Ultrasonigraphic Evidence of Abnormal Lymphatic Vessels in Young Men with Adult Wuchereria Bancrofti Infection in the Scrotal Area

Purpose

We determined the prevalence and magnitude of dilatation of the lymphatic vessels of the spermatic cord in men infected with Wuchereria bancrofti, which is a known major cause of hydrocele in the tropics.

Materials and Methods

Scrotal ultrasound was performed with a 7.5 MHz, transducer in 78 men from Recife, Brazil (endemic for filariasis) and in 15 from a nonendemic area.

Results

Among men from Recife the lymphatic vessels were dilated (1.3 to 15.0 mm., mean 3.8) at the location of the adult worm. Vessel diameter was not associated with hydrocele.

Conclusions

Lymphatic dilatation was observed in all men with ultrasonographically detectable W. bancrofti infection, even those who were asymptomatic.     

Immune-pineal axis protects rat lungs exposed to polluted air

Environmental pollution in the form of particulate matter <2.5 μm (PM_2.5) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM_2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pineal synthesis and increasing the extrapineal synthesis of melatonin. Herein, we report that the exposure of rats to polluted air for 6 hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM_2.5 engulfment and cell viability by activating high-affinity melatonin receptors. Diesel exhaust particles (DEPs) promoted the synthesis of melatonin in a cultured cell line (RAW 264.7 cells) and rat alveolar macrophages via the expression of the gene encoding for AANAT through a mechanism dependent on activation of the NFκB pathway. Expression of the genes encoding AANAT, MT1, and MT2 was negatively correlated with cellular necroptosis, as disclosed by analysis of Gene Expression Omnibus (GEO) microarray data from the human alveolar macrophages of nonsmoking subjects. The enrichment score for antioxidant genes obtained from lung gene expression data (GTEx) was significantly correlated with the levels of AANAT and MT1 but not the MT2 melatonin receptor. Collectively, these data provide a systemic and mechanistic rationale for coordination of the pineal and extrapineal synthesis of melatonin by a standard damage-associated stimulus, which activates the immune-pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

Chagasic patients are able to respond against a viral antigen from influenza virus

ABSTRACT: BACKGROUND: Trypanosoma cruzi, the etiological agent of Chagas' disease, is an obligate intracellular parasite which induces a CD8+ T cell immune response with secretion of cytokines and release of cytotoxic granules. Although an immune-suppressive effect of T. cruzi on the acute phase of the disease has been described, little is known about the capacity of CD8+ T cell from chronic chagasic patients to respond to a non-T. cruzi microbial antigen.Methods and resultsIn the present paper, the frequency, phenotype and the functional activity of the CD8+ T cells specific from Flu-MP*, an influenza virus epitope, were determined in 13 chagasic patients and 5 healthy donors. The results show that Flu-MP* peptide specific CD8+ T cells were found with similar frequencies in both groups. In addition, Flu-MP* specific CD8+ T cells were distributed in the early or intermediate/late differentiation stages without showing enrichment of a specific sub-population. The mentioned Flu-MP* specific CD8+ T cells from chagasic patients were predominately TEM (CCR7- CD62L-), producing IL-2, IFNgamma, CD107a/b and perforin, and did not present significant differences when compared with those from healthy donors. CONCLUSIONS: Our results support the hypothesis that there is no CD8+ T cell nonspecific immune-suppression during chronic Chagas disease infection. Nonetheless, other viral antigens must be studied in order to confirm our findings.     

Antimicrobial terpenoids from the oleoresin of the Peruvian medicinal plant Copaifera paupera

Twelve known diterpenes 1 - 11 and 13, and three known sesquiterpenes 14 - 16, along with a new C(20) - C(15) terpenoid 17, with a structure based on an unprecedented skeleton in which a labdane diterpene is linked to a monocyclic sesquiterpene by an ester bridge, were isolated from the oleoresin of the Peruvian medicinal plant Copaifera paupera (Herzog) Dwyer (Leguminosae). Their structures were elucidated on the basis of spectral analysis, including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HMQC and HMBC), and by comparison with data in the literature. The leishmanicidal, antimicrobial, cytotoxic, and aldose reductase inhibitory activities were studied. Compounds 1 and 11 showed significant antimicrobial activity (MIC < 10 microg/ml) against Gram-positive bacteria, comparable with cephotaxime used as control. Compound 2 exhibited moderate cytotoxic activity against four cancer cell lines.     

Screening of army soldiers for Wuchereria bancrofti infection in the metropolitan Recife region, Brazil: implications for epidemiological surveillance

Between 1989 and 1995, blood surveys were performed for Wuchereria bancrofti infection in several barracks of the Brazilian army in the metropolitan Recife region. For initial screening, 60 microliters of capillary blood were examined for microfilaria. All men who tested positive had microfilaria quantified by filtration of venous blood through a polycarbonate membrane. Of 23,773 men screened, 585 (2.5%) had microfilaria (mf). Microfilarial density ranged from < 1-8706 mf/ml of blood. Thirteen individuals had ultra-low microfilarial densities (1 mf/11 ml of blood). Characterization of 174 autochthonous cases made it possible to map 8 new districts in 4 cities within metropolitan Recife region where transmission of W. bancrofti was previously unknown. Routine screening of soldiers in the military may provide important surveillance data for national programmes to eliminate transmission of W. bancrofti.     

Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients

Background  

Antigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein_192-433, and the entire Trypanosoma rangeli HSP-70 protein.     

PTH Induces Systemically Administered Mesenchymal Stem Cells to Migrate to and Regenerate Spine Injuries

Osteoporosis affects more than 200 million people worldwide leading to more than 2 million fractures in the United States alone. Unfortunately, surgical treatment is limited in patients with low bone mass. Parathyroid hormone (PTH) was shown to induce fracture repair in animals by activating mesenchymal stem cells (MSCs). However, it would be less effective in patients with fewer and/or dysfunctional MSCs due to aging and comorbidities. To address this, we evaluated the efficacy of combination i.v. MSC and PTH therapy versus monotherapy and untreated controls, in a rat model of osteoporotic vertebral bone defects. The results demonstrated that combination therapy significantly increased new bone formation versus monotherapies and no treatment by 2 weeks (P < 0.05). Mechanistically, we found that PTH significantly enhanced MSC migration to the lumbar region, where the MSCs differentiated into bone-forming cells. Finally, we used allogeneic porcine MSCs and observed similar findings in a clinically relevant minipig model of vertebral defects. Collectively, these results demonstrate that in addition to its anabolic effects, PTH functions as an adjuvant to i.v. MSC therapy by enhancing migration to heal bone loss. This systemic approach could be attractive for various fragility fractures, especially using allogeneic cells that do not require invasive tissue harvest.