scholarly journals Podocytopathies

2020 ◽  
Vol 148 (9-10) ◽  
pp. 631-636
Author(s):  
Amira Peco-Antic ◽  
Bilsana Mulic
Keyword(s):  
Therapeutic Strategy ◽  
Morphological Changes ◽  
Wide Spectrum ◽  
Diffuse Mesangial Sclerosis ◽  
Glomerular Diseases ◽  
Urine Biomarkers ◽  
Collapsing Glomerulopathy ◽  
Cytoplasmic Proteins ◽  
Pharmacological Blockade ◽  
Injurious Stimulus

Podocytopathies include a wide spectrum of primary or secondary glomerular diseases that are the consequence of the podocyte injuries. The damage of podocytes can occur due to congenital or acquired disorders of podocyte transcriptional regulators, altered components of the slit diaphragm complex, abnormal assembly, or function of the actin-based cytoskeleton, dysfunction of membranes or cytoplasmic proteins, and mitochondrial injury. Podocytes reactions to injurious stimulus include FP effacement, apoptosis, and loss of podocyte, developmental arrest associated by mild proliferative activity, and dedifferentiation with moderated proliferation. Based on histopathological findings, podocytopathy may be diagnosed such as minimal change nephropathy; focal segmental glomerulosclerosis, diffuse mesangial sclerosis, or collapsing glomerulopathy while in relation to their etiology can be categorized as idiopathic, genetic, and reactive. Podocytopathies may be diagnosed due to podocyte morphological changes, immunohistochemistry, circulating and urine biomarkers, and genetic analysis. The primary clinical focus in prevention should be to reduce the factors that can damage the podocytes and cause hyperperfusion/hypertrophy of the glomerulus. Nowadays, control of systemic and intra glomerular hypertension by pharmacological blockade of angiotensin II is a central in the prevention strategy, while regeneration of podocytes by stem cells is therapeutic strategy of the future.

Advances in the Biology and Genetics of the Podocytopathies: Implications for Diagnosis and Therapy

2009 ◽  
Vol 133 (2) ◽  
pp. 201-216 ◽  
Author(s):  
Laura Barisoni ◽  
H. William Schnaper ◽  
Jeffrey B. Kopp
Keyword(s):  
Current Knowledge ◽  
Diffuse Mesangial Sclerosis ◽  
Therapeutic Approaches ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Collapsing Glomerulopathy ◽  
Novel Approach ◽  
Genes Encoding ◽  
Glomerular Morphology

AbstractContext.—Etiologic factors and pathways leading to altered podocyte phenotype are clearly numerous and involve the activity of different cellular function.Objective.—To focus on recent discoveries in podocyte biology and genetics and their relevance to these human glomerular diseases, named podocytopathies.Data Sources.—Genetic mutations in genes encoding for proteins in the nucleus, slit diaphragm, podocyte cytoplasm, and cell membrane are responsible for podocyte phenotype and functional abnormalities. Podocyte injury may also derive from secondary stimuli, such as mechanical stress, infections, or use of certain medications. Podocytes can respond to injury in a limited number of ways, which include (1) effacement, (2) apoptosis, (3) arrest of development, and (4) dedifferentiation. Each of these pathways results in a specific glomerular morphology: minimal change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy.Conclusions.—Based on current knowledge of podocyte biology, we organized etiologic factors and morphologic features in a taxonomy of podocytopathies, which provides a novel approach to the classification of these diseases. Current and experimental therapeutic approaches are also discussed.

scholarly journals Complement and Complement Targeting Therapies in Glomerular Diseases

2019 ◽  
Vol 20 (24) ◽  
pp. 6336 ◽  
Author(s):  
Sofia Andrighetto ◽  
Jeremy Leventhal ◽  
Gianluigi Zaza ◽  
Paolo Cravedi
Keyword(s):  
Complement Activation ◽  
Innate Immune System ◽  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Wide Spectrum ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Innate Immune ◽  
Glomerular Injury ◽  
Glomerular Diseases ◽  
Uremic Syndrome

The complement cascade is part of the innate immune system whose actions protect hosts from pathogens. Recent research shows complement involvement in a wide spectrum of renal disease pathogenesis including antibody-related glomerulopathies and non-antibody-mediated kidney diseases, such as C3 glomerular disease, atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. A pivotal role in renal pathogenesis makes targeting complement activation an attractive therapeutic strategy. Over the last decade, a growing number of anti-complement agents have been developed; some are approved for clinical use and many others are in the pipeline. Herein, we review the pathways of complement activation and regulation, illustrate its role instigating or amplifying glomerular injury, and discuss the most promising novel complement-targeting therapies.

scholarly journals The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 403 ◽  
Author(s):  
Neil Chernoff ◽  
Donna Hill ◽  
Johnsie Lang ◽  
Judy Schmid ◽  
Thao Le ◽  
...  
Keyword(s):  
Algal Blooms ◽  
Morphological Changes ◽  
Wide Spectrum ◽  
Serum Levels ◽  
Serum Glucose ◽  
Oral Exposure ◽  
Clinical Effects ◽  
Clinical Changes ◽  
Induced Changes ◽  
Dose Response Study

Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice. In a preliminary MCLR dose–response study of 3 to 9 mg/kg doses, ≥5 mg/kg induced clinical changes, increased serum levels of ALT, AST, and GLDH, liver congestion, increased liver/body weight ratios, and reduced serum glucose and total protein. Based on the extent of these effects, the 10 congeners were administered as single 7 mg/kg oral doses and toxicity evaluated. The greatest toxicity was observed with MCLA and MCLR including a high percentage of moribundity. In addition to eliciting effects similar to those listed above for MCLR, MCLA also induced serum alterations indicative of jaundice. MCLY, and MCYR induced changes like those noted with MCLR, but to lesser extents. MCLW and MCLF exhibited some serum and morphological changes associated with hepatic toxicity, while there were few indications of toxicity after exposures to MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, or MCWR. These data illustrate a wide spectrum of hepatic effects and different potencies of these MC congeners.

scholarly journals Combating Pathogenic Microorganisms Using Plant-Derived Antimicrobials: A Minireview of the Mechanistic Basis

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Abhinav Upadhyay ◽  
Indu Upadhyaya ◽  
Anup Kollanoor-Johny ◽  
Kumar Venkitanarayanan
Keyword(s):  
Plant Extracts ◽  
Pathogenic Bacteria ◽  
Therapeutic Strategy ◽  
Wide Spectrum ◽  
Potential Effect ◽  
Pathogenic Microorganisms ◽  
Active Components ◽  
Natural Remedy ◽  
Microbial Infections ◽  
Mechanistic Basis

The emergence of antibiotic resistance in pathogenic bacteria has led to renewed interest in exploring the potential of plant-derived antimicrobials (PDAs) as an alternative therapeutic strategy to combat microbial infections. Historically, plant extracts have been used as a safe, effective, and natural remedy for ailments and diseases in traditional medicine. Extensive research in the last two decades has identified a plethora of PDAs with a wide spectrum of activity against a variety of fungal and bacterial pathogens causing infections in humans and animals. Active components of many plant extracts have been characterized and are commercially available; however, research delineating the mechanistic basis of their antimicrobial action is scanty. This review highlights the potential of various plant-derived compounds to control pathogenic bacteria, especially the diverse effects exerted by plant compounds on various virulence factors that are critical for pathogenicity inside the host. In addition, the potential effect of PDAs on gut microbiota is discussed.

scholarly journals A Pattern of Glomerular Diseases in Egyptian Children: A Single-center Experience

2021 ◽  
Vol 9 (B) ◽  
pp. 1305-1312
Author(s):  
Hoda Atef Abdelsattar Ibrahim ◽  
Aya Amin ◽  
Ahmed Zeid ◽  
Samar Sabry ◽  
Hesham Safouh
Keyword(s):  
Nephrotic Syndrome ◽  
Iga Nephropathy ◽  
Glomerular Disease ◽  
Diffuse Mesangial Sclerosis ◽  
Gross Hematuria ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Study Results ◽  
Egyptian Children ◽  
Membranous Gn

BACKGROUND: Findings indicative of the glomerular disease are proteinuria, hematuria, nephrotic syndrome (NS), hypertension, and renal insufficiency. These presentations can be used to define different clinical patterns that resemble different underlying etiologies. METHODS: This study is a cross-sectional study enrolled in Children Hospital Cairo University. The study participants were recruited on two stages, retrospective and prospective stages. In the retrospective stage, all eligible patients across 5 years (between 2011 and 2015) with any glomerular disease were included in the study. In addition, prospectively, the new cases a long 6 months (from February 2016 till July 2016) with glomerular diseases were included in the study. RESULTS: A total of 594 cases with different glomerular diseases were identified. Cases were two groups: The retrospective group that involved 543 cases and the prospective group that included 51 cases. In the retrospective part of the study, the most common presentations were NS (68%), nephritis (16.4%), gross hematuria (10.5%), and nephrotic/nephritic syndrome (3.5%). The most common biopsies in the retrospective study were NS: MCNS (27.3%), NS: focal segmental glomerulosclerosis (FSGS) (23.4%), NS: Mesangioproliferative GN (9.4%), NS: Membranous GN (2.3%), Crescentric GN (3.9%), Membranous GN (0.8%), MPGN (0.8%), congenital nephrotic syndrome (CNS):Diffuse Mesangial Sclerosis (3.9%), CNS: Finnish type (2.3%), Alport (4.7%), IgA nephropathy (3.9%), IgM nephropathy (1.6%), lupus nephritis (LN) (3.1%), Thin basement membrane disease (3.1%), and others (9.4%) In the prospective study, the most common presentations were NS (76.5%), nephritis (11.8%), nephrotic/nephritic syndrome (7.8%), and gross hematuria (3.9%). The biopsies results were mainly NS: FSGS (33.3%) and NS: MCNS (33.3%). Other biopsies results in the prospective part were NS: Mesangioproliferative GN (16.7%), LN (8.3%), and IgA nephropathy (8.3%). CONCLUSION: The most common glomerular disease in childhood is NS. The most common pathology of glomerular diseases is minimal change NS.

scholarly journals CoViD-19: An early intervention therapeutic strategy to prevent developing a severe disease as an alternative approach to control the pandemic

2020 ◽  
Author(s):  
HAMID MERCHANT
Keyword(s):  
Early Intervention ◽  
Respiratory Tract ◽  
Therapeutic Strategy ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Antimicrobial Properties ◽  
The Body ◽  
Upper Respiratory Tract ◽  
Holistic Treatment ◽  
Upper Respiratory

While we wait for a confirmed drug or a vaccine for CoViD-19, it may be possible to intervene early to prevent the virus causing a severe disease to offer an alternative therapeutic strategy to control the pandemic. The global burden of CoViD-19 on the healthcare system can be significantly reduced by targeting CoViD-19 patients with or without symptoms who are self-isolating at home or in quarantine. If any therapeutic support can be offered to this group of patients that could attenuate the virus within the upper respiratory tract during the early stages of CoViD-19, it can give the body the time to produce enough antibodies to recover naturally from the disease before progressing into severe disease. An early intervention can, therefore, prevent the virus to get down the lower respiratory tract, reduce the number of cases with severe disease involving pneumonia and the need for hospitalisation. This article presents a simple yet holistic treatment strategy that involves inhaling steam supplemented with essential oils possessing wide spectrum antimicrobial properties in conjunction with oropharyngeal sanitisation to all those who are CoViD-19 positive or are under self-isolation due to symptoms. The approach is very simple, cheap, and effective in relieving the symptoms of the disease and is likely to reduce the viral load in the upper respiratory tract that may help recover from the infection. Since there is no vaccine or treatment yet approved to prevent or treat the CoViD-19, the importance of early intervention is invaluable in reducing the global disease burden. In the authors opinion, this strategy may be very effective to nip the infection in the bud before it gets difficult to treat and therefore, have a potential to significantly reduce the CoViD-19 associated hospitalisation.

scholarly journals Lamellar macular holes: evolving concepts and propensity for progression to full thickness macular hole

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Salim Zafar Asaad
Keyword(s):  
Macular Hole ◽  
Clinical Course ◽  
Morphological Changes ◽  
Wide Spectrum ◽  
Tissue Loss ◽  
Lamellar Macular Hole ◽  
Full Thickness ◽  
Macular Holes ◽  
Full Thickness Macular Hole ◽  
Tractional Forces

Abstract Currently the term lamellar macular hole (LMH) alludes to a wide spectrum of macular conditions including distinct clinical entities with different pathomorphologies. Classifications into subtypes, tractional and degenerative or based on the associated preretinal tissue had been proposed. Recent insights suggest that only lesions with tissue loss should be considered ‘true’ LMH and not those morphological changes caused by tractional forces. Inclusion of lesions with foveoschisis with contractile epiretinal membrane (ERM) in earlier studies on LMHs has resulted in imprecise information about its clinical course. This review provides an overview of the evolving concepts of LMHs and analyses its natural history from study cases in previously published literature.

Pharmacological Blockade of NF-kB Targets Both Imatinib-Sensitive or -Resistant Chronic Myeloid Leukemia Cells for Cell Death.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4793-4793
Author(s):  
Véronique Imbert ◽  
Nadia Lounnas ◽  
Catherine Frelin ◽  
Nadège Gonthier ◽  
Emmanuel Griessinger ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Therapeutic Strategy ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Survival Functions ◽  
Resistant Variant ◽  
Cellular Targets ◽  
First Line Therapy ◽  
Imatinib Resistant ◽  
Pharmacological Blockade

Abstract The Bcr-Abl inhibitor imatinib is now the first line therapy for all newly diagnosed CML patients in chronic phase. Nevertheless resistance to the drug emerges as CML progresses to an acute deadly phase. Additional cellular targets should thus be identified to develop alternative therapeutic strategies. The transcription factor NF-kB is a pro-survival factor, found abnormally active in numerous hematologic malignancies. In the present study we show that the constitutive and abnormal activation of NF-kB in Bcr-Abl transformed BaF3 cells and in the LAMA84 CML line could be downregulated after inhibition of Bcr-Abl. Pharmacological blockade of NF-kB by the IKK2 inhibitor AS602868 (Serono International S.A.) prevented proliferation of BaF3/Bcr-Abl, LAMA84 and primary CML cells. Importantly, AS602868 led to apoptosis of an imatinib resistant variant of LAMA84 and of BaF3 clones expressing mutated form of Bcr-Abl derived from imatinib resistant patients. Moreover, NF-kB inhibition affected proliferation and hematopoietic colony formation of primary imatinib resistant CML cells. Finally, the IKK2 inhibitor prolonged survival of mice intravenously injected with the imatinib resistant clone LAMA84-r. Our data strongly suggest that NF-kB mediates important survival functions in CML cells for bcr-abl and that targeting NF-kB with the IKK2 inhibitor AS602868 may represent a new promising therapeutic strategy for CML treatment.

Micromachining Characteristics of NiTi Based Shape Memory Alloy Using Femtosecond Laser

2008 ◽  
Vol 130 (3) ◽  
Author(s):  
Nitin Uppal ◽  
Panos S. Shiakolas
Keyword(s):  
Shape Memory Alloy ◽  
Femtosecond Laser ◽  
Shape Memory ◽  
Smart Materials ◽  
Morphological Changes ◽  
Wide Spectrum ◽  
Interaction Mechanism ◽  
Laser Pulses ◽  
Femtosecond Laser Pulses ◽  
Niti Shape Memory Alloy

Femtosecond laser micromachining (FLM) is a relatively new and promising technology for the micromachining of a wide spectrum of engineering materials with micron and submicron size features. The interaction mechanism of femtosecond laser pulses with matter is not the same as that found in traditional lasers. This manuscript presents a detailed study of the ablation characteristics of a nickel-titanium (NiTi) shape memory alloy in air with femtosecond laser pulses. The single- and multishot ablation threshold fluence and the incubation coefficient (predicting the extent to which accumulation could take place in a material) are evaluated. In addition, morphological changes, such as the emergence of a ripple pattern, are discussed along with the identification of gentle and strong ablation phases. This study provides for the understanding and characterization of NiTi micromachining using FLM technology, which could aid in the identification of new applications for smart materials in the macro-, nano-, and microelectromechanical system domains using this technology.

Albumin overload induces apoptosis in LLC-PK1cells

2001 ◽  
Vol 280 (6) ◽  
pp. F1107-F1114 ◽  
Author(s):  
Elif Erkan ◽  
Maryely De Leon ◽  
Prasad Devarajan
Keyword(s):  
Dna Cleavage ◽  
Morphological Changes ◽  
Prognostic Indicator ◽  
Caspase 8 ◽  
Death Domain ◽  
Tubulointerstitial Injury ◽  
Nuclear Condensation ◽  
Glomerular Diseases ◽  
Induced Apoptosis

The degree of albuminuria is a well-known adverse prognostic indicator in human glomerular diseases. However, the mechanisms by which albuminuria by itself contributes to tubulointerstitial injury and progression of renal disease remain unclear. We tested the hypothesis that apoptosis may represent one of the mechanisms by which tubule epithelial cells are damaged after albumin overload in vitro. Cultured LLC-PK1 proximal tubule cells were incubated with varying concentrations of BSA. This resulted in a dose- and duration-dependent induction of apoptosis, as evidenced by internucleosomal DNA cleavage (DNA laddering and nick-end labeling), externalization of plasma membrane phosphatidylserine (annexin labeling), and characteristic morphological changes (cell shrinkage and nuclear condensation). Albumin overload also resulted in a dose-dependent upregulation of Fas and Fas-associated protein with death domain (FADD), and activation of caspase 8. Incubation with the caspase 8 inhibitor IETD ameliorated the albumin-induced apoptosis. Collectively, our results indicate that albumin overload induces apoptosis of cultured LLC-PK1 cells, mediated at least in part by the Fas-FADD-caspase 8 pathway.

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