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Background The treatment of spinal intramedullary arteriovenous malformations (AVMs) presents the risk of spinal cord ischemia because of the vascular nidus and their feeding arteries involving and supplying the spinal cord parenchyma. The multimodal approach includes endovascular embolization and microsurgical excision, both benefiting from intraoperative neurophysiologic monitoring. We present a case study of a patient who underwent several staged embolizations and open surgery for microsurgical excision. Patient A 32-year-old man who presented with a recurrent glomus-type intramedullary AVM in the cervical spinal cord, located at the C5–C6 segment, with progressive neurologic deterioration. Methods Somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs) were performed during three embolizations, a provocative test, and surgery, in addition to D-wave during microsurgical excision. Results Abolished hand MEP and drop in SEP during a provocative test guided the surgeon to embolize from a safer vessel with no acute neurologic deficit after three embolizations. Before surgery, an angiography showed the left posterior spinal artery supplying the AVM. After resecting the vascular nidus from the spinal parenchyma, left-hand MEP decreased in amplitude and later abolished, and SEP decreased. Interestingly, no D-wave or distal MEPs were affected. Weakness in the left hand immediately and 2 weeks postoperatively advocates for metameric spinal cord ischemia with preservation of long spinal cord pathways. Conclusions Intraoperative neurophysiologic monitoring correlates with neurologic outcome after endovascular and surgical treatment of a cervical AVM. Intraoperative monitoring provides continuous functional information of long and metameric spinal cord pathways, which is critical when deciding on the vessel to be embolized and during microsurgical excision where the surgeon is in less control of the AVM hemodynamic flow.

The World Health Organization (WHO) declared coronavirus disease-2019 (COVID-19) a global pandemic on 11 March 2020. In Ecuador, the first case of COVID-19 was recorded on 29 February 2020. Despite efforts to control its spread, SARS-CoV-2 overran the Ecuadorian public health system, which became one of the most affected in Latin America on 24 April 2020. The Hospital General del Sur de Quito (HGSQ) had to transition from a general to a specific COVID-19 health center in a short period of time to fulfill the health demand from patients with respiratory afflictions. Here, we summarized the implementations applied in the HGSQ to become a COVID-19 exclusive hospital, including the rearrangement of hospital rooms and a triage strategy based on a severity score calculated through an artificial intelligence (AI)-assisted chest computed tomography (CT). Moreover, we present clinical, epidemiological, and laboratory data from 75 laboratory tested COVID-19 patients, which represent the first outbreak of Quito city. The majority of patients were male with a median age of 50 years. We found differences in laboratory parameters between intensive care unit (ICU) and non-ICU cases considering C-reactive protein, lactate dehydrogenase, and lymphocytes. Sensitivity and specificity of the AI-assisted chest CT were 21.4% and 66.7%, respectively, when considering a score >70%; regardless, this system became a cornerstone of hospital triage due to the lack of RT-PCR testing and timely results. If health workers act as vectors of SARS-CoV-2 at their domiciles, they can seed outbreaks that might put 1,879,047 people at risk of infection within 15 km around the hospital. Despite our limited sample size, the information presented can be used as a local example that might aid future responses in low and middle-income countries facing respiratory transmitted epidemics.

BACKGROUND: Knowing patients' ulcerative colitis history is essential to selecting the appropriate therapy according to risk stratification. OBJECTIVE: To evaluate and identify predictive factors of non-response to aminosalicylates judged as the need for a step-up approach over time. METHODS: A case-control study of ulcerative colitis patients treated with aminosalicylates after the diagnosis of disease flare included in the ENEIDA single-centre registry from 1997 to 2017. Long-term treatment maintenance with aminosalicylates and higher therapeutic requirements were recorded. The cumulative incidence of treatment escalation was estimated using Kaplan-Meier curves and compared by the log-rank test. Cox regression analysis was performed to identify predictive factors of treatment with immunomodulators, biological agents or surgery. RESULTS: A total of 457 patients were included, of whom 28% (n = 126) were non-responders to aminosalicylates. The cumulative probability for a step-up approach within 20 years of follow up was 35%, mainly due to steroid-dependent colitis. Risk factors for treatment escalation were age ≤27 years (hazard ratio 2.31, 95% confidence interval 1.36–3.92), extensive colitis (hazard ratio 1.65, 95% confidence interval 1.04–2.60), Mayo endoscopic subscore ≥2 (hazard ratio 1.45, 95% confidence interval 1.02–2.06) and extraintestinal manifestations (hazard ratio 2.04, 95% confidence interval 1.03–4.05). CONCLUSIONS: Aminosalicylates represent an effective maintenance therapy. Younger age, extensive colitis, endoscopic disease severity and extraintestinal manifestations are risk factors for higher therapeutic requirements.

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Huntington disease (HD) is a fatal neurodegenerative disorder without a cure that is caused by an aberrant expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene. Although a negative correlation between the number of CAG repeats and the age of disease onset is established, additional factors may contribute to the high heterogeneity of the complex manifestation of symptoms among patients. This variability is also observed in mouse models, even under controlled genetic and environmental conditions. To better understand this phenomenon, we analysed the R6/1 strain in search of potential correlates between pathological motor/cognitive phenotypical traits and transcriptional alterations. HD-related genes (e.g., Penk, Plk5, Itpka), despite being downregulated across the examined brain areas (the prefrontal cortex, striatum, hippocampus and cerebellum), exhibited tissue-specific correlations with particular phenotypical traits that were attributable to the contribution of the brain region to that trait (e.g., striatum and rotarod performance, cerebellum and feet clasping). Focusing on the striatum, we determined that the transcriptional dysregulation associated with HD was partially exacerbated in mice that showed poor overall phenotypical scores, especially in genes with relevant roles in striatal functioning (e.g., Pde10a, Drd1, Drd2, Ppp1r1b). However, we also observed transcripts associated with relatively better outcomes, such as Nfya (CCAAT-binding transcription factor NF-Y subunit A) plus others related to neuronal development, apoptosis and differentiation. In this study, we demonstrated that altered brain transcription can be related to the manifestation of HD-like symptoms in mouse models and that this can be extrapolated to the highly heterogeneous population of HD patients.

Background Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics. Methods Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (>60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and 82 CoC). Host characteristics associated with TB and latent Mycobacterium tuberculosis infection (LTBI) were identified in the elderly by univariable and confirmed by multivariable logistic regression. Results LTBI was more prevalent among the elderly CoC (55% vs. 23.2% in adults; pvs. adult 63.8%); p = 0.213). Risk factors for TB in the elderly included male sex (adj-OR 4.33, 95% CI 1.76, 10.65), smoking (adj-OR 2.55, 95% CI 1.01, 6.45) and low BMI (adj-OR 12.34, 95% CI 4.44, 34.33). Unexpectedly, type 2 diabetes was not associated with TB despite its high prevalence (adj-OR 0.38, 95% CI 0.06, 2.38), and BCG vaccination at birth was protective (adj-OR 0.16, 95% CI 0.06, 0.45). Conclusions We report novel distinctions in TB risk factors in the elderly vs. adults, notably in diabetes and BCG vaccination at birth. Further studies are warranted to address disparities in this vulnerable, understudied population.

We surveyed urgent care centers (UCCs) in the state of Arizona to determine whether they offered the influenza vaccine during the 2016-2017 influenza season. Overall vaccine availability was 80.3% at these facilities. During this season, one-third of the UCCs offered influenza vaccination to children 6 months or older; approximately two-thirds offered influenza vaccination to children and young adults 16 years or older. This is the first study of influenza vaccine availability at UCCs.

To determine the impact of non-adherence to 5-Aminosalicylates (5-ASA) on the risk of flares and to identify risk factors of non-adherence. Observational, cohort study of ulcerative colitis (UC) patients in clinical remission at least 6 months on 5-ASA monotherapy maintenance prescribed by an electronic management program. Adherence was considered when 80% of the prescribed 5-ASA had been dispensed at the pharmacy. The study analyzed the existence and degree of 5-ASA adherence, disease course, UC phenotypic expression, and 5-ASA dose and regimen, and consumption of non-UC chronic drugs during 2-year follow-up. The study included 274 patients, 49% males with a median age of 38 (27–49) years old. Overall, 41% of patients were non-adherent to 5-ASA. Risk of flares was reduced in the adherent group (36% vs 54%; OR = 0,484; p = 0,004), mainly the mild ones (26% vs 38%; OR = 0,559; p = 0,031). Non-adherence was associated with younger age at diagnosis (32 (26–45) vs 41.5 (21–50), p = 0.000) and no-consumption of other chronic treatments (1.1 vs 2.1; OR = 1709; p = 0,048). Non-adherence to 5-ASA evaluated by the pharmaceutical management system was at 41% with a higher risk of relapse. Younger patients and patients who do not receive non-UC chronic treatments showed lower adherence rate.

Background: Recent evidence endorses gut microbiota dysregulation in the pathophysiology of heart failure (HF). Small intestinal bacterial overgrowth (SIBO) might be present in HF and associated with poor clinical outcomes. Lactulose breath testing is a simple noninvasive test that has been advocated as a reliable indicator of SIBO. In patients with HF, we aimed to evaluate the association with clinical outcomes of the exhaled hydrogen (H-2) and methane (CH4) concentrations through the lactulose breath test. Methods and Results: We included 102 patients with HF in which lactulose SIBO breath tests were assessed. Cumulative gas was quantified by the area under the receiver operating characteristic curve of CH4 (AUC-CH4) and H-2 (AUC-H-2). Clinical end points included the composite of all-cause death with either all-cause or HF hospitalizations, recurrent all-cause hospitalizations, and recurrent HF hospitalizations. Medians (interquartile ranges) of AUC-H-2 and AUC-CH4 were 1290 U (520-2430) and 985 U (450-2120), respectively. In multivariable analysis, AUC-H-2 (per 1000 U) was associated with all-cause death/all-cause hospitalization (hazard ratio [HR] 1.21, 95% CI 1.04-1.40; P = .012), all-cause death/HF hospitalization (HR 1.20, 95% CI 1.03-1.40; P = .021), and an increase in the rate of recurrent all-cause (incidence rate ratio [IRR] 1.31, 95% CI 1.14-1.51; P < .001) and HF (IRR 1.41, 95% CI 1.15-1.72; P = .001) hospitalizations. AUC-CH4 was not associated with any of these end points. Conclusions: AUC-H-2, a safe and noninvasive method for SIBO estimation, is associated with higher risk of long-term adverse clinical events in patients with HF. In contrast, AUC-CH4 did not show any prognostic value.

Hemophagocytic lymphohistiocytosis is characterized by uncontrolled activation of the immune system that leads to systemic hyperinflammation. Lymphoproliferative syndrome linked to the X chromosome is a hereditary immunodeficiency characterized by an inability to mount an adequate immune response to an Epstein-Barr virus infection. Hemophagocytic lymphohistiocytosis is one of the main clinical features of X-linked lymphoproliferative syndrome. We report the case of a patient who presented with primary hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection without a familial history of immunodeficiency. A mutation in the SH2D1A gene was identified, which confirmed the diagnosis of type 1 X-linked lymphoproliferative syndrome.

Mutations in the L1CAM gene have been identified in the following various X-linked neurological disorders: congenital hydrocephalus; mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; spastic paraplegia; and agenesis of the corpus callosum. These conditions are currently considered different phenotypes of a single entity known as L1 syndrome. We present three families with L1 syndrome. Sequencing of the L1CAM gene allowed the identification of the following mutations involved: a known splicing mutation (c.3531-12G>A) and two novel ones: a missense mutation (c.1754A>C; p.Asp585Ala) and a nonsense mutation (c.3478C>T; p.Gln1160Stop). The number of affected males and carrier females identified in a relatively small population suggests that L1 syndrome may be under-diagnosed. Conclusion: L1 syndrome should be considered in the differential diagnosis of intellectual disability or mental retardation in children, especially when other signs such as hydrocephalus or adducted thumbs are present.

AIM To determine the genetic predisposition to celiac disease (CeD) in inflammatory bowel disease (IBD) patients by quantifying the frequency of CeD-related human leucocyte antigen (HLA) (HLA-CeD: HLA-DQ2 and -DQ8) in IBD patients globally, by type of IBD and gender, and by calculating the protective/risk contribution of these haplotypes in the development of the IBD disease. METHODS We conducted a prospective study with IBD patients from our Unit. Clinical information was gathered and blood was tested for HLA-CeD. The control group was made up of unrelated Valencian organ donors. RESULTS 1034 subjects were analyzed: 457 IBD [207 ulcerative coliti (UC) and 250 Crohn’s disease (CD)] patients and 577 healthy controls. 39% of the controls and 34% of the patients had HLA-CeD (P = 0.0852). HLA-DQ2 was less frequent in UC patients (P = 0.0287), and HLA-DQ8 in CD (P = 0.0217). In women with UC, the frequency of DQ2.5cis (DQB1*02:01-DQA1*05:01) was reduced ≥ 50% [P = 0.0344; preventive fraction (PF) = 13%]. PFs (7%-14%) were obtained with all HLA-CeD haplotypes. HLA DQB1*02:02-DQA1*02:01 (HLA-DQ2.2) was more frequent in CD patients with respect to controls (P = 0.001) and UC patients (etiological fraction = 15%). CONCLUSION HLA-CeD is not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and -DQ8 in UC and CD respectively. HLA-DQ2.5 confers protection from the development of UC, especially in women, and HLA-DQ8 does so for the appearance of CD. HLA-DQ2.2 is present in 34% of the CD patients and may constitute a genetic risk factor for CD development.

Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors. Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed. 14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn’s disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis. Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

Objectives This study aimed to compare primary surgical versus nonsurgical treatment in a series of patients with infected pancreatic necrosis (IPN) and to investigate whether the success of nonsurgical approach is related to a less severe disease. Methods Thirty-nine consecutive patients with IPN have been included and further subdivided into two groups: primary surgical (n = 21) versus nonsurgical (n = 18). Outcome measures were the differences in mortality, morbidity, and pancreatic function. Comorbidity, organ failure, and other severity indexes were compared between the two groups. Results Mortality occurred in 16.7% of cases in the nonsurgical group versus 42.9% in the surgical group. In the primary nonsurgical group, seven were operated on due to failure of initial conservative treatment. In this latter group, mortality was 28.6% and was performed significantly later than in the primary surgical group. The group of primary surgical treatment was associated with a significant higher rate of multiple organ failure (MOF) at IPN diagnosis, new onset or worsening of organ failure, and MOF and nosocomial infection after surgery. Conclusions Initial nonsurgical approach in IPN is associated with better results both in cases which respond to this treatment as well as in those who, failing this conservative approach, have to be operated on after a delayed period. Primary surgically treated patients had a more severe disease at the time of IPN.

Item does not contain fulltext Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure (1) on reactivity to novelty in an open-field (as an index of hyperarousal), and (2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a beta-adrenoreceptor antagonist, and clenbuterol, a beta-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of beta-adrenoreceptors (beta1 and beta2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86mA, and 6s per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to non-shocked animals during the first 5min in the open-field. In the amygdala, IFS animals showed an enhanced increase of noradrenaline induced by stress compared to control animals. Bilateral microinjections of propranolol (0.5mug) into the amygdala one hour before testing in the open-field normalized the decreased locomotion observed in IFS animals. On the other hand, bilateral microinjections of clenbuterol (30ng) into the amygdala of control animals did not change the exploratory activity induced by novelty in the open field. IFS modified the mRNA expression of beta1 and beta2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results suggest that an increased noradrenergic activity in the amygdala contributes to the expression of hyperarousal in an animal model of PTSD.

The aim of the present study was to investigate the effects of the stimulation and inhibition of the ventral part of the medial prefrontal cortex (infralimbic cortex) on basal and stress-induced plasma levels of corticosterone and on the acquisition of aversive memory in animals maintained in control and environmental enrichment (EE) conditions. Intracortical microinjections of the GABAA antagonist picrotoxin and agonist muscimol were performed in male Wistar rats to stimulate and inhibit, respectively, the activity of the infralimbic cortex. Injections were performed 60 min before foot shock stress and training in the inhibitory avoidance task. Picrotoxin injections into the infralimbic cortex increased basal plasma levels of corticosterone. These increases were higher in EE rats which suggest that EE enhances the control exerted by infralimbic cortex over the hypothalamus-pituitary-adrenal (HPA) axis and corticosterone release. Muscimol injections into the infralimbic cortex reduced the stress-induced plasma levels of corticosterone and the retention latency 24 h after training in the inhibitory avoidance performance in control and EE animals, respectively. These results further suggest that the infralimbic cortex is required for the activation of the HPA axis during stress and for the acquisition of contextual aversive memories.

Stress can be defined as a brain-body reaction towards stimuli arising from the environment or from internal cues that are interpreted as a disruption of homeostasis. The organization of the response to a stressful situation involves not only the activity of different types of neurotransmitter systems in several areas of the limbic system, but also the response of neurons in these areas to several other chemicals and hormones, chiefly glucocorticoids, released from peripheral organs and glands. Thus, stress is probably the process through which body-brain integration plays a major role. Here we review first the responses to an acute stress in terms of neurotransmitters such as dopamine, acetylcholine, glutamate and GABA in areas of the brain involved in the regulation of stress responses. These areas include the prefrontal cortex, amygdala, hippocampus and nucleus accumbens and the interaction among those areas. Then, we consider the role of glucocorticoids and review some recent data about the interaction of these steroids with several neurotransmitters in those same areas of the brain. Also the actions of other substances (neuromodulators) released from peripheral organs such as the pancreas, liver or gonads (insulin, IGF-1, estrogens) are reviewed. The role of an environmental enrichment on these same responses is also discussed. Finally a section is devoted to put into perspective all these environmental-brain-body-brain interactions during stress and their consequences on aging. It is concluded that the integrative perspective framed in this review is relevant for better understanding of how the organism responds to stressful challenges and how this can be modified through different environmental conditions during the process of aging. This article is part of a Special Issue entitled: Brain Integration.

The main purpose of this study was to evaluate the effect of aging on plasma and free corticosterone (CORT) levels in the brain in basal conditions and in response to an acute stressor. Microdialysis experiments were performed in the hippocampus (HC) and the prefrontal cortex (PFC) of young adult (6 months) and aged (24 months) male Wistar rats. Basal free levels of CORT in the HC and the PFC were higher in aged animals. Restraint stress increased plasma CORT and free CORT levels in the HC and the PFC both in young and aged animals. However, while the increase of plasma CORT was higher in aged rats compared with young rats, the increases of free CORT in the HC and the PFC were not different between these two groups of rats. These results suggest that the changes produced by aging in the brain may be related to the enhanced basal levels of free CORT and not to the CORT increases in response to stress.

Rapid tuberculosis (TB) detection is critical for disease control, and further quantitation of Mycobacterium tuberculosis (Mtb) in sputum is valuable for epidemiological and clinical studies. We evaluated a simple, robust and cost-efficient in-house DNA extraction and downstream Taqman approach for detection and quantitation of Mtb genomes from sputum of newly-diagnosed TB patients and non-TB controls. DNA was extracted using guanidine isothiocyanate and silica-based spin columns in less than 2 h, stored frozen, and Taqman assays were used to detect Mtb with IS6110 and quantify it targeting RD1 and IS1081. The Taqmans had a sensitivity >95% in 108 culture-confirmed TB patients and specificity of 100% in 43 non-TB controls. Genome counts were correlated with the Mycobacterial Growth Indicator Tubes' (MGIT) time-to-detection values (1/TTD × 1000; rho = 0.66; p < 0.001) in 91 TB patients (33 excluded with MGIT contamination). This linear relationship was nearly identical between mycobacteria isolated from sputum and H37Rv Mtb grown in-vitro to its log phase. TB treatment between 3 and 7 days was associated with lower 1/TTD × 1000 values but not with genome counts. Together, our protocol provides rapid, specific, inexpensive and quantitative detection of Mtb DNA in fresh or stored sputa making it a robust tool for prompt TB diagnosis, and with potential use for clinical and epidemiologic studies.

Aims: to assess oxidative stress in acute pancreatitis, its evolution over time and its relationship with the severity of the disease. Methods: during a two-year period, patients with acute pancreatitis with less than 24 hours of pain were evaluated. Serum was obtained the first, second and fourth day from admittance, if complications were detected, and after recovery. Malondialdehyde was determined by high performance liquid chromatography. Twenty healthy volunteers constituted the control group. Malondialdehyde between groups was compared with Mann-Whitney and Kruskal-Wallis tests; malondialdehyde evolution was studied with Wilcoxon test. Results: one hundred and sixty-nine patients were included (91 women, median age 67 years, range 20-95); 33 suffered a severe episode. Malondialdehyde decreased from first to fourth day (0.600 vs. 0.451 vs. 0.343 μM, respectively, p < 0.05). When complications were detected, malondialdehyde level was similar to that of first and second day (0.473 μM, p > 0.05). In severe attacks malondialdehyde was higher than in control group at day 2 (severe: 0.514; mild: 0.440; control: 0.347 μM, p < 0.05 severe vs. control). Conclusions: an early oxidative stress is observed in acute pancreatitis. In severe attacks, oxidative stress remains high longer than in mild episodes. The onset of complications is associated with high malondialdehyde concentration.

The present study was designed to elucidate the effects of environmental enrichment in adulthood (EE) on the in vivo basal and stimulated extracellular concentration of dopamine in the nucleus accumbens of awake rats. The effects of EE on novelty-induced motor activity in an open field and on the levels of brain-derived neurotrophic factor (BDNF) in the nucleus accumbens and striatum were also analysed. Male Wistar rats (3 months of age) were housed in enriched or control conditions during 12 months. After behavioural testing, animals were subdivided in two groups. In one of the groups, BDNF protein levels were determined. In the second group of rats, microdialysis experiments were performed to monitor dialysate concentrations of dopamine in the nucleus accumbens after the perfusion of the glutamatergic agonist α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA; 100 μM) or potassium (100 mM). Both basal and potassium stimulated dialysate concentrations of dopamine were higher in EE than in control rats (basal: 80%; potassium: 210%). EE did not significantly change the increases of dialysate concentrations of dopamine induced by AMPA although there was a trend towards an enhancement of the effects of AMPA. EE decreased novelty-induced locomotor activity but did not modify the levels of BDNF in the nucleus accumbens or in the striatum. These results suggest that the in vivo activity of the mesolimbic dopamine system is enhanced by housing rats in an enriched environment and that this effect is not mediated by BDNF. These findings may be relevant for the understanding of the effects of EE on motor behaviour.

Background Nocardiosis is a life-threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%-3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors. Methods We performed a retrospective review study on 54 SOT patients diagnosed with Nocardia between 1997 and 2016 at our center. To explore the association of various risk factors with both the development of disseminated disease and mortality, a series of Fisher's exact tests was used. Findings Incidence of nocardiosis in SOT patients was 2.65%. Fisher's exact tests revealed no association between development of disseminated disease and the following variables: transplant rejection (P = 1), elevated tacrolimus levels (P = .4), and CMV viremia (P = .06). Also, we did not find any association between mortality and the variables we evaluated: type of transplant, transplant rejection, renal failure, disseminated nocardia, and patient's age. Overall mortality and 1-year mortality were 17% and 11%. Interpretation Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).

One of the many consequences of the pandemic of type 2 diabetes [1] is an increased frequency and severity of infection in diabetic patients, including up to an 8-fold increase in the risk of developing pulmonary tuberculosis [2]. The molecular basis for this susceptibility to tuberculosis is unclear. One possibility is a compromised immune response in diabetic patients that facilitates either primary progressive tuberculosis or reactivation of a latent tuberculosis infection [3]. Studies evaluating immunity to other microbial antigens in diabetic patients suggest that adaptive and innate responses are compromised, particularly in patients with chronic hyperglycemia (measured by elevated glycosylated hemoglobin [HbA1c] level) [4–15]. Immune impairments appear to be reversible with improved glycemic control [10, 16, 17]. Although susceptibility to tuberculosis in diabetic patients has been recognized for more than a century, only now, when we are faced by the current type 2 diabetes epidemic, are we beginning to address the public health impact and potential mechanisms of this association. Cytokines of the innate and adaptive immune systems orchestrate the response to Mycobacterium tuberculosis, with subsequent induction of cellular type 1 immunity, which is critical for protection [18–23]. A recently developed mouse model for diabetes and tuberculosis revealed higher bacterial burden and altered expression of IFN-γ in mice with chronic, but not acute, diabetes [24]. Persistent hyperglycemia apparently plays a significant role in the pathology. In this context, we assessed differences in cytokine secretion in response to an M. tuberculosis antigen in diabetic and nondiabetic patients with tuberculosis, selected from a population of patients known to have elevated rates of type 2 diabetes [25, 26]. To do this, we adapted a relatively simple ex vivo stimulation procedure designed to screen for variations in innate and adaptive immune responses to M. tuberculosis antigens. We hypothesized that, if impairment of the immune response plays a role in susceptibility to tuberculosis in patients with diabetes, we should be able to detect differences in cytokine responses to M. tuberculosis antigens in such patients, particularly in those with poor glycemic control.

The present study investigates the effects of injections of a specific N-methyl-D-aspartic acid (NMDA) antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) into the prefrontal cortex (PFC) on the extracellular concentrations of dopamine and acetylcholine in the nucleus accumbens (NAc) and on motor activity in the freely moving rat.Sprague-Dawley male rats were implanted with guide cannulas into the medial PFC and NAc to perform bilateral microinjections and microdialysis experiments. Spontaneous motor activity was monitored in the open field.Injections of CPP (1 microg/0.5 microL) into the PFC produced a significant increase of the baseline extracellular concentrations of dopamine (up to 130%), dihydroxyphenylacetic acid (DOPAC; up to 120%), homovanillic acid (HVA; up to 130%), and acetylcholine (up to 190%) in the NAc as well as motor hyperactivity. In the NAc, perfusion of the NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate antagonists CPP (50 microM)+6,7-dinitroquinoxaline-2,3-dione (DNQX; 50 microM) through the microdialysis probe blocked acetylcholine release, but not DOPAC and HVA increases produced by CPP injections into the PFC. Also, increases in motor activity produced by prefrontal injections of CPP were significantly reduced by bilateral injections into the NAc of a mixed D1/D2 antagonist, flupenthixol (5 and 25 microg/0.5 microL). Injections into the NAc of the muscarinic antagonist scopolamine (1 and 10 microg/0.5 microL) further increased, and of the nicotinic antagonist mecamylamine (1 and 10 microg/0.5 microL) did not change, the increases in motor activity produced by prefrontal CPP injections.These results suggest that the dysfunction of NMDA receptors in the PFC could be a key factor in the neurochemical and motor effects associated with corticolimbic hyperactivity.

Objectives The aim of this investigation was to evaluate the pancreatographic findings and dynamics of pancreatic duct diameter, as determined by secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP), in patients with acute alcoholic pancreatitis or chronic alcoholic pancreatitis and in a control group. Methods S-MRCP was performed in patients with acute alcoholic pancreatitis who did not manifest the functional and radiological (ultrasonography and computed tomography) criteria of chronic pancreatitis (n = 21), in patients with chronic alcoholic pancreatitis (n = 28) and in a control group (n = 16). The diameter of the main pancreatic duct (MPD) was monitored before secretin administration and at 3 and 10 min after secretin administration. Morphological features were also assessed before and after the administration of secretin. Results All ductal diameters were significantly larger in chronic alcoholic pancreatitis (P < 0.0001). There were no differences in MPD caliber between patients with acute alcoholic pancreatitis and the control group. The percentage of variation between basal MPD diameter and at 3 min post-secretin administration was lower in patients with chronic (35.5%) pancreatitis than in those with acute alcoholic pancreatitis (52.3%) and the control group (52.5%). There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of the frequency of visualization of side branches, ductal narrowing, intraluminal filling defects, and ductal irregularity. One patient with acute alcoholic pancreatitis presented ductal criteria of chronic pancreatitis following the administration of secretin. Conclusions The dynamics of MPD visualized on S-MRCP in patients with acute alcoholic pancreatitis is similar to that observed in the control group and different from that observed in patients with chronic alcoholic pancreatitis. There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of morphological pancreatographic features.

The present study was designed to investigate the effects of a mild acute stress on the in vivo release of dopamine in the prefrontal cortex (PFC) during aging and whether housing animals in an enriched environment changes these effects. Behavioural parameters such as spontaneous motor activity (open-field) and working memory performance in a delayed alternation task (water T-maze) were also studied. Male Wistar rats (3 months of age) were housed during 3, 12, and 21 months (6, 15 and 24 months of age at the end of housing) in enriched or control conditions. After behavioural testing, animals were subdivided in two groups. In one of the groups BDNF protein levels were determined in PFC, hippocampus and amygdala. Rats of the second group were implanted with guide cannula in the PFC to perform microdialysis experiments and to monitor extracellular concentrations of dopamine. The release of dopamine in the PFC produced by handling stress (40 min) was significantly reduced in both enriched and control 24 months animals. However, the increases of dopamine produced by stress were significantly lower in enriched animals when compared to controls. Similarly, the increases of dopamine produced by perfusing K(+) 100 mM into the PFC were also reduced by aging and environmental enrichment. Both spontaneous motor activity and working memory performance were significantly reduced by aging. Moreover, animals housed in an enriched environment did show a lower spontaneous motor activity at all ages studied, though they did not show any change in performing the working memory task, either in basal conditions or after an acute stress. The BDNF protein levels were increased by environmental enrichment in the hippocampus and amygdala, but not in the PFC. These results suggest that both environmental enrichment and aging reduces the activity of the mesocortical dopamine system.

The present study was aimed to investigate the effects of a chronic treatment with the dopamine uptake blocker nomifensine on the in vivo extracellular concentrations of dopamine, acetylcholine, glutamate and GABA in the prefrontal cortex, striatum and nucleus accumbens. Male Wistar rats received intraperitoneal (i.p.) daily injections of nomifensine (10 mg/kg) or saline for 22 days. Microdialysis experiments were performed on days 1, 8, 15 and 22 of treatment to evaluate the effects of the injection of nomifensine or saline. Motor activity of the animals was monitored during microdialysis experiments. Injections of nomifensine increased extracellular concentration of dopamine in striatum and nucleus accumbens, but not in prefrontal cortex. Acetylcholine concentrations in striatum but not in nucleus accumbens were increased by nomifensine on days 15 and 22 of treatment. In prefrontal cortex, nomifensine increased acetylcholine levels without differences among days. No changes were found on glutamate and GABA concentrations in the three areas studied. Injections of nomifensine also increased spontaneous motor activity and stereotyped behaviour without differences among days. These results show that systemic chronic treatment with a dopamine uptake blocker produces differential effects on extracellular concentrations of dopamine and acetylcholine, but not glutamate and GABA, in different areas of the brain.

Extra-oesophageal autonomic dysfunction in idiopathic achalasia is not well documented, due to contradictory results reported. We aimed to study the cardiovascular and pancreatic autonomic function in patients with idiopathic achalasia. Thirty patients with idiopathic achalasia (16M/14F; 34.5 ± 10.8 years) and 30 healthy volunteers (13M/17F; 34.8 ± 10.7 years) were prospectively studied. Age >60 years and conditions affecting results of autonomic evaluation were excluded. Both groups underwent the sham feeding test and plasmatic levels of pancreatic polypeptide (PP) were determined by radioimmunoassay (basal, at 5, 10, 20 and 30 min). Cardiovascular parasympathetic (deep breathing, standing, Valsalva) and sympathetic function (postural decrease of systolic blood pressure, Handgrip test) were assessed. Statistical comparison of basal and increase levels of PP and parasympathetic/sympathetic cardiovascular parameters was performed between groups. Basal levels of PP were similar in controls and patients and maximum increase of PP during sham feeding test. A similar rate of abnormal cardiovascular tests was found between groups (P > 0.05). E/I ratio was the mostly impaired parameter (patients: 36.7%vs controls: 20%, P = 0.15, chi-squared test). Autonomic cardiovascular tests and pancreatic response to vagal stimulus are not impaired in patients with primary achalasia of the oesophagus.

The aim of the present study was to investigate whether environmental enrichment changes the effects of acute stress on both the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and working memory performance. Male Wistar rats (3 months of age) were housed in enriched or control conditions during 12 months. Behavioural testing was carried out to assess working memory performance in a delayed alternation task (water escape T-maze). Horizontal and vertical motor activity were also monitored in the open field. After behavioural testing (open field and water T-maze), animals were implanted with guide cannula in the PFC to perform microdialysis experiments and to monitor dopamine and acetylcholine extracellular concentrations. Handling stress (40min) produced similar increases of extracellular concentrations of dopamine in the PFC of both enriched and control animals. In contrast, handling stress increased significantly the extracellular concentrations of acetylcholine in the PFC of control, but not enriched, animals. Exposing animals to a lit open field during 10min significantly reduced working memory performance assessed immediately in the water T-maze just in control animals, though these effects were not significantly different between both groups of animals. Spontaneous motor activity in the open field was lower in enriched compared to control animals. These results suggest that environmental enrichment changes acetylcholine, but not dopamine, reactivity to stress in the PFC.

Background An increase in body mass index has been found to be associated with an increase in the prevalence of gastroesophageal reflux disease (GERD) symptoms, esophageal mucosal injury, and GERD complications. Few systematic studies with objective tests have evaluated esophageal disorders in the morbidly obese population. Objectives To define more precisely in morbidly obese people the incidence of esophageal symptoms and characterize the esophageal disorders using objective data. Setting University Hospital, Spain. Methods Two hundred twenty-four presurgical morbidly obese patients were submitted to a protocol including a clinical history and objective tests (endoscopy, stationary esophageal manometry, 24-hour esophageal pH monitoring and isotopic emptying of the esophagus). Results In a morbidly obese population, heartburn (50.9%) and regurgitation (28.6%) were the most prevalent symptoms of GERD. Endoscopy registered hiatus hernia (12.5%) and reflux esophagitis (17.3%). Manometry was often abnormal (33.4%), with a hypotensive lower esophageal sphincter as the most common finding. Esophageal pH-metry was abnormal in 54.2% of the cases. Finally, 9.1% of the patients presented with abnormal isotopic esophageal emptying. A correlation between the degree of obesity and the severity of symptoms/objective tests for esophageal abnormalities could not be found. Conclusions In morbidly obese patients, GERD is common, symptoms are unspecific, and there is a high prevalence of pH-metry and manometric abnormalities, unrelated to the degree of obesity.

Transanal advancement flap is a recognized technique for complex fistula. Management of the tract is open to discussion. Excision of the tract by the “core out” technique is difficult and could increase the risk of sphincter damage. Curettage is easier but it could increase the risk of recurrence. The aim of the present study was to assess the effect of both techniques on sphincter function and to study the clinical results. This is a retrospective analysis from a prospective database. One hundred nineteen consecutive patients with high cryptoglandular anal fistula were included. “Core out” technique was performed in 78 patients (group I) and “curettage” in 41 (group II). In both, a full-thickness rectal flap was advanced over the closed internal defect. Anorectal manometry was performed to assess sphincter function. Continence was assessed using the Wexner Scale. Recurrence was defined as the presence of an abscess or fistulization. Manometric results showed a significant decrease in the maximum resting pressure after surgery in both groups. The maximum squeeze pressure was significantly reduced only in group I (p

Environmental enrichment produces changes in spontaneous and psychostimulant-induced motor activity. Dopamine in the prefrontal cortex (PFC), through the activation of D1 receptors, has been suggested to play a role in modulating motor activity. The present study investigated the effects of environmental enrichment on spontaneous motor activity, prefrontal acetylcholine release following local D1 receptor stimulation and D1 receptor expression in the PFC. Male wistar rats (3 months of age) were housed in enriched or isolated conditions during 90 days. Animals were then implanted with guide cannulae to perform microdialysis experiments in the PFC. Spontaneous motor activity and acetylcholine extracellular concentrations were monitored simultaneously. Also spontaneous motor activity was measured in an open field. On completion of the experiments, the density of D1 receptors in the PFC was studied by immunocytochemistry. Rats housed in an enriched environment showed significantly lower spontaneous motor activity in the open field compared to isolated animals. Perfusion of the D1 agonist SKF38393 (50 microM; 40 min) in the PFC produced long lasting increases of spontaneous motor activity and of local dialysate concentrations of acetylcholine in both groups of rats. However, increases of both motor activity and acetylcholine concentrations were significantly lower in enriched compared to isolated animals. Moreover, the density of D1 receptors in the PFC was significantly reduced in animals housed in an enriched environment. These results are the first evidence suggesting that environmental enrichment during adult life changes the function of D1 dopamine receptors in the PFC.

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

Background and Aim. Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. Materials and Methods. We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A 13C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. Results. Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p

Background & Aims: The aim of this study was to establish a simple method to exclude the possibility of pelvic floor dyssynergia (PFD) in constipated patients and thus avoid unnecessary expensive physiologic studies. Methods: Patients with suspicion of functional constipation (FC) were studied prospectively between 1994 and 2002, excluding those with severe systemic, psychological, or symptomatic anorectal/colonic disorders or taking medications that might modify symptoms or results of studies. Diagnosis of PFD was established retrospectively by manometric plus defecographic findings according to Rome II criteria. Two groups of patients were identified: FC without PFD (FC group) and PFD group. A 30-day symptom diary and balloon expulsion test results were evaluated in all patients. Clinical differences and results of the expulsion test were statistically compared between groups. Results: Of 359 patients evaluated, 130 were included (FC group, 106; PFD group, 24). According to data from the diary, only anal pain was more frequent in the PFD group compared with the FC group (anal pain in >25% of defecations, 70.8% vs. 40.6%; P 2 test). The expulsion test was pathologic in 21 of 24 patients with PFD and 12 of 106 without PFD. The specificity and negative predictive value of the test for excluding PFD were 89% and 97%, respectively. Conclusions: The balloon expulsion test is a simple and useful screening procedure to identify constipated patients who do not have PFD. Symptoms are not enough to differentiate between subtypes of constipation.

The purpose of this study was to evaluate the potential usefulness of contrast-enhanced power Doppler ultrasound in the detection and follow-up of local complications (phlegmon and abscess) in Crohn's disease.With this aim, 28 patients with suspected abdominal inflammatory mass were examined with power Doppler ultrasound before and after intravenous administration of the ultrasound contrast agent Levovist, with evaluation of vascularity within and/or around the inflammatory mass. Colour Doppler flow was characterized as clearly visible, minimally visible or absent. All the patients underwent a post-contrast computed tomography exam.Power Doppler ultrasound, after administration of contrast medium, allows the detection of small inflammatory masses in Crohn's disease, particularly those under 2 cm in diameter, when compared with computed tomography.We conclude that contrast-enhanced power Doppler ultrasound is a sensitive method for the detection of small abdominal inflammatory masses and for differential diagnosis between phlegmon and abscess.

The present study was designed to determine the potential of CB1 cannabinoid receptor modulating compounds in the treatment of L-3,4-dihydroxyphenylalanine (L-dopa)-induced dyskinesia in Parkinson's disease. In the reserpine-treated rat model of parkinsonism, administration of a high dose of L-dopa (150 mg/kg) but not of Cl-APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1-3 mg/kg) reduced the increase in vertical activity elicited by L-dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212-2 (0.1-3 mg/kg) reduced the L-dopa-induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by L-dopa. WIN55,212-2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl-APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine-treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl-APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine-treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1-1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L-dopa (150 mg/kg) in the reserpine-treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of L-dopa and may be useful for the treatment of the dyskinesia associated with long-term L-dopa treatment of Parkinson's disease.

The levels of several neurochemicals, i.e., uric acid (UA), dopamine (DA), dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid, collected daily from the rat striatum with either fixed or removable microdialysis probes for 7 days after surgery were compared. The implantation of the fixed cannula was followed by a 10-fold increase in the UA content in the dialysates collected from the first day after surgery onward and by a steady decrease in dihydroxyphenylacetic acid levels, whereas those of DA remained fairly stable. With the removable cannula system, only a smaller, transient increase in UA during the first 3 days after surgery was observed, with no change in DA or monoamine metabolites. The glial reaction around the cannula tracks was assessed by both quantitative histological techniques and measuring the glutamine levels in the dialysates collected at the time of surgery and 7 days later. Both the glial cell number and nuclear size, as well as the glutamine outflow, were considerably larger in the animals implanted with the fixed probes. It is, therefore, likely that the UA levels in the dialysate reflect the glial reaction to the probe. The suitability of the removable probe system for behavioral experiments involving repeated microdialysis sampling was illustrated in an experiment showing that the DA release in the nucleus accumbens of male rats assessed daily at postsurgery days 5–10 was virtually identical in three alternating sessions of sexual behavior as was the smaller release of this neurotransmitter detected during intervening nonsexual social interactions.

Using microdialysis in the prefrontal cortex, this study investigated first the effects of the ionotropic glutamatergic agonists NMDA and AMPA on extracellular concentrations of GABA, and second, the modulation of these effects by increasing endogenous dopamine. NMDA (20, 100, and 500 microM) and AMPA (1, 20, and 100 microM), perfused through the microdialysis probe for 60 min, produced a dose-related increase of extracellular concentrations of GABA in the prefrontal cortex of the awake rat. NMDA 100 and 500 microM produced a maximal increase of extracellular GABA of 150 +/- 38% and 245 +/- 75% of baseline, respectively. AMPA 20 and 100 microM produced a maximal increase of extracellular GABA of 140 +/- 17% and 195 +/- 41% of baseline, respectively. NMDA and AMPA also increased extracellular concentrations of glutamate. Increases of extracellular GABA, and also of glutamate, produced by NMDA (500 microM) and AMPA (100 microM) were significantly blocked by the NMDA antagonist CPP (100 microM) and the AMPA/kainate antagonist DNQX (100 microM), respectively. To investigate whether dopamine modulates the increases of GABA produced by NMDA and AMPA, endogenous dopamine was increased with the dopamine uptake inhibitor nomifensine. Nomifensine (1, 100, and 1000 microM) produced a dose-related increase of dialysate dopamine (from 0.1 to 1.0 nM) but did not modify basal extracellular concentrations of GABA in the prefrontal cortex. However, increases of endogenous dopamine at 0.5-0.7 nM did potentiate the increases of extracellular GABA produced by AMPA (20 microM) (from 140% to 240% of baseline), but not by NMDA (100 microM), in this area of the brain. These effects were attenuated by the perfusion of (-)sulpiride (D2 antagonist), but not by the perfusion of SCH-23390 (D1 antagonist). These results suggest that glutamate, through the activation of both NMDA and AMPA/kainate ionotropic receptors, facilitates GABAergic transmission in the prefrontal cortex, and that dopamine can modulate the effects of glutamate through AMPA/kainate receptors on GABA transmission in this area of the brain.

A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia. The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event. Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory. Acute stress increased amygdala dialysate concentrations of dopamine (160 % of baseline), noradrenaline (145 % of baseline) and corticosterone (170 % of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test. These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.

Low-cost telemedicine is a viable and secure tool for preoperative evaluation of surgical mission patients. It increases efficiency and optimizes the use of existing resources. More specifically, it helps ensure an accurate assessment of patients before the surgical team arrives, reduces on-site prescreening time, and decreases the number of surgical candidates on the waiting list. Routine use of telemedicine in surgical missions most likely would reduce preoperative times and the number of operations canceled at the last minute. Moreover, it may be effectively used for long-term follow-up care, including the management of any postoperative complications.

Using microdialysis, the effects of endogenous glutamate on extracellular concentrations of taurine, in striatum and nucleus accumbens of the awake rat during the normal process of aging were investigated. The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was perfused through the microdialysis probe to increase the endogenous concentration of glutamate. Young (2-4 months), middle aged (12-14 months), aged (27-32 months) and very aged (37 months) male Wistar rats were used. PDC (1, 2 and 4 mM) produced a dose-related increase of extracellular concentrations of glutamate and taurine in striatum and nucleus accumbens in all groups of age. Increases of glutamate, but not of taurine, decreased during aging in striatum. In nucleus accumbens there were no age-related changes in the increases of glutamate and taurine induced by PDC. In all age groups, increases of extracellular taurine were significantly correlated with increases of extracellular glutamate. However, when these taurine-glutamate correlations for all groups of age were compared, no statistical differences were found. These results show first that a decrease in the increases of glutamate produced by the glutamate reuptake inhibitor in striatum, but not in nucleus accumbens, is produced by age; second that glutamate-taurine interaction in striatum and nucleus accumbens does not change during the normal process of aging.

Using microdialysis, the effects of endogenous glutamate on extracellular concentrations of taurine in striatum and nucleus accumbens of the awake rat were investigated. The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was used to increase the extracellular concentration of glutamate. PDC (1, 2 and 4 mM) produced a dose-related increase of extracellular concentrations of glutamate and taurine in striatum and nucleus accumbens. Increases of extracellular taurine were significantly correlated with increases of extracellular glutamate, but not with PDC doses, which suggests that endogenous glutamate produced the observed increases of extracellular taurine in striatum and nucleus accumbens. The role of ionotropic glutamate receptors on the increases of taurine was also studied. In striatum, perfusion of the antagonists of NMDA and AMPA/kainate glutamate receptors attenuated the increases of extracellular taurine. AMPA/kainate, but not NMDA receptors, also reduced the increases of extracellular taurine in nucleus accumbens. These results suggest that glutamate-taurine interactions exist in striatum and nucleus accumbens of the awake rat.

Using microdialysis, a study was made of the effects of an increase of endogenous GABA on basal and potassium-stimulated release of dopamine in striatum of the awake rat. The dopamine metabolites DOPAC and HVA were also measured. Extracellular concentrations of GABA were increased by inhibiting its uptake with nipecotic acid. TTX (10 microM) reduced basal extracellular concentrations of dopamine, and dopamine metabolites, but not GABA. Nipecotic acid (200, 500, and 1000 microM) produced a dose-related increase in basal extracellular concentrations of GABA, but did not change basal extracellular concentrations of dopamine and dopamine metabolites. However, nipecotic acid significantly enhanced the dopamine release produced by perfusion of potassium (50 mM) and also enhanced the extracellular increase of GABA produced by high potassium. These results suggest that an increase of endogenous GABA is facilitating the stimulated release, but not the basal release, of dopamine in the striatum of the awake rat.

This study investigated the role of nitric oxide (NO) in modulating the basal and N-methyl-D-aspartate (NMDA)-induced release of dopamine (DA), glutamate (GLU), and gamma-aminobutiric acid (GABA) in striatum of the freely moving rat using microdialysis. Intrastriatal infusion of NMDA (5 mM) for 15 min increased extracellular concentrations of DA, GLU, and GABA. NMDA also decreased extracellular concentrations of DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (HVA), and of the GLU and GABA precursor, glutamine (GLN). Perfusion of N-nitroarginine (1-5 mM), an inhibitor of the synthesis of NO, potentiated NMDA-induced increases in extracellular concentrations of DA and attenuated increases of extracellular GLU. NMDA-induced decreases of extracellular concentrations of DOPAC were also attenuated by N-nitroarginine. N-nitroarginine had no effect on NMDA-induced changes of extracellular concentrations of GABA, HVA, and GLN. N-nitroarginine decreased basal concentrations of DOPAC and HVA, and increase basal concentrations of GLN, but had no effect on basal DA, GLU, and GABA. These results suggest a role for NO in modulating the NMDA-induced release of DA and GLU in striatum. They also suggest that NO could be regulating the basal metabolism of DA, GLU, and GABA.

Interactions between glutamate (Glu), dopamine (DA), GABA, and taurine (Tau) were investigated in striatum of the freely moving rat by using microdialysis. Intrastriatal infusions of the selective Glu uptake inhibitor l-trans-pyrrolidine-3,4-dicarboxylic acid (PDC) were used to increase the endogenous extracellular [Glu]. Correlations between extracellular [Glu] and extracellular [DA], [GABA], and [Tau], and the effects of a selective blockade of ionotropic Glu receptors, were studied. PDC (1, 2, and 4 mM) produced a dose-related increase in extracellular [Glu]. At the highest dose of PDC, [Glu] increased from 1.55 ± 0.35 to 6.11 ± 0.88 µM. PDC also increased extracellular [DA], [GABA], and [Tau]. The increasing [Glu] was correlated significantly with increasing [DA], [GABA], and [Tau]. PDC also decreased extracellular concentrations of DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA). Perfusion with the NMDA-receptor antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (1 mM) or the AMPA/kainate-receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) (1 mM) attenuated the increases produced by PDC (4 mM) on [DA], [GABA], and [Tau], and decreases in [DOPAC] and [HVA]. DNQX also attenuated the increases in [Glu] induced by PDC. These data show that endogenous Glu plays a role in modulating the extracellular concentrations of DA, GABA, and Tau in striatum of the freely moving rat.

INTRODUCTION Diabetes knowledge among TB patients can contribute to improved TB treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in developing countries. Given its low cost, the sensitivity of urine glucose dipsticks for diabetes screening in TB patients was assessed. METHODS Glycosuria was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas, USA (n = 20) and northeast Mexico (n = 70) during January 2009-December 2010. RESULTS Glycosuria was detected in 65% of the diabetic patients with chronic hyperglycemia (positive predictive value 91%, negative predictive value 84%). CONCLUSION We propose that TB clinics with limited budgets where portable glucometers may not be available conduct universal screening for diabetes with urine dipsticks. This could be followed by blood glucose or HbA1c testing in the subset of patients requiring confirmation or higher sensitivity assessment, to improve the comanagement of TB and diabetes.