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American Journal of Physiology. Cell... Jan 2024Sarcoidosis embodies a complex inflammatory disorder spanning multiple systems, with its origin remaining elusive. It manifests as the infiltration of inflammatory cells... (Review)
Review
Sarcoidosis embodies a complex inflammatory disorder spanning multiple systems, with its origin remaining elusive. It manifests as the infiltration of inflammatory cells that coalesce into distinctive noncaseous granulomas within afflicted organs. Unraveling this disease necessitates the utilization of cellular or tissue-based imaging methods to both visualize and characterize the biochemistry of these sarcoid granulomas. Although hematoxylin and eosin stain, standard in routine use alongside cytological stains have found utility in diagnosis within clinical contexts, special stains such as Masson's trichrome, reticulin, methenamine silver, and Ziehl-Neelsen provide additional varied perspectives of sarcoid granuloma imaging. Immunohistochemistry aids in pinpointing specific proteins and gene expressions further characterizing these granulomas. Finally, recent advances in spatial transcriptomics promise to divulge profound insights into their spatial orientation and three-dimensional (3-D) molecular mapping. This review focuses on a range of preexisting imaging methods employed for visualizing sarcoid granulomas at the cellular level while also exploring the potential of the latest cutting-edge approaches like spatial transcriptomics and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), with the overarching goal of shedding light on the trajectory of sarcoidosis research.
Topics: Humans; Granuloma; Sarcoidosis
PubMed: 37955119
DOI: 10.1152/ajpcell.00507.2023 -
PLoS Pathogens May 2024The role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of...
The role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of dentin in advanced caries especially merits additional research. We evaluated the fungal and bacterial community composition and spatial distribution within carious dentin. Amplicon 16S rRNA gene sequencing together with quantitative PCR was used to profile bacterial and fungal species in caries-free children (n = 43) and 4 stages of caries progression from children with severe early childhood caries (n = 32). Additionally, healthy (n = 10) and carious (n = 10) primary teeth were decalcified, sectioned, and stained with Grocott's methenamine silver, periodic acid Schiff (PAS) and calcofluor white (CW) for fungi. Immunolocalization was also performed using antibodies against fungal β-D-glucan, gram-positive bacterial lipoteichoic acid, gram-negative endotoxin, Streptococcus mutans, and Candida albicans. We also performed field emission scanning electron microscopy (FESEM) to visualize fungi and bacteria within carious dentinal tubules. Bacterial communities observed included a high abundance of S. mutans and the Veillonella parvula group, as expected. There was a higher ratio of fungi to bacteria in dentin-involved lesions compared to less severe lesions with frequent preponderance of C. albicans, C. dubliniensis, and in one case C. tropicalis. Grocott's silver, PAS, CW and immunohistochemistry (IHC) demonstrated the presence of fungi within carious dentinal tubules. Multiplex IHC revealed that fungi, gram-negative, and gram-positive bacteria primarily occupied separate dentinal tubules, with rare instances of colocalization. Similar findings were observed with multiplex immunofluorescence using anti-S. mutans and anti-C. albicans antibodies. Electron microscopy showed monomorphic bacterial and fungal biofilms within distinct dentin tubules. We demonstrate a previously unrecognized phenomenon in which fungi and bacteria occupy distinct spatial niches within carious dentin and seldom co-colonize. The potential significance of this phenomenon in caries progression warrants further exploration.
Topics: Humans; Dental Caries; Dentin; Male; Child; Female; Child, Preschool; Bacteria; Fungi; RNA, Ribosomal, 16S
PubMed: 38805482
DOI: 10.1371/journal.ppat.1011865 -
International Journal of Pharmaceutical... 2023Onychomycosis is the most common fungal nail infection accounting for 50% of nail disorders. This infection is most common in the toenails than in the nails of the...
Onychomycosis is the most common fungal nail infection accounting for 50% of nail disorders. This infection is most common in the toenails than in the nails of the fingers. It is caused by various fungal species like Trichophyton rubrum, Trichophyton mentagrophytes, Scopulariopsis brevicaulis, Aspergillus spp, Fusarium spp, Acremonium spp, Alternaria spp, and Neoscytalidium. Among them, dermatophyte fungus is involved in 70% to 80% of infections. Clinically, there are five types of onychomycosis classified based on causative organism and location of infection origin. Diagnosis of this infection uses a mycological study of nail samples using multiple staining techniques like periodic acid-Schiff, calcofluor, Grocott methenamine silver, fluorescence, and microscopy. The major risk factors of this infection include diabetes mellitus, psoriasis, peripheral vascular diseases, obesity, metabolic syndrome, nail trauma, human immunodeficiency virus and/or acquired immunodeficiency syndrome, immune-compromised individuals, chronic kidney failure, athletic activity, smoking, and hyperlipidemia. The treatment options for onychomycosis include topical and systemic antifungal agents, nanoparticles, laser therapy, photodynamic therapy, and nail avulsion. This article describes several types of onychomycosis, symptoms, diagnosis, currently available therapy and its drawback, current research to rectify the issues, and future medicinal approaches to improve patient health.
Topics: Humans; Onychomycosis
PubMed: 38100667
DOI: No ID Found -
Cureus Oct 2023Emphysematous gastritis is a rare entity that has not much literature available. It is known to manifest as a diffused wall inflammation and air within the wall of the...
Emphysematous gastritis is a rare entity that has not much literature available. It is known to manifest as a diffused wall inflammation and air within the wall of the stomach and has been associated with gas-forming organisms. We present a complex case of a middle-aged woman with a previous history of fulminant complicated with colectomy and diverting colostomy. She was admitted due to diabetic ketoacidosis, later complicated with worsening abdominal pain, and a CT scan of the abdomen and pelvis without contrast revealed findings consistent with ischemic bowel, severe pneumatosis intestinalis, and extensive portal venous gas. A stomach biopsy revealed hemorrhagic necrosis; a Gomori methenamine silver stain was compatible with fungal organisms, , correlating with Candida emphysematous gastritis. This case highlights the importance of early diagnosis of this syndrome in order to provide appropriate management, and early identification, to improve survival.
PubMed: 38022357
DOI: 10.7759/cureus.47870 -
Biological Trace Element Research Dec 2023Fluoride (F) is widely distributed in the environment and poses serious health risks to humans and animals. Although a good body of literature demonstrates a close...
Fluoride (F) is widely distributed in the environment and poses serious health risks to humans and animals. Although a good body of literature demonstrates a close relationship between F content and renal system performance, there is no satisfactory information on the involved intracellular routes. Hence, this study used histopathology and mitochondrial fission to explore fluorine-induced nephrotoxicity further. For this purpose, mice were exposed to the F ion (0, 25, 50, 100 mg/L) for 90 days. The effects of different F levels on renal pathomorphology and ion metabolism were assessed using hematoxylin and eosin (H&E), periodic acid-Schiff stain (PAS), periodic acid-silver methenamine (PASM), Prussian blue (PB), and alkaline phosphatase (ALP) staining. The results showed that F could lead to glomerular atrophy, tubular degeneration, and vacuolization. Meanwhile, F also could increase glomerular and tubular glycoproteins; made thickening of the renal capsule membrane and thickening of the tubular basement membrane; led to the accumulation of iron ions in the tubules; and increased in glomerular alp and decreased tubular alp. Concomitantly, IHC results showed that F significantly upregulated the expression levels of mitochondrial fission-related proteins, including mitochondrial fission factor (Mff), fission 1 (Fis1), and mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), ultimately caused apoptosis. To sum up, excessive fluorine has a strong nephrotoxicity effect, disrupting the balance of mitochondrial fission and fusion, interfering with the process of mitochondrial fission, and then causing damage to renal tissue structure and apoptosis.
PubMed: 38057486
DOI: 10.1007/s12011-023-03994-5 -
Cureus Jul 2023Fungal rhinosinusitis (FRS) is a relatively common, but often misdiagnosed disease of paranasal sinuses. The FRS is classified into invasive and non-invasive forms. The...
Fungal rhinosinusitis (FRS) is a relatively common, but often misdiagnosed disease of paranasal sinuses. The FRS is classified into invasive and non-invasive forms. The non-invasive form includes fungal ball and allergic FRS, and invasive form includes acute invasive FRS, chronic invasive FRS, and granulomatous FRS. Invasive fungal infections are associated with high morbidity and mortality, hence requiring urgent medical and surgical intervention. The histomorphology can help identify certain fungal organisms that cannot be cultured or are rarely visible in exudates. The morphologic diagnosis of tissue invasive and non-invasive fungal infection is essential for appropriate treatment. We analyzed cases of rhinosinusitis from 2017 to 2019 in Pathology Department at a tertiary care cancer hospital, Lahore, Pakistan. All clinical information was retrieved from patient records. Paraffin-embedded tissue blocks were stained with hematoxylin and eosin (H&E), special Grocott methenamine silver stain (GMS), and periodic acid Schiff stain (PAS) according to standard protocol. They were reviewed by two pathologists blinded by fungus status. A total of 169 cases of rhinosinusitis were reviewed. FRS comprised 146 (86.4%) of them. The mean age of patients with FRS was 32.8±14 years. The male:female ratio was 1.4:1. Maxillary sinus was the main site of involvement in 39 (27%) FRS cases. Aspergillus was identified in 117 (80.1%) cases of FRS. The culture reports were available in 44/146 (30.14%) FRS cases. They were negative in 22/44 (50.0%), and Aspergillus species were isolated in 18/44 (40.9%) cases of FRS. There were 84 (57.5%) cases of non-invasive FRS and 59 (40.4%) cases of invasive FRS. Among invasive FRS, there were 56 (38.4%) chronic granulomatous FRS cases including mixed patterns. Majority cases, 54 (96.4%), of chronic granulomatous FRS showed a unique crowded giant cell pattern comprising of foreign body and Langhans type giant cells. These giant cells were arranged closely forming irregular non-caseating granulomas surrounded by lymphocytes and fibrosis. Interestingly, the giant cells were scattered haphazardly without forming a granuloma as well. Fungal organisms were identified in all 56 cases of chronic granulomatous FRS. Histologically, predominant organism was Aspergillus in 48 (85.7%) on GMS and PAS stain. Our study observed a unique crowded giant cell pattern, which is a hallmark of invasive fungal infection. If pathologists are familiar with this unique pattern, they can make a quick and accurate diagnosis on histology. The physician can start antifungal treatment timely for better prognosis.
PubMed: 37583719
DOI: 10.7759/cureus.41915 -
RMD Open Nov 2023Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development....
OBJECTIVES
Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans.
METHODS
A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed.
RESULTS
After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice.
CONCLUSIONS
Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.
Topics: Humans; Mice; Animals; Arthritis, Gouty; Gout; Uric Acid; Gout Suppressants; Disease Models, Animal
PubMed: 37973536
DOI: 10.1136/rmdopen-2023-003499 -
International Archives of... Apr 2024Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of...
Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of COVID-19 infection and mucormycosis. The present study was done to describe the clinical spectrum and histopathological findings of mucormycosis in COVID-19 patients and their outcomes. A cross-sectional study was done over a period of two and half months. The biopsy samples or scrapings from sinonasal or periorbital tissue of 38 patients were analyzed. Hematoxylin & Eosin (H&E stain) slides were evaluated along with Grocott-Gomori methenamine-silver and Periodic acid-Schiff stains to highlight the fungal elements. The male to female ratio was 2.5:1, and the mean age of the subjects was 53 years old. A total of 68.4% ( = 26/38) of the patients had diabetes as a comorbidity, 84.2% ( = 32/38) had a history of steroid intake, and 55.3% ( = 21/38) were given supplemental oxygen during their treatment. The common presentations were nasal blockage, discharge, eye pain, headache, and altered mentation. The sites of biopsy were: nasal cavity 76.3% ( = 29/38), periorbital fat/orbit 21.1% ( = 8/38), maxillary sinus 15.8% ( = 6/38) and ethmoid sinus 13.2% ( 5/38). In 76.3% ( = 29/38) cases, broad, irregular, nonseptate, and right-angle branching hyphae were seen on H&E-stained tissue sections. COVID-19 led to various complications in individuals affected by it. Mucormycosis was one such lethal complication. An early diagnosis and prompt treatment is crucial to control the progression of the disease and improve outcomes.
PubMed: 38618587
DOI: 10.1055/s-0043-1776729 -
Clinical Case Reports Nov 2023Lysozyme-induced nephropathy is a rare form of acute tubular injury that has almost exclusively been reported in patients with monocytic malignancies. Typically,...
Lysozyme-induced nephropathy is a rare form of acute tubular injury that has almost exclusively been reported in patients with monocytic malignancies. Typically, patients will present in acute renal failure A renal biopsy is necessary to confirm the diagnosis and will demonstrate proximal tubular cells with hypereosinophilic granules, which are periodic acid-Schiff and Jones methenamine silver-positive. Immunohistochemical staining for lysozyme will also be present. The following rare case will describe a case of lysozyme nephropathy in a patient without any underlying hematological malignancy, but instead with systemic granulomatous disease.
PubMed: 38028084
DOI: 10.1002/ccr3.8122 -
The American Journal of Dermatopathology Jun 2024A 53-year-old woman presented with a pruritic plaque on the left upper arm that appeared following an egg-free flu vaccine due to a history of reaction to the standard...
A 53-year-old woman presented with a pruritic plaque on the left upper arm that appeared following an egg-free flu vaccine due to a history of reaction to the standard vaccine. The affected area enlarged over a several month period immediately following vaccine administration. Physical examination revealed an 8 × 4 cm coalescent pink plaque on the left upper arm. A shave biopsy of the lesion showed dermal "naked" granulomas, or granulomas with sparse lymphocytic infiltrate at the margins, as typically seen in sarcoidosis. No foreign material was seen in the granulomatous reaction, including with polarization. Special stains, including acid fast bacilli, Grocott methenamine silver, periodic acid-Schiff, and Gram, were negative for organisms. The diagnosis of granulomatous dermatitis was made. Subsequent imaging demonstrated no findings suggestive of sarcoidosis. While vaccine-associated hypersensitivity reactions occur frequently, these reactions are typically due to individual vaccine components, such as egg protein, and do not normally result in the formulation of granulomas. Vaccination-induced granulomas are more often associated with the use of aluminum as an adjuvant; however, this is not present in the egg-free influenza vaccine. Thus, a granulomatous reaction to the egg-free influenza vaccine is very unusual and, to our knowledge, not previously reported.
PubMed: 38842398
DOI: 10.1097/DAD.0000000000002751