Resistance training does not have an effect on cognition or related serum biomarkers in nonagenarians: a randomized controlled trial.

The aim of this randomized controlled trial was to determine the effects of 8-week exercise-intervention on cognition and related serum biochemical markers in nonagenarians. We also studied the effects of a 4-week training cessation ('detraining') period on our study variables. Participants were randomly allocated to a standard-care (control) or intervention (exercise) group [n=20 (16 women)/group]. The intervention focused on supervised, light-to-moderate-intensity aerobic and resistance exercises (mainly leg press), and included 3 weekly sessions. Cognitive status was determined by the mini-mental state examination and geriatric depression scale. We analysed proteins with reported relation with mechanisms behind cognition changes such as serum levels of angiotensin converting enzyme, amyloid-precursor protein, epidermal growth factor, brain-derived neural factor and tumor necrosis factor. No significant change (P>0.05) in any of the variables studied was found following the exercise intervention compared with the standard-care group. Similarly, no significant changes (P>0.05) were observed following the detraining period compared with the standard-care group. Overall changes after the exercise intervention in serum biomarkers were not associated with changes in functional capacity and cognitive measures. An 8-week exercise intervention focusing on resistance exercises neither benefits cognitive function nor affects the levels of the serum proteins analysed in nonagenarians.

The interplay between antiviral immunity and allo-immune reactivity after renal transplantation: consortium between the Centres Amsterdam, Leiden and Nijmegen (ALLOVIR).

In the consortium "ALLOVIR" we aim to characterize the effect of CMV and BKV infections on the innate immune responses to viral and alloantigens. Furthermore, we want to characterize the interplay between adaptive immune responses to viral and alloantigens with emphasis on the role of heterologous immunity. Thirdly, we will characterize the manifestations of these immune responses in the allograft, as reflected in tissue and urine, and their correlation with graft function. Finally, we will assess how immunosuppressive drugs interfere with these cross-reactive immune responses.

ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

We examined the association of R577X polymorphism (rs1815739) in the α-actinin-3 (ACTN3) gene with "explosive" leg muscle power performance in a group of male and female elite volleyball players (n=66, 31 men, 35 women) and in a group of non-athletic male and female young adults (n=334, 243 men, 91 women). We assessed power performance by means of the vertical squat and counter-movement jump tests. We also determined whether the genotypic frequencies of the ACTN3 R577X genotypes differed between groups. We did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in both groups, regardless of gender (all P>0.05). Genotype frequencies were similar between volleyball and control groups (P=0.095). Moreover, we did not find an association between the ACTN3 R577X polymorphism and the likelihood of being an elite volleyball player using the dominant (RR vs RX+XX) and the recessive model (RR+RX vs XX). In summary, these findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

Rotated balance in humans due to repetitive rotational movement.

We show how asymmetries in the movement patterns during the process of regaining balance after perturbation from quiet stance can be modeled by a set of coupled vector fields for the derivative with respect to time of the angles between the resultant ground reaction forces and the vertical in the anteroposterior and mediolateral directions. In our model, which is an adaption of the model of Stirling and Zakynthinaki (2004), the critical curve, defining the set of maximum angles one can lean to and still correct to regain balance, can be rotated and skewed so as to model the effects of a repetitive training of a rotational movement pattern. For the purposes of our study a rotation and a skew matrix is applied to the critical curve of the model. We present here a linear stability analysis of the modified model, as well as a fit of the model to experimental data of two characteristic "asymmetric" elite athletes and to a "symmetric" elite athlete for comparison. The new adapted model has many uses not just in sport but also in rehabilitation, as many work place injuries are caused by excessive repetition of unaligned and rotational movement patterns.

ACE and ACTN3 genes and muscle phenotypes in nonagenarians.

We studied the association of ACE and ACTN3 polymorphisms with skeletal muscle phenotypes (i. e. upper and lower body muscular strength and functional tests) in Spanish nonagenarian subjects [n=41, 33 women, 8 men, age: 90-97 years]. Mean values of the study phenotypes were not significantly different (all P>0.05) between ACE and ACTN3 genotypes. The analyses of the combined effects between genotypes ( ACE DD & ACTN3 RR/RX vs. ACE II/ID & ACTN3 XX) did not yield any significant difference. Our data suggest that, in the elderly, the influence of genetic factors on muscle phenotype traits is not reducible to a few single polymorphisms, including ACE and ACTN3 variants.

Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young, non-athletic adults?

We investigated the association between ACTN3 R577X polymorphism and jumping (vertical squat and counter-movement jump tests) and sprint ability (30 m dash) in non-athletic, healthy young adults [N=284 (217 male), mean (SD) age: 21 (2) years]. We analyzed the differences in the study phenotypes among ACTN3 R577X genotypes by one-way analysis of covariance before and after adjusting for sex, age, weight and height (confounders). We also compared the genotype and allele frequencies between those with the best and worst results in the aforementioned tests (≥90th vs <90th of the sex-specific percentile, respectively). We used logistic regression to calculate the odds ratio (OR) for having the best performance. We did not observe a significant association between ACTN3 R577X genotypes and the study phenotypes before and after adjusting for potential confounders, nor after analyzing males and females separately. We did not observe significant differences in genotype frequencies between those with the best or the worst performance. The OR for an individual with the RR genotype to be in the top 10 percentile was <1.00 for jump tests and <1.015 for sprint tests (all P>0.05). In summary, α-actinin-3 deficiency does not negatively influence the ability to generate explosive leg muscle power in a young non-athletic population.

Does exercise training during pregnancy influence fetal cardiovascular responses to an exercise stimulus? Insights from a randomised, controlled trial.

In this study, the effects of maternal physical activity level on several fetal haemodynamic parameters such as pulsatility index of the fetal middle cerebral and umbilical arteries and cerebral-to-fetal ratio, as well as on fetal heart rate responses to one bout of moderate exercise (20 min cycle-ergometry at approximately 60% of age-predicted maximum heart rate) during the third pregnancy trimester were assessed. 26 Sedentary and 26 physically active gravidae aged 29 (3) and 30 (2) years, respectively, were studied. Maternal exercise did not have a deleterious effect on fetal haemodynamics (particularly, cerebral-to-fetal ratio remained within normal limits with exercise). Overall, maternal training status did not influence the fetal cardiovascular variables studied.

Glycoprotein Ib-IX-mediated activation of integrin alpha(IIb)beta(3): effects of receptor clustering and von Willebrand factor adhesion.

The interaction between the platelet glycoprotein (GP) Ib-IX complex and von Willebrand factor (VWF) initiates both hemostasis and pathological thrombosis. This interaction is not only the first adhesive event of platelets at sites of vessel injury, but also facilitates fibrinogen binding to alpha(IIb)beta(3), which subsequently results in platelet aggregation. Since it has been suggested that GP Ib-IX clustering may promote platelet activation, we investigated the effect of such clustering on both VWF-GP Ib-IX and fibrinogen-alpha(IIb)beta(3) bonds using optical tweezers. In our system, fusion of tandem repeats of FK506-binding protein (FKBP) to the cytoplasmic tail of the GP IX subunit of the GP Ib-IX complex allowed subsequent receptor clustering within the plasma membrane by the bivalent, cell-permeant small molecule ligand AP20187. We measured binding forces between polystyrene beads coated with either plasma-derived VWF or the VWF A1 domain and GP Ib-IX(FKBP)2, and those between fibrinogen-coated beads and alpha(IIb)beta(3) expressed on Chinese hamster ovary cells. The minimal detachment force between GP Ib-IX(FKBP)(2) and A1 or plasma-derived VWF doubled after AP20187 was added. The binding force between immobilized fibrinogen and alpha(IIb)beta(3) was not changed by the clustering agent; however, the strength of single fibrinogen-alpha(IIb)beta(3) bonds increased significantly after ligation of GP Ib-IX(FKBP)(2) by A1. These results demonstrate that GP Ib-IX clustering increases the overall strength of its interaction with VWF. Furthermore, signals from GP Ib-IX can activate alpha(IIb)beta(3), thereby increasing the strength of its interaction with fibrinogen.

CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells.

Experimental protocols for cancer immunotherapy include the utilization of autologous monocyte-derived dendritic cells (moDC) pulsed with tumor antigens. However, disease can alter the characteristics of monocyte precursors and some patients have increased numbers (up to 40%) of the minor CD16(+) monocyte subpopulation, which in healthy individuals represent 10% of blood monocytes. At the present, the capacity of CD16(+) monocytes to differentiate into DC has not been evaluated. Here, we investigated the ability of CD16(+) monocytes cultured with granulocyte- macrophage colony-stimulating factor, IL-4 and tumor necrosis factor-alpha to generate DC in vitro, and we compared them to DC derived from regular CD16(-) monocytes. Both monocyte subsets gave rise to cells with DC characteristics. They internalized soluble and particulate antigens similarly, and both were able to stimulate T cell proliferation in autologous and allogeneic cultures. Nevertheless, CD16(+) moDC expressed higher levels of CD86, CD11a and CD11c, and showed lower expression of CD1a and CD32 compared to CD16(-) moDC. Lipopolysaccharide-stimulated CD16(-) moDC expressed increased levels of IL-12 p40 mRNA and secreted greater amounts of IL-12 p70 than CD16(+) moDC, whereas levels of transforming growth factor-beta1 mRNA were higher on CD16(+) moDC. Moreover, CD4(+) T cells stimulated with CD16(+) moDC secreted increased amounts of IL-4 compared to those stimulated by CD16(-) moDC. These data demonstrate that both moDC are not equivalent, suggesting either that they reach different stages of maturation during the culture or that the starting monocytes belong to cell lineages with distinct differentiation capabilities.

Epitope mapping of inhibitory antibodies against platelet glycoprotein Ibalpha reveals interaction between the leucine-rich repeat N-terminal and C-terminal flanking domains of glycoprotein Ibalpha.

The interaction of von Willebrand factor (vWF) with the platelet receptor glycoprotein Ibalpha (GPIbalpha) is important for platelet adhesion at high shear stress. Two functionally important antigenic areas within GPIbalpha were identified through the characterization of 5 new inhibitory anti-GPIb monoclonal antibodies (mAbs). The binding sites of 3 of these anti-GPIb mAbs, which were intercompeting and potently inhibiting shear stress-induced binding of vWF, were mapped within the N-terminal amino acid (aa) 1-59 area by the use of canine-human chimeras. These antibodies, however, had little or no effect (approximately 40% inhibition) on the binding of vWF induced by either botrocetin or ristocetin. On the other hand, the anti-GPIb mAbs 24G10 and 6B4, which blocked GPIb-vWF binding under all conditions examined, bound to 2 different regions of GPIbalpha, aa 1-81 and aa 201-268, respectively. The epitope for 6B4 was further narrowed by phage display revealing 2 sets of peptide sequences aligning within aa 259-262 and aa 230-242. In the latter region of GPIbalpha, the gain-of-function platelet-type von Willebrand disease (PT-vWD) mutations have been identified. Alignment was partially confirmed because the binding of 6B4 to recombinant GPIbalpha fragments carrying either one of the PT-vWD mutations was considerably impaired but not completely abolished. In contrast, mAb 24G10 bound more strongly to mutant PT-vWD GPIbalpha. However, although 24G10 competed with 6B4 for binding to platelets, it bound to an epitope within aa 1-81 of GPIbalpha. In conclusion, 2 functionally important areas within GPIbalpha were identified: one localized within the leucine-rich repeat N-terminal aa 1-59 area and one composed of residues aa 1-81 in close contact with aa 201-268. Moreover, further support is provided for the existence of an intramolecular interaction between the N-terminal flanking (aa 1-81) and C-terminal flanking (aa 201-268) regions. (Blood. 2001;98:652-660)

Tyrosine sulfation of glycoprotein I(b)alpha. Role of electrostatic interactions in von Willebrand factor binding.

Glycoprotein I(b)alpha (GP I(b)alpha), the ligand binding subunit of the platelet glycoprotein Ib-IX-V complex, is sulfated on three tyrosine residues (Tyr-276, Tyr-278, and Tyr-279). This posttranslational modification is known to be critical for von Willebrand factor (vWF) binding; yet it remains unclear whether it provides a specific structure or merely contributes negative charges. To investigate this issue, we constructed cell lines expressing GP I(b)alpha polypeptides with the three tyrosine residues converted to either Glu or Phe and studied the ability of these mutants to bind vWF in the presence of modulators or shear stress. The mutants were expressed normally on the cell surface as GP Ib-IX complexes, with the conformation of the ligand-binding domain preserved, as judged by the binding of conformation-sensitive monoclonal antibodies. In contrast to their normal expression, both mutants were functionally abnormal. Cells expressing the Phe mutant failed to bind vWF in the presence of either ristocetin or botrocetin. These cells adhered to and rolled on immobilized vWF only when their surface receptor density was increased to twice the level that supported adhesion of cells expressing the wild-type receptor and even then only 20% as many rolled and rolled significantly faster than wild-type cells. Cells expressing the Glu mutant, on the other hand, were normal with respect to ristocetin-induced vWF binding and adhesion to immobilized vWF but were markedly defective in botrocetin-induced vWF binding. These results indicate that GP I(b)alpha tyrosine sulfation influences the interaction of this polypeptide with vWF primarily by contributing negative charges under physiological conditions and when the interaction is induced by ristocetin but contributes a specific structure to the botrocetin-induced interaction.

Milk composition and apparent digestibilities of dietary fatty acids in lactating dairy cows abomasally infused with Cis or Trans fatty acids.

Fat supplementation of diets for dairy cows produces changes in nutrient supply and milk composition. The effect of abomasal infusion of either cis-C18:1 or trans-C18:1 fatty acid isomers on the digestibility of fatty acids and milk composition was determined in lactating dairy cows. Six multiparous midlactation Holstein cows were used and fed a control diet containing 50% forage and 50% concentrate. Treatments were (per day): no infusion, infusion of a 630-g fat mixture high in cis-C18:1 isomers, and infusion of a 623-g fat mixture high in trans-C18:1 isomers using two 3 x 3 Latin squares with 4-wk experimental periods. Fat infusion did not affect total dry matter intake and increased apparent digestibilities of total fatty acids. Apparent digestibilities of C18 fatty acids were directly related to the number of double bonds within isomers, and cis-C18:1 isomers were slightly more digestible than trans-C18:1 isomers. The lower yield of C12:0, C14:0, and C16:0 fatty acids in milk fat and higher milk citrate observed when cows were infused with trans-C18:1 suggests a depressed de novo milk fatty acid synthesis. Effects of trans infusion on milk fat were independent of ruminal fermentation, fatty acid apparent absorption, and fatty acid plasma concentrations. Lower milk protein yield in cows infused with fat may have been caused by a decrease in milk protein synthesis.

Novel gain-of-function mutations of platelet glycoprotein IBalpha by valine mutagenesis in the Cys209-Cys248 disulfide loop. Functional analysis under statis and dynamic conditions.

Platelet-type von Willebrand disease is a bleeding disorder resulting from gain-of-function mutations of glycoprotein (GP) Ibalpha that increase its affinity for von Willebrand factor (vWf). The two known naturally occurring mutations, G233V and M239V, both enrich the valine content of an already valine-rich region within the Cys(209)-Cys(248) disulfide loop. We tested the effect of converting other non-valine residues in this region to valine. Of 10 mutants expressed in CHO cells as components of GP Ib-IX complexes, four displayed a gain-of-function phenotype (G233V, D235V, K237V, and M239V) based on (125)I-vWf binding and adhesion to immobilized vWf. The remainder displayed loss-of-function phenotypes. The gain-of-function mutants bound vWf spontaneously and had a heightened response to low concentrations of ristocetin or botrocetin, whereas the loss-of-function mutants bound vWf more poorly than wild-type GP Ibalpha. No distinct gain- or loss-of-function conformations were identified with conformation-sensitive antibodies. Compared with cells expressing wild-type GP Ibalpha, cells expressing the gain-of-function mutants rolled significantly more slowly over immobilized vWf under flow than wild-type cells and were able to adhere to vWf coated at lower densities. In aggregate, these data indicate that the region of GP Ibalpha bounded by Asn(226) and Ala(244) regulates the affinity for vWf.

Requirement of leucine-rich repeats of glycoprotein (GP) Ibalpha for shear-dependent and static binding of von Willebrand factor to the platelet membrane GP Ib-IX-V complex.

The platelet glycoprotein (GP) Ib-IX-V complex mediates adhesion to von Willebrand factor (vWf) in (patho)physiologic thrombus formation. The vWf-binding site on GP Ib-IX-V is within the N-terminal 282 residues of GP Ibalpha, which consist of an N-terminal flanking sequence (His-1-Ile-35), 7 leucine-rich repeats (Leu-36-Ala-200), a C-terminal flank (Phe-201-Gly-268), and a sulfated tyrosine sequence (Asp-269-Glu-282). We have used mammalian cell expression of canine-human chimeras of GP Ibalpha, corresponding to precise structural boundaries, to demonstrate the first specific requirement for individual leucine-rich repeats for binding of vWf either induced by a modulator, ristocetin, or under hydrodynamic flow. Implicit in this approach was that the GP Ibalpha chimeras retained a functional conformation, a supposition confirmed by analyzing restoration of function to reversed human-canine chimeras and demonstrating that all chimeras bound vWf activated by botrocetin, a modulator that is indiscriminate between species. Leucine-rich repeats 2, 3, and 4 of GP Ibalpha were identified as being critical for vWf adhesion to GP Ib-IX-V.

The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin.

We have identified platelet glycoprotein (GP) Ibalpha as a counterreceptor for P-selectin. GP Ibalpha is a component of the GP Ib-IX-V complex, which mediates platelet adhesion to subendothelium at sites of injury. Cells expressing P-selectin adhered to immobilized GP Ibalpha, and GP Ibalpha-expressing cells adhered to and rolled on P-selectin and on histamine-stimulated endothelium in a P-selectin-dependent manner. In like manner, platelets rolled on activated endothelium, a phenomenon inhibited by antibodies to both P-selectin and GP Ibalpha. Unlike the P-selectin interaction with its leukocyte ligand, PSGL-1 (P-selectin glycoprotein ligand 1), the interaction with GP Ibalpha required neither calcium nor carbohydrate core-2 branching or alpha(1,3)-fucosylation. The interaction was inhibited by sulfated proteoglycans and by antibodies against GP Ibalpha, including one directed at a tyrosine-sulfated region of the polypeptide. Thus, the GP Ib-IX-V complex mediates platelet attachment to both subendothelium and activated endothelium.

[Design and applicability of a clinical guide for appropriate attention in acute respiratory infections]. / Diseño y aplicabilidad de una guía clínica para la atención apropiada en las infecciones respiratorias agudas.

Clinical guidelines provide continuing education and help physicians in the clinical decision-making process. Clinical guidelines to manage acute respiratory infections (ARI) were developed comprehensively from a perspective where prevention, diagnosis, treatment and the patient's education were considered. Methodology. The guideline development process was comprised of two stages: 1. The building stage consisted of several steps: definition of the problem, definition of the potential users of the guidelines, and the appropriate level of care; review of updated bibliographies, and validation using the Delphi technique. 2. The start-up stage consisted of evaluating the guidelines applicable to out-patient settings. Twenty family physicians participated, using the guidelines with 115 patients. Agreement between the family physicians' diagnosis and the criteria stated in the guidelines was tested using unweighted kappa. Differences in the use of the guidelines to manage ARI patients were tested by using the X2 test or the exact Fisher test. Results. Development of guidelines considered the patient's age group. Therefore, guidelines to manage patients under five years of age and to manage patients above this age were constructed. The application of the guidelines was increased from 40 to 60%. As a result, inappropriate prescribing of antibiotics and cough syrups decreased. Although the guidelines could be helpful in treating ARI, its efficacy and effectiveness remain to be tested.

Identification and characterization of endothelial glycoprotein Ib using viper venom proteins modulating cell adhesion.

The expression and function of a glycoprotein Ib (GPIb) complex on human umbilical vein endothelial cells (HUVECs) is still a matter of controversy. We characterized HUVEC GPIb using viper venom proteins: alboaggregins A and B, echicetin, botrocetin, and echistatin. Echicetin is an antagonist, and alboaggregins act as agonists of the platelet GPIb complex. Botrocetin is a venom protein that alters von Willebrand factor (vWF) conformation and increases its binding affinity for the GPIb complex. Echistatin is a disintegrin that blocks alphavbeta3. Echistatin, but not echicetin, inhibited the adhesion to vWF of Chinese hamster ovary (CHO) cells transfected with alphavbeta3. We found the following: (1) Binding of monoclonal antibodies against GPIbalpha to HUVECs was moderately increased after stimulation with cytokines and phorbol ester. Echicetin demonstrated an inhibitory effect. (2) Both echicetin and echistatin, an alphavbeta3 antagonist, inhibited the adhesion of HUVECs to immobilized vWF in a dose-dependent manner. The inhibitory effect was additive when both proteins were used together. (3) Botrocetin potentiated the adhesion of HUVECs to vWF, and this effect was completely abolished by echicetin, but not by echistatin. (4) CHO cells expressing GPIbalphabeta/IX adhered to vWF (in the presence of botrocetin) and to alboaggregins; GPIbalpha was required for this reaction. Echicetin, but not echistatin, inhibited the adhesion of cells transfected with GPIbalphabeta/IX to immobilized vWF. (5) HUVECs adhered strongly to immobilized vWF and alboaggregins with extensive spreading, which was inhibited by LJ1b1, a monoclonal antibody against GPIb. The purified alphavbeta3 receptor did not interact with the alboaggregins, thereby excluding the contribution of alphavbeta3 in inducing HUVEC spreading on alboaggregins. In conclusion, our data confirm the presence of a functional GPIb complex expressed on HUVECs in low density. This complex may mediate HUVEC adhesion and spreading on immobilized vWF and alboaggregins.

Potenciales provocados auditivos de latencia corta en pacientes infectados por virus de inmunodeficiencia humana. Resultados preliminares / Brain stem auditory evoked potentials in HIV infected patients. Preliminary results

Objetivo: El propósito del presente trabajo es determinar el tipo y frecuencia de anormalidades en los potenciales provocados auditivos de latencia corta (PPALC), en los pacientes infectados con el VIH con y sin síndrome de inmunodeficiencia adquirida. Material y métodos: Los PPALC fueron realizados en cuarenta y cuatro pacientes infectados con VIH, veintidós de los mismos fueron seropositivos asintomáticos, los veintidós pacientes restantes presentaban manifestaciones de SIDA. Veinte adultos jóvenes sanos integraron el grupo control. Al momento del estudio, ninguno de los pacientes infectados con VIH mostraron hallazgos clínicos de disfunción neurológica. Resultados: Los intervalos interonda I-V mostraron diferencias significativas (P) entre los grupos infectados y el grupo control. No se encontraron diferencias significativas entre los dos grupos infectados con VIH. Conclusiones: Se concluye que la infección con VIH es capaz de producir cambios patológicos sub-clínicos en el nervio auditivo y el tallo cerebral

Changes in somatotropic axis response and body composition during growth hormone administration in progressive cachectic parasitism.

A multistage protozoan parasitic disease was used as a cachexia model to study the effects of daily administration of bovine growth hormone (GH) on endocrine and body composition changes of young calves from the onset of the acute phase response (APR). Male calves averaging 127.5 +/- 2.0 kg body weight were assigned to control, ad libitum fed, noninfected (C); ad libitum fed, infected (250,000 oocysts Sarcocystis cruzi, per os, I); noninfected, pair-fed (PF) to matched I-treatment calves and these respective same treatments in calves injected daily with GH (USDA-bGH-B1), 12.5 mg/calf/day, im) designated as CGH, IGH and PFGH. GH injections were initiated on Day 20 postinfection (PI), 3 to 4 d before the onset of clinical signs of APR, and continued to Day 56 PI, at which time animals were euthanized for tissue collections. Abrupt increases in rectal temperature commensurate with up to 70% reduction in voluntary feed intake were observed in I and IGH beginning 23-25 d PI. For the trial period between Days 20 and 56 PI, average daily carcass protein gains were 123, 52, 109, 124, 48, and 67 g/d and average daily carcass fat gains were 85, 11, 43, 71, -23, and 29 g/d for C, I, PF, CGH, IGH, and PFGH, respectively. Effects of GH were significant for fat accretion and plasma urea depression. Rectus femoris was highly refractory to catabolic effects of infection while psoas major was significantly catabolized during infection. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly in all GH-treated calves between Day 20 and 23 PI. Plasma IGF-I declined well below Day 20 values in all infected calves from the onset of the APR through the end of the study. The decrease in plasma IGF-I concentrations in I and IG was highly correlated with the magnitude of the fever response. Hepatic mRNA for GH receptor and IGF-I was decreased in infected calves. Hepatic microsomal membrane binding of 125I-GH did not differ between groups. The data suggest that effects of GH and parasitism on tissue metabolism during disease may vary among different specific tissue pools. The data demonstrate that daily GH administration in young calves does not prevent lean tissue losses and may accelerate fat depletion associated with cachectic parasitism. Furthermore, the onset of APR overrode the capacity for GH to maintain elevated plasma concentrations of IGF-I, an effect not readily explained through changes of GH-receptor binding.

Dietary fatty acids modulate hormone responses in lactating cows: mechanistic role for 5'-deiodinase activity in tissue.

Supplemental dietary fat provides excess fatty acids (FA), which can alter circulating concentrations of several hormones. To test the effects of fatty acid isomer type and possible sites of regulation, we abomasally infused fat mixtures high in cis-C18:1 FA (iCIS), high in trans-C18:1 FA (iTRS) or no infusion (NI) and performed intravenous arginine (ARG) and intramuscular thyrotropin-releasing hormone (TRH) challenges. The experimental design was a replicated 3 x 3 Latin square. Challenges were conducted on Days 10 (ARG) and 12 (TRH) after initiation of fat infusion on each of three 4-wk experimental periods. Plasma concentrations of IGF-I were lower (P < 0.01) when cows received iCIS or iTRS compared with NI. Plasma insulin concentrations increased with ARG but responses were not affected by FA. Plasma growth hormone (GH) was unchanged after ARG. Peak plasma GH and thyroid-stimulating hormone (TSH) responses to TRH were blunted (P < 0.05 and P < 0.1, respectively), whereas thyroxine (T4) and triiodothyronine (T3) responses were augmented post-TRH (P < 0.01) when cows received either FA isomer. Prolactin responses to TRH were not different between infusion treatments, although basal plasma concentrations before TRH were higher in cows infused with iTRS (P < 0.05). To focus on fat regulation of the thyroid axis, we tested directly in vitro the ability of fatty acids dissolved with sodium taurocholate to affect Type-I 5'-deiodinase (5'D) activity in bovine liver homogenates. Homogenate 5'D was not affected by C2:0-C10:0 fatty acids, but decreased linearly (P < 0.01) with increasing concentrations of C12:0-C16:0 and C18:1 isomers. Cis C18:1 decreased 5'D more than the trans-isomer (P < 0.01), but the difference was only apparent at concentrations greater than 0.25 mM. The data suggest that various aspects of pituitary hormone regulation are differentially affected by FA composition. Fatty acid infusion may accentuate end organ responses in the thyroid axis and decrease IGF-I in the somatotropic axis. The data also suggest that FA isomer may alter patterns of extrathyroidal generation of thyroid hormones via direct influences on 5'D.