The effect of infused fat emulsions on reticuloendothelial function in the rabbit

The effect of the infusion of different fat emulsions (Intralipid and MCT/LCT mixtures) on the reticuloendothelial function of the rabbit has been investigated. Emulsions containing 20% dispersed triglyceride were administered over 6 h to a total of 3 g/kg body weight. The extent of blockade of the reticuloendothelial system was measured using a labelled probe in the form of technetium-99m labelled albumin microspheres. Scintigraphic and blood and organ level determinations demonstrated that all emulsions caused an impairment of reticuloendoethlial function, but this was small.     

The sensitivity to Zn2+ discriminates between typical and atypical mast cells.

The effects of zinc gluconate have been studied on rat peritoneal mast cells and rat basophilic leukemia cells (RBL 2H3) stimulated by various secretagogues. The IC50's of zinc gluconate on peritoneal cells were (microM): 1.6, 1.9, 5.4 and 18 for ionophore A23187, phorbol 12-myristate 13-acetate, substance P and immunoglobulin E-antigen, respectively. Higher concentrations of zinc gluconate were required to inhibit histamine secretion from RBL 2H3 cells, i.e. 12 microM (ionophore A23187) and 140 microM (immunoglobulin E-antigen). Zinc gluconate (10(-4) to 10(-3) M) also inhibited the IgE-dependent contraction of guinea pig trachea but was unable to affect that induced by exogenous histamine. These results suggest that zinc gluconate acts intracellularly and is selective of "typical" or "connective tissue" mast cells.     

Innate immune inflammatory cell death: PANoptosis and PANoptosomes in host defense and disease

Regulated cell death (RCD) triggered by innate immune activation is an important strategy for host survival during pathogen invasion and perturbations of cellular homeostasis. There are two main categories of RCD, including nonlytic and lytic pathways. Apoptosis is the most well-characterized nonlytic RCD, and the inflammatory pyroptosis and necroptosis pathways are among the best known lytic forms. While these were historically viewed as independent RCD pathways, extensive evidence of cross-talk among their molecular components created a knowledge gap in our mechanistic understanding of RCD and innate immune pathway components, which led to the identification of PANoptosis. PANoptosis is a unique innate immune inflammatory RCD pathway that is regulated by PANoptosome complexes upon sensing pathogens, pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) or the cytokines produced downstream. Cytosolic innate immune sensors and regulators, such as ZBP1, AIM2 and RIPK1, promote the assembly of PANoptosomes to drive PANoptosis. In this review, we discuss the molecular components of the known PANoptosomes and highlight the mechanisms of PANoptosome assembly, activation and regulation identified to date. We also discuss how PANoptosomes and mutations in PANoptosome components are linked to diseases. Given the impact of RCD, and PANoptosis specifically, across the disease spectrum, improved understanding of PANoptosomes and their regulation will be critical for identifying new therapeutic targets and strategies.     

Somatic symptoms,pain, catastrophizing and the association with disability among children with heritable connective tissue disorders

The aim of the present study was to investigate the nature and prevalence of nonspecific somatic symptoms, pain and catastrophizing in children with Heritable Connective Tissue Disorders (HCTD), and to determine their association with disability. This observational, multicenter study included 127 children, aged 4–18 years, with Marfan syndrome (MFS) (59%), Loeys-Dietz syndrome (LDS) (8%), Ehlers-Danlos syndromes (EDS) (12%) and hypermobile Ehlers-Danlos syndrome (hEDS) (23%). The assessments included the Children's Somatization Inventory or parent proxy (CSI, PCSI), pain visual-analogue scale (VAS), SUPERKIDZ body diagram, Pain Catastrophizing Scale Child or parent proxy (PCS-C, PCS-P) and Childhood Health Assessment Questionnaire (CHAQ-30). Data from children aged ≥8 years were compared to normative data. In children ≥ 8 years (n = 90), pain was present in 59%, with a median of 4 (IQR = 3–9) pain areas. Compared to normative data, the HCTD group reported significantly higher on the CSI (p ≤ 0.001, d = 0.85), VAS pain intensity (p ≤ 0.001, d = 1.22) and CHAQ-30 (p ≤ 0.001, d = 1.16) and lower on the PCS-C (p = 0.017, d = −0.82) and PCS-P (p ≤ 0.001, d = −0.49). The intensity of nonspecific somatic symptoms and pain explained 45% of the variance in disability (r² = 0.45 F(2,48) = 19.70, p ≤ 0.001). In children ≤ 7 years (n = 37), pain was present in 35% with a median of 5(IQR = 1–13) pain areas. The mean(SD) VAS scores for pain intensity was 1.5(2.9). Functional disability was moderately correlated to the number of pain areas (r = 0.56, p ≤ 0.001), intensity of nonspecific somatic symptoms (r = 0.63, p ≤ 0.001) and pain (r = 0.83, p ≤ 0.001). In conclusion, this study supports the need for comprehensive assessment of nonspecific somatic symptoms, pain, and disability in children with HCTD to allow tailored treatment.     

Herpes zoster and multiple sclerosis

BACKGROUND: Clinical experience suggests that young multiple sclerosis patients may have herpes zoster (HZ) earlier and more often than the general population. As there is evidence of a relationship between varicella zoster virus (VZV) and MS, a study of HZ and MS was undertaken. METHODS: Eight hundred and twenty-nine patient-members of the Manitoba Chapter of the Canadian Multiple Sclerosis Society were surveyed by mail. Six hundred and thirty-three (76%) responded. Questions included: age at diagnosis of MS, history of HZ (yes, no, probably), number of episodes of HZ and age at each occurrence, date of birth, and sex of respondent. The controls were consecutive patients with other neurological diseases (OND) attending local neurological or neurosurgical clinics, plus practice-based and population-based surveys of herpes zoster without reference to any other disease. The OND controls were assessed at the time of their outpatient visits. RESULTS: In the MS group with a positive/probable history of HZ, the HZ/MS rate was 106/633 (16.8%); in the practice-based survey the rate was 192/3534 (5.4%); and among the patients with OND it was 42/616 (6.8%). The HZ occurred at an earlier age in the MS group. The majority of male patients had HZ prior to the diagnosis of MS. The date of diagnosis is more likely to be a precise memory as opposed to the onset of symptoms. More than one attack of HZ was also more common in the MS group. CONCLUSIONS: This survey adds to the evidence that patients with MS have a unique relationship with the herpes zoster virus.