IOC consensus statement: dietary supplements and the high-performance athlete.

Nutrition usually makes a small but potentially valuable contribution to successful performance in elite athletes, and dietary supplements can make a minor contribution to this nutrition programme. Nonetheless, supplement use is widespread at all levels of sport. Products described as supplements target different issues, including (1) the management of micronutrient deficiencies, (2) supply of convenient forms of energy and macronutrients, and (3) provision of direct benefits to performance or (4) indirect benefits such as supporting intense training regimens. The appropriate use of some supplements can benefit the athlete, but others may harm the athlete's health, performance, and/or livelihood and reputation (if an antidoping rule violation results). A complete nutritional assessment should be undertaken before decisions regarding supplement use are made. Supplements claiming to directly or indirectly enhance performance are typically the largest group of products marketed to athletes, but only a few (including caffeine, creatine, specific buffering agents and nitrate) have good evidence of benefits. However, responses are affected by the scenario of use and may vary widely between individuals because of factors that include genetics, the microbiome and habitual diet. Supplements intended to enhance performance should be thoroughly trialled in training or simulated competition before being used in competition. Inadvertent ingestion of substances prohibited under the antidoping codes that govern elite sport is a known risk of taking some supplements. Protection of the athlete's health and awareness of the potential for harm must be paramount; expert professional opinion and assistance is strongly advised before an athlete embarks on supplement use.

The effect of prolonged dietary nitrate supplementation on atherosclerosis development.

BACKGROUND: Short term dietary nitrate or nitrite supplementation has nitric oxide (NO)-mediated beneficial effects on blood pressure and inflammation and reduces mitochondrial oxygen consumption, possibly preventing hypoxia. As these processes are implicated in atherogenesis, dietary nitrate was hypothesized to prevent plaque initiation, hypoxia and inflammation. AIMS: Study prolonged nitrate supplementation on atherogenesis, hypoxia and inflammation in low density lipoprotein receptor knockout mice (LDLr(-/-)). METHODS: LDLr(-/-) mice were administered sodium-nitrate or equimolar sodium-chloride in drinking water alongside a western-type diet for 14 weeks to induce atherosclerosis. Plasma nitrate, nitrite and hemoglobin-bound nitric oxide were measured by chemiluminescence and electron parametric resonance, respectively. RESULTS: Plasma nitrate levels were elevated after 14 weeks of nitrate supplementation (NaCl: 40.29 ± 2.985, NaNO3: 78.19 ± 6.837, p < 0.0001). However, prolonged dietary nitrate did not affect systemic inflammation, hematopoiesis, erythropoiesis and plasma cholesterol levels, suggesting no severe side effects. Surprisingly, neither blood pressure, nor atherogenesis were altered. Mechanistically, plasma nitrate and nitrite were elevated after two weeks (NaCl: 1.0 ± 0.2114, NaNO3: 3.977 ± 0.7371, p < 0.0001), but decreased over time (6, 10 and 14 weeks). Plasma nitrite levels even reached baseline levels at 14 weeks (NaCl: 0.7188 ± 0.1072, NaNO3: 0.9723 ± 0.1279 p = 0.12). Also hemoglobin-bound NO levels were unaltered after 14 weeks. This compensation was not due to altered eNOS activity or conversion into peroxynitrite and other RNI, suggesting reduced nitrite formation or enhanced nitrate/nitrite clearance. CONCLUSION: Prolonged dietary nitrate supplementation resulted in compensation of nitrite and NO levels and did not affect atherogenesis or exert systemic side effects.

Metabolic long-term follow-up of functioning simultaneous pancreas-kidney transplantation versus pancreas transplantation alone: insights and limitations.

BACKGROUND: Pancreas transplantation involves a set of procedures that, in some cases, lead to different complications and outcomes. The aim of this study was to analyze the long-term effects of pancreas transplantation regarding carbohydrate and lipid metabolism parameters to determine differences between simultaneous pancreas-kidney (SPK) transplantation and pancreas transplantation alone (PTA). METHODS: Sixty-four patients (46 SPK and 18 PTA), with an immunosuppression protocol based on tacrolimus plus mycophenolate mofetil and prednisone, were evaluated for at least 1 year after transplantation. No patient made use of any hypoglycemic or hypolipidemic drugs. Comparisons were performed between SPK and PTA patients using the chi-square test, Fischer's exact test, and unpaired Student's t test, as appropriate. RESULTS: Patients were 39.8+/-9.3 years old, predominantly male (60.9%), with a mean follow-up of 25.4+/-10.4 months after transplantation. The PTA group exhibited worse renal function and higher tacrolimus levels than the SPK group. Fasting glucose, 2 hr plasma glucose after overload, C-peptide, and HbA1C were within the normal range, with no statistically significant differences between the PTA and SPK groups. Insulin (INS) and the homeostasis model assessment of INS resistance index were above the normal range in both the groups. Lipids were also similar between groups. CONCLUSIONS: The majority of patients with long-term functioning pancreas transplant achieved good glucose control without use of exogenous INS or oral antidiabetic drugs, although they were hyperinsulinemic. There were no significant differences concerning glucose and lipid parameters between the SPK and PTA groups, even though the PTA patients exhibited higher tacrolimus levels and worse renal function.

[Cutaneous non-Langerhans cells histiocytoses as cause of central diabetes insipidus]. / Histiocitose cutânea não-Langerhans como causa de diabetes insípido central.

The histiocytoses are rare diseases caused by alterations in the monocyte-histiocytic series with several clinical findings. Among the cutaneous syndromes of non-Langerhans cells, xanthoma disseminatum is the only disease of this group that has been classically associated to the central diabetes insipidus (CDI). The case reported describes a 30-year-old man that two years after presenting with CDI developed non confluent disseminated cutaneous brown papular lesions throughout the body. The histopathology, immunohistochemistry, and electronic microscopy were compatible with the diagnosis of non-Langerhans histiocytoses, suggesting the diagnosis of juvenile xanthogranuloma. The endocrine-metabolic evaluation did not show other alterations besides CDI in a 10-year follow up. The magnetic resonance of hypophysis showed absence of the pituitary hyperintense sign (bright spot). The radiologic and scinthigraphic evaluation of the bones did not show the presence of osteolytic lesions. This case prints out the importance of skin examination in cases of CDI and its association with cutaneous non-Langerhans histiocytoses in a broader spectrum, rather then restricted to the cases of xanthoma disseminatum.

Histiocitose cutânea não-Langerhans como causa de diabetes insípido central / Cutaneous non-Langerhans cells histiocytoses as cause of central diabetes inspidus

As histiocitoses são doenças raras, resultantes de alterações na linhagem monocítica-histiocítica, com manifestações clínicas diversas. Entre as síndromes cutâneas de células não-Langerhans, o xantoma disseminado é a única entidade desse grupo classicamente associada ao diabetes insípido central (DIC). O caso clínico relatado refere-se a um paciente de 30 anos de idade que, dois anos após o diagnóstico de DIC, evoluiu com lesões cutâneas papulosas, eritêmato-acastanhadas, difusas, discretas e não confluentes. Os achados histológicos, imuno-histoquímicos e a microscopia eletrônica mostraram resultados compatíveis com a histiocitose de células não-Langerhans e sugestivos do xantogranuloma juvenil. A avaliação endócrino-metabólica não mostrou alterações durante o seguimento por 10 anos, com exceção do DIC. A ressonância magnética da hipófise demonstrou ausência do sinal hiperintenso (mancha brilhante) correspondente à neuro-hipófise. As radiografias e a cintilografia dos ossos não mostraram lesões osteolíticas. Este caso desperta a atenção para a importância do exame da pele nos casos de DIC e de sua associação com a histiocitose de células não-Langerhans de maneira mais ampla, e não restrita aos casos de xantoma disseminado.

The histiocytoses are rare diseases caused by alterations in the monocyte-histiocytic series with several clinical findings. Among the cutaneous syndromes of non-Langerhans cells, xanthoma disseminatum is the only disease of this group that has been classically associated to the central diabetes insipidus (CDI). The case reported describes a 30-year-old man that two years after presenting with CDI developed non confluent disseminated cutaneous brown papular lesions throughout the body. The histopathology, immunohistochemistry, and electronic microscopy were compatible with the diagnosis of non-Langerhans histiocytoses, suggesting the diagnosis of juvenile xanthogranuloma. The endocrine-metabolic evaluation did not show other alterations besides CDI in a 10-year follow up. The magnetic resonance of hypophysis showed absence of the pituitary hyperintense sign (bright spot). The radiologic and scinthigraphic evaluation of the bones did not show the presence of osteolytic lesions. This case prints out the importance of skin examination in cases of CDI and its association with cutaneous non-Langerhans histiocytoses in a broader spectrum, rather then restricted to the cases of xanthoma disseminatum.

Do weak adapting backgrounds uncover multiple components in the electroretinogram of the horseshoe crab?

The lateral eye of the horseshoe crab, Limulus polyphemus, has been used as a model system for over a century to study visual and circadian processes. One advantage of this system is the relative simplicity of the retina. The input pathway of the retina consists of photoreceptor cells that are electrically coupled to the dendrite of a second-order cell, which sends action potentials to the brain. Electroretinograms (ERGs) recorded from the lateral eye show a biphasic shape, with a leading negative wave and a later positive peak. The purpose of these experiments was to determine whether adapting backgrounds could be used to uncover multiple adaptation mechanisms within the ERG. To test this idea, ERGs were elicited using variable intensity flashes presented under dark-adapted conditions, as well as in the presence of weak adapting backgrounds. Flashes and backgrounds were generated using green LEDs (lambda max = 525 nm) under software control. ERGs were recorded using a corneal wick electrode placed on the lateral eye of the horseshoe crab. Preliminary results suggest that ERGs recorded in the presence of adapting backgrounds are linearly scaled versions of dark-adapted FRGs. This suggests that there is a single adaptation stage in the Limulus retina. This is in contrast with analogous results from mammals, including mouse, cat and monkey, which show multiple stages of adaptation within their more complex retinas.

Importance of post-exercise hypotension in plasma volume restoration.

The aim of this study was to test the hypothesis that post-exercise hypotension was the mechanism for the plasma volume and albumin gain during recovery. Seven healthy young men completed two experiments (> or =1 week apart) to exercise continuously at 65% of peak aerobic capacity for 60 min followed by the recovery without (experiment 1) or with phenylephrine infusion (experiment 2) to counteract post-exercise hypotension. Heart rate, arterial pressure (Finapres), plasma volume (PV, Evans blue dye dilution), haematocrit, haemoglobin, plasma total solutes (refractometer), albumin, total proteins (colorimetric method), [Na+] and [K+] were not different prior to the experiments. Exercise decreased PV -13.7% (-521 mL) and -14.2% (-566 mL) at the end of 60 min in experiments 1 and 2, respectively, associated with increases in the concentrations of plasma albumin, total protein and solutes. These changes were similar between the two experiments. Following 30 min recovery in experiment 1 the decreased PV was not significantly different from the baseline. Although the volume restoration was complete at the end of 90 min recovery, the change in the albumin concentration was still above zero, indicating a gain of 11 g albumin (P < 0.05). When phenylephrine was infused during recovery, there was no gain in intravascular albumin associated with a sustained decrease in PV (-7% or -280 mL, P < 0.05) observed at the end of experiment 2. These data suggest that post-exercise hypotension may be the mechanism for a gain of intravascular albumin via the lymph return, which enhances plasma water retention and PV restoration during recovery from exercise induced hypovolaemia, even without rehydration.

Sustained-release delivery systems and their application for endoparasite control in animals.

A solid formulation of a potent anthelmintic macrocyclic lactone, moxidectin, was administered using a non-degradable delivery device to discharge the agent into the subcutaneous tissues of sheep. In vivo release was monitored in sheep indirectly using faecal egg counts. Using a dose of 0.2 mg moxidectin/kg body weight when applied in the form of a solid pellet, protection of sheep against Haemonchus contortus challenge was conferred to a level greater than that of sheep which received Cydectin, the commercial liquid injectable form delivered at the same dosage. The anthelmintic efficacy of the solid formulation was assessed at four dosage levels in sheep and it was demonstrated that the dosage of anthelmintic agent could be reduced to 1/6 of the present recommended injectable dose. When two pellets containing the recommended dose of moxidectin were loaded into a non-degradable delivery device, the period of H. contortus control was extended from 42 to 183 days. Antibody levels of sheep receiving repeated infections of H. contortus L3 larvae and treated with moxidectin-loaded devices were reduced significantly compared to the levels observed in sheep treated with Cydectin (p < 0.0005). This implies that the group treated with the moxidectin-loaded devices was exposed to a reduced antigenic load compared to sheep treated with placebo devices, and sheep treated with Cydectin. The antibody levels generated in the sheep treated with placebo devices were no different to those treated with Cydectin. Application of this sustained release device may allow the control of nematode diseases in livestock throughout an entire season with a single administration.

The influence of the anti-androgen flutamide on early sexual differentiation of the marsupial male.

The development of the prostate and the normal descent of the testes in the tammar wallaby (Macropus eugenii) were influenced by treatment with the non-steroidal anti-androgen flutamide. Male pouch young were treated daily from day 9 to day 45, or from day 20 to day 45, of pouch life. Prostate development was inhibited in both treatment groups to a similar extent. Since prostatic buds do not form until day 25 of pouch life, these results suggest that there is a window of androgen sensitivity operating between day 20 and day 25 of pouch life. The number of prostatic buds was significantly lower, but despite the duration of treatment there was never complete abolition of prostate development. Although testes had descended to the same position in treated and control pouch young, inguinal hernias developed in three of four animals treated with flutamide from day 9. These data demonstrate that virilization of the male reproductive tract in this marsupial is dependent on a relatively brief exposure to androgens. Blocking androgen receptor action interferes with normal development of the inguinal canal, which suggests that it is this aspect of inguinoscrotal testicular descent that is androgen dependent.

[Retinopathy of prematurity. The results after a 1-year follow-up]. / Retinopatía del prematuro. Resultados tras un año de seguimiento.

OBJECTIVE: To analyze prospectively the incidence and outcome of retinopathy of prematurity (ROP) in preterm infants admitted to a neonatal intensive care unit. PATIENTS AND METHODS: A high risk group of infants with birth weights less than 1,500 g, and/or a gestational age less than 30 weeks, was studied. Ophthalmoscopic examination was performed at six weeks of age. Frequent ophthalmoscopic examinations were then performed depending on the gravity of the ROP. RESULTS: ROP was found in 14 of the 20 preterm infants (70%). Two developed stage 3 and none of them stage 4 or 5. Cryotherapy for ROP was not used. None of the infants progressed to advanced stages of ROP and complete resolution was the rule. CONCLUSION: Despite the low incidence of advanced stages of ROP in our study, we suggest that all preterm infants less than 1,500 g and/or 30 weeks of gestational age, should be screened for ROP and repeated ophthalmoscopic examination performed in order to evaluate the progression and treatment of ROP.

Effect of fasting and refeeding on acetyl-CoA carboxylase in rat hindlimb muscle.

Previous studies have demonstrated marked differences in liver acetyl-CoA carboxylase (ACC) activity between fasted rats and fasted rats refed with a fat-free diet. This study was designed to determine whether skeletal muscle ACC responds to dietary manipulation similarly to liver. Male Sprague-Dawley rats were fasted 48 h (F), fasted 48 h and refed fat-free diet for 48 h (R), or were fed normal rat chow ad libitum (A). Liver ACC, measured on resuspended ammonium sulfate precipitates of 48,000 g supernatants of tissue homogenates, was markedly decreased in F (77 +/- 6 nmol.g-1.min-1) and increased in R (562 +/- 37 nmol.g-1.min-1) rats compared with A rats (210 +/- 23 nmol.g-1.min-1). The citrate concentration required to cause half-maximal activation of liver ACC (K0.5) was 1.34 +/- 0.14 mM for F, 0.77 +/- 0.09 mM for R, and 0.87 +/- 0.09 mM for A. The quadriceps muscle, on the other hand, showed no difference in ACC activity or in the K0.5 for citrate activation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots confirmed the biochemical measurements, showing marked differences in the size of the protein bands in the +260,000 mol wt range in F vs. R liver ACC preparations but not in skeletal muscle ACC preparations. We conclude that skeletal muscle ACC is controlled by different mechanisms than those observed in liver.