Search PubMed⌕ Search

Biomedical subjects

J A Cook

Publications and source records attributed to J A Cook.

At least 307 records · Page 17Linked to original sources
PubMed1981

Glucan-enhanced immunogenicity of killed erythrocyte stages of Plasmodium berghei.

Intravenous injections of glucan simultaneously with Formalin-killed erythrocytic stages of Plasmodium berghei elicited a greater degree of resistance in mice against subsequent infection with viable parasites than injections of killed erythrocytic stages alone. In two experiments with P. berghei strain NK 65, 100% of mice immunized with the glucan-dead parasite preparation survived challenge, whereas only 28.6% of mice receiving dead parasites alone survived. In the third experiment, using P. berghei strain NYU-2, the same proportion of mice survived after immunization with glucan and dead parasites as with dead parasites alone (i.e., 10 of 11 in each group), but mice immunized with the glucan-dead parasite preparation experienced parasitemias of significantly less intensity and shorter duration than mice which received only dead parasites before infection. Inoculation of glucan alone or with normal erythrocytes conferred no protection against challenge.

Adjuvants, Immunologic↗
PubMed1981

Immunization against Leishmania donovani: glucan as an adjuvant with killed promastigotes.

Mice were immunized by a series of intravenous injections of formalin-killed Leishmania donovani promastigotes alone and combined with glucan, a beta 1,3 polyglucose derivative of baker's yeast. In three separate experiments animals were challenged with viable parasites on day 21, 40 or 80 after immunization. Mice which received dead parasites and glucan exhibited resistance against challenge up to 80 days after immunization. Animals which had been injected with glucan alone exhibited a lesser degree of resistance but injections of killed promastigotes alone conferred no measurable resistance against infection.

Adjuvants, Immunologic↗
PubMed1981

Essential fatty acid deficient rats: a new model for evaluating arachidonate metabolism in shock.

Essential fatty acid deficient (EFAD) rats are significantly more resistant to the lethal effects of S. enteritidis endotoxin (20 mg/kg, IV) than normal control rats. Compared to endotoxin-treated normal rats, EFAD rats also manifested less severe alterations of hepatic and lysosomal integrity and became less hypoglycemic. Administration of the ethyl ester of the essential fatty acid, arachidonic acid (100 mp, IP) two days prior to challenge with S. enteritidis endotoxin (20 mg/kg) in EFAD rats restored their sensitivity to endotoxin, as denoted by a 100% mortality compared to a 24% mortality (P less than 0.01) in EFAD rats. Treatment of EFAD rats with the fatty acid docosahexaenoic acid, a non-prostaglandin and thromboxane precursor, (100 mg, IP) produced significantly less (less than 0.01) mortality than ethyl-arachidonate-treated groups (ie, 40% vs 100%). The arachidonate metabolite, thromboxane B2 (TxB2), increased from nondetectable plasma levels (less than 200 pg/ml) to 2285 +/- 449 pg/ml (N = 10) at 30 min and remained elevated for 180 minutes after endotoxin administration in nondeficient rats. However, plasma TxB2 was not detectable in endotoxin-treated EFAD rats and was only slightly elevated in groups supplemented with docosahexaenoic acid (273 +/- 104 pg/ml, N = 6) after 30 minutes. In ethyl arachidonate (100 mg, IP) supplemented EFAD rats, plasma TxB2 rose to 873 +/- 204 pg/ml (N = 8), 30 min after endotoxin. Pretreatment of the ethyl-arachidonate-supplemented EFAD group with a specific thromboxane synthetase inhibitor, 7-(1-imidazolyl)-heptanoic acid (30 mg/kg, IV), significantly reduced mortality 100% to 50% (P less than 0.05) from endotoxic shock. These observations suggest a deleterious role for arachidonic acid and its conversion to TxA2 in the pathogenesis of endotoxic shock.

Acid Phosphatase↗
PubMed1981

Protective effects of aspirin in endotoxic shock.

Endotoxic shock is associated with increased metabolism of arachidonic acid to thromboxanes (TX) and prostaglandins (PG). This study assessed the effects of varied doses of aspirin, an inhibitor of arachidonic acid metabolism, on Salmonella enteriditis endotoxin (20 mg/kg)-induced mortality, plasma levels of arachidonate metabolites and other pathophysiological sequelae in Long-Evans rats. Aspirin, in doses of 3.75, 15 an 30 mg/kg, given 30 min before endotoxin significantly (P less than .01) improved 24-hr survival from 11% to 60 to 70%, but 100 mg/kg afforded no protection. Pretreatment with aspirin (15 or 100 mg/kg) 30 min before endotoxin significantly (P less than .001) decreased the endotoxin-induced elevations in plasma levels of immunoreactive (i) TXB2, a stable metabolite of TXA2, i6-keto PGF1 alpha, a stable metabolite of PGI2 and significantly (P less than .05) inhibited thrombin-induced in vitro platelet iTXB2 synthesis. Endotoxin-induced hypoglycemia and elevations in serum acid phosphatase and beta-glucuronidase activities, lysosomal enzymes, were all significantly (P less than .01) attenuated by pretreatment with aspirin (15 mg/kg) 30 min before endotoxin. Aspirin (15 or 100 mg/kg) given 24 h before challenge with endotoxin significantly improved 24-hr survival to 42 (P less than .01) and 44% (P less than .005), respectively. Although 24 hr pretreatment with aspirin (15 or 100 mg/kg) significantly (P less than .001) reduced endotoxin-induced elevations in iTXB2, only the 100 mg/kg dose significantly lowered plasma levels of i6-keto PGF1 alpha. These observations are consistent with the notion that the beneficial effects of aspirin seen in experimental endotoxic shock may be mediated, in part, via reduction of platelet TXA2 synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Implications for thromboxane A2 in the pathogenesis of endotoxic shock.

During endotoxemia there is increased synthesis of arachidonic-acid-derived metabolites. We investigated the potential deleterious role of the proaggregatory vasoconstrictor, thromboxane A2, an arachidonic acid metabolite, in the endotoxic shocked rat. Plasma levels of thromboxane B2, the stable metabolite of thromboxane A2, 6-keto-PGF1 alpha, the stable metabolite of PGI2, and PGE were measured via radioimmunoassay. We also investigated the therapeutic efficacy of the fatty acid cyclo-oxygenase imidazole and 7(1-imidazolyl)-heptanoic acid (7-IHA), in endotoxic shocked rats. Thirty minutes after intravenous (IV) administration of Salmonella enteritidis endotoxin (20 mg/kg), plasma immunoreactive thromboxane B2 (TxB2) was increased from nondetectable levels (less than 200 pg/ml) in normal nonshocked rats to 2207 +/- 282 pg/ml (N = 16). The 6-keto-PGF1 alpha level was increased from nondetectable levels to 840 +/- 59 pg/ml (N = 8), and prostaglandin E rose from 146 +/- 33 to 2160 +/- 606 pg/ml (N = 5). Ibuprofen (3.75 mg/kg) or indomethacin (10 mg/kg) administered IV 30 min prior to endotoxin (20 mg/kg) improved the survival rate to 81% (N = 15, P less than 0.001) and 78% (N = 17, P less than 0.001), respectively, compared to the 24-hr survival of 8% (N = 26) in the vehicle-treated rats. Ibuprofen also inhibited the endotoxin-induced elevation of TxB2, 6-keto-PGF1 alpha, and fibrinogen/fibrin degradation products. Imidazole (30 mg/kg) or 7-IHA (30 mg/kg), IV, 30 min prior to endotoxin improved survival 65% (N = 11) and 81% (N = 15), respectively. These drugs also inhibited endotoxin-induced elevations in TxB2 and fibrinogen/fibrin degradation products, but did not inhibit endotoxin-induced elevations in plasma PGE. These results are consistent with the suggestion that TxA2 plays a role in the pathogenesis of endotoxic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Schistosoma mansoni control in Cul de Sac Valley, Saint Lucia. II. Chemotherapy as a supplement to a focal mollusciciding programme.

After an intensive area-wide mollusciciding campaign, over four and a half years, transmission of Schistosoma mansoni was reduced. A cheaper scheme suitable for the follow-up or consolidation stage of control was evaluated and two selective population chemotherapy campaigns using hycanthone (2 mg/kg b.w.) and oxamniquine (15 mg/kg b.w.) were mounted. Prevalence dropped to 6% and 3% in areas with previously high and low levels of transmission respectively. Calculations suggested that these figures were falsely low and that perhaps 20% of the population were still excreting S. mansoni ova in small numbers. The unco-operative groups in the population are probably more important in maintaining a reservoir of infection in the community than persons with light infections undetected by the sedimentation concentration stool examination technique used. The benefit of more sensitive but more costly examination techniques is not clear since the importance of very light infections in transmission is uncertain. Case detection absorbs an increasing proportion of the total cost of chemotherapy programmes with fewer cases being found amongst the same number screened. Using hycanthone (649 treated) the cost per person protected was $0.74 and using oxamniquine (264 treated) $0.94. The need to develop low cost consolidation or follow-up procedures for preventing a resurgence of transmission after successful control, when the infection is no longer of public health importance, is stressed.

Feces↗
PubMed1980

Elevated thromboxane levels in the rat during endotoxic shock: protective effects of imidazole, 13-azaprostanoic acid, or essential fatty acid deficiency.

The potential deleterious role of the proaggregatory vasoconstrictor, thromboxane A(2), in endotoxic shock was investigated in rats. Plasma thromboxane A(2) was determined by radioimmunoassay of its stable metabolite thromboxane B(2). After intravenous administration of Salmonella enteritidis endotoxin (20 mg/kg), plasma thromboxane B(2) levels increased from nondetectable levels (<375 pg/ml) in normal control rats to 2,054+/-524 pg/ml (n = 8), within 30 min to 2,071+/-429 at 60 min, and decreased to 1,119+/-319 pg/ml, at 120 min. Plasma levels of prostaglandin E also increased from 146+/-33 pg/ml in normal controls (n = 5) to 2,161+/-606 pg/ml 30 min after endotoxin (n = 5). In contrast to shocked controls, rats pretreated with imidazole, a thromboxane synthetase inhibitor, or essential fatty acid-deficient rats, which are deficient in arachidonate and its metabolites, did not exhibit significant elevations in plasma levels of thromboxane B(2). Imidazole did not however inhibit endotoxin-induced elevations in plasma prostaglandin E. Essential fatty acid deficiency significantly reduced mortality to lethal endotoxic shock. This refractoriness could be duplicated in normal rats pretreated with the fatty acid cyclo-oxygenase inhibitor, indomethacin (10 mg/kg), intravenously 30 min before endotoxin injection. Imidazole (30 mg/kg) administered intraperitoneally 1 h before or intravenously 30 min before endotoxin, also significantly (P < 0.01) reduced mortality from lethal endotoxin shock to 40% compared to a control mortality of 95% at 24 h. Likewise pretreatment with 13-azaprostanoic acid (30 mg/kg), a thromboxane antagonist, reduced mortality from endotoxic shock at 24 h from 100% in control rats to only 50% (P < 0.01). The results suggest that endotoxin induces increased synthesis of thromboxane A(2) that may contribute to the pathogenesis of endotoxic shock.

Animals↗
PubMed1980

Enhanced sensitivity to endotoxin induced by the RE stimulant, glucan.

Pretreatment of rats with the RES stimulant, glucan, markedly increases their sensitivity to endotoxic shock. Intravenous administration of S. enteritidis endotoxin (10 micrograms/100 gm B.W.) produced a more severe shock in glucan-pretreated rats than IV injection of 1 mg/100 gm B.W. of endotoxin in normal rats. Endotoxic shock in glucan-sensitized rats was associated with a precipitous increase in serum activity of lysosomal enzymes and a more severe hypoglycemic response. The shocked glucan-pretreated rats died before marked increases in plasma hepatocyte enzyme activity were apparent. Assessment of RE-phagocytic function with the 131I RE test-lipid emulsion revealed a rapid clearance and hepatic uptake of the emulsion in nonshocked glucan-control animals. This hyperphagocytic function, however, was abolished at two hours after injection of endotoxin. Hepatic ultrastructure in shocked glucan and normal rats revealed extensive sinusoidal changes. Hepatocytes, with the exception of a depletion of glycogen granules, were comparatively intact in the shocked-glucan group as opposed to the shocked control group. Pretreatment with methylprednisolone (60 mg/kg) protected the glucan-treated rats from endotoxin and was relatively more effective in diminishing the hypoglycemic response than preventing a loss of lysosomal integrity. Thus, despite the absence of overt ultrastructural changes in hepatocytes, altered glucoregulation appears to be a significant factor in the enhanced sensitivity of glucan-pretreated rats to endotoxin.

Animals↗
PubMed1980

Ibuprofen improves survival from endotoxic shock in the rat.

During endotoxemia, there is a significant increase in arachidonic acid-derived metabolites. To test the hypothesis that one or more of these metabolites play a significant role in the pathogenesis of endotoxic shock we investigated the therapeutic efficacy of varying doses of ibuprofen, a cyclooxygenase inhibitor, on the pathophysiologic sequelae of endotoxic shock in the Long-Evans rat, induced by S. enteritidis endotoxin (20 mg/kg). Pretreatment with ibuprofen (1-3.75 mg/kg) produced an optimal survival rate of 80% compared to only 11% in the vehicle-treated group. Doses of 0.1, 0.5 and 30 mg/kg of ibuprofen also significantly (P < .05) improved survival over nontreated shocked controls. Plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha(PGF1 alpha) levels rose from < 200 pg/ml to 2207 +/- 282 (N = 16) and 840 +/- 59 (N = 8), respectively, within 30 min after injection. The rise in plasma thromboxane B2 and 6-keto-PGF1 alpha levels was reduced with ibuprofen (3.75 and 30 mg/kg) to < 200 pg/ml. Ibuprofen (3.75 and 30 mg/kg) reduced thrombin-induced in vitro platelet thromboxane B2 synthesis by 95 and 99%, respectively. The severity of coagulopathies as reflected by elevations in serum fibrogen/fibrin degradation products and lysosomal integrity were likewise significantly reduced (40%) with ibuprofen (3.75 mg/kg) pretreatment. These results are consistent with the hypothesis that arachidonic acid metabolites play a significant early role in the pathogenesis of endotoxic shock. Our observations suggest potential benefits from agents which inhibit fatty acid cyclooxygenase.

Acid Phosphatase↗
PubMed1979

A serological survey of St Lucia.

A serological survey of a random sample of 541 of the population of St Lucia was undertaken. The prevalence of antibodies to dengue, herpes virus, VZ, rotavirus, rubella and syphilis is described and compared with other communities.

Adolescent↗
PubMed1979

Resistance of essential fatty acid-deficient rats to endotoxic shock.

The role of lipids in the altered energy metabolism of shock remains to be delineated fully. During the course of our studies of endotoxic shock, the susceptibility of essential fatty acid (EFA)-deficient rats to endotoxin was evaluated. Intravenous administration of S. Salmonella enteritidis endotoxin (1 mg/100 gm) in normal male Long-Evans rats (7--8 weeks old) produced severe shock with an 88% mortality. In marked contrast, injection of this dose of endotoxin in EFA-deficient rats of the same age resulted in only an 18% mortality. The deficient state afforded significant protection to even supralethal doses of endotoxin (2 mg/100 gm). Evaluation of reticuloendothelial (RE) phagocytic activity with colloidal carbon did not reveal significant differences in RE clearance rates. Within five hours after induction of shock, however, plasma acid hydrolase activity of shocked control rats was approximately double that of the EFA-deficient group. Likewise, the endotoxin induced hypoglycemic response was milder in the EFA-deficient rats. The lower plasma glutamic-oxaloacetic transaminase activity and glutamic-pyruvic transaminase activity of the EFA-deficient group also indicated a maintenance of hepatic integrity. These observations suggest that essential fatty acids of their products (ie, prostaglandins) contribute to the pathogenesis of endotoxic shock.

Alanine Transaminase↗
PubMed1978

Increased resistance to Staphylococcus aureus infection and enhancement in serum lysozyme activity by glucan.

Glucan is a potent reticuloendothelial stimulant whose immunobiological activity is mediated, in part, by an increase in the number and function of macrophages. In studying the role of glucan as a mediator of antibacterial activity, we attempted to ascertain the ability of glucan to modify the mortality of mice with experimentally induced Gram-positive bacteremia, and to enhance antibacterial defenses in rats as denoted by serum lysozyme and phagocytic activity. After intravenous administration of glucan, serum lysozyme concentrations were increased approximately sevenfold over control concentrations. The increase in serum lysozyme appeared to parallel the glucan-induced increase in phagocytosis and induced hyperplasia of macrophages. Prior treatment of mice with glucan significantly enhanced their survival when they were challenged systemically with Staphylococcus aureus. These studies indicate that glucan confers an enhanced state of host defense against bacterial infections.

Animals↗