Total hip arthroplasty. The role of antiinflammatory medications in the prevention of heterotopic ossification

Postoperative prophylaxis with antiinflammatory medications, primarily indomethacin, is extremely effective in preventing the severest degrees of heterotopic ossification (HO) after a total hip arthroplasty (THA) and the recurrence of excised HO developed after a previous hip surgery. Prophylaxis with indomethacin should be given in 25-mg doses three times daily for at least three weeks, starting on the first postoperative morning. However, a shorter treatment period may be equally effective in preventing the severest degrees of HO, and a postoperative delay of five days before the initiation of prophylaxis does not seem to be followed by the development of severe HO. As evaluated one year after surgery, treatment with antiinflammatory medications in the immediate postoperative weeks did not increase the incidence of implant-bone interface radiolucencies, aseptic loosening, or revisions in cemented or cementless THAs when compared with cases that did not have postoperative treatment. However, although no major complications have been reported regarding the use of antiinflammatory medications in the prevention of HO after THA, orthopedic surgeons prescribing such treatment should be aware of their contraindications as well as early and late side effects. Since several antiinflammatory agents are reported to be effective in preventing HO, future reports dealing with HO after THA should always include information about the postoperative antiinflammatory treatment used.     

Intestinal parasites in a rural community in Kenya: cross-sectional surveys with emphasis on prevalence, incidence, duration of infection, and polyparasitism

A cross-sectional survey of intestinal parasitic infection in a rural community, Nderu, in Kiambu District, Kenya, was carried out in 1985 by examining 1129 individuals from 203 households (about 25% of the total population). This was followed by 3 more cross-sectional surveys, in January, May and October 1986, of 56 families comprising 461 individuals, who had also participated in the first survey. In the first survey, 81.4% of the sample was positive for at least one intestinal parasite and 78% was positive for intestinal protozoa. 72.7% of those infected had multiple infections. The prevalence of most of the protozoa increased with age but that of Giardia lamblia peaked in the 0 to 4 year class at 35.5%. Females were infected more often with several of the protozoa, but males with Ascaris. People living in larger households were more often infected with Entamoeba histolytica and Iodamoeba butschlii, while the opposite was true of H. nana and tended to be for Giardia. Significant positive associations between parasite species were common at all surveys, especially among the amoebae. The majority of negative associations were for Giardia. Unformed stools were significantly associated with Giardia, Blastocystis, and trophozoites of Trichomonas hominis and Chilomastix mesnili. Endolimax nana and Entamoeba coli were found more often in formed stools. Estimates of daily incidence, and duration of infection in days, were calculated for 11 parasites. The longest mean estimated duration of infection for any species was 237 +/- S.D. 151.4 days for H. nana and the shortest was 41.6 +/- S.D. 0.4 days for T. hominis.     

Cloning and characterization of Ca(2+)-dependent and Ca(2+)-independent PKCs expressed in Aplysia sensory cells

We isolated cDNA clones from an Aplysia sensory-cell library encoding two isoforms of protein kinase C (PKC). Several isozyme-specific regions are conserved in the Aplysia kinases, notably the variable regions V5 in the Ca(2+)-dependent PKC (Apl I) and V1 in the Ca(2+)-independent PKC (Apl II). Neuronal proteins with the properties expected of these two isoforms can be identified with antibodies raised against peptides synthesized from the amino acid sequences deduced from the clones. Sacktor and Schwartz (1990) measured the proportion of kinase activity that can be translocated to membrane in Aplysia sensory neurons and ganglia by stimuli that produce the presynaptic facilitation underlying behavioral sensitization. Much less Apl I and Apl II are translocated, suggesting that still other isoforms of PKC exist in these cells.     

Dopamine D-1 receptor-mediated inhibition of nucleus accumbens neurons from the ventral tegmental area.

1. Spike generation by stimulation of the parafascicular nucleus of thalamus was extracellularly recorded in the nucleus accumbens of chloral hydrate-anesthetized adult Wistar rats using a silver-wire microelectrode attached along a seven-barreled micropipette, each of which was filled with dopamine, SKF 38393 (D-1 agonist), bromocriptine (D-2 agonist), haloperidol, SCH 23390 (D-1 antagonist) and domperidone (D-2 antagonist). The drugs were microiontophoretically applied to the target neurons recorded. 2. Effects of dopamine receptor antagonists on the inhibition of the spike generation by conditioning stimuli applied to the ventral tegmental area preceding the test stimulus to the parafascicular nucleus and those of dopamine agonists on the test stimulus-induced spikes were examined. 3. The parafascicular nucleus stimulation-induced spikes were inhibited by dopamine as well as D-1 and D-2 agonists and by the conditioning stimulation of the ventral tegmental area. The conditioning stimulation-induced inhibition was antagonized by haloperidol and SCH 23390, but not by domperidone. 4. Activation of D-1 receptors, which make probably synaptic contact with dopaminergic nerve terminals from the ventral tegmental area, is considered to result in inhibition of the neuronal activity of the nucleus accumbens neurons receiving input from the parafascicular nucleus of the thalamus. In addition, D-2 receptors located extrajunctionally may be involved in the inhibition of the same neurons in the nucleus accumbens.     

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

The use of rat brain slices as an in vitro model for mechanistic evaluation of neurotoxicity-studies with acrylamide

Biochemical mechanisms underlying acrylamide induced neurotoxicity were examined using an in vitro model consisting of sagittal slices of rat brain. Incubation of brain slices under oxygen in artificial cerebrospinal fluid containing acrylamide produced a dose and time dependent inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Lysosomal enzymes, acid phosphatase, N-acetyl glucosaminidase and beta-glucuronidase decreased in a similar manner, while no changes were observed in the activity of Na+K+ATPase, cytochrome c oxidase and lactate dehydrogenase. Incubation of slices with two structurally related compounds, acetamide (a non-neurotoxic amide) and methylene bis-acrylamide (a weak neurotoxin), indicated that acrylamide selectively inhibited GAPDH, enolase and N-acetyl glucosaminidase at low concentration; similar doses of acetamide and methylene bis-acrylamide did not have the same effect on brain slices. Incubation with acrylamide depleted glutathione levels in slices, and the addition of glutathione to the incubation medium prevented acrylamide induced inhibition of GAPDH and lysosomal enzymes. Time dependent inhibition of lysosomal enzymes was also observed in vivo, in the brain and sciatic nerve of rats following a single dose of acrylamide. These results demonstrate that both in vitro and in vivo, lysosomal enzymes are also inhibited following acrylamide exposure. The rat brain slice model exhibits both selectivity and sensitivity towards neurotoxicants and hence, may prove to be an useful in vitro model for the mechanistic evaluation of neurotoxicity.     

Opposite effects of phospholipase A2 on [3H]AMPA binding in adult and neonatal membranes.

In the present study, we compared the effect of phospholipase A2 (PLA2) treatment of synaptic membranes from adult and neonatal rats on the characteristics of [3H]AMPA binding sites. Whereas PLA2 treatment of membranes from adult rats produces an increased affinity for [3H]AMPA binding, the same treatment in neonatal rats results in a decrease in the maximal number of binding sites. Since activation of PLA2 has been proposed to play a critical role in the formation of long-term potentiation (LTP), possibly mediated through a modification of the AMPA receptors, the results strengthen the hypothesis that PLA2-induced modification of [3H]AMPA binding sites is an important component of synaptic plasticity.