Participation of microglial p38 MAPK in formalin-induced temporomandibular joint nociception in rats.

AIMS: To investigate nociceptive behavior and the immunoreactivity of microglia and phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) following intracisternal administration of SB203580, a p38 MAPK inhibitor, or minocycline, a microglia inhibitor, in rats with temporomandibular joint (TMJ) inflammation. METHODS: The number of nociceptive behavioral responses was recorded for nine successive 5-minute intervals following formalin injections into the left TMJ. SB203580 or minocycline was administered intracisternally 2 hours prior to the formalin injection. Statistical analysis used one-way analysis of variance followed by least significant difference post-hoc analysis. RESULTS: The intra-articular injection of formalin increased the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn. Most of the p-p38 MAPK co-localized with OX42, a microglial marker, but not with GFAP, an astrocyte marker. Intracisternal injections of SB203580 (0.5, 1, or 5 Μg) attenuated the number of nociceptive behavioral responses and the expression of p-p38 MAPK in the medullary dorsal horn. Intracisternal injections of minocycline (25 or 50 Μg) also attenuated the responses and the expression of OX42 and p-p38 MAPK in the medullary dorsal horn. CONCLUSION: These findings suggest that p38 MAPK in microglia plays an important role in the central processing of inflammatory TMJ nociception in rats. The data further indicate that a targeted blockade of the microglial p38 MAPK pathway is a potentially important new treatment strategy for inflammatory TMJ nociception.

Combination of multifaceted strategies to maximize the therapeutic benefits of neural stem cell transplantation for spinal cord repair.

Neural stem cells (NSCs) possess therapeutic potentials to reverse complex pathological processes following spinal cord injury (SCI), but many obstacles remain that could not be fully overcome by NSC transplantation alone. Combining complementary strategies might be required to advance NSC-based treatments to the clinical stage. The present study was undertaken to examine whether combination of NSCs, polymer scaffolds, neurotrophin-3 (NT3), and chondroitinase, which cleaves chondroitin sulfate proteoglycans at the interface between spinal cord and implanted scaffold, could provide additive therapeutic benefits. In a rat hemisection model, poly(ɛ-caprolactone) (PCL) was used as a bridging scaffold and as a vehicle for NSC delivery. The PCL scaffolds seeded with F3 NSCs or NT3 overexpressing F3 cells (F3.NT3) were implanted into hemisected cavities. F3.NT3 showed better survival and migration, and more frequently differentiated into neurons and oligodendrocytes than F3 cells. Animals with PCL scaffold containing F3.NT3 cells showed the best locomotor recovery, and motor evoked potentials (MEPs) following transcranial magnetic stimulation were recorded only in PCL-F3.NT3 group in contralateral, but not ipsilateral, hindlimbs. Implantation of PCL scaffold with F3.NT3 cells increased NT3 levels, promoted neuroplasticity, and enhanced remyelination of contralateral white matter. Combining chondroitinase treatment after PCL-F3.NT3 implantation further enhanced cell migration and promoted axonal remodeling, and this was accompanied by augmented locomotor recovery and restoration of MEPs in ipsilateral hindlimbs. We demonstrate that combining multifaceted strategies can maximize the therapeutic benefits of NSC transplantation for SCI. Our results may have important clinical implications for the design of future NSC-based strategies.

Bladder reconstitution with bone marrow derived stem cells seeded on small intestinal submucosa improves morphological and molecular composition.

PURPOSE: Tissue engineering has been used for bladder augmentations with small intestinal submucosa (SIS). Although favorable short-term outcomes have been reported, long-term followup has been poor. We investigate whether tissue engineering with stem cells improves the morphological and genetic composition. MATERIALS AND METHODS: A total of 33 Lewis rats (Harlan Laboratories, Indianapolis, Indiana) were used to investigate bladder augmentations with 4-layer SIS in certain groups, including the control group (sham operation), partial cystectomy with oversewn defect group (OG), augmentation with unseeded SIS group (USG) and augmentation with stem cell seeded SIS group (SSG). Bladders from 4 rats per group were harvested 1 and 3 months after surgery. Morphological analyses were performed using Masson's trichrome and immunohistochemical staining with cytokeratin AE1/AE3, smooth muscle alpha-actin and S100. Gene expression was evaluated using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for collagen I (CI), collagen III (CIII), cytokeratins 8 and 19, and smooth muscle myosin heavy chain (MHC). RESULTS: At 1 month trichrome staining revealed collagen admixed with indiscrete cells and morphology similar to that in controls in USG and SSG, respectively. Discrete smooth muscles fascicles and S100 staining were found in all groups except USG. Organized urothelium with increased basal cell layer staining was present in controls and SSG only. At 3 months increased collagen formation was present in OG and USG. Immunostaining showed hyperplasia of the urothelium with increased staining of the basal cell layer, discrete muscle fascicles and positive nerve staining in all groups. Using quantitative RT-PCR expression levels in SSG were more improved than in USG, especially for CI, CIII and MHC. This was further evident at 3 months when CI and CIII were over expressed in OG and USG but not in the control group or SSG. Furthermore, RT-PCR showed that cytokeratins 8 and 19, and MHC had greater expression levels in SSG than in USG. CONCLUSIONS: Bladder reconstitution occurs more rapidly using stem cell seeded SIS. Although in USG and SSG all 3 cellular constituents appear to develop by 3 months, only SSG had gene expression levels similar to those in controls. The results suggest an explanation for the fibrosis noted in unseeded SIS bladder augmentations and the possible solution using stem cells.

Ejaculatory duct obstruction.

PURPOSE OF REVIEW: We surveyed the growing literature on ejaculatory duct obstruction and provide suggestions regarding its diagnosis and management. RECENT FINDINGS: Ejaculatory duct obstruction is a rare cause of male infertility. With the advent of the high resolution transurethral ultrasound (TRUS) technology, there has been an increase in diagnosis of this disorder. As for the treatment, it appears that central cystic lesions and partial obstructions respond best to transurethral resection of the ejaculatory ducts (TURED). SUMMARY: Ejaculatory duct obstruction is a rare but surgically correctable cause of male infertility. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, the diagnosis should be suspected in an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes, and hormonal profile, and dilated seminal vesicles, midline cyst, or calcifications on TRUS. In select cases, TURED has resulted in marked improvement in semen parameters, and pregnancies have been achieved. More studies are needed in the areas of diagnosis and long-term surgical outcome.

Transurethral resection of the prostate: the new old standard.

A literature search was performed for articles between June 2000 and July 2001 pertaining to transurethral resection of the prostate. Eight of the most interesting and/or groundbreaking articles, as deemed by the authors, were selected for review. Topics discussed include transurethral vaporization of the prostate, laser prostatectomy, preoperative finasteride, pelvic floor rehabilitation, the impact of the quantity of tissue removed, bladder infusion prior to catheter removal, and ethanol-glycine in assessment of the absorption of irrigation fluid.