Emerging therapeutic options in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.     

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System

Antiretroviral therapy (ART) has transformed HIV into a chronic condition, lengthening and improving the lives of individuals living with this virus. Despite successful suppression of HIV replication, people living with HIV (PLWH) are susceptible to a growing number of comorbidities, including neuroHIV that results from infection of the central nervous system (CNS). Alterations in the dopaminergic system have long been associated with HIV infection of the CNS. Studies indicate that changes in dopamine concentrations not only alter neurotransmission, but also significantly impact the function of immune cells, contributing to neuroinflammation and neuronal dysfunction. Monocytes/macrophages, which are a major target for HIV in the CNS, are responsive to dopamine. Therefore, defining more precisely the mechanisms by which dopamine acts on these cells, and the changes in cellular function elicited by this neurotransmitter are necessary to develop therapeutic strategies to treat neuroHIV. This is especially important for vulnerable populations of PLWH with chemically altered dopamine concentrations, such as individuals with substance use disorder (SUD), or aging individuals using dopamine-altering medications. The specific neuropathologic and neurocognitive consequences of increased CNS dopamine remain unclear. This is due to the complex nature of HIV neuropathogenesis, and logistical and technical challenges that contribute to inconsistencies among cohort studies, animal models and in vitro studies, as well as lack of demographic data and access to human CNS samples and cells. This review summarizes current understanding of the impact of dopamine on HIV neuropathogenesis, and proposes new experimental approaches to examine the role of dopamine in CNS HIV infection.

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System. Both substance abuse disorders and the use of dopaminergic medications for age-related diseases are associated with changes in CNS dopamine concentrations and dopaminergic neurotransmission. These changes can lead to aberrant immune function, particularly in myeloid cells, which contributes to the neuroinflammation, neuropathology and dysfunctional neurotransmission observed in dopamine-rich regions in HIV+ individuals. These changes, which are seen despite the use antiretroviral therapy (ART), in turn lead to further dysregulation of the dopamine system. Thus, in individuals with elevated dopamine, the bi-directional interaction between aberrant dopaminergic neurotransmission and HIV infection creates a feedback loop contributing to HIV associated neurocognitive dysfunction and neuroHIV. However, the distinct contributions and interactions made by HIV infection, inflammatory mediators, ART, drugs of abuse, and age-related therapeutics are poorly understood. Defining more precisely the mechanisms by which these factors influence the development of neurological disease is critical to addressing the continued presence of neuroHIV in vulnerable populations, such as HIV-infected older adults or drug abusers. Due to the complexity of this system, understanding these effects will require a combination of novel experimental modalities in the context of ART. These will include more rigorous epidemiological studies, relevant animal models, and in vitro cellular and molecular mechanistic analysis.

     

Serodiagnosis of invasive amebiasis using a recombinant Entamoeba histolytica protein

One hundred eight serum samples from 106 patients were examined by Western blot analysis for the presence of antibodies to a recombinant fusion protein containing the sequence of the newly described serine-rich Entamoeba histolytica protein (SREHP). Among patients with invasive amebiasis from Durban, Republic of South Africa; San Diego, Calif; Mexico City, Mexico; and St Louis, Mo, 53 (82%) of 65 had antibodies to SREHP. In contrast, only one patient (2%) of 43 without acute invasive amebiasis had antibodies to SREHP. The predictive value of a positive test for anti-SREHP antibodies in the detection of acute invasive amebiasis was most marked when analyzed in the patients from Durban, where 11 (92%) of 12 patients who were seropositive for SREHP had acute invasive amebiasis vs 17 (65%) of 26 patients who had a positive serologic diagnosis as determined by agar gel diffusion. The use of a serologic test based on the recombinant SREHP fusion protein may be a useful adjunct to the diagnosis of acute invasive amebiasis in endemic regions.     

The role of somatic complaints in the diagnosis of depression in children and adolescents

The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety.     

Surface behavior of axolemma monolayers: Physico-chemical characterization and use as supported planar membranes for cultured Schwann cells

The axolemma membrane forms a stable and reproducible monomolecular layer at the air-aqueous interface. The major lipids and proteins are present in this monolayer in molar ratios similar to the original membrane. Acetylcholinesterase and Na-K-ATPase activities are preserved in the monolayer to levels of 64% and 25%, respectively. The total lipid fraction forms a homogeneously mixed phase. The presence of proteins in the monolayer introduces surface inhomogeneties. Among other features, this is revealed by the presence of two values of lateral pressure at which the monolayer shows partial or total collapse: a broad partial collapse at surface pressures between 13 to 30 mN/m and a sharp collapse point at 46 mN/m. The average molecular areas, the broad collapse point, and the variation of the surface potential per molecule suggest the relocation of protein components at surface pressures between 13 to 30 mN/m. The behavior is consistent with the extrusion and exposure of proteins toward the aqueous medium that depends on the lateral pressure. Schwann cells grown on coverslips coated with axolemma monolayers at 13 mN/m (beginning of the broad collapse) and 34 mN/m (above the broad collapse) recognize the difference in the surface organization of axolemma caused by the lateral pressure which affects their proliferation, morphology, and spatial pattern of organization. Our results show for the first time that response of Schwann cells depends on the intermolecular organization of the axolemma surface with which they interact. These results suggest that the local expression of putative surface molecules of axolemma that may mediate membrane recognition and the signalling of morphological and proliferative changes can be modulated by long range supramolecular properties. © 1993 Wiley-Liss, Inc.     

INFLUENCE OF IODOFORM ON ANTIMICROBIAL POTENTIAL OF CALCIUM HYDROXIDE

The purpose of this research was to verify the influence of Iodoform on antimicrobial potential of calcium hydroxide. S. aureus, E. faecalis, P. aeruginosa, B. subtilis, C. albicans were the biological indicators. The substances tested were: calcium hydroxide + saline; calcium hydroxide + Iodoform + saline; Iodoform + saline. For the agar diffusion test, 18 Petri plates with 20 ml of BHI agar were inoculated with the microbial suspensions. Fifty-four cavities were made and filled with the substances tested. The diameters of microbial inhibition were then measured. In direct exposure test, 162 #50 sterile absorbent paper points were immersed in the experimental suspensions for 5 min, and covered with the pastes. At intervals of 24, 48 and 72 hours, the paper points were immersed in 10 ml of Letheen Broth, followed by incubation at 37°°C for 48h. Microbial growth was evaluated by turbidity of the culture medium. A 0.1 ml inoculum obtained from the Letheen Broth was transferred to 7 ml of BHI, and incubated at 37°°C for 48h. Bacterial growth was again evaluated by turbidity of the culture medium. The calcium hydroxide associated with the saline or the iodoform plus saline showed antimicrobial effectiveness in both experimental methods. The iodoform paste presented antimicrobial ineffectiveness for the agar diffusion test on all biological microorganisms and for the direct exposure test on B. subtilis and on the mixture.     

Risk factors for surgical site infection in children.

OBJECTIVES: To assess the appropriateness of using the indices developed by the Study on the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infections Surveillance (NNIS) project to determine risk factors for surgical site infection (SSI) in children and, if not appropriate, to explore the factors related to SSI in children so these factors could be used in a risk index for pediatric patients. DESIGN: Cohort study during more than 4 years. SETTING: La Paz University Hospital, a national reference center that serves Health Area 5 of Madrid, Spain, which has approximately 500,000 inhabitants. PATIENTS: Convenience sample consisting of the 3,646 children admitted for surgery who had a postsurgical stay of more than 2 days. RESULTS: A model with 8 predictive factors (degree of surgical contamination; duration of surgery; type of surgery; use of a peripheral venous catheter, central venous catheter, or urinary catheter; number of diagnoses; and SSI exposition time) was created. Its relation to the SSI rate was better than that of the SENIC or NNIS indices. Its sensitivity, specificity, and area under the receiver-operating characteristic curve were higher than that of the SENIC index. CONCLUSIONS: The model that we created seems to be more adequate for predicting SSI and evaluating pediatric patients' intrinsic risk than the SENIC and NNIS indices.