Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study

BACKGROUND: The process of elimination of intracellular pathogens, such as Leishmania, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite. METHODS: Blood was collected from 31 patients with either localized cutaneous (LCL), mucosal (ML) or visceral (VL) leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-Leishmania humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry. RESULTS: A significant decrease in plasma Zn was observed in all three patient groups (p < 0.01 for LCL and ML, p < 0.001 for VL), as compared to controls, but only VL (7/10) and ML (1/7) patients displayed overt Zn deficiency. Plasma Cu was increased in LCL and VL (p < 0.001) but not in ML, and was strongly correlated to anti-Leishmania IgG (Spearman r = 0.65, p = 0.0028). Cu/Zn ratios were highest in patients with deficient cellular (VL<<LCL<ML) and exacerbated humoral (VL>LCL>ML) immune response. Ex vivo production of parasite-induced IFN-γ was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01). In vitro, increased Cu levels inhibited IFN-γ production. CONCLUSIONS: 1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-γ production

Hepatobiliary and pancreatic tuberculosis: A two decade experience

<p>Abstract</p> <p>Background</p> <p>Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis.</p> <p>Methods</p> <p>The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli.</p> <p>Results</p> <p>Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> intraabdominal abscess <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months).</p> <p>Conclusion</p> <p>Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.</p

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate