CNS activity of Pokeweed Anti-viral Protein (PAP) in mice infected with Lymphocytic Choriomeningitis Virus (LCMV)

BACKGROUND: Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein) against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV). METHODS: We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation. RESULTS: PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069). CONCLUSION: Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice

Post-streptococcal reactive arthritis in children: a distinct entity from acute rheumatic fever

There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question

Evaluation of the Novel Folate Receptor Ligand [18F] Fluoro-PEG-Folate for Macrophage Targeting in a Rat Model of Arthritis.

Introduction Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [18F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model. Methods [18F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [18F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[11C]PK11195. Results [18F]fluoro-PEG-folate was synthesized with a purity \u3e97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [18F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [18F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [18F]fluoro-PEG-folate were increased compared with those of (R)-[11C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [18F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios. Conclusions The novel PET tracer [18F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[11C]PK11195. These results warrant further exploration of [18F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients

E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer?

Loss of heterozygosity at the long arm of chromosome 16 is one of the most frequent genetic events in breast cancer. In the search for tumour suppressor genes that are the target of loss of heterozygosity at 16q, the E-cadherin gene CDH1 was unveiled by the identification of truncating mutations in the retained copy. However, only lobular tumours showed E-cadherin mutations. Whereas investigations are still devoted to finding the target genes in the more frequent ductal breast cancers, other studies suspect the E-cadherin gene to also be the target in this tumour type. The present article discusses the plausibility of those two lines of thought

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation

The optimal starting time of postoperative intraperitoneal mitomycin-C therapy with preserved intestinal wound healing

BACKGROUND: There is controversy about the effect of the timing of intraperitoneal administration of chemotherapeutic agents on the healing of intestinal anastomosis. We have investigated the effect on intestinal wound healing of mitomycin-C administered at different times post-operatively. METHODS: Eighty-four Wistar-Albino female rats underwent ileal resection and end-to-end anastomosis. The rats were randomly selected for intraperitoneal administration of mitomycin-C or saline as follows: mitomycin-C group (n = 65), 2 mg/kg mitomycin-C; control group (n = 13), 10 ml saline. The former was sub-divided into 5 equal groups (A 1–5) and mitomycin-C was administered postoperatively as follows: day 0 (A1), day 3 (A2), day 5 (A3), day 7 (A4) and day 10 (A5). All the rats were sacrificed on the 14th postoperative day and anastomotic bursting pressures and tissue hydroxyproline levels were determined. RESULTS: Five of the animals died postoperatively: 2 (15.4%) in group A1, 2 (15.4%) in group A2 and 1(7.7%) in group A3. Non-lethal anastomotic leakage was observed in a further five animals: 1 in group A1, 2 in group A2, 1 in group A5 and 1 in the control group. Groups A1 and A2 had significantly lower anastomotic bursting pressures than the other groups (P was <0.05 for each comparison). The anastomotic bursting pressures of group A3, A4 and A5 were comparable with those of the controls (P was >0.05 for each comparison). Tissue hydroxyproline levels in group A1 and A2 were significantly lower than in the controls (P values were <0.05 for each comparison) or the other mitomycin-C sub-groups (P was <0.05 for each comparison). CONCLUSIONS: Intraperitoneal chemotherapy impairs intestinal wound healing when applied before the 5th postoperative day. Additional therapeutic approaches are needed to prevent this potentially lethal side effect of early intraperitoneal mitomycin-C administration