Effect of dose of hypertonic saline on its potential to prevent lung tissue damage in a mouse model of hemorrhagic shock

Recent studies have shown that hypertonic saline (HS) resuscitation can reduce hemorrhage-induced lung damage by preventing neutrophil activation. In this study, we examined whether this protective effect can be improved by increasing the HS dose used for resuscitation. The protective effect of two HS doses was tested in a mouse model of hemorrhagic shock. BALB/c mice were bled to a mean arterial blood pressure of 35 +/- 5 mmHg for 1 h. Then the animals were resuscitated with lactated Ringer's (LR) or with HS (7.5% NaCl) at doses of 4 mL/kg or 6 mL/kg body weight, sacrificed after 24 h, and lung tissue samples were collected. Evidence of lung injury was evaluated morphologically by scoring histology specimens in a blinded fashion. In a separate set of mice, plasma Na+ and osmolarity were determined 15 min after resuscitation. Resuscitation of hemorrhaged mice with 4 and 6 mL/kg HS increased plasma Na+ concentrations by 5 and 11 mM, respectively. LR treatment reduced plasma Na+ concentrations by 6 mM and resulted in a lung injury score of 6.1 +/- 0.8, accompanied by focal thickening of alveolar membranes, congestion, pulmonary edema, and interstitial and intra-alveolar neutrophil infiltration. HS at 4 mL/kg decreased focal thickening, congestion, pulmonary edema, and neutrophil infiltration, and the injury score to 3.8 +/- 0.9, which was not significantly different from controls (3.6 +/- 0.8), and lung damage was lowest in animals that received 6 mL/kg HS (2.5 +/- 0.2, P < 0.005 vs. LR). Lung damage scores inversely correlated with plasma Na+ concentrations (r > 0.9999). Our data suggest that the protective effect of HS may be a function of the plasma Na+ concentration and that HS at 6 mL/kg is at least equally effective in reducing hemorrhage-induced lung damage compared to the more commonly used HS dose of 4 mL/kg.     

Relevance network between chemosensitivity and transcriptome in human hepatoma cells

Generally, hepatoma is not a chemosensitive tumor, and the mechanism of resistance to anticancer drugs is not fully elucidated. We aimed to comprehensively evaluate the relationship between chemosensitivity and gene expression profile in human hepatoma cells, by using microarray analysis, and analyze the data by constructing relevance networks. In eight hepatoma cell lines (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2), the baseline expression levels of 2300 genes were measured by cDNA microarray. The concentrations of eight anticancer drugs (nimustine, mitomycin C, cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) needed for 50% growth inhibition were examined and used as a measure of chemosensitivity. These data were combined and comprehensive pair-wise correlations between gene expression levels and the 50% growth inhibition values were calculated. Significant correlations with significance were used to construct networks of similarity. Fifty-two relations, including 42 genes, were selected. Among them, nearly 20% were various types of transporters, and most of them negatively correlated with chemosensitivity. Transporter associated with antigen processing 1 was associated with resistance to mitoxantrone, consistent with previous reports. Other transporters were not reported previously to associate with chemosensitivity. Resistance to doxorubicin and its analogue, epirubicin, were positively correlated with topoisomerase II beta expression, whereas it negatively correlated with expression of carboxypeptidases A3 and Z. Response to nimustine was associated with expression of superoxide dismutase 2. Relevance networks identified several negative correlations between gene expression and resistance, which were missed by hierarchical clustering. Our results suggested the necessity of systematically evaluating the transporting systems that may play a major role in resistance in hepatoma. This may provide useful information to modify anticancer drug action in hepatoma.     

A new method for closing tympanic membrane perforations using basic fibroblast growth factor

OBJECTIVE: To present a new method for closing tympanic membrane perforations using basic fibroblast growth factor (bFGF) combined with an atelocollagen/silicone bilayer membrane as a patch material. STUDY DESIGN: Closure of tympanic membrane perforations was attempted using bFGF, which is thought to facilitate the growth of fibroblasts and collagen fibers at the margin of the perforation. METHODS: Under an operating microscope, the margin of the perforation was trimmed, and a piece of an atelocollagen/silicone bilayer membrane infiltrated with 0.2 mL Trafermin (0.1% solution) (bFGF group) or saline (control group) was then placed in the perforation with the silicon layer facing outward. Nine patients were treated with bFGF, and five were treated with saline. Data obtained from patient records included patient age, perforation size, and duration of treatment, with a focus on hearing improvement and complete tympanic membrane closure. RESULTS: The mean perforation size before treatment was 16.5% in the bFGF group and 9.6% in the control group. Closure of the tympanic membrane perforation was achieved in all cases in the bFGF group, whereas it was achieved in only two of five cases in the control group. With bFGF treatment, the tympanic membrane perforations closed completely within 3.7 weeks, and hearing improved by 13.3 dB in the bFGF group. CONCLUSION: The study demonstrated that bFGF combined with an atelocollagen/silicone bilayer membrane is effective for the conservative treatment of tympanic membrane perforation.     

Magnetic materials in otoliths of bird and fish lagena and their function

The mystery of the homing ability of pigeons has been the subject of much interest and it is widely believed that information from the earth's magnetic field may be involved. However, no specific magnetic sensory organ has yet been identified. The recent finding of magnetic materials in the lagenal otolith of fish and birds raises the possibility that these structures may be key elements in the elusive magnetic sensory system. For the elemental analysis of materials X-ray fluorescence using synchrotron radiation is one of the most powerful techniques available and was used in this study for analysis of the otoliths. By comparing the compositions of the three different kinds of otoliths among several species of sea fish and birds, we found that the saccular and utricular otoliths rarely contain detectable levels of iron but that iron is present in significant quantities in the lagenal otoliths of the birds. The lagenal otolith comprises tiny magnetic particles of low inertia that are displaced by imposed magnetic fields, providing the animal with geomagnetic sensory input, from which the brain would infer navigational information.     

Tubulointerstitial nephritis associated with acute intermittent porphyria

Progressive renal impairment associated with acute intermittent porphyria is not well recognized and the mechanism of renal damage remains unclear. We report a case of a 51-year-old female with acute intermittent porphyria and long-term follow-up who developed proteinuria and renal insufficiency. Her biopsy showed marked tubulointerstitial damage with mitochondrial abnormalities. Urinary excretion of lipid peroxidation was increased compared to healthy controls. The porphyrin precursors may increase lipid peroxidation products and damage mitochondria leading to tubulointerstitial nephritis.     

Effects of 15-deoxy-delta(12,14) prostaglandin J(2) and interleukin-4 in Toll-like receptor-4-mutant glial cells

15-Deoxy-Delta(12,14) prostaglandin J(2) and interleukin-4 are endogenous anti-inflammatory substances. In this study, we examined the effects of 15-deoxy-Delta(12,14) prostaglandin J(2) and interleukin-4 in glial cells from the Toll-like receptor-4-mutant (C3H/HeJ) and wild-type (C3H/HeN) mouse brains. The lipopolysaccharide-induced expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2 in the Toll-like receptor-4-mutant glial cells have significantly lower levels (about half and quarter, respectively) than those in the wild-type cells. Treatment with both interleukin-4 (at 10 ng/ml, for 48 h) and 15-deoxy-Delta(12,14) prostaglandin J(2) (at 3 microM, for 30 min) completely inhibited the lipopolysaccharide-induced expression of inducible NO synthase and cyclooxygenase-2. In contrast, heme oxygenase-1 was induced by 15-deoxy-Delta(12,14) prostaglandin J(2) alone, but was not changed by interleukin-4 or lipopolysaccharide. The inhibitory protein of nuclear factor-kappa B was degraded by lipopolysaccharide in both mutant and wild-type glial cells, and this degradation was not inhibited by either 15-deoxy-Delta(12,14) prostaglandin J(2) or interleukin-4. These results suggest that the response to lipopolysaccharide is partially dependent on Toll-like receptor-4 in mouse glial cells, and that 15-deoxy-Delta(12,14) prostaglandin J(2) and interleukin-4 differently regulate the expression of inducible NO synthase and cyclooxygenase-2, and heme oxygenase-1.     

Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment

BACKGROUND AND OBJECTIVES: We studied antitumor effects and cell death induced by cationic liposome-mediated gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir treatment in cultured rat T9 glioma cells and in experimental gliomas produced from this cell line. METHODS: To transfer genes we used small unilamellar cationic liposomes containing N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride. Video-enhanced contrast differential interference contrast microscopy was used for morphologic observations of cultured cells. RESULTS: When we treated the cells or implanted gliomas with the liposomes and ganciclovir, a strong effect was seen against tumor cells, and survival of tumor-implanted rats was increased. Morphologically, cell death observed after HSV-tk gene/liposome and ganciclovir treatment in the cultured glioma cells included both apoptosis and necrosis. CONCLUSIONS: Introduction of the HSV-tk gene in a DNA-liposome complex followed by ganciclovir treatment induced both apoptosis and necrosis, which together resulted in a potent antitumor effect.     

A case of basal cell carcinoma of the nipple and areola with intraductal spread

We report an 82-year-old Japanese woman with basal cell carcinoma of the left nipple and areola extending into the lactiferous duct. The patient developed a small papular lesion of the left areola about 1 year before admission. The lesion, which had slowly progressed to involve the nipple, had become symptomatic showing weeping and bleeding. Mammography revealed microcalcification in the nipple. Although Paget's disease was suspected from these clinical features, histologically basal cell carcinoma was diagnosed. There was no axillary lymphadenopathy, and no evidence of distant metastasis. The lesion of the nipple and areola was resected with a 2 cm free margin along with the underlying mammary tissue. The patient has remained well without signs of recurrence for 2 years after surgery. We reviewed cases of basal cell carcinoma of the nipple or areola and discuss considerations and problems of this rare tumor.