Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives.

Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.

Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4-]pyridines.

Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-]pyridines targeting , the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines.

Antimalarial activity of tetrahydro-β-carbolines targeting the ATP binding pocket of the Plasmodium falciparum heat shock 90 protein.

A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment.

Self-immolative bioluminogenic quinone luciferins for NAD(P)H assays and reducing capacity-based cell viability assays.

Highly sensitive self-cleavable trimethyl lock quinone-luciferin substrates for diaphorase were designed and synthesized to measure NAD(P)H in biological samples and monitor viable cells via NAD(P)H-dependent cellular oxidoreductase enzymes and their NAD(P)H cofactors.

Sclerochoroidal calcifications imaged using enhanced depth imaging optical coherence tomography.

Purpose: To report a case of sclerochoroidal calcifications and describe the appearance of these lesions using optical coherence tomography with enhanced depth imaging (EDI-OCT) technology.

Design: Case Report

Methods: An 85-year-old patient who presented with bilateral retinal lesions suspected to be metastases was evaluated with slit-lamp biomicroscopy, funduscopy, fluorescein angiography, B-scan ultrasonography (U/S), and EDI-OCT.

Results: B-scan U/S demonstrated echo-dense consolidations in the choroid bilaterally with acoustic shadowing consistent with sclerochoroidal calcifications.

Confirmation of and differentiation among primary vascular lesions using ultrasonography.

Purpose: To demonstrate the utility of orbital ultrasound in the evaluation and management of suspected orbital vascular lesions.

Methods: Clinical case series of 15 patients with suspected orbital vascular lesions seen in the Neuro-ophthalmology clinic of the Wilmer Eye Institute. The techniques of standardized echography (combined use of a contact B-scan and standardized A-scan) were performed by an experienced echographer, and data obtained were compared with other available imaging modalities to determine appropriate management.

The suboptimal role of optical coherence tomography in diagnosing choroidal metastasis in the macula.

Purpose: To describe the clinical, optical coherence tomography, and echographic findings of a choroidal metastasis in the macula. An initial, erroneous diagnosis of a serous pigment epithelial detachment of the macula had been based on ophthalmoscopic and optical coherence tomography findings.

Methods: Case report of a patient with blurred vision in one eye and presumed serous pigment epithelial detachment.

Epibulbar foreign body granuloma masquerading as extrascleral extension following brachytherapy for choroidal melanoma.

Purpose: To describe a patient with epibulbar foreign body granuloma following brachytherapy for choroidal melanoma and to illustrate the echographic features that aided in the differential diagnosis.

Methods: Observational case report. Patient had multiple clinical exams over time to evaluate a treated choroidal melanoma.

Ultrasound features of orbital granular cell tumor.

The authors report the echographic characteristics of a rare orbital granular cell tumor and correlate these findings with histopathology. A 56-year-old woman presented with proptosis. Complete ophthalmic and ultrasound examinations were performed.

Prevalence of cystoid macular edema and stability in oct retinal thickness in eyes with retinitis pigmentosa during a 48-week lutein trial.

Purpose: To describe, in a group of patients with moderately advanced retinitis pigmentosa (RP), the prevalence of cystoid macular edema (CME), the variation in foveal thickness over a 48-week period, the correlation of visual acuity (VA) with retinal thickness, and the lack of response of CME to lutein administration.

Methods: Optical coherence tomography (OCT) imaging of the macula and clinical examination were evaluated for 77 eyes of 39 patients with RP over 11 months, with a scan done every 6 weeks.

Results: The prevalence of CME, defined by cysts visible on OCT, was 49%.

Recurrent vitreous hemorrhage secondary to haptic-induced chafing.

Case Report: After cataract extraction and placement of a posterior chamber intraocular lens, a 70-year-old man had 5 vitreous hemorrhages over 3 years. Iris transillumination defects and apposition of the nasal haptic and ciliary body were found.

Comments: Iris chafing is a rare complication of cataract extraction.

Optical coherence tomography of peripheral retinal lesions in enucleated human eye specimens with histologic correlation.

Purpose: To report optical coherence tomography (OCT) histologic correlations of three common peripheral retinal lesions and to explore the feasibility of the use of OCT to image retinal pathologic conditions in fixed tissue specimens.

Design: Experimental study.

Methods: We studied peripheral retinal lesions that were available to us in 11 formalin-fixed caps of seven human eyes that had been enucleated previously for choroidal melanoma.

Optical coherence tomography of enucleated human eye specimens with histological correlation: origin of the outer "red line".

Purpose: To further define the origin of the "outer red line" (ORL) present in retinal optical coherence tomograms.

Design: Laboratory investigation.

Methods: Eleven formalin-fixed caps of seven human eyes previously enucleated for choroidal melanoma at the Wilmer Eye Institute were studied.

Identification of visually significant operculum without macular hole by optical coherence tomography.

Case Report: We report a case that illustrates the effectiveness of optical coherence tomography (OCT) in identifying visually significant vitreoretinal interface opacities in the absence of a macular hole. A patient presented with a scotoma in the right eye. Fundoscopic examination revealed a small lesion in close proximity to the foveal avascular zone.

Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein.

Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters.

Detection of diabetic foveal edema: contact lens biomicroscopy compared with optical coherence tomography.

Objective: To compare contact lens biomicroscopy with optical coherence tomography (OCT) for the detection of diabetic foveal edema.

Methods: Study participants consisted of a convenient cohort of consecutive patients with diabetes mellitus seen at the Wilmer Eye Institute's Retinal Vascular Center, Baltimore, MD. Case characteristics were recorded and eyes were examined by 1 of 4 retina specialists by means of contact lens biomicroscopy.

Treatment compliance and outcome in obsessive-compulsive disorder.

Exposure and ritual prevention (EX/RP) is an effective treatment for obsessive compulsive-disorder (OCD), although it is neither universally nor completely helpful. Compliance with EX/RP treatment procedures has been linked theoretically to posttreatment outcome, yet empirical exploration of this relationship has been insufficient. In this study, therapists were asked to rate the treatment compliance of 28 consecutive patients who received EX/RP on a fee-for-service basis.