The structural effect of intravitreal Brilliant blue G and Indocyanine green in rats eyes.

PURPOSE: To compare the potential retinal toxicity of two commercially Brilliant blue G dyes (Brilliant Peel and Ocublue Plus) and Indocyanine green (ICG) at usual clinical concentration. METHODS: Brilliant Peel 0.025% (n=9), Ocublue Plus 0.025% (n=9), and ICG 0.05% (n=9) were injected intravitreally into Sprague-Dawley rat left eyes with balanced salt solution injected in the contralateral eyes as control. Evaluation of the effect of the dyes on retinal architecture was done by histological analysis of neurosensory retinal thickness and retinal ganglion cell (RGC) counts 7 days after intravitreal injection. Paired t-test was done to detect the presence of biologically significant thinning in neurosensory retina and five retinal layers for each dye (paired t-tests). One-way ANOVA and Tukey's Honestly Significant Difference test were used to assess whether different dyes caused significant thinning in mean neurosensory retinal thickness and reduction of mean RGC density. RESULTS: Eyes treated with ICG had significantly thinner mean total neurosensory retinal thickness compared with the control eyes (P-value=0.01), followed by those treated with Ocublue Plus (P-value=0.03). Brilliant Peel did not cause significant thinning in any of the five retinal layers (all P-values>0.05). No significant difference in mean thinning of the total retinal thickness was detected between dyes (P-value=0.11). The mean thickness of the photoreceptor outer segment and outer plexiform layers were significantly reduced in ICG-injected eyes when compared with the control eyes (P-value=0.02). No significant difference in mean thinning between the three dyes was detected at all five retinal layers using one-way ANOVA (all P-values>0.35). RGC density was significantly reduced for ICG (P-value=0.01) but only marginally for Ocublue Plus (P-value=0.05). No significant reduction in RGC density was observed for Brilliant Peel (P-value=0.2). CONCLUSION: Intravitreal Brilliant Peel is safe to rats retina. The retinal thinning and reduction in RGC density induced by Ocublue Plus requires further studies to determine the safety profile of this product. Potential retinal toxicity is seen with ICG 0.05%.

Lack of association between Gly82Ser, 1704G/T and 2184A/G of RAGE gene polymorphisms and retinopathy susceptibility in Malaysian diabetic patients.

Diabetic retinopathy is the most common diabetic eye disease, occurring in about 60% of type 2 diabetic patients. Other than known clinical risk factors, the influence of genes has been suggested as part of the development of diabetic retinopathy. We investigated the association of Gly82Ser, 1704G/T and 2184A/G polymorphisms in the RAGE gene with retinopathy in type 2 diabetic patients in Malaysia. Ninety-eight unrelated retinopathy patients and 185 unrelated healthy controls from all over Malaysia were recruited in this study. The allele and genotype frequencies of the three gene polymorphisms were investigated using PCR-RFLP. The allele frequency of the three polymorphisms did not differ significantly between the control and the retinopathy group (P > 0.05). Analysis of the frequency of GA+AA, GT+TT and AG+GG in the retinopathy group did not reveal significant differences (P > 0.05) compared to the control group. We conclude that RAGE gene Gly82Ser, 1704G/T and 2184A/G polymorphisms are not associated with retinopathy development in the Malaysian population.

Intravitreal injection of recombinant tissue plasminogen activator and pneumatic displacement of submacular haemorrhage.

We report a case of a patient with hypertension and ischaemic heart disease on anti-platelet treatment, who developed uniocular profound visual loss from a submacular haemorrhage secondary to valsalva retinopathy. He was treated with a combination of intravitreal recombinant tissue plasminogen activator (rtPA) and sulphur hexafluoride (SF6) gas followed by strict prone positioning. He demonstrated significant displacement of the haemorrhage and improvement of vision postoperatively.

Retinal laser photocoagulation.

Since its discovery in the 1940s, retinal photocoagulation has evolved immensely. Although the first photocoagulators utilised incandescent light, it was the invention of laser that instigated the widespread use of photocoagulation for treatment of retinal diseases. Laser permits choice of electromagnetic wavelength in addition to temporal delivery methods such as continuous and micropulse modes. These variables are crucial for accurate targeting of retinal tissue and prevention of detrimental side effects such as central blind spots. Laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy amongst many other retinal conditions. Considering the escalating prevalence of diabetes mellitus, it is important for physicians to grasp the basic principles and be aware of new developments in retinal laser therapy.

Photodynamic therapy combined with systemic corticosteroids for choroidal neovascularisation secondary to punctate inner choroidopathy.

AIM: To report on visual acuity (VA) and angiographic outcomes in patients presenting with subfoveal choroidal neovascular membranes (CNV) secondary to punctate inner choroidopathy (PIC), treated with photodynamic therapy (PDT) with verteporfin combined with systemic corticosteroids. METHODS: A prospective case series of patients with subfoveal CNV secondary to PIC was analysed. All patients were treated with PDT combined with oral prednisolone (1 mg/kg body weight/day) which was started 5 days before PDT. Fluorescein angiography was performed at baseline and every 3 months post-treatment to establish the size, position, and activity of the CNV. Visual acuity was measured using the ETDRS scale. Further PDT treatment was carried out at follow-up visits if there was angiographic evidence of ongoing CNV activity. RESULTS: Five female patients with a mean age of 30.4 years (range 25-43 years) were treated over a 12-month period. The mean greatest linear diameter (GLD) of the CNV was 1.66 mm (range 0.46-3.28 mm). A mean improvement in vision of nine ETDRS letters (range -15-20 letters) after treatment was found, which was maintained at final follow-up. The mean follow-up time was 12 months (range 10-14 months). The mean number of PDT treatments was two (range 1-3). CONCLUSIONS: The vaso-occlusive effect of PDT combined with the vasostatic and anti-inflammatory effect of systemic oral prednisolone appears to be a safe and effective option in the primary treatment of subfoveal CNV in patients with PIC.

Methicillin-resistant Staphylococcus aureus: a 5-year review of surveillance data in a tertiary care hospital in Saudi Arabia.

BACKGROUND: Staphylococcus aureus is an important pathogen that leads to serious infections in the community and in hospitals. Evidence has shown that the prevalence of infection and colonization with drug-resistant S. aureus, such as methicillin-resistant S. aureus (MRSA) and glycopeptide intermediately susceptible S. aureus, is increasing. Authorities must be aware of the prevalence of MRSA infection and colonization in their country in order to implement and monitor infection control policies that help curtail further emergence of this pathogen. OBJECTIVES: To examine the trend of hospital-acquired MRSA infection and colonization in a tertiary care institution in Saudi Arabia during a 5-year period in order to identify specific areas at high risk for MRSA transmission, and to review our MRSA decolonization procedure and outcomes. METHODS: Surveillance data prospectively collected from January 1, 2000, through December 31, 2004, on hospital-acquired (HA) MRSA were analyzed, with an emphasis on the trend of HA-MRSA infection and colonization, areas of high transmission, risk factors, and effectiveness of the implemented decolonization policy. RESULTS: During the study period, 442 cases of HA-MRSA infection and colonization were identified. Of these, 51.2% were infections, and 48.8% were colonizations. An increasing trend in the incidence rates of infection and colonization was noticed during the study period, and most cases were identified on the surgical ward (33.3%) and medical ward (32.1%). Of the 34 infected patients who underwent systematic decolonization, 35.3% were successfully decolonized, and of the 11 who underwent topical decolonization, 63.6% were successfully decolonized. CONCLUSION: The increasing trend of HA-MRSA infections has been a noticeable global problem. We identified a gradual increase in the rates of MRSA colonization and infection in a tertiary care center Saudi Arabia and recognize the importance of abiding by strict infection control policies, including hand hygiene and proper isolation practices. Continued surveillance for MRSA and other emerging multidrug-resistant pathogens is also needed.

Retinal artery macroaneurysms: clinical and fluorescein angiographic features in 34 patients.

AIM: To describe the clinical and fluorescein angiographic features of patients with macroaneurysms (MAs) attending an ophthalmology department over 8 years. METHODS: All the patients between 1997 and 2004 with a diagnosis of retinal artery MA were identified from hospital records. Photographs and fluorescein angiograms were examined, and the MAs classified according to their clinical (haemorrhagic or exudative) features, and angiographic (saccular or fusiform) features. Baseline data of the patients were taken including visual acuity and associated ocular and medical conditions. RESULTS: A total of 38 MAs were identified in 34 patients. The age at presentation ranged from 36 to 93 years, with a mean of 73.7 years. Of them, 24/34 (70%) were female patients, and 10/34 (30%) were male patients. There was a history of hypertension in 9/14 patients (64.3%). Of 38 MAs, 32 were identifiable as either saccular or fusiform. Of these, 22/32 (68.75%) were saccular, the rest fusiform. In all, 72.7% of the saccular MAs showed haemorrhage as the predominant feature. Of the 10 fusiform MAs, 90% showed haemorrhage as the predominant feature. CONCLUSION: Retinal artery macroaneurysm is a rare condition that may mimic a variety of other conditions. Most MAs do not require treatment. We suggest guidelines for diagnosis and propose a treatment algorithm for this condition.

Imaging of osteo-odonto-keratoprosthesis by electron beam tomography.

AIM: To describe the experience of using electron beam tomography (EBT) in imaging of osteo-odonto-keratoprosthesis (OOKP) to identify early bone and dentine loss which may threaten the viability of the eye. METHODS: Seven patients with an OOKP in one eye underwent EBT. The OOKP lamina dimensions were measured on EBT and compared to the manual measurements at the time of surgery. RESULTS: There was a high degree of resolution of the OOKP lamina noted with EBT. In particular, it identified three patients with a marked degree of thinning of the lamina edges. Two of these patients had OOKP that were allografts. The mean time from surgery to examination was 3.6 years (range 1.2-5 years) while the mean age of the patients was 56 years (range 31-79 years). CONCLUSIONS: It is important to monitor regularly the dimensions and stability of the OOKP lamina as it will help detect cases that are at risk of extrusion of the optical cylinder and consequent endophthalmitis. Prophylactic measures can then be taken to prevent such serious complications from occurring. In this series, the authors found EBT to have excellent resolution and speed and they would support regular scanning of the OOKP lamina in all patients.

Retrobulbar haemorrhage associated with chronic Gingko biloba ingestion.

Retrobulbar haemorrhage is a rare and potentially sight threatening complication after peribulbar local anaesthetic injection for cataract surgery. A case is reported of a woman who developed this complication and was subsequently found to have been taking Gingko biloba extract tablets which may have predisposed her to developing the haemorrhage.

Does frequency doubling technology perimetry reliably detect neurological visual field defects?

AIM: To determine the ability of frequency doubling technology (FDT) perimetry to detect visual field defects of neurological origin. METHODS: A total of 15 eyes of nine patients who all had complete hemianopias or quadrantanopias underwent the FDT 20-5 screening mode test and Humphrey 24-2 SITA Fast visual field test (HFA). The FDT results were scored according to the number of abnormal test locations (out of a maximum of 4) in each affected quadrant. FDT locations showing a defect of P< 2% were considered abnormal. RESULTS: Of the 15 eyes, six showed complete superior quadrantanopic and nine complete hemianopic field defects on HFA. Of 96 FDT test locations in these quadrants or hemifields only 38 were abnormal on FDT testing (40%). For the quadrantanopic field defects, five out of 24 locations were abnormal (21%). For the hemianopic field defects, 33 out of 72 locations were abnormal (49%). In three eyes (two with quadrantanopias and one with complete hemianopia), FDT perimetry failed to demonstrate any corresponding abnormality. CONCLUSIONS: The FDT screening test can fail to demonstrate complete hemianopic and quadrantanopic field defects. Users should be aware of this deficiency when using FDT to screen for field defects.

Glutamine synthetase expression in liver, muscle, stomach and intestine of Bostrichthys sinensis in response to exposure to a high exogenous ammonia concentration.

A previous study provided evidence that the adaptive strategy used by the teleost fish Bostrichthys sinensis (sleeper) for detoxifying ammonia during extended periods of air exposure was to synthesize and store glutamine, primarily in the muscle, accompanied by an increase in glutamine synthetase (GSase) activity in liver. The aim of the present study was to assess the effect on GSase expression in various tissues of exposure of B. sinensis to exogenous ammonia. Exogenous ammonia increases internal ammonia concentrations in fish, mimicking environmental situations such as air exposure that preclude loss of ammonia across the gills, and thus triggering alternative mechanisms for ammonia detoxification. The results reveal relatively high levels of GSase activity, not only in liver but also, unexpectedly, in muscle, and even higher levels in intestine and, in particular, stomach. Exposure to ammonia results in significant increases in GSase activity, GSase protein and GSase mRNA levels in all of these tissues except stomach. The amino acid sequences of GSases from liver and stomach deduced from the cDNA sequences are essentially identical and are >97 % identical to the amino acid sequences of GSases from Gulf toadfish (Opsanus beta) and marble goby (Oxyeleotris marmoratus).

Total synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 1. Racemic and asymmetric synthesis of bicyclo[4.3.1] key building blocks.

A brief introduction into the chemistry of the CP-molecules is followed by first-generation synthetic sequences toward key building blocks for their total synthesis. Processes for both racemic and enantiomerically enriched bicyclo[4.3.1] ketone 6 or its equivalent are described, and the absolute stereochemistries of the optically enriched intermediates are determined. The efficient route developed to racemic 6 and the ready access to both enantiomers of key building blocks provided the opportunity for the total synthesis of the CP-molecules and determination of their absolute stereochemistry.

Total synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 2. Model studies for the construction of key structural elements and first-generation strategy.

Crucial model synthetic and mechanistic studies directed toward the development of methodology for the construction of the maleic anhydride moiety of the CP-molecules are described. Studies directed toward the stereoselective attachment of the upper side chain, culminating in the discovery of long-range stereochemical control, are also discussed. In addition, a first-generation strategy toward the CP-molecules, establishing key intermediate 5 as a "beachhead" from which all future operations would diverge, is also presented. Although this first-generation strategy failed to yield the target molecules, the endeavor laid the important groundwork for the next-generation drives toward the CP-molecules.

Novel strategies to construct the gamma-hydroxy lactone moiety of the CP molecules. Synthesis of the CP-225,917 core skeleton.

[formula: see text] The array of challenging structural lineaments embodied in the CP molecules (1 and 2, Figure 1) offers synthetic chemists uncharted realms of exploration and discovery. In this communication, we focus on the chemical hurdies posed by the gamma-hydroxy lactone moiety of these exciting targets. Thus, the examination of the general reactivity of these systems, the development of a novel tandem oxidation sequence to construct the gamma-hydroxy lactone moiety, and the successful construction of the complete polycyclic core of 2 (compound 28, Scheme 5) is enumerated within.

New synthetic technology for the synthesis of hindered alpha-diazoketones via acyl mesylates.

[formula: see text] A mild and reliable one-pot protocol for the elaboration of sterically demanding carboxylic acids into alpha-diazoketones via acyl mesylates has been developed. Aside from delineating the reaction parameters which render this strategy quite general for hindered carboxylic acids, we have directly proven the existence of the fleeting acyl mesylate group as the reactive species in these reactions and shed light onto the differing mechanisms which are operative in the activation of hindered and simple carboxylic acids with methanesulfonyl chloride.

Remarkable tethering effect on DNA cleavage of propargylic sulfone conjugates with intercalating moieties.

A number of novel propargylic sulfone conjugates 3 and 4 with intercalating moieties were synthesized and evaluated for DNA cleavage activity through nucleic base alkylation. A remarkable enhancement in DNA cleaving potency was observed with those conjugates 3 possessing a suitable spacer, a right attachment point at the aromatic ring, and a good intercalator.