Treatment of soft tissue contour defects by a combination of surgical subcision with a Beaver tympanoplasty blade and autologous fat grafting.

This report describes a technique for treating depressed scars and soft tissue contour deformities. Surgical subcision with a Beaver tympanoplasty blade is undertaken for depressed or adherent scars to release the fibrous attachments beneath the scar before autologous fat grafting. Satisfactory results were observed, with an improvement in surface contour for 16 patients over a 3-year period. The authors recommend the described technique as a safe, minimally invasive, and precise method for subcutaneous dissection of scar tissue before fat injections.

Co-administration of conjugated linoleic acid and rosiglitazone increases atherogenic co-efficient and alters isoprenaline-induced vasodilatation in rats fed high fat diet.

The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (R(max)=53+/-4.7 %; pEC50=6+/-0.2) compared to endothelium-intact aortas (R(max)=100+/-9.9 %; pEC50=7+/-0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.

Endurance exercise promotes cardiorespiratory rehabilitation without neurorestoration in the chronic mouse model of parkinsonism with severe neurodegeneration.

Physical rehabilitation with endurance exercise for patients with Parkinson's disease has not been well established, although some clinical and laboratory reports suggest that exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. In this study, we used a chronic mouse model of Parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. This chronic parkinsonian model displays a severe and persistent loss of nigrostriatal neurons, resulting in robust dopamine depletion and locomotor impairment in mice. Following the induction of Parkinsonism, these mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we examined and compared their cardiorespiratory capacity, behavior, and neurochemical changes with that of the probenecid-treated control and sedentary parkinsonian mice. The resting heart rate after 4 weeks of exercise in the chronic parkinsonian mice was significantly lower than the rate before exercise, whereas the resting heart rate at the beginning and 4 weeks afterward in the control or sedentary parkinsonian mice was unchanged. Exercised parkinsonian mice also recovered from elevated electrocardiogram R-wave amplitude that was detected in the parkinsonian mice without exercise for 4 weeks. The values of oxygen consumption, carbon dioxide production, and body heat generation in the exercised parkinsonian mice before and during the Bruce maximal exercise challenge test were all significantly lower than that of their sedentary counterparts. Furthermore, the exercised parkinsonian mice demonstrated a greater mass in the left ventricle of the heart and an increased level of citrate synthase activity in the skeletal muscles. The amphetamine-induced, dopamine release-dependent locomotor activity was markedly inhibited in the sedentary parkinsonian mice and was also inhibited in the exercised parkinsonian mice. Finally, neuronal recovery from the loss of nigrostriatal tyrosine hydroxylase expression and dopamine levels in the severe parkinsonian mice after exercise was not evident. Taken all together, these data suggest that 4 weeks of treadmill exercise promoted physical endurance, resulting in cardiorespiratory and metabolic adaptations in the chronic parkinsonian mice with severe neurodegeneration without demonstrating a restorative potential for the nigrostriatal dopaminergic function.

Early signs of neuronal apoptosis in the substantia nigra pars compacta of the progressive neurodegenerative mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model of Parkinson's disease.

Parkinson's disease is associated with a progressive loss of substantia nigra pars compacta dopaminergic neurons. The cellular and molecular mechanisms underlying Parkinson's disease neurodegeneration have not been fully determined. Clinical investigations and subacute in vivo studies using the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine have generated some observations suggesting that apoptosis is involved in neurodegeneration; however, this view remains equivocal. In this study, the substantia nigra pars compacta neurodegenerative process was examined in the chronic mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model of Parkinson's disease treated with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250 mg/kg) over five weeks. One day after chronic treatment, numerous terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells were detected specifically in the substantia nigra pars compacta displaying shrunken volume, chromatin condensation, and DNA fragmentation. The number of apoptotic cells declined over time. No terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells were found in untreated or probenecid-treated control animals. Cytomorphometric analysis of substantia nigra pars compacta nuclear loci revealed eccentric nucleoli dislocation and vesicular degranulation in all of the apoptotic neurons for the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model for Parkinson's disease. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells phenotypically showed neuronal origin (NeuN-positive) with a loss of tyrosine hydroxylase immunoreactivity. While the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells were not co-localized with astroglial (GFAP-positive) cells, some apoptotic cells were clearly associated with the activated microglial (macrophage antigen complex-1 and isolectin B(4)-positive) cells suggesting an active process of dead cell removal. In the one-day and seven-day post-treated mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model for Parkinson's disease, marked depression of tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and striatum was observed, which was correlated with significant reductions of striatal dopamine content and uptake. These results suggest that initial neuronal apoptosis and morphological changes are involved, at least in part, in the chronic neurodegeneration of mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model for Parkinson's disease.

Surgical treatment of in-growing toenails performed by senior house officers: are they good enough?

BACKGROUND: Although the surgical treatment of in-growing toenails is a common procedure, the success of ingrown toenail surgery is extremely variable and recurrences frequently impair the quality of lift of those who have this condition. In most hospitals this procedure is commonly performed by junior surgical trainees who may have little experience. AIM: We proposed to find out if the success of this procedure is operator-dependent by comparing the results of standard of toenail surgery performed by basic surgical trainees (BSTs) in our hospitals with already published data. METHODS: A retrospective analysis of nail bed ablation surgery performed by BSTs under local anaesthesia over a 15-month period in a district general hospital was conducted. RESULTS: 106 phenol ablations and 46 germinal matrix excisions were prformed. Symptomatic recurrence rates 12 months following the procedure were 5.7% for phenol ablation and 4.3% for germinal matrix excisions. CONCLUSION: Our results are comparable to published data, and we conclude that toenail ablation surgery can be just as successfully performed by junior surgeons after relatively little training in the procedure.

Evaluation of the new red cell parameters on Beckman Coulter DxH800 in distinguishing iron deficiency anaemia from thalassaemia trait.

INTRODUCTION: The new red blood cell (RBC) parameters such as reticulocyte haemoglobin content and percentage of hypochromic red cells or equivalent, although useful in the laboratory assessment of iron deficiency anaemia (IDA), are confounded by thalassaemia trait (TT). We aim to evaluate the new red cell parameters on the Beckman Coulter DxH800 in distinguishing between IDA and TT. METHODS: A total of 246 normal subjects, 102 patients with IDA and 115 subjects with TT were accrued for the study. The parameters studied were red blood cell size factor (RSF), low haemoglobin density (LHD%), microcytic anaemia factor (MAF), standard deviation of conductivity of the nonreticulocyte population (SD-C-NRET) and unghosted cell (UGC). Comparison between groups was performed by Student's t-test, and the diagnostic performance was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Both the LHD% and RSF were significantly higher in IDA than TT, whereas MAF and SD-C-NRET were significantly lower. The SD-C-NRET showed the best diagnostic performance as a single parameter. A formula, [(RBC + Hb) × (HCT + SD-C-NRET)]/RDW-SD, was devised to distinguish between IDA and TT. With a cut-off value of 23, the area under the curve (AUC) was 0.995 (95% CI of 0.99-1.00), the sensitivity was 97%, and the specificity was 99.1%. CONCLUSIONS: The new RBC parameters on Beckman Coulter DxH800 provide useful information in distinguishing between IDA and TT, which is important for clinical decision-making and for streamlining laboratory testing. A new formula is devised that performs better than other discriminant functions in the literature.

Cerebrospinal fluid of Parkinson's disease patients inhibits the growth and function of dopaminergic neurons in culture.

We report the possible existence of an inhibitory factor in the CSF of Parkinson's disease patients that inhibits the function and growth of dopaminergic neurons in rat mesencephalic culture. After 40 hours' exposure to the < 10 kd fraction of CSF from PD patients, the high-affinity dopamine uptake was 66% of that of cultures exposed to CSF from controls. However, the number of dopaminergic neurons remained unchanged at this time. After 90 hours' exposure to the < 10 kd fraction of CSF from PD patients, the number of dopaminergic neurons decreased to 10% of that in cultures exposed to CSF from controls, and the size of the remaining dopaminergic neurons in the culture became smaller. This inhibitory factor did not affect the growth of other types of neurons. The chemical nature of this inhibitory factor is under investigation.

Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used to induce an animal model of Parkinsonism. The conventional mouse model, which usually involves acute or subacute injections of MPTP, results in a significant but reversible loss of dopaminergic functions. We have developed an alternative mouse model, in which co-administration of MPTP with probenecid results in the chronic loss of striatal dopamine for at least 6 months after cessation of treatment. In the present study, we compare the neurochemical, morphological and behavioral changes that occur in this alternative, chronic model with those in the conventional, subacute model. In the chronic model, we demonstrate an almost 80% loss of striatal dopamine and dopamine uptake 6 months after withdrawal from treatment. The neurochemical signs match unbiased stereological measures that demonstrate gradual loss of substantia nigra neurons. Rotarod performance further substantiates these findings by showing a progressive decline in motor performance. Based on the comparisons made in this study in mice, the chronic MPTP/probenecid model shows considerable improvements over the conventional, subacute MPTP model. The sustained alterations in the nigrostriatal pathway resemble the cardinal signs of human Parkinson's disease and suggest that this chronic mouse model is potentially useful to study the pathophysiology and mechanisms of Parkinsonism. It should also prove useful for the development of neuroprotection strategies.

Increase of calmodulin-stimulated striatal particulate phosphorylation response in chronic haloperidol-treated rats.

Calcium- and calmodulin-dependent protein kinase and phosphatase activities were studied in rat striatal particulate preparations. The effect of Ca2+ (0.1-0.5 mM) on phosphorylation was completely abolished in the preparation which had been washed 3 times with a buffer containing ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA, 1.2 mM). Ca2+-stimulated phosphorylation was restored in a dose-dependent manner after calmodulin (1 microgram) was added to the assays. Ca2+ and calmodulin promoted the phosphate incorporation into two major striatal protein bands with estimated Mr at 52 and 40 kdaltons. The presence of phosphatase in the EGTA-pretreated preparations was negligible. Chronic treatment in rats with haloperidol (1 mg/kg, 20 days) produced a significant decrease in the Ca2+-independent phosphorylation but an increase in the extent of Ca2+ and calmodulin-dependent phosphorylation in the striatum. The chronic haloperidol treatment did not alter the striatal [125I]calmodulin binding curve. In vitro, haloperidol (even at 10(-4) M) had no effect on calmodulin-dependent phosphorylation. Haloperidol (10(-4) M) did not reduce the number but decreased the rate of [125I]calmodulin bindign to the striatal particulates. These data suggest that the link between dopamine receptors and calmodulin-dependent enzyme is dissociated in vitro. On the other hand, the potentiated sensitivity of calmodulin-dependent protein kinase in the chronic haloperidol-treated rats correlated with the supersensitive dopamine receptor responses occurred in these rats. Therefore, calmodulin-dependent protein kinase may biochemically regulate dopamine receptor functions in the striatum in vivo.

Pharmacological effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine receptor system.

In mice, chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an increase in the maximum number of [3H]spiperone binding sites in the striatum. The sensitivity of striatal protein phosphorylation to calcium plus calmodulin is also potentiated in MPTP-treated mice. These observations are associated with an enhancement of apomorphine-induced climbing behavior in the drug-treated animals. The results of this study suggest that in an animal model for Parkinson's disease, MPTP interrupts the dopamine (DA) transmission by chemically denervating the nigrostriatal neurons and through a compensatory mechanism, it increases the number of DA receptors as well as the sensitivity of protein phosphorylation to calcium plus calmodulin in mouse striatum. The latter two events may contribute to the development of DA receptor supersensitivity.

Lysosomal malfunction accompanies alpha-synuclein aggregation in a progressive mouse model of Parkinson's disease.

We have detected granular and filamentous inclusions that are alpha-synuclein- and ubiquitin-immunoreactive in the cytoplasm of dopaminergic and cortical neurons of C57/black mice treated chronically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid. The immunoreactive aggregates only become evident several weeks after large-scale dopaminergic cell death and a downregulation of alpha-synuclein gene expression. Numerous lipofuscin granules accumulate alpha-synuclein in the nigral and limbic cortical neurons of treated mice. These data provide evidence that insoluble proteins, such as alpha-synuclein, build up as granular and filamentous inclusions in dopaminergic neurons that survive the initial toxic MPTP insult. They further suggest that defective protein degradation rather than altered gene expression underlies deposition of alpha-synuclein and that abundant lysosomal compartments are present to seal off the potentially toxic material.

The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a disruption of nigrostriatal dopaminergic function which resembles parkinsonism. On the cellular level, the disruption involves a Ca2+ independent release of dopamine, depletion of nigral and striatal dopamine, and the death of dopaminergic neurons. We have previously reported that MPTP can cause a non-reversible inhibition of neostriatal synaptic transmission. In this study we investigated the effect of altering Ca2+ concentration on MPTP's actions in the mouse nigrostriatal brain slice. We report finding that the MPTP induced non-reversible decrease in N-2 amplitude did not occur if synaptic transmission had been blocked using a low Ca2(+)-high Mg2+ artificial cerebrospinal fluid (ACSF) during MPTP application. Low Ca2(+)-high Mg2+ ACSF did not however alter the decrease in slice dopamine content caused by MPTP. These data provide initial support for the hypothesis that MPTP's ability to alter functional synaptic transmission is Ca2+ dependent whereas its releasing action on dopamine is Ca2+ independent.

Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats.

Rats were pretreated with saline or nicotine (1.5 mg/kg per day) by subcutaneously implanting each animal with an Alzet osmotic mini-pump which continuously released saline or nicotine for 1, 5 and 14 days. At the end of each pretreatment period, animals were used for (i) determining their locomotor response to acutely injected nicotine (0.2 mg/kg, s.c.) and (ii) measuring the density of L-[3H]nicotine and [3H]spiperone binding sites in the striatum. We observed no changes in nicotine-induced locomotor response, striatal L-[3H]nicotine and [3H]spiperone binding in the animals pretreated with nicotine for 1 day. In rats which were pretreated with nicotine for 5 days, there was a significant increase in the nicotine-stimulated locomotor response which was associated with an increase in the number of L-[3H]nicotine binding sites and also with an elevated dopamine (DA) level in the striatum. The number of striatal [3H]spiperone binding sites was not affected. In animals pretreated with nicotine for 14 days, the nicotine-induced locomotor response remained to be potentiated. However, this response was correlated with an elevated number of striatal [3H]spiperone binding sites, whereas the number of striatal L-[3H]nicotine binding sites and the striatal DA level were normal. These results suggest that chronic nicotine-treated rats develop locomotor hyperactivity in response to nicotine initially due to increases of both the density of nicotinic receptors and DA concentration, followed by inducing DA receptor supersensitivity in the striatum.

Prolonged inhibition of striatal dopamine receptor sites by isofloxythepin.

Using the [3H]spiperone binding technique to measure the residual drug effect of subcutaneously injected isofloxythepin (1 mg/kg, single dose) in the rat, we observed a significant blockade of [3H]spiperone-labeled, high affinity dopamine receptors (D2) in the striatum up to 4 days after drug administration. Higher doses of isofloxythepin (5 or 10 mg/kg) produced a receptor blockade and were associated with an inhibition of apomorphine-induced stereotypy which lasted more than a week. Neither dopaminergic behavior supersensitivity nor striatal D2 receptor up-regulation was observed in isofloxythepin-treated rats, even after the animals were withdrawn from the drug for an extended period of time. Isofloxythepin was shown to decrease the Bmax without altering the KD of [3H]spiperone binding (a non-competitive inhibition), and in vitro its binding was not readily dissociated even when the drug-receptor complex was washed repeatedly with large volumes of drug-free buffer. The IC50 of isofloxythepin for displacing [3H]spiperone binding was 0.8 nM. Isofloxythepin is therefore a potent dopamine receptor antagonist with prolonged pharmacological action and strong binding at D2 receptors.

Activation of group III metabotropic glutamate receptors inhibits basal and amphetamine-stimulated dopamine release in rat dorsal striatum: an in vivo microdialysis study.

Group III metabotropic glutamate (mGlu) receptors are negatively coupled to adenylate cyclase and are distributed pre-synaptically in the striatum. A behavioral study previously conducted in this laboratory shows that activation of this group of mGlu receptors attenuates acute amphetamine-stimulated motor activity. By administering a group III selective agonist or antagonist via the dialysis probe, the present study employed in vivo microdialysis to evaluate the capacity of the group III selective agents to alter extracellular levels of dopamine in the dorsal striatum of normal and amphetamine-treated rats. It was found that the group III agonist L-2-amino-4-phosphonobutyrate (L-AP4) dose-dependently (1, 10 and 100 microM) reduced basal levels of extracellular dopamine. In contrast, the group III antagonist alpha-methyl-4-phosphonophenylglycine (MPPG) dose-dependently (10, 50 and 250 microM) elevated the basal release of extracellular dopamine. This elevation was antagonized by co-perfusion of L-AP4. Perfusion of 5-microM amphetamine through the dialysis probe increased extracellular dopamine in the dorsal striatum. Co-perfusion of L-AP4 (100 microM) significantly reduced amphetamine-stimulated dopamine levels, whereas co-perfusion of L-AP4 (100 microM) and MPPG (100 microM) did not alter the capacity of amphetamine to elicit dopamine release. The data obtained from this study demonstrate the presence of a tonically active glutamatergic tone on group III mGlu receptors in the dorsal striatum to pre-synaptically regulate basal dopamine release in an inhibitory fashion. Moreover, activation of L-AP4-sensitive group III mGlu receptors can suppress the phasic release of dopamine induced by a dopamine stimulant amphetamine.

Profound astrogenesis in the striatum of adult mice following nigrostriatal dopaminergic lesion by repeated MPTP administration.

Neural progenitor cells are present in the rodent brain throughout adulthood, and can proliferate and differentiate into new neurons and/or glia to repair injury. To explore the repair processes mediated by brain progenitor cells, a selective lesion of the nigrostriatal dopaminergic pathway was induced in young adult mice by repeated administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A thymidine analog, bromodeoxyuridine (BrdU), was used as a tracer for DNA synthesis to label the dividing cells and their terminal progeny following injury. Three days after MPTP treatments (25 mg/kg, once daily for 5 days), an 8-fold increase in the number of BrdU-labeled newborn cells was observed in the dorsal striatum. A 5-fold increase was also seen in the substantia nigra (SN). Newborn cells in the striatum survived beyond 60 days after their birth whereas newborn cells in the SN survived for less than 31 days. The vast majority of newborn cells in the striatum differentiated into astroglia according to their radial morphology and co-expression with an astroglial marker, S100beta, within 10 days after birth. In contrast, most BrdU-positive cells in the SN failed to co-express S100beta. Little or none of BrdU-labeled cells in both the striatum and SN were found to co-localize with a neuronal marker, neuronal nuclear antigen, or tyrosine hydroxylase during the full course of survival days surveyed (3 to 60 days). Repeated MPTP also decreased dopamine content and uptake in the striatum, which showed a significant recovery 31 days after MPTP lesion. These results demonstrate a rapid and profound astrogenesis in the striatum of young adult mice in response to toxic dopaminergic insult. The lack of neurogenesis in the two affected brain areas indicates the relative importance of glial cell regeneration in repairing MPTP injury.

Dose-related alteration in nitric oxide synthase mRNA expression induced by amphetamine and the full D1 dopamine receptor agonist SKF-82958 in mouse striatum.

Neuronal nitric oxide synthase (nNOS) is normally expressed in one population of intrinsic interneurons of the striatum. Production of nitric oxide in the nNOS-containing neurons is sensitive to dopamine stimulation. Using quantitative in situ hybridization, the present study investigated the alteration in basal nNOS mRNA expression in striatal nNOS-containing neurons of mice treated with the psychostimulant amphetamine or a full D1 dopamine receptor agonist, SKF-82958. A single systemic injection of amphetamine induced a dose-related change in striatal nNOS mRNA expression. Whereas amphetamine at 4 mg/kg decreased basal levels of nNOS mRNA in both the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum, the drug at a higher dose (12 mg/kg) increased nNOS expression in the two regions. Similarly, an acute systemic injection of SKF-82958 decreased and increased nNOS mRNA levels in the dorsal and ventral striatum at 2 and 4 mg/kg, respectively. These data indicate that constitutive nNOS expression in nitric oxide-producing neurons of the mouse striatum is regulated by dopaminergic transmission. Altered nNOS expression may result in changes in nitric oxide synthesis and thus contribute to biological actions of dopamine stimulants.

MPTP, MPDP+ and MPP+ cause decreases in dopamine content in mouse brain slices.

MPTP causes a Parkinson's disease-like syndrome in which the dopamine content of the nigrostriatal system decreases. We have studied the relationship between physiological changes and dopamine content using a brain slice preparation developed for electrophysiological studies of corticostriate and nigrostriatal synaptic transmission. We report that MPTP, MPDP+ and MPP+ cause significant decreases in dopamine content of mouse brain slices. We also report that compounds (pargyline and GBR-12909) which block MPTP's toxicity in vivo and prevent non-reversible changes in synaptic transmission are not able to alter MPTP's ability to decrease slice dopamine contents. This indicates that the dopamine content in slices may not be causally related to the non-reversible decrease in synaptic transmission or in vivo neurotoxicity.

Assessment of left ventricular wall motion abnormalities with the use of color kinesis: a valuable visual and training aid.

Accurate interpretation of left ventricular segmental wall motion by echocardiography is an important yet difficult skill to learn. Color-coded left ventricular wall motion (color kinesis) is a tool that potentially could aid in the interpretation and provide semiquantification. We studied the usefulness of color kinesis in 42 patients with a history of congestive cardiomyopathy who underwent two-dimensional echocardiograms and a color kinesis study. The expert's reading of the two-dimensional wall motion served as a reference for comparison of color kinesis studies interpreted by the expert and a cardiovascular trainee. Correlation between two-dimensional echocardiography and the expert's and trainee's color coded wall motion scores were r = 0.83 and r = 0.67, respectively. Reproducibility between reviewers and between operators was also assessed. Interobserver variability for color-coded wall motion showed a correlation of r = 0.78. Correlation between operators was also good; r = 0.84. Color kinesis is reliable and appears promising as an adjunct in the assessment of wall motion abnormalities by echocardiography. It is both a valuable visual aid, as well as a training aid for the cardiovascular trainee.

Calcium-dependent protein kinase reactions associated with parotid gland secretory granule membranes.

Rat parotid secretory granule membranes were examined for the presence of calcium-dependent protein kinase activities and kinase substrates. Protein kinase C (C-kinase), which is stimulated by certain phospholipids, was present in the membranes, as indicated by its ability to catalyze the phosphorylation of histone. Two substrates for protein kinase C were seen in the granule membranes. The cytosolic fraction from the cell contained kinase activity, which was stimulated by phosphatidylserine and which caused the phosphorylation of two granule membrane polypeptides. In addition, when both granule membranes and cytosol were incubated together, phosphorylation of the cytosolic substrates was inhibited, indicating that the granule membrane substrates were phosphorylated preferentially. The results indicate that the granule membranes may react with cytosolic protein kinase C activity in a way which would direct an intracellular calcium and diacylglycerol signal toward the granule membrane. Since these signals occur during stimulation by various agonists, the mechanism may contribute to secretion.