Postnatal oxytocin alleviates adverse effects in adult rat offspring caused by maternal malnutrition

Repeated oxytocin administration to adult rats causes a long-term decrease of plasma levels of corticosterone and blood pressure and stimulates growth and fat retention. Maternal undernutrition increases blood pressure and plasma corticosterone in adult offspring. We hypothesized that oxytocin treatment early in life would alleviate adverse effects of intrauterine food restriction. Male pups from ad libitum-fed and food-restricted (fed 60% of ad libitum intake) dams were injected with oxytocin or saline in days 1-14 after birth. At 4 mo, blood pressure, plasma levels of corticosterone, and adiposity were assessed. Oxytocin treatment decreased blood pressure independently of nutrition, whereas the increased plasma levels of corticosterone were lowered to normal levels in food-restricted offspring. Blood pressure and adiposity were not affected by in utero food restriction, whereas birth and adult weight were. In conclusion, postnatal events may alleviate adverse effects caused by in utero food restriction. In contrast to more severe food restriction, a moderate general food restriction during gestation had no effect on blood pressure in the offspring.     

Photoperiod controls the induction,retention, and retrieval of antigen-specific immunological memory

Changes in day length affect several measures of immunity in seasonally breeding mammals. In Siberian hamsters (Phodopus sungorus), short day lengths suppress specific secondary antibody responses to the keyhole limpet hemocyanin (KLH) antigen and enhance cutaneous delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). These experiments tested whether day length affects secondary antibody and DTH responses by altering immune function solely during the interval after the initial exposure to each antigen, solely during the interval after the second exposure, or during both stages of the respective immune responses. Adult male Siberian hamsters were exposed to either a long (16 h light/day; LD) or a short (8 h light/day; SD) photoperiod for 7.5 wk before receiving an initial exposure to each antigen (KLH injection, cutaneous DNFB treatment; separate groups of animals for each antigen). A subset of LD hamsters was transferred to the SD photo-period, and a subset of SD hamsters was transferred to the LD photoperiod. Other hamsters remained in LD or SD. Eight weeks later, all hamsters were challenged with a second subcutaneous injection of KLH or a second application of DNFB to the ear, and immune responses were measured. Exposure to SD during the primary antibody response did not affect secondary IgG responses, but SD exposure during the secondary response significantly suppressed IgG production independent of day length during the initial KLH treatment. In contrast, exposure to SD during the DNFB challenge enhanced the ensuing DTH response, but this enhancement depended on the photoperiod prevailing during the initial exposure. Exposure to SD during the sensitization stage did not enhance DTH in hamsters subsequently exposed to LD. The data suggest that short photoperiods have enduring effects on immune responsiveness and on the establishment and retention of immunological memory.     

Ethane production rate in vivo is reduced with dietary restriction

Dietary restriction without malnutrition prolongs life and has a beneficial effect on age-related diseases and metabolic derangements. To test the effect of food restriction on ethane production rate, ethane exhalation was measured in rats with partial food restriction. Ethane production rate in room air in rats fed 60% of food consumed by ad libitum-fed animals for 2 wk was significantly reduced (3.50 +/- 0.25 vs. 5.21 +/- 0.34 pmol.min-1.100 g body wt-1, P less than 0.01). In 100% oxygen, ethane production in food-restricted rats was not different from that of ad libitum-fed rats (21.81 +/- 1.25 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Fifteen hours of fasting compared with ad libitum feeding reduced ethane production modestly in room air (4.37 +/- 0.45 vs. 5.21 +/- 0.34 pmol.min-1.100 g-1) and more significantly in 100% oxygen (12.37 +/- 0.78 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Thus, in 100% oxygen, 15 h of fasting, compared with ad libitum feeding, resulted in an approximately 40% decrease in ethane production rate. It is concluded that short-term food restriction significantly reduces ethane exhalation rate in rats when measured in room air.     

Oral immunization in adult mice to live and heat-killed Vibrio cholerae

Effects of systemic and intestinal local immune responses in mice fed ad libitum and forcedly with live or heat-killed Vibrio cholerae on the elimination of vibrios from the intestine were investigated. In mice fed with live vibrios, ad libitum feeding could induce potential delayed-type hypersensitivity and rapid production of vibriocidal antibody in the serum whereas forcedly feeding suppressed the delayed-type hypersensitivity and retarded the antibody production. In contrast, when killed microorganisms were used as antigens, significant delayed-type hypersensitivity and rapid response of vibriocidal antibody were induced in forcedly fed mice although ad libitum feeding suppressed the induction of the delayed-type hypersensitivity and retarded the production of vibriocidal antibody. The elimination of vibrios from the intestine of mice was promoted in both mice groups fed ad libitum and forcedly with live vibrios but not with killed microorganisms. Total IgA in the intestinal contents of mice fed with live vibrios both ad libitum and forcedly were higher than those of mice fed with killed antigens. In addition, when the extracts of intestinal contents were absorbed by live antigens, IgA contents in mice fed with live vibrios were reduced more markedly than those in mice immunized orally by the feeding with killed antigens. These findings suggested that the elimination of vibrios from the organ was closely related to local IgA antibody response to heat-labile substance of live Vibrio cholerae.     

Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin

Cholera toxin (CT) has been found to be an extremely potent immunogen for mucosal IgA responses when administered via the intestine. This study has examined both mucosal and systemic immune responses after feeding CT and compared these responses with those obtained after feeding keyhole limpet hemocyanin (KLH), another protein that is strongly immunogenic in mice. Feeding CT to mice resulted not only in IgA antibody in intestinal secretions but also resulted in substantial plasma IgG and IgA antibody levels. Feeding KLH in much larger quantity resulted in little or no antibody response in intestinal secretions or plasma. Lymphoid cells from various tissues of mice fed CT were cultured in vitro for 10 days and the supernatant was tested for antibody to CT. Spontaneous antibody synthesis (no antigen added to cultures) was present in cultures of each cell type, but IgG anti-CT was found mainly in cultures of spleen and mesenteric lymph node cells and IgA anti-CT mainly in cultures of Peyer's patch and lamina propria cells. Peyer's patch cells cultured with CT as antigen synthesized both IgG and IgA anti-CT, suggesting that the antibody response to both isotypes originated in this site. Helper T cell activity for both IgA and IgG anti-CT was detected in spleens, mesenteric lymph nodes, and Peyer's patches. Lastly, when KLH and CT were fed to mice at the same time, an intestinal IgA anti-KLH and plasma IgG anti-KLH response was stimulated, a response pattern similar to that occurring to CT after CT was fed alone. We conclude that mucosal stimulation by CT generates both a systemic IgG and mucosal IgA response to this antigen, and that CT can cause a similar pattern of response to an unrelated protein antigen when both are administered into the intestine at the same time. The data favor the idea that both the IgG and IgA responses originate in GALT and then disseminate to other tissues. We propose that CT accomplishes these effects by altering the regulatory environment within GALT.     

Reproductive responses to variation in temperature and food supply by house mice: II. Lactation

Lactating HS/Ibg house mice housed at 21 degrees C and 5 degrees C were assigned to 3 feeding regimes: ad libitum, daily rations of 80% of ad libitum, or 60% of ad libitum beginning on the day that they bore litters. Significant interaction between temperature and food restriction was found for litter survivorship, pup survivorship, litter size, female body weight, and cumulative biomass production. The interaction was due to a magnification of the effects of food restriction at the colder temperature: i.e. mice fed ad libitum were similar at the two temperatures, mice fed the 80% ration differed, and mice fed the 60% ration differed to a greater extent. The dominant response to food restriction was cannibalism by females, which might be associated with the rate of loss in body weight by the female on the days preceding cannibalism of one or more pups. Incidents of cannibalism tended to involve a limited number of pups and to be repeated until a sustainable litter size was reached. In 3 of the food-restricted treatments, females weaned relatively large litters of relatively small pups, but in the most severe treatment (in the group fed the 60% ration at 5 degrees C), the females weaned small litters of large pups. The patterns of cannibalism and variable relative investment in individual pups reflect the aggressive breeding strategy of this classic colonizing species.     

Transition in the Character of Immunological Memory in Mice after Immunization

The immunological memory in antibody response of mice to bovine serum albumin was investigated at the level of IgM and IgG antibody-forming cells. The antigen at a dose much lower than required for eliciting a detectable level of the primary antibody response could latently activate the immune machinery to an extent adequate for specific recall, whereas higher doses of antigen were effective in evoking strong anamnestic response. The potentiality to develop the anamnestic response was found even in the latent phase of the primary antibody response and was maintained for more than 2 months. The immunological memory acquired in an early phase after the primary immunization mainly involved IgM antibody response and late memory concerned IgG response.     

The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats

In operant conditioning experiments, two methods are commonly used to motivate laboratory rats to perform designated tasks. The first is restricting food so that rats are forced to lose 20% of body weight within one week, followed by maintenance at 80% of the baseline weight for the remainder of the experiment. The second is restricting access to water to 15 min in each 24 h period. These methods are effective in motivating the animals. There is, however, little information available on the effects on performance in tests of behaviour that are not related to operant conditioning. In addition, it is not clear if these commonly used methods of food and water restriction will lead to physiological stress as indicated by an elevation of serum corticosterone. Male rats were either food-restricted to reduce and maintain their weight at 80% of baseline weight, or were restricted to 15 min access to water every 24 h. Activity in the open field was significantly greater in food-restricted rats than in water-restricted or control rats, but freezing behaviour was similar in all experimental groups. Food-restricted rats had a higher mean serum corticosterone level than water-restricted and control rats 37 days after the start of the experimental period. These data suggested that chronically restricting food and maintenance of body weight at 80% of baseline body weight led to significant behavioural changes and physiological stress. In contrast, water restriction did not lead to changes in behaviour or corticosterone levels. A second experiment was conducted to compare the effects of food restriction to 80% of baseline body weight, as described above, with a less stringent protocol in which test rats were initially reduced to 80% of baseline weight, but were then maintained at 80% of an ad libitum fed control rat's weight. Serum corticosterone levels and adrenal gland weights were measured after the initial week of forced weight loss and after maintenance for 21 days. Forced loss of 20% of body weight in the first week led to significantly increased serum corticosterone levels and adrenal gland weights compared to ad libitum fed controls. Serum corticosterone levels and adrenal gland weights in rats maintained at 80% of their initial body weight for 21 days remained higher than ad libitum fed control rats. However, rats maintained at 80% of an ad libitum fed control rat's weight did not differ from control rats in serum corticosterone levels or adrenal gland weights at the end of the 21-day study period. Adjustment of the feeding regimen in this manner eliminated physiological evidence of chronic stress.     

Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats

Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent postischemic dysfunction in the aging heart. This phenomenon could be due to the reduction of cardiac norepinephrine release, and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction. We investigated the effects on mechanical parameters of PC against 20 min of global ischemia followed by 40 min of reperfusion in isolated hearts from adult (6 mo) and "ad libitum"-fed and food-restricted senescent (24 mo) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. Final recovery of percent developed pressure was significantly improved after PC in adult hearts versus unconditioned controls (85.2 +/- 19% vs. 51.5 +/- 10%, P < 0.01). The effect of PC on developed pressure recovery was absent in ad libitum-fed rats, but it was restored in food-restricted senescent hearts (66.6 +/- 13% vs. 38.3 +/- 11%, P < 0.05). Accordingly, norepinephrine release significantly increased after PC in both adult and in food-restricted senescent hearts, and depletion of myocardial norepinephrine stores by reserpine abolished the PC effect in both adult and in food-restricted senescent hearts. We conclude that PC reduces postischemic dysfunction in the hearts from adult and food-restricted but not in ad libitum-fed senescent rats. Despite the possibility of multiple age-related mechanisms, the protection afforded by PC was correlated with increased norepinephrine release, and it was blocked by reserpine in both adult and food-restricted senescent hearts. Thus caloric restriction may restore PC in the aging heart probably via increased norepinephrine release.     

Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men.

The aging immune system is characterized by the progressive decline in the antibody and T cell-mediated responses to antigen. Little is known, however, about the benefits of exercise in aging on the generation of a primary immune response to antigen and the subsequent antibody and memory T cell-mediated response. Most in vivo immune research to date has utilized vaccines or recall antigens to elicit an immune response. Therefore, the purpose of this experiment was to examine the association of aging and physical activity on the primary antibody and T cell response to the novel protein antigen keyhole-limpet hemocyanin (KLH). Forty-six physically active and sedentary, young (20-35 yr) and older (60-79 yr) men were recruited. Subjects were intramuscularly immunized with 100 microg of KLH, and blood samples were collected at days 0, 7, 14, 21, and 28. Samples were measured for anti-KLH IgM, IgG, IgG1, and IgG2 by ELISA. On day 21 after intramuscular KLH administration, subjects received an intradermal injection with 1 microg of KLH of inflammation recorded at 24, 48, 72, 96, and 120 h to assess anti-KLH delayed-type hypersensitivity response. There was a significant reduction in all anti-KLH measures with aging except for anti-KLH IgG2. The physically active older group had significantly higher anti-KLH IgM, IgG, IgG1, and delayed-type hypersensitivity responses, but not IgG2 compared with the sedentary older group. In conclusion, regular physical activity in older men is associated with a more robust immune response to novel antigenic challenge.     

Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks

Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone.     

Testicular regression in response to food restriction and short photoperiod in white-footed mice (Peromyscus leucopus) is mediated by apoptosis

Short day lengths or reduced food availability are salient cues for small mammals that breed seasonally. Photoperiod-mediated gonadal regression in white-footed mice (Peromyscus leucopus) is a slow, orderly process that involves testicular apoptosis. Testicular regression in response to restricted caloric intake is relatively rapid, and it is generally reversed quickly by ad libitum (ad lib) feeding. To determine the contribution of apoptotic cell death during food restriction, and to examine possible interactions with photoperiod, mice housed in long (16L:8D) or short (8L:16D) photoperiods were fed either ad lib or 70% of their average ad lib intake. Testes were removed at 2, 4, 6, or 8 wk of experimental treatment. Apoptotic activity was determined by in situ TUNEL labeling and assessment of DNA laddering. Significant (P < 0.05) gonadal regression in response to short days was first detected at 8 weeks in mice fed ad lib. Food-restricted, long-day mice also showed significant testicular regression at 8 wk. Combined exposure to short day lengths and food restriction resulted in significant testicular regression at 6 wk (P < 0.05). TUNEL labeling was slightly, though significantly, elevated in germ cells at 2 and 4 wk in long-day food-restricted mice (P < 0.05). TUNEL labeling was also elevated in short-day food-restricted males at these early times but then increased nearly 5-fold at 6 and 8 wk in these mice (P < 0.001). DNA laddering confirmed elevated apoptosis. Overall apoptotic activity negatively correlated with paired testis mass, plasma testosterone, and spermatogenic index measurements in both ad lib and food-restricted males. Few histological markers of necrotic cell death were observed in any group. Taken together, these results suggest that testicular regression in response to limited caloric intake or short days is mediated by apoptosis.     

Effects of exercise on immune functions of undernourished mice.

Regular moderate exercise may modulate the response to a stressor and thus improve immune functions in conditions commonly associated with immunodepression and elevated levels of stress hormones. For example, anorexia nervosa patients, many of whom engage in regular aerobic exercise, generally have normal immune function and viral disease resistance in spite of their severe undernutrition. To test the hypothesis that exercise can prevent undernutrition-induced immunodepression, mice were fed a nutritionally complete, semi-purified diet, either ad libitum or in restricted quantities to induce 25% loss of initial weight over 3 weeks. Half the animals from each dietary group were run on a treadmill for 30 min/day, 5 days/week. Exercise had no effect on several measures of nutritional status. Spleen weight and blastogenic response to lipopolysaccharide were significantly increased by exercise in undernourished mice. In vivo antibody response to sheep red blood cells, and in vitro splenic responses to concanavalin A and phytohemagglutin were not significantly affected by exercise. Serum corticosterone level was increased by food restriction and significantly decreased by exercise in the undernourished mice. Within a treatment group there were no significant correlations between serum corticosterone level and any immune system measure. Hypothalamic concentration of uric acid was increased in food restriction groups and concentration of norepinephrine was increased in exercise groups. The results suggest that regular exercise may help prevent undernutrition-induced immunodepression, possibly through modulation of the stress response.     

Patterns of the forming of an immunologic memory to staphylococcal corpuscular antigen

The experiments carried out on inbred mice have revealed that the level of the immunological memory to staphylococci depends on the intensity of the antigenic stimulation; high priming dose of antigen proving to be the most effective one. The opposite character of immune responsiveness observed during primary antibody response to particulate staphylococcal antigen in C3H and A/Sn mice increased after the second immunization. It is established that immunological memory to staphylococci may be induced in genetically athymic mice. Many antibody-forming cells are found in the bone marrow of the secondary immunized mice. This phenomenon may be due to the repopulation of the bone marrow tissue by recirculating memory cells.     

Food restriction compromises immune memory in deer mice (Peromyscus maniculatus) by reducing spleen-derived antibody-producing B cell numbers

Immune activity is variable in many wild animals, despite presumed strong selection against immune incompetence. Much variation may be due to changes in prevalence and abundance of pathogens (and/or their vectors) in time and space, but the costs of immune defenses themselves may also be important. Induction of immune activity often increases energy and protein expenditure, sometimes to the point of compromising fitness. Whether immune defenses are expensive to maintain once they are generated, however, is less well appreciated. If so, organisms would face persistent challenges of allocating resources between immunity and other expensive physiological processes, which would mandate trade-offs. Mild food restriction (70% ad lib. diet) reduces secondary antibody responses in deer mice (Peromyscus maniculatus), functionally representing a cost of immune memory. In this study, we asked whether compromised immune memory was mediated by a decrease in size of the B cell population responsible for producing antibodies (i.e., spleen-derived B lymphocytes producing immunoglobulin G [IgG]). Two weeks of food restriction reduced total splenocytes, total splenic B lymphocytes (B220+ cells), and splenic B lymphocytes producing IgG (B220+/IgG+ cells) but did not affect body mass or two circulating antibody subclasses (IgG1 and IgG2a) in deer mice. These results further indicate that maintenance of immune memory is expensive and may be subject to trade-offs with other physiological processes.     

Differential effects of amount of feeding on cell proliferation and progesterone production in response to gonadotrophins and insulin-like growth factor I by ovarian granulosa cells of broiler breeder chickens selected for fatness or leanness.

Strain differences in reproductive performance were demonstrated between broiler breeder female chickens selected for growth (GL line) or for food conversion efficiency (FC line) and the improvement in reproductive performance due to feed restriction also differed significantly. Feed allowance effects on the maturation of ovarian follicles, the incidence of atresia and egg production differed between the two lines exposed to similar feeding protocols. Feed restriction reduced body weights significantly and to a similar extent in both GL and FC lines. The number of normal and atretic yellow follicles was significantly higher under ad libitum feeding and in GL line than it was in the FC line. In both lines, feed restriction decreased multiple ovulation and increased egg production. In culture, granulosa cells from the three largest follicles (F1, F2 and F3) increased progesterone production in response to LH, FSH and insulin-like growth factor I but responses were different between the GL and FC lines fed either ad libitum or restricted diets. Granulosa cells from the two or three largest follicles in GL and FC (ad libitum) lines produced similar amounts of progesterone in response to LH, FSH and insulin-like growth factor I whereas, in restricted birds, the progesterone production was of the rank order F1 > F2 > F3 in both lines. The responsiveness of the GL line fed ad libitum was higher for LH than for either FSH or insulin-like growth factor I but in the GL line fed a restricted diet, it was high for all the hormones. In the FC line, responses to LH, FSH or insulin-like growth factor I were high in ad libitum-fed birds, but low in birds fed a restricted diet for all hormones. Insulin-like growth factor I combined with LH or FSH significantly increased the progesterone production of granulosa cells from birds fed restricted diets of both lines and this effect increased with increasing follicular size. There was a lack of interaction between insulin-like growth factor I and LH or FSH in the regulation of progesterone production by birds of both lines fed ad libitum. Insulin-like growth factor alone or in combination with LH or FSH increased granulosa cell proliferation in birds fed ad libitum more than it did in birds fed restricted diets. The greater proliferation rate of granulosa cells of chickens fed ad libitum, in response to insulin-like growth factor I alone or in combination with gonadotrophins, leading to the simultaneous differentiation of two or three large follicles with high progesterone production in response to LH or insulin-like growth factor I, accelerates the rate of maturation of follicles. This may also be the major cause of erratic and multiple ovulations in broiler breeder female chickens fed ad libitum. In conclusion, insulin-like growth factor I, alone or in combination with LH or FSH, is an important component in the control mechanisms for follicular development in broiler breeder hens. It is this component that is targeted by feed allowance and inadvertently altered by selection for growth.     

Immunological function of food-restricted germfree and specific pathogen-free mice.

The effects of food restriction on immune function was investigated in germfree (GF) and specific pathogen-free (SPF) mice. They were maintained from five weeks of age under either full-fed or food-restricted conditions to 4.5 grams per day (equivalent to approximately 80% of full-fed intake) of a commercial diet. Longest survival rate was attained in food-restricted SPF mice followed by food-restricted GF, full-fed GF, and full-fed SPF animals. Food-restricted GF mice showed shorter survival rate than their SPF counterparts. This result suggests that food restriction may be just as effective as GF status for extending life span. Immune function declined significantly with age in full-fed groups of GF and SPF mice. In both food-restricted GF and SPF mice, mitogenic response to concanavalin A or lipopolysaccharide and antibody response to sheep red blood cells were lower early in life and became higher later in life as compared with full-fed mice. Hence, the maintenance of effective immunological function until old age may be the reason for food-restricted groups to live slightly longer than full-fed groups.     

The ovine nasal mucosa: an alternative tissue site for mucosal immunization

The ovine nasal mucosal environment has histological and ultrastructural features that resemble well-known inductive sites of mucosa-associated lymphoid tissue. In the present study, the nasal mucosa was assessed as a potential mucosal tissue site for delivering vaccines to sheep. Sheep were immunized by either injection with the model antigen, Keyhole Limpet Haemocyanin (KLH), and aluminium hydroxide gel (alum) or by aerosol spray with KLH with and without cholera toxin (CT). Sheep immunized by injection with KLH/alum and aerosol spray with KLH/CT induced strong anti-KLH IgG and IgA serum antibody responses as well as specific T cell memory. Anti-KLH IgG1 responses were significantly higher following immunization by injection and no significant differences in anti-KLH IgG2 responses were detected between groups. Sheep immunized with KLH by aerosol spray without CT did not produce serum antibody and T cell memory responses. Antibody-secreting cells were present in the parotid lymph nodes (draining lymph nodes) of sheep immunized with KLH/alum and KLH/CT, but secreted only Ag-specific IgG1, and not IgG2 or IgA. These results suggest that aerosolization of soluble antigen formulations with CT may provide an alternative method of delivering nasal vaccines to sheep and other large animal species, and that further improvements in antigen penetration of nasal tissues may dramatically improve the strength of the immune response.     

Adjuvant Action of Capsular Polysaccharide of Klebsiella pneumoniae on Antibody Response

A study was performed to clarify the roles of primary and secondary injections of antigen and adjuvant (capsular polysaccharide of Klebsiella pneumoniae, CPS-K) in induction of antibody responses and in development of immunological memory in mice to bovine serum albumin (BSA). A primary injecion of BSA alone neither induced significant primary antibody response nor increased immunological memory for a secondary antibody response but, if primary injections of BSA and CPS-K were performed simultaneously, high antibody responses were induced. Moreover, a prior injection of BSA alone or CPS-K alone decreased the level of primary antibody response and the degree of increase in memory following the subsequent injection of BSA mixed with CPS-K. In contrast, a secondary injection of BSA alone into mice once primed with a mixture of BSA and CPS-K elicited very high secondary type antibody response and increased secondarily the memory for a tertiary antibody response. Injection of CPS-K simultaneously with or shortly before or after the secondary injection of BSA did not increase the level of the secondary antibody response and the degree of the secondary increase in memory. Augmentation of the secondary antibody response was elicited by simultaneous injection of CPS-K only when the secondary response was induced inadequately by a suboptimum or supraoptimum dose of antigen.     

Acute food restriction increases collagen breakdown and phagocytosis by mature decidual cells of mice

An ultrastructural study was undertaken on antimesometrial mature decidual tissue of fed and food-restricted mice, on day 9 of pregnancy. The mean ad libitum food intake was established on mice from the 8th till the 9th day of pregnancy. Fed mice were used as controls. Experimental animals were divided into two groups: one was allowed to feed 25% of normal diet and the other 50%. Extracellular collagen fibrils were scarce in fed animals and conspicuous in food restriction. Granular electron-dense deposits and filamentous aggregates of disintegrating collagen fibrils were observed in all food-deprived mice but were rarely noted in fed animals. Intracellular vacuolar structures exhibited other typical cross-banded collagen immersed in finely granular electron-translucent material (clear vacuole) or electron-dense material containing collagen fibrils with a faint periodicity (dark vacuole). The clear and dark vacuoles were scarce in fed animals and evident in food-restricted mice, mainly in those 25% food restricted. Although collagen breakdown may be part of the normal process of decidual tissue remodelling our results suggest that it is enhanced in food-restricted animals. Thus it seems that collagen breakdown is a normal mechanism that may be regulated by the food intake of the pregnant animal.