LIFT procedure: postoperative outcomes, risk factors for fistula recurrence and continence impairment.

Ligation of the intersphincteric fistula tract has been recently employed as definitive treatment of anal fistulas. However, it carries a potential risk of continence impairment, fistula recurrence, and repeated operations. This study aimed to assess postoperative outcomes related to this procedure and evaluate the potential influence of preoperative and intraoperative features. Patients who underwent LIFT procedure between June 2012 and September 2021 were retrospectively analyzed. Patients were divided according to whether they developed fistula recurrence and on the history of a surgery prior to the LIFT. Preoperative features, postoperative outcomes, and risk factors adverse outcomes were analyzed. Forty-eight patients were included, of which 25 received primary LIFT, being the high transsphincteric fistula pattern the most frequent (62.5%). The median follow-up was 13.3 months, with a recurrence rate of 20.8%, of which the majority presented an intersphincteric fistula pattern (50%); and continence impairment rate of 16.7%. A higher prevalence of diabetes (p = 0.026) and a trend towards a higher prevalence of patients with a history of high transsphincteric fistula (0.052) were observed in the group with fistula recurrence. The history of diabetes and the operation time with a cut-off value ≥ 69 min showed a trend as a risk factors for developing fistula recurrence (0.06) and postoperative continence impairment (0.07), respectively. The LIFT procedure seems to be safe in terms of morbidity, with a reasonable incidence of recurrences, showing better results when it is primarily performed. Preoperative characteristics should be considered as they may impact outcomes.

Characterization of the kisspeptin system in human spermatozoa.

Kisspeptin, the product of the KISS1 gene, plays an essential role in the regulation of spermatogenesis acting primarily at the hypothalamic level of the gonadotropic axis. However, the presence of kisspeptin and its canonical receptor, KISS1R, in spermatozoa has not been explored nor the direct effects of kisspeptin on sperm function have been studied so far. In the present study, we analysed the expression of kisspeptin and its receptor in sperm cells by western blot and immunocytochemistry assays and evaluated the effects of exposure to kisspeptin on sperm intracellular Ca(2+) concentration, [Ca(2+)]i, sperm motility, sperm hyperactivation and the acrosome reaction. Changes in [Ca(2+)]i were monitored using Fura-2, sperm kinematic parameters were measured using computer-assisted sperm analysis (CASA), and the acrosome reaction was measured using fluorescein isothiocyanate-coupled Pisum sativum agglutinin lectin (FITC-PSA method). We found that kisspeptin and its receptor are present in sperm cells, where both are mainly localized in the sperm head, around the neck and in the flagellum midpiece. Exposure to kisspeptin caused a slow, progressive increase in [Ca(2+)]i, which reached a plateau about 3-6 min after kisspeptin exposure. In addition, kisspeptin modulated sperm progressive motility causing a biphasic (stimulatory and inhibitory) response and also induced transient sperm hyperactivation. The effects of kisspeptin on sperm motility and hyperactivation were inhibited by the antagonist of KISS1R, peptide 234. Kisspeptin did not induce the acrosome reaction in human spermatozoa. These data show for the first time that kisspeptin and its receptor are present in human spermatozoa and modulate key parameters of sperm function. This may represent an additional mechanism for their crucial function in the control of male fertility.

Brassica sprouts exposed to microplastics: Effects on phytochemical constituents.

Microplastics (MPs) can affect plant biomass, tissue composition, and root traits. However, the effects of MPs on the synthesis of secondary metabolites and on the accumulation of bioactive compounds remain poorly studied. The objective of this work was to analyze accumulation of bioactive compounds in broccoli and radish sprouts grown hydroponically in a substrate containing seven different toxic amounts (from very low to extremely high) of low-density polyethylene (PE). Radish was more severely affected by microplastic pollution than broccoli. The effect on the phytochemical composition was statistically significant in both species compared to control. In this aspect, glucosinolate (GSL) content was negatively affected by MPs decreasing from 182 to 124 mg 100 g-1 at medium doses of MPs in broccoli, whereas these compounds drastically decreased from 253 to 151 mg 100 g-1 at the same doses in radish. Anthocyanin content significantly increased until medium doses of MPs ranging from 6.28 to 11.44 mg 100 g-1 in broccoli whereas in radish was from 2.44 to approximately 4 mg 100 g-1. In addition, other morphological and physiological parameter were considered. The analysis of malondialdehyde (MDA) showed significant effects on broccoli and radish in all the MP treatments. The results revealed that high loads of MPs in the substrate affect growth parameters, lipid peroxidation rate estimated by MDA, and phytochemicals of broccoli and radish sprouts, with differences in response to MPs pollution and intensity between species.

[Colonic poliposis and acromegaly. Colonoscopy prevalence and detection]. / Pólipos colónicos y acromegalia. Prevalencia y detección por colonoscopia.

BACKGROUND: The prevalence of colorectal polyps in the general population is 10%. Hormonal alterations in acromegaly stimulates adenomatose polyps development making that increase it prevalence. Colonoscopy has elevated sensibility and specificity in detection of colorectal adenomas. OBJECTIVE: Identify colonic polyps in patients with acromegaly and establish the importance of colonoscopy as a detection method. MATERIAL AND METHODS: Retrospective, observational and descriptive study made in Colon and Rectum Surgery Department from March 2000 to March 2007 in patients with acromegaly and colonoscopy. Analyzed variables were: gender,age, endoscopy findings and histopathological results. Descriptive statistics were used to analysis of results. RESULTS: Thirty-two patients were included: 14 (44%) men, 18 (56%) women. The mean age was 48 (range 22 to 75 years old). In 9 (28%) patients were detected colorectal polyps, predominately in the sigmoid. Fifteen polyps lesion were found: 7 (46.6%) adenomas: 5 (33.3%) tubular and 2 (13.3) villous, 6 (40%) hyperplasic, 1 (6.6%) inflammatory and 1 (6.6%) carcinoma. Colonoscopy was complete in 30 (93.7%) patients. CONCLUSIONS: The prevalence of colonic polyps inpatients with acromegaly undergoing colonoscopy,was 28%, higher than expected in the general population. Colonoscopy constitutes an important diagnosis technique in early neoplasia detection.

[Non Hodgkin lymphoma of the sigmoid colon: case report]. / Linfoma no Hodgkin de sigmoides: reporte de un caso.

Non-Hodgkin lymphoma (NHL) occurs in extranodal location in approximately 20% of patients with limited stage, high-grade disease. Colon is infrequently involved as a primary location, accounting for 4% of all extranodal NHL and far less than 1% of all colonic malignancies. Colonic NHL differs significantly in terms of presentation, therapy and outcome relative to other more common gastrointestinal sites, like stomach or small bowel. The most common location is the cecum (60-74% of cases), while the sigmoid is involved in 2.5-14%. Largely related to the lack of specific signs and symptoms, patients frequently present advanced locoregional disease. Moreover, more than half of patients require an emergent surgery, usually due to pain, bleeding, or obstruction. Therapy usually involves resection of the affected colon and regional lymph nodes followed by adjuvant chemotherapy or/and radiotherapy. Utilizing this approach 5 years survival rates range between 27-55%. We present a 59 years old man with weight loss,abdominal pain, palpable mass and intestinal obstruction. A sigmoidectomy was realized with histopathologic report of NHL. Systemic adjuvant chemotherapy and abdominal radiation were administered. After a 6 month follow-up from initial procedure he is now asymptomatic with Karnofsky of 90. Therefore a surgeon should consider the possibility of NHL when evaluating such patients.

Acute and chronic responses associated with adrenomedullin administration in experimental colitis.

Adrenomedullin (AM) is a 52 amino acid peptide and member of the calcitonin gene-related peptide (CGRP) super family. Given that AM has emerged as a potential immuno-regulatory and anti-inflammatory agent in various experimental models, this study has deepened into its possible therapeutic effect in intestinal inflammation analyzing the responses in both acute and chronic (14 and 21 days) phases of TNBS-induced colitis in rats. In the acute model, AM treatment reduced the incidence of diarrhea and the severity of colonic damage, and improved the survival rate at the three doses assayed (50, 100, and 200ng/kg animal). AM administration was able to reduce the early production of TNF-alpha and collaborated to maintaining basal levels of IFN-gamma and IL-10. In the chronic studies the peptide attenuated the extent of the damage with lesser incidence of weight loss and diarrhea (50 and 100ng/kg animal). Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase (MPO) levels caused by TNBS, was reduced after chronic AM administration. The peptide played a role in the evolution of Th1/Th2 cytokines balance and chronic disease recuperation: levels of proinflammatory TNF-alpha and IFN-gamma decreased and anti-inflammatory IL-10 increased significantly. Cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) protein expression were not modified by AM administration, although a reduction of nitric oxide (NO) production could be detected in the chronic model. These results support a role of AM as an anti-inflammatory factor with beneficial effects in intestinal inflammatory colitis.

Update on biosimilars in inflammatory bowel disease: Position and recommendations in Mexico. / Actualización sobre los medicamentos biocomparables en la enfermedad inflamatoria intestinal: posición y recomendación en México.

The biotechnology-derived medicines known as biosimilars are defined as non-originator treatments that have demonstrated quality, efficacy, and safety comparable to the reference biologic drug. Clinical trials have shown that the infliximab biosimilar, CT-P13, and the candidates for the adalimumab biosimilars, ABP 501 and ZRC 3197, are not significantly different, with respect to efficacy and safety, from the originator drugs in patients with other autoimmune diseases. However, controversy has arisen over the use of biosimilars in inflammatory bowel disease, due to the incipient evidence not only in patients with no previous biotechnology treatment, but also in patients in remission, that could be switched to a biosimilar for non-medical reasons. The present review is the first critical analysis by different specialists in the area of gastroenterology on the use of biosimilars in inflammatory bowel disease, the evidence on interchangeability, the extrapolation of indications, efficacy, safety, immunogenicity, and the clinical impact of the Mexican health regulations. The aim of our review was to make the positioning and recommendations of these new therapeutic options known, given that they have a potential cost-benefit for both patients and healthcare institutions.

Changes in extracellular amino acid concentrations in the rat hippocampus after in vivo actin depolymerization with latrunculin A.

The effect of latrunculin A microperfusion on hippocampal extracellular concentrations of glutamate, aspartate, glycine and GABA, as measured by in vivo microdialysis, was investigated. Latrunculin A (4 microg/ml) was perfused for three consecutive days (8h a day) to promote in vivo F-actin depolymerization. Intrahippocampal latrunculin A microdialysis induced seizures during the second and third day of perfusion, and the animals started showing spontaneous seizures 1 month after lartrunculin A administration. Hippocampal glutamate levels were significantly increased during the first day of latrunculin A microperfusion without significant changes during the second and third day of perfusion. Aspartate levels were significantly increased during the first and second days of treatment. The rise on glutamate and asparate levels was partially reversed by perfusion of NMDA antagonist MK-801. Glycine concentrations were significantly increased during the 3 days of latrunculin A microdialyis, but no significant effect was observed on baseline GABA levels. One month after latrunculin A microperfusion, no significant differences in glutamate and aspartate extracellular concentrations were detected as compared to controls, however, significant increases in glycine and GABA extracellular concentrations were observed. The immediate increases in glutamate, aspartate and glycine levels indicate a modulatory effect of the F-actin cytoskeleton on extracellular concentrations of glutamate, aspartate and glycine. The chronic elevations in GABA and glycine levels are more likely to be related with long-term epileptogenesis processes. Our results suggest that the in vivo biochemical study of actin-dependent processes seems to be a promising approach to the neuropathology and neuropharmacology of epileptic seizures.

6-Phosphofructo-2-kinase and control of cryoprotectant synthesis in freeze tolerant frogs.

A critical part of natural freeze tolerance is the production of low molecular weight cryoprotectants; in freeze tolerant frogs this involves a freezing-induced activation of liver glycogenolysis that leads to the accumulation of glucose as the cryoprotectant, in amounts up to 300 mM, in all organs. The present study shows that the synthesis and maintenance of high organ glucose pools is facilitated by changes in the levels of fructose-2,6-bisphosphate (F2,6P2) and an inhibition of liver 6-phosphofructo-2-kinase (PFK-2) activity that blocks the catabolism of glucose by glycolysis. Freezing exposure (24 h at -2.5 degrees C) resulted in a sharp drop in F2,6P2 levels in four organs, to 23-75% of control values, but F2,6P2 rebounded when frogs were thawed. Freezing also stimulated changes in the properties of liver PFK-2 including a decrease in maximal velocity, a basic shift in pH optimum, a 10-fold increase in Km for fructose-6-phosphate, and increased I50 values for enzyme inhibitors. I50 values for glycerol-3-phosphate and phosphoenolpyruvate were 60- and 2.4-fold higher, respectively, for liver PFK-2 from frozen frogs compared with controls. Changes in liver PFK-2 properties are consistent with a freezing-induced phosphorylation of the enzyme to produce a less active enzyme form, resulting in reduced organ F2,6P2 levels and a decrease in 6-phosphofructo-1-kinase activity.

Administration of L-arginine reduces the delay of the healing process caused by ibuprofen. Implication of COX and growth factors expression.

The objective of the present study has been to advance knowledge of the gastric role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen have been administrated in an experimental acetic acid chronic ulcer, analysing characteristic parameters of an active curative process, such as PGE2 production, COX expression, and also angiogenesis, proliferation/apoptosis and growth factors expression. Our results reveal that L-Arg is favourable in the healing process improving the curative course. Ibuprofen caused a delay in ulcer healing, more evident 14 days after ulcer induction; COX-2 expression was increased at the 7th day although no signal of protein could be detected after 14 days; PGE2 production was inhibited in intact and ulcerated areas at both times assayed. In contrast, treatment with L-Arg reduced the delay of the lesion, the increment in COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels similar to the control group after 14 days. Additionally, the histological study showed that the healing effects of L-Arg might be associated with an increased angiogenesis and FGF-2 expression. These actions could be considered key factors in the healing response associated with L-Arg administration. However, the proliferation study assayed with the PCNA-immunostaining method did not reveal significant differences, as the same as the apoptosis analysis. In conclusion, the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen administration alone because it not only attenuates but also improves the evolution of chronic lesions through mechanisms that implicate endogenous PG and FGF-2-associated pathways, which allow an increase of angiogenesis process.

Phosphorylation-activated 6-phosphofructo-2-kinase from mantle tissue of marine mussels.

PKF-2 from mussel mantle was phosphorylated by cAMP-dependent protein kinase. The phosphorylation does not change the enzyme activity at neutral pH values, but at acid pH the activity of the phosphorylated form is higher than the native PFK-2. With respect to the native enzyme, the activation consisted of a reduction in the Km for Fru-6-P and a decrease in the inhibitory effect of PEP. These results are in keeping with the stabilized concentration of Fru-2,6-P2 found in the mussel mantle during the physiological hypoxia caused by the closure of the valves.

Effect of ionotropic glutamate receptors antagonists on the modifications in extracellular glutamate and aspartate levels during picrotoxin seizures: a microdialysis study in freely moving rats.

Our previous studies have shown a local decrease in glutamate and aspartate levels during seizures, induced by picrotoxin microdialysis in the hippocampus of chronic freely moving rats. In this paper, we study the effect of continuous hippocampal microperfusion of the NMDA, AMPA and kainate glutamate receptor inhibitors 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801); 6,7-dinitroquinoxaline-2,3-dione (DNQX), and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466). We also examine the action of L(-)-threo-3-hydroxyaspartic acid (THA), a glutamate and aspartate reuptake blocker, on the modification of extracellular glutamate and aspartate levels induced by picrotoxin, using the microdialysis method in freely moving rats. We found that changes in extracellular hippocampal concentrations in both amino acids are prevented by NMDA, AMPA and kainate receptor inhibitors. Seizures elicited under DNQX also induce a transient increase in aspartate extracellular levels coincident with seizure time. L(-)-threo-3-hydroxyaspartic acid increased the basal extracellular concentrations of both amino acids, but did not prevent the seizure-related decrease. Our results suggest that glutamate, the major neurotransmitter at the synaptic level, may also play an important role in non-synaptic transmission during seizures.

Extracellular amino acids in the rat hippocampus during picrotoxin threshold seizures in chronic microdialysis experiments.

The relation between changes in the concentrations of some of the neuroactive extracellular amino acids (glutamate, aspartate, gamma-aminobutyric acid, glycine and taurine) and epileptic seizures has been tested in a new experimental model of seizures induced by picrotoxin microdialysis in chronic freely moving rats. During ictal discharges (paroxysmal electroencephalographic discharges associated with behavioral seizures), a significant decrease in the levels of extracellular aspartate and glutamate was observed. However, no changes were found during the interictal discharges (paroxysmal electroencephalographic discharges, without concomitant seizures). Our results suggest that modifications in extracellular aspartate and glutamate may be related to neuronal synchronization rather than to paroxysmal activity, supporting the neurophysiological differences between non-ictal and ictal paroxysmal activity.

Role of different inflammatory and tumor biomarkers in the development of ulcerative colitis-associated carcinogenesis.

BACKGROUND: Colorectal cancer (CRC) is the most severe complication in inflammatory bowel disease (IBD). In the present study we investigated different mechanistic links between chronic colonic inflammation and its progression to adenocarcinoma. Along these lines, given that adrenomedullin (AM) has been implicated in carcinogenesis, we also analyzed changes in its colonic expression. METHODS: Mice were exposed to 5, 10, and 15 cycles of dextran sulfate sodium (DSS); each cycle consisted of 0.7% DSS for 1 week followed by distilled water for 10 days. After each period, macroscopic and histological studies, as well as characterization of inflammatory and tumor biomarkers, were carried out. RESULTS: The disease activity index (DAI) showed that the disease was present from the third cycle and it gradually increased during the course of DSS treatment. Macroscopic tumors were only seen after 15 cycles, and microscopic study showed that inflammation, dysplasia, and adenocarcinomas correlated with DSS cycles. ß-Catenin and proliferating cell nuclear antigen expressions progressively increased in animals treated with the different cycles of DSS. TNF-α and IFN-γ showed the highest production at the tenth cycle. COX-2, mPGES-1, and iNOS levels were also appreciably higher at the fifth and tenth cycles. Moreover, we observed a progressive enhancement in AM expression and changes in its intracellular location during the progression of the disease. CONCLUSIONS: Our results show an early induction of proinflammatory factors, which may contribute to the development of colon cancer, as well as demonstrate, for the first time, the expression of AM in IBD-derived CRC.

Analysis of neuroactive amino acids from microdialysate samples by fluorescence detection using a modification of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate method.

A sensitive and rapid reversed-phase high-performance liquid chromatographic method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and fluorescence detection is reported. By directly derivatizing microdialysate samples with AQC, an automatic and rapid simultaneous measurement of aspartate, serine, glutamate, glycine and histidine was developed. Excellent linearity (r2 > or = 0.998) was achieved for the standard mixture used for the validation experiments. Within-day and between-day precision was less than 6.2%, and the accuracy ranged from 95 to 105.2% in standards. This method is suitable for single run analysis of a high number of small volume microdialysate samples from rat hippocampus. Amino acids from microdialysate samples were quantified with RSD for reproducibility below 2%, and at approximately 0.1% for retention time.

Regulation of fructose-2,6-bisphosphate content in mantle tissue of the sea mussel Mytilus galloprovincialis Lmk. Regulation of fructose-2,6-bisphosphatase activity.

Fructose-2,6-bisphosphatase (FBPase-2) from the mantle tissue of the mussel Mytilus galloprovincialis shows a hyperbolic kinetic with a Km value (0.40 mM) for its substrate, that suggest that the "in vivo" Fru-2,6-P2 concentration is not a limiting factor for activity. The enzyme possesses an optimum pH for activity between 6 and 7 units, similar to the reached in mussel mantle during physiological hypoxia. The modulation of activity by the pH, and in addition, the positive effect of ATP are in keeping with the little decrease in concentration of the Fru-2,6-P2 that occurs during the first hour of hypoxia due to the valve closure.

Phosphofructokinase from mantle tissue of Mytilus galloprovincialis. Purification and effects of phosphorylation on the enzymatic activity.

Phosphofructokinase purified from mantle tissue of the sea mussel Mytilus galloprovincialis, was phosphorylated "in vitro" by the catalytic subunit of cyclic AMP-dependent protein kinase. The incorporation of phosphate gave rise to an activation of the enzyme by increasing its affinity for fructose-6-phosphate, by decreasing its sensitivity to the inhibition by ATP and by enhancing the effect of allosteric activators (5'-AMP and fructose-2,6-bisphosphate). In addition, the effects of phosphorylation on the catalytic activity are pH-dependent.

Reclasificación de los linfomas, diagnosticados en un período de 12 años en el Hospital Militar, utilizando la clasificación de la OMS 2001 / Reclassification of lymphomas diagnosed in a 12 year period at the Hospital Militar, using the 2001 WHO Classification

La clasificación de la OMS de los Tumores hematopoyeticos y linfoides culminada en 2001, basada en la Clasificación REAL es la primera obtenida por un consenso internacional de expertos de todo el mundo, en un área de alta complejidad diagnóstica y con una nomenclatura muy variada. En Uruguay no hay cifras de frecuencia de los subtipos de linfomas dentro de los grandes grupos LNH y LH. Con el objetivo de conocer esta distribución, en la población de nuestro hospital, realizamos un estudio retrospectivo, homogeneizando el diagnostico usando dicha clasicación. Material y Método: Del archivo del Servicio de Anatomía del HC FFAA se recuperaron todos los casos diagnosticados como linfomas en un período de 12 años (1988 al 2000), en biopsias o piezas de resección no se consideraron las citologías. Sin conocimiento del diagnóstico original, se revisaron todas las láminas disponibles. Utilizando los criterios de la clasificación OMS, se realizó el planteo diagnóstico, así como la selección de anticuerpos primarios, del siguiente grupo: CD1ª, CD3, CD4, CD5, CD8, CD10, CD15, CD20, CD23, CD30, CD34, CD38, CD43, CD45, CD45RO, CD57, CD68, Cd79ª, DBA44, MPO, ë, ê, Ki67, bcl-2, bcl-1, ALK, lisozima, EBV y tdt, para técnicas de Inmunohistoquímica, con controles negativos y positivos apropiados. Se llegó a un diagnóstico final. Se estableció la frecuencia de cada tipo de linfoma, y se comparó con el diagnóstico original. Resultados. De 140 pacientes diagnosticados de linfoma en ese período, se reclasificaron 132 pacientes, de los que había material disponible. El 64,6 por ciento fueron hombres, la edad media fue de 52.5 años. Se diagnosticó Linfoma de Hodgkin (LH) en 23 pacientes (18.1 por ciento), el 71.4 por ciento de los cuales fue subtipo Esclerosis Nodular. Cientocuatro casos (79 por ciento), fueron Linfomas no Hodgkin (LNH). El 96,2 por ciento fueron LNH de línea B, de estos los grupos de mayor frecuencia fueron: el Linfoma Difuso de Células Grandes (34,6 por ciento) y...

Amiloidosis sistematica / Sistematic amyloidosis

La infiltracion por amiloide determina diversas manifestaciones clinicas, segun su entidad. El caso que presentamos se manifesto clinicamente como una miocardiopatia restrictiva. Exponemos los planteos y estudios realizados para confirmar el diagnostico