Microbubble-mediated delivery of human adenoviruses does not elicit innate and adaptive immunity response in an immunocompetent mouse model of prostate cancer.

BACKGROUND: Gene transfer to malignant sites using human adenoviruses (hAds) has been limited because of their immunogenic nature and host specificity. Murine cells often lack some of the receptors needed for hAds attachment, thus murine cells are generally non-permissive for human adenoviral infection and replication, which limits translational studies. METHODS: We have developed a gene transfer method that uses a combination of lipid-encapsulated perfluorocarbon microbubbles and ultrasound to protect and deliver hAds to a target tissue, bypassing the requirement of specific receptors. RESULTS: In an in vitro model, we showed that murine TRAMP-C2 and human DU145 prostate cancer cells display a comparable expression pattern of receptors involved in hAds adhesion and internalization. We also demonstrated that murine and human cells showed a dose-dependent increase in the percentage of cells transduced by hAd-GFP (green fluorescent protein) after 24 h and that GFP transgene was efficiently expressed at 48 and 72 h post-transduction. To assess if our image-guided delivery system could effectively protect the hAds from the immune system in vivo, we injected healthy immunocompetent mice (C57BL/6) or mice bearing a syngeneic prostate tumor (TRAMP-C2) with hAd-GFP/MB complexes. Notably, we did not observe activation of innate (TNF-α and IL-6 cytokines), or adaptive immune response (neutralizing antibodies, INF-γ+ CD8+ T cells). CONCLUSIONS: This study brings us a step closer to demonstrating the feasibility of murine cancer models to investigate the clinical translation of image guided site-specific adenoviral gene therapy mediated by ultrasound-targeted microbubble destruction.

Baclofen-induced neurotoxicity in patients with compromised renal function: Review.

Baclofen is a centrally-acting γ-amino butyric acid agonist used mainly in the symptomatic management of spasticity originating from the spinal cord. It is absorbed completely from the gastrointestinal tract, metabolized by the liver to a minor degree, and excreted unchanged by the kidneys. Baclofen is moderately lipophilic and can cross the blood-brain barrier easily. At the usual dosage, it acts mainly at the spinal level without central nervous system (CNS) side effects. During renal failure, however, the elimination of the drug will decrease with a prolonged half-life, resulting in a larger area-under-the-curve exposure and disproportionate CNS toxicity. Clinically, these patients with renal failure may present with a variety of toxic symptoms manifesting at therapeutic/sub-therapeutic doses of baclofen. In cases of unexplained mental status changes in a patient receiving baclofen therapy, a careful assessment of renal function and a high suspicion of baclofen-induced encephalopathy will be key to the diagnosis.
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Multifarious beneficial traits and plant growth promoting potential of Serratia marcescens KiSII and Enterobacter sp. RNF 267 isolated from the rhizosphere of coconut palms (Cocos nucifera L.).

Two plant growth promoting bacteria designated as KiSII and RNF 267 isolated from the rhizosphere of coconut palms were identified as Serratia marcescens and Enterobacter sp. based on their phenotypic features, BIOLOG studies and 16S rRNA gene sequence analysis. Both bacteria exhibited phosphate solubilization, ammonification, and production of indole acetic acid, ß-1, 3 glucanase activities and 1-aminocyclopropane-1-carboxylate-deaminase activity. They could also tolerate a range of pH conditions, low temperature and salinity (NaCl). In addition, S. marcescens KiSII exhibited N- fixation potential, chitinase activity, siderophore production and antibiotics production. Seed bacterization with these bacteria increased the growth parameters of test plants such as paddy and cowpea over uninoculated control in green house assay. In coconut seedlings, significant increase in growth and nutrient uptake accompanied with higher populations of plant beneficial microorganisms in their rhizospheres were recorded on inoculation with both the PGPRs. The present study clearly revealed that PGPRs can aid in production of healthy and vigorous seedlings of coconut palm which are hardy perennial crops. They offer a scope to be developed into novel PGPR based bioinoculants for production of elite seedlings that can benefit the coconut farming community and the coconut based ecology.

Rare case of Ralstonia mannitolilytica peritonitis in an adult peritoneal dialysis patient.

Peritonitis is a common complication of peritoneal dialysis (PD) usually caused by skin-dwelling Gram-positive bacteria and Gram-negative bacteria colonizing the gut and urinary tract. Occasionally, uncommon bacteria can cause peritonitis in PD patients. We describe a case of Ralstonia mannitolilytica peritonitis in a 67-year-old woman who has been on PD for more than 10 years with no prior episodes of peritonitis. To our knowledge, this is the first reported case of Ralstonia peritonitis in the United States. She initially presented with abdominal tenderness, right flank pain, and cloudy output from her nephrostomy tube. PD fluid and urine cultures grew E. coli which responded to treatment. However, her symptoms recurred after completion of antibiotic therapy with PD fluid growing Ralstonia species. She again responded to intraperitoneal antibiotics but had recurrence of symptoms after the completion of her second course of antibiotics. PD fluid grew Ralstonia mannitolilytica resistant to the prior antibiotic regimen. The PD catheter was removed, and she was transitioned to hemodialysis. Subsequent treatment led to the resolution of her symptoms. Ralstonia species are Gram-negative bacteria that are prevalent in water supplies and can form biofilms. They have been known to cause infection particularly in neonates, immunocompromised patients, or patients in intensive care. In our patient, prior antibiotic treatment for E. coli peritonitis is likely to have contributed to the development of Ralstonia peritonitis. Clinical improvement after removal of the PD catheter revealed that seeding from the PD catheter was the likely culprit for the recurrent infections.

An Extremely Rare Case of Streptococcus anginosus Bacteremia Associated With Colon Cancer and Infective Endocarditis.

Streptococcus anginosus (S. anginosus) is a subgroup of viridans streptococci that tend to form a deep-seated abscess. These bacteria can be part of healthy human flora and commonly found in the gastrointestinal tract and oral cavity. Infective endocarditis is most commonly caused by Staphylococcus aureus and Streptococcus. Among the Streptococcus group, anginosus is extremely rare to cause endocarditis, and there are only a few case reports available. We present a patient with S. anginosus bacteremia who subsequently got diagnosed with metastatic colon cancer along with aortic and mitral valve endocarditis.

New diagnosis of bullous pemphigoid after withdrawal of immunosuppressive therapy in a failed renal transplant recipient on hemodialysis.

The occurrence of the autoimmune blistering disease, bullous pemphigoid (BP), in patients with failed renal allograft is rare and the few reported cases suggest various provocative factors without reaching a consensus. Here we report the case of a patient presenting with bullous lesions soon after the complete discontinuation of immunosuppressant therapy following renal allograft failure. Skin biopsy confirmed the diagnosis of BP. Administration of systemic corticosteroid controlled the occurrence of BP lesions in our patient. Increased clinical suspicion is warranted in cases of patients with renal transplant failure, since withdrawal of the immunosuppressant therapy could lead to unmasking the underlying autoimmune skin disease.

Denosumab-Associated Severe Hypocalcemia in a Patient With Chronic Kidney Disease.

Denosumab is a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand (RANKL). Denosumab has been shown to reduce the risk of skeletal-related events, including spinal cord compression, pathologic fracture and hypercalcemia of malignancy in patients with bone metastases. Hypocalcemia is a known side effect of denosumab, occurring in an estimated 8-14% of the patients. Here, we present an asymptomatic patient with stage-5 chronic kidney disease and severe hypocalcemia who had received denosumab 1 month earlier.