Increases in ghrelin and decreases in leptin without altering adiponectin during extreme weight loss in male competitive bodybuilders

The aim of this study was to investigate responses of ghrelin, leptin, and adiponectin to a weight reduction period of 10 weeks in male subjects with high lean body mass and low body fat values. Fourteen male bodybuilders (7 competitors: 28.3 +/- 10.3 years, 175.3 +/- 5.4 cm, 82.2 +/- 9.3 kg; 7 controls: 22.4 +/- 3.0 years, 182.4 +/- 6.9 cm, 85.3 +/- 10.5 kg) participated in this study. The subjects were tested 3 times: 11 weeks (TEST1), 5 weeks (TEST2), and 3 days (TEST3) before the national championships. Testing procedure included dual-energy x-ray absorptiometry scan; calculation of daily energy intake and expenditure; and venous blood sampling for fasting ghrelin, leptin, and adiponectin. In the competitors' group, a significant (P < .05) 4.1-kg loss of body fat was observed that resulted in 6.5% +/- 1.5% of the body fat at the end of the study. Ghrelin increased significantly by 20.4% by TEST2. By TEST3, ghrelin was further increased by 6% (P > .05). The pattern of leptin was opposite, with a significant 27.7% decrease at TEST2 and no further decrease at TEST3 (P > .05). No significant change was observed in adiponectin concentration during the study. In the control group, no significant changes in biochemical parameters were observed. In conclusion, ghrelin concentration significantly increases, but is suppressed in conditions of limited energy availability that is accompanied by significant body mass loss in male subjects with initial low body fat values.     

The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01). CONCLUSION: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.     

Ein Beitrag zur Begutachtung von Rh-Ausschlüssen in Vaterschaftsblutgruppenuntersuchungen

Zusammenfassung In dem großen Material unserer Mutter-Kind-Paare, die anläßlich von Paternitätsuntersuchungen zur Beobachtung kamen, fand sich ein Fall entgegengesetzter Homozygotie im Rh-System, der nicht mit Untersuchungsfehlern oder Kindsvertauschung erklärt werden kann. D- - ist die wahrscheinlichste Erklärung. Wegen der Seltenheit dieser Funde werden wir vorerst wieHoppe undHain undProkop undSchneider an dem bisher geübten Gutachtentenor im Ausschlußfall festhalten. Fälle der Art, wie beschrieben, stellen jedoch eine Indikation zur Erweiterung der Untersuchung auf andere Sippenmitglieder.     

In vivo gene delivery of Ad-VEGF121 to full-thickness wounds in aged pigs results in high levels of VEGF expression but not in accelerated healing

We have previously reported that endogenous vascular endothelial growth factor (VEGF) concentration in older pig wounds peaked later and at one-fourth the level of young pigs. These data suggested that VEGF might play a major role in the healing of full-thickness wounds in the aged pig. By in vivo gene transfer using the microseeding technique, we treated full-thickness wounds with different doses of VEGF-expressing adenoviral vector (Ad-VEGF) varying from 1 x 10(7) to 2.7 x 10(11) particles per wound (ppw). We found that the VEGF expression in wound fluid followed a dose-response pattern. However, when wounds were microseeded with the highest concentration of Ad-VEGF (2.7 x 10(11) ppw), diminished healing rates were found. We then determined the minimal functional concentrations of Ad-VEGF. We used five aged Yucatan minipigs, all retired breeders, to analyze the role of over-expression of 1 x 10(8) and 1 x 10(9) ppw of Ad-VEGF (n= 78) in terms of healing of full-thickness wounds, all 2.5 x 2.5 x 1 cm in size (n= 158). The Ad-VEGF solutions were delivered to the wound floor and borders by in vivo microseeding. Control wounds (n= 80) were microseeded with Ad-Lac-Z (n= 25), treated with saline (n= 49) or treated dry (n= 6). All wounds except for the dry-treated ones were covered with a wound chamber and a wet environment was created by injecting 2.5 ml saline into the chamber. Peak VEGF expression (2300-4000 pg/ml) was detected on days 2 or 3 post gene delivery. This level of VEGF expression was not seen in the saline (n= 49) or Ad-null (n= 25) control groups. The VEGF expression in wounds treated with 1 x 10(8) and 3 x 10(8) ppw (n= 39) exhibited a slower onset with a peak concentration of 400-920 pg/ml on days 5-7. Although high levels of VEGF expression were achieved in the local wound environment, we could not show a significant increase in neovascularization as compared to saline-treated wounds. No significant differences were observed in the rate of reepithelialization and wound contraction among groups of full-thickness wounds treated with Ad-VEGF, Ad-null mutant, or saline in the aged "wet wound healing" pig model. These results indicate that increased levels of VEGF in wounds produced by in vivo gene transfer have little effect on the healing of full-thickness wounds in the aged pig model. Moreover, significantly higher levels of VEGF expression by Ad-VEGF could lead to impaired wound healing.     

No effect of menstrual cycle phase on fuel oxidation during exercise in rowers

The aim of this investigation was to examine the effects of menstrual cycle phase on substrate oxidation and lactate concentration during exercise. Eleven eumenorrheic female rowers (18.4 ± 1.9 years; 172.0 ± 4.0 cm; 67.2 ± 8.4 kg; 27.7 ± 4.8% body fat) completed 1 h rowing ergometer exercise at 70% of maximal oxygen consumption (VO_2max) during two different phases of the menstrual cycle: the follicular phase (FP) and the luteal phase (LP). Resting and exercise measurements of the whole body energy expenditure, oxygen consumption (VO₂), respiratory exchange ratio (RER), substrate oxidation and lactate blood levels were made. Energy expenditure, VO₂ and heart rate during the 1-h exercise were not significantly different (P > 0.05) among menstrual cycle phases. Resting RER and RER during the entire 1 h exercise period were not significantly different among menstrual cycle phases. There was an increase (P < 0.05) in RER in the transition between rest and exercise and a further increase in RER occurred after the first 30 min of exercise at both menstrual cycle phases. Blood lactate concentrations significantly increased in the transition between rest and exercise and remained relatively constant during the whole 1 h of exercise in both menstrual cycle phases. No menstrual cycle phase effect (P > 0.05) was observed for blood lactate concentrations. In conclusion, our results demonstrated no effect of menstrual cycle phase on substrate oxidation and blood lactate concentration during rowing exercise at 70% of VO_2max in athletes. Normally menstruating female rowers should not be concerned about their menstrual cycle phase with regard to substrate oxidation in everyday training.     

Pain management in the traumatic amputee

Traumatic amputees may experience a variety of acute and chronic pain issues, including phantom limb pain and residual limb pain. Research continues to determine the causes of these problems and to find the most appropriate and effective treatments for each of these phenomena. It is important for health care providers to be knowledgeable about the variety of treatments available, including medications, surgical procedures, complementary and alternative therapies, and self-treatment methods to ensure that amputees receive the best practices for individualized, effective pain management that they deserve.     

Wernicke’s Syndrome after Sleeve Gastrectomy

We report a case of Wernicke’s encephalopathy after sleeve gastrectomy, which had been complicated by stomach wall edema and aggravated by dietary noncompliance. Despite intense parenteral nutrition, thiamine deficiency became clinically evident. It suggests that nutritional preparations used were unable to cover the increased thiamine requirement. After intense thiamine supplementation, gradual improvement occurred during the 6 months after the diagnosis, without permanent cognitive impairment. Clinicians involved in postoperative management of bariatric surgery patients must consider Wernicke’s syndrome in hyper-emetic patients, who show unclear neurological deterioration. Early diagnosis and treatment can instantly improve the patient’s condition without permanent sequelae.     

Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury

Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair. We demonstrate here that stroma-iC3b tethers HPCs via the inserted (I) domain of HPC complement receptor 3 (CR3, CD11b/CD18, Mac-1). Following irradiation, stroma-iC3b was observed in the presence of purified IgM and normal mouse serum (NMS), but not serum from Rag-2(-/-) mice, implicating a role for antibody (Ab) and the classic pathway of C activation. Furthermore, a novel role for soluble yeast beta-glucan, a ligand for the CR3 lectin-like domain (LLD), in the priming of CR3(+) HPC is suggested. Soluble yeast beta-glucan could enhance the proliferation of tethered HPCs, promote leukocyte recovery following sublethal irradiation, and increase the survival of lethally irradiated animals following allogeneic HPC transplantation in a CR3-dependent manner. Taken together, these observations suggest a novel role for C, CR3, and beta-glucan in the restoration of hematopoiesis following injury.     

Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow

The mechanisms regulating the homing/mobilization of hematopoietic stem/progenitor cells (HSPCs) are not fully understood. In our previous studies we showed that the complement C3 activation peptide, C3a, sensitizes responses of HSPCs to stromal-derived factor 1 (SDF-1). In this study, mobilization was induced with granulocyte colony-stimulating factor (G-CSF) in both C3-deficient (C3-/-) and C3a receptor-deficient (C3aR-/-) mice as well as in wild-type (wt) mice in the presence or absence of a C3aR antagonist, SB 290157. The data indicated (1) significantly increased G-CSF-induced mobilization in C3-/- and C3aR-/- mice compared with wt mice, (2) significantly accelerated and enhanced G-CSF-induced mobilization in wt, but not in C3-/- or C3aR-/-, mice treated with SB 290157, and (3) deposition of C3b/iC3b fragments onto the viable bone marrow (BM) cells of G-CSF-treated animals. Furthermore, mobilization studies performed in chimeric mice revealed that wt mice reconstituted with C3aR-/- BM cells, but not C3aR-/- mice reconstituted with wt BM cells, are more sensitive to G-CSF-induced mobilization, suggesting that C3aR deficiency on graft-derived cells is responsible for this increased mobilization. Hence we suggest that C3 is activated in mobilized BM into C3a and C3b, and that the C3a-C3aR axis plays an important and novel role in retention of HSPCs (by counteracting mobilization) by increasing their responsiveness to SDF-1, the concentration of which is reduced in BM during mobilization. The C3a-C3aR axis may prevent an uncontrolled release of HSPCs into peripheral blood. These data further suggest that the C3aR antagonist SB 290157 could be developed as a drug to mobilize HSPCs for transplantation.