Inflammatory pain and hypersensitivity are selectively reversed by epidural bupivacaine and are developmentally regulated

BACKGROUND: Low doses of local anesthetics applied to the young rat spinal cord in vitro have been shown to inhibit C-fiber-evoked responses. The aim of this work was to investigate whether such low doses applied epidurally selectively reduce nociceptive responses in vivo and to investigate the influence of postnatal development on such local anesthetic actions. METHODS: Three groups of rat pups aged 3, 10, and 21 days were studied. The threshold of the flexion withdrawal reflex to mechanical stimulation was determined in the hind limb at each age. Inflammatory pain was induced in the right hind limb with 2% carrageenan, causing a reduction in the sensory threshold on that side. The difference in threshold between the two sides represents inflammatory hypersensitivity. The effect of low-dose epidural bupivacaine on sensory thresholds and thus the induced hypersensitivity was also determined for each age group. RESULTS: Inflammatory hypersensitivity was selectively attenuated by very low doses of bupivacaine (concentration range. 0.004-0.0625%), which did not affect the sensory threshold in the contralateral uninflamed limb. This effect was also age-related, with younger rats being more sensitive than older rats. CONCLUSIONS: The effects of epidural bupivacaine in the infant rat are developmentally regulated. Lower doses have a selective analgesic effect that decreases with increasing postnatal age.     

The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Controversies in transfusion medicine. Perioperative hemodilution: pro

Hemodilution can obviate the need for allogeneic transfusion in some patients. However, it is only one component of a comprehensive blood conservation program and should be combined with other techniques whenever possible. While most often employed in teenagers and healthy young adults, ANH has been used in small children, the elderly, and patients of all ages who are undergoing cardiac surgery. Extreme caution should be exercised if ANH is used in patients with coronary artery disease or aortic stenosis who are undergoing noncardiac surgery, because their normal compensatory mechanisms are impaired. What usually is a safe and relatively simple procedure can become a disaster if employed in inappropriately selected patients. Careful hemodynamic monitoring and maintenance of normovolemia are critical.     

Insulin Infusion Normalizes Cardiovascular Responses and Plasma Noradrenaline after Oral Glucose in Type 1 (Insulin-dependent) Diabetes

ABSTRACT. We examined whether the abnormal regulation of the cardiovascular system and plasma noradrenaline observed after oral glucose in insulin-dependent diabetic patients could be normalized by intravenous infusion of insulin. Eight patients with type 1 (insulin-dependent) diabetes were examined after an oral glucose load with and without simultaneous infusion of insulin. Insulin infusion increased plasma insulin from 0.07 to 0.31 nmol/1. In the control experiment (glucose only), mean heart rate and mean arterial systolic blood pressure remained unchanged and plasma noradrenaline (NA) decreased (p < 0.05). After oral glucose plus intravenous insulin, mean heart rate increased by 11 % and mean systolic blood pressure by 5 % (p < 0.05, p < 0.01), whereas plasma NA did not change significantly. The present study indicates that physiologic increments in plasma insulin concentration are of importance in the regulation of the cardiovascular system and plasma NA following an oral glucose load.     

Stimulation of oxidant production in alveolar macrophages by pollutant and latex particles

Air pollutant dusts as well as chemically defined particles were examined for their activating effect on oxidant production (O₂^? and H₂O₂) in guinea pig alveolar macrophages (AM). Oxidant production was measured as chemiluminescence of albumin-bound luminol. All particles examined stimulated the AM in a dose-dependent manner to different maximal levels of oxidant production. Amphibole asbestos samples were the most active of all agents studied. Various immune reactants as well as silica, metal-oxide-coated fly ash, polymethyl methacrylate beads, and chrysotile asbestos had intermediate activity, while fugitive dusts, polybead carboxylate microspheres, glass and latex beads, uncoated fly ash, and fiberglass had the lowest activity. In addition to direct stimulatory action on AM, particles also lowered the subsequent responsiveness of the cells to the bacterial peptide stimulant, N-formylmethionyl phenylalanine. This effect was only partially due to the cytotoxicity of the particles. While some relationship appeared to exist between stimulatory activity and cytotoxicity of the particles, the exact role of O₂^? in mediating cytotoxic effects is still open to question. Oxidant production in AM is a parameter which may be important in determining the pathological effects of particles as well as of materials adsorbed to their surfaces.     

Protein O-carboxylmethyltransferase in spermatozoa from normal and infertile men

In confirmation of several reports, suspensions of normal washed human spermatozoa exposed to a nonionic detergent exhibited considerable activity of the enzyme protein O-carboxylmethyltransferase (PCM), which catalyzes the methyl esterification of carboxyl groups of dicarboxylic amino acid residues in proteins. Various methods for assay of human spermatozoal PCM levels were evaluated, and some properties of the enzyme were studied. Normal human spermatozoa appear to be devoid of other types of protein methyltransferases that catalyze N-methylations of arginyl or lysyl residues in proteins. Spermatozoal PCM levels in infertile patients with motile sperm cells tended to be somewhat higher than those of normal control subjects, especially in those instances where the spermatozoal populations contained abnormally high proportions of immature forms of spermatozoa. Although totally immotile spermatozoa obtained from certain patients exhibited very low PCM activities (as recently reported by other investigators), in this study no invariant relationship between zero motility indexes and spermatozoal PCM was observed. These results are discussed in light of various current hypotheses regarding the functions of PCM in animal cells.     

Immediate toxicity of high multiplicities of Chlamydia psittaci for mouse fibroblasts (L cells).

One hour after suspensions of mouse fibroblasts (L cells) were exposed to 500 to 1,000 L-cell 50% infectious doses of Chlamydia psittaci (6BC), the L cells failed to attach to and spread out on solid substrates, phagocytosed polystyrene latex spheres at reduced rates, incorporated less [14C]isoleucine into protein, and had smaller soluble pools of nucleoside triphosphates. The infected L cells began to die at 8 h and were all dead by 20 h. Lower multiplicities of infection took correspondingly longer to kill the L cells. These effects of high multiplicities of C. psittaci on L cells will be referred to collectively as immediate toxicity. Similar effects were obtained with other strains of C. psittaci and C. trachomatis and with other cell lines. Ultraviolet-inactivated C. psittaci retained the ability to cause immediate toxicity, but heat-inactivated chlamydiae did not. C.psittaci cells had to be ingested by L cells before they were immediately toxic but, once they were phagocytosed, they did not need to multiply or to synthesize macromolecules in order to cause immediate injury to their hosts. Immediate toxicity was not the result of depression of energy metabolism, changes in the levels of intracellular cyclic nucleotides, or release of hydrolases from lysosomes. It was suggested that a lesion is produced in the plasma membrane of the L cell every time it ingests a chlamydial cell, that each act of ingestion produces an independent lesion, and that their injurious effects are additive. Thus, the more ingestion lesions there are, the faster the host cell dies. It was also suggested that induced phagocytosis, inhibition of lysosomal fusion, and death of mice and of cells in culture may all depend on a single activity of C. psittaci.