Home parenteral nutrition is beneficial in systemic sclerosis patients with gastrointestinal dysfunction.

OBJECTIVES: To assess 12-month changes in nutritional status and quality of life (QoL) in systemic sclerosis (SSc) patients requiring home parenteral nutrition (HPN). METHOD: We conducted a retrospective, single-centre database analysis of SSc patients regarding a 12-month period of HPN at an interdisciplinary University Unit/team for nutrition and rheumatic diseases. Nutritional status was analysed by nutritional risk screening (NRS) and body mass index (BMI). QoL was evaluated using Short-Form Health Survey (SF-36) questionnaires. RESULTS: Between 2008 and 2013, daily nocturnal HPN was initiated in five consecutive SSc patients (four females and one male, mean age 62.2 years) suffering severe malnutrition due to gastrointestinal tract (GIT) involvement. After 12 months of HPN, the mean NRS score decreased from 4.4 (range 4-5) to 1.4 (range 1-2), the mean BMI increased from 19.1 (range 17.4-20.3) to 21.0 kg/m2 (range 18.3-23.4). QoL improved in all patients, reflected by the summary of physical components with 33.92 points before vs. 67.72 points after 12 months of HPN, and the summary of mental components with 49.66 points before vs. 89.27 points after 12 months of HPN. Two patients suffered one catheter-related infection each with subsequent surgical removal and reinsertion. CONCLUSIONS: HPN is a feasible method for improving anthropometric parameters and QoL in SSc patients severely affected by GIT dysfunction. We recommend HPN in malnourished, catabolic SSc patients unable to otherwise maintain or improve their nutritional status.

A rare case of obstructive right atrial lipoma.

Benign cardiac tumours are rare and cardiac lipomas account only for a small fraction among those. Most of these tumours differ in terms of clinical manifestation, diagnosis, morphology and size, and are therefore not diagnosed easily unless they become symptomatic. We report the case of a 71-year-old Caucasian woman with recurrent episodes of shortness of breath presenting with an acute exacerbation of dyspnoea and hypertensive crisis. Diagnosis of a right atrial lipoma with a coexisting patent foramen ovale was established on echocardiography and computed tomography, and the patient was evaluated for elective surgery. Comprising the entire free wall of the right atrium, the tumour was removed during open heart surgery on cardiopulmonary bypass. The right atrium and the orifices of both the superior and inferior vena cava were reconstructed with bovine pericardium. No evidence of tumour relapse was observed during successive follow-up visits.

Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study.

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

Curcumin Micelles Improve Mitochondrial Function in a Mouse Model of Alzheimer's Disease.

Preventive strategies for late-onset Alzheimer's disease (AD) should start early at a prodromal stage. Mitochondrial dysfunction has been found to play an important role in the initiation of both aging and the pathogenesis of Alzheimer's disease. Curcumin, a widely used spice and food-coloring agent, is a polyphenol derived from the rhizome of Curcuma longa. It is known to have anti-oxidant, anti-inflammatory, and anti-protein-aggregate activities which are usually considered beneficial for mitochondrial function. We assessed brain mitochondrial function and concentrations of soluble Aß40 in a mouse model of AD (Thy1-APP751SL transgenic mice) after 3-week administration of curcumin micelles. Curcumin micelles are a newly developed formulation that account for increased curcumin bioavailability. Curcumin treatment had positive effects on mitochondrial membrane potential and respiratory control ratio. Additionally, it decreased levels of soluble Aß40 in brains of Thy1-APPSL transgenic mice. Hence, curcumin micelles are a promising neutraceutical for the prevention of AD.

Assessing most practical and effective protocols to sanitize hands of poultry catching crew members.

Catching crew members can heavily contaminate their hands with organic material. They can act as mechanical vector and spread diseases between farms. Hand hygiene is an important issue for the industry as a whole and for human health by reducing contamination risks. Many studies, in human medicine, tend to make hand rub a standard for hand hygiene. However, few studies have tested the effectiveness of hand hygiene products on visibly contaminated hands. The objective of this study was to evaluate the effectiveness of practical hand sanitization protocols: water and soap, degreasing cream and hand wipes, all combined with alcohol-based hand gel. The use of alcohol-based gel alone was also evaluated. For the reduction of coliforms after washing, there was no statistically significant difference between protocols when the initial level of bacterial contamination was low to moderate. When hands were highly contaminated, the alcohol-based gel alone was less effective than the degreasing cream combined with the alcohol-based gel (p=0.002). As for the reduction in total aerobic bacteria counts, there was no difference between protocols when the initial level of bacterial contamination was low. The water, soap and alcohol-based gel protocol was more effective than the scrubbing wipes and alcohol-based gel protocol when hands were moderately (p=0.002) and highly contaminated (p=0.001). All protocols were effective in neutralizing Salmonella on hands. Reducing the level of bacterial contamination on hands before using an alcohol-based gel seems important to ensure effective hand sanitation for highly and moderately contaminated hands. This can be done by using a degreasing cream or water and soap. Based on the survey, catching crew members preferred using warm water and soap compared to a degreasing cream.

Effects of Dietary Additives and Early Feeding on Performance, Gut Development and Immune Status of Broiler Chickens Challenged with Clostridium perfringens.

The effects of dietary additives and holding time on resistance and resilience of broiler chickens to Clostridium perfringens challenge were investigated by offering four dietary treatments. These were a negative control (basal), a positive control (Zn-bacitracin) and two dietary additives, mannanoligosaccharides (MOS), and acidifier. Two holding times included (a) immediate access to feed and water post hatch (FED) and (b) access to both feed and water 48 h post hatch (HELD). Chicks fed Zn-bacitracin had no intestinal lesions attributed to necrotic enteritis (NE), whereas chicks fed both MOS or acidifier showed signs of NE related lesions. All dietary treatments were effective in reducing the numbers of C. perfringens in the ileum post challenge. The FED chicks had heavier body weight and numerically lower mortality. The FED chicks also showed stronger immune responses to NE challenge, showing enhanced (p<0.05) proliferation of T-cells. Early feeding of the MOS supplemented diet increased (p<0.05) IL-6 production. The relative bursa weight of the FED chicks was heavier at d 21 (p<0.05). All the additives increased the relative spleen weight of the HELD chicks at d 14 (p<0.05). The FED chicks had increased villus height and reduced crypt depth, and hence an increased villus/crypt ratio, especially in the jejunum at d 14 (p<0.05). The same was true for the HELD chicks given dietary additives (p<0.05). It may be concluded that the chicks with early access to dietary additives showed enhanced immune response and gut development, under C. perfringens challenge. The findings of this study shed light on managerial and nutritional strategies that could be used to prevent NE in the broiler industry without the use of in-feed antibiotics.

Immediate, single stage, truly anatomic zirconia implant in lower molar replacement: a case report with 2.5 years follow-up.

This report demonstrates the clinical use of a modified, truly anatomic, root-analogue zirconia implant for immediate replacement of a two-rooted, left first mandibular molar. A 50-year-old female patient with chronic apical periodontitis of the left mandibulary first molar was referred and the tooth was extracted. The mesial root had to be removed surgically due to a root fracture. A truly anatomical, root identical, roughened zirconia implant modified by macro-retentions was manufactured and placed into the extraction socket by tapping 7 days later. After 4 months a composite crown was cemented in place. No complications occurred during the healing period. A good functional and aesthetic result was achieved with minimal bone resorption and soft tissue recession at 30 months follow-up. This report describes the successful clinical use of an immediate, single stage, truly anatomical root-analogue zirconia implant for replacement of a two-rooted tooth. Significant modifications such as macro-retentions yielded primary stability and excellent osseointegration. This novel approach is minimally invasive, respects the underlying anatomy, aids socket prevention, is time- and cost-saving with good patient acceptance as there is no need for bone drilling, sinus lift, bone augmentation or other traumatic procedures.

Functional interactions of manno-oligosaccharides with dietary threonine in chicken gastrointestinal tract. I. Growth performance and mucin dynamics.

1. An experiment was conducted to evaluate the interactive effects of manno-oligosaccharides (MOS; Bio-MOS®) and dietary threonine on the growth performance in relation to intestinal mucin dynamics in broiler chickens from 1 to 21 and from 22 to 35 d of age. Two concentrations of MOS (0 or 2 g/kg for d 1 to 21; and 0 or 1 g/kg for d 22 to 35) and three concentrations of threonine (0.0, 1.0 and 1.2 of National Research Council (NRC), 1994, recommendations) were included in the experimental diets for each age group. 2. Body weight gain was significantly lower in threonine-deficient birds compared with those fed on adequate or excess threonine diets. Positive interaction between MOS and threonine supplementation on body weight gain was apparent in all phases of growth due mainly to the significantly poorer performance of birds given excess threonine in the absence of MOS. 3. The duodenal and ileal adherent mucous thickness were reduced at 14 and 28 d in threonine-deficient birds. Nevertheless, MOS significantly increase duodenal adherent mucous thickness at 14 d and ileal mucous thickness at 14 and 28 d. At 14 d, a significant MOS and threonine interaction on the jejunal adherent mucous thickness was also noted in that there was no difference between adequate and excess threonine groups in the absence of MOS, but a significant increase with excess threonine and MOS supplementation. 4. Dietary threonine greatly influenced mucin synthesis at the translational stage with no effect on jejunal MUC2 gene expression. Conversely, MOS modulated the transcriptional stage of intestinal mucin synthesis by consistently up-regulating jejunal MUC2 gene expression which was independent of dietary threonine concentration. There were no significant interactions between threonine and MOS on all the goblet cell densities. However, there was a MOS and threonine interaction on the staining intensities of jejunal sulphomucins due mainly to the significantly lower staining intensities in birds fed excess threonine in the absence of MOS. 5. The ameliorative effect of MOS on the growth-suppressive effects of excess threonine is likely to be linked to its modulating effects on the intestinal mucin dynamics.

Functional interactions of manno-oligosaccharides with dietary threonine in chicken gastrointestinal tract. III. Feed passage rate.

1. A 3 × 2 factorial experimental design was used to investigate the interaction between threonine concentration (0.70, 1.0 and 1.3 of National Research Council (NRC), 1994, recommendations) and manno-oligosaccharides (0 and 2 g/kg) on feed passage rate in relation to intestinal microbial activities and crude mucin turnover. 2. There was no interaction between the effects of manno-oligosaccharides (MOS) and dietary threonine on total tract transit time. However, an interaction between MOS and threonine was apparent where increasing threonine in the absence of MOS led to a reduction in the mean retention time, but a trend in the opposite direction in the presence of MOS. The ileal mean retention time at deficient and adequate concentrations of threonine was also significantly shorter in the presence of MOS. 3. In the jejunum, dietary MOS interacted with threonine to increase the villus-to-crypt ratio with deficient and adequate concentrations of threonine but not with an excess. In the ileum, MOS had no effect on the villus-to-crypt ratio at the deficient and adequate concentrations of threonine but significantly increased the ileal villus-to-crypt ratio with an excess. 4. There were significant interactions between MOS and dietary threonine in their effects on ileal flow of crude mucin, with MOS supplementation increasing mucin concentration and output when threonine was adequate but not when deficient or in excess. 5. Neither MOS nor threonine affected volatile fatty acids and intestinal musculature. No effects of gut microflora or voluntary feed intake on feed passage rate was attributable to dietary threonine or MOS supplementation.

Functional interactions of manno-oligosaccharides with dietary threonine in chicken gastrointestinal tract. II. Mucosal development, mucin dynamics and nutrient utilisation.

1. A 3 × 2 factorial experimental design was used to investigate the interaction between threonine concentration (0.7, 1.0 and 1.3 of National Research Council (NRC), 1994, recommendations) and manno-oligosaccharides (MOS) supplemented at 0 and 2 g/kg on growth performance in relation to intestinal flow of crude mucins, mucosal development and nutrient utilisation. 2. There was no interaction between MOS and dietary threonine in any performance variable analysed, except for body weight gain during the period to 14 d of age, where body weight gain was significantly lower in birds fed excess threonine in the absence of MOS. Dietary MOS was also observed to significantly increase the body weight gain at deficient and adequate concentrations of threonine. 3. Dietary treatments had no significant effect on either the ileal external muscularis thickness or crypt depth. However, there was a MOS and threonine interaction in the ileal villus to crypt ratio and ileal crude mucin output with both being increased only at the adequate threonine concentration. 4. Dietary MOS tended to interact with threonine to increase the ileal uptake of D-glucose and L-threonine, but the effect was only apparent in birds fed on the deficient or excess threonine diet. There was no significant interaction between MOS and threonine on ileal digestibility of amino acids. Supplementation of MOS or increased dietary threonine significantly increased the apparent and standardised ileal digestibility of threonine. 5. Results from the current study indicate the possible link between the modulating effects of these supplements on intestinal mucosal development and mucin dynamics. This, in turn, may suggest a relatively higher proportion of mature enterocytes and absorptive area, which would be expected to improve the capacity for digestion and mucosal nutrient absorption.

Characterisation and response of intestinal microflora and mucins to manno-oligosaccharide and antibiotic supplementation in broiler chickens.

1. An experiment was conducted to characterise and evaluate, in comparison to zinc bacitracin (ZnB), the response of intestinal microflora and mucins to manno-oligosacchares (MOS, Bio-MOS(R), Alltech Biotechnology, Nicholasville, Kentucky, USA). 2. Supplementation of MOS and ZnB selectively increased the intensity of sulphomucins. As revealed by the plate culture method, MOS accelerated the maturation of gut microflora by promoting the growth of lactobacilli in the ileal mucosa and vice versa on ileal and caecal clostridia. Unlike MOS, ZnB suppressed the growth of intestinal bacteria, especially those of lactobacilli and clostridia. Use of T-RFLP further revealed that MOS increased the diversity of lactobacilli in the ileum and ileal mucosa but the opposite was observed for ZnB. It also appears that MOS and ZnB possessed a common property in differentially favouring the growth of certain Lactobacillus species. There was also evidence to show that both MOS and ZnB also increased the homogeneity of the gut microflora, possibly through the regulation of the overall gut bacterial communities. 3. Improvement in intestinal microbial homogeneity and mucin synthesis, coupled with the differential selections for certain specific beneficial bacterial species, may ultimately be proven to be the target mechanisms in the search for more effective alternatives to antibiotics.

Immediate, non-submerged, root-analogue zirconia implants placed into single-rooted extraction sockets: 2-year follow-up of a clinical study.

This study evaluated non-submerged, root-analogue zirconia implants with two different surfaces for immediate single-rooted tooth replacement in 18 patients. After tooth extraction the root was laser scanned and one-piece root analogue zirconia dental implants with one of two different surfaces were manufactured. In group A (n=6) the implant surface was roughened by sandblasting only, in group B (n=12) additional macroretentions limited to the interdental space, to avoid fracture of the thin buccal cortex, were designed prior to laser scanning. Implants were placed in the socket 1-8 days after extraction by tapping and restored with a composite crown 3-5 months later. Implant survival, level of marginal bone and adverse soft tissue changes were recorded. No complications occurred during the healing period. In group A, all implants were lost within 2 months, with an unaltered extraction socket. In group B, overall survival rate was 92% for implants that were functional for 1-33 months. Excellent aesthetic and functional results were achieved with the composite crown with minimal bone resorption and soft tissue recession. Significant modifications, such as macroretentions seem to indicate that primary stability and excellent osseointegration of immediate root-analogue zirconia implants can be achieved, while preventing unaesthetic bone resorption.

Effects of dietary mannanoligosaccharide on growth performance, nutrient digestibility and gut development of broilers given different cereal-based diets.

A feeding trial was conducted to evaluate the effects of mannanoligosaccharide (MOS) on the growth performance, nutrient digestibility and gut development of broilers given a corn or a wheat-based diet over a 21-day experimental period. Dietary MOS improved the growth performance of birds given the wheat-based diet compared to that of birds given the corn-based diet during 7-21 days of age. In line with this, the ileal digestibility of starch was increased by MOS at 21 days of age. The addition of MOS modulated the development of gut microflora. From day 7 to day 21, the numbers of mucosa-associated coliforms along the small intestine were decreased; whereas the numbers of mucosa-associated lactobacilli were increased by MOS, regardless of the cereal type in the diets. Dietary MOS also reduced the counts of coliforms and Clostridium perfringens in the caeca of birds by 21 days of age. Villus height at the jejunum was not affected by MOS but the crypt depth and the muscularis thickness were reduced. The specific activities of maltase and alkaline phosphatase were increased in birds given the MOS-supplemented diet; whereas the development of leucine aminopeptidase was delayed by MOS. All these changes in the mucosal morphology and function were dependent on the type of cereal and/or the age of the birds.

CCR3- and CXCR4-mediated interactions regulate migration of CD34+ human bone marrow progenitors to ischemic myocardium and subsequent tissue repair.

OBJECTIVE: Hematopoietic progenitor cells are able to induce neovascularization of ischemic myocardium, inhibit apoptosis, and prevent heart failure. They express functional CC chemokine-binding receptor 3 (CCR3) and CXC chemokine-binding receptor 4 (CXCR4); however, the role of those receptors in migration of progenitor cells into the ischemic myocardium is unknown. METHODS: Myocardial infarction was surgically induced in athymic nude rats, and human bone marrow-derived CD34+ cells or saline was injected into the tail vein. Cell chemotaxis was studied in vitro using chemotaxis chambers with or without concomitant stimulation with eotaxin or stromal cell-derived factor-1. Cell migration into ischemic myocardium was evaluated by immunohistochemistry. CCR3 and CXCR4 antibodies or local injections of stromal cell-derived factor-1 were used to investigate the role of chemokine expression in the migration capacity of the injected cells. Morphologic analysis included evaluation of apoptosis and capillary density in the ischemic myocardium. RESULTS: Ischemic rat myocardium demonstrated induced messenger RNA expression for the CCR3-binding chemokines eotaxin, RANTES (regulated on activation, normal T expressed and secreted), and monocyte chemotactic protein-3, but not the CXCR4-binding chemokine stromal cell-derived factor-1. Migration of human angioblasts to ischemic rat myocardium was inhibited by a blocking anti-CCR3 monoclonal antibody, but not by a blocking anti-CXCR4 monoclonal antibody, which instead inhibited migration to bone marrow. Finally, intramyocardial injection of stromal cell-derived factor-1 redirected migration of human angioblasts to ischemic rat hearts, resulting in augmented neovascularization, enhanced cardiomyocyte survival, and functional cardiac recovery. CONCLUSIONS: CCR3-dependent chemokine interactions regulate endogenous migration of CD34+ progenitors from bone marrow to ischemic but not to normal myocardium. Manipulating CXCR4-dependent interactions could enhance the efficacy of cell therapy after myocardial infarction.

Effects of mannanoligosaccharide and fructooligosaccharide on the response of broilers to pathogenic Escherichia coli challenge.

1. The effects of mannanoligosaccharide (MOS, Bio-Mos, Alltech Inc.) on the growth performance and digestive system, particularly gut microflora, were tested and compared with fructooligosaccharide (FOS, Raftilose P95, Orafti) using 1-d-old birds in an Escherichia coli challenge model. The experiment lasted for 3 weeks and zinc bacitracin (ZnB) was used as a positive control. 2. Dietary MOS had positive effects on body weight gain (BWG) or/and feed conversion efficiency (FCE) of the challenged birds compared to the negative control at the end of weeks 1 and 3. Similar results were obtained for ZnB treatment. In contrast, FOS supplementation improved only the BWG of the challenged birds at 21 d of age. Within the unchallenged birds, a large improvement in BWG was noticed for FOS treatment at the end of the experiment, with the BWG of birds on ZnB and MOS treatments being intermediate. The FCE of the unchallenged birds was not affected by the dietary additives. 3. The addition of MOS reduced the number of mucosa-associated coliforms in the jejunum of the challenged birds on d 7. On d 21, FOS tended to increase the number of jejunal mucosa-associated lactobacilli in both the challenged and unchallenged birds. The number of Clostridium perfringens in the gut lumen was reduced by only ZnB. 4. Dietary MOS reduced the jejunal crypt depth of birds on d 7, regardless of the challenge. The FOS supplement did not affect the gut morphology, however, the concentration of lactic acid in the ileum was increased and, depending on the challenge, the intestinal pH was decreased by FOS at different ages. 5. In conclusion, the effects of MOS or FOS on the composition and activities of gut microflora and mucosal morphology of birds were related to E. coli challenge as well as the age of birds, which may be involved in the observed different growth-improving effects of the tested dietary additives.

Effects of mannanoligosaccharide in broiler chicken diets on growth performance, energy utilisation, nutrient digestibility and intestinal microflora.

1. A study was undertaken to evaluate the effects of mannanoligosaccharide (MOS, Bio-MOS, Alltech Inc.) on the growth performance, energy utilisation, nutrient digestibility and intestinal microflora of birds given a sorghum-wheat based diet. Two MOS levels (1 and 2 g/kg) were included in the diet. 2. Inclusion of MOS at both levels in the diet improved the apparent metabolisable energy (AME) values of the diet. However, these effects were not as pronounced as those of zinc bacitracin (ZnB) treatment. Dietary ZnB also significantly improved the net energy value of the diet. No significant differences between the different levels of MOS were noticed in the growth performance, AME and net energy values of the diet. Compared to the negative control, inclusion of 2 g/kg MOS tended to improve feed conversion efficiency (FCE) in the starter phase. 3. Dietary MOS did not affect the apparent total tract digestibility of nutrients compared to the negative control. In contrast, ZnB significantly improved the protein digestibility and tended to increase the starch digestibility. The addition of MOS reduced the concentration of arabinose in the soluble non-starch polysaccharides (NSP) fraction in the excreta of birds; whereas, the concentrations of individual sugars in the insoluble NSP and free sugar fractions were increased by ZnB. 4. A decrease in the populations of lactobacilli and coliforms in the ileal and caecal lumen was observed for MOS and ZnB treatments. Correspondingly, pH and microbial fermentation in the gut was altered. The addition of MOS tended to reduce the coliform load at the gut mucosa. 5. Results from the current study suggest that MOS can improve the apparent energy utilisation of the diet and tend to improve FCE of birds in the first three posthatch weeks, which may be partly related to the modulatory effects of MOS on the gut microflora.

Immediate, non-submerged, root-analogue zirconia implant in single tooth replacement.

This report demonstrates the successful clinical use of a modified root-analogue zirconia implant for immediate single tooth replacement. A right maxillary premolar was removed and a custom-made, root-analogue, roughened zirconia implant with macro-retentions in the interdental space was fabricated and placed into the extraction socket 4 days later. Four months after root implantation a composite crown was cemented. No complications occurred during the healing period. An excellent esthetic and functional result was achieved with the composite crown. No clinically noticeable bone resorption or soft-tissue recession was observed at 26 months follow up. Significant modifications such as macro-retentions seem to indicate that primary stability and excellent osseointegration of immediate root-analogue zirconia implants can be achieved, while preventing unesthetic bone resorption. The macro-retentions must be limited to the interdental space to avoid fracture of the thin buccal cortex. This successful case warrants further clinical research in well controlled trials.

Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines.

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.

Cell- and gene therapy for ischemic heart disease.

Despite advances in pharmacological therapies, cardiovascular surgery, use of mechanical assist devices, and organ transplantation, more than half of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The use of cellular cardiomyoplasty and gene therapy offer a promising approach for both the prevention and treatment of heart failure. This review will discuss the current state of these emerging fields and the prospects of introducing the methods into clinical practice. Since functional restoration of the damaged heart presents a formidable challenge, developing strategies for the prevention of post-infarct heart failure remains of utmost priority. New strategies to optimize cell delivery, homing and survival on the one side and safe and efficient application of gene therapy to the failing myocardium on the other side are indispensable in order to achieve myocardial recovery after acute infarction or chronic ischemic damage.

Monitoring C2 level predicts exposure in maintenance lung transplant patients receiving the microemulsion formulation of cyclosporine (Neoral).

BACKGROUND: Dosing of the microemulsion formulation of cyclosporine (Neoral) is conventionally based on trough levels (C(0)). However, experience in renal transplantation has shown that cyclosporine exposure during the absorption phase (AUC(0-4)) is critical for optimizing immunosuppression, and that cyclosporine (CsA) concentration at 2 hours post-dose (C(2)) shows the closest correlation with AUC(0-4). This study evaluated whether C(2) values correlate more closely with AUC(0-4) than C(0) in lung transplant patients. METHODS: Pharmacokinetic data were collected prospectively from 20 clinically stable adult lung allograft recipients receiving CsA, mycophenolate mofetil and steroids. Indications for transplantation were emphysema (n = 15), idiopathic fibrosis (n = 2), primary pulmonary hypertension (n = 1), cystic fibrosis (n = 1) and lymphangioleiomyomatosis LAM (n = 1). Blood samples were collected at 0, 1, 2, 3 and 4 hours after administration of CsA, and then AUC(0-4) was calculated. The Correlation between cyclosporine concentration at each time-point and AUC(0-4) was also calculated. RESULTS: C(2) showed the closest correlation with AUC(0-4) (r(2) = 0.85). C(0) had the poorest correlation of all time-points (r(2) = 0.64). Two patients with radiologic signs of gastroparesis had no peak cyclosporine levels at all and were excluded from the correlation analysis. Mean AUC(0-4) was 3,700 ng . h/ml during Year 1 post-transplant, 2,400 ng . h/ml during Years 1 to 3, and 1,500 ng . h/ml thereafter. Mean C(2) values were 1.2 microg/ml during Year 1, 0.8 microg/ml during Years 1 to 3, and 0.5 microg/ml thereafter. CONCLUSIONS: C(2) is the single time-point that correlates most closely with AUC(0-4) in lung transplant recipients without gastroparesis. It remains to be demonstrated whether monitoring CsA based on C(2) levels results in a lower incidence of rejection without additional toxicity.