The ciguatera poisoning syndrome from farm-raised salmon.
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Biomedical subjects
Publications and source records attributed to Y Hokama.
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This study is an individual case report of an imported cultured salmon which may have caused ciguatera. The individual's documented clinical symptoms, along with our immunological tests and bioassays (hemolytic, mouse toxicity and guinea-pig atrial assays) of the salmon extracts, strongly suggest that the salmon may have contained a ciguatoxin-like toxin (or toxins). The unique ability of the toxin(s) to block the sodium channel of the guinea-pig atrium, however, distinguishes it from ciguatoxin-1 isolated from moray eel liver.
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This study presents data from the cross-reactivity analysis of purified ciguatoxin (CTX), okadaic acid (OA), and the East sphere or Fragment B-C of OA with their homologous antibodies, monoclonal antibodies to ciguatoxin (MAb-CTX) and okadaic acid (MAb-OA). The test system used was the stick enzyme immunoassay. MAb-CTX gave peak titers of 1.5ng, 10ng and 50ng respectively for CTX, East sphere and OA. Competitive inhibition analysis showed that 4ng purified CTX blocked completely MAb-CTX reaction with crude CTX, OA and East sphere of OA blocked at similar concentrations (approximately 50ng). The activity with MAb-OA in the homologous system with OA and East sphere was insignificant. This may be attributable to the improper concentrations used. The cross-reactivity between MAb-CTX with OA and its Fragment B-C may cause difficulty in the test system in its application to assess toxic fish due to ciguatoxin.
The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.
Ciguatera fish poisoning is a clinical syndrome consisting of a combination of gastrointestinal and neurological symptoms occurring after eating toxin-containing tropical reef fish; it is a major cause of morbidity in Hawaii, the South Pacific, Australia, and the Caribbean. In an effort to define pathophysiological mechanisms responsible for the diarrheal component of the illness, we examined the effect of crude and fractionated toxin preparations on isolated rabbit ileal tissue in a Ussing chamber model. Both the crude toxin preparation (prepared from toxic Ctenochaetus strigosus) and 10% and 50% methanol-chloroform toxin fraction (prepared from a pool of toxic fish samples) gave a striking increase in transepithelial electrical potential difference and short-circuit current. Enterotoxic activity seemed to be mediated by calcium. When examined by light microscopy, the intestinal mucosa was not damaged by the toxin preparations used. Our data demonstrate that toxins involved in ciguatera fish poisoning directly stimulate intestinal fluid secretion without accompanying tissue damage and suggest that calcium is the "second messenger" mediating the process.
The current study investigates the effect of megestrol acetate, a synthetic progestin, on the activity of interleukin-1. Murine thymocytes were suspended in vitro and stimulated with varying concentrations of interleukin-1. [3H]Thymidine uptake was observed as an index of thymocyte proliferation. A dose-dependent increase in [3H]thymidine uptake was observed with increasing concentrations of interleukin-1. When megestrol acetate was added to the solution, a marked suppressive effect was observed. Higher doses of megestrol acetate had a greater suppressive effect on thymocyte proliferation. Additional investigation is required to further delineate the potential systemic effects of megestrol acetate.
A 42-year-old woman developed an abrupt onset of severe headache, nausea, vomiting, unstable gait and numbness around the right side of her mouth and in her right hand. Neurological examination revealed bilateral pyramidal tract signs and hypesthesia of her right palmar tip and the right side of her mouth. However, pain and temperature sensibility was preserved. Cerebrospinal fluid was clear and colorless. CT scan showed an enhancing mass in the prepontine cistern compressing the pontine base. Vertebral angiography revealed irregular narrowing of bilateral vertebral arteries (string sign) proximal to a fusiform aneurysm on the entire length of the basilar artery. MRI showed double lumina in the wall of the aneurysm. The medial lemniscus conducts the discriminatory tactile and the deep sensory impulses from the extremities. The ventral ascending tract of the trigeminal nerve conducts the discriminatory tactile sensory impulses from the face. These two tracts lie close together in the pontine tegmentum, which is also a watershed area of the paramedian branches and circumferential branches of the basilar artery. We suggest that in this case the dissecting aneurysm caused ischemia of these two tracts in the left pontine tegmentum, presenting right cheiro-oral syndrome.
This study examined the development of a highly simplified solid-phase colored latex immunobead assay for the detection of ciguatoxin and related polyethers. This procedure was compared with the stick enzyme immunoassay previously reported. Chi-square analysis of two separate experiments on 153 and 283 fish of various species gave chi 2 values of p less than 0.001 and p less than 0.005, respectively. Agreement between the two procedures with 26 fish implicated in ciguatera poisoning was 100%. A preliminary assessment in the field showed encouraging results. The procedure appears to be simple and applicable to field use. Furthermore, this procedure should be applicable to other antibody-antigen detections, especially low dalton determinations.
This article reviews the clinical applications of C-reactive protein (CRP). This acute-phase protein is a distinct and sensitive marker for inflammation and tissue injury. It is a simple, fast, and relatively inexpensive latex agglutination test. The aspects of CRP reviewed include diagnostic support, serial measurements to evaluate disease course and therapeutic response, and screening studies.
The stick enzyme immunoassay (S-EIA) using monoclonal antibody to ciguatoxin (MAb-CTX) was used to examine clinically implicated fish and to pre-screen two species of fish, Caranx sp. (ulua or jack) and Seriola dumerili (kahala or amberjack), supplied by sports fishermen. All of the clinically implicated fish from the Department of Health gave S-EIA values greater than or equal to 1.3. The Caranx sp. and Seriola dumerili considered safe (less than or equal to 1.2 value) and consumed after testing gave no false-negative results. The S-EIA procedure using MAb-CTX proved to be specific, sensitive, and simple to use in the laboratory. It also proved to be useful in screening two large carnivorous fish for ciguatoxin and related polyethers prior to consumption.
Following the death of two Atlantic dolphins in a lagoon in March of 1989, the Hawaiian fishes in the lagoon were examined as a potential source of toxin(s). This study reports the findings of the causitive toxin(s) involved, utilizing the stick enzyme immunoassay (S-EIA) and the mouse and guinea pig atrium assays. The S-EIA proved effective in screening the toxic fishes (mullet, wrasse, manini, and aholehole). Following extraction, the major toxin was found in the viscera of these fishes, as confirmed in the mouse assay. The most toxic level was shown in the viscera of the mullet (13.2 mouse units/mg of extract). The viscera of the wrasse, aholehole, and manini also showed high levels of the toxic substance. The guinea pig atrium assay showed the presence of a potent Na+ channel inhibitor, characteristic of tetrodotoxin and saxitoxin. The toxin was also demonstrated in low levels in the dolphin liver and gut content and in the sand and algae extracts from the lagoon. This is the first report of this type of toxin in Hawaii.
C-reactive protein (CRP) is an acute phase reactant that appears to have a variety of biologic effects, including stimulation of prostaglandin production by peripheral blood monocytes. Both CRP and 6-keto prostaglandin F 1-alpha (6-keto PGF1-alpha) have been noted to be elevated in the sera of patients with malignant disease, therefore the current study was undertaken to determine whether any correlation exists between serum levels of these two substances. Thirty-five samples of sera from 16 patients undergoing treatment for primary gynecologic malignancies were tested. CRP was elevated above normal in 97% of samples and 6-keto PGF1-alpha was elevated in 91% of samples. No correlation between levels of CRP and 6-keto PGF1-alpha was identified. Serial serum samples were available for 6 patients undergoing therapy; in 5 of 6 patients CRP levels reflected the clinical disease course. There was no apparent correlation between 6-keto PGF1-alpha levels and clinical progression or regression of disease.
The effect of okadaic acid (OA), a non-TPA (12-0- tetradecanoylphorbol-13-acetate)-type tumor promoter, on interleukin 1 (IL-1) synthesis in human peripheral blood monocytes in vitro was examined using immunofluorescence and the mouse thymocyte assays. Stimulation of IL-1 was shown with 0.05 microgram OA/ml (the peak response), while concentrations of greater than 1.0 micrograms OA/ml showed significant inhibition of IL-1 synthesis by monocytes in the immunofluorescence analysis. Okadaic acid added directly to mouse thymocytes showed a peak response in IL-1 synthesis at 0.01 microgram OA/ml, while significant inhibition was shown for concentrations of OA greater than 0.1 microgram OA/ml. Supernatants of monocytes exposed to OA gave maximum stimulation at 0.05 microgram OA/ml for both 24 and 48 hr exposures. Significant inhibition of IL-1 synthesis in monocytes was shown by supernatants obtained from monocytes exposed 24 hr with 1.0 microgram OA/ml. Addition of various concentrations of OA to monocyte cultures in the presence of increasing concentrations of monoclonal antibody to OA showed significant reduction of the inhibition of IL-1 synthesis by OA at the 0.10 microgram level, but more significantly at the 1.0 microgram OA/ml level. The higher levels of OA associated with inhibition of IL-1 synthesis in monocytes in this study were comparable to the concentrations used in the tumor promotion studies by others. The reversal of the inhibitory effect of OA by the monoclonal antibody to OA is of interest and should be applicable to further studies on the mechanism of OA tumor promotion.
Ciguatera poisoning reports were examined for patterns of symptomatology when different types of fishes were consumed. Consumption of surgeon fish (Ctenochaetus strigosus), amberjack (Seriola dumerili) and jack (Caranx sp.) resulted in different symptom profiles with a number of statistically significant differences in the reported frequencies of specific symptoms. The results support the contention that the large variability in symptoms associated with ciguatera poisoning is caused by several closely related but distinct toxins.
A near fatal case of ciguatera-related intoxication following consumption of smoked Decapterus macrosoma is documented. In addition to some of the hallmark symptoms of ciguatera poisoning, the patient exhibited acute respiratory distress and severe muscle spasms. Laboratory results showed large elevations in a number of blood enzymes, indicative of muscle damage. The responsible agent was extracted from corresponding fish samples and identified as palytoxin.
In order to clarify the mechanism of action of recombinant human leucocyte interferon, the effect of local injection of it to the human malignant gliomas (one oligodendroglioma, the other glioblastoma) transplanted into nude mice were evaluated. The volume of the tumors were calculated as 1/2 (short diameter [cm])2 x (long diameter[cm]). And the ratio of tumor volume (T)/original size (C) were calculated in terms of experimental day. Among the groups of control (vehicle of IFN injected), 1 million units of IFN locally injected group, 3 million units injected group, and 9 million units injected group, the effects of the treatment were statistically evaluated in terms of T/C. At the end of the experiment, each animal was injected 4 mg of BrdU intraperitoneally, and the labeling indices of the tumor tissue were measured and compared among the groups above mentioned. Local injection of IFN to the tumor was effective even at the dose of 1 million units every other day for 16 days for glioblastoma and 50 days for oligodendroglioma. The labeling index of the treated groups was significantly reduced when compared to that of control group in both tumors. And the experiment was performed to evaluate the variation of NK activity and ADCC activity of mouse spleen cells among the experimental groups. For the oligodendroglioma, NK activities were significantly increased in the 9 million units of IFN injected group when compared to those of control group. For glioblastoma, there was no definite variation of NK and ADCC activities among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
The hamsters have been known to be the least sensitive mammalian species to the acute toxicity of highly toxic polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the present study, the tissue distribution, inductive effect of liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in male Golden Syrian hamsters were examined. The highest content (about 48% of dose) of PenCDF was found in the liver 5 days after a single i.p. dose of 1.0 mg/kg. The amount ranging about 5 to 10% of dose was also distributed to mesentery, skin and muscle. In liver, the distribution of PenCDF was just parallel to that of cytochrome P-450 (P-450), marker enzymes of liver endoplasmic reticulum, suggesting that PenCDF binds to P-450. The mode of inductive effects of PenCDF in hamsters was 3-methylcholanthrene-type as reported previously in rats. However, the typical enzymes such as benzo(a)pyrene 3-hydroxylase and DT-diaphorase were induced to a relatively less extent than did in rats. In hamsters pretreated with PenCDF at a dose of 0.5 mg/kg, the potent atrophy of thymus and the 3-fold increase of liver lipid peroxide were observed, whereas the body weight gain was not suppressed at all. These results suggest that the induction of liver enzymes and the atrophy of thymus might not be the direct cause of PenCDF-induced lethality in hamsters.