Caffeine ingestion decreases glucose disposal during a hyperinsulinemic-euglycemic clamp in sedentary humans.

The purpose of this investigation was to examine the effect of caffeine (an adenosine receptor antagonist) on whole-body insulin-mediated glucose disposal in resting humans. We hypothesized that glucose disposal would be lower after the administration of caffeine compared with placebo. Healthy, lean, sedentary (n = 9) men underwent two trial sessions, one after caffeine administration (5 mg/kg body wt) and one after placebo administration (dextrose) in a double-blind randomized design. Glucose disposal was assessed using a hyperinsulinemic-euglycemic clamp. Before the clamp, there were no differences in circulating levels of methylxanthines, catecholamines, or glucose. Euglycemia was maintained throughout the clamp with no difference in plasma glucose concentrations between trials. The insulin concentrations were also similar in the caffeine and placebo trials. After caffeine administration, glucose disposal was 6.38 +/- 0.76 mg/kg body wt compared with 8.42 +/- 0.63 mg/kg body wt after the placebo trial. This represents a significant (P < 0.05) decrease (24%) in glucose disposal after caffeine ingestion. In addition, carbohydrate storage was 35% lower (P < 0.05) in the caffeine trial than in the placebo trial. Furthermore, even when the difference in glucose disposal was normalized between the trials, there was a 23% difference in the amount of carbohydrate stored after caffeine administration compared with placebo administration. Caffeine ingestion also resulted in higher plasma epinephrine levels than placebo ingestion (P < 0.05). These data support our hypothesis that caffeine ingestion decreases glucose disposal and suggests that adenosine plays a role in regulating glucose disposal in resting humans.

Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response.

Vol. 34(3) 2004, DOI 10.1002/eji.200324514 Due to a technical error, the wrong affiliations were given for C. Moss and V. Lindo. These are correct as given above. See original article http://dx.doi.org/10.1002/eji.200324514.

Elevated serum parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D in lactating women nursing twins.

The roles of vitamin D, calcitonin, and parathyroid hormone in calcium metabolism during lactation may be more evident in women secreting very large amounts of milk for a number of months, as in mothers nursing twins. We report significant increases in serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D in mothers nursing twins compared to mothers nursing single infants. Serum concentrations of calcium actually increased in both groups during lactation. Maternal intakes of calories, calcium, and phosphorus were significantly higher in mothers nursing twins. Thus, mothers nursing twins were able to compensate for higher calcium losses in breast milk by increased dietary intakes of calcium as well as increased serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D.

Mineral homeostasis during lactation- relationship to serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, parathyroid hormone and calcitonin.

During lactation maternal losses of calcium and phosphorus through human milk average 220 to 340 and 110 to 170 mg/day, respectively. The present study reports maternal serum concentrations of vitamin D metabolites, parathyroid hormone, calcitonin, calcium, magnesium, and phosphorus during the first 6 months of lactation. Serum calcium and magnesium concentrations increased during the first 6 months of lactation. Serum 1,25-(OH)2 vitamin D was increased at 6 months of lactation compared to values in nonpregnant nonlactating controls. During this same period, serum parathyroid hormone decreased slightly and serum calcitonin remained unchanged. Our data do not support the observation that lactation represents a state of physiological hyperparathyroidism. On the contrary, our results suggest that lactating women are able to adequately compensate for the losses of calcium and phosphorus during the early months of lactation, although increased serum 1,25-(OH)2 vitamin D concentrations may be necessary to maintain calcium homeostasis with lactation beyond 6 months.

Vitamin K status of lactating mothers, human milk, and breast-feeding infants.

Hemorrhagic disease of the newborn is a disease of breast-feeding newborns. There is little information on longitudinal breast milk concentrations of phylloquinone (vitamin K1) or the effects of maternal phylloquinone supplements on breast milk. In study part 1, 11 lactating mothers, who received 20 mg of phylloquinone orally, had rises in plasma (less than 1 to 64.2 +/- 31.5 ng/mL by 6 hours) and breast milk concentrations (from 1.11 +/- 0.82 to 130 +/- 188 ng/mL by 12 hours). In part 2, 23 lactating mothers and their infants were observed longitudinally along with a formula-fed control group of infants (n = 11). Mean breast milk concentrations of phylloquinone at 1, 6, 12, and 26 weeks were 0.64 +/- 0.43, 0.86 +/- 0.52, 1.14 +/- 0.72, and 0.87 +/- 0.50 ng/mL, respectively, in the infants fed human milk. Maternal phylloquinone intakes (72-hour dietary recalls) exceeded the recommended daily allowance of 1 microgram/kg per day. Infant phylloquinone intakes did not achieve the recommended daily allowance of 1 microgram/kg per day in any infant. Plasma phylloquinone concentrations in the infants fed human milk remained extremely low (mean less than 0.25 ng/mL) throughout the first 6 months of life compared with the formula-fed infants (4.39 to 5.99 ng/mL). In this small sample, no infant demonstrated overt vitamin K deficiency. Despite very low plasma phylloquinone concentrations, vitamin K supplements (other than in the immediate newborn period) cannot be recommended for exclusively breast-fed infants based on these data.

Vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) status in newborns during the first week of life.

Since 1961 the Committee on Nutrition of the American Academy of Pediatrics has recommended that prophylactic vitamin K be administered parenterally to all newborn infants, although the exact requirement for vitamin K in the newborn infant is unknown. There is little information about the vitamin K1 (phylloquinone, present in green vegetables) and vitamin K2 (menaquinones, synthesized by intestinal flora) status of newborn infants. In this study during the first week of life vitamin K status was assessed by measuring serum concentrations of phylloquinone in 23 mother-infant pairs at the time of birth. Maternal phylloquinone concentration (1.7 +/- 1.0 ng/mL, mean +/- SD) was significantly higher (P less than .02) than cord serum concentration (1.1 +/- 0.6 ng/mL). All infants were then given a standard 1-mg injection of vitamin K1. Ten infants were fed formula (containing 58 ng/mL of vitamin K1) and 13 were exclusively breast-fed. On day 5 of life, serum concentrations of vitamin K1 did not differ between breast-fed (21.0 +/- 12.4 ng/mL) and formula-fed (27.5 +/- 9.7 ng/mL) infants, reflecting the large amounts of parenteral vitamin K1 at birth. During the first week of life, formula-fed infants had much higher fecal concentrations of vitamin K1 (due to large oral intake) and more significant quantities (greater than or equal to 200 pmol/g of dry weight) of fecal menaquinones (reflecting differences in bacterial flora) than did breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypomagnesemia masking the appearance of elevated parathyroid hormone concentrations in familial pseudohypoparathyroidism.

A 21-yr-old postpartum woman was found to be hypocalcemic and hypomagnesemic with a normal serum immunoreactive parathormone level (hypomagnesemic hypoparathyroidism). She was treated with calcitriol, calcium and magnesium. Two yr later the patient's son presented with tetany, hypocalcemia and the physical changes of pseudohypoparathyroidism. Subsequently, the patient's niece and nephew were also diagnosed with pseudohypoparathyroidism (low serum calcium, high serum phosphorus, high circulating immunoreactive parathormone). Re-evaluation of the patient on the above medical therapy showed a normal serum calcium, phosphorus and magnesium levels and an abnormally high serum immunoreactive parathormone level. The patient's magnesium supplementation was discontinued. No change in serum calcium, magnesium or parathormone levels resulted. We think that this patient demonstrates that hypomagnesemia can mask the laboratory presentation of pseudohypoparathyroidism by suppressing secretion of parathormone and further demonstrates that in pseudohypoparathyroidism the parathyroid gland retains its physiologic response to hypomagnesemia.

Caffeine, performance, and metabolism during repeated Wingate exercise tests.

Investigations examining the ergogenic and metabolic influence of caffeine during short-term high-intensity exercise are few in number and have produced inconsistent results. This study examined the effects of caffeine on repeated bouts of high-intensity exercise in recreationally active men. Subjects (n = 9) completed four 30-s Wingate (WG) sprints with 4 min of rest between each exercise bout on two separate occasions. One hour before exercise, either placebo (P1; dextrose) or caffeine (Caf; 6 mg/kg) capsules were ingested. Caf ingestion did not have any effect on power output (peak or average) in the first two WG tests and had a negative effect in the latter two exercise bouts. Plasma epinephrine concentration was significantly increased 60 min after Caf ingestion compared with P1; however, this treatment effect disappeared once exercise began. Caf ingestion had no significant effect on blood lactate, O2 consumption, or aerobic contribution at any time during the protocol. After the second Wingate test, plasma NH3 concentration increased significantly from the previous WG test and was significantly higher in the Caf trial compared with P1. These data demonstrate no ergogenic effect of caffeine on power output during repeated bouts of short-term, intense exercise. Furthermore, there was no indication of increased anaerobic metabolism after Caf ingestion with the exception of an increase in NH3 concentration.

Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance.

This two-part investigation compared the ergogenic and metabolic effects of theophylline and caffeine. Initially (part A), the ergogenic potential of theophylline on endurance exercise was investigated. Eight men cycled at 80% maximum O(2) consumption to exhaustion 90 min after ingesting either placebo (dextrose), caffeine (6 mg/kg; Caff), or theophylline (4.5 mg/kg Theolair; Theo). There was a significant increase in time to exhaustion in both the Caff (41.2+/-4.8 min) and Theo (37.4+/-5.0 min) trials compared with placebo (32.6+/-3.4 min) (P<0.05). In part B, the effects of Theo on muscle metabolism were investigated and compared with Caff. Seven men cycled for 45 min at 70% maximum O(2) consumption (identical treatment protocol as in part A). Neither methylxanthines (MX) affected muscle glycogen utilization (P>0.05). Only Caff increased plasma epinephrine (P<0.05), but both MX increased blood glycerol levels (P<0.05). Muscle cAMP was increased (P<0.05) by both MX at 15 min and remained elevated at 45 min with Theo. This demonstrates that both MX are ergogenic and that this can be independent of muscle glycogen.

Acid-base regulation after maximal exercise testing in late gestation.

This study employed Stewart's physicochemical approach to quantify the effects of pregnancy and strenuous exercise on the independent determinants of plasma H+ concentration ([H+]). Subjects were nine physically active pregnant women [mean gestational age = 33 +/- 1 (SE) wk] and 14 age-matched nonpregnant controls. Venous blood samples and respiratory data were obtained at rest and during 15 min of recovery from a maximal cycle ergometer test that involved 20 W/min increases in work rate to exhaustion. Mean values for [H+], PCO2, and total protein increased, whereas those for bicarbonate concentration ([HCO-3]) and the strong ion difference ([SID]) decreased in the transition from rest to maximal exercise within both groups. At rest and throughout postexercise recovery, the pregnant group exhibited significantly lower mean values for PCO2, [HCO-3], and total protein, whereas [SID] was significantly lower at rest and early recovery from exercise. [H+] was also lower at all sampling times in the pregnant group, but this effect was significant only at rest. Our results support the hypothesis that reduced PCO2 and weak acid concentration are important mechanisms to regulate plasma [H+] and to maintain a less acidic plasma environment at rest and after exercise in late gestation compared with the nonpregnant state. These effects are established in the resting state and appear to be maintained after maximal exertion.

Fast-atom-bombardment mass spectrometry of sulphated oligosaccharides from ovine lutropin.

The positive- and negative-ion f.a.b.-mass spectra and the fragmentation of sulphated oligosaccharides derived from ovine lutropin are described. Negative-ion f.a.b.-m.s. of methylated derivatives offers a sensitive and rapid method for screening glycans for sulphation, for defining the location of sulphated residues, and for sequencing sulphated branches. Positive-ion f.a.b.-m.s. gives complementary data on non-sulphated branches in both complex and hybrid-type sulphated structures.

Do breastfed infants need supplemental vitamins?

Table 2 shows that human milk will not meet the DRI for all vitamins in breastfeeding infants. The most glaring discrepancy between intake and the RDA is for vitamin D, although, as discussed, infants may synthesize this from sunlight exposure. Vitamin K must be given in the newborn period. Deficiencies of other vitamins are rare, especially if mothers are nourished adequately. If breastfeeding infants are to be supplemented with vitamin D or any other vitamins, the standard liquid preparations available all contain large amounts of the water-soluble and fat-soluble vitamins (except for vitamin K), which more than meets the RDA. The milk content of thiamin, pyridoxine, and niacin is correlated highly with maternal intake, and these vitamins are all present in relatively large amounts in standard multivitamin tablets given to lactating mothers. In conclusion, in healthy, breastfed infants of well-nourished mothers, there is little risk for vitamin deficiencies and the need for vitamin supplementation is rare. The exceptions to this are a need for vitamin K in the immediate newborn period and vitamin D in breastfed infants with dark skin or inadequate sunlight exposure.

Vitamin metabolism and requirements in the micropremie.

Vitamin metabolism and requirements are reviewed for the micropremie (1000 Pounds g birthweight), for parenteral and enteral feedings. Recommendations are presented in table format. Human milk fortifiers and special formulas for the preterm infant are reviewed. For parenteral nutrition, only MVI Pediatric is currently available in the United States. Two millimeters per kilogram is recommended for the micropremie as the most satisfactory method of providing supplemental vitamins in total parenteral nutrition solutions.

Vitamin K deficiency and hemorrhage in infancy.

Hemorrhage in the infant from vitamin K deficiency is still a concern in pediatrics. Vitamin K given intramuscularly will largely prevent hemorrhagic disease in the newborn, even in infants who are exclusively breast-fed and are thus at the greatest risk for bleeding. The vitamin K content of human milk is very low compared with standard infant formulas. Results with oral vitamin K prophylaxis, currently used in some countries following the association found in a single report between childhood cancer and intramuscular vitamin K, are far more controversial. Any role of vitamin K in the prevention of IVH in premature infants has not been sufficiently demonstrated. Ongoing developments in this field will lead to improved methods of detecting early vitamin K deficiency and perhaps suitable alternatives to intramuscular vitamin K prophylaxis in the newborn.

Are breast-fed infants vitamin K deficient?

Hemorrhagic disease of the newborn is a disease of breast-fed infants. We have followed 119 exclusively breast-fed infants for up to 6 months of age, who received 1 mg of vitamin K, intramuscularly at birth. As vitamin K is undetectable in cord blood, the only other source in breast-fed infants is human milk. We found persistently low vitamin K1 plasma concentrations in these infants by 4 weeks, and vitamin K concentrations at 2, 4, 6, 8, 12, and 26 weeks averaged 1.18+/-0.99, 0.50+/-0.70, 0.16 +/-0.07, 0.20+/-0.20, 0.25+/-0.34, and 0.24+/-0.23 ng/mL, respectively (lower limit of adult normal = 0.5ng/mL). Vitamin K, in breast milk at 2, 6, 12, and 26 weeks was also very low, averaging 1.17+/-0.70, 0.95+/-0.50, 1.15+/-0.62, and 0.87+/-0.50 mg/mL, respectively. This may be secondary to low maternal vitamin K1 intakes or inability of vitamin K1 to penetrate human milk. We had previously reported a relatively high mean vitamin K intake of 316+/-548 microg in 20 lactating women during the first 6 months of lactation (mean of 60, 3-day dietary recalls) which greatly exceeded the recommended daily allowance of 1 microg/kg/day. The vitamin K content of foods was recently revised downward utilizing newer analytical methods (Booth et al. 1995). Recalculating maternal vitamin K intakes in this original cohort resulted in a dramatic decrease in intake to 74+/-57 microg/day, an amount closely approximating 1 microg/kg/day. We have completed 69 new dietary recalls in 23 lactating women and, combining these data with the previous study, determined a maternal vitamin K1 mean intake of 65+/-48 microg/day (0.8-1.3 microg/kg/day). Other than plasma vitamin K1 concentrations, PIVKA (undercarboxylated prothrombin produced in the absence of vitamin K) is a marker of vitamin K deficiency. We measured PIVKA in 156 cord bloods of full-term infants. Seventy-five (48%) had a significantly elevated PIVKA (> or =0.1 absorption units per milliliter). Seventy-seven of these infants who were exclusively breast-fed subsequently had no detectable PIVKA at 4 weeks, but by 8 weeks, 3 were again positive for PIVKA (prothrombin times were normal). Breast-fed infants may benefit from increased maternal vitamin K intakes (>1 microg/kg/day) during pregnancy and lactation. A supplement of 5 mg of vitamin K to lactating mothers will increase the concentration in human milk to 80.0+/-37.7 ng/mL and significantly increase infant plasma vitamin K (Greer et al. 1997).

Neonatal depression after a protamine sulfate injection. A case report.

The intravenous administration of protamine sulfate in adults has been associated with acute hypotension, bradycardia and anaphylactoid reactions. However, no reports of its use in pregnancy have been available before. We describe a case of severe neonatal depression following maternal protamine sulfate injection immediately prior to delivery.

Differential effects of serial hemodilution with hydroxyethyl starch, albumin, and 0.9% saline on whole blood coagulation.

STUDY OBJECTIVES: To determine by thrombelastography assessed coagulation, the effects of progressive hemodilution with three intravascular volume expanders. DESIGN: Prospective, controlled, whole blood, volumetric ex vivo hemodilution study. SETTING: University of Pennsylvania Medical Center Operating Rooms. PATIENTS: 60 ASA physical status I and II patients; phlebotomy prior to administration of IV fluids or medications. INTERVENTIONS: Analysis of whole blood clotting determined by six thrombelastographic channels for control and five volumetric hemodilutions (11%, 25%, 33%, 50%, and 75%) with 0.9% saline, 5% albumin, and 6% hydroxyethyl starch (n = 20 for each diluent group). MEASUREMENTS AND MAIN RESULTS: Thrombelastographic parameters R (minutes), angle alpha (degree), MA (mm), and lysis (%) were measured and compared to the sample control for each dilution of the same specimen. There was no significant difference between control groups in any thrombelastographic variable (R, angle alpha, MA, or lysis). No changes were seen in any variable from any diluent at 11% hemodilution. Seventy-five percent hemodilution caused significantly hypocoagulable changes from control for all thrombelastographic parameters for all three diluents. Thrombelastographic indices differed significantly from controls at intermediate hemodilutions. Both colloids caused decreases in measured angle alpha and MA at lower hemodilution than did 0.9% saline. Albumin 5% caused significant hypocoagulable changes from control values at lower hemodilution than did either 0.9% saline or 6% hydroxyethyl starch for all thrombelastographic parameters. Saline 0.9% increased angle alpha significantly at 50% hemodilution. Abnormal lysis did not occur at any dilution. Differing ex vivo effects of three different intravascular fluids thrombelastography assessed coagulation are found. CONCLUSION: No differences were found after 11% hemodilution with any volume expanders. Hemodilution with up to 50% saline maintained thrombelastographic indices. Albumin produced early and profound hypocoagulable effects. Significant hypocoagulability occurred for all three diluents at 75% hemodilution. The study supports the use of albumin in patients at risk for thrombosis, and saline in patients with a need for normal hemostasis.

Vitamin K status of lactating mothers and their infants.

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 microg kg(-1) d(-1)) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.