Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice.

AIMS: In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. METHODS AND RESULTS: Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ) and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13). Consistent with these results, levels of IL-4, IL-5, IL-13, serum IgE and BP-specific serum IgG1 were decreased, whereas secretion of IFN-γ and BP-specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice. CONCLUSION: Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP-induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1-type immune response. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP-induced allergic rhinitis in an animal model.

Tubulointerstitial nephritis and uveitis syndrome (TINU) with Fanconi's syndrome.

We report a 57-year-old woman with concurrent tubulointerstitial nephritis and uveitis syndrome (TINU) and Fanconi's syndrome. She presented with sudden onset of bilateral ocular pain, blurred vision, acute renal failure, glucosuria and proteinuria. Slit lamp examination revealed acute bilateral anterior uveitis. Tubulointerstitial nephritis was confirmed by kidney biopsy. Laboratory examination revealed normoglycemic glucosuria, proteinuria, normal anion-gap metabolic acidosis, phosphaturia, urinary uric acid wasting and kaliuresis leading to hypokalemia. Her vision and renal function improved gradually after systemic steroid therapy. There have been rare reports of TINU syndrome which had features of Fanconi's syndrome. The prevalence of TINU syndrome may be underestimated, and its association with Fanconi's syndrome requires further investigation.

Prevalence of spondyloarthritis in 504 Chinese patients with HLA-B27-associated acute anterior uveitis.

OBJECTIVES: To estimate the prevalence of spondyloarthritis (SpA) and the clinical features of human leucocyte antigen (HLA)-B27-associated acute anterior uveitis (HLA-B27 uveitis) in Chinese patients. METHODS: We conducted a retrospective cohort study using a structured chart review to record the complete ocular history, including the onset of uveitis, month of uveitis attack, specific eye involvement, the time of first attack, and rheumatic manifestations from 1987 to 2004. A total of 504 patients with HLA-B27 uveitis were consequently enrolled consecutively from the uveitis clinic of Taipei Veterans General Hospital. RESULTS: In total, 1719 attacks of uveitis in 504 patients were recorded. Females tended to have a higher frequency of attack than males, and those with a disease course of less than 5 years showed more uveitis recurrence. The same eye attacks were observed in 156 of 332 patients (47%), more than the expected percentage compared with attacks with random-eye occurrence (p < 0.001). A significantly higher number of uveitis attacks occurred in winter. SpA-related acute anterior uveitis (AAU) was found in 387 patients (76.8%). Ankylosing spondylitis (AS) occurred in 214 patients (42.5%), with a significantly higher prevalence in males than in females (p < 0.001). Undifferentiated SpA (USpA)-related AAU occurred in 150 patients (29.8%), with a significantly higher prevalence in females than in males (p < 0.001). Patients with SpA had an earlier onset of uveitis (p = 0.01) and a greater number (> or = 6) of attacks (p = 0.03). CONCLUSIONS: The prevalence of SpA was high in the Chinese population with HLA-B27-associated uveitis. The association with SpA indicated an earlier age of uveitis onset and a greater likelihood of having a higher number of uveitis attacks.

Comparing the ethical challenges of forgoing tube feeding in American and Hong Kong patients with advanced dementia.

OBJECTIVES: To develop a cross-cultural dialogue for enriching our understanding of how an ethical environment can be constructed in fostering tube-feeding decisions in patients with advanced dementia (AD). DESIGN AND DATA SOURCE: Drawing on the findings of two prospective case studies conducted in Boston and Hong Kong, this paper compares the decision-making patterns of forgoing tube feeding for AD patients and their emergent ethical dilemmas typified in a special dementia care unit in Boston (BCU) and a long-term care unit in Hong Kong (HKCU). FINDINGS: Differences in forgoing tube feeding decision are delineated in the two places. No-tube-feeding practice was sustained in BCU in two ways: advance decision-making with respect paid to the patient's wishes and advance proxy decision-making focused on patient comfort. With life preservation as the prevailing value in the Hong Kong medical system, only strong family request coupled with medical evidence of patient's ability to continue hand-feeding that tube feeding would be discontinued. All patients died with some form of artificial feeding. CONCLUSION: A paradigm shift of values underpinning the practice of forgoing tube feeding in the context of palliative care is observed in three aspects. First, the emphasis on prognostication based on biomedical markers in predicting the length of survival is shifted to a focus on the "diagnosis of dying". Second, the overriding concern in conventional medical practice with preserving life is shifting to an overriding concern of "what is best for the patient." Third, in the last days of life, the conventional approach of "trying to do everything for the patient" had shifted from a technological to a relational one. Palliative measures for relieving discomfort and providing a peaceful and dignified environment in which the patient could die are the primary concern. Although the predominant medical culture in Hong Kong is biomedical, voices from the patients and family members challenge this conventional practice, and suggest that the alternative model may be a better choice.

The activity of 2'-benzoyloxycinnamaldehyde against drug-resistant cancer cell lines.

This study investigated the inhibitory effects of 2'-benzoyloxycinnamaldehyde (BCA) on cancer cells, including various drug-resistant cancer cell lines. To observe this activity, the anticancer drug-resistant cell lines were established by continuously exposing the parental cells to 5-fluorouracil (5-FU) and cyclophosphamide (CDDP), and examining the cells with the MTT assay and flow cytometric analysis. The BCA treatment produced similar growth inhibitory effects and apoptotic cell death on the drug-resistant cancer cells as their parental cells. The activation of the p38-mitogen activated protein kinase, an increased level of reactive oxygen species (ROS) generation and downregulation of Bcl-2 were observed in both the drug resistant and non-drug resistant cell lines. The GSH treatment effectively inhibited BCA-induced apoptosis by blocking ROS generation, suggesting that ROS is a major regulator in BCA-induced apoptotic cell death. These results suggest that BCA can be a useful drug candidate for treating drug-resistant cells.

Applications of the pulsatile flow versatile ECLS: in vivo studies.

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.

Activity coefficients of the peptide and the electrolyte in ternary systems water+glycylglycine+NaCl, +NaBr, +KCl and +KBr at 298.2 K.

The activity coefficients of glycylglycine in four aqueous electrolyte solutions (+NaCl, +NaBr, +KCl and +KBr) were obtained at 298.2 K. The mean ionic activity coefficient of the electrolyte in aqueous solutions containing the peptide was determined from measurements of the potential differences of a cation and an anion ion-selective-electrode, each vs. a double junction reference electrode. The results show that the nature of the anion has a major effect on the activity coefficients of glycylglycine. Comparison of activity coefficient data for glycylglycine with literature data for glycine, both in aqueous NaCl solutions, indicates that the effect of the electrolyte is larger for the peptide than for the amino acid. For the peptide, in all cases, the effect of the electrolyte is more important at low molalities of the electrolyte. The Wilson equation was used to correlate the activity coefficient data obtained. The correlation results were satisfactory for the region of concentrated electrolyte.

Increased expression of peroxiredoxin II confers resistance to cisplatin.

Peroxiredoxin II (Prx II) has been known to be induced by various oxidative stimuli and to play an important protective role from oxidative damage by hydrogen peroxide (H2O2). In this study, we observed that cisplatin as well as H2O2 induced Prx II expression. To examine the correlation between the increased expression of Prx II and chemoresistance, we prepared a Prx II-overexpressing cell line, SNU638 cells, and found it to be more resistant to cell death induced by cisplatin and H2O2 than neo-transfectant cells. We also observed that enhanced expression of Prx II inhibited cisplatin- and H2O2-induced apoptosis, demonstrating that resistance to these cytotoxic agents was due to inhibition of apoptosis. The above results led us to suggest that the overexpressed Prx II protein inhibits cisplatin-induced apoptosis, thereby contributing to chemoresistance of tumor cells, especially to oxidative stress producing anticancer drugs.

Hepatitis C virus core protein potentiates TNF-alpha-induced NF-kappaB activation through TRAF2-IKKbeta-dependent pathway.

Previous work has implicated that the core protein of hepatitis C virus (HCV) may play a modulatory effect on NF-kappaB activation induced by TNF-alpha. However, it is unclear how HCV core protein modulates TNF-alpha-induced NK-kappaB activation. Here we show that overexpression of HCV core protein potentiates NF-kappaB activation induced by TNF-alpha. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates NF-kappaB activation through TRAF2. Moreover, we demonstrate that HCV core protein potentiates TRAF2-mediated NF-kappaB activation via IKKbeta. In addition, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-kappaB induced by TNF-alpha. Thus, these observations indicate that HCV core protein may play an important role in the regulation of the cellular inflammatory and immune responses through NF-kappaB.

Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death.

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic pathways. Previous studies have suggested that TNF receptor-associated factor (TRAF) 2 can mediate crucial antiapoptotic signals during TNF stimulation. However, it is unclear how the antiapoptotic signals via TRAF2 in TNF-R1 signaling is regulated. Here we show that TRAF1 is cleaved by caspase-8 into two fragments during apoptosis induced by TNF. Overexpression of the C-terminal cleavage product, TRAF1-c, increased TNF-induced cell death of hybridoma T cells. Importantly, we demonstrate that the cleavage product of TRAF1 coimmunoprecipitates with TRAF2 that is released from the TNF-R1 complex in response to prolonged TNF treatment. These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF.

Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells.

Two 5-fluorouracil (5-FU)-resistant cell lines from a Korean gastric cancer cell line were established by incubation of the cells with increasing concentration of 5-FU, and the resultant cell lines showed an over 800-fold increased resistance to 5-FU. To identify the mechanism of 5-FU resistance, the expressions of genes involved in 5-FU metabolism were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Expressions of orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and uridine phosphorylase (UP) were significantly downregulated in these cell lines, resulting in low incorporation of 5-FU into nucleic acids. In contrast, an increased expression of thymidine kinase (TK) was observed in 5-FU-resistant cells. These results strongly indicate that blocking of 5-FU incorporation into nucleic acids and TK overexpression may play a major role in 5-FU resistance in these cells. Interestingly, these cell lines showed cross-resistance to paclitaxel, cisplatin, and doxorubicin, suggesting that other factors such as HSP27 and Mn-SOD could be also involved in the mechanism of multidrug resistance in these cell lines.

Diffuse toxoplasmic retinochoroiditis as the initial manifestation of acquired immunodeficiency syndrome.

Toxoplasmic retinochoroiditis is an important opportunistic retinal infection in human immunodeficiency virus (HIV)-infected patients. It may present as diffuse necrotizing retinochoroiditis instead of a focal lesion and may be the initial manifestation of HIV infection. A 50-year-old heterosexual man presented with blurred vision in his left eye of 3 months' duration. Fundus examination revealed diffuse necrotizing retinochoroiditis, mainly at the posterior pole, with marked vitritis in the left eye. Serologic studies and aqueous fluid antibody titers indicated recent toxoplasmic infection. Positive enzyme immunoassays (EIA) and Western blot tests proved HIV infection. The retinochoroiditis and vitritis improved after an antitoxoplasmic regimen with trimethoprim-sulfamethoxazole (TMP-SMX). Nonetheless, toxoplasmic encephalitis developed 6 months after the onset of ocular toxoplasmosis and responded well to TMP-SMX. This is the first case of toxoplasmic retinochoroiditis as the initial manifestation of AIDS reported in Taiwan. We suggest that Toxoplasma infection should be included in the differential diagnosis of diffuse necrotizing retinochoroiditis and vitritis. We also recommend that adults with newly diagnosed ocular toxoplasmosis be screened for HIV infection.

Ophthalmic findings in patients with acquired immunodeficiency syndrome.

Ocular manifestations have been reported in up to 60% of individuals infected with human immunodeficiency virus (HIV) in the United States, and it is becoming increasing apparent that these ocular manifestations almost invariably reflect extent of progression of the disease. The prevalence of ocular abnormalities among acquired immunodeficiency syndrome (AIDS) patients in Taiwan has not been reported. In the present study, we examined and followed up the ophthalmic conditions of a total of 274 HIV-infected patients during the period from March 1993 to May 1999. The results show that cotton-wool spots was the most common ocular finding in this series of patients with AIDS, occurring in 22 (32.8%) of 67 AIDS patients. Cytomegalovirus (CMV) retinitis was the most commonly seen opportunistic ocular infection, occurring in 14 (20.8%) of 67 AIDS patients. These findings suggest that AIDS patients should be closely followed for signs of opportunistic ocular disease which may initially be asymptomatic. Close co-operation between the ophthalmologist and the internist is essential to ensure timely therapeutic intervention, which can decrease the risk of further complications including visual impairment and blindness.

Antisense of human peroxiredoxin II enhances radiation-induced cell death.

Human peroxiredoxin II (Prx II) has been known to function as an antioxidant enzyme in cells. Using head-and-neck cancer cell lines, we investigated whether Prx II expression is related to the resistance of cells to radiation therapy in vivo and in vitro, and whether a Prx II antisense serves as a radiosensitizer. Increased expression of Prx II was observed in tissues isolated from the patients who did not respond to radiation therapy, whereas Prx II expression was weak in tissues from the patients with regressed tumors. Enhanced expression of Prx II in UMSCC-11A (11A) cells was also observed after treatment with gamma radiation. This increased expression conferred radiation resistance to cancer cells because overexpression of Prx II protected 11A cells from radiation-induced cell death, suggesting that blocking Prx II expression could enhance radiation sensitivity. Treatment of 11A cells with a Prx II antisense decreased induction of Prx II, enhancing the radiation sensitivity. From these results, we suggest that stress-induced overexpression of Prx II increases radiation resistance via protection of cancer cells from radiation-induced oxidative cytolysis and that a Prx II antisense can be used as a radiosensitizer.

Progression of cytomegalovirus retinitis in acquired immunodeficiency syndrome: a case report.

We report an AIDS patient with cytomegalovirus (CMV) retinitis that developed from an early minor lesion and progressed to extended involvement of the retina and severe deterioration of vision due to poor compliance with ganciclovir treatment. A 33-year-old man was known to have acquired immunodeficiency syndrome (AIDS) for eight months. The patient had no complaint of visual symptoms. A routine eye examination revealed his visual acuity to be 6/6 in both eyes. The dilated eye fundus examination using indirect ophthalmoscopy disclosed a localized white yellowish granular lesion in the peripheral retina of the right eye and a completely normal left eye. CMV retinitis with initial manifestation in the right eye was diagnosed. Due to incomplete treatment with ganciclovir, the retinal lesion rapidly enlarged and extended to the posterior pole, with eventual destruction of the nerve fiber layer and optic disc. The visual acuity of right eye dropped from 6/6 to 1/60 within six months. This case report indicates the importance of early, dilated eye fundus examination and recognition of early CMV retinitis in order to salvage visual function in AIDS patients. Completion of the anti-CMV treatment course in halting the progression of CMV retinitis is also emphasized.

Choroidal involvement in Wegener's granulomatosis: a case report.

Wegener's granulomatosis is a necrotizing, granulomatous vasculitis. It usually causes sinusitis, pneumonitis and glomerulonephritis. The common ocular manifestations include conjunctivitis, scleritis, peripheral keratitis and orbital inflammation. We report the case of a 50-year-old woman with Wegener's granulomatosis and very severe ocular complications who underwent bilateral enucleation. The pathologic findings of the eyeballs revealed granulomatous necrotizing scleritis, perivasculitis and granulomatous choroiditis. The last, as far as we know, has not yet been reported.

Endogenous Candida endophthalmitis after induced abortion.

PURPOSE: To report two young healthy women who developed endogenous Candida endophthalmitis after undergoing surgically induced abortion. METHOD: Case reports. RESULTS: In two eyes of two patients, a diagnosis of Candida endophthalmitis was established by typical fundus appearance, positive vaginal culture, and, in one case, positive vitreous culture. After vitrectomy and intravitreal amphotericin B injection, one eye of one patient had a best-corrected visual acuity of 20/200, whereas one eye of one patient, who had systemic corticosteroid treatment before the correct diagnosis, developed recurrent retinal detachment and a best-corrected visual acuity of counting fingers. CONCLUSIONS: Induced abortion may cause endogenous Candida endophthalmitis in young healthy pregnant women. Systemic corticosteroid treatment may increase the risk of endophthalmitis.

PIP: Reported, in this article, are the cases of two young women who developed endogenous Candida endophthalmitis after induced abortion. Both women experienced transient fever, chills, and abdominal pain after the abortion and were given antibiotics. The diagnosis of endophthalmitis was established on the basis of typical fundus appearance, positive vaginal culture, and (in one case) positive vitreous culture. In the first woman, who received vitrectomy and intravitreal amphotericin B injection, the affected eye had a best corrected visual acuity of 20/200. In the second woman, who was given systemic corticosteroid treatment before the correct diagnosis was reached, recurrent retinal detachment developed and the best corrected visual acuity was counting fingers. It appears that Candida organisms harbored in the genital tract are directly inoculated into the venous system during induced abortion. Once in the blood, if sufficient fungal load is present, Candida albicans tends to localize in the choroid and to spread toward the retina and vitreous cavity. The immunosuppressive effect of corticosteroids further increases the risk of endophthalmitis.

Effects of antiglaucoma drugs and corticosteroids on the cellular glucose uptake in cultured porcine corneal endothelial cells.

In this study, various commercially used antiglaucoma drugs and corticosteroids were investigated in their effects on porcine corneal endothelial cells especially in cellular glucose uptake. Cellular glucose uptake directly affects the pumping efficiency in corneal endothelial cells. Following the cells' treatment with various antiglaucoma eyedrops for 100 min, the 3H-2-deoxyglucose uptake in cultured porcine corneal endothelial cells was affected by betaxolol from 3.1% (1.6 mM), 181% (0.16 mM) to 158% (0.016 mM), by timolol from 93% (0.79 mM), 227% (0.079 mM) to 151% (0.0079 mM), by carteolol from 141% (3.4 mM), 180% (0.34 mM) to 97% (0.034 mM), by levobunolol from 80% (1.5 mM), 98% (0.15 mM) to 90% (0.015 mM), by dipivefrin from 116% (0.2 mM), 176% (0.02 mM) to 108% (0.002 mM) and by pilocarpine from 115% (9.6 mM), 210% (0.96 mM) to 210% (0.096 mM) when the cells were compared with a control medium. In the presence of various corticosteroids, the glucose uptake in corneal endothelial cells was affected by fluorometholone from 160% (0.26 mM), 139% (0.026 mM) to 107% (0.0026 mM), by dexamethasone from 85% (0.25 mM), 117% (0.025 mM) to 109% (0.0025 mM) and by betamethasone from 95% (0.25 mM), 96% (0.025 mM) to 99% (0.0025 mM). These results show that the commercial eyedrops of antiglaucoma drugs and corticosteroids will not decrease the cellular glucose uptake in cultured porcine corneal endothelial cells except when incubated with high concentrations of betaxolol, levobunolol and dexamethasone.