Nutrition and immunity

It is well recognised that dietary factors play an important role in maintaining immune defences. Malnourished populations are known to have increased incidence and duration of infectious diseases, and data from numerous clinical and experimental studies have demonstrated impaired immunocompetence in the malnourished host. Restoring the food supply to an affected individual restores cell-mediated immunity, except when malnutrition has occurred during foetal development. The developing immune system is particularly susceptible to nutritional deprivation. The problem of malnourishment is not restricted to developing countries. Malnutrition has been reported among hospitalized patients, generally as a result of illness but also as a consequence of surgery and sometimes from inappropriate feeding regimes. Alterations of the immune response can be demonstrated in obesity as well as in the malnourished state, and excess intake of polyunsaturated fatty acids (PUFA) has been shown to suppress immunity. Vitamins and trace minerals are also important in maintaining immunocompetence. Selenium and vitamin E have enhancing effects, probably due to their ability to prevent peroxidation of PUFA, and deficiency of pyridoxine (B6), zinc and vitamin A has been associated with impairment of immune functions. Knowledge gained of the interactions between nutritional factors and immunity offer the possibility of altering dietary regimes in order to modulate immune function and thus improve resistance to infectious disease and other diseases associated with impaired immunity.     

CARDIOVASCULAR AND NEUROLOGICAL EFFECTS OF LAUDANOSINE: Studies in Mice and Rats, and in Conscious and Anaesthetized Dogs

The effects of laudanosine, a metabolite of atracurium, on thebehaviour of conscious mice, rats and dogs, and on cardiovascularfunction in conscious and anaesthetized dogs have been evaluated:EEG studies were performed in anaesthetized dogs. In mice andrats, i. v. bolus doses of laudanosine 10–20 mg kg^–1,caused convulsions and hind limb extensions; these effects wereprevented by pretreatment with diazepam. After the continuousinfusion of laudanosine to conscious dogs, plasma concentrationsin the order of 1.2 µg ml^–1 did not cause behaviouraldisturbances. In anaesthetized dogs, laudanosine plasma concentrationsof more than 6 µ ml^– caused hypotension and bradycardia,laudanosine concentrations greater than 10 µg ml^–1induced epileptic EEG spiking and plasma concentrations greaterthan 17 µg ml^–1 produced prolonged seizures. Thereis a wide difference between laudanosine plasma concentrationsin patients given atracurium by bolus injection or by short-terminfusion for surgical use and those required to induce epilepticactivity in dogs. However, during the prolonged infusion ofatracurium to patients this difference will be decreased. Itis unlikely that the use of atracurium, in patients, would resultin plasma concentrations of laudanosine capable of producingneurological or cardiovascular disturbances.     

Species Differences in Susceptibility to 1,3-Dinitrobenzene-lnduced Testicular Toxicity and Methemoglobinemia

The testicular toxicity and methemoglobinemia induced by 1,3-dinitro-benzene(1,3-DNB) was compared in two species, the Sprague-Dawley ratand the golden Syrian hamster. A marked difference in susceptibilityto both endpoints of toxicity was observed. The hamster showedno testicular lesions at dose levels up to 50 mg/kg whereas,as previously reported by others, damage to rat testicular tubulesin later stages of spermatogenesis was readily apparent at a25 mg/kg dose level. Similarly, administration of 1,3-DNB inducedsubstantially less methemoglobinemia in the hamster than inthe rat. For example, at the 25 mg/kg dose level peak levelsof methemoglobin in the hamster were 15% compared with 80% inthe rat. Mortality in the rat also occurred at lower doses thanin the hamster (50 vs 100 mg/kg, respectively). In in vitrostudies,the capacity of 1,3-DNB and 1,3-DNB metabolites (nitroaniline,nitroacetanilide, aminoacetanilide, diacetamidobenzene) to inducemethemoglobinemia was examined in suspensions of red blood cellsobtained from both species. Only 1,3-DNB caused the formationof methemoglobin and rat red blood cells were twice as sensitiveas hamster red blood cells. The species difference in susceptibilityto both methemoglobinemia and testicular toxicity could indicatedifferences in 1,3-DNB clearance and/or formation of toxic metabolites.Additional metabolic work is under way. This study demonstratesthat the hamster is more resistant than the rat to the testicularlesion and methemoglobinemia induced by 1,3-DNB. c 1991 Societyof Toxicoiofy.     

MODIFICATION OF CENTRAL NERVOUS SYSTEM EFFECTS OF LAUDANOSINE BY INHALATION ANAESTHETICS

To determine the effect of inhalation anaesthetics on the plasmaconcentration of laudanosine necessary to produce CNS excitation,we administered laudanosine 0.5 mg kg^–1 min^–1 i.v.to 40 rabbits under eight study conditions: 1.0 or 0.7% halothane,1.6% isoflurane, 2.0% enflurane, during normocapnia and hypocapnia;70% nitrous oxide, alone and with 1.0% halothane, and room air(control). At the onset of purposeless, unco-ordinated movementsof the entire body, blood samples were obtained to determinethe CNS excitation-threshold plasma concentration (ETPC) oflaudanosine. During normocapnia, 1.0% halothane, 1.6% isofluraneand 2.0% enflurane increased ETPC (mean (SD) 11.8 (2.5), 11.3(2.8) and 9.1 (1.4) µg ml^–1, respectively) fromcontrol (5.0 (0.9) µg ml^–1). ETPC during enfluraneanaesthesia did not change significantly with hypocapnia. Nitrousoxide, alone or in combination with halothane, did not changeETPC. The combination of nitrous oxide with 1.0% halothane significantlydecreased ETPC to less than that for halothane alone (6.7 (1.2)v. 11.8 (2.5) µg ml^–1, respectively). ^*Present address: Department of Anesthesia, Peking Medical College,Beijing, People's Republic of China.