechanisms involved are not clearly defined. We investigated the effects of i.v. 0.5 M sodium lactate or saline, in control and panic-prone rats on c-Fos expression in serotonergic neurons within subdivisions of the midbrain/pontine raphe nuclei. Rats were chronically infused with either the GABA synthesis inhibitor l-allylglycine into the dorsomedial hypo thalamus to make them panic-prone, or the enantiomer d-allylglycine (d-AG) in controls. Lactate increased c-Fos expression in serotonergic neurons located in the ventrolateral part of the dorsal raphe nucleus (DRVL) and ventrolateral periaqueductal gray (VLPAG) of control, but not panic-prone, rats. The distribution of lactate-sensitive serotonergic neurons in d-AG-treated rats is virtually identical to previously defined pre-sympathomotor serotonergic neurons with multisynaptic projections to peripheral organs mediating 'fight-or-flight'-related autonomic and motor responses. We hypothesized that serotonergic neurons within the DRVL/VLPAG region represent a 'sympathomotor control system' that normally limits autonomic/behavioral responses to innocuous interoceptive and exteroceptive stimuli, and that dysfunction of this serotonergic system contributes to an anxiety-like state and increases vulnerability to panic in animals and humans.

Sodium lactate addition on the quality and shelf life of refrigerated sliced poultry sausage packaged in air or nitrogen atmosphere.

The aim of this study was to determine the effect of sodium lactate addition on shelf-life extension of sliced poultry sausage packaged both in air and nitrogen atmospheres and stored in refrigerated conditions. Basic chemical composition, pH, and malonaldehyde content were assayed and color measurement using the reflection method was carried out. Microbiological examination consisted of determination of total number of aerobic psychrotrophic bacteria and number of lactic acid bacteria. Sensory evaluation of products was performed. Microbiological and sensory quality of sliced poultry meat sausage was dependent on the addition during production of sodium lactate and the composition of gases (air or nitrogen) used in packaging. Slices of poultry sausage with 1% as well as 2% of sodium lactate maintained their initial quality of evaluated sensory attributes longer, irrespective of the applied gases. Sodium lactate inhibited growth of aerobic psychrotrophic bacteria and lactic acid bacteria during refrigerated storage. Sodium lactate also inhibited the formation of malonaldehyde in sliced poultry sausage during refrigerated storage. The effectiveness of this process depended on the concentration of sodium lactate addition. It was concluded that 1% as well as 2% addition of sodium lactate could extend the shelf life of sliced poultry sausage packaged in air atmosphere and stored at 5 to 7 degrees C by 3 or 4 times, respectively. Sliced poultry sausage treated with 2% sodium lactate packed in nitrogen had the longest (35-day) shelf life. This was a sevenfold increase in the shelf life of sliced poultry sausage compared with the control.

Increased response to a putative panicogenic nocebo administration in female patients with panic disorder.

Experimental challenge studies may generate and test hypotheses regarding the pathophysiology of panic disorder and may serve to identify pathophysiologically relevant subtypes. It has been suggested that gender-related differences may be relevant in the development and maintenance of panic disorder. In a randomized double blind design the effects of placebo and sodium lactate administration in 14 female and 16 male patients with panic disorder and 23 healthy control subjects were compared using the Acute Panic Inventory (API) score and derived formal criteria for a panic attack. Panic attack frequency following sodium lactate was 76.6% in the patient group. Although control subjects had a lactate-induced increase in the API score as well, this effect was much weaker. No panic attacks occurred in patients with panic disorder or healthy control subjects receiving a placebo. However, a gender effect was observed in the putative panicogenic placebo condition: female patients with panic disorder had more subthreshold panic anxiety as measured with the API score. The data give evidence for an increased nocebo response in female patients with panic disorder.

Antioxidant mechanisms in human peritoneal mesothelial cells (HPMC) exposed in vitro to the constituents of dialysis fluid.

OBJECTIVE: To assess effects of hyperosmolarity, high glucose concentration, and low pH with or without lactate sodium at the level of antioxidant mechanisms, such as the concentration of total intracellular glutathione (GSH/GSSG), the activity of catalase (CAT) and total superoxide dismutase (SOD) in mesothelial cells (MC) in vitro. METHODS: HPMC were obtained from omentum from nonuremic donors. The effect of pH (5.2-7.3) with or without sodium lactate (35 mM/L) was tested in Earle's salt after 30 min exposure, whereas the osmotic and metabolic effects of glucose, glycerol, mannitol, and amino acids were studied in a medium with 10% FCS after 4, 24, 72 and 104 h of exposure. The activity of antioxidant mechanisms was determined by spectrophotometry. RESULTS: In the cells exposed to Earle's salt pH 5.2 with lactate, the GSH/GSSG level, and CAT and SOD activity were substantially reduced. After 4 h of exposure, glycerol, glucose and mannitol increased the GSH/GSSG content in MC; after 24 h only glucose slightly increased the GSH/GSSG level. CONCLUSION: We conclude that although low pH with high lactate concentration decreased the activity of all studied antioxidant mechanisms in MC, the clinical relevance of these observations needs to be studied further.