Expression profiles of the duplicated matrix metalloproteinase-9 genes suggest their different roles in apoptosis of larval intestinal epithelial cells during Xenopus laevis metamorphosis.

Matrix metalloproteinases (MMPs) play a pivotal role in development and/or pathogenesis through degrading extracellular matrix (ECM) components. We have previously shown that Xenopus MMP-9 gene is duplicated. To assess possible roles of MMP-9 and MMP-9TH in X. laevis intestinal remodeling, we here analyzed their expression profiles by in situ hybridization and show that their expression is transiently up-regulated during thyroid hormone-dependent metamorphosis. Of interest, MMP-9TH mRNA is strictly localized in the connective tissue and most highly expressed just beneath the larval epithelium that begins to undergo apoptosis. On the other hand, cells expressing MMP-9 mRNA become first detectable in the connective tissue and then, after the start of epithelial apoptosis, also in the larval epithelium. These results strongly suggest that MMP-9TH is responsible in the larval epithelial apoptosis through degrading ECM components in the basal lamina, whereas MMP-9 is involved in the removal of dying epithelial cells during amphibian intestinal remodeling.     

Clinical manifestations of influenza a myocarditis during the influenza epidemic of winter 1998-1999.

OBJECTIVES: The clinical features of myocarditis that developed during the influenza epidemic of winter 1998-1999 were investigated to emphasize the need for medical attention to this disease. METHODS: Nine patients were treated under diagnoses of acute myocarditis during the winter of 1998-1999. Five (two males and three females, mean age 52 +/- 18 years) were examined with myocarditis associated with influenza A. The diagnosis of influenza A myocarditis was based on electrocardiographic and echocardiographic abnormalities, increased creatine kinase levels and at least a four-fold increase in influenza A virus titers using paired sera. RESULTS: All patients had preceding flu-like symptoms and fever. Cardiac involvement developed between 4 and 7 days after the onset of influenza symptoms. Dyspnea progressively worsened in three patients, one went into shock and one had persistent fever, cough and mild dyspnea without apparent cardiac symptoms. Three patients had ST elevation associated with Q waves and one had complete left bundle branch block. The creatine kinase levels were abnormally increased and global wall motion of the left ventricle on echocardiography was decreased in all patients. Two patients had diagnoses of fulminant myocarditis. One patient died of pneumonia following cerebral infarction, but the left ventricular dysfunction normalized in the remaining four patients. CONCLUSIONS: Cardiac involvement occurred between 4 and 7 days after the onset of influenza symptoms, and worsening dyspnea was the most common symptom. Electrocardiography, echocardiography and creatine kinase levels should be checked to determine the potential for cardiac involvement when patients present with suspected influenza associated with worsening dyspnea or prolonged weakness. Increasing the awareness of influenza myocarditis may help in the earlier identification and treatment of this disease during influenza epidemics.     

Investigation on safety climate for preventing dispensing errors in community pharmacies

We investigated consciousness of the prevention of dispensing errors with the pharmacists and clerical staffs which work in community pharmacies and analyzed the structure of those subconscious to examine preventive measures of dispensing errors. Questionnaire survey was performed for all pharmacists and clerical staffs working in community pharmacies where each is affiliated with four pharmacy groups. The questionnaire consisted of 38 questions about "atmospheres for the prevention of dispensing errors" in the pharmacy along their attributions. And data were analyzed by occupation to confirm the difference. As a result of factor analysis, five factors such as "the posture of the boss", "information exchange", "the order of the pharmacy" were extracted from the pharmacists. Moreover, in the case of the clerical staffs, five similar factors have been extracted besides "a sense of responsibility to duties" replaced "the order of the pharmacy". As a result of structural equation modeling, the pass model with high goodness of fit to which "measures for dispensing error prevention" and "consciousness to the dispensing error of a pharmacy" were assumed to be a subordinate concept respectively by each occupational category. It became clear that a suggestion of the concrete preventive measures drafting was provided even from the investigation of the consciousness level.     

Lipid microsphere formulation containing rifampicin targets alveolar macrophages

The study demonstrated that lipid microspheres (LM) containing rifampicin (LM-RFP) could deliver the drug to alveolar macrophages in vitro and in vivo, and that intranasal administration to animals could achieve preferential accumulation in the lungs with less effect on the liver. The LM-RFP particles had a mean diameter of 247.2 ± 75.7 nm, and their size remained stable when stored at 4°C or 25°C for at least 4 weeks. In vitro uptake of [³H]LM-RFP by alveolar macrophages was over 4 times higher than that of unencapsulated [³H]RFP, whereas the in vivo uptake was 30 times higher. Flow cytometric analysis and confocal laser scanning microscopy confirmed that LM could deliver the encapsulated drug effectively to alveolar macrophages in vitro and in vivo. Intranasal administration of [³H]LM-RFP to normal mice resulted in preferential pulmonary uptake of the drug and lower levels in the blood and liver compared with administration of unencapsulated [³H]RFP. In conclusion, LM-RFP could be a promising preparation for delivery via the respiratory tract to tuberculosis (TB) and TB/HIV patients.     

Pathological findings of multifocal choroiditis with panuveitis and punctate inner choroidopathy

PURPOSE: To compare the pathological findings between multifocal choroiditis with panuveitis (MCP) and punctate inner choroidopathy (PIC). METHODS: Fourteen eyes of 14 patients clinically diagnosed as having MCP or PIC who underwent surgical excision of choroidal neovascularization (CNV) were studied. Immunohistochemical findings of the excised CNV in MCP (eight eyes) and PIC (six eyes) cases were compared. Antibodies against vascular endothelial growth factor (VEGF), CD68, CD3, and CD20 were used as primary antibodies. RESULTS: Expression of VEGF and CD68 in the CNV was observed in all MCF and PIC cases. In three of eight eyes with MCP, intraocular inflammatory findings were found clinically, while immunohistochemical study demonstrated infiltration of CD20-positive B lymphocytes in the CNV. No B lymphocyte infiltration was found in the six eyes with PIC. No differences in pathological findings were found between the five MCP eyes without intraocular inflammation and the six PIC eyes, with all eyes showing no B lymphocyte infiltration. CONCLUSIONS: In MPC cases showing clinical inflammatory findings, infiltration of B lymphocytes was also observed histopathologically, suggesting that the presence of inflammatory cells in the anterior chamber or vitreous body clinically is an indicator of active inflammatory CNV. However, this study clarifies that MCP eyes without intraocular inflammation and PIC eyes are not different in histopathological findings.     

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma,Leishmania, and Plasmodium parasites

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti‐Trypanosoma, anti‐Leishmania, and anti‐Plasmodium activities in vitro and investigated their mechanisms of action. Twenty‐three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC₅₀ values less than 20 μg/ml. Eleven extracts showed high anti‐Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC₅₀ (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti‐Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC₅₀ (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti‐Plasmodium activity with the leaf and stem‐bark extracts of Terminalia ivorensis recording the highest activity. Their IC₅₀ (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis‐like cell death in Trypanosoma parasites. Anti‐Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.     

Psychometric properties of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), Japanese version

Background  

The importance of evaluating the outcomes of health care from the standpoint of the patient is now widely recognized. The purpose of this study is to develop and test a Japanese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).     

General practitioner's recognition of service cooperation with community pharmacists related to home care in a suburban area

OBJECTIVES: To clarify the factors affecting a general practitioner's demands and the recognition of service cooperation with community pharmacists related to home care in a suburban area. METHODS: A questionnaire on pharmacy services and functions was administered to 215 general practitioners in a suburban area. Gender, age, specialty, length of practice, status of home visiting, requests for community pharmacists, awareness of a home visiting service by community pharmacists, status of issues about home visiting orders to community pharmacists and the criteria for deciding to issue an order, recognition of the necessity of a home visiting service by pharmacists, expectation value to the community of the pharmacists' participation in the home care service and requests, recognition of cooperation with other home care related professions, ease of cooperation with community pharmacists, disincentives for cooperation with community pharmacists, factors necessary to promote cooperation between practitioners and community pharmacists, and factors necessary to promote the home care system were surveyed. Using the results, chi 2 test and principal component analysis were performed. RESULTS: It was found that the general practitioners' main demands were support and management of pharmaceutical therapy. Meanwhile, the practitioners' low cognition of pharmacists' home visiting seemed to be one disincentive to cooperation with pharmacists. Every practitioner who had issued visiting orders to pharmacists practiced home visiting and issued the visiting orders based on patients' condition at home. Practitioners who practiced home visiting were more active in promoting the home care system and had a better cognition and more extensive demands for pharmacists' home visiting compared to practitioners with no home visiting. Practitioners with good recognition of cooperation with community pharmacists had better cognition, realized the necessity of, and expected pharmacist's home visiting compared to practitioners with low awareness. However, practitioners' overall recognition of cooperation with pharmacists was relatively low. As disincentives, practitioners pointed out lack of acquaintance, the unclear function of pharmacists, and no opportunity for cooperation. So, enhancing practitioners' awareness of home care, clarifying the pharmacist's role, establishing a relationship of mutual trust through information feedback and/or exchange based on practice would be effective in promoting service cooperation with community pharmacists.     

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment.DESIGN: Randomized controlled clinical trial.METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes.RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes.CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.     

Treatment or prevention of herpes simplex virus retinitis with intravitreally injectable crystalline 1-O-hexadecylpropanediol-3-phospho-ganciclovir

PURPOSE: To evaluate an intraocular drug delivery system consisting of the crystalline ammonium salt of 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV) as a slow-release form of the drug. METHODS: A dosage of 0.885, 1.57, 2.8, 4.486, or 8.85 micromol of ammonium salt HDP-P-GCV in 0.1 mL was intravitreally injected into rabbit vitreous. The toxicity and safety were evaluated with ophthalmoscopy, electroretinography, and pathology. Drug vitreous levels were determined at various time intervals by means of HPLC. The treatment efficacy and duration of efficacy were tested in a herpes simplex virus (HSV)-1 retinitis rabbit model. RESULTS: Intravitreal injections of the compound revealed clear vitreous of optic axis, a desirable drug depot in the inferior vitreous cavity, and no clinical toxicity, except for variable mild local posterior subcapsular cataract and local retinal toxicity with high doses. HPLC analysis showed free ammonium salt of HDP-P-GCV in the upper vitreous at a level of 0.2 microM 12 weeks after the 2.8-micromol initial intravitreal dose. Drug concentration was still 1.95 microM 20 weeks after the 8.85-micromol initial intravitreal dose. These concentrations (0.2 and 1.95 microM) were 10 and 100 times higher, respectively, than the median inhibitory concentration (IC(50)) of HSV-1 (0.023 microM). Treatment with the highest nontoxic dose (2.8 micromol) and the highest dose (8.85 micromol) showed significant protection from HSV-1 infection (P < 0.05) and provided sustained antiviral effect after a single intravitreal drug injection. CONCLUSIONS: The crystalline ammonium salt of HDP-P-GCV may be a very useful local therapy for herpes family viral retinitis.