Control of trachoma and prevention of blindness in rural communities in Burma.

Trachoma was identified as the single most important cause of blindness in central Burma in a study carried out in 1961-1962. Control measures started in 1964 considerably reduced the degree of endemicity and severity of the disease in the areas treated. According to recent simplified criteria of evaluation, the prevalence of active trachoma has been reduced by more than 60% and that of active inflammatory disease of moderate and severe intensity from 7.4% to 1.8% of the active cases. A reduction in the risk of becoming infected is evident from changes that have occurred among the younger age groups.     

BMK1 is activated in glomeruli of diabetic rats and in mesangial cells by high glucose conditions

BACKGROUND: High glucose causes renal cell injury through various signal transduction pathways, including mitogen-activated protein (MAP) kinases cascades. Big MAP kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a recently identified MAP kinase family member and was reported to be sensitive to osmotic and oxidative stress. However, the role of BMK1 in diabetic nephropathy has not been elucidated yet. METHODS: We investigated whether BMK1 is activated in the glomeruli of Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus in comparison with the control Long Evans Tokushima Otsuka (LETO) rats. We also examined the effect of high glucose on BMK1 activity in cultured rat mesangial cells. RESULTS: BMK1 and ERK1/2 but not p38 were activated in the glomeruli of OLETF rats, which showed diabetic nephropathy at 52 weeks of age. High glucose, in addition to a high concentration of raffinose, caused rapid and significant activation of BMK1 in rat mesangial cells. MAP kinase/ERK kinase (MEK) inhibitors, U0126 and PD98059, both inhibited BMK1 activation by high glucose in a concentration-dependent manner. Protein kinase C (PKC) inhibition by GF109203X and PKC down-regulation with long-time phorbol myristate acetate (PMA) treatment both inhibited BMK1 and Src kinase activation. Src kinase inhibitors, herbimycin A and PP2, also inhibited high glucose-induced BMK1 activation. PKC inhibitors, Src inhibitors and MEK inhibitors, all inhibited cell proliferation by high glucose. Finally, transfection of dominant-negative MEK5, which is an upstream regulator of BMK1, abolished the BMK1-mediated rat mesangial cell proliferation stimulated by high glucose. CONCLUSION: In the present study, we demonstrated that high glucose activates BMK1 both in vivo and in vitro. It was suggested that high glucose induces PKC- and c-Src-dependent BMK1 activation. It could not be denied that BMK1 activation is induced through an osmotic stress-sensitive mechanism. BMK1-mediated mesangial cell growth may be involved in the pathogenesis of diabetic nephropathy.     

Outcomes of sulcus implantation of Array multifocal intraocular lenses in second-eye cataract surgery complicated by vitreous loss

PURPOSE: To evaluate the outcomes of implantation of the Array((R)) multifocal intraocular lens (IOL) (model SA-40N, AMO) in the ciliary sulcus in second-eye cataract surgery complicated by vitreous loss. SETTING: Department of Ophthalmology, Arrowe Park Hospital, Wirral, United Kingdom. METHODS: This retrospective study comprised 15 patients who had complicated second-eye cataract surgery with loss of posterior capsule support leading to sulcus implantation of an Array multifocal IOL. The patients were recalled for assessment. Objective evaluation included uncorrected and corrected distance and near visual acuities, complications, and IOL centration. Subjective assessment was performed using a questionnaire that included the VF-14 index of visual function; the questions were related to satisfaction with vision, limitations from halos and glare, and the frequency of spectacle wear. RESULTS: Fourteen eyes (93%) had postoperative visual improvement. The best corrected distance acuity was 6/12 or better in 11 eyes (73%). The best corrected near acuity was J2 or better in 12 eyes (80%). The IOL was well centered in 11 eyes (73%) and slightly decentered in 4 eyes (27%). Subjectively, patients indicated a high level of satisfaction with their distance and near vision. The VF-14 indicated high levels of visual function, with 73% of patients having a score higher than 90 (out of 100). Seventy-three percent of patients were not troubled by glare or halos, and 40% did not wear spectacles. CONCLUSION: Implantation of the Array multifocal IOL in the sulcus during complicated phacoemulsification led to good visual outcomes based on objective and subjective patient measures.     

Ebselen inhibits p38 mitogen-activated protein kinase-mediated endothelial cell death by hydrogen peroxide

Ebselen (2-phenyl-1, 2-benzisoselenazol-3[2H]-one) is a seleno-organic compound exhibiting both glutathione peroxidase and antioxidant activity. Although it has been reported that ebselen is effective against hydrogen peroxide (H(2)O(2))-induced cell death in several cell types, its effect on endothelial cell damage has not yet been elucidated. In the present study, we examined the effect of ebselen on H(2)O(2)-induced human umbilical vein endothelial cells (HUVECs) death, and its intracellular mechanism. Our findings showed that pretreatment of HUVECs with ebselen resulted in a significant recovery from H(2)O(2)-induced cell death in a concentration-dependent manner. In addition to the inhibition of lactate dehydrogenase (LDH) leakage, ebselen inhibited H(2)O(2)-induced cytochrome c release and caspase-3 activation and the resultant apoptosis in HUVECs. Moreover, it was observed that H(2)O(2) significantly stimulated activation of mitogen-activated protein (MAP) kinases, i.e., p38 MAP kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2). Ebselen inhibited H(2)O(2)-induced p38 MAP kinase, but not JNK or ERK1/2 activation. Furthermore, SB203580 (4-[4-fluorophenyl]-2-[4-methylsulfinylphenyl]-5-[4-pyridyl]-1H-imidazole), a specific p38 MAP kinase inhibitor, inhibited H(2)O(2)-induced p38 MAP kinase phosphorylation, cytochrome c release, caspase-3 activation, as well as cell death in HUVECs. These findings suggest that ebselen attenuates H(2)O(2)-induced endothelial cell death through the inhibition of signaling pathways mediated by p38 MAP kinase, caspase-3, and cytochrome c release. Thus, inhibition of p38 MAP kinase by ebselen may imply its usefulness for prevention and/or treatment of endothelial cell dysfunction, which was suggested to be the first step in the development of atherosclerosis.     

Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cells via extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation

Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK.     

Systemic remission of non-Hodgkin's lymphoma after intralesional interferon alpha-2b to bilateral conjunctival lymphomas

PURPOSE: To report the beneficial systemic effect of a 5-week course of intralesional interferon alpha-2b (IFN-A) injections to bilateral conjunctival lymphomas in a patient with relapsing non-Hodgkin's lymphoma. DESIGN: Interventional case report. METHODS: A patient in relapse with non-Hodgkin's lymphoma who declined further systemic therapy received 1.5-million IU IFN-A injected intralesionally to each of two conjunctival lymphomas to reduce ocular discomfort. This dose was repeated 10 times over 5 weeks. RESULTS: Conjunctival, postauricular, and facial lesions clinically resolved within 3 months of the start of treatment. Inguinal lymph nodes reduced in size, and the patient reported increased well-being and less fatigue. Side effects included injection discomfort and mild flulike symptoms, which were well tolerated. The improvement lasted 6 months from the first IFN-A injection. CONCLUSIONS: Intralesional treatment of conjunctival lymphomas with IFN-A induced disappearance of the tumors and also had a beneficial systemic effect.     

Pneumococcal vaccination: opinion of general practitioners and hospital doctors in Scotland, 1999-2000

A cross sectional survey by postal questionnaire was carried out to examine general practitioners' (GPs) and hospital doctors' (HDs) knowledge, attitudes and practice (KAP) with regard to pneumococcal vaccination in primary and hospital care in Scotland. Most GPs and HDs considered patients with chronic medical conditions, as recommended by the Department of Health (DoH), to be candidates for pneumococcal vaccination. Although the DoH does not currently recommend the vaccine for all the elderly, 47% of GPs and 46% of HDs reported that the vaccine should be given to this group. GPs (61-85%) and HDs (48-55%) indicated that they considered the vaccine to be safe and effective. The acceptance of pneumococcal vaccine was much lower than for influenza vaccine however, and 79% of HDs and 17% of GPs had never used the vaccine. Documented policies (with or without set targets) for pneumococcal vaccine existed in only 14% of general practice and 3% of hospital settings. Over 70% of respondents indicated that GPs should take responsibility for pneumococcal vaccination. The main sources of knowledge about pneumococcal vaccines were stated to be discussion with colleagues, review of medical literature, past experience, and the DoH recommendations. A clear immunisation policy and financial support for vaccination were identified as important strategies to improve pneumococcal vaccine coverage. Strategies directed toward these factors could enhance vaccine delivery and coverage of vaccine in high-risk individuals.