Development of Anxiolytic and Depression-like Behavior in Mice Infected with Mycobacterium lepraemurium.

Murine leprosy is a systemic infectious disease of mice caused by Mycobacterium lepraemurium (MLM) in which the central nervous system (CNS) is not infected; nevertheless, diseased animals show measurable cognitive alterations. For this reason, in this study, we explored the neurobehavioral changes in mice chronically infected with MLM. BALB/c mice were infected with MLM, and 120 days later, the alterations in mice were evaluated based on immunologic, histologic, endocrine, neurochemical, and behavioral traits. We found increases in the levels of IL-4 and IL-10 associated with high bacillary loads. We also found increase in the serum levels of corticosterone, epinephrine, and norepinephrine in the adrenal gland, suggesting neuroendocrine deregulation. Mice exhibited depression-like behavior in the tail suspension and forced swimming tests and anxiolytic behavior in the open field and elevated plus maze tests. The neurobehavioral alterations of mice were correlated with the histologic damage in the prefrontal cortex, ventral hippocampus, and amygdala, as well as with a blood-brain barrier disruption in the hippocampus. These results reveal an interrelated response of the neuroimmune--endocrinological axis in unresolved chronic infections that result in neurocognitive deterioration.

Lupeol acetate isolated from Chrysophyllum cainito L. fruit as a template for the synthesis of N-alkyl-arylsulfonamide derivatives and their synergistic effects with metronidazole against Trichomonas vaginalis.

Pentacyclic triterpenes are found in a great variety of natural products and constitute an organic template for the development of new derivative compounds with therapeutic applications. In the present work, lupeol acetate isolated from Chrysophyllum cainito L. fruit was used as a template for the synthesis of novel N-alkyl-arylsulfonamide derivatives, and their synergistic effects with metronidazole against strains of Trichomonas vaginalis were tested. A library of 18 derivatives was synthesized. Ten compounds exhibited an IC50 < 100 µM against a metronidazole-sensitive strain of T. vaginalis. Only seven of these compounds (12, 15, 18-22) also showed activity against metronidazole-resistant strains. The compounds 20 (N-cyclohexyl-p-chlorobenzenesulfonamidolupeol acetate) and 22 (N-cyclohexyl-p-nitrobenzenesulfonamidolupeol acetate) exhibited a similar IC50 against both susceptible and resistant T. vaginalis strains and enhanced the efficacy of metronidazole in a partial and total synergistic way, respectively. These data provided evidence of the trichomonicidal effect of N-alkyl-arylsulfonamide derivatives of lupeol acetate, representing highly promising novel antiparasitic agents.

Suturas transconjuntivales del tapete escleral en maculopatía hipotónica tardía tras esclerectomía profunda no perforante / Transconjunctival suturing of the scleral flap in late hypotony maculopathy after non-penetrating deep sclerectomy

CASO CLÍNICO: Un hombre de 63 años desarrolla una maculopatía hipotónica tardía tras una esclerectomía profunda no perforante. La sutura transconjuntival del tapete escleral permite resolver la hipotonía y la normalización de la agudeza visual. DISCUSIÓN: La maculopatía hipotónica puede presentarse de forma diferida tras una cirugía de glaucoma. Las suturas transconjuntivales del tapete escleral son una alternativa en el tratamiento de la hipotonía cuando las medidas conservadoras han fracasado

CLINICAL CASE: A 63-year-old man presents with late hypotony maculopathy after non-penetrating deep sclerectomy. Hypotonia and visual acuity are improved after transconjunctival suturing of the scleral flap. DISCUSSION: Hypotony maculopathy may occur as a late complication after glaucoma surgery. Transconjunctival suturing of the scleral flap can be useful when conservative measures have failed

Transconjunctival suturing of the scleral flap in late hypotony maculopathy after non-penetrating deep sclerectomy. / Suturas transconjuntivales del tapete escleral en maculopatía hipotónica tardía tras esclerectomía profunda no perforante.

CLINICAL CASE: A 63-year-old man presents with late hypotony maculopathy after non-penetrating deep sclerectomy. Hypotonia and visual acuity are improved after transconjunctival suturing of the scleral flap. DISCUSSION: Hypotony maculopathy may occur as a late complication after glaucoma surgery. Transconjunctival suturing of the scleral flap can be useful when conservative measures have failed.

Genome-wide identification, in silico characterization and expression analysis of ZIP-like genes from Trichomonas vaginalis in response to Zinc and Iron.

Trace elements such as Zinc and Iron are essential components of metalloproteins and serve as cofactors or structural elements for enzymes involved in several important biological processes in almost all organisms. Because either excess or insufficient levels of Zn and Fe can be harmful for the cells, the homeostatic levels of these trace minerals must be tightly regulated. The Zinc regulated transporter, Iron regulated transporter-like Proteins (ZIP) comprise a diverse family, with several paralogues in diverse organisms and are considered essential for the Zn and Fe uptake and homeostasis. Zn and Fe has been shown to regulate expression of proteins involved in metabolism and pathogenicity mechanisms in the protozoan pathogen Trichomonas vaginalis, in contrast high concentrations of these elements were also found to be toxic for T. vaginalis trophozoites. Nevertheless, Zn and Fe uptake and homeostasis mechanisms is not yet clear in this parasite. We performed a genome-wide analysis and localized the 8 members of the ZIP gene family in T. vaginalis (TvZIP1-8). The bioinformatic programs predicted that the TvZIP proteins are highly conserved and show similar properties to the reported in other ZIP orthologues. The expression patterns of TvZIP1, 3, 5 and 7 were diminished in presence of Zinc, while the rest of the TvZIP genes showed an unchanged profile in this condition. In addition, TvZIP2 and TvZIP4 showed a differential expression pattern in trophozoites growth under different Iron conditions. These results suggest that TvZIP genes encode membrane transporters that may be responsible for the Zn and Fe acquisition in T. vaginalis.

Tratamiento con plasma autólogo rico en plaquetas en una paciente estéril con un endometrio refractario / Treatment with rich platelets autologous plasma in a sterile patient with suspected refractory endometrium

Paciente de 36 años con esterilidad primaria de 2 años. Tras estudio completo se decide donación de ovocitos. En los controles se observa un grosor endometrial adelgazado. Con el diagnóstico de endometrio refractario, se realiza un tratamiento con estrógenos a altas dosis, vitamina E y pentoxifilina durante 3 meses. Como el grosor endometrial no aumenta, asociamos AAS. Finalmente se administra intraútero plasma autólogo rico en plaquetas. A las 96 horas se observa un endometrio de 7,3 mm, transfiriéndose dos embriones vitrificados, resultando en un aborto bioquímico. Discusión: El tratamiento médico del endometrio refractario constituye un reto. Existen numerosas opciones terapéuticas, hormonales y no hormonales. Sin embargo, la mayoría de estas opciones están escasamente evaluadas por lo que se requieren de estudios mejor diseñados y con mayor tamaño muestral (AU)

36 years old patient with primary sterility of 2 years. An oocyte donation was decided after the study. An endometrial thickness slimmed was observed in different visits. With the diagnosis of refractory endometrium, a treatment was performed with high-dose estrogen, vitamin E and pentoxifylline for 3 months. As the endometrial thickness did not increase, we associated AAS. Finally intrauterine platelet-rich autologous plasma was administered. At 96 hours 7.3 mm of endometrium was observed, two vitrified embryos transferred, resulting in a biochemical abortion. Discussion: The medical treatment of refractory endometrium is a challenge. There are many therapies, hormonal and nonhormonal options. However, most of these options are poorly evaluated so they require better designed studies and larger sample size (AU)

The midpoint between ventilatory thresholds approaches maximal lactate steady state intensity in amateur cyclists.

The aim was to determine whether the midpoint between ventilatory thresholds (MPVT) corresponds to maximal lactate steady state (MLSS). Twelve amateur cyclists (21.0 ± 2.6 years old; 72.2 ± 9.0 kg; 179.8 ± 7.5 cm) performed an incremental test (25 W·min-1) until exhaustion and several constant load tests of 30 minutes to determine MLSS, on different occasions. Using MLSS determination as the reference method, the agreement with five other parameters (MPVT; first and second ventilatory thresholds: VT1 and VT2; respiratory exchange ratio equal to 1: RER = 1.00; and Maximum) was analysed by the Bland-Altman method. The difference between workload at MLSS and VT1, VT2, RER=1.00 and Maximum was 31.1 ± 20.0, -86.0 ± 18.3, -63.6 ± 26.3 and -192.3 ± 48.6 W, respectively. MLSS was underestimated from VT1 and overestimated from VT2, RER = 1.00 and Maximum. The smallest difference (-27.5 ± 15.1 W) between workload at MLSS and MPVT was in better agreement than other analysed parameters of intensity in cycling. The main finding is that MPVT approached the workload at MLSS in amateur cyclists, and can be used to estimate maximal steady state.

Assessing the non-motor symptoms of Parkinson's disease: MDS-UPDRS and NMS Scale.

BACKGROUND AND PURPOSE: Although Parkinson's disease (PD) is characterized by typical motor manifestations, non-motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part I - Non-Motor Aspects of Experiences of Daily Living (nM-EDL) compared with the Non-Motor Symptoms Scale (NMSS). METHODS: To this purpose, 434 consecutive patients with PD were included in an international, observational, cross-sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin's Concordance Correlation Coefficient (LCCC) and Bland-Altman plot. RESULTS: As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (r(S) > 0.60). The total score correlation of the MDS-UPDRS Part I with the NMSS was high (r(S) = 0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60-64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland-Altman plot; LCCC < 0.60 for severe patients). CONCLUSIONS: (i) MDS-UPDRS Part I (nM-EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant.

Relationship between the MDS-UPDRS domains and the health-related quality of life of Parkinson's disease patients.

BACKGROUND AND PURPOSE: The Movement Disorder Society sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument for assessing Parkinson's disease (PD). The present study was aimed at determining the relationships between MDS-UPDRS components and health-related quality of life (HRQoL) evaluations in PD patients. METHODS: An international, multicenter, cross-sectional study was carried out of 435 PD patients assessed with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ-5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation coefficients, exploratory factor analysis and multiple linear regression models (dependent variables EQ-5D and PDQ-8) were performed. RESULTS: The participants' age was 66.71 ± 10.32 years (51.5% men). PD duration was 8.52 ± 6.14, and median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS-UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from 0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS-UPDRS domains as independent variables, the main determinant for both the EQ-5D index and the PDQ-8 was Part II followed by Part I. After factorial grouping of the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes. CONCLUSIONS: The MDS-UPDRS component most tightly related with the HRQoL measures was a combination of motor and non-motor experiences of daily living.

Systematic pancreatic stenting after endoscopic snare papillectomy may reduce the risk of postinterventional pancreatitis.

BACKGROUND: Pancreatitis is the most feared complication of endoscopic papillectomy (EP). Prevention by pancreatic duct stenting following EP has been advocated but not proven by a randomized trial. The purpose of the present retrospective review is to compare a period of systematic stenting with the period before in which stents were placed selectively. METHODS: A total of 107 patients undergoing EP from February 1999 to December 2009 were retrospectively reviewed. After an initial period with selective stenting (dilated duct, previous pancreatitis) between 1999 and 2002 (n = 24, group 1), stents were placed routinely after EP unless pancreas divisum was diagnosed (2002-2009; n = 83, group 2) to reduce postpapillectomy acute pancreatitis (PAP). PAP rates defined by Consensus Criteria were compared in the two periods. RESULTS: Five patients in group 1 were selected to receive a pancreatic stent (21%); in group 2 stenting was successful in 75 of 78 patients (success rate 96%) without pancreas divisum (n = 5). Overall, PAP occurred in 11% of patients. PAP rate was significantly reduced after introduction of systematic pancreatic stenting (5 vs 25%; p = 0.01) and occurred less often in stented than in nonstented patients: (5% (4/80) vs 27% (6/22), p = 0.0019). PAP also occurred in one of five patients with pancreas divisum. Selective stenting of patients also was an independent risk factor for PAP (OR 13, p = 0.001) in a multivariate analysis. CONCLUSIONS: Attempts at systematic stenting after EP pancreatic stenting appears to prevent PAP. Results should be corroborated by a randomized trial.

Efficacy of moxidectin long-acting injectable formulation (1 mg/kg bodyweight) against first instar larvae of Oestrus ovis in naturally infected sheep.

The objective of the current study was to evaluate the efficacy of a single treatment with a long-acting injectable formulation of moxidectin (MOX) at 1.0 mg/kg bodyweight (b.w.) against natural infection by nasal bots (Oestrus ovis) in sheep with special attention to first instar larvae (L1). Firstly, a local farm with clinical history of oestrosis was chosen to conduct the assay. A total of 49 sheep were pre-selected at the end of the summer according to the presence of evident clinical signs of infection and confirmed later by means of an indirect ELISA against excretory-secretory products from L1 to detect IgG antibodies. After that, 24 sheep were chosen to carry out the study on the basis of positive serology and age since the oldest ones were selected. The day 0 of the assay, the treatment group was administered with the MOX formulation by subcutaneous injection at the base of the left ear and the control group was administered with a saline solution in the same way. All sheep were slaughtered on day 28 post-treatment (pt). At the necropsy, the head of all sheep were cut off and split into two sagital sections and all larvae from nasal passages, septum, middle meatus, conchae and sinuses were recovered. After the necropsy, a significant number of L1 was only found in the control group and therefore the efficacy of the MOX formulation was only calculated against this stage. As a result, the formulation was 90.2% effective against L1 for sheep slaughtered at day 28 pt.

The effects of environmental factors on the virulence of Trichomonas vaginalis.

This review focused on potential regulatory mechanisms of Trichomonas vaginalis virulence properties, cytoadherence, cytotoxicity, phagocytosis, hemolysis, induction of apoptosis, and immune evasion in response to environmental factors of the human urogenital tract, iron, zinc, and polyamines. Understanding the multifactorial nature of trichomonal pathogenesis and its regulation may help to unravel the survival strategies of trichomonads and to implement prevention policies, opportune diagnosis, and alternative treatments for control of trichomoniasis.

Effect of infection with Teladorsagia circumcincta on milk production and composition in Assaf dairy sheep.

Infection by gastrointestinal nematodes (GIN) in grazing sheep can negatively influence the growth of lambs and milk yield. In the current study we evaluated the effect of high and low levels of infection with Teladorsagia circumcincta on production parameters of lactating ewes. Two groups of ewes were infected with 50,000 T. circumcincta third stage larvae (L3) 30 days before lambing. To obtain a high level of infection, Group HI was challenged with 30,000 L3 30 days post-partum (pp) and again 90 days pp with the same dose. The low infection group (LI) was treated with an intraruminal controlled-release albendazole bolus one-month pp. We determined the effect of the differing parasite loads on milk yield, milk composition, weight gain, and body condition (BC). Throughout the trial the milk yield was higher in the LI group and, consequently, at the end of the lactation, this group produced 11.1% more milk than the HI group. In the final third of lactation there was an overall increase in milk fat, protein, and lactose although the factor most affected by infection level was the protein percentage, with an increment of 11.9% in the HI group. The somatic cell counts remained low during the experiment indicating the absence of udder infection. Regarding weight and BC, significant differences were found only in BC although LI ewes weighed 2% more than the HI group. In conclusion, a low level of GIN infection in sheep leads to a better BC and a higher milk production with high protein percentage.

Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study.

BACKGROUND AND STUDY AIMS: Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. PATIENTS AND METHODS: 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. RESULTS: The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CONCLUSIONS: CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

Identification of two novel Trichomonas vaginalis eif-5a genes.

The eukaryotic translation initiation factor 5A (eIF-5A) is highly conserved and is the only protein that is known to contain the unique and essential amino acid residue hypusine. Synthesis of hypusine is essential for the function of eIF5A in eukaryotic cell proliferation and survival. In this study, we identified two novel eukaryotic translation initiation factor 5A (eIF-5A) genes in Trichomonas vaginalis. The tveif-5a1 and tveif-5a2 putative genes were localized in different contigs, both containing ORFs encoding proteins of 168 amino acids that share high sequence identity with eIF-5A sequences from other eukaryotic organisms. A phylogenetic tree constructed with TveIF-5A1 and TveIF-5A2 from T. vaginalis and 13 other eIF-5A sequences of eukaryotic and archaebacterial origin revealed that both trichomonal TveIF-5As show the highest degree of similarity to bacteria. Using an anti-TveIF-5A antibody, we detected two protein bands and spots of 19 and 20kDa with isoelectric points (pI) of 5.2 and 5.5, respectively, by one and two-dimensional Western blot assays. In addition, we used reverse transcription polymerase chain reaction (RT-PCR) to demonstrate that both of these tveif-5a genes are expressed in T. vaginalis. Immunofluorescence assays showed that the TveIF-5A protein was dispersed throughout the parasite cytoplasm. In conclusion, T. vaginalis has two eif-5a genes, and both genes are expressed as highly conserved proteins of 19kDa, which are localized in the cytoplasm of this parasite.

Carcinoma epidermoide pancreático que inicia como conglomerado adenopático supraclavicular izquierdo / Virchow's node as the form of onset of squamous cell carcinoma of the pancreas

El carcinoma escamoso del páncreas es un tumor extraordinariamente infrecuente.Caso clínicoPaciente varón de 63 años que acude a la consulta del gastroenterólogo por un cuadro constitucional acompañado del hallazgo de una masa pétrea supraclavicular izquierda. El escáner demostró la existencia de una neoplasia de cuerpo pancreático que interesaba tronco celíaco. La histología de la adenopatía supraclavicular y del páncreas fue de carcinoma epidermoide queratinizante.ConclusionesEn el artículo se realiza una revisión sobre la incidencia, las características de este tumor tan infrecuente y las nuevas indicaciones de tratamiento (AU)

Squamous carcinoma of the pancreas is a highly uncommon tumor.Case reportA 63-year-old man was referred to the gastroenterology department because of hyporexia, cachexia and weight loss. A left supraclavicular node was noted. The computed tomography scan showed a tumor in the pancreatic body involving the celiac axis. Histological examination of the supraclavicular node and pancreatic mass revealed squamous cell carcinoma.ConclusionsThe incidence and characteristics of this highly infrequent tumor, as well as new treatment indications, are reviewed (AU)

[Congenital retinal macrovessels: a discovery by chance]. / Macrovasos congénitos retinianos: un hallazgo casual.

CLINICAL CASE: Congenital retinal macrovessels, where an aberrant retinal vessel, usually a venule, is present in the posterior pole and may cross the avascular foveal region, are seen rarely. DISCUSSION: Most of these cases are unilateral and stable with excellent visual prognosis and are detected on routine examination. Foveal cysts, hemorrhages and displaced foveola may also be seen. These entities must be distinguished from racemose angiomas, capillary hemangiomas of the retina and even when associated with neurological symptoms, should be considered as part of the Wyburn-Masson syndrome.

Macrovasos congénitos retinianos: un hallazgo casual / Congenital retinal macrovessels: a discovery by chance

Caso clínico: Los macrovasos congénitos retinianos son raros, son ramas aberrantes, vénulas en su mayoría, localizadas en el polo posterior que de forma típica cruzan la zona avascular foveal. Discusión: En la mayoría de los casos son lesiones unilaterales y estables, sin repercusión visual por lo que su diagnóstico es casual. En ocasiones se asocian a localizaciones atípicas de la fóvea, quistes foveales e incluso hemorragias. Por lo general debe realizarse un diagnóstico diferencial con otras entidades vasculares retinianas como el hemangioma capilar, angioma racemoso e incluso si se acompaña de síntomas neurológicos descartar el síndrome de Wyburn-Masson

Clinical case: Congenital retinal macrovessels, where an aberrant retinal vessel, usually a venule, is present in the posterior pole and may cross the avascular foveal region, are seen rarely. Discussion: Most of these cases are unilateral and stable with excellent visual prognosis and are detected on routine examination. Foveal cysts, hemorrhages and displaced foveola may also be seen. These entities must be distinguished from racemose angiomas, capillary hemangiomas of the retina and even when associated with neurological symptoms, should be considered as part of the Wyburn-Masson syndrome (Arch Soc Esp Oftalmol 2008; 83: 273-276)

[Subluxation of the lens: etiology and results of treatment]. / Luxación del cristalino: etiología y resultados.

OBJECTIVE: To evaluate the indications for surgery, visual results and postoperative complications of pars plana vitrectomy (PPV), in patients with retained lens fragments in the vitreous cavity. METHODS: 86 Eyes from 83 patients who underwent PPV for retained lens fragments at the Hospital Central de Asturias between April 1997 and December 2004 were reviewed. The average age was 68 years (12-90 years). Patients with proliferative diabetic retinopathy, maculopathy and inadequate follow-up examination (less than 3 months) were excluded. The results have been analysed according to the etiology of the subluxation. RESULTS: The average follow-up time was 32.5 months (6-73 months). The most common cause for subluxation of the lenses was cataract surgery and trauma. In 48.15% an intraocular lens was implanted. The average preoperative visual acuity (VA) was 0.06 (logMAR 1.0) and postoperative VA 0.4 (logMAR 0.4). 61.7% of the eyes had increased preoperative intraocular pressure, whereas only 32 eyes (39.5%) had this postoperatively. The most common intra-operative complications were retinal tears (4) and retinal detachment (1). The most common postoperative complications were retinal detachment (3) and bullous keratopathy (2). CONCLUSION: PPV is a relatively simple and low risk technique, which allows good visual restoration and minimizes complications of the subluxated lenses.