Human Urine-derived Stem Cells Seeded Surface Modified Composite Scaffold Grafts for Bladder Reconstruction in a Rat Model

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold^heparin-bFGF group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 µL/cm H₂O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 µL/cm H₂O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 µL/cm H₂O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 µL/cm H₂O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 µL/cm H₂O for the scaffold^heparin-bFGF group, respectively). In histological and immunohistochemical analysis, the USC-scaffold^heparin-bFGF group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold^heparin-bFGF exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.     

Identification of a novel nonsense mutation in the rod domain of GFAP that is associated with Alexander disease

Alexander disease (AxD) is an astrogliopathy that primarily affects the white matter of the central nervous system (CNS). AxD is caused by mutations in a gene encoding GFAP (glial fibrillary acidic protein). The GFAP mutations in AxD have been reported to act in a gain-of-function manner partly because the identified mutations generate practically full-length GFAP. We found a novel nonsense mutation (c.1000 G>T, p.(Glu312Ter); also termed p.(E312*)) within a rod domain of GFAP in a 67-year-old Korean man with a history of memory impairment and leukoencephalopathy. This mutation, GFAP p.(E312*), removes part of the 2B rod domain and the whole tail domain from the GFAP. We characterized GFAP p.(E312*) using western blotting, in vitro assembly and sedimentation assay, and transient transfection of human adrenal cortex carcinoma SW13 (Vim⁺) cells with plasmids encoding GFAP p.(E312*). The GFAP p.(E312*) protein, either alone or in combination with wild-type GFAP, elicited self-aggregation. In addition, the assembled GFAP p.(E312*) aggregated into paracrystal-like structures, and GFAP p.(E312*) elicited more GFAP aggregation than wild-type GFAP in the human adrenal cortex carcinoma SW13 (Vim⁺) cells. Our findings are the first report, to the best of our knowledge, on this novel nonsense mutation of GFAP that is associated with AxD and paracrystal formation.     

Decreased Serum Epinephrine in Children With Positive Skin Prick Test

Objectives

To evaluate the association between catecholamine levels and skin prick test results among children.

Methods

Two hundred eight first grade children from one elementary school were invited to participate in this study. Skin prick test (SPT) for six allergens (2 house dust mites, cat, dog, mugwort, and pollen mixture) was performed, and patient demographic information was recorded. The parents were surveyed using questionnaires about rhinitis-related symptoms. Finally, venous blood sampling was done to measure catecholamine levels (epinephrine, norepinephrine, and dopamine) by high-performance liquid chromatography.

Results

Out of 208 children, 174 (106 boys and 68 girls) enrolled in this study. Ninety-six of the children (55%) had negative SPT (nonsensitization group), while 78 (45%) had a positive SPT to at least one of six allergens (sensitization group). The diagnosis of chronic rhinitis was more prevalent in the sensitization group (35.9%) than nonsensitization group (26.0%), however the finding was not significant (P=0.186). Epinephrine levels were decreased between the sensitization group compared to the nonsensitization group (P=0.004). There was no difference in norepinephrine and dopamine levels (P>0.05).

Conclusion

Epinephrine levels are lower in children with positive SPT compared to controls, however, the level of the catecholamine was not associated with the presence or absence of rhinitis symptoms.     

Five-Year Subjective Outcomes of Obstructive Sleep Apnea Surgery: A Multiinstitutional Study

Objectives

To evaluate the effect of obstructive sleep apnea (OSA) surgery on long-term (5-year) subjective outcomes, including sleep disordered breathing (SDB) symptoms and other complications, in patients with OSA.

Methods

We enrolled patients who underwent diagnostic polysomnography for OSA between January 2006 and December 2006 in ten hospitals. Patients either were treated for OSA or were not treated for OSA. All patients completed a brief telephone survey regarding their SDB signs and symptoms (e.g., snoring, apnea, nocturnal arousals, and daytime sleepiness), positive airway pressure (PAP) compliance, and any adverse effects of either the surgery or PAP. A positive subjective outcome for either surgery or no treatment was taken to be the alleviation of apnea, defined as a ≥50% increase in score. A positive subjective outcome (compliance) for PAP was defined as a PAP usage of ≥4 hours per night and ≥5 days per week.

Results

A total of 229 patients were included in this study. Patients were divided into three groups: a surgery group (n=87), a PAP group (n=68), and a control (untreated) group (n=74). The surgery group exhibited significant improvement in all SDB symptoms compared with the control group. The long-term subjective outcomes of the surgery (52.9%) and PAP (54.4%) groups were significantly better than those of the control group (25.0%). The subjective outcome of the surgery group was not significantly different from that of the PAP group. The overall surgical complication rate was 23.0% (20 of 87) in the surgery group, and 55.0% (22 of 40) of all patients with PAP experienced adverse effects.

Conclusion

The extent of SDB symptoms was consistently improved in patients with OSA at 5 years postsurgery. Information about the potential long-term subjective outcomes should be provided to patients when considering surgery.     

Inhibition of S6 kinase by rapamycin blocks maturation of Rana dybowskii oocytes

Studies were carried out to define the hormone-induced signal transduction pathway during maturation of Rana dybowskii oocytes. Rapamycin, a specific inhibitor of S6 kinase, blocked progesterone-induced oocyte germinal vesicle breakdown (GVBD) in a dose-dependent manner indicating that S6 kinase is required for meiotic maturation of Rana oocytes. Addition of rapamycin within 3 h, but not 6 h, of progesterone treatment inhibited GVBD. In contrast, cycloheximide, a general protein synthesis inhibitor, blocked GVBD even when added 9 h after progesterone addition. A twofold increase in S6 kinase activity occurred within 1 h of progesterone stimulation and rapamycin inhibited this activity. Rapamycin also suppressed, in a dose-dependent manner, progesterone-induced protein synthesis during the first 12 h of culture but less effectively later. Histone H1 kinase activity (maturation-promoting factor, MPF) was observed in oocyte extracts at two different times (between 6 and 9 h and at 24 h) following progesterone stimulation. Rapamycin blocked H1 kinase activity between 6 and 9 h of culture but not that observed at 24 h. In contrast, cycloheximide suppressed progesterone-induced H1 kinase activity as well as protein synthesis throughout the course of incubation. Such results indicate that rapamycin and cycloheximide have common and unique effects on oocyte maturation and suggest that progesterone-induced S6 kinase activity is closely associated with induction of protein synthesis and activation of MPF during oocyte maturation. Results in Rana contrast with those obtained in Xenopus where rapamycin inhibited S6 kinase but failed to inhibit GVBD or protein synthesis. Differences in the response of Rana and Xenopus oocytes to rapamycin are discussed in relation to seasonal, biochemical, and species variations.     

Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis

OBJECTIVES:  Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese population.
METHODS:  NAFLD patients were prospectively recruited for liver biopsy and blood tests. The NAFLD fibrosis score was calculated as −1.675 + 0.037 × age (yr) + 0.094 × BMI (kg/m²) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio–0.013 × platelet (×10⁹/L)−0.66 × albumin (g/dL). Advanced fibrosis was defined as stage 3 to 4 fibrosis.
RESULTS:  One hundred sixty-two patients (age 46 ± 10 yr, male 59%) were included in the study. Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with the NAFLD fibrosis score below the proposed low cutoff point (<−1.455) were under-staged, resulting in a high negative predictive value of 91%. Only two patients exceeded the proposed high cutoff point (>0.676), but neither had advanced fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population, 79% of liver biopsies could be avoided.
CONCLUSIONS:  The NAFLD fibrosis score has high negative predictive value in excluding advanced fibrosis in the Chinese population, and can reduce the burden of liver biopsy in the vast majority of cases. Since there were few cases of advanced fibrosis in this cohort, this study had limited power in validating the high cutoff point.     

A case of intestinal obstruction caused by strangulated femoral hernia accompanying soft tissue necrosis]

Intestinal obstruction involves a partial or complete blockage of the bowel which results in the failure of intestinal contents to pass through. The mechanical causes of obstruction may include the followings: hernias, postoperative adhesions or scar tissue, impacted feces, gallstones, tumors, granulomatous processes, intussusception, volvulus, foreign bodies, and etc. Hernias are the third leading cause of intestinal obstruction by 10% approximately. However, most hernias are the cases with abdominal wall, inguinal or internal hernia. Femoral, obturator, lumbar, or sciatic hernia as the cause of obsturction is rare. Furthermore, the cases accompanying soft tissue necrosis are seldomly reported. Herein, we report a case of intestinal obstruction caused by strangulated femoral hernia accompanying soft tissue necrosis in a 78-years-old female patient.     

Cardiovascular and respiratory considerations with pharmacotherapy of glaucoma and ocular hypertension

Glaucoma and ocular hypertension are highly prevalent conditions in individuals over the age of 40 and are commonly seen together in patients with cardiovascular disease. Many of the antiglaucoma medications, when systemically absorbed, affect the sympathetic and parasympathetic nervous systems of patients and can cause cardiovascular toxicity. Such adverse effects are frequently associated with the long-term use of potentially toxic agents in elderly people, who are most prone to chronic eye disease. Moreover, patients may not associate their symptoms with the topical eye medications, and consequently may not report adverse drug effects. Drug-drug interactions can also occur when patients are taking medications for both cardiovascular disease and glaucoma. In this review, the systemic toxicity of these agents is reviewed, along with possible drug-drug interactions. Mention is made of other antiglaucoma medications used alone and in combination with topical beta-blockers. Identification of genetic loci-a bold new step toward glaucoma treatment-is mentioned briefly at the end of the article.