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Life Extension Magazine April 2011

Immune Function

Production of hen egg yolk immunoglobulins simultaneously directed against Salmonella enteritidis and Salmonella typhimurium in the same egg yolk.

The present study was an attempt to raise hen egg yolk Ig (IgY) simultaneously directed against Salmonella Enteritidis (SE) and Salmonella Typhimurium (ST) in the same egg yolk. The immunopotentiating effect of 2 different adjuvants -- Freund’s adjuvants (FA) and immunostimulating complexes matrix (IM) -- on antibody response was also evaluated. Bacterial outer membrane proteins (OMP) were selected as target antigens. The ISA Brown hens, specific-Salmonella spp.-free status, divided into 6 groups were intramuscularly injected with a mono-compound antigen preparation: SE-OMP (treatment SE-FA or SE-IM) or ST-OMP (treatment ST-FA or ST-IM), or a combined antigen preparation: (1/2) SE-OMP and (1/2) STOMP (treatment SEST-FA or SEST-IM). Titers of antibodies in yolk were evaluated biweekly with ELISA. There was no antigen x adjuvant interaction on antibody titers. Anti-SE IgY titers in hens that received treatment SEST-FA or SEST-IM were statistically similar (P > 0.05) as compared with those obtained from hens immunized with treatment SE-FA or SE-IM. Anti-ST IgY titers in hens immunized with treatment SEST-FA or SEST-IM were slightly lower than those of hens that received treatment ST-FA or ST-IM. The cross-reactivity of anti-SE IgY, induced by treatment SE-FA or SE-IM, with ST-OMP antigen and that of anti-ST IgY, induced by ST-FA or ST-IM, with SE-OMP antigen were arbitrarily assessed on d 43 and 155 by ELISA. The average cross-reactivity of anti-SE IgY with ST-OMP antigen was 71.7%. The average cross-reactivity of anti-ST IgY with SE-OMP antigen was 78.8%. In FA groups, antibody titers were found higher (P < 0.05) than those in IM groups. Furthermore, no extensive lesions or clinical abnormalities were detected in hens injected with FA. These findings showed the opportunity to raise IgY antibody against 2 Salmonella serovars in the same yolk and that FA was more efficient than IM in mediating antibody response.

Poult Sci. 2008 Jan;87(1):32-40

The impact of egg limitations on coronary heart disease risk: do the numbers add up?

For over 25 years eggs have been the icon for the fat, cholesterol and caloric excesses in the American diet, and the message to limit eggs to lower heart disease risk has been widely circulated. The “dietary cholesterol equals blood cholesterol” view is a standard of dietary recommendations, yet few consider whether the evidence justifies such restrictions. Over 50 years of cholesterol-feeding studies show that dietary cholesterol does have a small effect on plasma cholesterol concentrations. The 167 cholesterol feeding studies in over 3,500 subjects in the literature indicate that a 100 mg change in dietary cholesterol changes plasma total cholesterol by 2.2 mg/dL. Today we recognize that dietary effects on plasma cholesterol must be viewed from effects on the atherogenic LDL cholesterol as well as anti-atherogenic HDL cholesterol since the ratio of LDL:HDL cholesterol is a major determinant of heart disease risk. Cholesterol feeding studies demonstrate that dietary cholesterol increases both LDL and HDL cholesterol with little change in the LDL:HDL ratio. Addition of 100 mg cholesterol per day to the diet increases total cholesterol with a 1.9 mg/dL increase in LDL cholesterol and a 0.4 mg/dL increase in HDL cholesterol. On average, the LDL:HDL ratio change per 100 mg/day change in dietary cholesterol is from 2.60 to 2.61, which would be predicted to have little effect on heart disease risk. These data help explain the epidemiological studies showing that dietary cholesterol is not related to coronary heart disease incidence or mortality across or within populations.

J Am Coll Nutr. 2000 Oct;19(5 Suppl):540S-548S

Oral administration of specific yolk antibodies (IgY) may prevent Pseudomonas aeruginosa infections in patients with cystic fibrosis: a phase I feasibility study.

Respiratory infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Chronic Pseudomonas aeruginosa (PA) infections ultimately occur in virtually all patients. It is impossible to eradicate PA when a patient has been chronically colonized. Immunotherapy with specific egg-yolk antibodies (IgY) may be an alternative to antibiotics for the prevention of PA infections. We wanted to determine if treatment with specific IgY can prolong the period between the first and the second PA colonization? And long-term, can the treatment diminish the number of positive PA cultures and postpone the onset of chronic colonization? CF patients gargled daily with an IgY-antibody preparation, purified from eggs of hens immunized with PA bacteria. They were compared to a group of patients who did not gargle with the preparation. Both groups had their first colonization with PA eradicated by antibiotics. The basic treatment was essentially the same in both groups. In the initial study, the period between the first and second colonization with PA was significantly prolonged for the treated vs. the control group (Kaplan-Meier P = 0.015, Breslow test). In the prolonged study, the treated group had only 2.5 sputum cultures positive for PA per 100 months of observation, and none of these patients became chronically colonized with PA. No adverse events were reported. In the control group, 13.7 cultures per 100 months of observation were positive for PA, and 5 (24%) patients became chronically colonized with PA. This feasibility study shows that antipseudomonal IgY has the potential to effectively prevent PA colonization without any severe adverse effects. A phase III study should be initiated.

Pediatr Pulmonol. 2003 Jun;35(6):433-40

Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum.

BACKGROUND: Oral ingestion of immunoglobulins in humans has been shown to be effective as prophylaxis against enteric infections. However, its therapeutic effect in children with infectious diarrhea has hitherto not been proven. We treated children with rotavirus diarrhea with immunoglobulins extracted from immunized bovine colostrum (IIBC) containing high titers of antibodies against four rotavirus serotypes. METHODS: In this double blind placebo-controlled trial, 80 children with rotavirus diarrhea were randomly assigned to receive orally either 10 g of IIBC (containing 3.6 g of antirotavirus antibodies) daily for 4 days or the same amount of a placebo preparation. The daily stool output (grams/kg/day), intake of oral rehydration solution (ml/kg/day), stool frequency (number of stools/day) and presence of rotavirus in stool were monitored for the 4 days during treatment. RESULTS: Children who received IIBC had significantly less daily and total stool output and stool frequency and required a smaller amount of oral rehydration solution than did children who received placebo (P < 0.05). Clearance of rotavirus from the stool was also earlier in the IIBC group compared with the placebo group (mean day, 1.5 vs. 2.9, P < 0.001). No adverse reactions from the colostrum treatment were observed. CONCLUSIONS: Treatment with antirotavirus immunoglobulin of bovine colostral origin is effective in the management of children with acute rotavirus diarrhea.

Pediatr Infect Dis J. 1998 Dec;17(12):1149-54

Effect of oral egg antibody in experimental F18+ Escherichia coli infection in weaned pigs.

The protection conferred by egg antibody specific for F18-fimbriae against infection with F18+ Escherichia coli was studied in controlled passive immunization trials involving weaned pigs. Parameters of protection consisted of body weight gain, frequency and severity of diarrhea and recovery of the challenge strain of F18+ E. coli. Weaned pigs at four weeks of age were challenge exposed once daily for three days by oral inoculation with 10(11) cfu of virulent F18+ E. coli followed by daily administration of antibody supplemented feed for 9 days starting from the first challenge day 0. Results showed a dose-dependent response to antibody treatment. The group of pigs given 1:50 titer of antibody in feed had less frequency of diarrhea (P < 0.01-0.05), higher rate of gain (P < 0.01) and lower isolation rate of challenge strain in rectal and intestinal swabs (P < 0.01) compared to non-treated control. In the same manner, the anti-F18 antibody significantly reduced adherence of F18+ E. coli to pig intestinal epithelial cells in vitro (P < 0.01). Results suggest that egg antibodies specific for the F18 fimbriae is a suitable immunotherapeutic agent for pigs infected with F18+ E. coli and that pigs can be protected from overt clinical disease and the subsequent reduced performance arising from infection with this pathogen.

J Vet Med Sci. 1997 Oct;59(10):917-21

Prevention of human rotavirus infection with chicken egg yolk immunoglobulins containing rotavirus antibody in cat.

A study was made on the passive protection against rotavirus-induced diarrhea. Chickens were immunized with bovine rotavirus (serotype 1) and the egg yolk immunoglobulins containing a high titer anti-rotavirus neutralizing antibody (CEYI) was obtained. The CEYI was then orally administered to specific-pathogen-free cats, and the cats were infected with human rotavirus. The cats treated with the CEYI remained clinically healthy after challenge, whereas diarrhea occurred in the placebo-fed cats as control. Virus antigens were detected in feces in all the diarrheal cases in the placebo-fed cats but were only sporadically detected in the CEYI-fed cats. However, the cats were only protected against rotavirus infection by the presence in the gut at the time of infection of the antibody. These results suggested that continuous administration of the CEYI is capable of preventing children from diarrhea induced by human rotavirus infection and viral shedding.

Kansenshogaku Zasshi. 1990 Jan;64(1):118-23

Gastroenteritis in suckling mice caused by human rotavirus can be prevented with egg yolk immunoglobulin (IgY) and treated with a protein-bound polysaccharide preparation (PSK).

Oral inoculation of human rotavirus MO strain (serotype 3) into 5-day-old BALB/c mice cause gastroenteritis characterized by diarrhea. Clinical symptoms, histopathological changes in the small intestine, and the detection of rotavirus antigen in enterocytes were all characteristic of rotavirus-induced gastroenteritis. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of immunoglobulin (IgY) from the yolks of eggs of rotavirus-immunized hens. When IgY against a rotavirus strain homotypic to the challenge virus (MO strain) was administered in the mice, complete protection against rotavirus infection was achieved. On the other hand, with oral administration of IgY against a heterotypic strain (serotype 1, Wa strain), a lower protective effect was nevertheless obtained. The four different strains of human rotavirus (Wa, KUN, MO, and ST3) were inactivated in vitro by treatment with PSK, a protein-bound polysaccharide preparation, in a dose-dependent manner. Oral administration of 2.5 mg of PSK caused a therapeutic effect on experimentally MO-infected suckling mice. The antiviral effect of PSK was indicated by the reduction of the duration of diarrhea.

Microbiol Immunol. 1990;34(7):617-29

Oral passive immunization against experimental salmonellosis in mice using chicken egg yolk antibodies specific for Salmonella enteritidis and S. typhimurium.

The efficacy of chicken egg yolk homotypic antibodies specific for outer membrane proteins (OMP), lipopolysaccharide (LPS) or flagella (Fla) in controlling experimental salmonellosis in mice was investigated. Mice challenged orally with 2 x 10(9) c.f.u. of Salmonella enteritidis or 2 x 10(7) c.f.u. of S. typhimurium were orally treated with 0.2 ml anti-OMP, -LPS or -Fla yolk antibody three times a day for three consecutive days. In mice challenged with S. enteritidis, antibody treatment resulted in a survival rate of 80%, 47% and 60% using OMP, LPS or Fla specific antibodies respectively, in contrast to only 20% in control mice. In the S. typhimurium trial, survival rate was 40%, 30% and 20% using OMP, LPS or Fla specific antibodies respectively in contrast to 0% in control mice. In vitro adhesion of S. enteritidis and S. typhimurium to HeLa cells was significantly reduced by anti-OMP, -LPS, and -Fla homotypic antibodies. Results suggest that egg yolk antibodies specific for Salmonella OMP, LPS, and Fla may protect mice from experimental salmonellosis when passively administered orally. Of these antibodies, anti-OMP exhibited the highest level of protection in vivo and in vitro.

Vaccine. 1998 Feb;16(4):388-93

Prevention of fatal salmonellosis in neonatal calves, using orally administered chicken egg yolk Salmonella-specific antibodies.

OBJECTIVE: To protect neonatal calves against fatal salmonellosis within the first 2 weeks after birth, using chicken egg yolk antibodies specific against Salmonella typhimurium or S dublin. ANIMALS: 38 neonatal Holstein calves from Salmonella-free farms.PROCEDURE: After removal of the lipid components with hydroxypropylmethylcellulose phthalate, egg yolk antibodies were spray dried. At 4 days of age, calves were challenge exposed by oral inoculation with 10(11) virulent S typhimurium (experiment 1) or S dublin (experiment 2). Starting from the challenge-exposure day, egg yolk antibody preparations were administered orally 3 times a day for 7 to 10 days.RESULTS: In passive immunization trials, the orally administered antibodies conferred dose-dependent protection against infection with each of the homologous strains of Salmonella. Within 7 to 10 days after challenge exposure, all control calves died, whereas low-titer antibody-treated calves had 60 to 100% mortality. Only fever and diarrhea, but no deaths (P < 0.01), were observed in calves given the highest titer of antibody. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with that in control calves, survival was significantly higher among calves given antibodies with titers of 500 (P < 0.05) and 1,000 (P < 0.01) homotypic for S typhimurium and with titer of 5,000 (P < 0.01) for S dublin. Egg yolk antibodies specific for whole cell S typhimurium or S dublin are protective against fatal salmonellosis when given in sufficiently high concentration, and may be clinically useful during a salmonellosis outbreak.

Am J Vet Res. 1998 Apr;59(4):416-20

Cancer statistics, 2010.

Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data regarding cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,529,560 new cancer cases and 569,490 deaths from cancer are projected to occur in the United States in 2010. Overall cancer incidence rates decreased in the most recent time period in both men (1.3% per year from 2000 to 2006) and women (0.5% per year from 1998 to 2006), largely due to decreases in the 3 major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and 2 major cancer sites in women (breast and colorectum). This decrease occurred in all racial/ethnic groups in both men and women with the exception of American Indian/Alaska Native women, in whom rates were stable. Among men, death rates for all races combined decreased by 21.0% between 1990 and 2006, with decreases in lung, prostate, and colorectal cancer rates accounting for nearly 80% of the total decrease. Among women, overall cancer death rates between 1991 and 2006 decreased by 12.3%, with decreases in breast and colorectal cancer rates accounting for 60% of the total decrease. The reduction in the overall cancer death rates translates to the avoidance of approximately 767,000 deaths from cancer over the 16-year period. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, geographic area, and calendar year. Although progress has been made in reducing incidence and mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons younger than 85 years. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population and by supporting new discoveries in cancer prevention, early detection, and treatment.

CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300