PLC Group Research Articles

Tendon collagen synthesis declines with immobilization in elderly humans: no effect of anti-inflammatory medication.

In elderly humans, 2 wk of inactivity reduces tendon collagen protein synthesis, while tendon stiffness and modulus are only marginally reduced, and NSAID treatment does not affect this. This indicates that mechanical loading is important for maintenance of tendon collagen turnover and that changes in collagen turnover induced by short-term immobilization may only have minor impact on the internal structures that are essential for mechanical properties in elderly tendons.

The Digital Economy Act 2010: subscriber monitoring and the right to privacy under Article 8 of the ECHR

This paper critically assesses the compatibility of s3 Digital Economy Act 2010 (DEA) with Article 8 of the European Convention on Human Rights (1950) (ECHR). The analysis draws on Ofcom’s Initial Obligations and two UK cases, namely: British Telecommunications Plc & Anor, R (on the application of) v The Secretary of State for Business, Innovation and Skills,1 and R (British Telecommunications plc and TalkTalk Telecom Group plc) v Secretary of State for Culture, Olympics, Media and Sport and others.2 It argues that the implementation of this obligation allows directed surveillance of subscribers’ activities without legal authorisation under the Regulation of Investigatory Powers Act 2000 (RIPA). It also analyses compliance with the Strasbourg Court’s three-part, non-cumulative test, to determine whether s3 of the DEA is, firstly, ‘in accordance with the law’; secondly, pursues one or more legitimate aims contained within Article 8(2) of the Convention; and thirdly, is ‘necessary’ and ‘proportionate’. It concludes that unless the implementation of s3 of the DEA required the involvement of State authorities and was specifically targeted at serious, commercial scale online copyright infringement cases it could infringe part one and part three of the ECtHR’s test, thereby violating subscribers’ Article 8 ECHR rights.

Oxytocin blurs the self-other distinction during trait judgments and reduces medial prefrontal cortex responses.

The neuropeptide oxytocin (OXT) may act either to increase or blur the distinction between self and other and thereby promote either more selfish or altruistic behaviors. To attempt to distinguish between these two possibilities we performed a double-blind, between-subject, placebo-controlled design study to investigate the effect of intranasal OXT on self and other (mother, classmate, or stranger) trait judgments in conjunction with functional magnetic resonance imaging. Results showed that OXT reduced response times for making both self and other judgments, but also reduced the accuracy of their subsequent recall, thereby abolishing the normal self-bias observed in this task. OXT also abolished the positive correlation between response and self-esteem scale scores seen in the PLC group, suggesting that its effects were strongest in individuals with higher levels of self-esteem. A whole-brain functional magnetic resonance imaging analysis revealed that OXT also reduced responses during both self and other trait judgments in the dorsal (dmPFC) and ventral (vmPFC) medial prefrontal cortex. A subsequent region of interest analysis revealed that behavioral performance and self-esteem scale scores were associated with dmPFC activation and its functional connectivity with the anterior cingulate and between the vmPFC and posterior cingulate. Thus overall, while OXT may improve speed of decision making in self -vs. other trait judgments it also blunts the normal bias towards remembering self-attributes and reduces mPFC responses and connectivity with other cortical midline regions involved in self-processing. This is consistent with the view that OXT can reduce self-centered behavior. Hum Brain Mapp 37:2512-2527, 2016. © 2016 Wiley Periodicals, Inc.

Failure of a single dose of medroxyprogesterone acetate to induce uterine infertility in postnatally treated domestic cats

In mice and sheep, neonatal administration of progesterone or progestins inhibited development of uterine glands. The aims of the present study were (1) to describe uterine gland development on postnatal Days 6 to 8 and (2) to evaluate the effects of a single postnatal administration of a progestin on reproduction and adult uterine glands morphology and function in domestic cats. Necropsy was performed on three 1-week-old female cats which had died unrelated to this study. Ten female kittens were randomly assigned within the first 24 hours of birth to: medroxyprogesterone acetate 10 mg/animal subcutaneously (MPA; n = 6) or placebo (PLC; n = 4) and followed up until puberty when they were mated. Twenty-four days after the end of estrus, ovulation and pregnancy were diagnosed by serum progesterone measurement and ultrasonography, respectively. Then, all the cats were ovariohysterectomized. After necropsy or surgery, the excised organs were histologically evaluated. Seven queens ovulated (4 of 6 MPA and 3 of 4 PLC; P > 0.1) and were pregnant (P > 0.1). Four MPA cats presented endometrial hyperplasia and one of them developed a pyometra. The 1-week-old females presented uterine glands in the stage of budding and incipient penetration of the glandular epithelium into the underlying stroma. The MPA-treated queens revealed that the area occupied by uterine glands per square-micrometer (0.55 ± 0.2 vs. 0.49 ± 0.2; P > 0.1) and the height of the glandular epithelium (μm; 24.5 ± 6.7 vs. 24.4 ± 7.2; P > 0.1) did not differ from those of the PLC group. Neither significant gross nor microscopical differences were also found for ovaries (P > 0.1). It is concluded that 1-week-old kittens had an incipient stage of uterine gland development and that a single postnatal supraphysiological dose of MPA did not alter uterine adenogenesis in this species. Furthermore, this treatment seemed to predispose to uterine disease without prevention of fertility.

Short-term creatine supplementation has no impact on upper-body anaerobic power in trained wrestlers.

BackgroundCreatine (CR) is considered an effective nutritional supplement having ergogenic effects, which appears more pronounced in upper-body compared to lower-body exercise. Nevertheless, results regarding the impact of CR loading on repeated high-intensity arm-cranking exercise are scarce and in some cases conflicting. Interestingly, few of the conducted studies have structured their research designs to mimic real world sporting events. Therefore, our purpose was to address the hypothesis that CR ingestion would increase anaerobic power output in consecutive upper-body intermittent sprint performance (UBISP) tests designed to simulate wrestling matches on a competition-day.MethodsIn a double-blind, placebo-controlled, parallel-group study, 20 trained wrestlers were assigned to either placebo or CR supplemented group (0.3 g ∙ kg−1 of body mass per day). Four 6-min UBISP tests interspersed with 30-min recovery periods were performed before (trial 1) and after 5 days (trial 2) of supplementation. Each test consisted of six 15-s periods of arm-cranking at maximal executable cadence against resistance of 0.04 kg ∙ kg−1 body mass interspersed with 40-s unloaded easy cranking periods and 5-s acceleration intervals (T1–T4). Mean power (MP), peak power (PP), fatigue index and heart rate parameters were measured during UBISP tests. Also, body weight and hydration status were assessed. Principle measures were statistical analysed with mixed-model ANOVAs.ResultsMean individual CR consumption in the CR group was 24.8 ± 2.5 g ∙ d−1. No significant (P > 0.05) differences occurred in body mass or hydration status indices between the groups or across trials. MP, PP and fatigue index responses were unaffected by supplementation; although, a significant reduction in MP and PP did occurred from T1 to T4 in both trial 1 and 2 (P < 0.001). Overall heart rate responses in the tests tended to be higher in the CR than PLC group (P < 0.05); but, trends in responses in trials and tests were comparable (P > 0.05).ConclusionThese results suggest that 5-day CR supplementation has no impact on upper-body muscle anaerobic power output in consecutive UBISP anaerobic tests mimicking wrestling matches on a competition day.

Effect of Conjugated Linoleic Acid Associated With Aerobic Exercise on Body Fat and Lipid Profile in Obese Women: A Randomized, Double-Blinded, and Placebo-Controlled Trial.

The aim of this study was to analyze the effects of 8 weeks of conjugated linoleic acid (CLA) supplementation associated with aerobic exercise on body fat and lipid profile on obese women. We performed a randomized, double-blinded and placebo-controlled trial with 28 obese women who received 3.2 g/day of CLA or 4 g/day of olive oil (placebo group) while performing an 8-week protocol of aerobic exercise. Dietary intake (food record), body fat (dual-energy X-ray absorptiometry), and biochemical analysis (blood sample) were assessed before and after the intervention period. Independent of CLA supplementation, both groups improved (p < .05) oxygen uptake (CLA group, 13.2%; PLC group, 14.8%), trunk fat (CLA group, -1.0%; PLC group, -0.5%), leg fat (CLA group, -1.0%; PLC group, -1.6%), and total body fat (CLA group, -1.7%; PLC group, -1.3%) after the 8-week intervention. No main effect or Group × Time interaction was found for total cholesterol, triglycerides, and plasma lipoproteins (p > .05). We conclude that CLA supplementation associated with aerobic exercise has no effect on body fat reduction and lipid profile improvements over placebo in young adult obese women.

Оценка оптимальной структуры капитала компаний MD Medical Group и X5 Retail Group

Авторы: Дмитрий Александрович Воронцов dmit.vorontsov@gmail.com &#x0D; Никита Александрович Зубков nik.al.zubkov@gmail.com&#x0D; Поддержание оптимальной структуры капитала является одним из факторов, способствующих успешному развитию компании. Существующие теоретические модели позволяют определить оптимальный уровень долга с высокой точностью, однако зачастую при принятии решений по финансированию менеджмент руководствуется не только вопросами эффективности.Цель данной работы – рассмотреть ситуацию со структурой капитала и принятием решений по финансированию в российских компаниях. В статье определяется оптимальная структура капитала для двух публичных компаний – MD Medical Group Investments PLC и X5 Retail Group N.V., и проводится ее сравнение с фактической. Для анализа используются методы средневзвешенных затрат на капитал (WACC) и операционной прибыли. В результате мы пришли к выводу, что у MD Medical Group структура капитала близка к оптимальной, тогда как у X5 Retail Group уровень долговой нагрузки чрезмерен. Используя различные новостные источники, было выявлено, что при принятии решений менеджмент MD Medical Group с большой вероятностью руководствовался концепцией порядка выбора источников финансирования, тогда как на принятие решение в X5 Retail Group оказал влияние агентский конфликт.Исходя из новостей, связанных с компаниями, мы сделали предположение, что структура капитала MD Capital Group будет поддерживаться на оптимальном уровне, а X5 Retail Group начнет постепенно снижать чрезмерный уровень долга.Результатами данной статьи может воспользоваться широкий круг лиц: как исследователи теории корпоративных финансов, так и институциональные инвесторы и менеджмент компаний. Наибольший интерес представляют результаты MD Medical Group как единственной публичной российской компании сферы медицинских услуг; для лучшего понимания мотивов принятия финансовых решений в ней следует изучить структуру капитала компаний сферы здравоохранения на развитых и развивающихся рынках.

Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation

It is unknown whether loss in musculotendinous tissue during inactivity can be counteracted by growth hormone (GH), and whether GH accelerate rehabilitation in aging individuals. Elderly men (65-75 yr; n = 12) had one leg immobilized 2 wk followed by 6 wk of retraining and were randomly assigned to daily injections of recombinant GH (rhGH; n = 6) or placebo (Plc; n = 6). Cross-sectional area (CSA), muscle strength (MVC), and biomechanical properties of m. quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analyzed for gene expressions (mRNA) of collagen (COL1A1/3A1) and insulin-like growth factors (IGF-1Ea/Ec). Fibril morphology was analyzed by transmission electron microscope (TEM). In tendon, CSA and biomechanical properties did not change following immobilization, but an increase in CSA was found after 6 wk of rehabilitation in both groups. The changes were more pronounced when GH was injected. Furthermore, tendon stiffness increased in the GH group. Muscle CSA declined after immobilization in the Plc but not in the GH group. Muscle CSA increased during retraining, with a significantly larger increase in the GH group compared with the Plc group. Both a time and a group effect were seen for IGF-1Ea/Ec and COL1A1/3A1 mRNA expression in muscle, with a difference between GH and Plc. IGF-1Ea/Ec and COL-1A1/3A1 mRNA expression increased in muscle following immobilization and retraining in subjects receiving GH, whereas an increase in IGF-1Ec mRNA expression was seen in the Plc group only after retraining. In conclusion, in elderly humans, GH seems to have a matrix stabilizing effect during inactivity and rehabilitation by stimulating collagen expression in the musculotendinous tissue and increasing tendon CSA and stiffness.

Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: effect of growth hormone administration

We examined the effect of growth hormone (GH) on connective tissue of tendon and skeletal muscle during immobilisation and re-training in humans. Young men (20-30 years; n = 20) were randomly assigned to daily recombinant human GH (rhGH) (33-50 μg kg(-1) day(-1)) or placebo (Plc), and had one leg immobilised for 2 weeks, followed by 6 weeks of strength training. The cross-sectional area (CSA), maximal muscle strength (maximal voluntary contraction, MVC) and biomechanical properties of the quadriceps muscle and patellar tendon were determined. Muscle and tendon biopsies were analysed for mRNA of collagen (COL1A1/3A1), insulin-like growth factors (IGF-1Ea/Ec), lysyl oxidase (LOX), matrix metalloproteases (MMP-2 and MMP-9), decorin and tenascin-C. Fibril morphology was analysed by transmission electron microscopy (TEM) to detect changes in the fibril diameter distribution. In muscle, CSA and MVC declined with immobilisation and recovered with rehabilitation similarly in both groups. Likewise, both groups showed increased IGF-1Ea/Ec and COL1A1/3A1 expression in muscle during re-training after immobilisation compared with baseline, and the increase was more pronounced when subjects received GH. The tendon CSA did not change during immobilisation, but increased in both groups during 6 weeks of rehabilitation (∼14%). A decline in tendon stiffness after immobilisation was observed only in the Plc group, and an increase during 6 weeks of rehabilitation was observed only in the GH group. IGF-1Ea and COL1A1/3A1 mRNA increased with immobilisation in the GH group only, and LOX mRNA was higher in the GH group than in the Plc group after immobilisation. Both groups showed an increase in MMP-2 with immobilisation, whereas no changes in MMP-9, decorin and tenascin-C were observed. The tendon fibril diameter distribution remained unchanged in both groups. In conclusion, GH stimulates collagen expression in both skeletal muscle and tendon, abolishes the normal inactivity-related decline in tendon stiffness and LOX, and results in increased tendon CSA and stiffness during rehabilitation. GH has a matrix-stabilising effect during periods of inactivity and rehabilitation in humans.

Dietary sodium citrate supplementation enhances rehydration and recovery from rapid body mass loss in trained wrestlers

This study assessed the effects of dietary sodium citrate supplementation during a 16 h recovery from 5% rapid body mass loss (RBML) on physiological functions, affective state, and performance in trained wrestlers. Sixteen wrestlers performed an upper body intermittent sprint performance (UBISP) test under three conditions: before RBML, after RBML, and after a 16 h recovery from RBML. During recovery, the subjects ate a prescribed diet supplemented with sodium citrate (600 mg·kg(-1); CIT group, N = 8) or placebo (PLC group, N = 8) and drank water ad libitum. RBML reduced (p < 0.05) UBISP mean power and increased urine specific gravity (USG). Reduction in mean power was associated with changes in plasma volume (PV) (r = 0.649, p = 0.006) and USG (r = -0.553, p = 0.026). During the 16 h recovery, increases in body mass (BM) and PV were greater (p < 0.05) in the CIT group than in the PLC group. BM gain was associated with water retention in the CIT group (r = 0.899, p = 0.002) but not in the PLC group (r = 0.335, p = 0.417). Blood pH, HCO(3)(-) concentration, and base excess increased (p < 0.05) only in the CIT group. Changes in UBISP, general negative affect, and general positive affect did not differ in the two groups. In conclusion, ingestion of sodium citrate increases blood buffering capacity and PV and stimulates BM regain during a 16 h recovery from RBML in trained wrestlers. However, sodium citrate does not improve UBISP nor does it have an impact on the affective state.

The Combined Dexamethasone/TSST Paradigm – A New Method for Psychoneuroendocrinology

The two main physiological systems involved in the regulation of the stress response are the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). However, the interaction of these systems on the stress response remains poorly understood. To better understand the cross-regulatory effects of the different systems involved in stress regulation, we developed a new stress paradigm that keeps the activity of the HPA constant when exposing subjects to psychosocial stress. Thirty healthy male participants were recruited and randomly assigned to either a dexamethasone (DEX; n = 15) or placebo (PLC; n = 15) group. All subjects were instructed to take the Dexamethasone (2 mg) or Placebo pill the night before coming to the laboratory to undergo the Trier Social Stress Task (TSST). Salivary cortisol, salivary alpha amylase (sAA), heart rate, blood pressure and subjective stress were assessed throughout the protocol. As expected, the DEX group presented with suppressed cortisol levels. In comparison, their heart rate was elevated by approximately ten base points compared to the PLC group, with increases throughout the protocol and during the TSST. Neither sAA, nor systolic or diastolic blood pressures showed significant group differences. Subjective stress levels significantly increased from baseline, and were found to be higher before and after the TSST after DEX compared to placebo. These results demonstrate a significant interaction between the HPA and the SNS during acute stress. The SNS activity was found to be elevated in the presence of a suppressed HPA axis, with some further effects on subjective levels of stress. The method to suppress the HPA prior to inducing stress was found to completely reliable, without any adverse side effects. Therefore, we propose this paradigm as a new method to investigate the interaction of the two major stress systems in the regulation of the stress response.

Evaluation of outcomes in conservatively managed concomitant Type A and B posterolateral corner injuries in ACL deficient patients undergoing ACL reconstruction

IntroductionThere is paucity of literature regarding the outcomes of ACL reconstruction in ACL deficient knees with concomitant Type A and Type B PLC injuries. Materials and methodsA total of 102 patients undergoing isolated ACL reconstruction for an ACL injury were evaluated prospectively in this study. The patients with divided into three groups: group A with isolated ACL injury, group B1 with concomitant Type A PLC injury and group B2 with concomitant Type B PLC injury. The associated PLC injury in all these patients was managed conservatively. Outcome assessment was based on IKDC scores measured preoperatively and at last follow up visits. ResultsThe mean age of the patients was 25.33years (16–38years) with 95 males and seven females. The average follow up was almost 2.5years (13–46months). Group A had 88 patients while groups B1 and B2 had six and eight patients respectively. The preoperative IKDC scores were comparable for all the groups. The follow up IKDC scores were similar (statistically insignificant, p value: 0.421) for group A and group B1. Group B2 had poorer follow up IKDC scores as compared to group A and this result was found to be statistically significant (p value: 0.0001). ConclusionConservative management of a concomitant Type B PLC injury adversely affects the outcomes of ACL reconstruction in these patients. Type A PLC injuries, on the other, do well without surgery and can be left as such even when associated with a concomitant ACL tear.Level of evidence: Level 2

Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation

BackgroundThe present experiment examined the responses of peripheral modulators and indices of brain serotonin (5-HT) and dopamine (DA) function and their association with perception of effort during prolonged exercise in the heat after creatine (Cr) supplementation.MethodsTwenty one endurance-trained males performed, in a double-blind fashion, two constant-load exercise tests to exhaustion at 63 ± 5% O2 max in the heat (ambient temperature: 30.3 ± 0.5 °C, relative humidity: 70 ± 2%) before and after 7 days of Cr (20 g·d-1 Cr + 140 g·d-1 glucose polymer) or placebo (Plc) (160 g·d-1 glucose polymer) supplementation.Results3-way interaction has shown that Cr supplementation reduced rectal temperature, heart rate, ratings of perceived leg fatigue (P < 0.05), plasma free-tryptophan (Trp) (P < 0.01) and free-Trp:tyrosine ratio (P < 0.01) but did not influence the ratio of free-Trp:large neutral amino acids or contribute in improving endurance performance (Plc group, n = 10: 50.4 ± 8.4 min vs. 51.2 ± 8.0 min, P > 0.05; Cr group, n = 11: 47.0 ± 4.7 min vs. 49.7 ± 7.5 min, P > 0.05). However, after dividing the participants into "responders" and "non-responders" to Cr, based on their intramuscular Cr uptake, performance was higher in the "responders" relative to "non-responders" group (51.7 ± 7.4 min vs.47.3 ± 4.9 min, p < 0.05).Conclusionalthough Cr influenced key modulators of brain 5-HT and DA function and reduced various thermophysiological parameters which all may have contributed to the reduced effort perception during exercise in the heat, performance was improved only in the "responders" to Cr supplementation. The present results may also suggest the demanding of the pre-experimental identification of the participants into "responders" and "non-responders" to Cr supplementation before performing the main experimentation. Otherwise, the possibility of the type II error may be enhanced.

Addition of Pioglitazone and Ramipril to Intensive Insulin Therapy in Type 2 Diabetic Patients Improves Vascular Dysfunction by Different Mechanisms

We examined the relationship between glycemic control, vascular reactivity, and inflammation in type 2 diabetic subjects. Thirty subjects with type 2 diabetes were initiated on intensive insulin therapy (continuous subcutaneous insulin infusion [n = 12] or multiple daily injections [n = 18]) and then randomized to either pioglitazone (PIO group;45 mg/day), ramipril (RAM group; 10 mg/day), or placebo (PLC group) for 36 weeks. Euglycemic-hyperinsulinemic clamp was used to quantify insulin resistance, and plethysmography was used to assess changes in forearm blood flow (FBF) after 1) 5 min of reactive hyperemia and 2) brachial artery infusion of acetylcholine (7.5, 15, and 30 microg/min) and sodium nitroprusside (3 and 10 microg/min). The decreases in A1C (approximately 9.0-7.0%) and fasting plasma glucose (approximately 190-128 mg/dl) were equal in all groups. In the PIO group, glucose disposal increased from 3.1 to 4.7 mg x kg(-1) x min(-1), and there was a greater decrease in plasma triglycerides ( approximately 148 vs. 123 mg/dl) and free fatty acids (approximately 838 vs. 595 mEq/l) compared with the RAM or PLC groups (P < 0.05). Plasma adiponectin doubled with pioglitazone treatment (6.2 +/- 0.7 to 13.1 +/- 1.8 microg/ml), while endothelin-1 decreased only with ramipril treatment (2.5 +/- 0.2 to 1.1 +/- 0.2 pg/ml) (P < 001). The increase in FBF during reactive hyperemia (215%) and acetylcholine (from 132 to 205%, 216 to 262%, and 222 to 323%) was greater in the PIO versus RAM or PLC groups. In contrast, FBF during sodium nitroprusside treatment was greater in the RAM group (141-221% and 218-336%) compared with the PIO or PLC groups (all P < 0.05). Addition of pioglitazone or ramipril to intensive insulin therapy in type 2 diabetes further improves vascular dysfunction. Pioglitazone enhances endothelial-mediated vasodilation, whereas ACE inhibition enhances endothelial-independent vasodilation. These different vascular effects, combined with the observation that pioglitazone decreases free fatty acids and triglycerides and increases adiponectin, while ramipril reduces endothelin-1, suggest that different mechanisms underlie the vascular responses.

The Effect of Pioglitazone on the Liver

Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect on the liver is less clear. The goal of this study was to examine the effect of TZDs on GNG. Twenty sulfonylurea-treated type 2 diabetic subjects were randomly assigned (double-blind study) to receive pioglitazone (PIO group; 45 mg/day) or placebo (Plc group) for 4 months to assess endogenous glucose production (EGP) (3-(3)H-glucose infusion), GNG (D2O technique), and insulin sensitivity by two-step hyperinsulinemic-euglycemic clamp (240 and 960 pmol/min per m2). Fasting plasma glucose (FPG) (10.0 +/- 0.8 to 7.7 +/- 0.7 mmol/l) and HbA1c (9.0 +/- 0.4 to 7.3 +/- 0.6%) decreased in the PIO and increased in Plc group (P < 0.05 PIO vs. Plc). Insulin sensitivity increased approximately 40% during high insulin clamp after pioglitazone (P < 0.01) and remained unchanged in the Plc group (P < 0.05 PIO vs. Plc). EGP did not change, while GNG decreased in the PIO group (9.6 +/- 0.7 to 8.7 +/- 0.6 micromol x min(-1) x kg(ffm)(-1)) and increased in the Plc group (8.0 +/- 0.5 to 9.6 +/- 0.8) (P < 0.05 PIO vs. Plc). Change in FPG correlated with change in GNG flux (r = 0.63, P < 0.003) and in insulin sensitivity (r = 0.59, P < 0.01). Plasma adiponectin increased after pioglitazone (P < 0.001) and correlated with delta FPG (r = -0.54, P < 0.03), delta GNG flux (r = -0.47, P < 0.05), and delta insulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased after pioglitazone and correlated with delta GNG flux (r = 0.54, P < 0.02). From stepwise regression analysis, the strongest determinant of change in FPG was change in GNG flux. Pioglitazone improves FPG, primarily by reducing GNG flux in type 2 diabetic subjects.

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.

Amantadine for weight gain associated with olanzapine treatment

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score ≤45]; treated with olanzapine for 1–24 months; and who had gained ≥5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5–20 mg/day) was co-administered with double-blind treatment of 100–300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 ( P=0.042), 12 ( P=0.029), and 16 (primary endpoint, mean±S.D.: −0.19±4.58 versus 1.28±4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety–depression scores improved comparably in both groups, and Montgomery–Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.

Amantadine for weight gain associated with olanzapine treatment

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score ≤45]; treated with olanzapine for 1–24 months; and who had gained ≥5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5–20 mg/day) was co-administered with double-blind treatment of 100–300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean±S.D.: −0.19±4.58 versus 1.28±4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety–depression scores improved comparably in both groups, and Montgomery–Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.

P.2.125 A six-month, double-blind, controlled trial in schizophrenic patients comparing amisulpride and olanzapine

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score ≤45]; treated with olanzapine for 1–24 months; and who had gained ≥5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5–20 mg/day) was co-administered with double-blind treatment of 100–300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean±S.D.: −0.19±4.58 versus 1.28±4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety–depression scores improved comparably in both groups, and Montgomery–Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.

P.2.126 Evidence for aspartate as a neurotransmitter in the mediodorsal thalamus-medial prefrontal cortex pathway

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score ≤45]; treated with olanzapine for 1–24 months; and who had gained ≥5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5–20 mg/day) was co-administered with double-blind treatment of 100–300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean±S.D.: −0.19±4.58 versus 1.28±4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety–depression scores improved comparably in both groups, and Montgomery–Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.