A Rare Case of Phytobezoar Related to Occupational Exposure.

Bezoars constitute a compacted collection of undigested or partially digested material, potentially leading to intestinal obstruction. They most frequently occur in the stomach, with classification based on their composition. Many gastric bezoars are asymptomatic and frequently manifest in patients with gastrointestinal disturbances or psychiatric issues.  We present a rare case of a bezoar related to occupational exposure that illustrates the least-discussed health risks associated with certain jobs.

Association between self-reported drug hypersensitivity reactions and psychological disorders.

Background: Medically unexplained physical symptoms are a well-recognized problem and, in some cases, there is a well-established relationship between behavior and psychopathological disturbances. However, the association between drug hypersensitivity reactions and psychoactive disorders stills under discussion. Objective: Our main goal was to establish if there is an association between self-reported drug hypersensitivity reaction and psychopathology with need for psychoactive drug consumption. Methods: Retrospective study of adult patients evaluated in a first Immunoallergology appointment because of self-reported drug hypersensitivity over 1 year and register of data concerning psychoactive drugs use. Compare the study group with patients observed for allergic respiratory disease along the same year. Results: The study group included 70 patients that referred a total of 92 self-reported drug hypersensitivity reactions. Twenty-nine (41.4%) were under treatment with psychoactive drugs: 20 (70%) were treated with anxiolytics, 13 (18.6%) with antidepressants, 15 (21.4%) with sedatives, and 1 (1.4%) with antipsychotics. The control group included 160 patients and 38 patients (23.8%) were under treatment with psychoactive drugs: 31 (19.4%) where treated with antidepressants, 29 (18.1%) with anxiolytics, and 3 (1.9%) with sedatives. The use of psychoactive drugs in the study group is higher than in the control group (p = 0.007), the difference is especially important for sedative drugs (p < 0.001). Besides a higher use of psychoactive drugs, the study group also has a higher frequency of use of several psychoactive drug (p = 0.002). Conclusion: Patients with a self-report drug hypersensitivity have more tendency to be under treatment with psychoactive drugs and could have more tendency to somatization. Personality traces and psychopathology must be taken into account during an allergy workup.

Publisher Correction: Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Host-pathogen systems for early drug discovery against tuberculosis.

Tuberculosis (TB) is a global disease causing 1.8 million deaths each year. The appearance of drug-resistant strains raised the demand for new anti-mycobacterial drugs and therapies, because previously discovered antibiotics are shown to be inefficient. Moreover, the number of newly discovered drugs is not increasing in proportion to the emergence of drug resistance, which suggests that more optimized methodology and screening procedures are required including the incorporation of in vivo properties of TB infection. A way to improve efficacy of screening approaches is by introducing the use of different host-pathogen systems into primary screenings. These include whole cell-based screenings, zebrafish larvae-based screenings and the impact of artificial granuloma research on the drug discovery process. This review highlights current screening attempts and the identified molecular targets and summarizes findings of alternative, not fully explored host-pathogen systems for the characterization of anti-mycobacterial compounds.

Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling.

Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS) protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH), which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive.

Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles.

Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered "booster" molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster. The efficacy of the designed formulations was evaluated in TB infected macrophages using an automated confocal high-content screening platform, showing that the drugs maintained their activity after incorporation in NPs. Among tested formulations, "green" ß-cyclodextrin (pCD) based NPs displayed the best physico-chemical characteristics and were selected for in vivo studies. The NPs suspension, administered directly into mouse lungs using a Microsprayer®, was proved to be well-tolerated and led to a 3-log decrease of the pulmonary mycobacterial load after 6 administrations as compared to untreated mice. This study paves the way for a future use of pCD NPs for the pulmonary delivery of the [ETH:Booster] pair in TB chemotherapy.

Clofazimine encapsulation in nanoporous silica particles for the oral treatment of antibiotic-resistant Mycobacterium tuberculosis infections.

AIM: First extensive reformulation of clofazimine (CLZ) in nanoporous silica particles (NSPs) for tackling antibiotic-resistant tuberculosis (TB) infections. MATERIALS & METHODS: Solid-state characterization of several CLZ-encapsulated NSP formulations was followed by in vitro drug solubility, Caco-2 intestinal cells drug permeability and TB antibacterial activity. RESULTS: NSPs stabilize the amorphous state of CLZ (shelf stability >6 months) and dramatically increase the drug solubility in simulated gastric fluid (up to 20-fold) with different dissolution kinetics depending on the NSPs used. CLZ encapsulation in NSP substantially enhances the permeation through model intestinal cell layer, achieving effective antimicrobial concentrations in TB-infected macrophages. CONCLUSION: Promising results toward refurbishment of an approved marketed drug for a different indication suitable for oral anti-TB formulation.

How can nanoparticles contribute to antituberculosis therapy?

Therapeutic approaches using nanoparticles are being successfully used in foods and in several fields of medicine, including infectious diseases. Regarding tuberculosis (TB) treatment, nanoparticles can be a useful strategy for two distinct applications: (i) for their intrinsic antimycobacterial activity; (ii) as vehicles for known antitubercular drugs to allow reduction of dose- and drug-associated side-effects and administration via user-friendly administration routes such as pulmonary or oral ones. Promising results were obtained in vitro and in animal Mycobacterium tuberculosis models and need now to be translated into clinical drug candidates. Such a prospect can provide an opportunity regarding the current limited therapeutic options for drug-resistant TB and the scarcity of novel antituberculosis drugs in the drug discovery pipeline.