Risk factors for granulomas in children following immunization with aluminium-adsorbed vaccines: A Danish population-based cohort study.

BACKGROUND: Aluminium-adsorbed vaccines may in some children cause severely itching nodules at the injection site, known as vaccination granulomas. OBJECTIVE: To investigate vaccine-, child- and maternal-level risk factors for the development of vaccination granulomas following immunization with aluminium-adsorbed vaccines. METHODS: A Danish population-based cohort study with 553 932 children born in Denmark from 1 January 2009 to 31 December 2018, vaccinated with an aluminium-adsorbed vaccine during the first year of life, followed until 31 December 2020. Poisson regression was used to estimate granuloma rate ratios according to the type of adjuvant, accumulated dose of aluminium, timing of vaccination appointments, sex, gestational age, having siblings with granulomas, maternal age and maternal ethnicity. RESULTS: We identified 1901 vaccination granuloma cases (absolute risk, 0.34%). Among vaccine level factors, revaccination (third vs. first vaccination appointment, adjusted rate ratio [RR] 1.26, 95% confidence interval [CI] 1.03-1.55), the specific adjuvant used (aluminium phosphate vs. hydroxide, RR 0.58, 95% CI 0.48-0.70) and dosage (≥1.0 mg vs. <1.0 mg, RR 1.34, 95% CI 1.19-1.52) were associated with risk of granulomas; the timing of vaccination appointments was not. Among child-level factors, female sex (vs. males, RR 1.12, 95% CI, 1.02-1.22), prematurity (vs. term birth, RR 0.71, 95% CI, 0.54-0.93) and having sibling(s) with granulomas (vs. no siblings with granulomas, RR 46.15, 95% CI, 33.67-63.26) were associated with risk of granulomas. Among maternal-level factors, non-Danish ethnicity (vs. Danish, RR 0.51, 95% CI, 0.42-0.63) and young maternal age (<20 years vs. 20-39 years, RR 0.46, 95% CI 0.25-0.83) were associated with risk of granulomas. CONCLUSIONS: Several risk factors for vaccination granulomas at the vaccine, child and maternal levels, were identified. Reducing the dose of aluminium or replacing aluminium hydroxide with aluminium phosphate could reduce the risk of granulomas. However, this must be balanced against the potential for reduced immunogenicity.

FOLFOX and capecitabine-induced hepatic granuloma mimicking metastasis in a rectal cancer patient.

A 49-year-old male carcinoma rectum patient was treated with neoadjuvant FOLFOX (folinic acid, fluorouracil (5-FU) and oxaliplatin) chemotherapy, chemoradiotherapy with capecitabine, surgery and adjuvant FOLFOX. On follow-up, the patient developed a metabolically active liver lesion mimicking metastasis. Liver biopsy and histopathology showed sinusoidal dilatation with non-caseating granulomas. Follow-up fluorodeoxyglucose positron-emission tomography CT scan demonstrated increase in size of the lesion with metabolic activity suspicious of metastasis. The patient underwent segmental liver resection and histopathology showed non-necrotising granuloma with no evidence of malignancy. It is crucial to consider potential side effects of chemotherapeutic agents and have an unbiased approach when evaluating new liver lesions during post treatment follow-up of colorectal cancer. A multidisciplinary tumour board approach comprising of gastroenterologists, medical oncologists, pathologists, radiologists and surgeons is suggested in the management of such patients. The patient is currently doing well and on regular follow-up.

Anti-Inflammation Effect of Small Molecule Oligopeptides Prepared from Panax ginseng C. A. Meyer in Rats.

The present study was designed to investigate the anti-inflammatory effects of ginseng oligopeptides (GOPs). For the anti-inflammatory activity, dextran-induced paw edema and granuloma models were used in Sprague-Dawley rats (180⁻200 g, 12 weeks old, n = 10). Rats were treated orally with GOPs (0, 62.5, 125, 250 and 500 mg/kg) for prophylaxis. In the granuloma model, the levels of NO, Tumor necrosis factor-α (TNF-α), interleukin IL-ß, and interleukin IL-10 in serum were evaluated. In addition, in the edema model, the level of TNF-α, prostaglandin E2 (PGE2), Leukotriene D4 (LTD4), and the platelet activating factor (RAF) in paw tissue were detected. PCR assessed the effect of GOPs on the expression of MAPK and NF-κB. The results showed that oral administration of GOPs inhibited inflammation caused by cotton pellet and dextran. GOPs significantly inhibited the edema formation via MAPK and NF-κB. These findings suggested that GOPs have a beneficial effect on acute and chronic inflammation, and the mechanism possibly mediated by inhibiting gene expression involved in inflammation and downregulating inflammatory mediators.

Physicochemical characterization of inorganic deposits associated with granulomas in cutaneous sarcoidosis.

BACKGROUND: Sarcoidosis, characterized by epithelioid granulomas, is considered to be caused by a complex interplay between genetics and environmental agents. It has been hypothesized that exogenous inorganic particles as crystalline silica could be a causal or adjuvant agent in sarcoidosis onset. OBJECTIVES: To investigate the location, frequency and physicochemical characteristics of foreign materials and mineral tissue deposits in the granulomatous area of cutaneous sarcoidosis. METHODS: Skin biopsies (n = 14) from patients diagnosed with cutaneous sarcoidosis (mean age 43 years; 11 patients with extracutaneous involvement) were investigated using polarized light examination (PLE), µFourier Transform Infra-Red (µFT-IR) spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (FE-SEM/EDX). RESULTS: Combined PLE, µFT-IR, FE-SEM/EDX analysis allowed to characterize mineral deposits in 7/14 biopsies (50%). It identified crystalline silica (SiO2 ) inside granulomas in three biopsies and calcite (CaCO3 ) at their periphery in 4. CONCLUSION: This study emphasizes the need of using combined methods for assessment of mineral deposits in granulomatous diseases. According to the location and characteristics of deposits, we can hypothesize that SiO2 particles contribute to the granuloma formation, whereas CaCO3 deposits are related to the granuloma biology. However, the significance of the association between SiO2 deposits and sarcoidosis is still disputed.

Methanolic Extract of Leathery Murdah, Terminalia coriacea (Roxb.) Wight and Arn. Leaves Exhibits Anti-Inflammatory Activity in Acute and Chronic Models.

OBJECTIVE: The aim of the present study was to evaluate anti-inflammatory activity of methanolic extract of Terminalia coriacea. MATERIALS AND METHODS: A methanolic extract of T. coriacea leaves was studied in albino Wistar rats with carrageenan-induced paw edema, an acute model, and cotton pellet-induced granuloma, a chronic model, at 3 oral test doses (125, 250, and 500 mg/kg). Aspirin 100 mg/kg was used as a positive control. Paw volume and wet and dry weights of cotton pellets were determined. The data were analyzed by one-way ANOVA followed by Dunnett's multiple comparison test. RESULTS: The test extract at doses of 125 and 250 mg/kg decreased paw volume and wet and dry weights of cotton pellets. The highest test dose (500 mg/kg) displayed a response comparable to that of the standard drug (p < 0.01) on paw volume. The extract produced similar (p < 0.05) decrease in wet weight of the cotton pellet at 125 and 250 mg/kg, whereas the effect of 500 mg/kg of the extract was comparable to that of aspirin 100 mg/kg (p < 0.01). The extract of T. coriacea at 500 mg/kg induced the most significant (p < 0.01) effect on wet weight of granulomatous tissue. CONCLUSION: The methanolic extract of T. coriacea leaves successfully decreased paw edema as well as dry and wet weights of granulomatous tissue in both acute and chronic inflammatory models thus confirming the anti- edematogenic, antitransudative, and antiproliferative properties of T. coriacea.

Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclay in Mice.

Organomodified nanoclays (ONCs) are increasingly used as filler materials to improve nanocomposite strength, wettability, flammability, and durability. However, pulmonary risks associated with exposure along their chemical lifecycle are unknown. This study's objective was to compare pre- and post-incinerated forms of uncoated and organomodified nanoclays for potential pulmonary inflammation, toxicity, and systemic blood response. Mice were exposed via aspiration to low (30 µg) and high (300 µg) doses of preincinerated uncoated montmorillonite nanoclay (CloisNa), ONC (Clois30B), their respective incinerated forms (I-CloisNa and I-Clois30B), and crystalline silica (CS). Lung and blood tissues were collected at days 1, 7, and 28 to compare toxicity and inflammation indices. Well-dispersed CloisNa caused a robust inflammatory response characterized by neutrophils, macrophages, and particle-laden granulomas. Alternatively, Clois30B, I-Clois30B, and CS high-dose exposures elicited a low grade, persistent inflammatory response. High-dose Clois30B exposure exhibited moderate increases in lung damage markers and a delayed macrophage recruitment cytokine signature peaking at day 7 followed by a fibrotic tissue signature at day 28, similar to CloisNa. I-CloisNa exhibited acute, transient inflammation with quick recovery. Conversely, high-dose I-Clois30B caused a weak initial inflammatory signal but showed comparable pro-inflammatory signaling to CS at day 28. The data demonstrate that ONC pulmonary toxicity and inflammatory potential relies on coating presence and incineration status in that coated and incinerated nanoclay exhibited less inflammation and granuloma formation than pristine montmorillonite. High doses of both pre- and post-incinerated ONC, with different surface morphologies, may harbor potential pulmonary health hazards over long-term occupational exposures.

Evaluation of the anti-inflammatory effect of an anti-platelet agent crinumin on carrageenan-induced paw oedema and granuloma tissue formation in rats.

The present study was designed to explore the anti-inflammatory activity of an anti-platelet agent crinumin, by various in vitro and in vivo inflammation models. Firstly, crinumin protein was purified through cation exchange chromatography; then, in vitro activity was estimated by albumin denaturation assay and HRBC membrane stabilization assay. Carrageenan-induced paw oedema and cotton pellet-induced granuloma models were used for in vivo anti-inflammatory activity assessment in rats. In both models, rats were pre-treated for 7 days with crinumin (25-50 µg/ml) and diclofenac sodium (50 µg/ml). Expression of P-selectin (in serum and plasma) through ELISA and NF-κB (in paw and granulomatous tissues) through western blotting was checked. Our results showed that crinumin at both doses (25 or 50 µg/kg of b.w.) significantly (p < 0.05) reduced the paw oedema formation in a dose-dependent manner in the second phase of inflammation and significant (p < 0.05) reduction of wet and dry weight of granuloma was observed indicating the anti-inflammatory potential of crinumin. Crinumin decreased the expression of P-selectin and NF-κB indicating its potential role in decreasing platelet activation and healing inflammation. Histopathological studies additionally proved the efficacy of drug in treating inflammation. The results of the study suggest that the crinumin might have an inhibitory role in atherosclerosis as platelet aggregation and inflammation are the key processes involved in atherosclerotic disorders.