Temperature-responsive silk-elastinlike protein polymer enhancement of intravesical drug delivery of a therapeutic glycosaminoglycan for treatment of interstitial cystitis/painful bladder syndrome.

Interstitial cystitis (IC), also known as painful bladder syndrome, is a debilitating chronic condition with many patients failing to respond to current treatment options. Rapid clearance, mucosal coating, and tight epithelium create strong natural barriers that reduce the effectiveness of many pharmacological interventions in the bladder. Intravesical drug delivery (IDD) is the administration of therapeutic compounds or devices to the urinary bladder via a urethral catheter.

IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model.

Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is a debilitating chronic condition that afflicts over 3 million women above the age of 18 in the U.S., and most patients fail to respond to current treatment options.

Bladder pain in an LL-37 interstitial cystitis and painful bladder syndrome model.

Our goal was to evaluate the pain response in an LL-37 induced murine model for interstitial cystitis/painful bladder syndrome (IC/PBS). In particular, we sought to characterize the dose dependence, time-course, and relationship of LL-37 induced bladder inflammation and pain. The IC/PBS model was induced in C57Bl/6 mice by instilling 50 μL of LL-37, an immunomodulatory human cathelicidin (anti-microbial peptide), in the bladder for 1 hr.

Combination of Extracorporeal Shockwave Lithotripsy and Ureteroscopy for Large Staghorn Calculi in a Pediatric Patient: Case Report.

Extracorporeal shockwave lithotripsy (SWL) is a procedure commonly performed to treat nephrolithiasis, with promising results in pediatric patients. However, increasing renal calculi size is directly related to worsening stone-free rates. There are few reports in the literature of >2-cm staghorn calculi that expound on the exact mechanism of treatment in the pediatric population.

Silk-elastinlike protein polymers enhance the efficacy of a therapeutic glycosaminoglycan for prophylactic treatment of radiation-induced proctitis.

Radiation-induced proctitis (RIP) is the most common clinical adverse effect for patients receiving radiotherapy as part of the standard course of treatment for ovarian, prostate, colon, and bladder cancers. RIP limits radiation dosage, interrupts treatment, and lowers patients' quality of life. A prophylactic treatment that protects the gastrointestinal tract from deleterious effects of radiotherapy will significantly improve patient quality of life and may allow for higher and more regular doses of radiation therapy.

Topical cathelicidin (LL-37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model.

Background: Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that: (1) LL-37 topically delivered would elicit profound OE inflammation; and (2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells.

Peptide Decoration of Nanovehicles to Achieve Active Targeting and Pathology-Responsive Cellular Uptake for Bone Metastasis Chemotherapy.

To improve bone metastases chemotherapy, a peptide-conjugated diblock copolymer consisting of chimeric peptide, poly(ethylene glycol) and poly(trimethylene carbonate) (Pep--PEG--PTMC) is fabricated as a drug carrier capable of bone-seeking targeting as well as pathology-responsive charge reversal to ensure effective cellular uptake at the lesion sites. The chimeric peptide CKGHPGGPQAsp consists of an osteotropic anionic Asp8, a cathepsin K (CTSK)-cleavable substrate (HPGGPQ) and cationic residue tethered to polymer chain. Pep--PEG--PTMC can spontaneously self-assemble into negatively charged nanomicelles (~75 nm).

LL-37 induced cystitis and the receptor for advanced glycation end-products (RAGE) pathway.

To elucidate pathways in bladder inflammation, we employed our physiologically relevant LL-37 induced cystitis model. Based on inflammatory studies involving other organ systems implicating the receptor for advanced glycation end-products (RAGE), we first hypothesized that RAGE is critically involved in LL-37 induced cystitis. We further hypothesized a common RAGE ligand - high mobility group box 1 (HMGB1) is up-regulated in bladders challenged with LL-37.

Prevention of anti-microbial peptide LL-37-induced apoptosis and ATP release in the urinary bladder by a modified glycosaminoglycan.

Interstitial cystitis (IC), often referred to in combination with painful bladder syndrome, is a chronic inflammatory disease of the bladder. Current therapies primarily focus on replenishing urothelial glycosaminoglycan (GAG) layer using GAG analogs and managing pain with supportive therapies. However, the elusive etiology of IC and the lack of animal models to study the disease have been major hurdles developing more effective therapeutics.

Physiological relevance of LL-37 induced bladder inflammation and mast cells.

Purpose: We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells.

Materials And Methods: To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients.

A murine model of inflammatory bladder disease: cathelicidin peptide induced bladder inflammation and treatment with sulfated polysaccharides.

Purpose: Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can treat/prevent LL-37 mediated bladder inflammation.

[Effects of irrigation fluid absorption on system during mini-percutaneous nephrolithotomy].

Objective: To determine the effects of irrigation fluid absorption on system hemodynamics, fluid-electrolyte and hormone during mini-percutaneous nephrolithotomy.

Methods: In this study 128 patients with renal calculus or calculus of superior ureter from January 2007 to February 2008 were collected. Hemoglobin (Hb), hematocrit (Hct), plasma osmotic pressure (POP), fluid-electrolyte, serum creatinine (Cre), renin, angiotensin II and aldosterone were determined before and after operation.