Fred Joseph

Treatment of asthma in children with triamcinolone acetonide aerosol

Triamcinolone acetonide aerosol, 100 microgram qid, was administered for 8 wk to 5 steroid-dependent asthmatic children and 10 who had not previously required continual corticosteroid treatment. Symptomatic control and pulmonary function improved in all 15 children despite discontinuation of oral corticosteroids in 3 of the steroid-dependent children. Determination of morning plasma cortisol concentrations disclosed no evidence of substantial adrenal suppression. Satisfactory symptomatic control has subsequently been maintained for 6 to 32 mo with doses of 100 microgram bid to 300 microgram qid without more extreme changes in plasma cortisol concentrations than were observed during the first 8 wk.

Effects of different levels of caffeine supplemented to the maternal diet on the brains of newborn rats and their dams

At birth, dams with 8 randomly assigned pups were divided into three groups. Dams of group 1 were fed a control diet. Dams of groups 2 and 3 were fed the control diet supplemented with caffeine (1 mg and 2 mg/100 g body weight, respectively). Pups were killed at day 15 and their brains removed. After weighing, brains were analyzed for DNA, protein, cholesterol, zinc and alkaline phosphatase activity. Brain and plasma caffeine levels were also determined on groups 2 and 3. The dams were milked to measure caffeine levels. The brains from the dams were analyzed for the same parameters as the pups. Caffeine levels in group 3 were consistently higher than in group 2. In the pups, body and brain weights were heavier in group 3 than in the controls. Protein and cholesterol concentrations in group 2 were less than either controls or group 3. Alkaline phosphatase activity in group 2 was higher than either controls or group 3. In the dams, DNA concentration in groups 2 and 3 was less than the controls. Protein and cholesterol concentration in group 2 was less than group 3. It was concluded that low levels of caffeine in the maternal diet during lactation could affect various parameters in the newborn brain. These effects were different from those when the dietary caffeine level was doubled. In contrast, the effects of caffeine on brains of the dams were relatively minor.

The effects of caffeine on the maxillary composition in the newborn rat

SummaryThe possible influence of caffeine on maxillary structure was studied. Seventeen pregnant rats at days 9 of gestation were randomly divided into two groups. The dams of group 1 received a 20% protein diet ad libitum throughout the experimental period. The dams of group 2 were pair-fed, with group 1, a 20% protein diet supplemented with 2 mg/100 g body weight (B.W.) caffeine. At birth, pups were mixed within the same group and 8 randomly selected pups were assigned to each dam and continuously fed the respective diet. On day 22, 11 male pups from the control and 12 males from the caffeine group were randomly selected, separated from the dams, and continued to be fed their respective diets. On day 44, a rubber elastic band was inserted between the first and second maxillary right molars. The size of the elastic band was increased throughout the next 5 days. Animals were sacrificed at day 49 and the composition of the maxillas was analyzed. After pulverization, organic and inorganic contents of the bones were measured. Zinc (Zn) and hydroxyproline concentration of the caffeine group showed a significant decrease when compared with those of the controls. However, Ca, P, Mg, and hexosamine concentration showed no difference between the groups. The interdental space measured occlusally and laterally with the visual method, and occlusally in histological sections showed no significant difference between the control and caffeine groups, although variation of the space in the caffeine group was less than in the control group. The present study suggests that caffeine intake during the gestational and lactational period by their dams and the growing period of pups affect the maxillary composition of their offspring.

Interaction between Caffeine Intake and Nutritional Status on Growing Brains in Newborn Rats

The purpose of this study was to determine whether caffeines effects on the growing brain in suckling pups are modified by the nutritional status of the dams. Upon delivery, 8 randomly selected pups were assigned to each dam. They were divided into four groups; group 1 was fed a 20% protein diet as a control; group 2 was fed a 6% protein diet as a malnourished group; group 3 was pair-fed to group 1, but the 20% protein diet was supplemented with caffeine (2 mg/100 g body weight of dams), and group 4 was pair-fed to group 2 with a 6% protein diet with caffeine. At day 15, pups were killed. Brains were removed, weighted and homogenized. Caffeine content of plasma, brain of the pups and maternal milk in groups 3 and 4 were determined. Brains were analyzed for zinc, alkaline phosphatase activity, DNA, protein, and cholesterol. Body weight and protein content of group 3 were greater than group 1, but the zinc contents and alkaline phosphatase activity of group 3 were less than group 1. DNA and cholesterol contents of group 4 were greater than group 2. Supplementation of caffeine to the maternal diet appeared to have various effects on the growing brains of the suckling pups. Caffeines effects and nutritional status are closely interrelated.

Prenatal effects of maternal caffeine intake and dietary high protein on mandibular development in fetal rats.

The purpose of the present study was to determine the effects of caffeine on the mandibles of newborn rats whose dams were given a normal diet (200 g protein/kg diet) compared with those given a high-protein diet (400 g protein/kg diet) during gestation. A total of twenty pregnant Sprague-Dawley rats were randomly divided into four groups of five each. Starting on day 7 of gestation, groups 1 and 2 were fed on control and high-protein diets respectively, and groups 3 and 4 were pair-fed with groups 1 and 2 respectively, but with caffeine added to their diets. The caffeine supplement was 20 mg/kg body-weight. At birth, pups were killed and various measurements of their mandibles were made. The mandibular weights, calcium contents, and alkaline (EC 3.1.3.1) and acid (EC 3.1.3.2) phosphatase activities of the group given the caffeine-supplemented control diet were significantly lower than those of the corresponding unsupplemented group. Alkaline and acid phosphatase activities, collagen synthesis and hydroxyproline contents of the caffeine-supplemented high-protein group were greater than those of the corresponding unsupplemented group, whereas Ca and protein contents of the caffeine-supplemented high-protein group were lower than those of the corresponding unsupplemented group. There were no significant differences in plasma caffeine levels for either dams or pups between the caffeine-supplemented control and high-protein groups. The effects of caffeine on the development of fetal mandibles are apparently modified by different levels of maternal dietary protein.

Effects of Caffeine on the Saturated and Monounsaturated Fatty Acids of the Newborn Rat Cerebellum

Caffeine (1,3,7-trimethylxanthine) is one of the most commonly consumed drugs in our daily life, and its use is increasing. However, very little attention has been paid to its potential effects on early growth and development. Because of the steady increase in breast feeding of infants and because caffeine diffuses readily into breast milk, the present study examined if caffeine intake by newborn rats during lactation would affect the saturated and monounsaturated fatty acids in the growing cerebellum. A total of 10 timed pregnant rats were purchased from the breeder. At birth litters were combined, and 8 pups were randomly assigned to each dam without regard to the sex of the pups. Dams with litters were divided into 2 groups. Dams of group 1 received a 20% protein diet as a control, and dams of group 2 received a 20% protein diet plus caffeine (4 mg/100 g BW). Pups were killed at day 10. The cerebellums were removed, weighed and homogenized. Gas chromatograph-mass spectrometry was used to identify and quantify free fatty acids. Chronic caffeine exposure from birth to day 10 in pups through the maternal milk resulted in a decrease in cerebellum weight, a significant increase in the saturated fatty acids, and a tendency toward an increase of monounsaturated fatty acids. In addition, there was a slight increase of some of the polyunsaturated fatty acids. However, there was no difference in food intake of the lactating dams and weight gain of the pups between the groups. These data indicate that early caffeine intake by the suckling pups alters the composition of fatty acids of the cerebellum; thus, avoidance of caffeine during lactation is critical. The risks and benefits of caffeine administration in premature infants must be carefully evaluated during this rapid period of brain growth.

Interaction between Caffeine and Zinc on Brain in Newborn Rats

The purpose of this study was to determine whether adding zinc to the caffeine-supplemented diet of dams during gestation and lactation would affect brain development in newborn rats. On day 9 of gestation, dams of group 1 were fed to a 20% protein diet as a control. Dams of group 2 were fed a 20% protein diet supplemented with caffeine. Dams of group 3 were fed a 20% protein diet supplemented with caffeine and zinc. The amount of caffeine added to the maternal diet was 2 mg/100 g of body weight. The amount of zinc chloride added to diet was 0.6 g/kg of diet. At birth, 8 randomly selected pups from each group were assigned to each dam of the respective group and were continuously fed the same diet. On day 15, the pups were killed and brains were removed. Zinc, protein, DNA, alkaline phosphatase activity and cholesterol contents were measured. Milk and maternal and neonatal blood were collected to determine caffeine levels. There was a significant correlation between the milk caffeine and brain caffeine concentrations in group 3. A significant correlation between the neonatal plasma caffeine and brain caffeine concentrations was observed in groups 2 and 3. There was no correlation between neonatal brain weight and zinc content per brain in each group. The correlation between neonatal brain weight and alkaline phosphatase activity was significant in groups 1 and 3. The neonatal zinc content and concentration of group 2 was less than that of group 1. The DNA content and concentration of group 3 was greater than that of either groups 1 or 2. Supplementation of zinc to the caffeine-added diet could restore the brain zinc levels observed in brains of newborn rats.

Effects of Caffeine on Heart Mitochondria in Newborn Rats

Caffeine consumption has been implicated in the development of cardiovascular disease. Therefore, in the present study, litters of rats were combined upon birth, and 8 pups were randomly assigned to each dam. Dams with pups were divided into 2 groups: group 1 received a 20% protein diet as a control, and group 2 received the 20% protein diet supplemented with caffeine (4 mg/100 g body weight). Pups from both groups were killed on days 11 and 15. Transmission electron microscopy revealed swollen, disrupted, degenerating mitochondria and intracellular edema in the hearts of rats in the caffeine groups when compared with those of the controls. Plasma Cu concentration was significantly decreased. These results indicate that early exposure to caffeine through maternal milk adversely affects cardiac mitochondria of rat pups and may be associated with decreased plasma Cu levels. It is unclear whether these results apply to the human infant. Interspecies extrapolation from rat to human must be made with caution.

Combined effects of caffeine and malnutrition during pregnancy on suckling behavior in newborn rats

Six groups of pregnant dams were fed a 20%, 12%, and 6% protein diet with and without caffeine (2 mg/100 g b.wt.), starting on day 7 of gestation. At day 18 of gestation, randomly selected dams of each group were used to record prenatal fetal behavior. The remaining dams were continuously fed their respective diets until the birth of their pups. Upon delivery, newborn pups from the dams fed a 20%, 12%, or 6% protein diet with caffeine were placed with foster dams that the dietary regimen during gestation was a 20%, 12%, or 6% protein diet, respectively. Dams fed a noncaffeine diet, along with their newborns, were fed their respective diets until day 15. Suckling behavior tests for newborns were conducted on days 2, 8, and 15. On day 15, both nondeprived and deprived newborn rats were studied. Caffeine in combination with a malnourished diet has different effects on general activity in prenatal stages compared to postnatal stages. Our findings support the view that prenatal exposure to caffeine may produce greater effects because: a) caffeine and its metabolites pass freely into the embryo and attain a concentration slightly lower than in the maternal plasma; and b) caffeine may be poorly metabolized during pregnancy, causing an accumulation in the fetal tissues. Prenatal caffeine at the dosage we have used in combination with malnutrition may produce lasting metabolic alterations in the nervous system related to the emergence of suckling behavior and general motor activity.