What some patients can eat during migraine attacks: therapeutic and conceptual implications

Although nausea and vomiting are diagnostic migraine symptoms, most patients can take tablets by mouth and a few say they can eat some food. This study was conducted to determine the proportion who could eat or drink, what was consumable and with what effect. One-hundred-and-nine migraineurs were asked what they could eat or drink at the beginning or height of their attacks; 59 could not take any food by mouth, but 50 could eat during the headache phase of their migraine attacks. Four ate normally, 5 took smaller amounts of their normal dietary intake, and 3 took lighter meals. Dry, carbohydrate foods were consumable by the remaining 38: a few had specific cravings, most stated the precise variety which, when eaten, reduced nausea, headache, other symptoms or length of attacks. Patients should therefore be encouraged to eat what they can tolerate, with their tablets taken as early as possible after the onset of attacks. Simultaneous nausea, tolerance or even craving for specific foods occur in other conditions, particularly high altitude headaches which share other features of migraine attacks. The observations in this paper support the notion that migraine is a central neuronal metabolic disturbance.     

Deacetylation and further metabolism of the mercapturic acid of hexachloro-1,3-butadiene by rat kidney cytosol in vitro

Hexachloro-1,3-butadiene (HCBD) is more nephrotoxic to female than male rats. Metabolism of HCBD involves conjugation with glutathione followed by formation of the cysteine conjugate S-(pentachloro-1,3-butadienyl) cysteine (PCBD-CYS) and then the mercapturic acid N-acetyl-S-pentachloro-1,3-butadienyl-cysteine (PCBD-NAC). PCBD-NAC is also more nephrotoxic to female rats than male rats. The deacetylation of [¹⁴C]-PCBD-NAC to PCBD-CYS and the binding of radiolabelled metabolites to protein has been studied using renal cytosol preparations from male and female rats in vitro, since a sex-related difference in these reactions could explain the difference in nephrotoxicity found in vivo. PCBD-NAC was rapidly metabolised by renal cytosol. The rate of metabolism was similar with either male or female renal cytosol, and the major metabolite identified was PCBD-CYS. N-Acetylation of PCBD-CYS to PCBD-NAC was not detected in the presence of either male or female renal cytosol. Covalent binding of radioactivity from [¹⁴C]-PCBD-NAC to cytosolic protein could be detected after 5 min incubation, and although the extent of binding was similar for both male and female cytosol at early time periods, after 60 min incubation more binding was found in the presence of male cytosol. Covalent binding was largely prevented by aminooxyacetic acid, an inhibitor of cysteine conjugate -lyase, suggesting a role for this enzyme in the activation of HCBD. These results indicate that the sex differences in the nephrotoxicity of HCBD and PCBD-NAC in the rat are not attributable to differences in the rate of deacetylation of PCBD-NAC to give the proximate nephrotoxin PCBD-CYS.This work was supported by a fellowship from the European Science Foundation granted to I. S. P.     

Phase I study of 4′-deoxydoxorubicin (esorubicin) in children with malignant solid tumors

Summary 4 -Deoxydoxorubicin was given to 15 patients with drug-resistant pediatric malignant solid tumors with the objectives of determining the maximum tolerated dosage and dose-limiting toxicity. Maximum tolerated dosage was 36 mg/m₂ given IV once every 3 weeks. Dose limiting toxicity was myelosuppression, which was severe and prolonged. Therapeutic benefits were not observed for these patients.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced cleft palate in the mouse: evidence for alterations in palatal shelf fusion

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including the C57BL/6J, but not in certain other strains (AKR/J). The purpose of the present study was to examine various biochemical and morphological aspects of TCDD-induced changes in the developing palatal shelves. Our results indicate that when TCDD (100 micrograms/kg) was given on individual days between days 8 and 10 of gestation, a high percentage of cleft palate was observed. Receptors specific for TCDD were detected in the C57BL/6J but not AKR/J palatal shelves. The amount of TCDD receptors is highest in the palatal shelves on day 13 as compared to other embryonic tissues including the liver. Examination of cryostat sections taken from embryos during the time of palatal elevation and fusion demonstrated that TCDD does not interfere with growth, elevation, or initial contact of the palatal shelves, but does interfere with firm adhesion and/or degeneration of the medial epithelial cells. Our results suggest that TCDD exerts a direct effect on the embryonic palatal shelves which results in formation of cleft palate.     

The activation of red blood cell transketolase in groups of patients especially at risk from thiamin deficiency

Erythrocyte transketolase activation by thiamin diphosphate has been studied in elderly patients with moderate or severe chronic dementia, acute alcoholic admissions and chronic alcoholics with evidence of brain damage, mostly of the Wernicke-Korsakoff type. Significantly more patients in each group than controls showed abnormal activation of transketolase, not only by 0.3 mM thiamin diphosphate (TDP) but also in further activation by increase to 3 mM. This indicated the presence in a proportion of the alcoholic and the demented patients of an abnormal enzyme variant, similar to that previously found in vitro. The modified transketolase activation test may warn not only of marginal thiamin deficiency but also independently, of susceptibility to brain damage in patients at risk.     

Effects of complement inhibition with soluble complement receptor-1 on vascular injury and inflammation during renal allograft rejection in the rat.

Complement is both an effector of the humoral immune response and a stimulator of leukocyte activation. To examine the influence of complement on the allograft response, we inhibited complement using recombinant human soluble complement receptor-1 (sCR1; TP10), in an unsensitized model of rat renal allograft rejection. Lewis to DA renal transplant recipients were treated daily with 25 mg/kg sCR1 or saline and sacrificed on days 1 to 5 after transplant. Transplanted organs were examined histologically and immunohistochemically for leukocyte subset markers and for the third component of complement, C3, and membrane attack complex deposition. A second set of recipients was followed from day 5 to day 9 to assess graft survival. sCR1-treated recipients displayed > 90% inhibition of plasma complement activity and a marked reduction in tissue C3 and membrane attack complex deposition. Inactivation of complement reduced the vascular injury such that there was almost complete sparing of vascular damage in day 5 sCR1-treated rats. There was a significant reduction in infiltrating leukocytes by day 5 after transplant, and complement inhibition delayed the time to reach a histologically defined end point of graft survival from 5 days in controls to 9 days in the sCR1-treated group. These results imply that the vascular and cell-mediated injury arises, in part, from complement activation. The partial inhibition of these injuries by sCR1 may have functional implications for strategies to inhibit allograft rejection.     

Cat hindlimb motoneurons during locomotion. III. Functional segregation in sartorius

Cat sartorius has two distinct anatomical portions, anterior (SA-a) and medial (SA-m). SA-a acts to extend the knee and also to flex the hip. SA-m acts to flex both the knee and the hip. The objective of this study was to investigate how a "single motoneuron pool" is used to control at least three separate functions mediated by the two anatomical portions of one muscle. Discharge patterns of single motoneurons projecting to the sartorius muscle were recorded using floating microelectrodes implanted in the L5 ventral root of cats. The electromyographic activity generated by the anterior and medial portions of sartorius was recorded with chronically implanted electrodes. The muscle portion innervated by each motoneuron was determined by spike-triggered averaging of the EMGs during walking on a motorized treadmill. During normal locomotion, SA-a exhibited two bursts of EMG activity per step cycle, one during the stance phase and one during the late swing phase. In contrast, every recorded motoneuron projecting to SA-a discharged a single burst of action potentials per step cycle. Some SA-a motoneurons discharged only during the stance phase, whereas other motoneurons discharged only during the late swing phase. In all cases, the instantaneous frequencygram of the motoneuron was well fit by the rectified smoothed EMG envelope generated by SA-a during the appropriate phase of the step cycle. During normal locomotion, SA-m exhibited a single burst of EMG activity per step cycle, during the swing phase. The temporal characteristics of the EMG bursts recorded from SA-m differed from the swing-phase EMG bursts generated by SA-a.(ABSTRACT TRUNCATED AT 250 WORDS)     

Screening of Twenty-Four South African Combretum and Six Terminalia Species (Combretaceae) for Antioxidant Activities

The dried leaves of Combretum and Terminalia species (Combretaceae) were extracted with acetone, hexane, dichloromethane and methanol. Thin layer chromatography (TLC) plates were developed under saturated conditions and sprayed with 0.2% 2,2-diphenyl-1-picryl hydrazyl (DPPH) in methanol for antioxidant screening. Visualization of separated bands exhibiting antioxidant activities enabled the localization and the subsequent identification of the potential active compounds. The acetone and methanol extracts displayed the presence of antioxidant activity after spraying the chromatogram with DPPH. Hexane and dichloromethane extracts did not have any antioxidant activity. C. hereroense had the highest number of active compounds, followed by C. collinum ssp. taborense, which were 16 and 10, respectively. Acetone extracts of all tested Combretum species had 53 active bands and methanol had 55. All Terminalia species extracted with acetone and methanol had antioxidant activity. T. gazensis and T. mollis methanol extracts had 11 and 14 active compounds respectively in one of the solvent systems used. The qualitative DPPH assay on TLC was successfully used in this study to systematically assess the total antioxidant activity of the Combretum and Terminalia species extracts.     

Chromosome losses in tumorigenic revertants of EJ/ras-expressing somatic cell hybrids.

Tumorigenic transformation of SV40-immortalized human uroepithelial cells (SV-HUC) after transfection with EJ/ras was previously reported to be a rare event. To test the hypothesis that ras transformation requires loss of suppressor genes, somatic cell hybrids were generated between a rare tumorigenic transformant and an isogeneic nontumorigenic EJ/ras transfectant obtained in the same experiment. Both parental cell lines, as well as all hybrid progeny, expressed mutant p21 ras protein, but injections of three such independent hybrids into athymic nude mice at passage (P) 4 demonstrated that tumorigenicity was suppressed at 20 of 22 sites. Two tumors developed, after a relatively long 17-week latent period, as compared with a 4-week latent period for the tumorigenic parent. All three hybrids produced tumors at P8, but these showed different latent periods (3-14 weeks). Revertant hybrid tumors were high-grade carcinomas. Cell lines derived from these tumors expressed mutant p21 ras and retained at least 1 EJ/ras integration site. Karyotypic analysis of six independent hybrid tumor revertants showed that each had a unique clonal karyotype. Losses of two or more homologues of 1p, 3p, 4, 8, 10p, 11p, 13q, and 18 were identified in one or more tumorigenic revertants. Losses of all these chromosomes were previously associated with transformation of SV-HUC by EJ/ras, but were also associated with chemical transformation of SV-HUC in tumors that did not express mutant ras. Genetic losses involving most of these chromosomes have also been identified in clinical bladder cancers (i.e., 1p, 3p, 8, 11p, 13 and 18q). These data show that expression of EJ/ras does not negate or significantly alter requirements for multiple genetic losses in HUC tumorigenesis.     

Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos.

Inhalation of chrysotile asbestos fibers causes interstitial lung disease in animals and man. For examination of the anatomic localization of inhaled asbestos and its relationship to alveolar tissue responses of the lung during and after chronic exposure, male and female Fischer 344 rats were exposed to aerosolized chrysotile for 7 hours/day, 5 days/week for 3 or 12 months. A number of exposed animals were kept in filtered air for an additional 12 months. Lung tissue from randomly selected animals in each group was studied by morphometric analysis of electron micrographs. Our findings show that during exposure to asbestos fibers, macrophages and alveolar epithelial cells contain statistically significant amounts of asbestos and are associated with histologic changes indicating marked epithelial injury. Increased amounts of fibers are also localized in the lung interstitium with continued exposure to asbestos and are associated with a progressive interstitial fibrotic reaction. Following cessation of exposure, macrophages and epithelial cells are cleared of fibers and resolve toward normal proportions. However, significant clearance of fibers from the lung interstitium does not occur after cessation of exposure, and there is a continuing process of fibrogenesis. These data provide new insights related to the pathogenesis of diffuse lung disease and the role each alveolar tissue compartment plays in the early and late phases of the disease.