Mixture of Arginine,Glutamine, and β‐hydroxy‐β‐methyl Butyrate Enhances the Healing of Ischemic Wounds in Rats

Background: This study investigated the effects of an amino acid mixture containing arginine, glutamine, and β‐hydroxy‐β‐methyl butyrate on secondary healing of ischemic wounds in a rat model (N = 18). Methods: After the formation of a bipediculated flap on each rat, 2 full‐thickness excisional skin wounds (2 × 2 cm) were created on every flap. The rats were then randomized into the control and treatment groups. Every rat received standardized rat food throughout the study. The rats in the treatment group were administered an extra 200 mg/kg of L‐arginine, 200 mg/kg of L‐glutamine, and 40 mg/kg of β‐hydroxy‐β‐methyl butyrate per day. Wound sizes were measured on days 0, 4, 10, and 14. The rats were sacrificed, and the wounds were excised for biochemical and histologic examination on the 14th day. Results: As compared with the control group, the treatment group's wound sizes were significantly smaller on days 10 and 14 (P < .001), as was its inflammatory cell accumulation score (P = .008). There was no significant difference between the 2 groups in collagen accumulation (P = .340), granulation tissue maturation (P = .161), angiogenesis (P = .387), or reepithelialization (P = .190) and no significant difference between hydroxyproline concentrations in wounds (P = .287). Discussion: This amino acid combination seems to have a positive impact on the secondary healing of experimental ischemic wounds when introduced as a supplement to the standard diet, and the reduction in the inflammatory process appears to play a role in this effect.     

Pilot Experimental Study on the Effect of Arginine,Glutamine, and β‐Hydroxy β‐Methylbutyrate on Secondary Wound Healing

Background: Wound healing is a complex process, dependent on available nutrition substrates. When used together with β‐hydroxy β‐methylbutyrate, arginine and glutamine have been shown to increase collagen deposition in human subjects. However, there are no experimental investigations on the influence of this amino acid mixture with regard to secondary wound healing. The aim of this study is to investigate the effects of the supplementation of these 3 amino acids on the healing of open wounds in otherwise healthy animals. Materials and Methods: Twelve rats were divided into control and treatment groups. Two 2‐cm × 1‐cm full‐thickness skin defects were prepared on each subject. The rats in both groups received a diet containing 1.2 g of protein per 100 g of body weight per day. The treatment group, in addition, received 200 mg/kg L‐arginine, 200 mg/kg L‐glutamine, and 40 mg/kg β‐hydroxy β‐methylbutyrate every day. Wound sizes were measured every 2 days. On the 10th day, tissue samples were taken for histopathologic evaluation and also for the measurement of hydroxyproline concentrations. Results: There was no statistically significant difference between mean wound sizes for the 2 groups (P > .05). There was also no statistically significant difference between the groups with regard to histological healing parameters (reepithelialization [P = 1.00], granulation tissue [P = 1.00], collagen accumulation [P = .455], inflammatory cell accumulation [P = .455], angiogenesis [P = .242]) or tissue hydroxyproline concentrations (P = .240). Conclusion: Diet supplemented with arginine, glutamine, and β‐hydroxy β‐methylbutyrate is not beneficial in enhancing secondary healing of open wounds in rats. Further research regarding this topic is warranted.     

Effect on an Oral Nutritional Supplement with β-Hydroxy-β-methylbutyrate and Vitamin D on Morphofunctional Aspects,Body Composition,and Phase Angle in Malnourished Patients

This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with β-hydroxy-β-methylbutyrate (HMB) on nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6–3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (n = 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. −0.36 (0.4), and 2.98 (0.5) vs. −0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.     

Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: a cohort study

Background: Older adults supplemented for 1 year with β‐hydroxy‐β‐methylbutyrate, arginine, and lysine (HMB/ARG/LYS) were previously shown to have significant gains in fat‐free mass (FFM) but not muscular strength. Objective: Recently, increasing levels of serum vitamin D have been associated with an increase in muscle function, particularly in the elderly. To determine if vitamin D status may have limited strength gain in participants supplemented with HMB/ARG/LYS, the authors performed post hoc analysis of strength based on the participants' vitamin D status. Methods: Elderly (age 76.0 ± 1.6 years) adults were recruited for a double‐blinded, controlled study and were randomly assigned to either an isonitrogenous control (n = 37) or HMB/ARG/LYS (n = 40) for the yearlong study. Participants were further segregated based on their vitamin D status of either <30 or ≥30 ng 25OH‐vitD₃/mL serum, and an analysis was performed on the 4 cohorts. Results: Regardless of vitamin D status, HMB/ARG/LYS resulted in significantly increased FFM (P < .02), but only in those with vitamin D status ≥30 ng 25OH‐vitD₃/mL was there a significant increase in strength with HMB/ARG/LYS (P < .01). Control‐supplemented participants, regardless of vitamin D status, and the HMB/ARG/LYS‐supplemented participants with vitamin D status <30 ng 25OH‐vitD₃ failed to show improvements in strength. Conclusions: The nutrient cocktail of HMB/ARG/LYS alone was effective in increasing muscle mass regardless of vitamin D status, but accompanying strength increases were observed only when participants also had adequate vitamin D status indicating a synergistic effect between the HMB/ARG/LYS and vitamin D.     

Soybean and Fish Oil Mixture With Different ω‐6/ω‐3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium–Induced Changes in Small Intestinal Intraepithelial γδT‐Lymphocyte Expression in Mice

Background: This study investigated the effect of different ω‐6/ω‐3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)–induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT‐cell expression. Methods: Mice were assigned to 3 control and 3 DSS‐treated groups and were maintained on a low‐fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω‐3 and Lω‐3) groups and 2 other DSS (DHω‐3 and DLω‐3) groups were fed either a soybean and fish oil mixture with a ω‐6/ω‐3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT‐cell subset was isolated for analysis. Results: DSS treatment resulted in a lower small intestinal IEL γδT‐cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω‐3 group, the DHω‐3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator‐activated receptor (PPAR)–γ gene by small intestinal IEL γδT cells. Conclusions: Fish oil diets with a ω‐6/ω‐3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS‐induced small intestinal injury, and activation of PPAR‐γ in IEL γδT cells may be associated with resolution of small intestinal inflammation.     

Effects of β-Hydroxy β-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents

β-hydroxy β-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase.     

ω‐3 Fatty Acids Prevent Hepatic Steatosis,Independent of PPAR‐α Activity,in a Murine Model of Parenteral Nutrition–Associated Liver Disease

Objectives: ω‐3 Fatty acids (FAs), natural ligands for the peroxisome proliferator‐activated receptor–α (PPAR‐α), attenuate parenteral nutrition–associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω‐3 FAs are still unknown. The aim of this study was to determine the effects of ω‐3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR‐α and microsomal triglyceride transfer protein (MTP) in this experimental setting. Methods: 129S1/SvImJ wild‐type or 129S4/SvJaePparatm/Gonz/J PPAR‐α knockout mice were fed chow and water (controls); oral, fat‐free PN solution only (PN‐O); PN‐O plus intraperitoneal (IP) ω‐6 FA‐predominant supplements (PN–ω‐6); or PN‐O plus IP ω‐3 FA (PN–ω‐3). Control and PN‐O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR‐α messenger RNA were assessed after 19 days. Results: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN‐O and PN–ω‐6 groups accumulated significantly greater amounts of TG when compared with PN–ω‐3 mice. Studies in PPAR‐α null animals showed that PN feeding increases hepatic TG as in wild‐type mice. PPAR‐α null mice in the PN‐O and PN–ω‐6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω‐3 FAs. Conclusions: PN induces TG accumulation (steatosis) in wild‐type and PPAR‐α null mice. In PN‐fed wild‐type and PPAR‐α null mice given IP ω‐3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω‐3 FAs results from PPAR‐α–independent pathways.     

Rapid Incorporation of ω‐3 Fatty Acids Into Colonic Tissue After Oral Supplementation in Patients With Colorectal Cancer

Background: The purpose of the study was to examine whether a preoperative supplement with ω‐3 fatty acids (FAs) leads to their incorporation into colonic tissue in patients scheduled for colorectal cancer surgery. This would be of interest because ω‐3 FAs have potential beneficial (local) immunological effects that might benefit these patients. Methods: In a randomized, double‐blind, prospective, placebo‐controlled, single‐center intervention trial, patients referred for elective colorectal cancer surgery received either an ω‐3 FA–enriched oral nutrition supplement (ONS) (200 mL twice daily) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for 7 days before surgery. Tissue samples from healthy colonic tissue (mucosa and muscular layer) were obtained during surgery, and tissue fatty acid composition was analyzed by gas chromatography. Results: EPA was significantly higher in colonic mucosa (P = .001) and in the colonic muscular layer (P = .004) in the ω‐3 FA group compared with controls. Patients in the ω‐3 FA group also tended to have higher docosapentaenoic acid and DHA levels in colonic tissue. Conclusions: EPA is incorporated rapidly into colonic mucosa and colonic muscular layer in patients given 3 g of ω‐3 FA daily for 7 days before surgery for colorectal cancer. This may lead to potential beneficially effects on (local) immune function, which might benefit these patients.     

Long‐Term Body Composition Changes in Women Following Roux‐en‐Y Gastric Bypass Surgery

Background: Although most individuals experience successful weight loss following Roux‐en‐Y gastric bypass (RYGB), weight regain is a concern, the composition of which is not well documented. Our aim was to evaluate changes in body composition and handgrip strength as a measure of functional status in participants from a previous 1‐year post‐RYGB longitudinal study who had undergone RYGB approximately 9 years prior. Methods: Five women from an original larger cohort were monitored pre‐RYGB and 1.5 months, 6 months, 1 year, and 9 years post‐RYGB. Body composition was assessed at all time points using dual energy x‐ray absorptiometry and multiple dilution. Handgrip strength was measured using a digital isokinetic hand dynamometer (Takei Scientific Instruments, Ltd, Tokyo, Japan). Results: Mean time to final follow‐up was 8.7 years. Lean soft tissue (LST) loss over the ~9‐year period was on average 11.9 ± 5.6 kg. Compared with 1‐year post‐RYGB, 9‐year LST was 4.4 ± 3.0 kg lower (P = .03). Fat‐free mass decreased over the 9‐year period by 12.6 ± 5.8 kg. Mean fat mass (FM) decreased from 75.4 ± 22.6 kg pre‐RYGB to 35.5 ± 21.5 kg 1 year post‐RYGB but then trended toward an increase of 8.6 ± 7.0 kg between 1 year and 9 years post‐RYGB (P = .053). Loss of LST was correlated with loss of handgrip strength (r = 0.64, P = .0005). Conclusion: The continued loss of lean mass associated with decreased handgrip strength occurring with long‐term trend toward FM regain post‐RYGB is concerning. The loss of LST and functional strength carries particular implications for the aging bariatric population and should be investigated further.     

Parenteral ω‐3 Fatty Acid Lipid Emulsions for Children With Intestinal Failure and Other Conditions

Background: There is growing interest in the use of ω‐3 fatty acid (n‐3FA) lipid emulsions to prevent complications associated with parenteral nutrition. The authors systematically reviewed the evidence on the benefits and safety of n‐3FA compared with standard lipid emulsions in children with intestinal disease, critical illness, trauma, or postoperative complications. Materials and Methods: The authors searched 4 bibliographic databases from their inception to March 2011, conference proceedings, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodological quality, and rated the strength of the evidence. One reviewer extracted and a second reviewer verified data. The authors summarized findings qualitatively and conducted meta‐analysis when appropriate. Results: Five randomized controlled trials with unclear risk of bias and 3 high‐quality prospective cohort studies were included. The studies examined premature, low birth weight infants (n = 6) and children with heart disease (n = 1) or intestinal failure (n = 1). The strength of evidence was consistently low or very low across all lipid emulsion comparisons and outcomes. In young children, n‐3FA emulsions resulted in improvement in some biochemical outcomes of intestinal failure–associated liver disease but no difference in mortality. Few studies examined patient‐important outcomes, such as length of hospital and intensive care stay; need for transplantation, growth, and cognitive development; or the long‐term effects and potential harms associated with these therapies. Conclusions: Currently, there is a lack of sufficient high‐quality data to support the use of parenteral n‐3FA lipid emulsions in children. Future trials examining long‐term clinical outcomes and harms are needed.     

Accuracy of octa‐polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in children and adolescents with HIV: comparison with dual energy X‐ray absorptiometry and air displacement plethysmography

Background

Body composition analysis has been used to investigate fat mass (FM ) and bone mineral content (BMC ) in children and adolescents diagnosed with HIV . Investigating the validity of bioelectrical impedance analysis (BIA ) is interesting with respect to testing useful techniques for monitoring body composition in children and adolescents in clinical practice. The present study aimed to determine the validity of body composition analysis by BIA compared to dual‐energy X‐ray absorptiometry (DXA ) and air displacement plethysmography (ADP ) in children and adolescents an HIV diagnosis.

Methods

Sixty‐four children and adolescents (35 females and 29 males) with a mean (SD ) age of 12.22 (2.13) years and with an HIV diagnosis participated in the study. Fat‐free mass (FFM ), FM and body fat percentage (%BF ) were obtained by BIA for comparison with DXA and ADP . Segmented FM (trunk, legs and arms), lean soft tissue mass (LSTM ) (total and segmented) and BMC were obtained by BIA for comparison with DXA .

Results

BIA presented a clinically acceptable correlation with DXA and ADP for FFM . Values found by BIA were underestimated compared to ADP , and overestimated compared to DXA . BIA presented a clinically acceptable correlation with DXA for LSTM estimates (total and segmented parameters) in both sexes (underestimating FM and overestimating LSTM ). For other components (%BF , FM and BMC ), BIA had a clinically unacceptable correlation with the reference methods in both sexes.

Conclusions

BIA was suitable for evaluating FFM and LSTM in children and adolescents with an HIV diagnosis. For FM , %BF and BMC , BIA was not suitable for performing an evaluation in both sexes.

     

Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study

BACKGROUND: The current study was designed to examine whether a combination of three nutrients, consisting of beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of leucine, L-glutamine (Gln) and L-arginine (Arg), each of which has been previously shown to slow muscle proteolysis, could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome (AIDS). METHODS: Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5% in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center. The subjects were randomly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture (HMB/Arg/Gln) containing 3 g HMB, 14 g L-glutamine, and 14 g L-arginine given in two divided doses daily for 8 weeks. Body weights (BW) were recorded weekly and lean body mass (LBM) and fat mass (FM) were measured by air displacement plethysmography and by a single computerized tomography (CT) slice through the thigh at 0, 4, and 8 weeks. RESULTS: Forty-three subjects completed the 8-week protocol, (placebo, n = 21; HMB/Arg/Gln, n = 22). At 8 weeks, the subjects consuming the HMB/Arg/Gln mixture gained 3.0 +/- 0.5 kg of BW while those supplemented with the placebo gained 0.37 +/- 0.84 kg (p = .009). The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM (2.55 +/- 0.75 kg) compared with the placebo-supplemented subjects who lost lean mass (-0.70 +/- 0.69 kg, p = .003). No significant change in FM gain was observed (0.43 +/- 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 +/- 0.64 kg for the group receiving the placebo, p > .20). Similar percentage changes in muscle mass and fat mass were observed with CT scans. Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation. CONCLUSIONS: The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting.     

Intravenous ω‐3 Fatty Acids Plus Gemcitabine

Background: Marine‐derived ω‐3 fatty acids (ω‐3FAs) have proven antitumor activity in vivo and in vitro and improve quality of life (QOL) in clinical cancer studies. These changes may be mediated by reduction in circulating proangiogenic and proinflammatory factors. In this first study of intravenous ω‐3FAs as a therapy in cancer patients, we aimed to assess if it could augment the antitumor activity of gemcitabine in patients with advanced pancreatic cancer and improve QOL. Materials and Methods: Patients were administered gemcitabine 1000 mg/m³ weekly followed by up to 100 g (200 mg/mL) of ω‐3 rich lipid emulsion for 3 weeks followed by a rest week. This was continued for up to 6 cycles, progression, unacceptable toxicity, patient request, or death. The primary outcome measure was objective response rate, with secondary outcome measures of overall and progression free survival, QOL scores, and adverse events. Results: Fifty patients were recruited. Response rate was 14.3% and disease control rate was 85.7%. Overall and progression free survival were 5.9 and 4.8 months, respectively. Increase in global health of > 10% over baseline was seen in 47.2% of patients. More than 50% of patients had > 10% increase in QOL scores in generic symptom scores and both disease‐specific domains. Grade 3/4 adverse events were thrombocytopenia (8%), neutropenia (12%), nausea or vomiting (4%), and chills (6%). Conclusion: Intravenous ω‐3FAs in combination with gemcitabine shows evidence of improved activity and benefit to QOL in patients with advanced pancreas cancer and is worthy of investigation in a randomized phase III trial.     

Effects of the ω‐6:ω‐3 Fatty Acid Ratio of Fat Emulsions on the Fatty Acid Composition in Cell Membranes and the Anti‐Inflammatory Action

Background: This study investigated the effects of parenterally administered fish oil (FO) on the fatty acid composition in rats to determine the optimal ω‐6:ω‐3 polyunsaturated fatty acid (PUFA) ratio of fat emulsions to achieve an anti‐inflammatory effect. Methods: Male Sprague‐Dawley rats were infused a parenteral nutrition (PN) solution containing fat emulsions with different ω‐6:ω‐3 PUFA ratios. The fatty acid content of phospholipids in the membranes of splenocytes was analyzed by gas chromatography (experiment 1). In addition, the amounts of leukotriene (LT) B₄ and LTB₅ released from peritoneal polymorphonuclear leukocytes (PMNs) were measured by high‐performance liquid chromatography (experiment 2). Results: In experiment 1, after infusion of the fat emulsion containing FO, the ω‐3 PUFA content in cell membranes rose to 70% of the peak value on day 1 and nearly reached a plateau on day 3. The highest ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) was achieved by administrating a PN solution with the smallest ω‐6:ω‐3 PUFA ratio. In experiment 2, a larger amount of LTB₅ was released from Ca‐ionophore‐stimulated PMNs taken from rats given a larger quantity of FO. The ratio of LTB₅:LTB₄ released from PMNs correlated positively with the EPA:AA ratio in the membranous phospholipid and in serum. Conclusions: The ω‐3 PUFAs were readily incorporated into the cell membrane within 3 days of infusion with the fat emulsion. The EPA:AA ratio in membranous phospholipid in PMNs was positively correlated with the LTB₅:LTB₄ production ratio and was a good indicator of anti‐inflammatory effects.     

Preliminary Safety and Efficacy of L‐carnitine Infusion for the Treatment of Vasopressor‐Dependent Septic Shock

Background: Sepsis is characterized by metabolic disturbances, and previous data suggest a relative carnitine deficiency may contribute to metabolic dysfunction. Studies regarding safety and patient‐centered efficacy of carnitine during septic shock are lacking. Methods: This was a double‐blind randomized control trial of levocarnitine (L‐carnitine) infusion vs normal saline for the treatment of vasopressor‐dependent septic shock. Patients meeting consensus definition for septic shock with a cumulative vasopressor index ≥3 and sequential organ failure assessment (SOFA) score ≥5 enrolled within 16 hours of the recognition of septic shock were eligible. The primary safety outcome was difference in serious adverse events (SAEs) per patient between groups. Efficacy outcomes included proportion of patients demonstrating a decrease in SOFA score of 2 or more points at 24 hours and short‐ and long‐term survival. Results: Of the 31 patients enrolled, 16 were in the L‐carnitine and 15 were in the placebo arm. There was no difference in SAEs between placebo and intervention (2.1 vs 1.8 SAEs per patient, P = .44). There was no difference in the proportion of patients achieving a decrease in SOFA score of 2 or more points at 24 hours between placebo and treatment (53% vs 44%, P = .59). Mortality was significantly lower at 28 days in the L‐carnitine group (4/16 vs 9/15, P = .048), with a nonsignificant improved survival at 1 year (P = .06). Conclusion: L‐carnitine infusion appears safe in vasopressor‐dependent septic shock. Preliminary efficacy data suggest potential benefit of L‐carnitine treatment, and further testing is indicated.     

Effects of ω‐3 Polyunsaturated Fatty Acids on the Homeostasis of CD4+ T Cells and Lung Injury in Mice With Polymicrobial Sepsis

Background: Sepsis is a common cause of death in critically ill patients. An overwhelming inflammatory response and imbalance of helper T (Th) cells and regulatory T (Treg) cells are thought to be involved in the progression of sepsis. ω‐3 Polyunsaturated fatty acids (PUFAs) were found to have anti‐inflammatory and immunomodulatory properties. This study investigated the effects of ω‐3 PUFAs on the balance of Th subsets, Treg cells, and the inflammatory response in septic mice. Methods: Mice were randomly assigned to soybean oil (SO) and fish oil (FO) groups. The 2 groups received an identical nutrient distribution except for the sources of the fat. The SO group was fed soybean oil, while part of the soybean oil was replaced by fish oil in the FO group. The FO group had an ω‐6/ω‐3 PUFA ratio of 2:1. After feeding the diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed on days 0, 1, and 3. Results: Compared with the SO group, the FO group had lower inflammatory mediator levels in the plasma and peritoneal lavage fluid after CLP. Also, the FO group had lower Th1, Th2, and Th17 percentages and a higher Th1/Th2 ratio in blood. In lung tissues, neutrophil infiltration was reduced, whereas peroxisome proliferator–activated receptor γ expression was upregulated. Conclusions: A fish oil diet with an ω‐6/ω‐3 PUFA ratio of 2:1 may elicit more balanced Th polarization, alleviate inflammatory responses, and attenuate lung injury in CLP‐induced sepsis.     

β-Alkoxy-substituted phenethylamines: a family of compounds potentially active at the dopamine and α-adrenergic receptors

A series of β-alkoxy-substituted phenethylamines were synthesized and tested for their affinity at the D₁ and D₂ dopaminergic receptors and the α₁ and α₂ adrenoceptors. None of the tested compounds exhibited D₂ receptor affinity. Among the nonhydroxylated compounds that were resolved to their antipodes, the (−)-enantiomers generally showed a moderate but distinct activity at the α₂ receptor. Ring hydroxylation appears to be a necessary requirement for D₁ activity. These results are discussed in terms of the structural elements of the tested drugs as compared to those of known active compounds.     

Effect of whey and soy protein supplementation combined with resistance training in young adults

The purpose was to compare changes in lean tissue mass, strength, and myofibrillar protein catabolism resulting from combining whey protein or soy protein with resistance training. Twenty-seven untrained healthy subjects (18 female, 9 male) age 18 to 35 y were randomly assigned (double blind) to supplement with whey protein (W; 1.2 g/kg body mass whey protein + 0.3 g/kg body mass sucrose power, N = 9: 6 female, 3 male), soy protein (S; 1.2 g/kg body mass soy protein + 0.3 g/kg body mass sucrose powder, N= 9: 6 female, 3 male) or placebo (P; 1.2 g/kg body mass maltodextrine + 0.3 g/kg body mass sucrose powder, N = 9: 6 female, 3 male) for 6 wk. Before and after training, measurements were taken for lean tissue mass (dual energy X-ray absorptiometry), strength (1-RM for bench press and hack squat), and an indicator of myofibrillar protein catabolism (urinary 3-methylhistidine). Results showed that protein supplementation during resistance training, independent of source, increased lean tissue mass and strength over isocaloric placebo and resistance training (P < 0.05). We conclude that young adults who supplement with protein during a structured resistance training program experience minimal beneficial effects in lean tissue mass and strength.