Effects Of Different Doses Research Articles

Effects of Gamma-Ray Irradiation of Bacteria Colonies in Animal Feeds and on Growth and Gut Health of Weaning Piglets

Animal feeds contain a substantial number and diversity of microorganisms, and some of them have pathogenic potential. The objectives of this study were to investigate the effects of different doses of gamma (γ)-ray irradiation on the bacteria count in different types of feed and then to test the effect of γ-ray-irradiation-treated fishmeal on the gut health and growth performance of weaning piglets. In trial 1, three fishmeal samples, two feather meal samples, three meat meal samples, three soybean meal samples, and three vitamin complexes were treated with γ-ray irradiation doses of 0, 3, 6, or 9 kGy. The 6 and 9 kGy doses eliminated most of the bacteria in the feed but also resulted in a loss of vitamin C and B1. In trial 2, 96 weaning piglets were fed one of the following three diets with eight replicates (pens) per group over a 14-day period: (1) the control diet—the basal diet supplemented with 6% fishmeal with a low bacteria count (40 CFU/g) and no E. coli; (2) the fishmeal-contaminated diet (FM-contaminated) diet—the basal diet supplemented with 6% fishmeal with a high bacteria count (91,500 CFU/g) and E. coli contamination; and (3) the irradiated fishmeal (irradiated FM) diet—the basal diet supplemented with γ-ray-irradiation-treated E. coli-contaminated fishmeal. The piglets that received the FM-contaminated diet had significantly lower average daily gain and a greater diarrhea index compared to those fed the control diet, whereas γ-ray irradiation treatment abrogated the negative effect of the E. coli-contaminated fishmeal. Collectively, γ-ray irradiation at a dose of 6–9 kGy was sufficient to eliminate the microorganisms in the feed, thereby benefitting the growth performance and gut health of the weaning piglets.

Phytochemical characterization and anti-arthritic potential of Croton bonplandianus leaves extract: In-vivo and in-silico approach

Croton bonplandianus, a natural source traditionally used for treating various illnesses, including rheumatoid arthritis, was evaluated in this study. The effects of ethanolic extracts (CBEE) and aqueous fractions (CBAF) of C. bonplandianus leaves on arthritis-induced inflammation were studied using an albino rat model of inflammation induced by Freund's complete adjuvant. Eight test groups (n = 5 per group) and one vehicle control were used to evaluate the antiarthritic effects of different doses of CBEE and CBAF (125 mg.kg−1, 250 mg.kg−1, and 500 mg.kg−1) on days 5, 10, 15, and 20 compared to arthritic and vehicle controls. Arthritis severity was assessed using macroscopic arthritis grading, histological analysis, body weights, and paw thickness. CBEE and CBAF were found to reduce the prevalence of arthritis, increase body weight, and decrease paw inflammation compared to the vehicle control group by the 23rd day. In addition, they showed no effect on biochemical parameters, but a significant difference (p < 0.05) in hematological parameters compared to the arthritic control group. The study identified Hentriacontane compound as a potential contributor to the anti-inflammatory effect of C. bonplandianus, as it showed the lowest dock score for IL-1β and IL-6. Palmitoylethanol amide was identified as a potential contributor to the anti-inflammatory effect of TNF-α. Gene expression of IL-6, IL-1β, and TNF-α was down-regulated significantly (p < 0.05) in a dose-dependent manner in all treatment groups compared to the arthritic control group. In conclusion, this study validated the anti-arthritic and anti-inflammatory properties of CBEE and CBAF in a time and dose-dependent manner.

Blocking salt-inducible kinases with YKL-06-061 prevents PTZ-induced seizures in mice.

Epilepsy is one of the most common neurological diseases, while over one third of adults with epilepsy still have inadequate seizure control. Although mutations in salt-inducible kinases (SIKs) have been identified in epileptic encephalopathy, it is not known whether blocking SIKs can prevent pentylenetetrazole (PTZ)-induced seizures. We first determined the time course of SIKs (including SIK 1, 2, and 3) in the hippocampus of PTZ treated mice. And then, we evaluated the effects of anti-epilepsy drug valproate acid (VPA) on the expression of SIK 1, 2, and 3 in the hippocampus of PTZ treated mice. Next, we investigated the effect of different dose of SIKs inhibitor YKL-06-061 on the epileptic seizures and neuronal activation by determining the expression of immediate early genes (IEGs) in the PTZ treated mice. We found that PTZ selectively induced enhanced expression of SIK1 in the hippocampus, which was blocked by VPA treatment. Notably, YKL-06-061 decreased seizure activity and prevented neuronal overactivity, as indicated by the reduced expression of IEGs in the hippocampus and prefrontal cortex. Our findings provide the first evidence that SIK1 affects gene regulation in neuronal hyperactivity, which is involved in seizure behavior. Targeting SIK1 through the development of selective inhibitors may lead to disease-modifying therapies that reduce epilepsy progression.

Comparison of anesthetic effects of different doses of alfentanil combined with ciprofol in elderly patients undergoing ERCP: a randomized controlled trial

Background and objectsPatients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are often old and poor in physical fitness. The purpose of this study was to investigate the anesthetic effect of different doses of alfentanil combined with ciprofol in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).MethodsIn this clinical trial, 137 patients, who were candidates for ERCP were randomly divided into three groups. Group A were given 0.15 μg/kg/min of alfentanil in maintenance stage, Group B were given 0.25 μg/kg/min and Group C were given 0.35 μg/kg/min. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2) of the patients at each time point including the entry into the operation room (T0), at the beginning of surgery(T1), 10 min after surgery(T2), 20 min after surgery(T3), 30 min after surgery(T4),endoscopy withdrawal (T5) were recorded. Adverse events(including respiratory depression, body movement and hypoxemia),the dosage of ciprofol, the time of operation time and awakening were recorded.ResultsCompared with Group A, MAP and HR in Group B and Group C was decreased during T1-T5 (P < 0.05). Compared with group B, MAP and HR in group C was decreased during T1-T5 (P < 0.05). Compared with Group A and Group C,the number of adverse reactions of Group B was decreased(P < 0.05). There was no statistical difference in surgical time among the three groups(P > 0.05),but a statistically significant difference in recovery time (P < 0.05).ConclusionThe adverse events of alfentanil 0.25μg/kg/min combined with ciprofol were low, and the anesthetic effect was the best.

Effects of different doses of ionizing radiation on alveolar bone repair in post-extraction tooth socket: an experimental study in rats.

This study aimed to evaluate the dose-response effects of ionizing radiation (IR) on alveolar bone repair and bone strength after tooth extraction. A total of 32 male Wistar rats were used in the study, 28 animals were included in the final analysis, and n = 7 for each experimental group. Mandibular first molars were extracted. After 7days, the animals were randomly divided into four groups according to single-dose irradiation: NIr, control group; Ir15, irradiated at 15Gy; Ir20, irradiated at 20Gy; and Ir30, irradiated at 30Gy. The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric, and biomechanical analyses 14days after extraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test (α = 0.05). Micro-CT analysis revealed that IR led to lower values of bone volume (BV, in mm3) (0.68 ± 0.08, P < 0.001) and bone volume fraction, ratio of the segmented bone volume to the total volume of the region of interest (BV/TV, in %) (44.1 ± 8.3, P < 0.001) for the Ir30 group compared to the control group. A significantly lower amount of newly formed bone was observed in the Ir30 (P = 0.005) than in the Ir15 group. The histomorphometric results of quantification of bone matrix neoformation and the micro-CT were in agreement, demonstrating greater damage to the Ir30 group. IR30 cells showed a lower percentage of densely packed collagen than control cells. No significant differences were found in the biomechanical parameters. IR affects alveolar bone repair. A dose of 30Gy reduced the bone healing process owing to a smaller amount of newly formed bone and a lower percentage of densely packed collagen. Therefore, a dose of 30Gy can be used to successfully establish an animal model of an irradiated mandible that mimics the irradiated clinical conditions. Radiotherapy can lead to severe side effects and tooth extraction is a major risk factor. A proper understanding of the pathological mechanisms of radiation in alveolar bone repair requires the establishment of a suitable animal model of clinical conditions.

Effect of Reactive Oxygen Scavenger N,N'-Dimethylthiourea (DMTU) on Seed Germination and Radicle Elongation of Maize.

Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic stress may be mediated by hydrogen peroxide (H2O2). The effects of the ROS scavenger N,N'-dimethylthiourea (DMTU) on maize seed germination through endogenous H2O2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H2O2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H2O2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes (ZmAPX2 and ZmCAT2) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm-3 DMTU). We suggest the use of 200 mmol·dm-3 DMTU as an H2O2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.

Evaluating the hepatotoxic versus the nephrotoxic role of iron oxide nanoparticles: One step forward into the dose-dependent oxidative effects

The present study has been designed to detect the dose-dependent effect of iron oxide nanoparticles (IONPs) on the liver and kidney of rats by evaluating three different doses 30, 300, 1000 mg/kg/day IONPs for 28 days. Forty rats were divided into four groups; I (control), II (low dose), III (medium dose) and IV (high dose).There also was a statistically-significant elevation in the serum levels of hepatic enzymes; AST and ALT in medium & high dose. The elevation of serum ALP, on the other hand, was significant in all IONPs doses.There was significant elevation in the levels of urea creatinine, and MDA in the medium and high doses of IONPs. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed significant decrease in the high dose only compared to the control group.The serum iron levels increased in a dose-dependent manner in the IONPs-treated groups with highly significant increase in the moderate and high dose groups.On comparing the effect of different doses of IONPs between the liver and kidney, the high dose revealed statistically significant difference (p < 0.05) in the area percent of collagen deposition (54.4 ± 3.9 versus 6.1 ± 2.6) and alpha smooth muscle actin (α-SMA) reaction (7.7 ± 1.5 versus 17.8 ± 4.3) in the liver relative to the kidney. The medium and high doses revealed statistically significant difference in optical density of Periodic acid Schiff (PAS) reaction (45 ± 3.4 versus 50.3 ± 1.8 in the medium dose, and 38.9 ± 6 versus 63 ± 3 in the high dose) and area percent of inducible nitric oxide synthase (iNOS) reaction (12.98 ± 2.7 versus 3.5 ± 0.5 in the medium dose, and 27.91 ± 1.5 versus 7.7 ± 0.6 in the high dose) in the liver relative to the kidney.

Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract.

Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to determine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their effect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The effects of different doses (0.0390625-20 µg/mL) of NPs on cell viability were determined by MTT assay. The effect of ZnO NPs doses (0.0390625 µg/mL, 0.078125 µg/mL, 0.15625 µg/mL, 0.3125 µg/mL, 0.625 µg/mL, 1.25 µg/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fixed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that inflammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-β associated with wound healing. The findings reveal the antimicrobial effect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.

Blood Glucose Levels and Diabetic Ulcers Amelioration in Mice After Mangrove (Bruguiera gymnorrhiza) Leaves Extract Treatments

Physical injuries accompanied by hyperglycemia can develop into diabetic ulcers. The potency of B. gymnorrhiza as an antioxidant and anti-inflammatory can reduce blood glucose levels (KGD) and heal ulcers. This study aims to determine the effect of different doses of B. gymnorrhiza leaf extract on KGD and ulcers. A total of 24 Mice were divided into six groups: normal control (KN), negative control (K-), dose I (42 mg/kg BW), dose II (84 mg/kg BW), dose III (126 mg/kg BW), positive control (KP). Mice in each group other than KN were induced by alloxan 2.5 mg/kg BW. The KGD was measured using a glucometer. The percentage of ulcer closure was calculated by the length of the ulcers. The blood glucose levels data were analyzed using the ANOVA, and the percentage of ulcers using the Kruskal-Wallis test. B. gymnorrhiza leaf extract significantly affected blood glucose levels and the percentage of ulcers with p&lt;0.05. The most optimal effect on reducing KGD and ulcer amelioration in mice shown by dose II (84 mg/kg BW) and dose III (126 mg/kg BW) B. gymnorrhiza leaf extract. Thus, the leaves of B. gymnorrhiza have the potential as a formula in herbal medicine for diabetes and ulcer amelioration.

The use of condensed tannin in lambs' diet alters the rumen protozoa population without affecting growth performance

The aim of this study was to evaluate the effect of different doses of Black Wattle (Acacia mearnsii) condensed tannin on performance, dry matter intake, blood parameters, and identification and quantification of the rumen protozoa population at fasting and after feeding of feedlot lambs. Sixteen Santa Ines intact ram lambs and sixteen Santa Ines ewe lambs were distributed and randomly assigned to 1 of 4 dietary treatments with different doses of condensed tannin (0 %, 1 %, 2 %, and 3 %) in the concentrate, on a feedlot system. No significant treatment effect (P > 0.05) was observed for growth performance, dry matter intake, and blood parameters. No significant effects of treatment (P > 0.05), phase (fasting and after feeding) (P > 0.05), and interaction between treatment and phase (P > 0.05) were observed for total and differential protozoa percentage. However, differences were observed for total and differential protozoa count. A quadratic effect (P = 0.03) was observed for total counts of Diplodiniinae in the rumen fluid of animals fed 3 % of condensed tannin. A phase effect was observed for counts of Isotricha spp, Entodinium spp. Diplodiniinae, and total protozoa count with higher numbers observed at fasting when compared to after feeding. Results of this research suggest that up to 3 % of black wattle condensed tannin in the diet of lambs does not affect dry matter intake, animal performance, and blood parameters.

Acute effect of different doses of caffeinated chewing gum on exercise performance in caffeine-habituated male soccer players.

The ergogenic benefits of caffeine have been well established, but there is scarce research on its chewing gum form. The present research aimed to examine the effects of different doses (100 and 200 mg) of caffeinated chewing gum on muscle strength, vertical jump performance, and ball-kicking speed in trained male soccer players. In a double-blind, randomized counterbalanced, and crossover research design, 14 male soccer players (age = 22 ± 2 y; body mass = 74.2 ± 7.1 kg; height = 180.0 ± 6.8 cm; habitual caffeine intake = 358.9 ± 292.4 mg/day) participated in three experimental trials. In each trial, participants performed isometric handgrip strength, quadriceps and hamstring strength, ball-kicking speed, and 15 s countermovement jump test 10 min after chewing 100 mg (LCAF) or 200 mg (MCAF) of caffeinated gum or placebo (PLA). MCAF improved quadriceps strength (53.77 ± 5.77 kg) compared to LCAF (49.62 ± 8.81 kg, p = 0.048) and PLA (49.20 ± 7.20 kg, p = 0.032). However, neither LCAF nor MCAF had a significant effect on the isometric handgrip and hamstring strength, ball-kicking speed, and 15 s countermovement jump test (all p > 0.05). These findings support chewing gum as an alternative mode of caffeine administration which can be used as a nutritional ergogenic aid for trained soccer players, at least for quadriceps strength.

The effect of low- and high-dose levothyroxine on the expression, protein level, and function of P-glycoprotein in mice

The study was investigated the effect of different doses of levothyroxine on the mRNA expression, protein level and function of Pgp. Mice were divided into 6 groups as control, low dose levothyroxine, high dose levothyroxine, fexofenadine, low dose levothyroxine+fexofenadine and high dose levothyroxine+fexofenadine. Mice received levothyroxine at doses of 8 and 80 µg/kg daily for 21 days. Fexofenadine was administered at dose of 40 mg/kg at the 24 h following the last administration of levothyroxine. The mRNA levels and protein level of Pgp in liver and small intestine were determined by RT-PCR and western blot analysis, respectively. Plasma concentrations of fexofenadine were determined using HPLC. Levothyroxine at low and high doses caused an insignificant increase intestinal mRNA expression of mdr1a, while high dose levothyroxine+fexofenadine caused a significant increase. Levothyroxine caused a dose-dependent decrease in intestinal mRNA expression of mdr1b. In liver, levothyroxine caused a dose-dependent increase in the mRNA expression of mdr1a. Fexofenadine significantly reduced the effect of levothyroxine on mRNA expression of mdr1a in liver. Levothyroxine increased the protein level of Pgp in liver and decrease in intestines. Low dose levothyroxine significantly increased the plasma concentration of fexofenadine. The effects of levothyroxine on the mRNA expression of mdr1a and b in small intestine and liver and protein level of Pgp varied depending on the dose, tissue type, and fexofenadine administration.

The effect of different doses of liquid vermicompost application on yield and yield components of some potato (Solanum tuberosum L.) varieties

The effect of different doses of liquid vermicompost application on yield and yield components of some potato (Solanum tuberosum L.) varieties

Fucoxanthin extract ameliorates obesity associated with modulation of bile acid metabolism and gut microbiota in high-fat-diet fed mice.

Fucoxanthin extract (FX) is a type of carotenoid with a beneficial effect against obesity. The purpose of this study was to explore its precise action mechanism of losing weight. A high-fat diet induced obesity mouse model was established to study the effects of different doses of FX on C57BL/6J male mice for 12weeks. Following intervention, serum indices, tissue sections, liver gene expression, and intestinal microorganisms were analyzed. FX at low, medium, and high dosages (80, 160, and 320mg/kg/day, respectively) for 12weeks was associated with the lower body weight of mice when compared to that of high-fat-diet fed mice. It also improved glucose tolerance as well as serum lipid levels, and reduced fat accumulation. Significant regulation of bile acid metabolism and intestinal microbiota may contribute to the above effects. The bile acids in the FXH group were significantly increased. A low-dose and a medium-dose FX increased the level of transmembrane G protein-coupled receptor 5 (TGR5); a low-dose and high-dose FX increased the farnesoid X receptor (FXR) expression, and a medium-dose had no effect. 16S rRNA sequencing indicated that the Lachnospiraceae and Oscillospiraceae contributed to the beneficial effects of FX. Our study sheds light on mechanisms behind the weight-lowering of FX, and manifested that bile acid metabolism and gut microbiota may be potential therapies. These results support that FX is a valuable candidate for promoting health and alleviating obesity.

The Effects of the Fungicide Myclobutanil on Soil Enzyme Activity

(1) Background: The use of pesticides, although needed to protect crops and increase production, represents an environmental and human health issue. Therefore, measures must be taken in order to develop a better understanding of the risks involved in the overuse of these compounds. Myclobutanil is a chiral triazole fungicide widely used for the protection of crops against fungal diseases. Published data have shown that, although effective in preventing fungal infections, high doses of myclobutanil can affect the soil environment. The aim of this study was to evaluate the effect of different doses of myclobutanil on soil enzyme activity, as well as the possible specificity of the interactions of the two stereoisomers of myclobutanil with these enzymes. (2) Methods: A combination of experimental and computational approaches was considered. An experimental method was applied in order to assess the effect of different doses of myclobutanil on the activity of dehydrogenase, phosphatase, catalase, urease and protease. The computational approach was based on the molecular docking of the two enantiomers of myclobutanil with the above-mentioned enzymes to assess the possible enantioselectivity of the interactions. (3) Results: High doses of myclobutanil significantly affected the enzymatic activity of dehydrogenase and led to a slight increase in the activity of catalase. Molecular docking data showed that both enantiomers of myclobutanil were able to bind to the active sites of dehydrogenase, phsosphatase and protease, with higher interacting energies observed for (S)-myclobutanil, the enantiomer known to be less active against target organisms but have a higher toxicity against non-target organisms. (4) Conclusions: The results of our study confirm the need to implement better management practices regarding the use of myclobutanil (and of pesticides in general) by using the enantiomer that is most effective on target organisms and less toxic to non-target organisms.

Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China

BackgroundBlonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ).MethodsA 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions.Results364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild.ConclusionsBNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ.Trial registration number: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered).

Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency.

With the improvement of economy and living standards, the attention paid to short stature in children has been increasingly highlighted. Numerous causes can lead to short stature in children, among which growth hormone deficiency (GHD) is a significant factor. To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in the treatment of GHD in children. We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018. Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week, forming the high-dose group. Meanwhile, 21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week, establishing the low-dose Group. The total treatment period was 2 years, during which we monitored the patients' height, annual growth velocity (GV), height standard deviation score (HtSDS), chronological age (CA), bone age (BA), and serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) before treatment and at 6 mo, 1 year, and 2 years after treatment initiation. We also monitored thyroid function, fasting plasma glucose, fasting insulin, and other side effects. Furthermore, we calculated the homeostatic model assessment for insulin resistance. After 1 year of treatment, the GV, HtSDS, IGF-1, BA, and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels (P < 0.05). Moreover, when comparing GV, HtSDS, IGF-1, BA, and IGFBP-3 between the two groups, there were no statistically significant differences either before or after the treatment (P > 0.05). During the treatment intervals of 0-1.0 years and 1.0-2.0 years, both patient groups experienced a slowdown in GV and a decline in HtSDS improvement (P < 0.05). The use of PEG-rhGH in treating GHD patients was confirmed to be effective, with similar outcomes observed in both the high-dose group and low-dose groups, and no significant differences in the main side effects.

Influence of the dose of ketamine used on schizophrenia-like symptoms in mice: A correlation study with TH, GAD67, and PPAR-γ

Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20–40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.

The dose-response relationship of quercetin on the motor unit firing patterns and contractile properties of muscle in men and women.

Quercetin is one type of ergogenic aid and its effects on the neuromuscular system have recently attracted interest, but its dose-effect is not yet fully understood. The aim of this study was to examine the effect of different doses of quercetin ingestion on motor unit firing patterns and muscle contractile properties in humans. Thirteen young males and females conducted neuromuscular performance tests before (PRE) and 60 min after (POST) ingestions of 500 or 200 mg of quercetin glycosides (Qg500/Qg200, respectively) or placebo (PLA) on three different days. At PRE and POST, motor unit firing rates were calculated from high-density surface electromyography of the vastus lateralis muscle during 120-s isometric contraction of knee extension at 10% of maximal voluntary contraction. Electrically elicited forces in knee extensor muscles were also measured. After 60 s of voluntary contraction, motor unit firing rates, normalized by the exerted muscle force at POST, were significantly lower at POST than PRE with Qg500 and Qg200 (p < 0.05), but not with PLA (p > 0.05). Changes in motor unit firing rates normalized by the exerted force from PRE to POST were significantly greater with Qg500 than Qg200 at the end of contraction (p < 0.05). Under all three conditions, the electrically elicited force did not significantly change from PRE to POST (p > 0.05). These results suggest that both 500 and 200-mg quercetin ingestions alter motor unit firing patterns, and that quercetin's effect is at least partially dose-dependent.

A dose–response study of resistance exercise training for brain-derived neurotrophic factor in people with type 2 diabetes mellitus: Study protocol for a randomized controlled trial

Abstract Background: Low brain-derived neurotrophic factor (BDNF) has been reported in people with type 2 diabetes mellitus (T2DM). Resistance exercise improves levels of BDNF in T2DM; however, it is unknown what amount of exercise intensity will alter its therapeutic effects. The present study aims to investigate the effect of different doses of resistance exercise intensity on BDNF in people with T2DM. Methods and Outcome Assessments: The study will recruit 106 T2DM who will be randomly allocated to one of the four groups to receive resistance exercise training: Group 1 (50% of 1 repetition maximum [RM]), Group 2 (60% of 1 RM), Group 3 (70% of 1 RM), and Group 4 (control group). All the participants will be assessed for the levels of serum BDNF. The data will be checked for normal distribution, and data having non-normal distribution will be log-transformed. Baseline values between the groups will be compared, and the effect of treatment will be determined using one-way analysis of variance. Discussion: Despite the available research demonstrating the effectiveness of resistance exercise training on BDNF in T2DM people, there is no unequivocal exercise prescription for the same. BDNF is susceptible to regulation by exercise. Therefore, it would be interesting to investigate the optimal intensity for bringing about improvement in BDNF and its interaction with chronic exposure to different intensities of resistance exercise.