Keynote address: PDA/FDA joint conference

The crude methanol extract of the Kenyan shrub Leucas volkensii Gürke (Labiatae) displayed in a radiorespirometric bioassay antimycobacterial activity against Mycobacterium tuberculosis. Bioassay-guided fractionation of the crude extract led to the identification of (E)-phytol as the principal active component with a minimum inhibitory concentration (MIC) of 2 micrograms/ml, a value also observed for (3R,S,7R,11R)-phytanol, (Z)-phytol, and a commercially available 2:1 mixture of (E)- and (Z)-phytol. The derivatives (E)-phytol acetate, a mixture of the (2S,3S)- and (2R,3R)-isomers of (E)-phytol epoxide and (3R,S,7R,11R)-phytanic acid displayed lower activities with MICs of 8, 16, and > 128 micrograms/ml, respectively. Geraniol and farnesol, displayed MICs of 64 and 8 micrograms/ml, respectively. The activities of (E)-phytol, (Z)-phytol and (3R,S,7R,11R)-phytanol were found to be in the same range as ethambutol, a clinically useful drug with an MIC in the range 0.95-3.8 micrograms/ml.     

Expression of interleukin-6 in polymorphic reticulosis--immunohistochemical study of 5 cases

Peripheral T cell lymphoma encompasses lymphomas with a variety of histologic appearances and clinical patterns. Recently, it has been suggested that almost all of the histologic features described under the name of polymorphic reticulosis(PR), lethal midline granuloma, and midline malignant reticulosis can be included in those generally described for malignant lymphomas of peripheral T cell origin(PTCL). There have been few studies of pathogenesis or tissue damage mechanism in PR patients. The need for a precise mechanism for tissue damage has important therapeutic implications. Using immunohistochemical methods with polyclonal anti IL-6 antibody, the authors describe 5 cases of PR with clinically and pathologically typical PR demonstrating a high expression of IL-6. According to classification, 2 cases of grade 1 PR showed the highest expressions, and 2 cases of grade 2 PR with atypical lymphoid cells showed moderate activity, but one case progressed into frank lymphoma(grade 3) and lost IL-6 expression. This strongly implies that some cases of PR have a different mechanism of tissue damage from frank PTCL, despite the one disease spectrum. Further studies on more cases may help clarify the pathogenesis.     

Evidence that acetyl-CoA carboxylase isoforms play different biological roles in H9c2 cardiomyocyte

Twelve patients with cervical dystonia (CD) and predominant rotation were studied to determine the effects of changes in head posture on the specific patterns of cervical muscle activity. Turns analysis was used to quantify muscle activity underlying head rotation, recorded simultaneously from the agonist and antagonist muscle pairs bilaterally (sternocleidomastoid [SCM] and splenius [SPL]). Muscle activity was compared between the uncompensated dystonic posture and during the maintenance of midposition. In addition, patients were separated into two groups (geste = 6; no geste = 6) based on whether they had a clinically efficacious geste to determine the effect of geste on patterns of cervical muscle activity. Muscle activity was measured during the maintenance of midposition with and without a clinical or simulated geste. Differences in muscle activity between the groups and postures were compared using repeated measure analysis of variance (ANOVA) analyses. The four muscles tested showed a significant difference in muscle activity in the uncompensated dystonic posture as a result of the increased activity in the agonist muscle pair (SCM and SPL responsible for the dystonic posture) (EMG amplitude: F[1,11] = 18.81, p = 0.0012; EMG frequency: F[1,11] = 32.07, p = 0.0001). Maintaining the head in the midposition was associated with a significant reduction in muscle activity compared with the uncompensated dystonic posture (EMG amplitude: F[1,9] = 6.36, p < 0.033; EMG frequency: F[1,9] = 10.96, p < 0.0091). This reduction in midposition muscle activity was significantly greater in the agonist muscle pair (EMG amplitude: F[1,10] = 19.70, p = 0.0013; EMG frequency: F[1,10] = 44.67, p < 0.0001). In the patients with clinically effective geste, there was no additional reduction in muscle activity observed in the midposition when they performed their geste (EMG amplitude: F[1,9] = 4.63, p = 0.060; EMG frequency: F[1,9] = 1.22, p = 0.298). These findings suggest that CD with rotation is characterized by predominantly increased agonist muscle activation. Patients with CD retain the ability to modulate this involuntary agonist muscle activity to maintain the head in the midposition. The maintenance of the midposition does not seem to be facilitated by geste.     

Interleukin-6-associated inflammatory processes in Alzheimer's disease: new therapeutic options

The cytokine interleukin-6 is consistently detected in the brains of Alzheimer's disease patients but not in the brains of nondemented elderly persons. Until recently it was unclear whether an interleukin-6-associated inflammatory mechanism is an early or late event in the pathological cascade of Alzheimer's disease. We investigated whether interleukin-6 could be detected in plaques of Alzheimer's disease patients prior to the onset of neuritic degeneration. We found interleukin-6 mostly in plaques where neuritic pathology has not yet developed. This indicates that the appearance of interleukin-6 may precede neuritic changes and is not just a consequence of neuritic degeneration. Therefore, one may hypothesize that activation of inflammatory mechanisms may cause neuritic degeneration in plaques. A suppression of interleukin-6 synthesis could, therefore, be of therapeutic value. Upon screening a number of substances, we found that a small number of nonsteroidal antiinflammatory drugs, including tenidap, were able to inhibit interleukin-6 synthesis in cultured human astrocytoma cells. These substances may be therapeutically useful in Alzheimer's disease and should be evaluated in clinical studies.