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A role of haemopexin in transporting haem to hepatocytes for degradation has been inferred from the high affinity of haemopexin for haem. We have examined this question in primary cultures of chick-embryo and adult rat liver cells. We present here the results of four sets of experiments which indicate that haemopexin retarded haem uptake by hepatocytes in culture. (1) Haem bound to bovine serum albumin is known to repress the activity of delta-aminolaevulinate synthase in chick cultures as indicated by decreased porphyrin accumulation. When haem-albumin was added in the presence of excess purified or freshly secreted chicken haemopexin, no haem-mediated repression of porphyrin production was observed. The haem-mediated repression of porphyrin accumulation was partially prevented when human, but not chicken, albumin was added to cultures. This finding reflected the higher affinity of human albumin for haem compared with that of chicken albumin. (2) Haemopexin inhibited the ability of haem to be incorporated into cytochrome P-450 induced in the chick cultures in the presence of the iron chelator desferrioxamine. (3) The rate of association of [55Fe]haem with cultured rat hepatocytes when [55Fe]haem-haemopexin was added was one-eighth of the rate observed when [55Fe]haem-bovine serum albumin was used as the haem donor. (4) The presence of haemopexin also diminished the catabolism of haem by both rat and chick-embryo liver cell cultures. It is concluded that the uptake and subsequent metabolic effects of haem are inhibited in cultured hepatocytes by proteins such as haemopexin which have a high affinity for haem.

Cell-free preparations from liver of chick embryo treated with 3-methylcholanthrene catalyzed oxidation of uroporphyrinogen I in the presence of NADPH and 3,4,3′,4′-tetrachlorobiphenyl. Extracts of untreated embryo liver or liver from embryo treated with glutethimide, a phenobarbital-like inducer of cytochrome P450 in this system, did not catalyse the oxidation. Direct involvement of cytochrome P450 was demonstrated by inhibition of the oxidation by CO, piperonyl butoxide and specific antisera to the methylcholanthrene-induced cytochrome P450. 2,4,2′,4′-tetrachlorobiphenyl was inactive in the oxidation. These results may explain the role of induced cytochrome P450 in experimental uroporphyria. The oxidation may be useful as a simple assay for reactive O 2 species.

This paper investigates the changing social organization of the fishermen in northwest Newfoundland, especially Port au Choix. Until the mid-sixties these fishermen worked as domestic commodity producers utilizing simple inshore technologies. Subsequently, a minority adopted more capital intensive technologies based on individual property ownership and the hiring of wage-labour. Shrimp and cod dragging became the preferred form of fishing. Yet domestic commodity producers also increased in number in a context where alternative employment was scarce and state policy permitted survival. The significance of state intervention is emphasized and implications of the Kirby Task Force report are considered. The experience of the fishermen is examined in relation to theories of primary production in advanced capitalism which are found to be inadequate to cope with the complexities of change in this area due to an excessively lineal and structuralist orientation.

Drug mediated induction of cytochrome P450 was studied in cultures of hepatocytes that had never been cultured in the presence of serum. Propylisopropylacetamide induced a five-fold increase in cytochrome P450, approximating in ovo induced levels, when triiodothyronine and/or dexamethasone were included in the culture medium. Insulin was apparently not required for this induction. Cytochrome P450, free of cytochrome oxidase, could be fully recovered from cell homogenates in a 8700g supernatant, by use of a buffer containing 0.2% Emulgen.

This study investigated the effects of estrogens on the induction of cytochrome P-450 by polycyclic aromatic hydrocarbons in primary cultures of chick embryo hepatocytes. Exposure to polycyclic aromatic hydrocarbons, such as 3-methylcholanthrene led to 2- to 3-fold increases of cytochrome P-450. The amount of cytochrome P-450 induced by 3-methylcholanthrene was increased 40-50% when the synthetic estrogen, 17 alpha-ethynylestradiol, was also present. The rate of decay of cytochrome P-450 in the presence of cycloheximide as measured spectrophotometrically was similar in cells previously treated with either 3-methylcholanthrene or 3-methylcholanthrene plus 17 alpha-ethynylestradiol, suggesting that 17 alpha-ethynylestradiol did not affect the stability of the 3-methylcholanthrene-induced cytochrome P-450. In contrast, 17 alpha-ethynylestradiol did not potentiate the induction of cytochrome P-450 by phenobarbital-like inducers, such as 2-propyl-2-isopropylacetamide, as indicated by a lack of increase in both the content of cytochrome P-450 and benzphetamine demethylase activity. The naturally occurring estrogens, 17 beta-estradiol and estrone, and the synthetic estrogen, diethylstilbestrol, did not affect cytochrome P-450 induction by 3-methylcholanthrene, suggesting that the effect of 17 alpha-ethynylestradiol was not mediated via the estrogen receptor. We investigated whether the amount of cytochrome P-450 increased in the presence of 17 alpha-ethynylestradiol was the same or different from that induced by 3-methylcholanthrene. Treatment with 17 alpha-ethynylestradiol alone resulted in a small increase in ethoxyresorufin deethylase activity. The enzymatic activities of 7-ethoxyresorufin and aryl hydrocarbon hydroxylase, when expressed per cytochrome P-450 content, were identical in microsomes from cells treated with either 3-methylcholanthrene or the combination of 3-methylcholanthrene and 17 alpha-ethynylestradiol. The data suggest that the additional cytochrome P-450 induced by the combination of 17 alpha-ethynylestradiol and 3-methylcholanthrene was the same isozyme as that induced by 3-methylcholanthrene alone.

SUMMARY This article presents a critical review of recent organizational change in the GDR's rural society, including the formation of specialized production co-operatives and a more intensive vertical integration in the agro-industrial complex. This more centralised, bureaucratic structure is explained in relation to the historical development of the mode of production, particular immediate problems and the ideological orientation of the leadership. In opposition to the harmonious, functionalist interpretation of GDR authors, it is suggested here that most contemporary developments serve to expand the bureaucracy, are likely to increase alienation and thus to deepen contradictions in the rural sector, despite certain real material achievements which are outlined. Reume Cette etude presente un examen critique du changement recent des organisations dans la societe rurale de la RDA, y compris la formation des cooperatives specialisees de production et l'integration verticale plus intense du complexe agro-industriel. On explique cette structure plus centralisee et bureaucratique en se rapportant au developpement historique du mode de production agricole, a des problemes particuliers et immediats et a l'orientation ideologique des chefs. Contrairement a L'interpretation harmonieuse et fonctionaliste des auteurs de la RDA, on soutient ici que la plupart des developpements contemporains servent a amplifier la bureaucratic, a augmenter probablement l'alienation et, done, a renforcer les contradictions du secteur rural, malgre certains vrais accomplissements materiels qu'on decrit. Zusammenfassung Dieser Artikel gibt einen kritischen Uberblick uber die jungsten organisatorischen Veranderungen in der landlichen Gesellschaft der DDR. Eingeschlossen in diese Betrachtung sind die Bildung spezialisierter Produktionsgenossenschaften und die verstarkte vertikale Integration im agro-industriellen Komplex. Diese verstarkt zentralistische, burokratische Struktur wird aus der historischen Entwicklung des Systems landwirtschaftlicher Produktion, aus besonderen augenblick-lichen Schwierigkeiten und aus der ideologischen Ausrichtung der Fuhrung erklart. Im Gegensatz zur harmonisch funktionellen Interpretation ostdeutscher Autoren vertritt dieser Beitrag die Auffassung, die meisten zeitgenossischen Entwicklungen fuhrten dazu, das sich die Burokratie ausdehnt, die Entfremdung sich sehr wahrscheinlich vergrosert und die Widerspruche im landlichen Raum sich damit verstarken. Dies trotz einiger materieller Errungenschaften, die ebenfalls umrissen werden.

Rats chronically exposed to hypobaric conditions develop pulmonary hypertension, right heart failure, hemoglobinemia, and in preliminary studies were recently found to have increased hepatic cytochrome P-450 content and activity of heme oxygenase, the rate-limiting enzyme for heme breakdown. To further delineate effects of chronic hypoxic, hypobaric exposure, on hepatic physiology and biochemistry, we have studied heme and drug metabolism in male Sprague-Dawley rats exposed to hypoxic conditions for 4-5 wk. Hypoxia, produced by exposure of rats to room air under hypobaric conditions (approximately 380 Torr), caused marked polycythemia [hematocrit (Hct) 70% vs. control Hct 43%], plasma hemoglobinemia, depletion of plasma haptoglobin, and decreased hemopexin concentrations. It also led to significant (20-30%) increases in concentrations of total hepatic heme and microsomal cytochrome P-450 and increased activities of heme oxygenase. In contrast, activity of 5-aminolevulinate synthase, the rate-limiting enzyme of hepatic heme synthesis, was significantly decreased in hypoxic rats and was not as inducible as in control normoxic rats. Hypoxia did not alter the rest of the heme synthetic pathway, as shown by a normal rate of conversion of 5-aminolevulinate to heme. Hypoxic exposure had no effect on the concentration of hepatic cytochrome-b5 but decreased activity of NADPH-cytochrome c reductase. Rates of metabolism of aminopyrine, benzphetamine, ethoxyresorufin, and warfarin were similar in hepatic microsomes obtained from hypoxic and normoxic rats. Thus the oxygen-requiring processes of hepatic heme and drug metabolism were well maintained despite chronic profound hypoxia sufficient to cause cardiopulmonary complications.

DNA damage by chromate in chick embryo hepatocytes has been correlated with the effect of chromate on inducible cell functions. Treatment of chick embryo hepatocytes with chromium(VI) in the form of sodium chromate resulted in the rapid uptake of chromate and the induction of DNA lesions in a time- and concentration-dependent manner. DNA interstrand cross-links, strand breaks and DNA-protein crosslinks, as measured by the alkaline elution technique, were observed after treatment of the hepatocytes with chromate concentrations (2.5- 0 microM) which did not affect cell viability. The effect of chromate on inducible cell functions was measured by assaying propylisopropylacetamide-induced accumulation of porphyrin and glucuronidation of phenol red by intact cells. Chromate inhibited propylisopropylacetamide-induction of porphyrin accumulation and phenol red glucuronidation in a time- and concentration-dependent manner which paralleled DNA damage. DNA damage was removed and inducibility of porphyrin accumulation by propylisopropylacetamide plus deferoxamine methanesulfonate was restored 21 h following a 2 h pretreatment with chromate. Chromium(III) in the form of chromic nitrate at concentrations up to 25 times those used with chromate had no effect on DNA damage or the induction of porphyrin accumulation and phenol red glucuronidation by propylisopropylacetamide in the cultured chick hepatocytes.

Limited-entry schemes have recently been widely touted as solutions to economic and biological problems in coastal fisheries. Here the experience of licensing in the shrimp and cod dragging fisheries of northwest Newfoundland is assessed in relation to the theoretical advantages claimed for it. After reviewing the development of the region's fisheries prior to limited entry, it is argued that the economic objectives of licensing were partially achieved but that the social consequences, principally the creation of state- supported social divisions among fishermen and maldistribution of incomes, suggest limited-entry licensing is a flawed management strategy in isolated, fishery-dependent regions.

Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.

Addition of oxidizable substrates to aerobic suspensions of Hemophilus parainfluenzae containing no endogenous substrate results in rapid reduction of b and c type cytochromes to the aerobic steady state. The extent of reduction depends upon the relative activities of the dehydrogenases and oxidases involved. Addition of oxygen to anaerobic cells containing substrate rapidly oxidizes the cytochromes to the aerobic steady state. The rapid kinetics observed on mixing with oxygen show no evidence that the initial rate of oxidation of part of the b or c type cytochromes is higher, even within bacteria with a large stoichiometric imbalance of these cytochrome types. Cytochrome a2 reacts rapidly enough with oxygen to be considered a terminal oxidase, and indirect evidence indicates that cytochrome o reacts as rapidly with oxygen as does the mammalian oxidase (pseudofirst order rate constant around 80 sec-1 at room temperature).

The composition of the membrane-bound electron transport system of Haemophilus parainfluenzae underwent modification in response to the terminal electron acceptor in the growth medium. H. parainfluenzae was able to grow with O 2 , nitrate, fumarate, pyruvate, and substrate amounts of nicotinamide adenine dinucleotide (NAD) as electron acceptors. When O 2 served as the electron acceptor and its concentration was lowered below 20 μ m , the bacteria formed more cytochromes b, c, a 1 , a 2 , and o than were present in the cells grown at 150 to 200 μ m O 2 . Nitrate and nitrite reductase activities also appeared during growth at the low O 2 concentrations in the absence of added nitrate. Cytochrome levels in cells grown anaerobically with fumarate, pyruvate, or NAD as terminal acceptors were similar to those formed in cells grown at low O 2 concentrations. Cells grown with nitrate had higher levels of cytochromes c, b , and o , and of nitrate and nitrite reductases, than did cells grown with the other acceptors. The formation of cytochrome oxidase a 2 was repressed by the presence of nitrate in the growth medium. The critical O 2 concentration (the O 2 concentration at which the rate of O 2 uptake becomes demonstrably dependent on the O 2 concentration) was about 100 μ m in cells grown with nitrate and about 15 μ m in cells grown with the other acceptors. A mutant of H. parainfluenzae was found to make about 10% as much cytochrome c as the wild type, and its formation of cytochrome a 2 was not repressed by nitrate. The critical O 2 concentration of the mutant was high when it was grown with nitrate, suggesting that the high levels of cytochrome c and the absence of cytochrome a 2 from the wild type are not responsible for the high critical O 2 concentration. The modifications of the respiratory system induced by changing the terminal electron acceptor were inhibited by the presence of chloramphenicol, which suggests that protein synthesis is involved.

A l'aide d'une technique immunologique, on compare les 2 formes de cytochrome P-450 induits dans des cultures d'hepatocytes de poulet, induction provoquee soit par l'association de 3-methylcholanthrene et de 17α-ethynylœstradiol soit par le 3-methylcholanthrene seul. Des anticorps de lapin inhibent l'activite de l'enzyme ethoxyresorufin-O-deethylase

Kinetic analysis of hepatic heme turnover, for 49h after labelling with 14 C-δ-aminolevulinate (ALA), revealed the existence of two heme pools. A single injection of allylisopropylacetamide, 4h after 14 C-ALA, led to production of “green pigments” and increased heme turnover. This increased turnover was due to an increase in the size of the more rapidly turning-over pool, not to an increase in the rate constants for turnover from either pool. Green pigments also underwent rapid biphasic turnover.

We have studied effects of single doses of 2-allyl-2-isopropylacetamide and ferric citrate on hepatic haem turnover in rats. Haem was pre-labelled by intraperitoneal administration of 5-amino-[4-14C]laevulinate 4h before other treatments. Computer-assisted analysis of the haem decay curve showed that at least two exponential components were involved implying two haem pools. In control rats the size of the rapidly-turning-over pool was 38% of the total. Treatment with 2-allyl-2-isopropylacetamide alone resulted in a 2.3-fold increase in the fractional size of this pool. Treatment with ferric citrate alone increased the size of this pool 1.8-fold; treatment with both agents together had no measurable effect beyond that produced by 2-allyl-2-isopropylacetamide. The apparent rate constant for disappearance of labelled haem from the first pool was not affected by treatment with 2-allyl-2-isopropylacetamide or ferric citrate, indicating that these treatments affect hepatic haem turnover primarily by altering the distribution of haem synthesized in the liver. The increased haem degradation after treatment with 2-allyl-2-isopropylacetamide alone was associated with the accumulation of ‘green pigments’ in the liver. These pigments were detectable 1.5h after drug treatment; their total amount increased steadily for 28h and then declined. Despite this increase in amount, radioactivity of the ‘green pigment’ fraction fell rapidly in a biphasic fashion. Some of the radioactivity that initially was found in the ‘green pigment’ fraction was later found in an aqueous fraction, not extractable by acidic ethyl acetate. Rats given ferric citrate together with 2-allyl-2-isopropylacetamide accumulated less ‘green pigments’.

Cytochromes of the a-, b-, c- and d-type become reduced when intact cells of Hemophilus parainfluenzae have become anaerobic following respiration with substrates such as formate or succinate, as shown previously (J. Biol. Chem. (1970) 254, 5096–5100). In the presence of formate after depletion of O2, there is an unusual two-step time course of reduction of the membrane-bound cytochrome c. The proportion of the cytochrome c which is reduced during the second stage is oxidizable by either nitrate or H2O2 and is reduced again when the nitrate or H2O2 have been depleted. We conclude that the observed two-stage reduction of cytochrome c results from the presence of an oxidant, probably H2O2, produced by reaction of formate dehydrogenase with O2. This was shown by the effects of cyanide, catalase and O2. In addition, no evidence for the production of the oxidant is seen when succinate is the substrate oxidized. Although measurements of absorption spectra indicated only one species of cytochrome c, kinetic evidence is presented for some separation of the cytochrome c into more than one electron transport pathway.

Iron-loaded male C57BL/6 mice allowed free access to an aqueous solution of 5-aminolaevulinic acid (ALA) (2 mg/ml) as their only drink, develop severe uroporphyria within 9 days of a single intraperitoneal dose of 20-methylcholanthrene (MC) (125 mg/kg). At 21 days, uroporphyrinogen decarboxylase (EC 4.1.1.37) activities are less than 10% of control activities. The porphyria is not dependent on pretreatment with iron and persists for at least 21 days after withdrawal of ALA. The same intraperitoneal dose of MC does not produce porphyria within 21 days when given without ALA. Continuous administration of ALA markedly accelerates the onset of porphyria in iron-loaded male C57BL/6 mice after a single intraperitoneal dose of hexachlorobenzene (200 mg/kg); mice given phenobarbitone and ALA do not become porphyric. MC with ALA does not produce porphyria in iron-loaded male DBA/2 mice. At least two separate events are needed to produce uroporphyria in mammals: induction of a specific form of cytochrome P-450 and stimulation of the formation of intermediates of haem biosynthesis in the liver. These results show that severe, persistent porphyria can be produced in mammals by compounds other than polyhalogenated aromatic hydrocarbons and suggest that a similar mechanism underlies the porphyrogenic action of halogenated and non-halogenated compounds.

Uroporphyrin (URO) accumulation caused by 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and 3,4,3′,4′-tetrachlorobiphenyl (TCB) in cultured chick embryo hepatocytes was found to depend on the concentration of the added polyhalogenated aromatic compound, and on either the addition of 5-aminolevulinic acid or the induction of 5-aminolevulinic acid synthase. TCDD alone did not cause more than a slight increase in uroporphyrin, whereas TCB alone caused considerable uroporphyrin accumulation associated with increased 5-aminolevulinic acid synthase activity. However, in the presence of exogenous 5-aminolevulinic acid, TCDD was more potent than TCB in causing uroporphyrin accumulation. The concentrations of TCDD or TCB which maximally induced ethoxyresorufin deethylase activity, an indicator of induced cytochrome P450 activity, were lower than those required for maximal uroporphyrin accumulation. Furthermore, ethoxyresorufin deethylase activity was found to decline at concentrations of TCDD or TCB which caused maximum uroporphyrin accumulation. Pretreatment with 3-methylcholanthrene enhanced uroporphyrin accumulation, whereas addition of inhibitors of cytochrome P450 decreased uroporphyrin accumulation. Uroporphyrin accumulation occurred without a decrease in uroporphyrinogen decarboxylase activity, and was unrelated to the degree of conversion of the polyhalogenated aromatic compounds to water-soluble metabolites. Our results indicate that URO accumulation caused by TCDD and TCB requires two separate actions; (1) induction of cytochrome P450 which occurs at low concentrations of the halogenated chemicals, and (2) increased uroporphyrinogen oxidation which is catalyzed by the induced cytochrome P450 and which occurs at higher concentrations of the halogenated chemicals.

The chlorinated hydrocarbons, lindane (gamma-hexachlorocyclohexane), polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin, induce chick embryo liver cells in culture to rapidly accumulate uroporphyrin III. This is in marked contrast to the delayed effect in animals. The induction is dependent on protein synthesis (cycloheximide inhibited), endogenous iron (chelators inhibited) and perhaps cytochrome P-450 (SKF-525A inhibited). Evidence was obtained for an unstable intermediate that is generated in the liver from chlorinated hydrocarbons which inhibits uroporphyrinogen decarboxylase thus causing uroporphyrin to accumulate. The data suggest that the intermediate may be a hydroxylated derivative of the chlorinated hydrocarbon.

1. Treatment of rats with small doses of CoCl2 decreases liver 5-aminolaevulinate synthase (EC 2.3.1.37) activity and impairs incorporation of 5-amino[14C]laevulinate into liver haem. Salts of other metals (cadmium, nickel, manganese and zinc) are all relatively inactive. 2. The dose-response curves obtained for both these effects closely mirror the accumulation in the liver of a compound that is labelled by 5-amino[14C]laevulinate and is unextractable by acetone/HCl. 3. Incorporation of 5-amino[14C]laevulinate into unextractable compound is also obtained in vitro by incubating liver homogenates with label in the presence of cobalt:isotope-dilution experiments show that the radioactivity passes through pools of porphobilinogen and protoporphyrin, but not of haem. 4. The unextractable compound is not covalently bound to protein and possesses the same extraction and spectral properties as authentic cobalt protoporphyrin. 5. It is concluded (a) that cobalt protoporphyrin is readily formed not only in vitro, but also in vivo, and (b) that its formation accounts for the impaired incorporation of 5-aminolaevulinate into haem and may also be responsible for the action of cobalt on 5-aminolaevulinate synthase.

Cytochrome P450 and conjugation of phenol red are inducible in cultures of chick embryo hepatocytes. Cobaltous and manganous ions cause decreases in P450, which is partially restored in the intact cells by hemin.

Protoheme is essential for the growth of some strains of Bacteroides melaninogenicus . At low concentrations in the growth medium, protoheme determines the doubling time, total cell yield, and amount of cytochrome per bacterium. At high protoheme concentrations, the doubling time, total cell yield, and amount of enzymatically reducible cytochrome appear to remain nearly constant, and protoheme is accumulated by the cell. The accumulated protoheme can support the growth of the bacterium for at least eight generations in a protoheme-free medium. When growth and cytochrome content are proportional during growth at low protoheme concentrations, the bacteria incorporate 10 to 20% of the total available protoheme into a membrane-bound respiratory system. This respiratory system includes cytochrome c , a carbon monoxide-binding pigment, and possibly flavoproteins. The pigments can be reversibly reduced by reduced nicotinamide adenine dinucleotide or endogenous metabolism and can be oxidized anaerobically by fumarate or by shaking in air. Electron transport is inhibited by 2- n -nonyl-4-hydroxy-quinoline- N -oxide.

Publisher Summary This chapter emphasizes on an aspect of the electron-transport system in bacteria and discusses some microbial electron-transport systems for which there are sufficient data for obtaining an insight into the functioning of these systems. Some bacteria can form a membrane-bound electron transport system that is considerably more complex than the system found in the mitochondria of eukaryotic cells. These systems are more complex, as they contain many membrane-bound dehydrogenases, which are the donors of electrons to the respiratory system and the many reductases by which electrons reduce oxygen and alternative terminal electron acceptors. The multiple primary dehydrogenases and oxidases are linked by pathways, which overlap and interconnect to varying degrees. These interactions result in “branching” in the electron-transport systems. Electrons can enter the system through numerous dehydrogenases and leave by way of various oxidases. At the risk of being teleological, it appears that bacteria gain evolutionary efficiency in having the capacity to synthesize branched electrontransport systems. For example, Haemophilus parainjluenzae produces a more extensive and complex electron-transport system as the oxygen tension in the growth medium is lowered. The chapter also discusses the methodology of the electron-transport system such as spectrophotometry and oxygen electrodes.

Seizures may occur in acute intermittent porphyria or other hepatic porphyrias. Management is difficult, because barbiturates and hydantoins exacerbate the porphyric state. We studied one patient with major motor seizures and acute intermittent porphyria. The seizure disorder was exacerbated by phenytoin and did not respond to a high-carbohydrate diet or to intravenous hematin. Clonazepam was ineffective in treating the seizures and, in high doses, seemed to exacerbate the porphyria. Both clonazepam and valproate were porphyrinogenic in experimental test systems. Because both drugs may exacerbate the acute hepatic porphyrias, bromide remains the drug of choice to treat these seizures.

A central problem for students of capitalist society is to analyse the social consequences of crisis. What happens when the ruling class is weakened or experiences some threat to its hegemony? One development, but by no means an inevitable one, is the emergence of fascist politics within the context of an ongoing capitalism. Fascists are typically newcomers to power and rarely have their origins in the old ruling strata. Relations with old political and economic leaders are often tense, even hostile. Yet, lacking a revolutionary policy, fascist leaders come to depend on old sources of power and actually prop up capitalism during a period of weakness. In this respect, fascism has had very similar consequences to social democracy and the rise of the welfare