A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer

Context

Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results.

Upregulation of CD4+ T-Lymphocytes by Isomeric Mixture of Quercetin-3-O-Rutinoside and Quercetin-3-O-Robinobioside Isolated from Millettia aboensis

Background: Millettia aboensis (Hook. F.) Baker (Fabaceae) is popular in ethnomedicine for its acclaimed efficacy in a number of disease conditions. This study evaluated the immunomodulatory effect of the leaf extract as a possible mechanism of its ethnomedicinal uses.

Methods: Humoral and cellular immune responses of Balb/c mice to tetanus toxoid and cyclophosphamide, respectively, were used to monitor immunomodulatory activities of the ethanol leaf extract and fractions of M. aboensis at 200, 300 and 400 mg/kg. Active (butanol) fraction of the extract was subjected to chromatographic purifications to isolate the active compound and the structure elucidated by a combination of 1D and 2D NMR and mass spectrometry. Stimulation of specific T-lymphocytes using intracellular cytokine staining technique was used to evaluate immune-enhancing activity of the isolated compound.

Results: The extract and fractions evoked increase in both humoral and cellular immunity. At 400 mg/kg of butanol fraction, the normalized mean secondary production of IgG1 and IgG2a antibodies were 9.0 and 7.7, respectively. Serum cytokine production by butanol fraction following secondary challenge with tetanus toxoid showed that IL-12, IL-17A and IFN-γ were expressed by 48.14, 41.37 and 38.22%, respectively. Structural elucidation of the active compound revealed presence of isomeric mixtures of quercetin-3-O-rutinoside and quercetin-3-O-robinobioside (Compound 1a/b). Compound 1a/b exhibited in vitro upregulation of specific CD4⁺ T-lymphocytes that were largely IFNγ releasing with up to 43.7% stimulation at 6.25 μg/mL compared to the baseline effect in DMSO vehicle control group.

Conclusion: M. aboensis expressed strong immune-enhancing properties, which may explain its ethnopharmacological use in disease management.     

Molecular epidemiology of carbapenem-resistant <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> in an endemic area: comparison with global data

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an endemic problem in certain countries including Greece. CRPA and multidrug-resistant P. aeruginosa (MDRPA) firstly emerged in our region during the 80s, right after the launch of imipenem and meropenem as therapeutic agents against P. aeruginosa infections. The role of outer membrane protein (Opr) inactivation has been known to contribute to imipenem resistance since many years, while efflux overexpression systems have been mainly associated with meropenem resistance. Among carbapenemases, metallo-β-lactamases (MBL) and mostly Verona integron-mediated (VIM) MBL’s have played the most crucial role in CRPA emergence. VIM-2 and VIM-4 producing CRPA, usually belonging to clonal complexes (CC) 111 and 235 respectively, have most frequently been isolated. Bla_VIM-2 and bla_VIM-4 are usually associated with a class 1 integron. VIM-17 also has appeared in Greece. On the other hand, other VIM subtypes detected in a global level, such as VIM-3, VIM-5, VIM-6, VIM-7, VIM-11, VIM-14, VIM-15, VIM-16 and VIM-18 have not yet emerged in Greece. However, new VIM subtypes will probably emerge in the future. In addition, MBL carbapenemases other than VIM, detected worldwide have not yet appeared. A single CRPA isolate producing KPC has emerged in our region several years ago. The study of the molecular basis of Opr deficiency and efflux overexpression remains a challenge for the future. In this article, we review the molecular epidemiology of CRPA in an endemic area, compared to global data.