Questions relating to premenstrual asthma

The study of asthma in fertile women needs to consider its potentially recurrent exacerbation in a specific phase of the menstrual cycle. Premenstrual asthma (PMA) refers to the deterioration of asthma in some women of fertile age during the premenstrual phase. Prevalence varies considerably according to studies (11%-47.44%) mainly because there is no standardized definition of the illness. There is a possible link between PMA and premenstrual syndrome, which is a set of physical and psychic manifestations that occur in some fertile women during the same premenstrual phase. This relation has been widely studied but there are still several unknowns. PMA etiopathogeny is not known. It involves possible causes such as hormonal variations in the premenstrual phase, the coexistence of atopy, variations during the cycle in substances related to inflammation, like LTC4 leukotrienes, catecholamines, E2 and F2α prostaglandins and certain cytokines. Also considered are psychological factors related to this phase of the menstrual cycle, a high susceptibility to infection or increased bronchial hyperreactivity prior to menstruation. Yet no factor fully explains its etiology, consequently no specific treatment exists. Researchers have investigated hormones, anti-leukotrienes, prostaglandin synthesis inhibitors, diuretics, phytoestrogens and alternative therapies, but none has been shown to be effective.     

New tools,new tick-borne diseases?

Tick-borne diseases (TBDs) are a major public health concern that has increased in the past three decades. Nevertheless, emerging or reemerging TBDs may be still misdiagnosed. Molecular biology techniques for the screening of ticks, use of “Omics” approaches and the incorporation of analytical methods such as mass spectrometry or nuclear magnetic resonance, to the study of ticks and their associated pathogens or potential pathogens are promising tools for a more accurate differential diagnosis of TBDs. However, this huge amount of data needs to be carefully interpreted before being incorporated to the routine of clinical practice. In the meantime, a clinical approach and high level of suspicion keep being essential for the diagnosis and proper handling of TBDs.     

Fate of meta-analyses: The case of Helicobacter pylori

AIM: To overview the current diversity of meta-analysis and the implementation of their results in international guidelines. METHODS: Relevant meta-analysis were identified from PubMed/Medline. The topics of meta-analyses were determined. Some topics (genetics, extragastric tumors) were analysed separately. Core journals publishing meta-analyses on Helicobacter pylori were ranked. The rate of citation of meta-analysis in major guidelines was calculated. RESULTS: Between 1992 and 2014, some 356 meta-analyses were published on PubMed. These mainly appeared in core journals, but were also found in 128 other journals. Eradicating of the infection was the most addressed topic with 134 articles. Meta-analyses were rarely used in formulating statements and recommendations in the international guidelines. In other topics - genetics, extraintestinal manifestations - meta-analyses were rather overused. CONCLUSION: The implementation of meta-analysis in current guidelines is rather rare, while other topics benefit from many studies. A more extensive use of meta-analyses in evidence-based medicine is recommended in the future, otherwise their continuous proliferation will lose reason and scientific significance.     

Role of cytokines and other factors involved in the Mycobacterium tuberculosis infection

Mycobacterium tuberculosis (Mtb) is a pathogen that is widely distributed geographically and continues to be a major threat to world health. Bacterial virulence factors, nutritional state, host genetic condition and immune response play an important role in the evolution of the infection. The genetically diverse Mtb strains from different lineages have been shown to induce variable immune system response. The modern and ancient lineages strains induce different cytokines patterns. The immunity to Mtb depends on Th1-cell activity [interferon-γ (IFN-γ), interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α)]. IL-1β directly kills Mtb in murine and human macrophages. IL-6 is a requirement in host resistance to Mtb infection. IFN-γ, TNF-α, IL-12 and IL-17 are participants in Mycobacterium-induced granuloma formation. Other regulating proteins as IL-27 and IL-10 can prevent extensive immunopathology. CXCL 8 enhances the capacity of the neutrophil to kill Mtb. CXCL13 and CCL19 have been identified as participants in the formation of granuloma and control the Mtb infection. Treg cells are increased in patients with active tuberculosis (TB) but decrease with anti-TB treatment. The increment of these cells causes down- regulation of adaptive immune response facilitating the persistence of the bacterial infection. Predominance of Th2 phenotype cytokines increases the severity of TB. The evolution of the Mtb infection will depend of the cytokines network and of the influence of other factors aforementioned.     

T3-induced liver AMP-activated protein kinase signaling: Redox dependency and upregulation of downstream targets

AIM: To investigate the redox dependency and promotion of downstream targets in thyroid hormone (T₃)-induced AMP-activated protein kinase (AMPK) signaling as cellular energy sensor to limit metabolic stresses in the liver. METHODS: Fed male Sprague-Dawley rats were given a single ip dose of 0.1 mg T₃/kg or T₃ vehicle (NaOH 0.1 N; controls) and studied at 8 or 24 h after treatment. Separate groups of animals received 500 mg N-acetylcysteine (NAC)/kg or saline ip 30 min prior T₃. Measurements included plasma and liver 8-isoprostane and serum β-hydroxybutyrate levels (ELISA), hepatic levels of mRNAs (qPCR), proteins (Western blot), and phosphorylated AMPK (ELISA). RESULTS: T₃ upregulates AMPK signaling, including the upstream kinases Ca²⁺-calmodulin-dependent protein kinase kinase-β and transforming growth factor-β-activated kinase-1, with T₃-induced reactive oxygen species having a causal role due to its suppression by pretreatment with the antioxidant NAC. Accordingly, AMPK targets acetyl-CoA carboxylase and cyclic AMP response element binding protein are phosphorylated, with the concomitant carnitine palmitoyltransferase-1α (CPT-1α) activation and higher expression of peroxisome proliferator-activated receptor-γ co-activator-1α and that of the fatty acid oxidation (FAO)-related enzymes CPT-1α, acyl-CoA oxidase 1, and acyl-CoA thioesterase 2. Under these conditions, T₃ induced a significant increase in the serum levels of β-hydroxybutyrate, a surrogate marker for hepatic FAO. CONCLUSION: T₃ administration activates liver AMPK signaling in a redox-dependent manner, leading to FAO enhancement as evidenced by the consequent ketogenic response, which may constitute a key molecular mechanism regulating energy dynamics to support T₃ preconditioning against ischemia-reperfusion injury.     

Hematologic manifestations of Helicobacter pylori infection

Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B₁₂ (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.     

Pure motor stroke as the most frequent lacunar syndrome: A clinical update

Pure motor stroke (PMS), also known as pure motor hemiparesis, is the most common of any lacunar form (between one half and two thirds of cases, depending on the series). In an acute stroke registry, 733 patients presented a lacunar infarct and PMS accounted for 12.7% (n = 342) of all first-ever stroke patients and for 48% of all lacunar syndromes. The posterior limb of the internal capsule, corona radiata, and pons are the most frequent brain topographies. Infarcts in the mesencephalus or medullary pyramid have been exceptionally reported. This present update is focused on the clinical evidence and mechanisms underlying the relationship between PMS and different stroke etiologies.     

Medication adherence in schizophrenia

Non-adherence is a major problem in the treatment of schizophrenia. Its high prevalence, potentially severe consequences and associated costs make the study of this phenomenon a priority issue. In this article, basic non-adherence concepts of prevalence, consequences, evaluation methods, methodological restrictions of available studies, risk factors and intervention strategies, are reviewed. Studying non-adherence risk factors is a necessary step toward designing adequately oriented intervention strategies. An operative definition of adherence and good knowledge of its evaluation methods are essential to study this phenomenon. Unfortunately, most available studies contain methodological restrictions, especially concerning the evaluation methods, and an agreed operative definition of adherence has only very recently been reached. Knowing non-adherence risk factors, intervention strategies and available evidence on their effectiveness is essential in making treatment decisions in daily clinical practice.     

Colorectal endoscopic submucosal dissection from a Western perspective: Today’s promises and future challenges

Over the last few years, endoscopic submucosal dissection (ESD) has shown to be effective in the management of early colorectal neoplasms, particularly in Asian countries where the technique was born. In the Western world, its implementation has been slow and laborious. In this paper, the indications for ESD, its learning model, the available methods to predict the presence of deep submucosal invasion before the procedure and the published outcomes from Asia and Europe will be reviewed. Since ESD has several limitations in terms of learning achievement in the West, and completion of the procedure for the first cases is difficult in our part of the world, a short review on colorectal assisted ESD has been included. Finally, other endoscopic and surgical treatment modalities that are in competition with colorectal ESD will be summarized.     

Increased duodenal expression of miR-146a and -155 in pediatric Crohn’s disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast cells. METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well. RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of miR-122. CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs.