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Pharmaceutics Jan 2024Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of but limited activity against the...
Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of but limited activity against the long-lived, tissue dwelling adult nematodes. As this neglected tropical disease has now been targeted for elimination, there is an urgent need for new drugs to combat these parasites, ideally with macrofilaricidal activity. In this study, we have examined the anti- activity of a range of existing FDA-approved drugs with a view to repurposing, which can lead to rapid and relatively inexpensive development. From the Pharmakon-1600 library, 106 drugs were selected and tested against adult male parasites using a concentration of 1.25 × 10 M in an in vitro 5-day standard assay to assess motility and viability (using MTT/formazan colorimetry). The findings revealed that 44 drugs produced marginal/moderate activity (50-99% motility and/or MTT reductions) including cefuroxime sodium, methenamine, primaquine phosphate and rivastigmine tartrate, while 23 drugs produced good activity (100% motility reductions and significant MTT reductions), including atovaquone, isradipine, losartan, rifaximin, cefaclor and pyrantel pamoate. Although this study represents only a first step, some of the identified hits indicate there are potential anti- drug candidates worthy of further investigation.
PubMed: 38399264
DOI: 10.3390/pharmaceutics16020210 -
Indian Journal of Pathology &... Apr 2024Cryptococcosis usually occurs in immunocompromised patients and presents as meningitis and lung disease. Adrenal gland involvement may be observed, yet primary adrenal...
Cryptococcosis usually occurs in immunocompromised patients and presents as meningitis and lung disease. Adrenal gland involvement may be observed, yet primary adrenal insufficiency by cryptococcal infection is infrequent. We present a case of a middle-aged immunocompetent man with primary adrenal insufficiency and bilateral adrenal lesions, splenomegaly, and miliary mottling in the lungs on imaging. No evidence of meningitis was witnessed. The clinico-radiological findings led toward the differential diagnosis of disseminated tuberculosis or fungal infection. Detection of cryptococcus organism was done on fine-needle aspiration cytology and biopsy on periodic acid-Schiff stain and Gomori`s methenamine silver stain. Thus, it is recommended to keep the possibility of cryptococcosis in mind while dealing with instances that have a tuberculosis-like clinico-radiological presentation. The detection of the causal organism on Fine needle aspiration (FNA)/biopsy examination may be useful in confirming the diagnosis and determining the appropriate medical treatment.
Topics: Humans; Male; Cryptococcosis; Biopsy, Fine-Needle; Adrenal Insufficiency; Middle Aged; Adrenal Glands; Cryptococcus; Diagnosis, Differential; Tomography, X-Ray Computed; Lung; Microscopy; Adrenal Gland Diseases; Immunocompetence; Histocytochemistry
PubMed: 38391340
DOI: 10.4103/ijpm.ijpm_185_22 -
Archives of Pathology & Laboratory... Feb 2024The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of...
Digital Pathology in the Detection of Infectious Microorganisms: An Evaluation of Its Strengths and Weaknesses Across a Panel of Immunohistochemical and Histochemical Stains Routinely Used in Diagnostic Surgical Pathology.
CONTEXT.—
The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated.
OBJECTIVE.—
To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology.
DESIGN.—
Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images.
RESULTS.—
Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa.
CONCLUSIONS.—
Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.
PubMed: 38385999
DOI: 10.5858/arpa.2023-0214-OA -
Prague Medical Report 2024A middle-aged man in his 50s, active smoker, presented to the pulmonary office for lung cancer evaluation. On a low-dose computed tomography for lung cancer screening,...
A middle-aged man in his 50s, active smoker, presented to the pulmonary office for lung cancer evaluation. On a low-dose computed tomography for lung cancer screening, he was found to have an 8 mm endobronchial lesion in the right main stem bronchus. A PET-CT revealed no endobronchial lesion, but incidentally, fluorodeoxyglucose (FDG) avidity was present in the right hilar (SUV 13.2) and paratracheal lymph nodes (LNs). He underwent bronchoscopy and EBUS-TBNA of station 7 and 10 R LNs. The fine needle aspiration (FNA) revealed necrotizing epithelioid granuloma. The acid-fast bacilli (AFB) and Grocott methenamine silver (GMS) stains were negative. He had suffered from pneumonic tularemia 13 months ago and immunohistochemical staining for Francisella tularensis on FNA samples at Center for Disease Control and Prevention was negative. The intense positron emission tomography (PET) avidity was attributed to prior tularemic intrathoracic lymphadenitis without active tularemia, a rare occurrence. To the best of our knowledge, PET-positive intrathoracic lymph node beyond one year without evidence of active tularemia has not been previously reported.
Topics: Male; Middle Aged; Humans; Lung Neoplasms; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Early Detection of Cancer; Tularemia; Lymph Nodes; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Neoplasm Staging; Retrospective Studies
PubMed: 38380456
DOI: 10.14712/23362936.2024.8 -
The Science of the Total Environment Mar 2024Among personal care products, quaternium-15 is prominently featured as a preservative in items such as shampoos, soaps, shaving products, and cosmetics. The widespread...
Among personal care products, quaternium-15 is prominently featured as a preservative in items such as shampoos, soaps, shaving products, and cosmetics. The widespread use of these products in people's daily routines contributes to quaternium-15 release into aquatic ecosystems. In this context, the primary aim of the study was to assess the physiological and cellular responses of the digestive gland and gills in Mytilus galloprovincialis to quaternium-15 exposure. Cell viability and the ability of digestive gland cells to regulate their volume were evaluated. Additionally, the expression of the genes involved in oxidative stress response was assessed to further substantiate the compound's harmful effects. Results indicated a significant decrease in both the viability of digestive gland cells and their RVD (regulatory volume decrease) capacity when exposed to a hypotonic solution. Furthermore, impairment of digestive gland cell function was corroborated by the modulation of oxidative stress-related gene expression, including SOD, Cat, as well as Hsp70 and CYP4Y1. Similar gene expression alterations were observed in the gills, reflecting impaired functionality in this vital organ as well. In summary, the outcomes of the study provide conclusive evidence of the toxicity of quaternium-15. This underscores the urgent need to further investigate the toxicological effects of this contaminant on aquatic ecosystems and emphasises the necessity of limiting the use of products containing quaternium-15.
Topics: Humans; Animals; Mytilus; Ecosystem; Oxidative Stress; Digestion; Water Pollutants, Chemical; Gills; Biomarkers; Methenamine
PubMed: 38309339
DOI: 10.1016/j.scitotenv.2024.170568 -
Journal of Cardiology Cases Jan 2024infection is infrequently considered in the differential diagnoses for acute pericarditis in immunocompetent hosts when presenting with tamponade physiology, given its...
UNLABELLED
infection is infrequently considered in the differential diagnoses for acute pericarditis in immunocompetent hosts when presenting with tamponade physiology, given its gradual infective nature. We describe a case of a young male presenting solely with acute pericarditis with pericardial effusion and early cardiac tamponade physiology secondary to a pulmonary histoplasmosis infection. Our patient had no pulmonary symptoms; the only pulmonary manifestation of histoplasmosis included incidental findings of subcarinal lymphadenopathy and a left lingular nodule abutting the pericardium. Given failure of symptom improvement with pericardiocentesis and first-line therapy for idiopathic/viral pericarditis, further workup of the pulmonary nodule was pursued. Histopathologic analysis of tissue showed caseating granulomas and fungal Grocott-Gömöri's methenamine silver stain revealed yeast consistent with species. The patient improved with itraconazole therapy.
LEARNING OBJECTIVE
Pulmonary histoplasmosis has potential to present as a pericardial effusion in the immunocompetent individual. In addition to pericardiocentesis, antifungal therapy can be curative.
PubMed: 38188317
DOI: 10.1016/j.jccase.2023.10.002 -
Cureus Nov 2023Background Mucormycosis, attributed to a group of molds known as mucormycosis, is a rare yet life-threatening fungal infection often colloquially referred to as black...
Background Mucormycosis, attributed to a group of molds known as mucormycosis, is a rare yet life-threatening fungal infection often colloquially referred to as black fungus. While its incidence notably surged during the second wave of COVID-19 infections in India, it's essential to recognize that mucormycosis was a significant concern even before the advent of the pandemic. Understanding the prevalence and characteristics of this infection in the pre-COVID era provides a crucial context for evaluating its impact and dynamics during the pandemic. Multiple diagnostic methods, such as potassium hydroxide (KOH) mount, culture, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and histopathological examination (HPE), are available for identifying this lethal infection. The primary objective of this study is to ascertain the sensitivity of various diagnostic methods for mucormycosis and to analyze the comparative effectiveness of microbiological versus histopathological diagnoses. Methods We conducted a retrospective observational study spanning six months, from May 2021 to October 2021, encompassing all mucormycosis cases meeting the inclusion criteria and diagnosed via histopathological examination (HPE) in the departments of pathology and microbiology. Microbiological tests were performed prior to the histopathological examinations. Sensitivity was assessed through statistical analysis, and the relationship between microbiological and histopathological diagnoses was evaluated using the chi-square test. Results Biopsy samples of 77 patients were collected, comprising 56 male and 21 female patients. Regarding age distribution, most patients fell within the 41-60 age bracket, while the smallest proportion was over 60 years old. The sensitivity and specificity of histopathological diagnosis, confirmed with periodic acid-Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) staining, both recorded a flawless 100%. KOH mount sensitivity stood at 88.3%, while fungal culture and MALDI-TOF exhibited sensitivities of 75.3%. Histopathological analysis revealed that 17% of cases displayed minimal fungal hyphae alongside necrotic tissue, whereas 58% exhibited abundant fungal hyphae accompanied by inflammatory cells. Additionally, absolute neutrophilia was observed in 55% of cases. Conclusions In our study, histopathology and KOH mount emerged as not only compassionate but also cost-effective diagnostic tools for identifying mucormycosis. The economic aspect of these diagnostic methods is highlighted in the results section to provide a comprehensive understanding of their cost-effectiveness. Additionally, we utilized MALDI-TOF MS as a straightforward, economically viable, and expeditious method specifically for confirming the fungal subtype in mucormycosis cases. The rationale behind choosing either MALDI-TOF MS or KOH for the diagnosis is elucidated, contributing to a clearer interpretation of our diagnostic approach. Furthermore, our findings indicate that absolute neutrophilia consistently manifests in 55% of mucormycosis cases.
PubMed: 38106762
DOI: 10.7759/cureus.48925 -
Indian Dermatology Online Journal 2023A few recent studies have shown fungal elements within the hair follicle epithelium, which may act as a reservoir and responsible for recurrent dermatophytosis.
BACKGROUND
A few recent studies have shown fungal elements within the hair follicle epithelium, which may act as a reservoir and responsible for recurrent dermatophytosis.
OBJECTIVES
To assess the clinical patterns, mycological profile, and histopathology of recurrent dermatophytosis and to determine the prevalence of fungal hyphae in the hair follicle epithelium and other appendages.
MATERIALS AND METHODS
One hundred and fifty clinically diagnosed cases of recurrent dermatophytic infection were included. Skin samples were taken for direct microscopy, fungal culture, and histopathological analysis. Haematoxylin and eosin and special staining with periodic acid Schiff (PAS) and Gomori's methenamine silver (GMS) were performed to detect the fungal hyphae in the skin and hair follicle epithelium.
RESULTS
The most common clinical pattern observed was tinea corporis et cruris in 64 patients (42.66%). On direct microscopy and fungal culture, positive results were obtained in 116 cases (77.33%) and 78 (52%) cases, respectively. Presence of fungal hyphae in the stratum corneum, hair follicle, and acrosyringium was seen in 107 patients (71.33%), 47 patients (31.33%), and five patients (3.33%), respectively. Out of the 52 cases with hair follicle and eccrine gland involvement, history of fixed drug combinations (FDC) cream use was present in 42 cases (80.76%) and absent in ten cases (19.24%) ( = 0.000062).
LIMITATIONS
Skin samples were taken only from a single skin lesion. Higher incidence of follicular invasion may have been detected if multiple biopsy samples were taken.
CONCLUSION
Hair follicle/eccrine sweat gland involvement was observed in nearly one-third of the patients, which may act as a reservoir and may be responsible for recurrence and chronicity. Histopathology should be considered as an important adjuvant tool in recurrent dermatophytosis to establish the extent of the infection, which guides the further management.
PubMed: 38099009
DOI: 10.4103/idoj.idoj_670_22 -
The European Physical Journal. E, Soft... Dec 2023It is well established that deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) exhibit a reentrant condensation (RC) phase behavior in the presence of the trivalent...
It is well established that deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) exhibit a reentrant condensation (RC) phase behavior in the presence of the trivalent hexamine cobalt(III) cations (Hac) which can be important for their packing and folding. A similar behavior can be observed for negatively charged globular proteins in the presence of trivalent metal cations, such as Y or La. This phase behavior is mainly driven by charge inversion upon an increasing salt concentration for a fixed protein concentration (c). However, as Hac exhibits structural differences compared to other multivalent metal cations, with six ammonia ligands (NH) covalently bonded to the central cobalt atom, it is not clear that Hac can induce a similar phase behavior for proteins. In this work, we systematically investigate whether negatively charged globular proteins β-lactoglobulin (BLG), bovine serum albumin (BSA), human serum albumin (HSA) and ovalbumin (OVA) feature Hac-induced RC. Effective protein-protein interactions were investigated by small-angle X-ray scattering. The reduced second virial coefficient (B/B) was obtained as a function of salt concentration. The virial coefficient analysis performed confirms the reentrant interaction (RI) behavior for BLG without actually inducing RC, given the insufficient strengths of the interactions for the latter to occur. In contrast, the strength of attraction for BSA, HSA and OVA are too weak to show RC. Model free analysis of the inverse intensity [Formula: see text] also supports this finding. Looking at different q-range by employing static (SLS) and dynamic light scattering experiments, the presence of RI behavior can be confirmed. The results are further discussed in view of metal cation binding sites in nucleic acids (DNA and RNA), where Hac induced RC phase behavior.
Topics: Humans; Chlorides; Cobalt; Methenamine; Serum Albumin, Bovine; Cations; DNA; RNA; Solutions
PubMed: 38051398
DOI: 10.1140/epje/s10189-023-00376-6 -
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