[Low-intensity extracorporeal shock wave therapy for erectile dysfunction: A systematic review]. / Traitement de la dysfonction érectile par ondes de choc extracorporelles de faible intensité : revue de la littérature.

INTRODUCTION: Our purpose was to assess the efficacy of low intensity extracorporeal shock waves (SW) for the treatment of organic erectile dysfunction (ED). METHODS: A systematic review of the literature published between 2000 and 2020 was conducted using the PRISMA methodology. We used Medline data with the following key words (MesH): "extracorporeal shock wave therapy"; "erectile dysfunction"; "sexuality". RESULTS: Nineteen articles were selected: thirteen randomised controlled trial and six meta-analyses. Most of them studied vascular etiology. Low intensity SW is beneficial ED is evaluated by the IIEF, EHS scores and penile hemodynamic. CONCLUSION: SW may have a theoretical impact on the vascular etiology of organic DE. Their use in this context is supported by the European Society of urology and the European Society of sexual medecine. However, there are discrepancies in current data to establish a protocol to follow in daily practice.

[Extracorporeal shock wave therapy for Peyronie's disease]. / Traitement de la maladie de Lapeyronie par ondes de choc extracorporelles.

INTRODUCTION: The efficiency of extracorporeal shock waves (SW) for Peyronie's disease (PD) is controversial. METHODS: A systematic review of the literature published between 2000 and 2019 was conducted using the PRISMA methodology. We used Medline data with the following. KEYWORDS: "extracorporeal shock wave therapy" ; "Peyronie's disease"; "Sexuality"; Penile erection. RESULTS: Thirteen articles were selected. Our review showed that SW were beneficial in terms of pain. Regarding plaques size and penile curvature, the results remain divergent. CONCLUSION: SW may be useful in the management of pain in selected patients with PD. Its effectiveness on plaques size and penile curvature needs to be demonstrated through controlled and randomized trials. The population has to be targeted, and the treatment protocol must also be standardized.

[Prostatic urethral lift using Urolift® system for benign prostatic hyperplasia: 7years experience]. / Pose d'implants Urolift® intra-prostatique pour hyperplasie bénigne de la prostate : résultats après 7 ans d'expérience.

INTRODUCTION: Urolift® system is a mini-invasive technique, proposed as an alternative treatment for classic surgery of benign prostatic hyperplasia (BPH). Our objective was to report the results of Urolift® system in our center after 7years experience. PATIENTS AND METHODS: Urolift® implants were proposed between February 2012 and March 2019 for patients presenting symptomatic BPH in our center, as an alternative for classic surgery. The efficacy was evaluated with questionnaires about lower urinary tract symptoms (IPSS) and its impact on quality of life (IPSS-QdV). Tolerance was evaluated with questionnaires about erectile (IIEF5) and ejaculatory function (MSHQ-EjD) and complication rate. Survival without additional treatment was assessed using Kaplan-Meier method. RESULTS: Forty patients were treated during this period, with a median follow-up of 32months [12-67]. Three months after the procedure, IPSS and IPSS-QdV were significantly improved (respectively 8 [4-11] vs 20 [17-24]; P<0.0001 and 2 [1-2] vs 5 [4-6]; P<0.0001). MSHQ-EjD and IIEF5 were not modified (respectively 13 [11-14] vs 12 [9-13]; P=0.69 and 21 [18-23] vs 21 [18-23]; P=0.13). Two patients (5%) experienced a urinary retention and needed a bladder catheter. No complication with a Clavien-Dindo score>2 were reported. Survival without additional treatment at 5years was 63%. CONCLUSION: Urolift® implants improved significantly the lower urinary tract symptoms in our population, with a good tolerance profile. More than 60% of the patients did not need an additional treatment after 5years of follow-up. LEVEL OF EVIDENCE: 3.

Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target.

BACKGROUND: Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology. OBJECTIVE: We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach. METHODS: OVA- and house dust mite (HDM)-induced murine asthma models were used in this study. RESULTS: Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO by re-purposing existing drugs approved for the treatment of heart disease may provide a novel therapeutic approach for the treatment of asthma.

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT).

The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.

Effectiveness of Physical Exercise on Alzheimer's disease. A Systematic Review.

OBJECTIVE: A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life in a population of older people with Alzheimer´s disease. DATA SOURCES: Pubmed, Scopus, PEDro, Web of Science, CINAHL, Cochrane Library, grey literature and a reverse search from inception to April 2021 were searched to identify documents. STUDY SELECTION: Publications investigating the effect of any type of physical exercise-based intervention in any of its multiple modalities on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life were searched. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated through the PEDro scale and its internal validity scale. DATA SYNTHESIS: A total of 8 different randomized controlled trials with a total sample of 562 non-overlap Alzheimer disease patients between 50-90 years and a mean age of 75.2 ± 3.9 years were eligible for analyses. Physical-functional capacity was evaluated in 6 of 8 studies and cognitive performance was evaluated in 5 of 8 studies, all of them showed improvements in these variables when compared with the controls, except for two studies in physical-functional capacity and one study for cognitive performance. In the physical-functional capacity and cognitive performance variables, aerobic physical exercise was used in isolation, or in a multimodal way, combining aerobic, strength and balance exercise, from 2 to 7 weekly sessions with doses between 30 and 90 minutes, and a duration of the program comprised of 9 weeks to 6 months. Neuropsychiatric symptoms and quality of life were evaluated in 2 of 8 studies, which the intervention groups experienced significant improvements when compared with the control groups, except for one study that found similar differences in quality of life between both groups. In the neuropsychiatric symptoms and quality of life variables, only aerobic physical exercise was used, in a more homogeneous way, from 2 to 3 weekly sessions with doses of 30 to 60 minutes, and a total program duration of 9 to 16 weeks. CONCLUSIONS: Despite the scarcity of studies, especially those based on multimodal proposals, and the heterogeneity in the protocols, this systematic review found moderate to limited evidence that aerobic physical exercise on its own or combined in a multimodal program that also includes strength and balance exercise can be a useful tool in the management of patients with Alzheimer's disease with the aim of maintaining and/or improving physical-functional capacity and cognitive performance. In addition, this review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving quality of life in patients with Alzheimer´s disease. PROSPERO registration number: CRD42021229891.

In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types.

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell-matrix interactions in rare cancer types using higher passage PDX tissue.

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice.

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

Mature T-lineage leukemia with growth factor-induced multilineage differentiation.

We report an acute T-lymphoblastic leukemia with a predominantly mature CD3+ CD7+ WT31+ phenotype that was induced to differentiate into different cell lineages by various recombinant human growth factors. In the presence of IL-3 or GM-CSF, the leukemic cells gave rise to myeloid and monocytic cells including terminally differentiated, partially functional, segmented neutrophilic granulocytes as assessed by morphologic, cytochemical, immunophenotypic, and functional criteria. In the presence of IL-2, leukemic granulated lymphoid cells exhibiting MHC-unrestricted cytotoxicity and expressing a CD2+ CD3+ CD5+ CD7+ CD8+ CD33+ WT31+ Leu19+ phenotype arose. Leukemic cell cultures initiated with IL-3 yielded growth factor-independent cells with a mixed lineage phenotype and morphologic and cytochemical evidence of immature blasts. These were T lymphocyte and myeloid surface antigen (CD2,CD3,CD5,CD7,CD13,CD33,WT31) positive. Identical rearrangements of the constant region of the TCR-delta gene and of the joining regions of the TCR-beta, -gamma, and -delta genes were observed in the fresh and all cultured leukemic cells, indicating that they were derived from the same malignant clone. Consistent with the molecular genetic data, the cytogenetic analyses of the GM-CSF-, IL-3-cultured and the growth factor-independent leukemic cells showed the presence of multiple, closely related abnormal clones, all of which had an interstitial deletion of part of the long arm of chromosome 6 and a complex 1;10;12 translocation. In conclusion, these data demonstrate the involvement of a multipotent leukemic precursor cell in this predominantly mature CD2+ CD3+ CD5+ CD7+ WT31+ T-ALL. This multipotent leukemic precursor may be susceptible to various growth factors and respond with ordered differentiation and maturation.

Complications associated with inferior alveolar nerve reposition technique for simultaneous implant-based rehabilitation of atrophic mandibles. A systematic literature review.

INTRODUCTION: Surgical inferior alveolar nerve (IAN) reposition techniques offer an alternative approach to implant-based rehabilitation in patients with severe mandibular atrophy The aim of this systematic review, was to determine the complications associated with the technique and to determine which of two variants (lateralization or transposition) is less invasive. MATERIALS AND METHODS: An electronic search was conducted in databases complimented by a manual search to identify clinical studies investigating complications derived from these surgical techniques. Only studies of adult humans, published in English during the last seven years were included. The initial search located 78 articles, of which seven were included in analysis on the basis of the following characteristics: four investigated inferior alveolar nerve lateralization (IANL), one inferior alveolar nerve transposition (IANT), and two investigated both reposition techniques. RESULTS: This review included data from 289 patients who were recruited for lateralization (N=319) or transposition surgery (N=33) making a total of 352 reposition procedures. Five patients (1.73%) suffered persistent damage to the IAN at the end of the follow-up periods. The overall implant survival rate was 99.26% of a total of 817 implants. The most common complications were neurosensory problems, mandibular fracture, infection, implant loss, and insufficient anatomical reconstruction of the atrophic mandible; neurosensory complications (hypoesthesia, paraesthesia, and hyperesthesia caused by traumatic damage to the nerve) were the most prevalent. CONCLUSIONS: Lateralization of the inferior alveolar nerve would appear to be less invasive as it produces lower percentages of persistent neurosensory disorders (1.56%) than transposition (12.12%). Nevertheless, both techniques offer a viable approach to implant placement in edentulous atrophic mandibles, obtaining predictable clinical and radiological results after 5 years implant loading.

Myocardial Inflammatory Changes Before and After Antiretroviral Therapy Initiation in People With Advanced Human Immunodeficiency Virus Disease.

Because of the high frequency of late presentation of human immunodeficiency virus (HIV) disease in our population, we decided to explore the presence of myocarditis among people with HIV infection and advanced immunosuppression (less than 200 CD4+ cells/µL) and to describe the inflammatory changes observed after combined antiretroviral therapy initiation in an observational, longitudinal, prospective cohort. We performed both cardiovascular magnetic resonance imaging and doppler transthoracic echocardiogram.

Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice.

Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8+ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-alpha and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3 gamma and completely lacked CD3 zeta, which was replaced by the Fc epsilon gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.

Health indicators in the European regions: expanding regional comparisons to the new countries of the European Union - ISARE III.

OBJECTIVES: Most comparisons of health in Europe take place at the national level. However, there is increased interest in looking at health data at a sub-national level. This study aimed to establish the availability of health data at a regional level and to develop a methodology for the comparisons of health indicators at a sub-national level. In previous work on indicators at a regional level in the European Union, the authors recommended the development of such indicators. This paper takes into account the expansion of the European Union which took place in 2004. STUDY DESIGN: Observational study using routinely available data. METHODS: Similar to previous projects, a network of country correspondents was used and data were collected on a similar range of topics. In addition, a supplementary list of data was collected from one region of each country. RESULTS: Twenty-three countries out of the 25 member states of the European Union participated in the study. Where available, data were of relatively good quality. Data on mortality were most readily available, but data on important public health topics such as obesity were much more difficult to obtain. CONCLUSIONS: A database and a set of indicators for relevant sub-national areas of countries in the European Union, including new countries, were constructed. Data collection from the new countries was more straightforward due to the requirement for them to adhere to the nomenclature of territorial units for statistics (NUTS) levels. The lack of adherence to NUTS levels in the 'old' countries of the European Union continues to create problems. There remains an urgent need to introduce comprehensive sub-national data collection on important public health topics such as obesity and smoking.

Confocal scanning optical microscopy of a 3-million-year-old Australopithecus afarensis femur.

Portable confocal scanning optical microscopy (PCSOM) has been specifically developed for the noncontact and nondestructive imaging of early human fossil hard tissues, which here we describe and apply to a 3-million-year-old femur from the celebrated Ethiopian skeleton, "Lucy," referred to Australopithecus afarensis. We examine two bone tissue parameters that demonstrate the potential of this technology. First, subsurface reflection images from intact bone reveal bone cell spaces, the osteocyte lacunae, whose density is demonstrated to scale negatively with body size, reflecting aspects of metabolism and organismal life history. Second, images of a naturally fractured cross section near to Lucy's femoral mid-shaft, which match in sign those of transmitted circularly polarized light, reveal relative collagen fiber orientation patterns that are an important indicator of femoral biomechanical efficacy. Preliminary results indicate that Lucy was characterized by metabolic constraints typical for a primate her body size and that in her femur she was adapted to habitual bipedalism. Limitations imposed by the transport and invasive histology of unique or rare fossils motivated development of the PCSOM so that specimens may be examined wherever and whenever nondestructive imaging is required.

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis.

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.

Tyrosine kinase inhibitors in iodine-refractory differentiated thyroid cancer: experience in clinical practice.

PURPOSE: The aim of this study is to describe our clinical experience with tyrosine kinase inhibitors (TKIs) and to evaluate their efficacy and tolerability in patients with iodine-refractory differentiated thyroid cancer (DTC). METHODS: There were 17 patients (47.1% women, mean age: 65.7) with DTC iodine-refractory (9 papillary, 2 follicular and 3 Hürthle cell), treated with TKIs: 16 with sorafenib and 1 with lenvatinib as first-line treatment; 7 required second-line treatment (4 lenvatinib and 3 axitinib). Primary endpoints were progression-free survival (PFS) and radiographic response (determinate at 3, 6, 12, 18, and 24 months after the initiation of treatment) and second endpoints were determining differences in baseline characteristics depending on clinical course and describing toxicities and tolerability. RESULTS: Median PFS was 18 months. During the first 24 months of treatment with TKIs PR rate was 35.3% (only 5.8% ≥ 6 months) and SD ≥ 6 months was observed in 58.8%. There were no significant differences in baseline characteristics between patients with good and poor evolution. Adverse events (AEs) were present in 100% of patients, but most of them were grade 1 and 2. CONCLUSIONS: In our population of patients with iodine-refractory DTC, treatment with sorafenib, lenvatinib, and axitinib allows the stabilization of the disease in a high percentage of cases, with acceptable tolerability.

Pancreatic metastases from ductal and lobular carcinomas of the breast.

The pancreas is an uncommon target for metastases from other primary tumours. We discuss clinical, diagnostic and therapeutic aspects of pancreatic metastases through presentation of two surgically treated cases of metastases originating from breast cancer.

Isolation of Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum ß-lactamases from dog urine of the Metropolitan Area of the Aburrá Valley (Antioquia, Colombia) / Aislamiento de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido a partir de orina de perros del Área metropolitana del Valle de Aburrá (Antioquia, Colombia)

ABSTRACT Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing urinary tract infections in humans and animals. Close contact between humans and companion animals can facilitate the spread of multidrug resistant pathogens between both species. The objective of the research was to characterize extended-spectrum ß-lactamases (ESBL) -producing E. coli and K. pneumoniae isolated from dogs with urinary tract infections in the metropolitan area of Valle del Aburrá (Antioquia, Colombia). Three-hundred seventy-one urine samples collected from March 2018 to March 2019 in a veterinary clinical laboratory were analyzed. E. coli and K. pneumoniae isolates were detected in chromogenic agar and identified by biochemical tests. Susceptibility testing was performed by disc diffusion and ESBL production was evaluated by the double disk test in all isolates. MIC determination of ESBL-positive isolates were performed on the automated VITEK®2 system. Multiple PCR was used for the detection of CTX-M beta-lactamases (group 1, 2, 9 and 8/25), SHV, TEM, and AmpC of plasmid origin in ESBL-positive isolates. In total 22 out 371 isolates were positive for ESBL production by double disc test, 11 E. coli (ESBL-Ec) and 11 K. pneumoniae (ESBL-Kp). The multiple PCR detected CTX-M group 1 in the 22 ESBL-positive isolates. Multi-drug resistance was observed in all ESBL-producing isolates. In conclusion, a high frequency of antibiotic multi-resistance was found in ESBL-Ec and ESBL-Kp. The main ESBL detected was CTX-M group 1, which also prevails in human isolates.

RESUMEN Escherichia coli y Klebsiella pneumoniae son los patógenos más comunes causantes de infecciones en tracto urinario en humanos y animales. El contacto estrecho con los animales de compañía puede favorecer la diseminación de patógenos multiresistentes entre ambas especies. El objetivo de la investigación fue caracterizar E. coli (Ec -BLEE) y K. pneumo-niae (Kp -BLEE) productores de betalactamasas de espectro extendido provenientes de aislados de caninos con infecciones del tracto urinario del Área Metropolitana del Valle de Aburrá. 371 muestras de orina de caninos colectadas entre marzo de 2018 y marzo 2019 en un laboratorio clínico veterinario fueron analizadas. E. coli y K. pneumoniae se detectaron en agar cromogénico y se identificaron mediante pruebas bioquímicas. La prueba de susceptibilidad se realizó por difusión en disco y la producción de BLEE se evaluó por test de doble disco en todos los aislados. La determinación de la CIM en aislados positivos a BLEE se realizó en el sistema automatizado VITEK®2. Se utilizó PCR múltiple para la detección de betalactamasas tipo CTX-M (grupo 1, 2, 9 y 8/25), SHV, TEM y AmpC de origen plasmídico en aislados positivos a BLEE. Un total de 22 de 371 aislados fueron positivos a BLEE por test de doble disco, 11 E. coli (Ec -BLEE) y 11 K. pneumoniae (Kp-BLEE). La PCR detectó CTX-M grupo 1 en los 22 aislados positivos a BLEE. Se observó multirresistencia en todos los aislamientos productores de BLEE. En conclusión, se encontró una alta frecuencia de multirresistencia en Ec-BLEE y Kp-BLEE. La principal BLEE detectada fue CTX-M grupo 1, que también predomina en aislados humanos.

Gradual loss of T-helper 1 populations in spleen of mice during progressive tumor growth.

BACKGROUND: The carefully orchestrated events that result in a protective immune response are coordinated to a large extent by cytokines produced by T helper 1 (Th1) and T helper 2 (Th2) T-cell subsets, which are two arms of the immune system. Th1 cells preferentially produce interleukin 2 (IL-2), interferon gamma (IFN gamma), and tumor necrosis factor (TNF), resulting in a cellular response that helps to eliminate infected cells. In contrast, Th2 cells produce IL-4, IL-5, IL-6, and IL-10 and stimulate an antibody response that helps to prevent the cells from becoming infected. The clinical progression of several infectious diseases, including human immunodeficiency virus, some types of parasitoses, and tuberculosis, is thought to be associated with the predominance of a Th2-type T-cell response. Recent reports have demonstrated the presence of T cells producing Th2 lymphokines (IL-4, IL-6, and IL-10) in tumor-infiltrating lymphocytes of renal cell carcinoma. PURPOSE: The purpose of this study was to investigate at the molecular level whether there was any change in the splenic T cells of mice with progressively growing tumors from a Th1 to a Th2 DNA-binding pattern or phenotype. METHODS: Splenic T cells from mice bearing renal cell carcinoma or MCA-38 colon carcinoma were tested for cytokine production after in vitro activation. Nuclear extracts of splenic T cells were used for the DNA-binding assay using IFN-gamma core promoter region, the kappa B (kappa B) site from immunoglobulin gene, and the nuclear factor of activated T-cell (NFAT) site from IL-2 gene. RESULTS: Splenic T cells from mice bearing renal cell carcinoma or MCA-38 colon carcinoma preferentially produced Th2 cytokines (i.e., IL-4) upon activation and showed a marked decrease in Th1 cytokine (particularly IFN gamma) production compared with the production observed in normal splenic T cells. The DNA-binding assay with the IFN-gamma core promoter region confirmed the gradual decline in the nuclear transcription factors associated with the Th1 phenotype during tumor progression in both tumor models. Renal cell carcinoma-bearing mice, successfully treated with flavone-8-acetic acid and recombinant human IL-2, showed a reversion to a Th1-like pattern. In addition, nuclear extracts of T cells from tumor-bearing animals showed a Th2-type kappa B-binding pattern. Moreover, the NFAT complex present in the normal splenic T cells was lost at the later stages of tumor progression; instead, a new complex was present in mice bearing long-term tumors. CONCLUSION: T cells from tumor-bearing mice lose the Th1 phenotype with progressive tumor growth.

Increased circulating nitrogen oxides after human tumor immunotherapy: correlation with toxic hemodynamic changes.

BACKGROUND: Toxicity to interleukin-2 (IL-2) tumor immunotherapy is manifested principally by the vascular leak syndrome, hypotension, and a hyperdynamic response with low systemic vascular resistance. Nitric oxide (.N = O), a recently discovered biological mediator of vascular smooth muscle relaxation, is produced in increased amounts by numerous cell types exposed to a number of inflammatory cytokines. PURPOSE: Our purpose was to determine if there is an increased production of .N = O in patients receiving IL-2 tumor immunotherapy, and, if so, whether increases in .N = O production correlate with hemodynamic instability. METHODS: Twelve patients undergoing immunotherapy trials with IL-2 and anti-CD3 monoclonal antibody-activated lymphocytes (T-AK cells) were studied. Plasma levels of nitrate (NO3-), the stable end metabolic product of .N = O synthesis, were measured before and at the end of IL-2 treatment cycles. RESULTS: We observed a ninefold increase in plasma levels of NO3- in patients after 7 days of treatment (P less than .0001). A significant decrease in both systolic and diastolic blood pressures was observed in all patients (P less than .001). CONCLUSIONS: We propose that mediated induction of .N = O synthase enzyme leads to progressive increases in .N = O production which, in turn, produces clinically significant hypotension. IMPLICATIONS: Since .N = O synthesis can be competitively inhibited by L-arginine analogues, a possible pharmacologic modulation of .N = O production could potentially contribute to better management of toxic side effects seen in IL-2 cancer therapies.