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Anaemia is a global health concern, with iron deficiency anaemia (IDA) causing approximately 50% of cases. Affecting mostly the elderly, pregnant and adult women and children, physiopathology of IDA in relation to the gut microbiome is poorly understood. Therefore, the objective of this study is to analyse, in an animal model, the effect of IDA on the gut microbiome along the gastrointestinal tract, as well as to relate intestinal dysbiosis to changes in microbial metabolites such as short chain fatty acids (SCFA). IDA was experimentally induced through an iron deficient diet for a period of 40 days, with twenty weaned male Wistar rats being randomly divided into control or anaemic groups. Blood samples were collected to control haematological parameters, and so were faecal and intestinal content samples to study gut microbial communities and SCFA, using 16S rRNA sequencing and HPLC–UV respectively. An intestinal dysbiosis was observed as a consequence of IDA, especially towards the distal segments of the gastrointestinal tract and the colon. An increase in SCFA was also noticed during IDA, with the major difference appearing in the colon and correlating with changes in the composition of the gut microbiome. Clostridium_sensu_stricto_1 and Clostridium_sensu_stricto_4 showed the greatest correlation with variations in butyric and propionic concentrations in the colon of anaemic animals. Composition of intestinal microbial communities was affected by the generation of IDA. An enrichment in certain SCFA-producing genera and SCFA concentrations was found in the colon of anaemic animals, suggesting a trade-off mechanism against disease.

BACKGROUND The aim of our study was to evaluate the effects of a hyaluronic acid (HA) gel at 45 days on the microbiome of implants with peri-implantitis with at least 1 year of loading. METHODS A randomized controlled trial was conducted in peri-implantitis patients. Swabs containing the samples were collected both at baseline and after 45 days of treatment. 16S rRNA sequencing techniques were used to investigate the effect of HA gel on the subgingival microbiome. RESULTS One hundred and eight samples of 54 patients were analyzed at baseline and after follow-up at 45 days. Three strata with different microbial composition were obtained in the samples at baseline, representing three main microbial consortia associated with peri-implantitis. Stratum 1 did not show any difference for any variable after treatment with HA, whereas in stratum 2, Streptococcus, Veillonella, Rothia, and Granulicatella did decrease (P < 0.05). Similarly, Prevotella and Campylobacter (P < 0.05) decreased in stratum 3 after treatment with HA. Microbial diversity was found to be decreased in stratum 3 (P < 0.05) after treatment with HA compared with the control group, in which an increase was found (P < 0.05). CONCLUSIONS HA reduced the relative abundance of peri-implantitis-related microorganisms, especially the early colonizing bacteria, suggesting a specific action during the first stages in the development of the disease. HA did not alter relative abundances of non-oral genera. The use of HA in advanced stages of peri-implantitis resulted in a decrease in microbial alpha diversity, suggesting a protective action of the peri-implant site against bacteria colonization.

Veillonella dispar is a Gram-negative anaerobic coccus involved in only a few human diseases. We report the second case of bacteremia due to this microorganism in an elderly patient. A 72-year-old man with a history of bladder cancer presented with diarrhea, vomiting, and fever for 48 hours. After the diagnosis of septic shock, four sets of blood cultures were taken, and three of them yielded V. dispar. Resistance to metronidazole, penicillin, and piperacillin-tazobactam was documented. Treatment with clindamycin was started, and the patient was discharged after improvement in his general condition., Highlights • Veillonella dispar is rarely associated with bloodstream infections. • This is the second case of bacteraemia caused by this pathogen in pure culture. • Caution should be taken with anaerobes and mass spectrometry. • The strain, as in other published cases, was resistant to metronidazole.

OBJECTIVES The goal of this study was to describe the clinical features and outcomes of thoracic surgery patients during the coronavirus disease 2019 (COVID-19) pandemic. METHODS Thirty-five patients were treated at the 12 de Octubre University Hospital in Madrid between 1 March 2020 and 24 April 2020 during the COVID-19 pandemic. Patient demographics, surgical procedures, complications, COVID-19 symptoms and outcomes were recorded. A protocol was introduced to reduce the risk of operating on patients with COVID-19, including symptom screening, a polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 and computed tomography scans of the chest. Surgical activity changed significantly during this time, from an initial period of near-normal activity, through an emergency-only period and finally a recovery period when some oncological surgical cases were restarted. Selection criteria for surgical patients are also described. RESULTS A total of 34 patients underwent surgery during the pandemic period. We performed 22 lung resections (11 lobectomies and 11 sublobar resections). No hospital deaths were recorded. An elective surgery patient and an emergency surgery patient were diagnosed with COVID-19 (5.88%). The former died within 30 days after surgery. CONCLUSIONS Severe acute respiratory syndrome coronavirus 2 represents a tremendous limitation for thoracic surgical practice. Preoperative practices to exclude asymptomatic cases infected with the virus allowed us to perform thoracic surgical procedures.

Porphyromonas species are Gram-negative anaerobic bacilli mainly involved in human periodontal diseases. We report an uncommon case of bacteremia due to P. asaccharolytica in a patient with necrotizing fasciitis. A 52-year-old woman with a history of diabetes mellitus was admitted for an extensive necrotizing lesion on the left lower limb. After she developed septic shock, two sets of blood cultures were taken. Anaerobic bottles yielded a pure culture of a microorganism initially identified as P. uenonis by MALDI-TOF MS but with a low log score, and a gene sequencing technique was therefore applied, identifying the isolate as P. asaccharolytica. Only resistance to penicillin and clindamycin was documented. Treatment with meropenem was administered, and the patient was discharged following her recovery.

The objectives of this study were to report 10 episodes of clinically significant bacteremia caused by species of the genus Anaerococcus isolated between July 2018 and February 2021 from the microbiology laboratory of a tertiary hospital in Granada (Spain). None of the isolates were identified by MALDI-TOF MS, and the definitive species identification was performed by 16 S rRNA gene sequencing. No reference spectra of the Anaerococcus species were present in the MALDI-TOF MS database. Eight isolates were finally identified as A. octavius, one isolate as A. tetradius and the other as A. urinomassiliensis. The majority of these infections were seen in patients aged >70 years. Risk factors for anaerobic infection were observed in eight patients, especially diabetes mellitus, surgery, and the presence of cancer. Fever was present in all patients. Three patients died, but only one death was attributed to the infection. Mean detection time of positive blood cultures was 47.5 h (range 24-92 h). Antimicrobial susceptibility to penicillin, amoxicillin-clavulanate, imipenem, moxifloxacin, clindamycin, metronidazole, and piperacillin-tazobactam was tested using the gradient diffusion technique and EUCAST breakpoints (except for moxifloxacin). No resistance to amoxicillin-clavulanate, metronidazole, imipenem, or piperacillin-tazobactam was detected; however, the majority of isolates were resistant to clindamycin. When MALDI-TOF MS does not provide a correct identification at genus or species level, as in some isolates of Gram-positive anaerobic cocci, microbiologists should perform an additional confirmatory technique, such as gene sequencing analysis, to obtain a definitive diagnosis.

Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs., 3TR, IMI2 H2020-JTI538 IMI2-2018, Instituto de Salud Carlos III AC18/00008, Government of Spain FPU16/05822

Bacteroides fluxus is a Gram-negative anaerobic bacillus isolated from human faeces in healthy individuals. Until now, this bacterium had not been involved in human diseases. We report the first case of abdominal infection due to this microorganism in an elderly patient. A 76-year-old man with a history of chronic pulmonary obstructive disease presented with dyspnea, orthopnea and cough. The clinical evolution worsened with both a colonic ischemia and further diffuse peritonitis of pancreatic origin. Peritoneal fluid was obtained and the culture yielded B. fluxus in pure culture. Resistance to penicillin, amoxicillin-clavulanate, clindamycin and moxifloxacin was documented. Treatment with meropenem + linezolid was started, but the patient finally died due to a multiorganic failure.

Alistipes spp is a genus of Gram-negative anaerobic rods involved in very few human diseases. We report the first case of abdominal infection due to Alistipes onderdonkii in a 58-year-old man with a history of chronic obstructive pulmonary disease. He presented with abdominal pain and general malaise after retrogastric drainage for a pancreatitis episode a few days earlier. After the diagnosis of diffuse peritonitis with perforation and necrotizing pancreatic collection, abundant pancreatic fluid was drained and yielded the isolation of A. onderdonkii in pure culture. Resistance to penicillin and moxifloxacin was documented for this strain. Treatment with metronidazole was prescribed, and the patient was discharged after improvement of his general condition.

Propionibacterium (Propionimicrobium) lymphophilum is a Gram-positive anaerobic rod involved in few human diseases. We report a rare case of bacteremia due to this microorganism in an elderly patient. A 95-year-old woman without a remarkable medical history presented with dyspnea, chest pain and fever for seven days. Blood cultures resulted in isolation of P. lymphophilum. Resistance only to metronidazole was found. Treatment with amoxicillin-clavulanic acid was established, and the patient was discharged and improvement of her general condition was documented.

Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients. © 2015 by the authors; licensee MDPI, Basel, Switzerland., This work was support in part by Consejería de Salud y Bienestar Social (Junta de Andalucía) Grant (PI05142012), RETICEF (RD06/0013/1014-RD12/0043/0014) and Fondo de Investigación Sanitaria (Instituto Carlos III) Grants (PI12/02141) with co-financing from FEDER (Fondo Europeo de Desarrollo Regional). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogenTrypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug forT. b. gambienseacute infection. Anin vitroeffectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore,in vivotherapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases.

OBJECTIVE Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561–2.586], P = 0.003) and IMT (β = 0.330 [14.237–67.693], P = 0.003) were positively correlated with sclerostin. CONCLUSIONS Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.

Leishmania and Trypanosoma are members of the Trypanosomatidae family that cause severe human infections such as leishmaniasis, Chagas disease, and sleeping sickness affecting millions of people worldwide. Despite efforts to eradicate them, migrations are expanding these infections to developing countries. There are no vaccines available and current treatments depend only on chemotherapy. Drug resistance is a major obstacle for the treatment of these diseases given that existing drugs are old and limited, with some having severe side effects. Most resistance mechanisms developed by these parasites are related with a decreased uptake or increased efflux of the drug due to mutations or altered expression of membrane transporters. Different new approaches have been elaborated that can overcome these mechanisms of resistance including the use of inhibitors of efflux pumps and drug carriers for both active and passive targeting. Here we review new formulations that have been successfully applied to circumvent resistance related to drug transporters, opening alternative ways to solve drug resistance in protozoan parasitic diseases.

Aims To analyze the relationship between serum levels of osteocalcin and parameters of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods This cross-sectional study of 78 patients with T2DM evaluated intima–media thickness, and the prevalence of coronary heart disease, atherosclerotic plaques and aortic calcifications. Serum osteocalcin levels were also determined by radioimmunoassay. Results The patients' mean age was 57.8±6.4 years (duration of diabetes: 13.4 years; mean HbA 1c level: 8.01%), and 37.2% had coronary heart disease, 56% had an abnormal intima–media thickness, 26.9% had carotid plaques and 32.1% had aortic calcifications. Coronary heart disease was associated with higher levels of osteocalcin in male vs female patients (1.95±1.36 vs 0.93±0.86ng/mL, respectively; P =0.006). Also, higher concentrations of osteocalcin were found in female patients with vs without abnormal intima–media thicknesses (2.17±1.84 vs 1.25±0.67ng/mL, respectively; P =0.042), carotid plaques (2.86±2.10 vs 1.43±1.09ng/mL, respectively; P =0.03) and aortic calcifications (2.85±1.97 vs 1.26±0.83ng/mL, respectively; P =0.002). Serum osteocalcin levels were associated with coronary heart disease on multivariate logistic regression (odds ratio: 2.27, 95% confidence interval: 1.21–4.25; P =0.01). Conclusion In T2DM patients, serum osteocalcin levels were associated with parameters of atherosclerosis, suggesting that osteocalcin is involved not only in bone metabolism, but also in atherosclerotic disease.

Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus (T2DM).The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism.This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures.Sclerostin levels were significantly higher in T2DM patients than control subjects (P0.001) and in T2DM males than in T2DM females (P0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P0.05). Sclerostin concentrations were positively associated with duration of T2DM (P = 0.064) and glycated hemoglobin (P = 0.074) independently of age in T2DM patients. Sclerostin was inversely related to bone turnover markers (P0.05) and positively related to lumbar spine, femoral neck, and total hip BMD (P0.05) in the T2DM group. Sclerostin was significantly lower in osteoporotic than nonosteoporotic patients with T2DM (P = 0.048).Circulating sclerostin is increased in T2DM independently of gender and age. Serum sclerostin is also correlated with duration of T2DM, glycated hemoglobin, bone turnover markers, and BMD in T2DM patients. Additional studies are needed to evaluate the role of sclerostin on bone metabolism in this population.

Diabetes mellitus causes an increase of morbidity and mortality. Advanced glycosilation end products (AGE) are formed by non-enzymatic glycation between proteins and reducing sugars as glucose. Oxidative reactions (glycoxidations) are essential for the formation of some AGE, for example pentosidine. Increased concentrations of pentosidine can be found in pathological conditions associated with hyperglycaemia and also related to increased oxidative stress. In individuals with diabetes mellitus, pentosidine formation and accumulation is developed at an accelerated rate in cells without insulin control for glucose uptake. Pentosidine has a pivotal role in diabetic complications, probably as a consequence of the diverse properties of this compound, which alters the structure and function of molecules in biological systems. The following review discusses the alterations in the concentration of pentosidine in the body, particularly in relation to changes occurring in diabetes and its complications such as vascular and bone disease, nephropathy, neuropathy and retinopathy. Novel therapeutic approaches which can prevent or ameliorate the toxic effects of AGE in the initiation and progression of diabetic complications are reviewed.

African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs., Author Summary Drug resistance is complicating the treatment of parasitic diseases including African trypanosomiasis, a fatal disease if left untreated. Development of a vaccine is unlikely due to parasite antigenic variation. Current chemotherapy relies primarily on four drugs. Three of these drugs access the cell’s interior through surface transporters and resistance mechanisms are largely associated with loss-of-function mutations in the involved surface drug transporters. We reasoned that using an alternative drug entrance would circumvent parasite resistance due to mutation in a surface transporter. We have developed a drug nanocarrier that consists of polymeric nanoparticles coated with a single domain antibody that targets the trypanosome surface. This new formulation reduces the minimal curative dose and, most importantly, circumvents drug resistance in a resistant cell line as a result of mutations in the surface transporter that mediate drug uptake. This study presents a proof-of-concept of a novel technology for reversing transporter-related drug resistance with applications to other infectious diseases.

The treatment of African trypanosomiasis has essentially remained unchanged for decades. A mountain of excellent work has been produced on many aspects of trypanosome biochemistry, biology, genetics, etc., but this has not translated into new therapies, although the disease burden has steadily increased through the latter half of the twentieth century. The only new drug to be introduced in the last 50 years or so is eflornithine, in the late 1970s, for the treatment of late-stage gambiense sleeping sickness only. However, this was in many ways unsatisfactory and melarsoprol remained the first-line treatment for late-stage sleeping sickness until an alarming increase in treatment failures necessitated change. Since the emerging sleeping sickness epidemic became widely recognised, around the year 2000, needs-driven development of new drugs, and the preservation of the production of old drugs, has been the result of dedicated work by organisations such as the World Health Organisation, the Drugs for Neglected Diseases initiative (DNDi), the Access to Essential Medicines campaign, and the Consortium for Parasitic Drug Development (CPDD) among others, much of it in partnership with academia and the pharmaceutical industry. This has already resulted in milestones such as the donations of free treatments by producers; improved drug distribution, case finding and clinical care; an improved 10-day melarsoprol treatment; the first clinical trial for an oral sleeping sickness drug—pafuramidine and the introduction of eflornithine–nifurtimox combination therapy to begin replacing melarsoprol. While these efforts have undoubtedly contributed to reducing the disease burden in central Africa, newer treatments are still very necessary, especially as most current treatments are threatened by drug resistance. Here, we review recent advances in understanding drug resistance mechanisms, progress towards new drugs, and new delivery systems to improve efficacy.

The role of sclerostin on bone metabolism and its relation to sex steroids in patients with prostate cancer (PC) is not well known. We found that sclerostin levels are significantly increased in PC patients, particularly in those with androgen deprivation therapy (ADT), and there is an inverse relationship between sclerostin levels and testosterone. Recent studies have evaluated sclerostin levels in bone diseases as osteoporosis. However, there are few data in PC patients, particularly in patients with hypogonadism related to ADT. The aim of the present study was to compare serum sclerostin levels in ADT/non-ADT-treated PC patients and healthy controls and to evaluate their relationship with sex steroids and bone metabolism. We performed a cross-sectional study involving 81 subjects: 25 ADT-treated PC patients, 34 PC patients without ADT treatment, and 22 healthy controls. We measured serum sclerostin levels, bone turnover markers, bone mineral density (BMD) in all individuals, and sex steroids levels in PC patients. Serum sclerostin levels were significantly higher in PC patients compared to those in control subjects. ADT-treated patients had significantly higher sclerostin levels than PC patients without ADT treatment: ADT 64.52 ± 27.21 pmol/L, non-ADT 48.24 ± 15.93 pmol/L, healthy controls 38.48 ± 9.19 pmol/L, p

Nicotinamide, a soluble compound of the vitamin B3 group, has antimicrobial activity against several microorganisms ranging from viruses to parasite protozoans. However, the mode of action of this antimicrobial activity is unknown. Here, we investigate the trypanocidal activity of nicotinamide on Trypanosoma brucei, the causative agent of African trypanosomiasis. Incubation of trypanosomes with nicotinamide causes deleterious defects in endocytic traffic, disruption of the lysosome, failure of cytokinesis, and, ultimately, cell death. At the same concentrations there was no effect on a cultured mammalian cell line. The effects on endocytosis and vesicle traffic were visible within 3 h and can be attributed to inhibition of lysosomal cathepsin b-like protease activity. The inhibitory effect of nicotinamide was confirmed by a direct activity assay of recombinant cathepsin b-like protein. Taken together, these data demonstrate that inhibition of the lysosomal protease cathepsin b-like blocks endocytosis, causing cell death. In addition, these results demonstrate for the first time the inhibitory effect of nicotinamide on a protease.

Trypanosoma brucei is the causative agent of African sleeping sickness. Available treatments are ineffective, toxic and susceptible to resistance by the parasite. Here we show that various endogenous neuropeptides act as potent antitrypanosome agents. Neuropeptides exerted their trypanolytic activity through an unusual mechanism that involves peptide uptake by the parasite, disruption of lysosome integrity and cytosolic accumulation of glycolytic enzymes. This promotes an energetic metabolism failure that initiates an autophagic-like cell death. Neuropeptide-based treatment improved clinical signs in a chronic model of trypanosomiasis by reducing the parasite burden in various target organs. Of physiological importance is the fact that hosts respond to trypanosome infection producing neuropeptides as part of their natural innate defense. From a therapeutic point of view, targeting of intracellular compartments by neuropeptides suppose a new promising strategy for the treatment of trypanosomiasis.