Effects Of Caffeine Dose Timing On Total Urine Excretion During Sodium-Aided Hyperhydration Protocols

When used alone, both caffeine and sodium-aided hyperhydration (SAH) can be ergogenic. Although caffeine use in conjunction with SAH promotes diuresis, hyperhydration can be achieved, albeit at lower levels compared to SAH alone. Previous caffeine and SAH work has suggested most of the caffeine induced diuresis occurs within 15 min of consumption of a bolus of caffeine, sodium and water. This response suggests that caffeine-induces diuresis for only 15 min following its consumption, and/or that the diuretic effects of caffeine are dependent on hydration levels. PURPOSE: To determine the effects of caffeine, consumed at different time-points, on diuresis during SAH protocols. METHODS: Subjects were 17 healthy males (23 ± 5 yr, 177 ± 8 cm, 83.4 ± 15.3 kg). Each performed 4, 90 min hyperhydration trials in a randomized, double-blind fashion. Protocols began with a bladder void and measurement of urine specific gravity (USG) followed by ingestion of 15 mL H2O ∙ kg bm-1 with one of four treatments: Placebo (PL), 70.5 mg NaCl ∙ kg bm-1 (Na), or a combination of NaCl and caffeine consumed in two different strategies: 70.5 mg NaCl + 5 mg caffeine ∙ kg bm-1 taken at the start of the trial (NaCaf0), or 70.5 mg NaCl ∙ kg bm-1 taken at the start and 5 mg caffeine ∙ kg bm-1 taken at 75 min of the trial (NaCaf75). After consuming the water, subjects rested for 90 min performing a measured bladder void every 15 min. Total urine excreted (TUE) was expressed as a percentage of the total fluid consumed during the hyperhydration protocols. USG and TUE were compared using one-way repeated measures ANOVA with Sidak post hoc analyses. Levels of significance were set a priori at P \u3c 0.05. RESULTS: USGs were 1.007 ± 0.003 (PL), 1.008 ± 0.003 (Na), 1.007 ± 0.004 (NaCaf0), and 1.009 ± 0.004 (NaCaf75) (P \u3e 0.05). TUE for PL (87 ± 30%) was significantly higher than all other protocols (P \u3c 0.05). TUE for NaCaf0 (73 ± 16%) was significantly higher than Na (56 ± 18%, P = 0.02) and NaCaf75 (52 ± 13% P \u3c 0.01). NSD in TUE was observed between Na and NaCaf75. CONCLUSION: The results reaffirm that, when caffeine is consumed at the beginning of a SAH strategy, hyperhydration can be achieved, but at a lower level compared to SAH without caffeine. The results also suggest that waiting to consume caffeine until 75 min after water is consumed does not result in caffeine induced diuresis during a SAH protocol

Effects of Dose Timing on Fluid Excretion During Sodium-Aided Hyperhydration Protocols

Co-consumption of sodium and water has been shown to be superior in promoting hyperhydration compared to consumption of an equal amount of water alone. Most sodium-aided hyperhydration studies have provided subjects with a bolus of fluid followed by a urine collection period. However the effect of providing equal amounts of fluid in a single vs. multiple doses over time on fluid retention has not been systematically studied. PURPOSE: To compare the effects of different dosing strategies on urine excretion levels following the consumption of consistent amounts of sodium and water. METHODS: Urine excretion was measured during five separate 2-hr hyperhydration protocols in 13 well hydrated male subjects (23 ± 3 yr, 176.1 ± 10.1 cm, 82.2 ± 19.4 kg) who were free from known renal, digestive, and cardiovascular disease. Each protocol began with a complete bladder void and assessment of urine specific gravity (USG). Subjects then consumed 20 mL H2O ∙ kg bm-1 and 110 mg NaCl ∙ kg bm-1 in five different dosing strategies: the entire dose was consumed at the beginning of the period (1X), ½ of the dose was consumed at the beginning and ½ consumed after 60 min (2X), and 1/3 of the dose was consumed at the beginning and 1/3 was consumed after 45 and 90 min (3X), ¼ of the dose was consumed at the beginning and after 30, 60, and 90 min (4X), and 1/7 of the dose was consumed at the beginning and after 15, 30, 45, 60, 75, 90 min (7X). Protocols were administered in a randomized, crossover fashion. Total urine excretions (TUE) during the 2 hr collection periods were expressed as a percent of the H2O consumed. USG and TUE were compared using repeated-measures ANOVA and Sidak post hoc analyses. RESULTS: USGs were 1.006 ± 0.004 (1X), 1.007 ± 0.003 (2X), 1.009 ± 0.005 (3X). 1.007 ± 0.004 (4X), and 1.007 ± 0.005 (7X) (P = 0.37 – 1.00) indicating that subjects were well and similarly hydrated for each trial. TUE expressed as a percentage of H2O consumed were 75 ± 18% (1X), 69 ± 11% (2X), 52% ± 15% (3X), 59 ± 15% (4X), and 60 ± 16% (7X). Significant differences in TUE were seen between 1X and 3X (P = 0.03) and 2X and 3X (P = 0.006). No significant difference in TUE was detected between any of the other protocols (P = 0.16 – 1.00). CONCLUSION: The data suggest that hyperhydration is better achieved when water and sodium are consumed in three equal doses over 90 min when compared to consuming an equal amount of a sodium and water dose in a single bolus or in two equal doses over a 60 min period. Consuming water in four or seven equal doses over 90 min did not result in better fluid retention than consuming an equal amount of water in a single bolus or in two equal doses over a 60 min period

Effects of Fluid Consumption Volumes on Fluid Retention during Sodium-Aided Hyperhydration Protocols

Numerous investigations have supported the use of sodium-aided hyperhydration to improve hydration status and exercise performance in the heat. Sodium-aided hyperhydration studies typically utilize fluid volumes ranging from 10 - 25 mL ∙ kg bm-1; however, optimum fluid consumption volumes have not been identified. While it may seem logical that larger fluid consumption volumes would promote greater hyperhydration, excessive expansion of plasma volume could stimulate high-pressure baroreceptors and promote excessive diuresis. PURPOSE: To compare the effects of different fluid consumption volumes on fluid retention during a sodium-aided hyperhydration protocol. METHODS: Urine excretion was measured during four separate sodium-aided hyperhydration protocols in thirteen male subjects (24 ± 4 yrs, 75.2 ± 9.5 kg, 177.0 ± 8.9 cm) who were free from known renal, digestive, and cardiovascular disease. Each protocol began with a complete bladder void and assessment of urine specific gravity (USG). Subjects then consumed one of four different isotonic volumes of sodium and water in three equal doses separated by 45 min. Total water consumptions for the four protocols were 20 mL ∙ kg bm-1 (20), 15 mL ∙ kg bm-1 (15), 10 mL ∙ kg bm-1 (10), and 5 mL ∙ kg bm-1 (5). Subjects remained in the lab for two hours following the consumption of the initial fluid-sodium dose and performed a measure bladder void every 20 min. USGs and total fluid retentions (total fluid consumed – total urine excreted) for each protocol were compared using separate, one-way, repeated measures ANOVA and Sidak post-hoc analyses. RESULTS: USGs for the four protocols were 1.009 ± 0.005 (20), 1.010 ± (0.002), 1.016 ± 0.028 (10), and 1.009 ± 0.005 (5) (P \u3e 0.90), indicating that all subjects were well and similarly hydrated for each protocol. Fluid retentions for the four protocols were 10.8 ± 2.7 mL ∙ kg bm-1 (20), 7.5 ± 2.3 mL ∙ kg bm-1 (15), 5.6 ± 2.5 mL ∙ kg bm-1 (10), and 2.6 ± 1.4 mL ∙ kg bm-1 (5) (P ≤ 0.04). CONCLUSION: Subjects retained approximately 50% of the fluid that they consumed regardless of their fluid consumption volumes. These results suggest that, when consuming 5 – 20 mL ∙ kg bm-1 of fluid during sodium-aided hyperhydration protocols, fluid retention levels increase linearly with an increase in fluid consumption volumes and, to attain the highest level of hyperhydration, at least 20 mL ∙ kg bm-1 of fluid should be consumed

Specific CD8+ T cell responses correlate with control of simian immunodeficiency virus replication in Mauritian cynomolgus macaques

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8+ T cells, but it is not clear whether particular CD8+ T cell responses or a broad repertoire of epitope-specific CD8+ T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth

Pest population dynamics are related to a continental overwintering gradient

Overwintering success is an important determinant of arthropod populations that must be considered as climate change continues to influence the spatiotemporal population dynamics of agricultural pests. Using a long-term monitoring database and biologically relevant overwintering zones, we modeled the annual and seasonal population dynamics of a common pest, Helicoverpa zea (Boddie), based on three overwintering suitability zones throughout North America using four decades of soil temperatures: the southern range (able to persist through winter), transitional zone (uncertain overwintering survivorship), and northern limits (unable to survive winter). Our model indicates H. zea population dynamics are hierarchically structured with continental-level effects that are partitioned into three geographic zones. Seasonal populations were initially detected in the southern range, where they experienced multiple large population peaks. All three zones experienced a final peak between late July (southern range) and mid-August to mid-September (transitional zone and northern limits). The southern range expanded by 3% since 1981 and is projected to increase by twofold by 2099 but the areas of other zones are expected to decrease in the future. These changes suggest larger populations may persist at higher latitudes in the future due to reduced low-temperature lethal events during winter. Because H. zea is a highly migratory pest, predicting when populations accumulate in one region can inform synchronous or lagged population development in other regions. We show the value of combining long-term datasets, remotely sensed data, and laboratory findings to inform forecasting of insect pests

Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques

Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius

Nonhuman primates are widely used to study correlates of protective immunity in AIDS research. Successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (MHC) genes results in quantitative and qualitative differences in immune responses. Here we use microsatellite analysis to show that simian immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC genetics, with six common haplotypes accounting for two-thirds of the MHC haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques carry at least one complete copy of the most frequent MHC haplotype, and 8% of these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely conserved in unrelated Indian rhesus macaques. After intrarectal infection with highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus macaques mounted concordant cellular immune responses comparable to those previously reported for a pair of monozygotic twins infected with the same strain of human immunodeficiency virus. Our identification of relatively abundant SIV-susceptible, MHC-identical macaques will facilitate research into protective cellular immunity