Feasibility of allogeneic hematopoietic stem cell transplantation in advanced age.

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.

Effects of a Novel Infant Formula on the Fecal Microbiota in the First Six Months of Life: The INNOVA 2020 Study.

Exclusive breastfeeding is highly recommended for infants for at least the first six months of life. However, for some mothers, it may be difficult or even impossible to do so. This can lead to disturbances in the gut microbiota, which in turn may be related to a higher incidence of acute infectious diseases. Here, we aimed to evaluate whether a novel starting formula versus a standard formula provides a gut microbiota composition more similar to that of breastfed infants in the first 6 months of life. Two hundred and ten infants (70/group) were enrolled in the study and completed the intervention until 12 months of age. For the intervention period, infants were divided into three groups: Group 1 received formula 1 (INN) with a lower amount of protein, a proportion of casein to whey protein ratio of about 70/30 by increasing the content of α-lactalbumin, and with double the amount of docosahexaenoic acid/arachidonic acid than the standard formula; INN also contained a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis). Group 2 received the standard formula (STD) and the third group was exclusively breastfed (BF) for exploratory analysis. During the study, visits were made at 21 days, 2, 4, and 6 months of age, with ±3 days for the visit at 21 days of age, ±1 week for the visit at 2 months, and ±2 weeks for the others. Here, we reveal how consuming the INN formula promotes a similar gut microbiota composition to those infants that were breastfed in terms of richness and diversity, genera, such as Bacteroides, Bifidobacterium, Clostridium, and Lactobacillus, and calprotectin and short-chain fatty acid levels at 21 days, 2 and 6 months. Furthermore, we observed that the major bacteria metabolic pathways were more alike between the INN formula and BF groups compared to the STD formula group. Therefore, we assume that consumption of the novel INN formula might improve gut microbiota composition, promoting a healthier intestinal microbiota more similar to that of an infant who receives exclusively human milk.

Innova 2020: A Follow-Up Study of the Fecal Microbiota of Infants Using a Novel Infant Formula between 6 Months and 12 Months of Age.

The World Health Organization recommends exclusive breastfeeding on demand until at least the sixth month of life. Breast milk or infant formula is the infant's primary food source until the age of one year, followed by the gradual introduction of other foods. During weaning, the intestinal microbiota evolves to a profile close to that of the adult, and its disruption can result in an increased incidence of acute infectious diseases. We aimed to determine whether a novel starting formula (INN) provides gut microbiota compositions more similar to those of breastfed (BF) infants from 6 to 12 months of age compared to a standard formula (STD). This study included 210 infants (70 per group) who completed the intervention until they reached the age of 12 months. In the intervention period, infants were divided into three groups. Group 1 received an INN formula with a lower protein content, a casein to whey protein ratio of approximately 70/30, twice as much docosahexaenoic acid as the STD formula, a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis, BPL1TM HT), and twice as much arachidonic acid as the STD formula contained. The second group received the STD formula, while the third group was exclusively BF for exploratory purposes. In the course of the study, visits were conducted at 6 months and 12 months of age. Compared to the BF and STD groups, the Bacillota phylum levels in the INN group were significantly reduced after 6 months. At the end of 6 months, the alpha diversity indices of the BF and INN groups differed significantly from those of the STD group. At 12 months, the Verrucomicrobiota phylum levels in the STD group were significantly lower than those in the BF and INN groups. Based on the comparison between 6 and 12 months, the Bacteroidota phylum levels in the BF group were significantly higher than those in the INN and STD groups. When comparing the INN group with the BF and STD groups, Clostridium sensu stricto 1 was significantly higher in the INN group. The STD group had higher levels of calprotectin than the INN and BF groups at 6 months. The immunoglobulin A levels in the STD group were significantly lower than those in the INN and BF groups after 6 months. Both formulas had significantly higher levels of propionic acid than the BF group at 6 months. At 6 months, the STD group showed a higher quantification of all metabolic pathways than the BF group. The INN formula group exhibited similar behavior to the BF group, except for the superpathway of phospholipid biosynthesis (E. coli). We hypothesize that the novel INN formula may promote an intestinal microbiota that is more similar to the microbiota of an infant who consumes only human milk before the weaning period.

Effect of Remote Ischemic Preconditioning on the Incidence of Contrast-Induced Nephropathy in Patients Undergoing Endovascular Aneurysm Repair (Remote Ischemic Preconditioning-Endovascular Aneurysm Repair Study).

BACKGROUND: Contrast-induced nephropathy (CIN) is a major inconvenience in the use of iodinated contrast media (ICM) and it is associated with a significant increase in morbidity and mortality and cost of hospitalization. Remote ischemic preconditioning (RIPC) is a noninvasive and cost-effective tissue protection technique that has showed to be beneficial in decreasing renal insult in patients receiving intravascular contrast. AIM: The primary outcome of this study is to evaluate the impact of RIPC on the incidence of CIN in patients undergoing endovascular aneurysm repair. METHODS: Patients suffering from aortic aneurysm were recruited prior to the administration of ICM. Randomization was used to assign patients into the control/RIPC groups. Biochemical parameters determined renal function before and after surgery in immediate (24-72 hr) and at 30 days of follow-up. RESULTS: Of the 120 patients included in the study, 98,3% were male. Mean age was 73 years (range: 56-87 years). Diabetes and chronic renal failure (considering estimated glomerular filtration [eGFR] <60) was present prior to administration of ICM in 29.16% and 38.33%, respectively. RIPC was applied in 50% (n = 60) of the patients. A total of 24.17% developed CIN regardless of fluidotherapy, RIPC, and other protective strategies. RIPC did not influence outcomes in terms of incidence on CIN, serum creatinine, urea, eGFR, or microalbuminuria in immediate postoperative period. However, the group of RIPC patients showed a statistically significant benefit in renal function in terms of serum creatinine (1.46 ± 0.3 vs. 1.03 ± 0.5; P < 0.001), urea (61.06 ± 27.5 mg/dL vs. 43.78 ± 12.9 mg/dL; P = 0.003), and an increase in eGFR (56.37 ± 23.4 mL/min/1.73 m2 vs. 72.85 ± 17.7 mL/min/1.73 m2; P = 0.004) at 30 days of follow-up. CONCLUSIONS: RIPC seems to be a reasonable, effective, and low-cost technique to alleviate effects of ICM on the renal parenchyma in endovascular aneurysm repair procedures during short-term postoperative period.

6q deletion in Waldenström macroglobulinaemia negatively affects time to transformation and survival.

Deletion of the long arm of chromosome 6 (del6q) is the most frequent cytogenetic abnormality in Waldenström macroglobulinaemia (WM), occurring in approximately 50% of patients. Its effect on patient outcome has not been completely established. We used fluorescence in situ hybridisation to analyse the prevalence of del6q in selected CD19+ bone marrow cells of 225 patients with newly diagnosed immunoglobulin M (IgM) monoclonal gammopathies. Del6q was identified in one of 27 (4%) cases of IgM-monoclonal gammopathy of undetermined significance, nine of 105 (9%) of asymptomatic WM (aWM), and 28/93 (30%) of symptomatic WM (sWM), and was associated with adverse prognostic features and higher International Prognostic Scoring System for WM (IPSSWM) score. Asymptomatic patients with del6q ultimately required therapy more often and had a shorter time to transformation (TT) to symptomatic disease (median TT, 30 months vs. 199 months, respectively, P < 0·001). When treatment was required, 6q-deleted patients had shorter progression-free survival (median 20 vs. 47 months, P < 0·001). The presence of del6q translated into shorter overall survival (OS), irrespective of the initial diagnosis, with a median OS of 90 compared with 131 months in non-del6q patients (P = 0·01). In summary, our study shows that del6q in IgM gammopathy is associated with symptomatic disease, need for treatment and poorer clinical outcomes.

Real-World Results of Supera Stent Implantation for Popliteal Artery Atherosclerotic Lesions: 3-Year Outcome.

BACKGROUND: Reports our experience for the first 50 cases of use of Supera stent for popliteal atherosclerotic lesions treatment. METHODS: This prospective single-arm trial enrolled the first 50 limbs (46 patients) treated in our center with a Supera stent for symptomatic atherosclerotic disease of the popliteal artery. Also, a follow-up of 36 months is reported. RESULTS: The mean preoperative ankle-brachial index increased from 0.38 ± 0.37 before intervention to 0.63 ± 0.46 postoperatively at 12 months (P = 0.014), 0.66 ± 0.39 at 24 months (P = 0.023), and 0.74 ± 0.46 at 36 months (P = 0.029). Primary patency at 12, 24, and 36 months were 89.6%, 72.3%, and 70.2%, and primary assisted patency was 93.8%, 87.2%, and 85.1%, respectively, by Kaplan-Meier estimates. After 3 years of follow-up, age <75 years (P = 0.034) and Trans-Atlantic Inter-Society Consensus (TASC)-II D lesions (P = 0.041) constituted risk factors for stent occlusion. During the follow-up of the patients, none of them developed stent fracture as evidenced on plain radiographs during follow-up. Implantation defects did not constitute a risk factor for stent restenosis. CONCLUSIONS: Based on the results of this study, Supera stent has shown an excellent 3-year patency in this difficult-to-treat anatomic segment. In our experience, younger patients and complex lesions (TASC-II type D) were positive significant predictors for restenosis. In our cohort, post deployment stent conformation did not influence patency. Nevertheless, further investigations, including randomized studies comparing the Supera stent with other stent platforms, drug eluting angioplasty, or atherectomy devices, are mandatory.

Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma.

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.

Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P<0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival.

Effects of rosuvastatin as an adjuvant treatment for deep vein thrombosis.

BACKGROUND: Statins have been reported to help prevent the development and the recurrence of deep vein thrombosis (DVT). We conducted a prospective randomized clinical trial to compare the effects of rosuvastatin plus a low-molecular-weight heparin (LMWH), bemiparin, with conventional LMWH therapy in the treatment of DVT. PATIENTS AND METHODS: In total, 234 patients were randomized into two groups, 116 in the LMWH group and 118 in the statin plus LMWH group. All patients underwent lower limb duplex ultrasound and analytic markers at diagnosis and three months of follow-up. The final analysis included 230 patients. RESULTS: No significant differences were observed in D-dimer levels after three months of follow-up between patients treated with LMWH+rosuvastatin compared to the LMWH group (802.51 + 1062.20 vs. 996.25 + 1843.37, p = 0.897). The group of patients treated with statins displayed lower levels of CRP (4.17 + 4.27 vs. 22.39 + 97.48, p = 0.018) after three months of follow-up. The Villalta scale demonstrated significant differences between groups (3.45 + 6.03 vs. 7.79 + 5.58, p = 0.035). There was a significant decrease in PTS incidence (Villalta score> 5) in the rosuvastatin group (38.3 % vs. 48.5%, p = 0.019). There were no differences in EuroQol score between groups. CONCLUSIONS: Adjuvant rosuvastatin treatment in patients diagnosed of DVT improve CRP levels and diminish PTS incidence.

Endovascular treatment of posttraumatic pseudoaneurysm of the internal mammary artery.

Pseudoaneurysm of the internal mammary artery is an unusual complication of wounds to the chest. We report a case of a 41-year-old man who sustained a stab chest wound and posttraumatic pseudoaneurysm of the internal mammary artery, resulting in hemomediastinum and hemothorax. The patient was successfully treated using emergency endovascular coil embolization. Because this injury is extremely rare, the literature is reviewed, and several principles are suggested to improve the management.

[Readability of surgical informed consent in Spain]. / Legibilidad del consentimiento informado quirúrgico en España.

INTRODUCTION: To assess the readability of informed consent documents (IC) of the different national surgical societies. METHODS: During January 2012 we collected 504 IC protocols of different specialties. To calculate readability parameters the following criteria were assessed: number of words, syllables and phrases, syllables/word and word/phrase averages, Word correlation index, Flesch-Szigriszt index, Huerta Fernández index, Inflesz scale degree and the Gunning-Fog index. RESULTS: The mean Flesch-Szigriszt index was 50.65 ± 6,72, so readability is considered normal. There are significant differences between specialties such as Urology (43.00 ± 4.17) and Angiology and Vascular Surgery (63.00 ± 3.26, P<.001). No IC would be appropriate for adult readability according to the Fernández-Huerta index (total mean 55.77 ± 6.57); the IC of Angiology and Vascular Surgery were the closest ones (67.85 ± 3.20). Considering the Inflesz scale degree (total mean of 2.84 ± 3,23), IC can be described as «somewhat difficult¼. There are significant differences between the IC of Angiology and Vascular Surgery (3.23 ± 0.47) that could be qualified as normal, or Cardiovascular Surgery (2.79 ± 0.43) as «nearly normal readability¼; and others such as Urology (1, 70 ± 0.46, P<.001) and Thoracic Surgery (1.90 ± 0.30, P<.001), with a readability between «very¼ and «somewhat¼ difficult. The Gunning-Fog indexes are far from the readability for a general audience (total mean of 26.29 ± 10,89). CONCLUSIONS: IC developed by scientific societies of different surgical specialties do not have an adequate readability for patients. We recommend the use of readability indexes during the writing of these consent forms.

Low-molecular-weight heparin for prevention of venous thromboembolism after varicose vein surgery in moderate-risk patients: a randomized, controlled trial.

BACKGROUND: Deep vein thrombosis (DVT) after varicose vein surgery (VVS) is not well recognized. Observational studies have yielded variable estimates of the risk, but evidence from randomized trials is lacking. Our aim was to compare the use of thromboprophylaxis with and without low-molecular-weight heparin (LMWH). METHODS: We prospectively randomized moderate-risk patients scheduled for VVS in two arms. The first group of patients received bemiparin for 10 days at a prophylactic dose, early ambulation, and compression therapy for 3 months; the second group received early ambulation and compression therapy alone. The primary efficacy outcome was the composite of DVT (symptomatic or asymptomatic detected by mandatory, bilateral duplex scan). Secondary efficacy and primary safety end points were superficial venous thrombosis, postoperative bleeding, and clinical pulmonary embolism (PE). We assessed transient and permanent risk factors for venous thromboembolism. RESULTS: Two-hundred sixty-two patients were eligible for evaluation. There were no cases of DVT. There were also no cases of clinical PE, death, or major bleeding. No significant differences were seen between groups in the rates of bleeding episodes. CONCLUSION: The data show no superiority of a short-term regimen of LMWH and early ambulation and compression therapy, as compared with early ambulation and compression therapy alone, in patients undergoing VVS in a moderate-risk population.

Bifidobacterium animalis subsp. lactis BPL1™ and Its Lipoteichoic Acid Modulate Longevity and Improve Age/Stress-Related Behaviors in Caenorhabditis elegans.

Life expectancy has increased globally in recent decades, driving interest in maintaining a healthy life that includes preservation of physical and mental abilities, particularly in elderly people. The gut microbiome becomes increasingly perturbed with aging so the use of probiotics can be a strategy for maintaining a balanced gut microbiome. A previous report showed that Bifidobacterium animalis subsp. lactis BPL1™ induces through its lipoteichoic acid (LTA) fat reduction activities via the insulin/IGF-1 signaling pathway. Here, we have delved into the mechanism of action, eliminating alternative pathways as putative mechanisms. Furthermore, we have identified that BPL1™, its heat treated form (BPL1™ HT) and its LTA prolong longevity in Caenorhabditis elegans (C. elegans) in an insulin/IGF-1-dependent mechanism, and its consumption improves the oxidative stress response, gut permeability and protection against pathogenic infections. Furthermore, positive effects on C. elegans stress-related behaviors and in the Alzheimer's Disease model were found, highlighting the potential of the strain in improving the cognitive functions and proteotoxicity in the nematode. These results indicate the pivotal role of the IGF-1 pathway in the activity of the strain and pave the way for potential applications of BPL1™, BPL1™ HT and its LTA in the field of longevity and age-related markers.

Intraoperative embolization with poloxamer 407 during surgical resection of a carotid body tumor.

Surgical excision is the preferred definitive treatment for carotid body tumors, although postoperative morbidity rate as quoted in the literature is rather high. Morbidity includes cranial nerve dysfunction, stroke, and the majority severe blood loss. Embolization of the feeding branches of the external carotid artery can be performed a few days prior to surgery with the intention to decrease blood loss during operation, facilitate surgical resection, and reduce operating time and morbidity. The special risk of embolization is migration into the intracranial circulation. Poloxamer 407, a reverse-thermal polymer, is a nontoxic compound that is a viscous liquid at room temperatures but instantly changes to a firm water-soluble gel when warmed to body temperature. It dissolves spontaneously or can be dissolved at will by cooling. We describe an intraoperative technique for complete devascularization of carotid body tumor by using an intraarterial temporary occlusion technique with a poloxamer 407.

Lipoteichoic acid from Bifidobacterium animalis subsp. lactis BPL1: a novel postbiotic that reduces fat deposition via IGF-1 pathway.

Obesity and its related metabolic disorders, such as diabetes and cardiovascular disease, are major risk factors for morbidity and mortality in the world population. In this context, supplementation with the probiotic strain Bifidobacterium animalis subsp. lactis BPL1 (CECT8145) has been shown to ameliorate obesity biomarkers. Analyzing the basis of this observation and using the pre-clinical model Caenorhabditis elegans, we have found that lipoteichoic acid (LTA) of BPL1 is responsible for its fat-reducing properties and that this attribute is preserved under hyperglycaemic conditions. This fat-reducing capacity of both BPL1 and LTA-BPL1 is abolished under glucose restriction, as a result of changes in LTA chemical composition. Moreover, we have demonstrated that LTA exerts this function through the IGF-1 pathway, as does BPL1 strain. These results open the possibility of using LTA as a novel postbiotic, whose beneficial properties can be applied therapeutically and/or preventively in metabolic syndrome and diabetes-related disorders.

Coil embolization of persistent false lumen after stent graft repair of type B aortic dissection.

Patent false lumen after endovascular stent graft treatment of type B aortic dissection is a predictor for late death and retreatment. Between June 2008 and March 2010, five men with patent false lumen, due to a type B dissection previously treated with thoracic stent graft, underwent endovascular coiling treatment. Within a 30-day period, there were no deaths or major complications. The follow-up duration ranged from 1 to 22 months (mean 10.6 ± 8.5). Endovascular coiling of patent false lumen after endovascular stent graft treatment for type B aortic dissection avoided the risk of rupture or death due to secondary aneurysm formation.

Selectivity and antimicrobial action of bovine lactoferrin derived peptides against wine lactic acid bacteria.

In this study, the antibacterial activities of a bovine Lactoferrin pepsin hydrolysate (LFH) and a synthetic peptide derived from bovine lactoferricin (LfcinB(17-31)) have been evaluated against Oenococcus oeni and three additional lactic acid bacteria (LAB) known to cause spoilage during winemaking processes. Inhibition of bacterial growth was demonstrated in vitro in synthetic broth media (MRS) for both LFH and LfcinB(17-31). The bactericidal activity of the synthetic peptide was also assayed and found to vary depending on the bacterial species and the matrix in which exposure to peptide occurred (either MRS broth or white must). Specificity of LfcinB(17-31) for Lactobacillus brevis, Pediococcus damnosus, and O. oeni was demonstrated in must fermentation experiments in which these three LAB co-existed with the winemaking Saccharomyces cerevisiae T73 in the presence of the peptide. Finally, fermentation experiments also showed that LfcinB(17-31) at inhibitory concentrations did not alter either fermentation kinetics or specific enological parameters.

Inhibition of the wine spoilage yeast Dekkera bruxellensis by bovine lactoferrin-derived peptides.

The antimicrobial action of lactoferrin (LF)-derived peptides against Dekkera bruxellensis strains isolated from spoiled wines has been examined. The study included a fifteen-residue peptide (LfcinB(17-31)) derived from bovine lactoferricin B and a bovine LF pepsin hydrolysate (LFH). In vitro assays showed the inhibitory properties of LfcinB(17-31) on D. bruxellensis growth with IC(50) and MIC values in the micromolar range. Strains tested showed different sensitivity to the peptide. LfcinB(17-31) showed fungicidal properties towards all strains tested in laboratory growth medium. However, the extent of fungicidal activity was strain-dependent in must and wine, confirming the different antimicrobial action of peptides depending on both the food matrix and the target micro-organism. The binding of LfcinB(17-31) to D. bruxellensis cells was visualized by fluorescence microscopy and correlated with the fungicidal activity in the different matrixes. LfcinB(17-31) and LFH showed growth inhibitory properties in wine suggesting their potential use for spoilage control.

Antimicrobial action of synthetic peptides towards wine spoilage yeasts.

The antimicrobial action of selected short synthetic peptides against wine spoilage yeasts such as Cryptococcus albidus, Dekkera bruxellensis, Pichia membranifaciens, Saccharomyces cerevisiae, Zygosaccharomyces bailii and Zygosaccharomyces bisporus has been examined. Peptides analyzed include nine sequence-related antifungal hexapeptides (PAFs) previously developed by a combinatorial approach, and two representative lactoferricin B (LfcinB)-derived peptides. Different peptides had distinct activity profiles. In vitro assays identified the peptides PAF26, PAF36, and LfcinB(17-31), as having growth inhibitory properties towards several of the yeasts at low micromolar concentrations. Z. bailii and Z. bisporus were the most sensitive yeasts. In addition to their fungistatic activity, the three peptides showed fungicidal properties towards Z. bailii, Z. bisporus, and S. cerevisiae in laboratory growth medium. Remarkably, only LfcinB(17-31) against Z. bisporus had inhibitory and fungicidal properties in wine at the concentrations assayed, showing that the antimicrobial action of each peptide is dependent on both the food matrix and the target micro-organism. Lack of fungicidal activity of peptides against Z. bailii in wine is related to the presence of salt ions other than divalent cations. On the contrary, fungicidal activity of LfcinB(17-31) towards Z. bisporus was not significantly affected by wine salts. Our data identify a bioactive peptide from natural origin with potential use against the food spoilage yeast Z. bisporus, and indicate that the application of antimicrobial peptides in wine preservation deserves further investigation.

Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.

A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH2) and PACEI34 (Ac-RKWLFW-NH2), and also a LfcinB-derived peptide, LfcinB17-31 (Ac-FKCRRWQWRMKKLGA-NH2). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.