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Journal of Visceral Surgery Sep 2015Microbial contamination of the liver parenchyma leading to hepatic abscess (HA) can occur via the bile ducts or vessels (arterial or portal) or directly, by contiguity.... (Review)
Review
Microbial contamination of the liver parenchyma leading to hepatic abscess (HA) can occur via the bile ducts or vessels (arterial or portal) or directly, by contiguity. Infection is usually bacterial, sometimes parasitic, or very rarely fungal. In the Western world, bacterial (pyogenic) HA is most prevalent; the mortality is high approaching 15%, due mostly to patient debilitation and persistence of the underlying cause. In South-East Asia and Africa, amebic infection is the most frequent cause. The etiologies of HA are multiple including lithiasic biliary disease (cholecystitis, cholangitis), intra-abdominal collections (appendicitis, sigmoid diverticulitis, Crohn's disease), and bile duct ischemia secondary to pancreatoduodenectomy, liver transplantation, interventional techniques (radio-frequency ablation, intra-arterial chemo-embolization), and/or liver trauma. More rarely, HA occurs in the wake of septicemia either on healthy or preexisting liver diseases (biliary cysts, hydatid cyst, cystic or necrotic metastases). The incidence of HA secondary to Klebsiella pneumoniae is increasing and can give rise to other distant septic metastases. The diagnosis of HA depends mainly on imaging (sonography and/or CT scan), with confirmation by needle aspiration for bacteriology studies. The therapeutic strategy consists of bactericidal antibiotics, adapted to the germs, sometimes in combination with percutaneous or surgical drainage, and control of the primary source. The presence of bile in the aspirate or drainage fluid attests to communication with the biliary tree and calls for biliary MRI looking for obstruction. When faced with HA, the attending physician should seek advice from a multi-specialty team including an interventional radiologist, a hepatobiliary surgeon and an infectious disease specialist. This should help to determine the origin and mechanisms responsible for the abscess, and to then propose the best appropriate treatment. The presence of chronic enteric biliary contamination (i.e., sphincterotomy, bilio-enterostomy) should be determined before performing radio-frequency ablation and/or chemo-embolization; substantial stenosis of the celiac trunk should be detected before performing pancreatoduodenectomy to help avoid iatrogenic HA.
Topics: Anti-Bacterial Agents; Catheter Ablation; Chemoembolization, Therapeutic; Combined Modality Therapy; Drainage; Humans; Liver Abscess
PubMed: 25770745
DOI: 10.1016/j.jviscsurg.2015.01.013 -
Acta Neuropathologica Jan 2010Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential... (Review)
Review
Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.
Topics: Animals; Astrocytes; Central Nervous System; Central Nervous System Diseases; Humans; Models, Neurological
PubMed: 20012068
DOI: 10.1007/s00401-009-0619-8 -
Nature Reviews. Gastroenterology &... Jan 2017A fundamental function of the intestinal epithelium is to act as a barrier that limits interactions between luminal contents such as the intestinal microbiota, the... (Review)
Review
A fundamental function of the intestinal epithelium is to act as a barrier that limits interactions between luminal contents such as the intestinal microbiota, the underlying immune system and the remainder of the body, while supporting vectorial transport of nutrients, water and waste products. Epithelial barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. Compromised intestinal barrier function has been associated with a number of disease states, both intestinal and systemic. Unfortunately, most current clinical data are correlative, making it difficult to separate cause from effect in interpreting the importance of barrier loss. Some data from experimental animal models suggest that compromised epithelial integrity might have a pathogenic role in specific gastrointestinal diseases, but no FDA-approved agents that target the epithelial barrier are presently available. To develop such therapies, a deeper understanding of both disease pathogenesis and mechanisms of barrier regulation must be reached. Here, we review and discuss mechanisms of intestinal barrier loss and the role of intestinal epithelial barrier function in pathogenesis of both intestinal and systemic diseases. We conclude with a discussion of potential strategies to restore the epithelial barrier.
Topics: Animals; Celiac Disease; Diabetes Mellitus, Type 1; Graft vs Host Disease; Homeostasis; Humans; Inflammatory Bowel Diseases; Intercellular Junctions; Intestinal Mucosa; Permeability
PubMed: 27848962
DOI: 10.1038/nrgastro.2016.169 -
Frontiers in Immunology 2014As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and... (Review)
Review
As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and plasticity are hallmarks of macrophages. Classical M1 and alternative M2 activation of macrophages, mirroring the Th1-Th2 polarization of T cells, represent two extremes of a dynamic changing state of macrophage activation. M1-type macrophages release cytokines that inhibit the proliferation of surrounding cells and damage contiguous tissue, and M2-type macrophages release cytokines that promote the proliferation of contiguous cells and tissue repair. M1-M2 polarization of macrophage is a tightly controlled process entailing a set of signaling pathways, transcriptional and posttranscriptional regulatory networks. An imbalance of macrophage M1-M2 polarization is often associated with various diseases or inflammatory conditions. Therefore, identification of the molecules associated with the dynamic changes of macrophage polarization and understanding their interactions is crucial for elucidating the molecular basis of disease progression and designing novel macrophage-mediated therapeutic strategies.
PubMed: 25506346
DOI: 10.3389/fimmu.2014.00614 -
Microbiology Spectrum Nov 2016Many Fungi have a well-developed secondary metabolism. The diversity of fungal species and the diversification of biosynthetic gene clusters underscores a nearly... (Review)
Review
Many Fungi have a well-developed secondary metabolism. The diversity of fungal species and the diversification of biosynthetic gene clusters underscores a nearly limitless potential for metabolic variation and an untapped resource for drug discovery and synthetic biology. Much of the ecological success of the filamentous fungi in colonizing the planet is owed to their ability to deploy their secondary metabolites in concert with their penetrative and absorptive mode of life. Fungal secondary metabolites exhibit biological activities that have been developed into life-saving medicines and agrochemicals. Toxic metabolites, known as mycotoxins, contaminate human and livestock food and indoor environments. Secondary metabolites are determinants of fungal diseases of humans, animals, and plants. Secondary metabolites exhibit a staggering variation in chemical structures and biological activities, yet their biosynthetic pathways share a number of key characteristics. The genes encoding cooperative steps of a biosynthetic pathway tend to be located contiguously on the chromosome in coregulated gene clusters. Advances in genome sequencing, computational tools, and analytical chemistry are enabling the rapid connection of gene clusters with their metabolic products. At least three fungal drug precursors, penicillin K and V, mycophenolic acid, and pleuromutilin, have been produced by synthetic reconstruction and expression of respective gene clusters in heterologous hosts. This review summarizes general aspects of fungal secondary metabolism and recent developments in our understanding of how and why fungi make secondary metabolites, how these molecules are produced, and how their biosynthetic genes are distributed across the Fungi. The breadth of fungal secondary metabolite diversity is highlighted by recent information on the biosynthesis of important fungus-derived metabolites that have contributed to human health and agriculture and that have negatively impacted crops, food distribution, and human environments.
Topics: Biosynthetic Pathways; Diterpenes; Fungi; Genome, Fungal; Humans; Mycophenolic Acid; Mycotoxins; Polycyclic Compounds; Secondary Metabolism; Synthetic Biology; Pleuromutilins
PubMed: 27809954
DOI: 10.1128/microbiolspec.FUNK-0009-2016 -
Respiratory Medicine Aug 2018Both asthma and rhinosinusitis are complex and heterogeneous diseases and, importantly, they often coexist: these diseases can be concomitant in 35-65% of affected... (Review)
Review
Both asthma and rhinosinusitis are complex and heterogeneous diseases and, importantly, they often coexist: these diseases can be concomitant in 35-65% of affected children, according to different studies. Thus, evaluating this comorbidity in the clinical practice should be paramount. In this review, we focused our discussion on the multiple pathophysiological aspects that may link rhinosinusitis and asthma in the pediatric population. Although rhinosinusitis may exacerbate asthma through several mechanisms occurring by contiguity, actually this aspect seems to be only one component of the complex interplay between upper and lower airways. In particular, the onset of an important and persistent Th2-driven inflammatory process dominated by eosinophils presence at one site of the airways, may release into the bloodstream several cytokines; in their turn, those can lead to the stimulation of the bone marrow, which may function as a systemic amplifier of such an eosinophilic inflammation.
Topics: Asthma; Child; Comorbidity; Eosinophils; Female; Humans; Male; Rhinitis; Sinusitis; Th2 Cells
PubMed: 30053979
DOI: 10.1016/j.rmed.2018.06.016 -
Orphanet Journal of Rare Diseases Jul 2014Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a rare, mild inflammatory pulmonary disorder that occurs almost exclusively in current or... (Review)
Review
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a rare, mild inflammatory pulmonary disorder that occurs almost exclusively in current or former heavy smokers, usually between the third and sixth decades, most likely with no gender predilection. The onset is usually insidious with exertional dyspnea and persistent cough, which may be non-productive, developing over a course of weeks or months. RB-ILD may also be diagnosed in asymptomatic patients with functional impairment and chest radiograph or high-resolution computed tomography (HRCT) abnormalities. Histologically, RB-ILD is characterized by the accumulation of yellow-brown pigmented macrophages within the lumens of respiratory bronchioles and alveolar ducts, associated with a patchy submucosal and peribronchiolar chronic inflammation. Common findings also include mild bronchiolar and peribronchiolar alveolar fibrosis that expands contiguous alveolar septa and leads to architectural distortion as well as centrilobular emphysema. Chest radiographs in patients with RB-ILD typically show fine reticulonodular interstitial opacities, while on HRCT central and peripheral bronchial wall thickening, centrilobular nodules, and ground-glass opacities associated with upper lobe centrilobular emphysema are most frequently reported. Pulmonary function testing may be normal but usually demonstrates mixed, predominantly obstructive abnormalities, often combined with hyperinflation and usually associated with a mild to moderate reduction in carbon monoxide diffusion capacity (DLco). The course of RB-ILD is heterogeneous. Some patients respond favorably to corticosteroids and/or smoking cessation, but often there is no functional improvement and the disease progresses despite smoking cessation and treatment.
Topics: Biopsy; Bronchiolitis; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; Humans; Lung Diseases, Interstitial; Prognosis
PubMed: 25011486
DOI: 10.1186/s13023-014-0106-8 -
Microorganisms May 2022Osteomyelitis is an infection of the bone characterized by progressive inflammatory destruction and apposition of new bone that can spread via the hematogenous route... (Review)
Review
Osteomyelitis is an infection of the bone characterized by progressive inflammatory destruction and apposition of new bone that can spread via the hematogenous route (hematogenous osteomyelitis (HO)), contiguous spread (contiguous osteomyelitis (CO)), and direct inoculation (osteomyelitis associated with peripheral vascular insufficiency (PVI)). Given the significant financial burden posed by osteomyelitis patient management, the development of new preventive and treatment methods is warranted. To achieve this objective, implementing animal models (AMs) of infection such as rats, mice, rabbits, avians, dogs, sheep, goats, and pigs might be of the essence. This review provides a literature analysis of the AMs developed and used to study osteomyelitis. Historical relevance and clinical applicability were taken into account to choose the best AMs, and some study methods are briefly described. Furthermore, the most significant strengths and limitations of each species as AM are discussed, as no single model incorporates all features of osteomyelitis. HO's clinical manifestation results in extreme variability between patients due to multiple variables (e.g., age, sex, route of infection, anatomical location, and concomitant diseases) that could alter clinical studies. However, these variables can be controlled and tested through different animal models.
PubMed: 35744653
DOI: 10.3390/microorganisms10061135 -
Journal of Medical Genetics Sep 1999We have reviewed published reports on patients with segmental aneusomy for chromosome 1p36 to help geneticists and other health professionals in the recognition of this... (Review)
Review
We have reviewed published reports on patients with segmental aneusomy for chromosome 1p36 to help geneticists and other health professionals in the recognition of this emerging chromosomal syndrome. Terminal deletions of the short arm of chromosome 1 are associated with hypotonia and developmental delay (usually severe), growth abnormalities (growth retardation, microcephaly, obesity), and craniofacial dysmorphism with a large anterior fontanelle, prominent forehead, deep set eyes, flat nasal bridge and midface hypoplasia, ear asymmetry, a pointed chin, and orofacial clefting. Minor cardiac malformations, cardiomyopathy, seizures, and ventricular dilatation are the more common additional findings. Sensorineural hearing loss and variable ophthalmological anomalies have also been frequently observed. Although the deletions can be detected by high resolution cytogenetic studies, confirmation by fluorescence in situ hybridisation is required in most cases. The majority of deletions are maternally derived. Molecular characterisation of 1p36 deletions has been undertaken in several cases, and it is likely that this condition is a contiguous gene deletion syndrome.
Topics: Adolescent; Adult; Child; Child, Preschool; Chromosome Aberrations; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 1; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Syndrome
PubMed: 10507720
DOI: No ID Found