The effects of immunostimulatory herbal supplements on autoimmune skin diseases.

The use of herbal supplements that promise to improve immune health has gained popularity among dermatology patients. However, there is little to no evidence that herbal supplements improve dermatologic conditions. Several in vitro and in vivo studies have shown that Spirulina platensis, Aphanizomenon flos-aqua, Chlorella, Echinacea, and alfalfa activate immune cells via certain cytokines and chemokines. Case reports suggest the association of ingesting immunostimulatory herbs and the clinical onset or flares of diseases characterized by an exaggerated immune response such as lupus erythematosus, dermatomyositis, and autoimmune blistering disorders. Therefore, it is imperative to investigate the prevalence of herbal supplement use in this patient population. In addition, in vitro studies should examine the underlying mechanisms by which herbs stimulate immune pathways that are already overactive in autoimmune patients.

Risk Assessment of Salmonellosis from Consumption of Alfalfa Sprouts and Evaluation of the Public Health Impact of Sprout Seed Treatment and Spent Irrigation Water Testing.

We developed a risk assessment of human salmonellosis associated with consumption of alfalfa sprouts in the United States to evaluate the public health impact of applying treatments to seeds (0-5-log10 reduction in Salmonella) and testing spent irrigation water (SIW) during production. The risk model considered variability and uncertainty in Salmonella contamination in seeds, Salmonella growth and spread during sprout production, sprout consumption, and Salmonella dose response. Based on an estimated prevalence of 2.35% for 6.8 kg seed batches and without interventions, the model predicted 76,600 (95% confidence interval (CI) 15,400-248,000) cases/year. Risk reduction (by 5- to 7-fold) predicted from a 1-log10 seed treatment alone was comparable to SIW testing alone, and each additional 1-log10 seed treatment was predicted to provide a greater risk reduction than SIW testing. A 3-log10 or a 5-log10 seed treatment reduced the predicted cases/year to 139 (95% CI 33-448) or 1.4 (95% CI <1-4.5), respectively. Combined with SIW testing, a 3-log10 or 5-log10 seed treatment reduced the cases/year to 45 (95% CI 10-146) or <1 (95% CI <1-1.5), respectively. If the SIW coverage was less complete (i.e., less representative), a smaller risk reduction was predicted, e.g., a combined 3-log10 seed treatment and SIW testing with 20% coverage resulted in an estimated 92 (95% CI 22-298) cases/year. Analysis of alternative scenarios using different assumptions for key model inputs showed that the predicted relative risk reductions are robust. This risk assessment provides a comprehensive approach for evaluating the public health impact of various interventions in a sprout production system.

Desempenho de vacas leiteiras em pastagem de alfafa suplementada com silagem de milho e concentrado e viabilidade econômica do sistema / Performance of dairy cows on alfalfa pasture supplemented with corn silage and concentrate and its economic viability

Avaliou-se o efeito da substituição parcial de silagem de milho por pastagem de alfafa no desempenho de vacas leiteiras e na viabilidade econômica do sistema. Utilizaram-se 24 vacas da raça Holandesa, em estádio médio de lactação, em delineamento em blocos ao acaso. Os tratamentos foram: dieta à base de silagem de milho em confinamento, silagem de milho substituída parcialmente por pastejo restrito (PR) e pastejo irrestrito (PI) de alfafa. O sistema de pastejo foi rotacionado, e a quantidade de concentrado igual em todos os tratamentos. A massa de forragem foi de 2.338 e de 1.878kg de MS/ha, e a oferta de 1,8 e 4,2kg de MS/100kg de peso vivo, nos tratamentos PR e PI, respectivamente. A produção de leite não diferiu entre os tratamentos, cujas médias foram de 25,9; 25,8 e 25,2 litros por vaca por dia no confinamento, no PR e no PI, respectivamente. A produção diária de leite por área foi de 59,3L/ha no PR e de 63,0L/ha no PI, enquanto no confinamento foi de 45,7L/ha. A substituição parcial de silagem de milho por alfafa em pastejo não limitou o desempenho produtivo dos animais e mostrou-se economicamente vantajosa em relação ao confinamento.

The effect of partial replacement of corn silage for alfafa grazing on dairy cows performance and profitability was evaluated. Twenty-four Holstein dairy cows in mid-lactation were used in a randomized block design. Treatments were: a corn silage-based diet fed on drylot, or partial replacement of corn silage for either restricted alfalfa grazing or unrestricted grazing. A rotational grazing system was used and the amount of concentrate fed was the same in all treatments. Forage availabilities were 2,338 and 1,878kg/ha of dry matter (DM) and offered at 1.8 and 4.2kg of DM/100kg of live weight under restricted and unrestricted grazing, respectively. No difference in milk production was observed among treatments, averaging 25.9, 25.8, and 25.2 liters per cow on feedlot, restricted grazing, or unrestricted grazing, respectively. Milk production per hectare was 59.3L/day on restricted grazing and 63L/day on unrestricted grazing, whereas it was 45.7L/day on drylot. Partial replacement of corn silage for alfalfa grazing did not limit animal performance and it would be economically advantageous as compared to drylot feeding.

Alfalfa pellet-induced subacute ruminal acidosis in dairy cows increases bacterial endotoxin in the rumen without causing inflammation.

A study was conducted to determine if subacute ruminal acidosis (SARA) induced by feeding alfalfa pellets results in increases in free bacterial lipopolysaccharide (LPS) in rumen fluid and peripheral blood, and acute phase proteins in plasma, and to determine the effect of alfalfa pellet-induced SARA on feed intake, rumen fermentation characteristics, milk production and composition, and blood metabolites. Eight lactating Holstein cows, 4 of which were ruminally cannulated, were used in a 6-wk experiment and were fed once daily at 0900 h. During wk 1, cows received a diet containing 50% of DM as concentrate and 50% of DM chopped alfalfa hay. Between wk 2 and wk 6, alfalfa hay was gradually replaced with alfalfa pellets at the rate of 8% per week to reduce rumen pH. Rumen pH was monitored continuously in the ruminally cannulated cows using indwelling pH probes. Rumen fluid and peripheral blood were sampled 15 min before feed delivery and at 6 h after feed delivery. Based on adopted threshold of SARA of at least 180 min/d below pH 5.6, SARA was induced from wk 3 onwards. Replacing 40% of alfalfa hay with alfalfa pellets quadratically increased the DMI from 18.1 kg/d in wk 1 to 23.4 kg/d in wk 6. This replacement linearly decreased milk yield (32.7 vs. 35.9 kg/d) and milk fat percentage and yield (2.32 vs. 3.22%, and 0.77 vs. 1.14 kg/d, respectively), but increased milk protein percentage and yield (3.80 vs. 3.04%, and 1.23 vs. 1.07 kg/d, respectively). This gradual replacement also linearly increased the daily averages of total volatile fatty acids (90 to 121.9 mM), acetate (53.9 to 66.8 mM), propionate (21.5 to 39.6 mM), and osmolality (277.7 to 293.8 mmol/kg) in the rumen and decreased the acetate to propionate ratio from 2.62 to 1.73. Replacing alfalfa hay with alfalfa pellets linearly increased blood lactate from 1.00 mM in wk 1 to a peak of 3.46 mM in wk 5. Induction of SARA in this study increased free rumen LPS concentration from 42,122 endotoxin unit (EU)/mL in wk 1 to 145,593 EU/mL in wk 6. However, this increase was not accompanied by an increase in LPS (<0.05 EU/mL) and in acute phase proteins serum amyloid-A, haptoglobin, and LPS-binding protein in peripheral circulation. Results suggest that SARA induced by alfalfa pellets increased LPS in the rumen without causing translocation of LPS and an immune response.

Role of non-protein amino acid L-canavanine in autoimmunity.

Association of SLE and alfalfa was first reported in a volunteer who developed lupus-like autoimmunity while ingesting alfalfa seed for a hypercholesterolemia study. This was corroborated with studies in monkeys fed with alfalfa sprout that developed SLE. Re-challenge with L-canavanine relapsed the disease. Arginine homologue L-canavanine, present in alfalfa, was suspected as a cause. L-canavanine can be charged by arginyl tRNA synthetase to replace L-arginine during protein synthesis. Aberrant canavanyl proteins have disrupted structure and functions. Induction or exacerbation of SLE by alfalfa tablets reported in a few cases remains controversial. Epidemiological studies on the relationship between alfalfa and SLE are sparse. In mice, NZB/W F1, NZB, and DBA/2 mice fed with L-canavanine show exacerbation/triggering of the SLE, however, BALB/c studies were negative. L-canavanine incorporation may be more efficient in the presence of inflammation or other conditions that can cause arginine deficiency. The L-canavanine induced apoptotic cells can be phagocytosed and a source of autoantigens processed by endosomal proteases. Endogenous canavanyl proteins are ubiquitinated and processed via proteasome. Incorporation of L-canavanine into proteasome or endosome can also cause disruption of antigen processing. Alfalfa/L-canavanine-induced lupus will be an interesting model of autoimmunity induced by the modification of self-proteins at the translational level.

Acute renal transplant rejection possibly related to herbal medications.

Use of herbal and alternative medications in the United States is increasing. Many of these medications have unknown mechanisms of actions, and possible metabolic interactions with prescribed medications. We report a case of late acute rejection after exposure to two popular herbal medications.

The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria.

The breast cancer resistance protein (BCRPABCG2) is a member of the ATP-binding cassette family of drug transporters and confers resistance to various anticancer drugs. We show here that mice lacking Bcrp1Abcg2 become extremely sensitive to the dietary chlorophyll-breakdown product pheophorbide a, resulting in severe, sometimes lethal phototoxic lesions on light-exposed skin. Pheophorbide a occurs in various plant-derived foods and food supplements. Bcrp1 transports pheophorbide a and is highly efficient in limiting its uptake from ingested food. Bcrp1(-/-) mice also displayed a previously unknown type of protoporphyria. Erythrocyte levels of the heme precursor and phototoxin protoporphyrin IX, which is structurally related to pheophorbide a, were increased 10-fold. Transplantation with wild-type bone marrow cured the protoporphyria and reduced the phototoxin sensitivity of Bcrp1(-/-) mice. These results indicate that humans or animals with low or absent BCRP activity may be at increased risk for developing protoporphyria and diet-dependent phototoxicity and provide a striking illustration of the importance of drug transporters in protection from toxicity of normal food constituents.

Use of spent irrigation water for microbiological analysis of alfalfa sprouts.

Numerous outbreaks of foodborne illness have been linked to the consumption of raw sprouts. Sprout producers have been advised by the Food and Drug Administration to include microbiological testing of spent irrigation water during production as part of an overall strategy to enhance the safety of sprouts. Alfalfa sprouts and irrigation water were analyzed to show the feasibility of using irrigation water for monitoring the microbiological safety of sprouts. Sprouts and water were produced and harvested from both commercial-scale (rotary drum) and consumer-scale (glass jars) equipment. Rapid increases of aerobic mesophiles occurred during the first 24 h of sprouting, with maximum levels achieved after 48 to 72 h. The counts in irrigation water were on average within approximately 1 log of their respective counts in the sprouts. Similar results were obtained for analysis of Escherichia coli O157:H7 in irrigation water and sprouts grown from artificially inoculated seeds. Testing of spent irrigation water indicated the contamination status of alfalfa sprouts grown from seeds associated with outbreaks of Salmonella infection.

Lupus erythematosus and nutrition: a review of the literature.

The purpose of this review was to search the scientific literature for dietary compounds that alleviate or exacerbate symptoms of lupus erythematosus (LE) in both animal and human models. A detailed literature review was undertaken to find articles showing a relationship between LE and nutrition by using MEDLINE/INDEX MEDICUS (1950-March 2000) for English-language articles, followed by cross-referencing. Aggravating substances appear to include excess calories, excess protein, high fat (especially saturated and omega-6 polyunsaturated fatty acids), zinc, iron, and L-canavanine found in alfalfa tablets. Possible beneficial dietary compounds include vitamin E, vitamin A (beta-carotene), selenium, fish oils (omega-3 polyunsaturated fatty acids), evening primrose oil, flaxseed, a plant herb (Tripterygium wilfordii), dehydroepiandrosterone, and calcium plus vitamin D (if taking corticosteroids). Some people with systemic LE placed on food allergy elimination diets reported improvement in their LE symptoms; however, this may be related to a decrease of other substances in the diet. Also, although no direct evidence was reported on the beneficial effects of either bromelain or a vegetarian diet (possibly allowing fish), it is suggested that they might be beneficial. Limitations to this research are that the findings are based on relatively few studies, many of which were without control groups or extrapolated from animal models. No large-scale studies have been performed with LE patients to substantiate the benefit, if any, of these individual dietary interventions, and if they were conducted, the remission and exacerbation pattern of LE may interfere with elucidating their effectiveness. Also, dietary changes should not be attempted without a physician's approval/monitoring.

Primary photosensitization related to ingestion of alfalfa silage by cattle.

A herd of 650 Holstein cows was examined for skin disease. Approximately 400 of the lactating adults were affected, but heifers, calves, and nonlactating cows were clinically normal. The condition was characteristic of primary photosensitization. Milk production of the affected cows was normal. Affected cows did not appear to be ill, and none of the cows was icteric. Three of 7 cows had high serum gamma-glutamyltransferase activities, but in the other 4 cows, activity was within the reference range. Serum activities of other hepatic enzymes were within reference ranges in the 7 cows that were examined. Hepatic biopsy specimens from 3 cows were normal. Specimens from 4 other cows had changes that ranged from minimal to mild, chronic, lymphoplasmacytic periportal hepatitis to acute, random, necrotizing hepatitis. Development of photosensitivity was related to ingestion of alfalfa silage. Acetone extracts of the alfalfa silage, but not of other feedstuffs, were found to inhibit growth of Candida albicans under ultraviolet light. Cows experimentally fed a diet composed exclusively of the alfalfa silage developed skin lesions after 6 days, but did not have detectable serum concentrations of phylloerythrin.

Histopathological changes in the reproductive organs of Manchego ewes grazing on lucerne.

The effects of prolonged exposure to phyto-oestrogens (coumestrol) on the morphology of the reproductive organs of ewes were studied in 28 lucerne-grazing animals, and compared with 28 control ewes given a standard coumestrol-free diet. The anatomical studies showed that 43% of the ewes fed lucerne displayed macroscopic changes within the genital tract, of which the uterine alterations were especially prominent. The microscopic examination of the test group ewes identified specific histopathological features of the uterus and cervix. A greater than normal development of the cervical folds was observed, as well as cystic formations of different sizes whose content was eosinophilic. In the rest of the uterus, more glandular activity was detected in the lucerne-grazing group than in the control ewes, although cystic formations were not seen.

Liver disease in cattle induced by consumption of moldy hay.

Normally innocuous forages are sporadically associated with hepatogenous photosensitization outbreaks at certain times of the year or when grown and harvested during unusual environmental conditions, such as periods of excessive rainfall. Allegations of livestock illness following consumption of such moldy hays are associated with clinical syndromes uncharacteristic of known forage-related diseases, suggesting that unidentified toxin(s) may be responsible. This study was instigated by field observations of hepatogenous photosensitization in cattle fed alfalfa-grass forage. To document the toxic nature of the hay, large bales of hay (450 kg) were fed, ad libitum, to 3 groups of 2 calves each. Elevated serum liver enzymes provided evidence of hepatobiliary disease. Gamma glutamyl transferase activities in serums of the calves sustained at least a 10-fold increase above baseline during the feeding trials. Histologic examination of liver biopsies and postmortem sections revealed mild periportal fibrosis and biliary hyperplasia. Culture material from 12 fungal isolates from the hay failed to induce liver disease in calves.

Pasture management strategies for reducing the risk of legume bloat in cattle.

Results from two decades (1973-1993) of bloat research at Kamloops are reviewed. The trials were conducted with groups of ruminally fistulated cattle either grazing or fed daily fresh-cut alfalfa (Medicago sativa) herbage. Studies were conducted during the growing season (May to September) and in the fall (October and November). The alfalfa was usually in the vegetative to early bloom stages of growth. Visual assessments of bloat severity on a scale of 1 to 5 were made .5 to 2 h after feeding started, at which time ruminal cannulas were opened to relieve ruminal pressure. Every cultivar of alfalfa tested caused bloat, but sainfoin (Onobrychis viciifolia), birdsfoot trefoil (Lotus corniculatus), and cicer milkvetch (Astragalus cicer) did not. This confirms the bloat-safe features of these alternate legume forages. Bloat was positively associated with the level of Fraction 1 protein and total soluble protein in alfalfa, supporting the concept of a decreased probability of bloat with advancing stages of plant maturity. There was no association between alfalfa saponins and bloat. Prefeeding ruminal chlorophyll levels were higher and ruminal clearance rates were lower in cattle that were susceptible to bloat. Cattle that bloated on a given day consumed 18 to 25% less alfalfa immediately before bloat than non-bloaters did in the same time period. Ruminal cations were associated with bloat incidence but cation manipulation through supplementation did not prevent bloat. Of all the feed additives tested, only poloxalene (Bloat Guard) completely prevented bloat.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of two supplements for the prevention of alfalfa bloat.

Poloxalene and a mineral mixture feed supplement patented for the treatment of emphysema, polyarthritis, and other pectin related diseases were tested in two trials for their ability to prevent bloat in cattle fed fresh alfalfa. Each trial had a crossover design using three Jersey steers with rumen fistulas per group. Each trial period continued until the total number of cases of bloat reached > or = 24. Treatments were given at 0800 each day. The mineral mixture was given at 100 g/d and 190 mg/kg body weight per day in the first and second trials, respectively. Poloxalene, which was tested only in the second trial, was given at 23 mg/kg body weight per day. Each group of steers was then fed 200 kg of freshly harvested alfalfa in the vegetative to early bloom stages of growth at 0830. In the first trial, only 69% as many cases of bloat occurred on the mineral mixture as on the control treatment, but no significant difference was detected in the second trial. The potency of the alfalfa may have been higher in the second trial, when forage dry matter was lower, magnesium and soluble nitrogen were higher, and bloat occasionally occurred twice a day. Bloat did not occur when the steers were treated with poloxalene. In these trials, poloxalene was completely effective in preventing bloat, but the mineral mixture was only partially so.

Botulism associated with feeding alfalfa hay to horses.

Botulism was believed to be the cause of progressive symmetric myasthenia in 8 horses on a farm in North Carolina. One horse was found dead, 6 were euthanatized after becoming recumbent, and 1 affected horse recovered. Cecal and colonic contents of 2 horses were determined to contain Clostridium botulinum spores. Alfalfa hay that was fed to the horses contained spores and toxin.

Dietary amino acid-induced systemic lupus erythematosus.

The effects of dietary manipulations on autoimmune disease are understood poorly. In this article, we detail our experience with a human subject who developed autoimmune hemolytic anemia while participating in a research study that required the ingestion of alfalfa seeds. Subsequent experimental studies in primates ingesting alfalfa sprout seeds and L-canavanine (a prominent amino acid constituent of alfalfa) is presented. The results of these studies indicate a potential toxic and immunoregulatory role of L-canavanine in the induction of a systemic lupus-like disease in primates.

Hepatic enzyme changes in bovine hepatogenous photosensitivity caused by water-damaged alfalfa hay.

In the winter of 1983, practitioners reported extensive photosensitization in 7 herds of cattle. All herds had a history of having been fed water-damaged alfalfa hay. A cow from one herd was referred to the veterinary teaching hospital at Oklahoma State University. In this herd of approximately 40 adult Polled Herefords, all cattle had had some degree of clinical involvement over the past 4 to 6 weeks. Clinical signs included scaling and erythema of sparsely haired skin, muzzle, and teats, as well as icterus, anorexia, and weight loss. One cow died, and the remaining cattle recovered over an 8- to 10-week period after removal of the hay from the ration. In the referred cow, values for total and conjugated bilirubin, BUN, creatinine, sorbitol dehydrogenase, serum alkaline phosphatase, serum aspartate transaminase, and serum gamma-glutamyl transferase were higher than normal. In the herd of origin, extremely high serum gamma-glutamyl transferase values (180 to 1,400 IU/L) persisted (normal, 2 to 35 IU/L). Feeding the same alfalfa hay to 2 clinically normal cows reproduced the syndrome. The characteristic hepatic lesion was bile duct necrosis, with secondary bile duct hyperplasia.

Rumen clearance rates in relation to the occurrence of alfalfa bloat in cattle. 1. Passage of water-soluble markers.

Ruminal chlorophyll and rates of passage of two water-soluble markers were simultaneously determined in cattle with different susceptibilities to alfalfa bloat. The markers showed a slower rate of passage from the rumens of more susceptible cattle where the average half-lives for cobalt-ethylenediaminetetraacetic acid and chromium-ethylenediaminetetraacetic acid were 12 to 17 h. Average half-life of the markers was 8 h in the rumens of the less susceptible animals. In agreement, chloroplast particles in the liquid phase of rumen contents showed greater accumulation in animals susceptible to bloat, but many more observations were required to detect differences in chlorophyll among animals. This was partly due to the unhomogeneous dispersion of chloroplast fragments in the reticulorumen compared with the uniform distribution of the inert markers. Differences in rumen volumes (estimated from the quantity of marker administered and its initial concentration) were detected among animals, but these did not show a relationship to bloat susceptibility. In vitro studies indicated that alfalfa chloroplast particles were not readily degraded by rumen microorganisms. Our results support earlier conclusions on slower rates of salivation for cattle that bloat compared with those that do not.