Physiological responses of rats fed loline and ergot alkaloids from endophyte-infected tall fescue.

Sixty-three male sprague Dawley rats were randomly assigned to dietary treatments containing 1) N-formylloline alkaloid (NFL), 2) N-acetylloline alkaloid (NAL), 3) NFL + NAL, 4) NFL + a mixture of ergot alkaloids, 5) NAL + a mixture of ergot alkaloids, 6) NFL + NAL + a mixture of ergot alkaloids, 7) a mixture of ergot alkaloids, 8) endophyte-free tall fescue seed (EFTF), and 9) endophyte-infected tall fescue (EITF) seed (negative control). All diets were prepared by mixing the prepared treatments and Laboratory Chow (1:1 ratio) and were fed at a maximum of 15 g per rat per day. All rats were killed at termination (d 18). Rats fed the EITF consumed less (P < .05) than those fed all other treatments. Feed intake for rats fed the NFL + ergot alkaloids was lower than for those fed NAL, NAL + ergot alkaloids, NFL + NAL + ergot alkaloids, ergot alkaloids, and EFTF treatments. Average daily weight gains (ADG) followed a trend similar to feed intake with some exceptions. Rats fed the NFL + NAL treatments had higher (P < .05) ADG than those fed all other treatments except the NFL + NAL + ergot alkaloid treatment. Rats fed the EITF had lower (P < .05) ADG than those fed all other treatments except those fed ergot alkaloids and NAL + ergot alkaloids. Epididymides, testes, hypothalamus, corpus striatum weights, prolactin and alkaline phosphatase content were not altered by dietary treatments. Results suggest that loline alkaloids may have a slight depressing effect on feed intake.

In vitro and in vivo ruminal and physiological responses to endophyte-infected tall fescue.

Relationships between alkaloid compounds in endophyte-infected tall fescue and ruminal metabolism were studied in two experiments. In the first experiment, different combinations of the pyrrolizidine alkaloids, N-formyl and N-acetyl loline, were incubated with ruminal fluid for 0, 24, or 48 h. Rate of disappearance of N-formyl and N-acetyl loline increased over time. After 48 h, disappearance of N-formyl loline and combinations of N-formyl and N-acetyl loline was greater than N-acetyl loline. Significant amounts of N-formyl and N-acetyl loline were metabolized and converted to loline. In the second experiment, abomasally cannulated sheep were fed increasing amounts of endophyte-infected feed to compare diet digestibility, alkaloid metabolism, and physiological responses. Total tract DM digestibility was greatest for the endophyte-free diet, as were ruminal and total tract ADF, ruminal NDF, and total tract CP digestibilities. N-Formyl and N-acetyl loline recoveries averaged 5% from abomasal contents and 0% in feces. Sixty-eight percent of the pyrrolizidine alkaloids recovered in abomasal contents had been metabolizable to loline. Ergot alkaloids administered in the diet were recovered (50 to 60%) in the abomasal contents, but recovery was only 5% in fecal collections. No significant differences occurred in the physiological parameters measured. Results indicate that response to endophyte-infected tall fescue may be influenced by ruminal metabolism.

Inappropriate electrical countershocks by an automated external defibrillator.

A 79-year-old man who was in normal sinus rhythm with a palpable pulse was inappropriately shocked twice by a fully automated external defibrillator. The second shock resulted in ventricular tachycardia. The device then countershocked a third time, restoring normal sinus rhythm. The problem occurred primarily because the rescuers did not follow the device's instructions warning against applying the device in analysis mode to a patient with a palpable pulse, and they attempted to analyze the rhythm in a moving vehicle. Motion artifact and T waves that were relatively tall compared with the QRS amplitude were misinterpreted as ventricular fibrillation by the device. This example of inappropriate countershocks delivered by rescuers using a fully automated device illustrates the importance of proper training and continuing education.

The effect of alkaloids and seed extracts of endophyte-infected tall fescue on prolactin secretion in an in vitro rat pituitary perfusion system.

The objective of this research was to measure the effects of endophyte-infected tall fescue seed extract and various alkaloids associated with the endophyte on in vitro prolactin secretion by rat hemipituitaries. Rat anterior pituitaries (AP) were dissected into halves and placed in temperature-controlled culture chambers (37 degrees C). The tissue was perfused with culture media at a flow rate of 12 mL/h. After perfusion for at least 90 min with control media, AP halves were exposed to their respective treatments for 15 min before they were returned to the control media. The treatments for Exp. 1 were .01 micrograms of alpha-ergocryptine/mL of culture medium, .01 microgram of ergonovine/mL of culture medium, .01 gram-equivalents of endophyte-infected tall fescue seed/mL of culture medium, and .01 gram-equivalents of endophyte free tall fescue seed/mL of culture medium. Treatments for Exp. 2 consisted of 10(-4), 10(-6), and 10(-8) M concentrations of perloline, N-formyl loline, N-acetyl loline, N-methyl loline, and alpha-ergocryptine. alpha-Ergocryptine suppressed (P less than .10) prolactin secretion in both experiments. Ergonovine and perloline both stimulated (P less than .10) prolactin secretion. The loline alkaloids (N-formyl loline, N-acetyl loline, N-methyl loline) had no effect on prolactin secretion. The endophyte-infected seed extract treatment suppressed (P less than .10) prolactin secretion. The endophyte-free seed extract treatment had no effect on prolactin secretion. In Exp. 2, prolactin secretion from AP responded to alpha-ergocryptine treatment in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

A new fumonisin from solid cultures of Fusarium moniliforme.

A new fumonisin has been isolated from Fusarium moniliforme isolate MRC826 grown on corn. It was shown by NMR and mass spectrometry to be an isomer of fumonisin B2 that has free hydroxyl groups at C-3 and C-10 instead of the normal C-3 and C-5. This new fumonisin was detected in cultures of most isolates of F. moniliforme that were examined and was usually present at concentrations similar to those of fumonisin B2. Two isolates of F. moniliforme that produce significantly higher levels of this new isomer were identified.

Alkaloids of Stipa robusta (sleepygrass) infected with an Acremonium endophyte.

Stipa robusta (= Stipa vaseyi) is a perennial grass found in certain areas of the southwestern United States. It is commonly known as sleepygrass, as horses that ingest this grass may become profoundly somnolent or stuporous for periods of time lasting up to several days. In an attempt to determine the active principle(s), fractionation of a methanolic extract of sleepygrass infected with an Acremonium endophyte has yielded lysergic acid amide (20 micrograms/g dry wt), isolysergic amide (8), 8-hydroxylsergic acid amide (0.3), ergonovine (7), chanoclavine-I (15), and N-formylloline (18). Related alkaloids have been found in many endophyte-infected grasses. The dominant alkaloid constituent in sleepygrass, lysergic acid amide, has not previously been identified in a grass in such high concentration. Lysergic acid amide is likely to be the basis for the extreme sedative effects on animals, given past pharmacological work on the compound from the ergot fungus Claviceps paspali.

Alkaloid toxins in endophyte-infected grasses.

Grasses infected with clavicipitaceous fungi have been associated with a variety of diseases including classical ergotism in humans and animals, fescue foot and summer syndrome in cattle, and rye-grass staggers in sheep. During the last decade it has been recognized that many of these fungal infections are endophytic; a fungal endophyte is a fungus that grows entirely within the host plant. Inspection of field collections and herbarium specimens has revealed that such infections are widespread in grasses. The chemistry associated with these grass-fungal interactions has proved to be interesting and complex, as each grass-fungal pair results in a unique "fingerprint" of various alkaloids, of which some are highly toxic to herbivores. In many cases the presence of an endophyte appears to benefit the plant by increasing drought resistance, or by increasing resistance to attack by insects, thus improving the overall survivability of the grass. This review will focus on alkaloids that have been reported in endophyte-infected grasses.

Dithyreanitrile: an unusual insect antifeedant from Dithyrea wislizenii.

Dithyreanitrile, a novel sulfur-containing indole alkaloid, was isolated from the seeds of Dithyrea wislizenii (Cruciferae). Dithyreanitrile inhibits feeding of fall armyworm (Spodoptera frugiperda) and European corn borer (Ostrinia nubilalis) larvae. Dithyreanitrile, the first natural product with two sulfur atoms and a nitrile attached to the same carbon, was characterized by X-ray diffraction, spectroscopy, and chemical synthesis.

Severe diabetic retinopathy at presentation in a young man.

A 22 year old man presented with a severe ischaemic diabetic retinopathy and, in spite of photocoagulation therapy, was blind in one eye 16 months after diagnosis. Four similar cases of aggressive diabetic retinopathy are reviewed. There is increasing evidence that a small group of young men with insulin dependent diabetes (IDD) may develop severe diabetic retinopathy at, or soon after, diagnosis.

Limonoid antifeedants from seed of Sandoricum koetjape.

An extract of the seed of Sandoricum koetjape has yielded two new limonoids, sandoricin [1] and 6-hydroxysandoricin [2]. Both compounds are effective antifeedants when incorporated into artificial diets and fed to fall armyworm (Spodoptera frugiperda) or European corn borer (Ostrina nubilalis) larvae. Reduced growth rates and increased times to pupation were evident at lower dose levels while significant mortality was noted at higher dose levels. Structures of both compounds were determined by 1H nmr, 13C nmr, and ms and confirmed by X-ray crystallography.

Physiological responses in rats fed extracts of endophyte-free and endophyte-infected tall fescue seed relative to some known ergot alkaloids.

Ethanol and ethanol-water extracts of endophyte-infected tall fescue seed were effective for extracting toxin(s) responsible for feed intake and average daily weight gain (ADG) depression in Sprague Dawley rats. Although the ethanol extract of endophyte-infected seed depressed serum prolactin (Prl) concentrations, the data were less reflective of overall toxicity than feed intake and weight gain. Inclusion of commercially available ergonovine maleate, ergocryptine and ergotamine tartrate had no effect on rat feed intake, ADG or serum Prl at the levels tested. Dietary addition of a recombination of hexane, ethanol and ethanol-water extracts caused a toxicity response (depressed feed intake, ADG, and serum Prl) equivalent to that of the whole seed. The toxic factor(s) were extracted primarily in more polar solvents such as ethanol and ethanol-water. Rat assays can be used successfully in lieu of cattle assays as a routine evaluation of toxic components in endophyte-infected tall fescue. However, species differences dictate that eventually all suspected toxins be evaluated in the bovine.

Cerebrospinal fluid eosinophilia and sterile shunt malfunction.

Cerebrospinal fluid (CSF) eosinophilia is a rare finding most often associated with central nervous system inflammatory processes, including parasitic, bacterial, and mycotic infections. It has also been seen as an allergic phenomenon. We present two cases of CSF eosinophilia occurring concurrently with sterile shunt malfunction. We speculate that CSF eosinophilia in our patients might have resulted from an allergic response to a foreign material such as suture, surgical glove powder, hair, cotton fibers, antibiotics, or silicone rubber. The incidence of sterile CSF eosinophilia after shunting is not known. Information concerning the role of eosinophilia in the development of shunt malfunctions is also lacking. An increased awareness of this possibility and further investigation are warranted.

Postural response of intraocular pressure in chronic open-angle glaucoma following trabeculectomy.

Forty-six eyes with chronic open-angle glaucoma (COAG) and 24 eyes which had previously undergone trabeculectomy for COAG were studied and the postural response of the intraocular pressure compared with that of 70 normal eyes. In all three groups the greatest rise in intraocular pressure (IOP) occurred when the subject changed from the sitting to the lying position. In the control group this was never more than 2 mmHg in any subject. The rise was greater than 2 mmHg in 93% of the patients suffering from COAG who were treated medically and in 100% of the eyes of those on which trabeculectomy had been performed. The well recognised abnormal postural response of intraocular pressure in COAG appears both to be retained and to be unaffected in those eyes which have undergone trabeculectomy.