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Purpose. This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and Methods. Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results. Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions. These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.

Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine β-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease.

Nitric oxide (NO) and hydrogen sulfide (H2S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H2S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover, roflumilast produced a much more potent smooth muscle relaxation than that induced by tadalafil. In porcine samples, H2S generation was diminished by H2S and NO synthase inhibition and augmented by roflumilast. Relaxations elicited by EFS were potentiated by roflumilast. These results suggest that PDE4, mainly PDE4A, is mostly located within nerve fibers of the pig and human bladder neck, where roflumilast produces a powerful smooth muscle relaxation. In pig, the fact that roflumilast increases endogenous H2S production and EFS-induced relaxations suggests a modulation of PDE4 on NO- and H2S-mediated inhibitory neurotransmission.

The lack of an adequate therapy for Alzheimer's Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm “Multi-Target-Directed Ligands” (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.

Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.

The digesta is a highly active biological system where epithelial cells, microbiota, nondigestible dietary components, and a large number of metabolic products interact. The gut microbiota can be modulated by both endogenous and exogenous substrates. Undigested dietary residues are substrates for colonic microbiota and may influence gut microbial ecology. The objective of this work was to study the capacity of grape antioxidant dietary fiber (GADF), which is rich in polyphenols, to modify the bacterial profile in the cecum of rats. Male adult Wistar rats were fed for 4 wk with diets containing either cellulose or GADF as dietary fiber. The effect of GADF on bacterial growth was evaluated in vitro and on the cecal microbiota of rats using quantitative real time polymerase chain reaction (RT-PCR). The results showed that GADF intake stimulates proliferation of Lactobacillus and slightly affects the composition of Bifidobacterium species. GADF was also found to have a stimulative effect on Lactobacillus reuteri and Lactobacillus acidophilus in vitro. These findings suggest that the consumption of a diet rich in plant foods with high dietary fiber and polyphenol content may enhance the gastrointestinal health of the host through microbiota modulation.Grape antioxidant fiber combines nutritional and physiological properties of dietary fiber and natural antioxidants from grapes. Grape antioxidant fiber could be used as an ingredient for functional foods and as a dietary supplement to increase the intake of dietary fiber and bioactive compounds.

Grape antioxidant dietary fibre (GADF) is a grape product rich in dietary fibre and natural antioxidants. We showed previously that the GADF intake induced an epithelial hypoplasia in the rat colonic mucosa. In the present study, we propose that the antioxidant effect of GADF could modulate mucosal apoptosis via modulation of the cellular redox environment. Male Wistar rats (n20) were fed with diets containing either cellulose (control diet group) or GADF (GADF diet group) as fibre for 4 weeks. The GSH:GSSG ratio, the redox state of the GSSG/2GSH couple (Ehc), the mitochondrial and/or cytosolic antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), lipid peroxidation (LPO) and apoptosis were evaluated. GADF enhanced the cytosolic GSH:GSSG ratio, shifting the redox potential (Ehc) to a more pro-reducing status. Decreased Cu,ZnSOD:CAT, Cu,ZnSOD:GPx and MnSOD:GPx ratios could indicate an enhanced capacity for reducing H2O2, contributing to decreased cytosolic LPO. Reduced apoptosis in GADF-treated mucosa was inversely related to MnSOD activity. Furthermore, apoptosis increased directly as GSSG content increased. These results suggest that the reduction in apoptosis associated with GADF intake may be due to a modulation of the glutathione redox system and endogenous antioxidant enzymes.

Grape antioxidant dietary fiber (GADF) is a source of dietary fiber obtained from grape seeds from wine production with antioxidant capacity. The effects of GADF on cecal and distal colonic mucosal growth and the architecture of male Wistar rats were studied. Tissue DNA, RNA, and protein concentrations as well as mucosal thickness, crypt depth, and crypt density were assessed. Two groups of 10 animals were fed diet containing fiber either from cellulose or from GADF for 4 weeks. Feeding rats with GADF diet decreased mucosal DNA and protein concentrations in cecum (39%) and DNA concentration in colon (29%) compared with control ( P

We studied the influence of dietary protein concentration (PC) on the adaptation mechanism of maternal glucose metabolism to gestation, and on maternal body weight (BW) gain using pregnant rats fed 4% (low protein, LP), 10% (medium protein, MP) or 20% (high protein, HP) dietary protein concentration. Feed (FI), energy (EI) and protein (PI) intakes were recorded. Plasma glucose, insulin and GH were determined, and insulin:glucose (insulin resistance) and insulin:GH ratios computed. Correlation and regression analyses were used to determine the physiological relationships between metabolic and ponderal variables. MP dams with greater FI and EI (12%), and lower PI (44%) than HP dams showed similar maternal and fetal growth performance because of the maintained energy efficiency (EE). LP dams, with similar FI and EI, and lower PI (81%) than HP dams, failed to catch up due to the low EE. PC exerted a non-linear influence on BW gain, insulin and GH, through EI and EE modifications. The EI linearly influenced hormone concentrations with the maximum and minimum hormone response in MP and LP dams, respectively. Insulin resistance increased as PC decreased, whereas the GH lipolytic effect appeared to predominate over insulin action. Circulating hormones and metabolites affected nutrient partitioning between dam and fetus, with the result that the competing demands for materno-fetal growth of HP and MP dams, but not the LP dams, were satisfied. A deeper knowledge of the nature of the materno-fetal energy relationships will enhance the manipulation of the growth performance of the fetus in several animal species.

Previously we have found that recombinant human growth hormone (rhGH) (GH; 74 ng g body wt.(-1)) administration to weaned BALB/c male mice (fed 12% or 20% protein diet) induced a growth lag and subsequent repletion similar to the catch-up growth process. We studied the partitioning of feed and protein intakes between adipose and protein body stores through the linear relationships among them. The non-linear relationship of protein intake with body fat gain/protein gain (FG/PG) ratio was especially adequate in determining the partitioning of substrates. rhGH induced an increase in feed and protein intake utilization for body weight gain (50%) and fat gain (75-140%) over saline; macronutrient utilization was the greatest in rhGH-treated mice fed 20% protein. However, growth recovery of rhGH mice was anomalous and protein intake was derived primarily for fat gain. Mice fed 12% protein (treated and control) also derived protein intake in preference to fat stores. Treatment and diet had a cumulative effect with the result that rhGH-treated animals fed 12% protein showed the greatest FG/PG ratio (1.6), and therefore, the lowest efficiency to gain protein. Weaning is a critical stage in mice when treating with rhGH, as this could provoke a growth lag. The study showed that a high protein level is required to surpass the rhGH-induced lag, but it is not enough to obtain an enhanced protein deposition. Feeding a 12% protein diet was even worse as mice did not improve on the growth lag and substrates were directed mainly to body fat.

The exogenous recombinant human growth hormone (rhGH) administration on gastrocnemius muscle growth performance and its contribution to body growth of male and female BALB/c mice fed a 12 % protein diet from 25 to 50 days of age, as well as the mechanism of utilization of feed intake to the lean muscle deposition were studied. Male and female weaning mice (21 days of age) were injected subcutaneously for 29 days with rhGH (74 ng x g(-1)) or saline vehicle (control). Feed intake and body weight (BW) were measured daily. At 25, 30, 35, 40, 45 and 50 days of age twenty mice were killed by cervical dislocation and the gastrocnemius muscle was isolated, weighed and the protein content was measured. The rhGH administration caused a biphasic response of BW and muscle growth as a consequence of age-specific feed intake changes. The initial feed intake fall induced the allometric proportion decreases in both muscle growth versus body growth and protein muscle versus muscle growth. That effect was due to ineffient utilization of energy and protein intake on protein muscle store. Later on, the self-controlled increase of feed intake leads to the recovery of muscle weight to control values, through nutrient partitioning toward non protein tissue showing a compensatory muscle growth. This suggests that a higher dietary protein level should be necessary for promoting the protein anabolic effect of GH during weaning.

Numerous lines of evidence support a relationship between intestinal inflammation and cancer. Therefore, much attention has recently been focused on the identification of natural compounds with anti-inflammatory activities as a strategy to suppress the early stages of colorectal cancer. Because cocoa is a rich source of bioactive compounds, the present study investigated its anti-inflammatory properties in a rat model of azoxymethane (AOM)-induced colon carcinogenesis and in TNF-α-stimulated Caco-2 cells. A total of forty male rats were fed with control or cocoa-enriched diets (12Â %) during 8 weeks and injected with saline or AOM (20Â mg/kg body weight) during the third and fourth week (n 10 rats/group). At the end of the experiment, colon samples were evaluated for markers of inflammation. The anti-inflammatory activity of a cocoa polyphenolic extract (10Â μg/ml) was examined in TNF-α-stimulated Caco-2 cells, an in vitro model of experimentally induced intestinal inflammation. The signalling pathways involved, including NF-κB and the mitogen-activated protein kinase family such as c-Jun NH2-terminal kinases (JNK), extracellular signal-regulated kinases and p38, were also evaluated. The results show that the cocoa-rich diet decreases the nuclear levels of NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase induced by AOM in the colon. Additionally, the experiments in Caco-2 cells confirm that cocoa polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation. We conclude that cocoa polyphenols suppress inflammation-related colon carcinogenesis and could be promising in the dietary prevention of intestinal inflammation and related cancer development., This study was supported by the grant AGL2007-64042/ALI and project CSD 2007-00063 from Programa Consolider-Ingenio from the Spanish Ministry of Science and Innovation (CICYT). I. R.-R. is a predoctoral JAE-Predoc fellow of the Consejo Superior de Investigaciones Científicas co-funded by the European Social Fund. M. A. M. is affıliated to CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.

The effects of age, dietary protein level [12% (medium protein) or 20% (high protein)], and sex on muscle growth of female (f) and male (m) BALB/c mice between weaning (21 d) and 50 d of age were studied. Animals were housed individually and feed intake and body weight (BW) were recorded daily. In the total experimental period (29 d), six partial experimental periods were established. At 25, 30, 35, 40, 45 and 50 d of age, five mice of each group (MPf, MPm, HPf, HPm) were slaughtered and gastrocnemius muscle growth was studied. Based on BW and muscle weight (MW) measures, values of growth parameters were estimated. Feed consumption rate (FCR) increased in all groups, but it nearly stabilized with age in HP mice. BW, estimated muscle weight (EMW), muscle weight gain (MWG), absolute muscle protein (AMP) and muscle protein gain (MPG) increased in MP and HP mice during the experiment. Relative muscle protein (RMP) increased in MP while it decreased in HP mice with age. Also, absolute and fractional muscle weight growth rates (AWGR and FWGR, respectively) and absolute and fractional muscle protein growth rates (APGR and FPGR, respectively) decreased in all mice tested (age-dependent), except in HPf mice where it remained plateaued in time (age-independent). At 21 d the highest AWGR, FWGR, APGR, and FPGR values were registered in MP mice. Diet and sex influenced the relative allometric proportions of muscle to the organism as a whole. Muscle protein growth of MP mice versus MW growth was enhanced, resulting in an increase of growth coefficients as compared to HP mice. Also, the contribution of muscle protein to carcass protein and the efficiency of protein intake utilization were higher in MP mice than in HP mice, while efficiency of energy intake was similar in both groups. In conclusion, hyperphagia and increased efficiency of protein utilization induced a near-normal muscle growth in MP growing BALB/c mice. Key words: Age, protein level, sex, muscle growth, BALB/c mice

Cocoa is a rich source of bioactive compounds with potential chemopreventive ability but up to date its effectiveness in animal models of colon carcinogenesis has not been addressed. Herein, we investigated the in vivo effect of a cocoa-rich diet in the prevention of azoxymethane (AOM)-induced colon cancer and the mechanisms involved. Our results showed that cocoa feeding significantly reduced AOM-induced colonic aberrant crypt foci formation and crypt multiplicity. Oxidative imbalance in colon tissues seems to be prevented by cocoa as indicated by reduced oxidation markers levels and increased enzymatic and non-enzymatic endogenous defences. Cocoa-rich diet also exhibited antiproliferative effects by decreasing the levels of extracellular regulated kinases, protein kinase B and cyclin D1 together with pro-apoptotic effects evidenced by reduced Bcl-xL levels and increased Bax levels and caspase-3 activity. Our findings provide the first in vivo evidence that a cocoa-rich diet may inhibit the early stage of colon carcinogenesis probably by preventing oxidative stress and cell proliferation and by inducing apoptosis. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., This work was supported by the grant AGL2007-64042/ALI and project CSD 2007-00063 from Programa Consolider Ingenio from the Spanish Ministry of Science and Innovation (CICYT). I. Rodríguez-Ramiro is a predoctoral fellow of the Consejo Superior de Investigaciones Científicas and M. Gómez Juaristi is a predoctoral fellow of the Spanish Ministry of Science and Education.

The effect of growth hormone (GH) on arylesterase (AE), one of the activities of paraoxonase, has never been studied. The aims of the present study in mice were: (a) to compare the effect of age and sex on serum lipid and lipoprotein levels after consumption of lactalbumin-v.chow-based diets and (b) to study the effect of GH administration, age and sex on serum AE activity, lipid and lipoprotein and body fat levels in mice fed a lactalbumin diet. Seventy-two mice were divided into three age- and sex-matched experimental groups: (1) control chow (CC), (2) non-GH lactalbumin (NGL) and (3) GH-treated lactalbumin (GL) mice. Lactalbumin increased total cholesterol, (LDL+VLDL)-cholesterol and TAG and diminished HDL-cholesterol in all animals (P P P P P P P

Objective The purpose of this work is to determine whether changes in dietary protein level could alter the modulator effect that GH has on the muscle lysosomal system by influencing the hydrolytic activities of cathepsin D, acid RNase and DNase II and the participation of these enzymes in muscle growth. Design BALB/c female mice were fed a diet containing 20% (HP) or 12% (MP) protein ad libitum and were treated with either saline (s) or rhGH (GH) (74 ng/g) for 29 days. Body weight and feed intake were recorded daily. At 25, 30, 35, 40, 45 and 50 days of age, five mice from each group were slaughtered and nucleic acids and protein concentrations and cathepsin D, acid RNase and DNase II activities in gastrocnemius muscle were analysed. Correlation coefficients were used to analyse the links between the activity of each enzyme with its substrate. Results GH-treatment induced a depletion–recovery response in muscle growth through a compensatory mechanism. Changes in protein content, DNA and RNA concentrations were related to changes in lysosomal enzyme activities. Muscle cathepsin D activity in saline mice fell as the dietary protein concentration increased. GH-treatment reversed this effect by enhancing the proteolytic activity in muscle of well-fed mice and inhibiting it in mice fed a 12% protein diet. This inversion appears to be related to the different mechanism elicited by GH-treatment on skeletal muscle protein growth in each dietary group. An opposite trend was observed in muscle acid nuclease activities. Acid RNase and DNase II increased according to the dietary protein concentration, since a 12% protein diet induced a lower catabolism, especially on muscle DNA of saline mice. In contrast, GH-treatment decreased acid RNase and DNase II activities, but only in mice fed a 20% protein diet, perhaps leading to spare muscle RNA for protein synthesis, as well as to the inhibition of DNA degradation during catch-up growth. A lower dietary protein concentration appeared to reverse the GH protective effect on nucleic acids. Conclusions GH seems to act as a dietary protein-dependent modulator of the skeletal muscle lysosomal enzyme activity. These lysosomal enzymes play a role during muscle growth in GH-treated post-weaning mice by modifying muscle protein and DNA and RNA degradation.

We determined whether recombinant human growth hormone (rhGH) administration might modulate the enzyme degradative capacity of the muscle lysosomal system and influence muscle growth. Muscle cathepsin D, acid RNase and DNase II activities are determined in the gastrocnemius muscle of rhGH-treated post-weaning female BALB/c mice. Linear regressions were used to analyze the relationships of each enzyme with their respective substrate. GH induced a depletion-recovery response of muscle growth through a mechanism which is similar to catch-up growth. In these conditions, cathepsin D activity decreased with age in all animals (GH: 40%; saline: 79%), showing a substantial developmental decline that could reflect changes in the rate of protein breakdown. However, the degradative capacity of cathepsin D was paradoxically unmodified in rhGH-mice compared with saline mice (according to the enzyme vs. substrate linear regression slope), in spite of the increase in enzyme activity elicited by GH. This suggests that the muscle protein breakdown is not increased by GH-treatment in post-weaning mice. The enhancement of muscle protein deposition as indicated by the augmented muscle cell size (protein:DNA ratio) of rhGH-mice (increased 178% from 25 to 50 days) vs. saline, can be attributed to a higher muscle K(RNA). In contrast, acid RNase and DNase II activities directly participate in muscle RNA and DNA degradation. Both nucleases were inhibited by GH treatment (a decrease of 48% and 63%, respectively, vs. saline at 50 days). The decrease in RNase activity suggests an inverse relation between the rate of protein synthesis (high) and acid RNase activity (low), leading to spare muscle RNA for synthesizing protein during catch-up growth. Also, low DNase II activity could contribute to inhibiting of muscle DNA degradation, facilitating muscle growth. Thus, GH seems to act as a direct modulator of the degradative capacity of skeletal muscle nucleases but not of cathepsin D, influencing DNA and RNA degradation during the depletion-recovery response to GH of gastrocnemius muscle in female post-weaning mice.

Chronic treatment, of SH-SY5Y cells, with KCl (20 mM) for 4 days decreased 100 mM KCl-evoked noradrenaline (NA) release by 50% and nicotine (100 microM)-evoked NA release by 55%. Pretreatment with the L-type calcium channel antagonist, nifedipine, prevented this inhibitory effect of chronic exposure to 20 mM KCl on NA release. In contrast pretreatment with 10 microM nicotine for 4 days had no effect on 100 mM KCl -evoked secretion and decreased nicotinic -evoked NA release by only 25%. Inclusion of nifedipine prevented the inhibition of NA release by chronic nicotine treatment. These data are discussed in relation to effects of chronic moderate, depolarisation by either K(+) or nicotine on influx of Ca(2+) via L-type voltage sensitive calcium channels.

The present study was undertaken to elucidate the effect of the exogenous administration of rhGH on the time course of the cellular muscle growth in male and female BALB/c mice fed 20% dietary protein between weaning and 50 days of age. Also, the efficiency of utilization of protein and energy intake to muscle DNA content and protein per cell (protein to DNA ratio) storage were studied. 120 weaned mice (21 d) were assigned to four groups based on rhGH-treatment (rhGH-treated: 7.4 ng x g(-1) BW and control: saline vehicle; via s.c. every two days) and gender. Feed intake was measured daily. At 25, 30, 35, 40, 45 and 50 days of age twenty mice were killed by cervical dislocation and the samples of gastrocnemius muscles were isolated, weighed and protein and DNA contents were measured. The rhGH administration caused a biphasic response altering the muscle cellular growth as a consequence of age-specific feed intake changes. The GH-induced fall of feed intake between 25 and 30 days of age caused decreases in muscle weight and myonuclei number (DNA), whereas muscle cell size was maintained. Later on, the self-controlled increase of feed intake led to the muscle weight recovery to control level, in spite of the irreversible DNA fall, as a consequence of the increase of cellular protein deposition and an enhancement of utilization of protein and energy intakes to deposit protein per cell. These results demonstrate that in spite of the initial (25-30 d of age) muscle DNA fall, rhGH-administration from weaning ensures the recovery of cellular muscle growth to control level through a compensatory muscle hypertrophy.

In education, models and analogies are developed to help in making it easier to understand physiological concepts. The effectiveness of the chosen model depends to a great extent on the capacity of the analogy to transfer understanding from frames that are familiar to the student to the new concept

BALB/c mice weaned at 21 days were used to investigate the effects of exogenous recombinant human growth hormone (rhGH) administration on the growth performance and carcass composition in females and males allowed to consume feed ad libitum. Forty mice were assigned within each sex (female [F] and male [M] to treatment of either 20 microL g-1 saline (Fs and Ms groups) or 74 ng rhGH g-1 body weight (BW) in 20 microL saline (FGH and MGH groups). At 50 d of age the mice were weighed and then killed by cervical dislocation. Treatment with rhGh improved feed conversion only in growing female mice by enhancing weight gain relative to feed protein intake and weight growth rate without modification of feed consumption, according to a multiple comparison test (LSD). Ms mice showed less carcass fat gain (162%), less fat accretion rate (129%), higher carcass water gain (12%) and higher water accretion rate (28%) than Fs mice. The administration of rhGH modified this distribution inducing an increase in gain and accretion rates of protein (34%), water (41%) and ash (33%) and a reduction in gain and accretion rate of fat (50%) in FGH mice, and only an increase of gain (91%) and accretion rate of fat (67%) in MGH mice compared to saline mice. As result, a decrease in protein gain:fat gain ratio of MGH mice compared to FGH (34%) and Ms (63%) mice was elicited by rhGH, inverting the inherent sexual propensity for fat and protein deposition in growing male mice, due to GH, sex, and to GH x sex interaction influence.