ABSTRACT
PURPOSE: MKNR3 is a paternally expressed gene whose mutations are the main cause of central precocious puberty (CPP). Protein circulating levels can be easily measured, as demonstrated in idiopathic CPP and healthy controls. No data are available for patients harboring an MKRN3 mutation. Our aim was to perform MKRN3 mutation screening and to investigate if circulating protein levels could be a screening tool to identify MKRN3 mutation in CPP patients. METHODS: We enrolled 140 CPP girls and performed MKRN3 mutation analysis. Patients were stratified into two groups: idiopathic CPP (iCPP) and MKRN3 mutation-related CPP (MKRN3-CPP). Clinical characteristics were collected. Serum MKRN3 values were measured by a commercially available ELISA assay kit in MKRN3-CPP and a subgroup of 15 iCPP patients. RESULTS: We identified 5 patients with MKRN3 mutations: one was a novel mutation (p.Gln352Arg) while the others were previously reported (p.Arg328Cys, p.Arg345Cys, p.Pro160Cysfs*14, p.Cys410Ter). There was a significant difference in circulating MKRN3 values in MKRN3-CPP compared to iCPP (p < 0.001). In MKRN3-CPP, the subject harboring Pro160Cysfs*14 presented undetectable levels. Subjects carrying the missense mutations p.Arg328Cys and p.Gln352Arg showed divergent circulating protein levels, respectively 40.56 pg/mL and undetectable. The patient with the non-sense mutation reported low but measurable MKRN3 levels (12.72 pg/mL). CONCLUSIONS: MKRN3 defect in patients with CPP cannot be predicted by MKRN3 circulating levels, although those patients presented lower protein levels than iCPP. Due to the great inter-individual variability of the assay and the lack of reference values, no precise cut-off can be identified to suspect MKRN3 defect.
Subject(s)
Mutation , Puberty, Precocious , Ubiquitin-Protein Ligases , Humans , Puberty, Precocious/genetics , Puberty, Precocious/blood , Puberty, Precocious/diagnosis , Female , Ubiquitin-Protein Ligases/genetics , Child , Ribonucleoproteins/genetics , Ribonucleoproteins/blood , Child, Preschool , DNA Mutational Analysis , Case-Control Studies , Biomarkers/bloodABSTRACT
Chimeric antigen receptor (CAR) T cell therapy targeting CD-19 has revolutionized the treatment of refractory B-cell malignancies. However, patients undergoing this therapy face an increased risk of infections due to compromised immune function, lymphodepleting chemotherapy, hospitalization, and therapy-related complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Patients with systemic corticosteroid use, low immunoglobulin levels, and severe CRS, are at higher risk of infection. This review article highlights the spectrum of infections encountered in CAR T cell therapy, including bacterial, viral, and fungal infections. Following consensus guidelines for vaccination and immunoglobulin replacement is recommended. Clear criteria for antibiotic usage and vaccinating household members against respiratory viruses are crucial. Understanding the risk factors, spectrum of infections, and implementing appropriate prophylactic measures are essential to optimize outcomes in patients undergoing CAR T cell therapy. By prioritizing infection prevention strategies, healthcare professionals can effectively improve patient care.
Subject(s)
Neoplasms , Neurotoxicity Syndromes , Humans , T-Lymphocytes , Immunotherapy, Adoptive/adverse effects , Neurotoxicity Syndromes/complications , Neurotoxicity Syndromes/therapy , Cytokine Release Syndrome/etiology , Neoplasms/complications , ImmunoglobulinsABSTRACT
OBJECTIVE: The purpose of the study is to assess body hydration in patients with posterior vitreous detachment (PVD) by bioelectrical impedance analysis (BIA). PVD, one of the most common eye diseases, is associated in both research and the collective image with reduced daily water intake, but this finding is not supported by strong evidence in the literature. PATIENTS AND METHODS: Based on Spectral Domain Optical Coherence Tomography (SD-OCT) evaluation, different PVD stages are identified: absent posterior vitreous detachment, partial posterior vitreous detachment (P-PVD), or complete posterior vitreous detachment (C-PVD). BIA is a simple, non-invasive bedside method used to assess body composition. Patients underwent BIA and completed a floaters symptoms. 30 patients were enrolled and divided into two groups according to the degree of vitreous detachment, in P-PVD (n=12) and C-PVD (n=18). Patients underwent BIA and completed a floaters symptoms questionnaire. BIA measured the Resistance (R), Reactance (Xc), Phase Angle (PhA), Total Body Water (TBW), Extracellular Water (ECW), Fat Mass (FM), Fat-Free Mass (FFM), and Body Cell Mass Index (BCMI). Finally, patients received a test to assess adherence to the Mediterranean diet (Mediterranean Diet Test Score, MDTS) with the addition of daily water intake. RESULTS: Relevant data were obtained from the BIA evaluation: the values of R and Xc were lower in the P-PVD group than C-PVD group (respectively 417.08±58.12 Ω vs. 476.94±51.29 Ω p=0.006 and 41.33±8.23 Ω vs. 50.61±7.98 Ω p=0.004). Instead, patients in the P-PVD group reported higher values of TBW and ECW than C-PVD group (respectively 44.13±7.57 L vs. 37.96±6.27 L p=0.021 and 21.03±4.06 L vs. 17.24±2.63 L p=0.004). CONCLUSIONS: In the present study, we reported a significant correlation between vitreous pathology and anthropometric and BIA measurements.
Subject(s)
Vitreous Detachment , Humans , Electric Impedance , Anthropometry , Body Composition , Body Mass Index , WaterABSTRACT
PURPOSE: We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. METHODS: We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. RESULTS: A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. CONCLUSION: A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.
Subject(s)
Dwarfism , Sexual Maturation , Male , Female , Humans , Ubiquitin-Protein Ligases/genetics , Mutation , Membrane Proteins/genetics , Phenotype , Calcium-Binding Proteins/geneticsABSTRACT
OBJECTIVE: Hypertensive retinopathy (HR) is the most common ocular manifestation of systemic arterial hypertension. This paper aims to summarize the current knowledge of HR, reviewing its classical features, such as epidemiology, pathophysiology, clinical manifestations, classifications, management and the most significant systemic correlations. We also provide an update on the latest advances in new technologies focusing on novel instrumental classifications. MATERIALS AND METHODS: A literature search was performed to identify articles regarding HR listed in Embase, PubMed, Medline (Ovid) and Scopus database up to 1 December 2021. The reference lists of the analyzed articles were also considered a source of literature information. The following keywords were used in various combinations: hypertensive retinopathy, hypertension and eye, hypertensive retinopathy and systemic correlations, optical coherence tomography (OCT) and hypertensive retinopathy, optical coherence tomography angiography (OCTA) and hypertensive retinopathy, adaptive optics (AO) and hypertensive retinopathy. The authors analyzed all English articles found using the aforementioned keywords. All the publications were thoroughly reviewed to create a detailed overview of this issue. RESULTS: HR signs have a significative association with cardiovascular, cerebrovascular and other systemic diseases. Patients with arteriosclerotic changes and, at the same time, severe HR, are at increased risk for coronary disease, peripheral vascular disease, stroke and dementia. HR is even now diagnosed and classified by its clinical appearance on a fundoscopic exam that is limited by interobserver variability. New technologies, like OCT, OCTA, AO and artificial intelligence may be used to develop a new instrumental classification that could become an objective and quantitative method for the evaluation of this disease. They could be useful to evaluate the subclinical retinal microvascular changes due to hypertension that may reflect the involvement of other vital organs. CONCLUSIONS: The eye is the only organ in the human body where changes in the blood vessels due to systemic hypertension can be studied in vivo. All doctors should be familiar with this disease because it has been largely demonstrated that signs of HR are correlated to patient's health and mortality. Researchers should develop a new common, standardized, and objective method to assess hypertensive retinal changes; new technologies may have a significant role in this field. This review takes most of the literature published so far, including the OCTA studies in order to stimulate new points of reference to standardize parameters and new diagnostic markers of this disease.
Subject(s)
Hypertension , Hypertensive Retinopathy , Artificial Intelligence , Humans , Hypertension/complications , Hypertensive Retinopathy/complications , Hypertensive Retinopathy/diagnosis , Retina , Tomography, Optical Coherence/methodsABSTRACT
[This corrects the article DOI: 10.1016/j.heliyon.2019.e02291.].
ABSTRACT
Tea (Camellia Sinensis) is one of the most popular drink, consumed as infusion or bottled ready to drink beverages. Although tea leaves contain many antioxidants compounds, after processing they can drastically decrease, sometimes up to a full degradation, as in the case of catechin, a very healthy flavan-3-ol. In this context, the synthesis of a cocrystal between (+)-catechin and L-(+)-ascorbic acid, was proved to be a useful strategy to make a new ingredient able to ameliorate the antioxidant profile of both infusions and bottled teas. The obtained cocrystal showed a three-fold higher solubility than (+)catechin and its formation was elucidated unambiguously by FT-IR, thermal (DSC) and diffraction (PXRD) analyses. Antioxidant characteristics of the samples were evaluated by colorimetric assays. As expected, infusions showed much better antioxidant features than ready-to-use lemon and peach teas. The same trend was confirmed after the addition of the cocrystal at two concentration levels. In particular, supplementation at concentration of 2 mg mL-1 improved the bottled tea antioxidant values to the level showed by the not-added infusion tea.
ABSTRACT
Five new pinocembrin derivatives (MC1-MC5) were synthesized by Steglich reaction, and investigated for their antimicrobial, antioxidant, and anti-inflammatory activity. MC2 (oleoyl derivative) and MC3 (linoleoyl derivative) have shown the highest inhibitory effects on bacterial proliferation, with MIC values of 32 µg/mL against Staphylococcus aureus. The docosahexaenoyl derivative MC5 displayed the highest anti-inflammatory activity, decreasing NO production in LPS-stimulated macrophages with an IC50 value of 15.51 µg/mL higher than the positive control diclofenac (IC50 of 39.71 µg/mL). All new synthesized compounds showed no anti-proliferative effects on RAW 264.7 cells. Results demonstrated as the introduction of fatty acid substituents improved the biological profile of pinocembrin. Moreover, the chemical nature of substituents significantly affects the bioactivity. These preliminary results outline the importance to investigate the synthesis of pinocembrin fatty acids derivatives as new and safe anti-microbial/anti-inflammatory agents.
Subject(s)
Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Flavanones/chemistry , Glycyrrhiza/chemistry , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Drug Evaluation, Preclinical/methods , Drug Repositioning , Fatty Acids/chemistry , Mice , Microbial Sensitivity Tests , Plant Extracts/pharmacology , RAW 264.7 Cells , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
BACKGROUND: Keratoconus (KC) is a common ectatic disorder resulting in progressive corneal thinning and irregular astigmatism. It has been observed that patients affected by KC are more likely to develop lens opacities earlier compared to non-keratoconic patients. OBJECTIVE: Intraocular lens (IOL) selection and refractive outcome prediction are among a number of factors that can make cataract surgery in keratoconic patients challenging. Accurate biometry is often difficult to obtain due to unreliable K measurements and lack of dedicated biometric formulae. The use of toric IOLs has also been investigated. CONCLUSIONS: Determining the stage of KC, pre-operative patient counselling and the preferred method of refractive correction are all crucial to obtain successful postoperative outcomes and good patient satisfaction. The use of toric IOLs can achieve good results only in selected low-grade keratoconic eyes.
ABSTRACT
Efficient enantiodiscrimination of some alanine-containing di- and tri-peptides by using chiral protonated bis(diamido)-bridged basket resorcin[4]arenes depends on several factors, including the basicity of the amino acid residues at the C- and N-termini of the peptide.
Subject(s)
Alanine/chemical synthesis , Calixarenes/chemistry , Diamide/chemistry , Peptides/chemical synthesis , Phenylalanine/analogs & derivatives , Alanine/chemistry , Kinetics , Molecular Conformation , Peptides/chemistry , Phenylalanine/chemistry , Protons , Quantum Theory , StereoisomerismABSTRACT
Keratoconus provides a decrease of quality of life to the patients who suffer from it. The treatment used as well as the method to correct the refractive error of these patients may influence on the impact of the disease on their quality of life. The purpose of this review is to describe the evidence about the conservative surgical treatment for keratoconus aiming to therapeutic and refractive effect. The visual rehabilitation for keratoconic corneas requires addressing three concerns: halting the ectatic process, improving corneal shape, and minimizing the residual refractive error. Cross-linking can halt the disease progression, intrastromal corneal ring segments can improve the corneal shape and hence the visual quality and reduce the refractive error, PRK can correct mild-moderate refractive error, and intraocular lenses can correct from low to high refractive error associated with keratoconus. Any of these surgical options can be performed alone or combined with the other techniques depending on what the case requires. Although it could be considered that the surgical option for the refracto-therapeutic treatment of the keratoconus is a reality, controlled, randomized studies with larger cohorts and longer follow-up periods are needed to determine which refractive procedure and/or sequence are most suitable for each case.
ABSTRACT
Most drugs used to treat pain and inflammation act through inhibition of the enzymes prostaglandin G/H synthase, commonly known as cyclooxygenase (COX). Among these, the simultaneous inhibition of cyclooxygenase 1 (COX-1) would explain the unwanted side effects in the gastrointestinal tract and many adverse cardiovascular effects, such as high blood pressure, myocardial infarction and thrombosis. These side effects led in time to the development of NSAIDs that behave as selective COX-2 inhibitors. This manuscript highlights the structure-activity relationships which characterize the chemical scaffolds endowed with selective COX-2 inhibition. Additionally, the role of COX-2 inhibitors in the pain phenomenon and cancer is discussed.
ABSTRACT
PURPOSE: To evaluate the long-term outcomes after femtosecond laser (FSL)-assisted mushroom-configuration keratoplasty in advanced keratoconus. PATIENTS AND METHODS: Thirteen eyes with Amsler-Krumeich stage IV keratoconus underwent FSL-assisted mushroom-configuration penetrating keratoplasty (PKP) and deep anterior lamellar keratoplasty (DALK) at a tertiary referral centre. Preoperative risk factors included low orneal thickness, high keratometry measurements, previous hydrops, and central stromal scarring. Main outcome measures were visual acuity and refractive outcome. RESULTS: The median follow-up was 33 months (range: 4-43). Preoperatively, the mean corrected distance visual acuity (CDVA) was 1.22±0.47 LogMAR (range: 0.5-1.9 LogMAR), mean minimum corneal thickness was 282±100.8 µm (range: 147-478 µm), and mean average keratometric (K) value was 63.4±7.63 dioptre (D; range: 57.0-75.7 D). Four patients underwent PKP and nine underwent DALK (two converted to PKP). Five patients subsequently underwent a modified arcuate mushroom interface dissection (AMID) procedure for astigmatic correction. At the final follow-up, the mean CDVA was 0.05±0.13 LogMAR (range: -0.10 to 0.20 LogMAR), mean spherical equivalent was -3.21±3.21D, mean cylindrical refractive error was 3.23±2.20 D, and mean average K was 43.1±1.53 D. Complications included early graft dehiscence, corneal vascularisation, stromal rejection, and sclerokeratitis. Sutures were completely removed at the mean 18.4 months for PKP and 9.1 months for DALK postoperatively. CONCLUSION: FSL-assisted mushroom-configuration keratoplasty is feasible and safe in patients with stage IV keratoconus. AMID could further enhance the refractive outcome safely.
Subject(s)
Corneal Surgery, Laser/methods , Corneal Transplantation/methods , Keratoconus/surgery , Keratoplasty, Penetrating/methods , Adult , Female , Humans , Intraoperative Complications , Keratoconus/classification , Keratoconus/physiopathology , Male , Middle Aged , Postoperative Complications , Refraction, Ocular/physiology , Visual Acuity/physiologyABSTRACT
Late arterial hypertension has been identified as a major predictor for morbidity and mortality in aortic coarctation (AoC) patients. Few data are available about efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta-blockers in young AoC patients. This study aimed to evaluate the tolerability and efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7) (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive patients with (a) no history of BP treatment or after >48 h of withdrawn, (b) aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d) >12 months from a successful AoC repair and (e) no major associated cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP monitoring, standard echocardiography, strain-strain rate imaging, at enrolment, 3, 6 and 12 months of treatment. We studied 51 AoC patients (13±3.9 years, BMI: 21.4±4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11±2 months. Both drugs were able to significantly reduce 24-systolic BP (SBP; atenolol: 133±11 mm Hg vs 124±16 mm Hg, P=0.016; enalapril: 135±6 mm Hg vs 127±7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI (47±12 vs 39.6±10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases (7.7%) drug withdrawal was needed because of adverse events. Enalapril and atenolol are similarly effective in reducing SBP. However, only enalapril demonstrated a significant reduction of LVMI. In no case, enalapril was stopped because of adverse events.
Subject(s)
Adrenergic beta-1 Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Aortic Coarctation/surgery , Atenolol/therapeutic use , Blood Pressure/drug effects , Cardiac Surgical Procedures , Enalapril/therapeutic use , Hypertension/drug therapy , Adolescent , Adrenergic beta-1 Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Aortic Coarctation/complications , Aortic Coarctation/diagnosis , Aortic Coarctation/physiopathology , Atenolol/adverse effects , Child , Enalapril/adverse effects , Female , Humans , Hypertension/diagnosis , Hypertension/etiology , Hypertension/physiopathology , Italy , Male , Prospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Therapeutic hypothermia (HT) has been shown to decrease death and severe disability in infants with hypoxic-ischemic encephalopathy (HIE). Rectal temperature (RT) is used to determine the temperature set-points for treatment with HT, however experimental studies have shown significant differences between RT and brain temperature during HT. Knowledge of actual brain temperature during HT might allow better determination of optimal degree of cooling and improve outcomes. OBJECTIVES: To compare measurements of brain temperature obtained by non-invasive radiometric thermometry (RadT) to direct tissue measurements in an experimental model of HT, and to use RadT in newborn infants with HIE undergoing HT. STUDY DESIGN: RadT measurements of brain temperature were compared to fiber optic (Luxtron) thermometry measurements placed at a depth of 1.5 centimeters into the brain of cooled miniswine. Following validation studies, brain RadT and RT measurements were continuously recorded in thirty infants with HIE during HT and rewarming. RESULTS: RadT and Luxtron probe temperatures were comparable in miniswine throughout a temperature range similar to therapeutic HT. RadT measurements of brain temperature were higher than RT in 60% of infants with HIE undergoing HT. Higher RadT measurements compared to RT were associated with cerebral white matter abnormalities (p = 0.01). CONCLUSIONS: RadT provides a safe, passive and non-invasive way to measure brain temperature that can be used in the clinical setting. RadT may be helpful in determining the optimal degree of cooling and identifying infants at highest risk of brain injury.
Subject(s)
Asphyxia Neonatorum/physiopathology , Body Temperature/physiology , Hypoxia-Ischemia, Brain/physiopathology , Animals , Disease Models, Animal , Humans , Hypothermia, Induced/methods , Hypoxia-Ischemia, Brain/therapy , Infant, Newborn , Magnetic Resonance Imaging/methods , Swine , Thermometry/methodsABSTRACT
BACKGROUND: Placebo-controlled studies in maintaining remission of symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking. AIM: To assess the effectiveness of mesalazine and/or probiotics in maintaining remission in SUDD. METHODS: A multicentre, double-blind, placebo-controlled study was conducted. Two hundred and ten patients were randomly enrolled in a double-blind fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24 billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp. DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG placebo plus mesalazine placebo). Patients received treatment for 10 days/month for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal pain during follow-up, scored as ≥5 (0: best; 10: worst) for at least 24 consecutive hours. RESULTS: Recurrence of SUDD occurred in no (0%) patient in group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs. L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P = 0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six group P cases and in one group L case (P = 0.003). CONCLUSION: Both cyclic mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given in combination, appear to be better than placebo for maintaining remission of symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov: NCT01534754).
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diverticulum, Colon/drug therapy , Mesalamine/therapeutic use , Probiotics/therapeutic use , Abdominal Pain/etiology , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Diverticulum, Colon/pathology , Double-Blind Method , Female , Follow-Up Studies , Humans , Lactobacillus , Male , Mesalamine/administration & dosage , Middle Aged , Secondary Prevention , Treatment OutcomeABSTRACT
Androgens' metabolism and activity are gaining a more and more important role in human physiology particularly referring to aging and to neurodegenerative diseases. Androgen treatment is often required for long-lasting disorders. In order to improve their duration and effects, androgens can be administered as esters of carboxylic acids. The novelty of our research is the use of esters of androgens with specific unsaturated fatty acids, in order to reduce possible side effects particularly related to chronic pathologies with altered lipid homeostasis such as X-linked adrenoleukodystrophy and cardiovascular disorders. Thus the esters of the main androgenic substances testosterone, dihydrotestosterone (DHT) and their metabolite 5α-androstan-3α,17ß-diol were chemically obtained by coupling with different unsaturated fatty acids. To this aim, fatty acids with various degree of unsaturation and belonging to different series were selected. Specifically, oleic acid (18:1, n-9), linoleic acid (18:2, n-6), and the n-3 fatty acids, α-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) were used obtaining corresponding esters with acceptable yields and good degree of purity. All the synthesized compounds were tested for their cytotoxic activities in mouse NIH3T3 and human astrocyte cell lines. The esters demonstrated good tolerability and no in vitro cytotoxic effect in both cell cultures. After these promising preliminary results, the esters will be suitable for in vivo studies in order to ascertain their pharmacokinetic characteristics and their biological effects.
Subject(s)
Esters/chemical synthesis , Fatty Acids, Unsaturated/chemistry , Testosterone Congeners/chemical synthesis , Testosterone Congeners/therapeutic use , Adipocytes/drug effects , Adipocytes/physiology , Animals , Astrocytes/drug effects , Astrocytes/physiology , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Esters/pharmacology , Esters/therapeutic use , Hormone Replacement Therapy/methods , Humans , Mice , Models, Biological , NIH 3T3 Cells , Testosterone Congeners/pharmacologyABSTRACT
ExtraMedullary Plasmacytoma (EMP) is a rare plasma cell tumor. It can occur in the upper aerodigestive tract and presents as a large nodule causing local compressive symptoms. A 79-year old woman presented to Otorhinolaryngology Department with progressive hearing loss and no other symptoms. Following PET/TC examination due to the suspicion of a lymphoproliferative disease, the patient underwent tonsillectomy and the diagnosis of solitary EMP was formulated. In addition to that, the histological examination of the tonsillar tissue revealed large colonies of filamentous bacteria, showing abundant sulphur granules and Splendore-Hoeppli phenomenon; these evidences indicating the presence of a chronic Actinomyces infection. Immunohistochemical analysis demonstrated a marked IL-6 immunoreactivity of the neoplastic plasma cells. Interestingly, a marked IL-6 immunoreactivity was also found in the tissue surrounding the Actinomyces colonies. In the present study we report for the first time a solitary EMP associated with Actinomycosis. It is tempting to speculate that the unsuspected and untreated Actinomyces infection, through chronic IL-6 production, could contribute to the neoplastic transformation of plasma cells.
Subject(s)
Actinomyces , Actinomycosis , Cell Transformation, Neoplastic , Interleukin-6/metabolism , Plasmacytoma , Tonsillar Neoplasms , Actinomycosis/complications , Actinomycosis/metabolism , Actinomycosis/microbiology , Actinomycosis/pathology , Aged , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Humans , Plasma Cells/metabolism , Plasma Cells/microbiology , Plasma Cells/pathology , Plasmacytoma/etiology , Plasmacytoma/metabolism , Plasmacytoma/microbiology , Plasmacytoma/pathology , Tonsillar Neoplasms/etiology , Tonsillar Neoplasms/metabolism , Tonsillar Neoplasms/microbiology , Tonsillar Neoplasms/pathologyABSTRACT
In renal transplant patients, glomerulitis may be present in all types of acute rejection, often accompanied by diffuse C4d staining of peritubular capillaries: C4d3 positivity in more than 50% of peritubular capillaries. It may progress to chronic transplant glomerulopathy, characterized by capillary basement membrane multilayering, proteinuria, and progressive loss of renal function. While C4d3 is a recognized marker of an antibody-mediated reaction, the significance of glomerular C4d (GlC4d) staining is unknown. The aim of this study was to evaluate GlC4d immunoreactivity and its correlation with C4d3 in acute rejection biopsies. Paraffin-embedded acute rejection biopsies from 90 renal transplant patients were evaluated according to the Banff classification. Biopsies showing C4d-positive endothelial cells in more than 50% of glomeruli were considered GlC4d-positive. C4d3-positive staining prevalence was 23%. GlC4d-positive staining showed an 89% concordance rate (r = 0.81, P < .0001; Cohen's k = 0.80, P < .0001). GlC4d detection sensitivity was 0.80 and specificity 0.97. C4d3 and GlC4d immunoreactivity was significantly associated with glomerulitis (P < .006 and P < .03, respectively) and with proteinuria at the time of biopsy (P < .03 and P < .01, respectively). Interestingly, GlC4d positivity correlated better than C4d3 positivity with the presence of posttransplant circulating anti-human leukocyte antigen alloantibodies (P < .04 and P = .7, respectively). Patients with C4d3- or GlC4d-positive acute rejections underwent graft loss due to interstitial fibrosis and tubular atrophy more frequently than those with C4d0- or GlC4d-negative rejections (P < .0001 and P < .005, respectively), whereas no differences were observed in graft loss due to death. In conclusion, C4d3 and GlC4d stains showed a high correlation rate. Compared with C4d3, GlC4d staining demonstrated good sensitivity and excellent specificity. Our results suggested that GlC4d staining may indicate glomerular endothelial damage and be of prognostic value.
Subject(s)
Graft Rejection , Kidney Glomerulus/immunology , Kidney Transplantation , Biopsy , Humans , Kidney Glomerulus/pathology , Paraffin EmbeddingABSTRACT
AIM: Information about fecal calprotectin (FC) in segmental colitis associated with diverticulosis (SCAD) is lacking. We assessed FC in SCAD, comparing it healthy controls (HC), irritable bowel syndrome (IBS), diverticular disease (DD), ulcerative colitis (UC). Moreover, we compared FC levels in different degrees of SCAD and assessed FC SCAD before and after treatment. METHODS: Twenty-seven consecutive patients with a new endoscopic diagnosis of SCAD, and 16 patients for each control group, underwent to FC assessment. FC was assessed by semi-quantitative method. RESULTS: FC was not increased in HC and in IBS patients, whilst it was increased in DD, SCAD, and UC. FC concentration was higher in SCAD and UC than in DD (SCAD vs. DD, P=0.05). No difference was found in FC concentration between SCAD and UC (P=0.213), as well as between different degree of SCAD (P= 0.178). After treatment, FC values decreased to normal values in all patients obtaining remission (P<0.0005). Three patients experienced still symptoms (one SCAD type B and two SCAD type D patients), and in all of them FC was still detectable. CONCLUSION: FC may be useful in differentiating SCAD from functional syndromes. Moreover, it may be useful in assessing response to therapy.