[Gallstone ileus as a cause of mechanical intestinal obstruction: a case report]. / íleo biliar como causa de obstrucción intestinal mecánica: reporte de un caso.

Biliary ileus is a mechanical intestinal obstruction characterized by symptoms such as abdominal pain, jaundice and fever. The treatment of choice in these cases is associated with a surgical approach according to the clinical condition of the patient. It is important to study this pathology since its timely diagnosis and treatment are essential to avoid serious complications associated with high morbidity and mortality. This article describes a case related to biliary ileus.

Íleo biliar como causa de obstrucción intestinal mecánica: reporte de un caso / Gallstone ileus as a cause of mechanical intestinal obstruction: a case report

RESUMEN El íleo biliar es una causa obstrucción mecánica intestinal caracterizada por presentar síntomas como dolor abdominal, ictericia y fiebre. El tratamiento de elección en estos casos está asociado al abordaje quirúrgico acorde al estado clínico del paciente. Es importante estudiar esta patología ya que su diagnóstico y tratamiento oportunos son fundamentales para evitar complicaciones graves asociadas a una gran morbilidad y mortalidad. El presente artículo describe un caso relacionado al íleo biliar.

ABSTRACT Biliary ileus is a mechanical intestinal obstruction characterized by symptoms such as abdominal pain, jaundice and fever. The treatment of choice in these cases is associated with a surgical approach according to the clinical condition of the patient. It is important to study this pathology since its timely diagnosis and treatment are essential to avoid serious complications associated with high morbidity and mortality. This article describes a case related to biliary ileus.

Sympathetic-Immune Interactions during Different Types of Immune Challenge.

BACKGROUND: The neuro-endocrine regulation of immune functions is based on a complex network of interactions. As part of this series of articles, we refer here to immune-sympathetic interactions that are triggered by different types of immune challenge. SUMMARY: We mention the initial hypothesis that led to the proposal that the sympathetic nervous system (SNS) is involved in immunoregulation. We next refer mainly to our initial work performed at a time when most immunologists were concentrated in clarifying aspects of the immune system that are essential for its regulation from within. The first approach was to explore whether immune responses to innocuous antigens and superantigens can elicit changes in the activity of the SNS, and their potential relevance for the regulation of the activity of the immune system. The following step was to explore whether comparable immune-SNS interactions are detected in different models of diseases with immune components, such as parasitic and viral infections and autoimmune pathologies. KEY MESSAGES: We pose some general considerations that may at least partially explain seemly discrepant findings, and remark the importance of interpreting immunoregulatory effects of the SNS together with other neuro-endocrine inputs that simultaneously occur when the activity of the immune system changes. Finally, we provide some arguments to re-consider the use of the expression "reflex" in immunology.

Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes.

The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology.

Analysis of the costs incurred by patients with Chagas disease: The experience in endemic municipalities in Colombia.

BACKGROUND: Out-of-pocket expenditure (OOP) are key costs (medical and non-medical) that many individuals incur to receive health services. They have been identified as a key access barrier for vulnerable populations, in particular for populations affected by neglected diseases with a chronic progression, such as Chagas disease. It is important to understand the costs of accessing healthcare services that are borne by patients with T. cruzi infection. METHODOLOGY: We prepared a structured survey for patients with T. cruzi infection/Chagas disease who were all treated by the healthcare system in endemic municipalities in Colombia. The results were analyzed according to three categories: 1. The socioeconomic profiling of the patients; 2. The costs of accommodation, food and transportation, in addition to the time spent commuting; and 3. the income losses (money that was not earned due to absence from work) related to treatment at the local primary care hospital or at the high-complexity reference hospital. MAIN FINDINGS: Ninety-one patients answered the survey voluntarily. The data revealed that, when treated at the specialized reference hospital, patients spent 5.5 times more on food and accommodation, transportation costs were five times higher, and the loss of earnings was three times higher than when they were treated at the local primary care hospital. Moreover, the amount of time spent on transportation was 4 times higher at the reference hospital. CONCLUSIONS: Providing comprehensive healthcare services for Chagas management at local primary healthcare hospitals would allow the most vulnerable patients to save on expenses related to medical and non-medical costs, in turn leading to higher adhesion to treatment thus benefiting the health system as a whole. These findings are in alignment with the WHO's World Health Assembly 2010 Resolution on the importance of treating Chagas at local primary care hospitals, thereby saving patients time and money, allowing for timely care, and promoting access to healthcare.

To protect or to kill: A persisting Darwinian immune dilemma.

The immune system, which evolved as a protective system, can paradoxically mediate lethal effects when it is over-activated. These effects can be traced back to infected insects and are mainly mediated by phylogenetically old cytokines that have been found already in starfishes and sponges. We hypothesize that these anti-homeostatic effects are important for restricting the cumulative risk of transmission of highly mutating environmental pathogens that may endanger species, particularly when they start to originate and expand. Considering the Darwinian view that evolution is a permanent process, this anti-homeostatic program is preserved and expressed even when there is no risk for the species. Here, we review these aspects and discuss how evolutionary-imposed anti-homeostatic immune programs are expressed during acute and chronic human diseases, which can be further aggravated in the absence of medical interventions. The relevance of early identification of ancestral biomarkers that predict a shift from protective to deleterious immune outcomes is emphasized.

Expression of the α7 Nicotinic Acetylcholine Receptor Is Critically Required for the Antifibrotic Effect of PHA-543613 on Skin Fibrosis.

INTRODUCTION: Targeting the α7 nicotinic acetylcholine receptor (α7nAChR) has recently been suggested as a potential new treatment for fibrotic skin diseases. Here, we performed a genetic and pharmacologic approach to clarify the role of this receptor in the bleomycin (BLM) mouse model of skin fibrosis using α7nAChR KO mice. METHODS: We analyzed the expression of extracellular matrix (ECM) components in murine skin using quantitative RT-PCR, pepsin digestion/SDS-PAGE of proteins and performed hydroxyproline assays as well as histological/immunohistochemical staining of skin sections. To identity the target cells of the α7nAChR agonist PHA-543613, we used murine dermal fibroblasts (MDF). We tested their response to the profibrotic cytokine transforming growth factor-ß1 (TGF-ß1) and utilized gene silencing to elucidate the role of the α7nAChR. RESULTS: We confirmed our previous findings on C3H/HeJ mice and detected a suppressive effect of PHA-543613 on BLM-induced skin fibrosis in the mouse strain C57BL/6J. This antifibrotic effect of PHA-543613 was abrogated in α7nAChR-KO mice. Interestingly, α7nAChR-KO animals exhibited a basal profibrotic signature by higher RNA expression of ECM genes and hydroxyproline content than WT mice. In WT MDF, PHA-543613 suppressed ECM gene expression induced by TGF-ß1. Gene silencing of α7nAChR by small interfering RNA neutralized the effects of PHA-543613 on TGF-ß1-mediated ECM gene expression. CONCLUSION: In summary, we have identified the α7nAChR as the essential mediator of the antifibrotic effect of PHA-543613. MDF are directly targeted by PHA-543613 to suppress collagen synthesis. Our findings emphasize therapeutic exploitation of α7nAChR receptor agonists in fibrotic skin diseases.

Glucocorticoids and sympathetic neurotransmitters modulate the acute immune response to Trypanosoma cruzi.

Evidence suggests that natural and adaptive immune responses can trigger neuroendocrine responses. Here, we discuss changes in the activity of the hypothalamus-pituitary-adrenal axis and in autonomic nerves, predominantly of the sympathetic nervous system, in a mouse model of acute infection with Trypanosoma cruzi. The endocrine response includes a marked increased release of glucocorticoid and a decrease of immune-stimulatory hormones, such as dehydroepiandrosterone sulfate, prolactin, and growth hormone during infection. These endocrine changes result in reduced proinflammatory cytokine production, increased regulatory/effector T cell ratio, and thymus atrophy. The sympathetic activity in the spleen of infected mice is also markedly reduced. However, the residual sympathetic activity can modulate the immune response to the parasite, as shown by increased mortality and production of proinflammatory cytokines in sympathetically denervated, infected mice. The outcome of the neuroendocrine response is the moderation of the intensity of the immune response to the parasite, an effect that results in delayed mortality in susceptible mice, and favors the course toward chronicity in more resistant animals.

Immunity and ultrasonic vocalization in rodents.

Ultrasonic vocalizations (USVs) serve important communicative functions in rodents. Different types of USVs can be triggered in the sender, for example, by maternal separation, social interactions, or exposure to predators, and they evoke affiliative or alarming behaviors in recipients. This review focusses on studies evaluating possible links between immunity and USVs. Most studies have been performed in a murine model of maternal immune activation and subsequent evaluation of effects in the offspring. This model has received large attention in recent years because it mimics behavioral abnormalities observed in certain human neuropsychiatric disorders, including autism spectrum disorder. Although there is still some controversy, the results indicate that stimulation of the immune system of mice and rats during pregnancy affects ultrasonic calling in pups. Few studies are available on immunization during adulthood and USVs. In most cases, immune stimulation led to disease, complicating conclusions about a possible direct link between vocalization and immunity. Although much work is still needed, this is certainly a rather new and promising aspect of interactions between the immune system and behavior.

Reduced Efficacy of d-Amphetamine and 3,4-Methylenedioxymethamphetamine in Inducing Hyperactivity in Mice Lacking the Postsynaptic Scaffolding Protein SHANK1.

Genetic defects in the three SH3 and multiple ankyrin repeat domains (SHANK) genes (SHANK1, SHANK2, and SHANK3) are associated with multiple major neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BPD). Psychostimulant-induced hyperactivity is a commonly applied paradigm to assess behavioral phenotypes related to BPD and considered to be the gold standard for modeling mania-like elevated drive in mouse models. Therefore, the goal of our present study was to test whether Shank1 plays a role in the behavioral effects of psychostimulants and whether this is associated with genotype-dependent neurochemical alterations. To this aim, male and female null mutant Shank1-/- mice were treated with d-amphetamine (AMPH; 2.5 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, commonly known as ecstasy; 20 mg/kg), and psychostimulant-induced hyperactivity was compared to heterozygous Shank1+/- and wildtype Shank1+/+ littermate controls. Results show that Shank1-/- mice display reduced psychostimulant-induced hyperactivity, although psychostimulants robustly stimulated locomotor activity in littermate controls. Shank1 deletion effects emerged throughout development, were particularly prominent in adulthood, and seen in response to both psychostimulants, i.e., AMPH and MDMA. Specifically, while AMPH-induced hyperactivity was reduced but still detectable in Shank1-/- mice, MDMA-induced hyperactivity was robustly blocked and completely absent in Shank1-/- mice. Reduced efficacy of psychostimulants to stimulate hyperactivity in Shank1-/- mice might be associated with alterations in the neurochemical architecture in prefrontal cortex, nucleus accumbens, and hypothalamus. Our observation that psychostimulant-induced hyperactivity is reduced rather than enhanced in Shank1-/- mice clearly speaks against a behavioral phenotype with relevance to BPD. Lack of BPD-like phenotype is consistent with currently available human data linking mutations in SHANK2 and SHANK3 but not SHANK1 to BPD.

Treatment-Resistant Human Extraparenchymal Neurocysticercosis: An Immune-Inflammatory Approach to Cysticidal Treatment Outcome.

OBJECTIVE: The aim of this study is to analyze the immune-endocrine profile in neurocysticercosis (NC) patients resistant to cysticidal treatment. METHODS: The inflammatory and regulatory responses of 8 resistant NC patients with extraparenchymal parasites and 5 healthy controls were evaluated through flow cytometry. Serum interleukin levels were measured by ELISA and catecholamines levels by high performance liquid chromatography. RESULTS: Higher percentages of Tr1, CD4+CD25+FOXP3+CD127- and CD4+CD45RO+FOXP3HI were found in NC patients compared with healthy controls, but no difference was found in catecholamine levels. Antigen-specific proliferative immune response was observed in NC patients. Neither anti-inflammatory nor pro-inflammatory cytokines showed differences between patients and controls, but IL-6 levels were lower in treatment-resistant NC patients. In addition, TGFß showed a significant negative correlation with dopamine. CONCLUSIONS: Altogether, these results may point to a modulation of the neuroinflammation in these patients that could indirectly favor cysticercal survival in CNS microenvironment.

Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics.

Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

The clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses.

Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0, TB patients showed increased plasma levels of interleukin-6 (IL-6), C reactive protein, interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-ß). These mediators decreased during treatment, reaching levels similar to those from healthy controls (n = 26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRα/GRß ratio in their peripheral blood mononuclear cells. Furthermore, multivariate analysis showed that cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery.

Immune-Neuro-Endocrine Reflexes, Circuits, and Networks: Physiologic and Evolutionary Implications.

The existence of a network of interactions between the immune and nervous systems that influences host defenses and brain functions is now well-established. Here we discuss how immune and classical neuro/sensorial signals are processed in the brain and how neuro-endocrine immunoregulatory and behavioral responses are integrated. Considering the ability of brain cells to produce cytokines, originally described as immune cell products, we propose that the tripartite synapse plays a central role in the integration of neuro-endocrine-immune interactions. We also propose that the immune-neuro-endocrine responses that influence the course of transmissible and other diseases predisposing to infections can be relevant for evolution, either by restoring health or by mediating an active process of negative selection.

Enfermedad de Crohn fibroestenótica en íleon medio como manifestación inicial de la enfermedad. Reporte de un caso / A Case Report of Fibro-Stenotic Crohn's Disease in the Middle Ileum as the Initial Manifestation

Resumen La enfermedad de Crohn (EC) es una enfermedad inflamatoria intestinal que puede afectar todo el tracto gastrointestinal; el intestino delgado es el segmento afectado en cerca del 50% de los pacientes, en los cuales el íleon terminal es el área más comúnmente comprometida por la enfermedad. Las estenosis intestinales son una complicación frecuente en la EC y aproximadamente 30% a 50% de los pacientes presentan estenosis o lesiones penetrantes al momento del diagnóstico. Las técnicas endoscópicas convencionales no permiten evaluar las lesiones del intestino delgado; es por esto que se desarrollaron técnicas como la enteroscopia y la videocápsula endoscópica, teniendo cada una de ellas sus ventajas e indicaciones. Se presenta un caso de un paciente con EC con fibroestenosis localizada en el íleon medio. No es una localización frecuente para este tipo de lesiones.

Abstract Crohn's disease (CD) is an inflammatory bowel disease that can affect the entire gastrointestinal tract. The small intestine is affected in about 50% of patients among whom the terminal ileum is the area most commonly affected. Intestinal stenosis is a common complication in CD and approximately 30% to 50% of patients present stenosis or penetrating lesions at the time of diagnosis. Because conventional endoscopic techniques do not allow evaluation of small bowel lesions, techniques such as enteroscopy and endoscopic video-capsule were developed. Each has advantages and indications. We present the case of a patient with CD with localized fibrostenosis in the middle ileum which is not a frequent site for this type of lesion.

The sympathetic nervous system affects the susceptibility and course of Trypanosoma cruzi infection.

Trypanosoma cruzi (T. cruzi) is an intracellular parasite that causes Chagas' disease, a major health problem in Latin America. Using a murine model of infection with this parasite, we have previously shown that corticosterone blood levels are markedly elevated during the course of the disease in C57Bl/6 male mice and that this increase is protective for the host by restricting the production of pro-inflammatory cytokines. Since the hypothalamus-pituitary-adrenal (HPA) axis usually operates in a concerted way with the sympathetic nervous system (SNS), we have now studied whether noradrenergic nerves can affect the course of T. cruzi infection and the sexual dimorphism observed in the disease. We found a decreased splenic noradrenaline concentration and content, paralleled by a reduction in noradrenergic nerve fibers in the spleen of infected mice, and increased HPA axis activity. These alterations were more marked in males than in females. When the spontaneous loss of noradrenergic nerve fibers was advanced by chemical sympathectomy prior to infection, males died earlier and mortality significantly increased in females. Chemical denervation did not significantly affect the concentration of specific IgM and IgG2a antibodies to T. cruzi, and did not worsen myocarditis, but resulted in increased parasitemia and IL-6 and IFN-γ blood levels. The results obtained in this model of parasitic disease provide further indications of the relevance of interactions between the immune system and the SNS for host defense.

Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections.