Analysis of the efficacy,safety, and regulatory status of novel forms of creatine

Creatine has become one of the most popular dietary supplements in the sports nutrition market. The form of creatine that has been most extensively studied and commonly used in dietary supplements is creatine monohydrate (CM). Studies have consistently indicated that CM supplementation increases muscle creatine and phosphocreatine concentrations by approximately 15–40%, enhances anaerobic exercise capacity, and increases training volume leading to greater gains in strength, power, and muscle mass. A number of potential therapeutic benefits have also been suggested in various clinical populations. Studies have indicated that CM is not degraded during normal digestion and that nearly 99% of orally ingested CM is either taken up by muscle or excreted in urine. Further, no medically significant side effects have been reported in literature. Nevertheless, supplement manufacturers have continually introduced newer forms of creatine into the marketplace. These newer forms have been purported to have better physical and chemical properties, bioavailability, efficacy, and/or safety profiles than CM. However, there is little to no evidence that any of the newer forms of creatine are more effective and/or safer than CM whether ingested alone and/or in combination with other nutrients. In addition, whereas the safety, efficacy, and regulatory status of CM is clearly defined in almost all global markets; the safety, efficacy, and regulatory status of other forms of creatine present in today’s marketplace as a dietary or food supplement is less clear.     

In vivo transformation of human skin with human papillomavirus type 11 from condylomata acuminata.

Human papillomaviruses (HPVs) have been implicated in the development of a number of human malignancies, but direct tests of their involvement have not been possible. We describe a system in which human skin from various sites was infected with HPV type 11 (HPV-11) extracted from vulvar condylomata and was grafted beneath the renal capsule of athymic mice. Most of the skin grafts so treated underwent morphological transformation, resulting in the development of condylomata identical to those which occur spontaneously in patients. Foreskins responded with the most vigorous proliferative response to HPV-11. The lesions produced the characteristic intranuclear group-specific antigen of papillomaviruses. Both dot blot and Southern blot analysis of DNA from the lesions revealed the presence of HPV-11 DNA in the transformed grafts. These results demonstrate the first laboratory system for the study of the interaction of human skin with an HPV. The method may be useful in understanding the mechanisms of HPV transformation and replication and is free of the ethical restraints which have impeded study. This system will allow the direct study of factors which permit neoplastic progression of HPV-induced cutaneous lesions in human tissues.     

Body condition during pregnancy and lactation and reproductive efficiency of mares

In Experiment I, 32 mares were equally allotted to the following treatments: mares fed to A) high body condition from 90 days prepartum to foaling and maintained in high body condition to 90 days postpartum, B) high body condition from 90 days prepartum to foaling and allowed to lose body condition to 90 days postpartum, C) lose body condition from 90 days prepartum to foaling and maintained in low body condition to 90 days postpartum, and D) lose body condition from 90 days prepartum to foaling and allowed to gain weight after foaling to attain a high level of body condition by 90 days postpartum. After three cycles, pregnancy rate at 30 days postovulation was lower (P<0.05) in C mares (50%) than in those in the other three groups (100%). Maintenance of pregnancy to 90 days was also reduced (P<0.05) in C mares (25%) when compared with A, D (both 100%) and B mares (88%). Foal growth to 90 days of age was similar in all treatments. In Experiment II, 927 mares were evaluated for body condition and monitored for reproductive performance. Pregnancy rate was lower (P<0.05) and number of cycles/conception was higher (P<0.05) for barren and maiden mares entering the breeding season in thin condition and for pregnant mares foaling in thin condition (condition score less than 5.0) when compared with mares with a higher level of condition. Also, onset of estrus and ovulation appeared to be delayed in barren and maiden mares entering the breeding season in thin condition. Breeding efficiency was enhanced in mares entering the breeding season or foaling at a condition of 5.0 or above. Initial excess stores of body fat enhanced fertility. There were no detrimental effects of excess body fat stored in late gestation.     

Regulatory role of monomorphic and polymorphic determinants of HLA class I antigens in the proliferation of T cells stimulated by autologous and allogeneic B and T lymphoid cells

Monoclonal antibodies (mAb's) to monomorphic and polymorphic determinants of HLA Class I antigens were shown to inhibit proliferation of T cells stimulated with autologous and allogeneic B and T lymphocytes. Inhibition of proliferative responses was lower when T cells were used as stimulators than when B cells were used. The inhibitory activity was similar for mAb's to monomorphic and polymorphic determinants of HLA Class I antigens, suggesting that the density of antigen-antibody complexes on the cell membrane does not play a major role in the phenomenon. The anti-HLA Class I mAb's exerted their inhibitory effect at the level of both the responding and the stimulating cells. Addition of exogenous interleukin 2 to the mixed cultures did not affect the mAb-mediated inhibition.     

Nonsurgical recovery of degenerative ova from the uteri of mares

Degenerated ova were recovered with and without viable embryos 6 days after ovulation in 30 of 210 collections from 24 of 66 mares. All ova were approximately 150 mum in diameter, with an intact zona pellucida and at various stages of cytoplasmic degeneration. Most of the ova were collapsed, although some had an oval appearance. Most of the ova were from maiden 2-year-old mares. Thirty-four of the ova were recovered from the first or second collections. Two ova were recovered from the third collection from two mares. Two degenerative ova per collection were recovered from five collections; three of these collections also contained viable embryos. Degenerated ova were recovered from three mares twice; but not from consecutive collection attempts. Recovered ova were fixed in 2% glutaraldehyde-PBS for scanning electron microscopy. These data indicate that not all unfertilized ova remain permanently in the oviduct; many traverse it and enter the uterus. Furthermore, these data also suggest that when degenerative ova pass into the uterus they either degenerate further and (or) move into the vagina. This is supported by the fact that not all ova can be accounted for when the uterus and (or) the oviducts are washed.     

Control of estrus in the lactating postpartum mare with fluprostenol (ICI-81,008)

During the 1976 breeding season 68 mares (56 Thoroughbred and 12 Quarter Horse) were allotted to 4 treatment groups. On day 7, 8 or 9 post-ovulation or day 6, 7 or 8 after foal heat each of 28 mares was injected intramuscularly with 250 μg of the prostaglandin analogue ICI-81,008 (generic name fluprostenol). In the second group, 32 mares were bred at foal heat. Group 3 consisted of 9 mares, which were passed at foal heat and bred at the second postpartum estrus. In group four, 12 of the mares which had failed to conceive at foal heat were bred at the second estrus. Twenty-four prostaglandin treated mares returned to estrus 4.2±.4 days post-injection. The interestrual interval was shorter (P<.05) for prostaglandin treated mares (11.4±.6 days) than for previously mated second heat control mares (19.2±2.3). Also, the interval between parturition and second estrus was decreased (P<.05) in treated mares (24.5±.8 days) compared to group three (32.8±2.5 days). Duration of the second postpartum estrus was similar for both treated and control mares. Plasma progesterone levels in prostaglandin treated mares as determined by RIA were 7.5±.5 and 6.9±.5 ng/ml before treatment and at l hour post-injection, then dropped precipitously to near undetectable levels at 48 hours after injection. Pregnancy rate at 45 days was significantly higher (P<.05) in prostaglandin treated mares (78%) as compared to foal heat mares (48%) and mares which were passed at foal heat and bred at the second postpartum estrus (44%).     

Settlement of the serpulid polychaete Hydroides elegans (Haswell) on the arborescent bryozoan Bugula neritina (L.): evidence of a chemically mediated relationship

The tube building polychaete Hydroides elegans Haswell was found living attached to colonies of the arborescent bryozoan Bugula neritina (L.) in Port Shelter, Hong Kong. Field data collected during the period of January through May 1996, showed that H. elegans density reached 77.6 individuals of H. elegans per g wet weight of B. neritina. Density of H. elegans on B. neritina at depths from the surface to 0.5 m was lower than that at depths below 1 m. In January–March, when there were no H. elegans settling on PVC plates or found on natural substrata, numbers on B. neritina were ca. 5 per g wet weight. H. elegans settled on B. neritina and grew rapidly as mean diameter of tubes increased from 605 μm in February to 936 μm in March. In laboratory experiments, larvae of H. elegans settled and metamorphosed on branches of B. neritina and on the bottom of dishes containing B. neritina leachate. Compounds extracted from the leachate of B. neritina induced 74% of H. elegans larvae to metamorphose at a concentration of 16 μg/ml seawater, compared to 5% in dishes containing only filtered seawater (controls). Metabolites from the leachate of B. neritina which were bound to amberlite XAD-2, indicating they are lipophilic in nature, induced over 70% metamorphosis in H. elegans larvae at 56 μg/ml seawater. A biofilm from one of four strains of bacterial isolates associated with the surface of B. neritina induced low levels of metamorphosis in H. elegans larvae, while other bacterial isolates were detrimental to the survival of juvenile H. elegans. Field experiments further demonstrated that H. elegans settled preferentially on Phytagel discs embedded with whole extracts of B. neritina over control Phytagel discs. Metabolites from B. neritina deterred feeding on alginate pellets by assemblages of local fishes in field assays. Metabolites originating from B. neritina, bacteria colonizing B. neritina, and the complex structure of B. neritina contributed to the recruitment of H. elegans to B. neritina surfaces. Hydroides elegans may gain a refuge from predation by associating with B. neritina colonies both from its structural and chemical attributes.     

Monoclonal antibody-mediated neutralization of infectious human papillomavirus type 11.

Monoclonal antibodies recognizing human papillomavirus type 11 (HPV-11) were prepared from BALB/c mice immunized with intact HPV-11 virions obtained from morphologically transformed human foreskin xenografts grown subrenally in athymic mice. Four of five monoclonal antibodies that were reactive by enzyme-linked immunosorbent assay only to intact virions neutralized HPV-11 infectivity in the athymic mouse xenograft system.     

Strength/power augmentation subsequent to short-term training abstinence

Strength augmentation has been demonstrated in resistance-trained men subsequent to 4 days of training abstinence. However, this phenomenon was exhibited in an unusual circumstance in which the exercise test (seated heel raise) primarily involved an isolated skeletal muscle (soleus) that is normally comprised almost exclusively of 1 fiber type. It is unclear if similar results would be found for aggregate muscle actions. Therefore, a comparable study was designed with this in mind. Subjects were apparently healthy, young, strength-trained men (n = 25). All performed various tests of bench press strength at the beginning of their last standardized dynamic constant external resistance (DCER) training session. Subjects were subsequently randomly assigned to 1 of 4 groups and repeated the identical tests at intervals of either 2, 3, 4, or 5 days with no intervening training. Strength tests consisted of 1 repetition maximum (1RM) concentric-only isokinetic bench presses performed at 1.49 and 0.37 m.s(-1) as well as a 1RM DCER bench press. Measures of peak force and power were obtained from the isokinetic tests and maximum load from the DCER test. Results were expressed in both absolute and relative (to body weight) terms. Subsequent to the 4 abstinence intervals, groups performed similarly (p > 0.05) for all dependent variables. Concurrently, however, a small effect size (ES) was found for the group having a 4-day respite for both absolute and relative expressions of peak force and power at the slowest isokinetic bench press velocity. A small ES was also identified for the group having 2 days of rest for relative peak force at the slowest isokinetic test velocity and for relative DCER strength. Therefore, modest and transient strength augmentation appears likely in aggregate muscle actions following 2-4 days of training abstinence in resistance-trained men, but only at relatively slow velocities.     

Effects of resistance exercise intensity on extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activation in men

Extracellular signal-regulated kinase (ERK) 1/2 signaling has been shown to be increased after heavy resistance exercise and suggested to play a role in the hypertrophic adaptations that are known to occur with training. However, the role that ERK1/2 may play in response to lower intensities of resistance exercise is unknown. Therefore, the purpose of this study was to determine the effects of resistance exercise intensity on ERK1/2 activity in human skeletal muscle. Twelve recreationally active men completed separate bouts of single-legged resistance exercise with 8-10 repetitions (reps) at 80-85% 1 repetition maximum (1RM) (85%) and 18-20 reps at 60-65% 1RM (65%) in a randomized crossover fashion. For both resistance exercise sessions, vastus lateralis biopsies and blood draws were taken immediately before exercise (PRE) and at 30 minutes (30MPST), 2 hours (2HRPST), and 6 hours (6HRPST) post exercise, with an additional blood draw occurring immediately after exercise (POST). The phosphorylated levels of pIGF-1R, pMEK1, pERK1/2, and activated Elk-1 were assessed by phosphoELISA, and serum insulin-like growth factor 1 (IGF-1) was assessed via enzyme-linked immunosorbent assay. Statistical analyses used a 2 × 4 (muscle responses) and 2 × 5 (serum responses) multivariate analysis of variance on delta values from baseline (p < 0.05). Both exercise intensities significantly increased the activity of insulin-like growth factor 1 receptor (IGF-1R), mitogen-activated protein kinase 1, ERK1/2, and Elk-1, with peak activity occurring at 2HRPST (p < 0.001). However, 65% resulted in a preferential increase in IGF-1R and Elk-1 activation when compared with 85% (p < 0.05). No differences were observed for serum IGF-1 levels regardless of intensity and time. These findings demonstrate that resistance exercise upregulates ERK1/2 signaling in a manner that does not appear to be preferentially dependent on exercise intensity.