Frequency Of Common Bacteria And Their Antibiotic Sensitivity Pattern In Diabetics Presenting With Foot Ulcer.

BACKGROUND: Foot ulcers are one of the most important complications of diabetes mellitus and often lead to lower limb amputation. Diabetic foot ulcers are susceptible to infection. The objective of this study was to determine the frequency of common bacteria infecting these ulcers and their antibiotic sensitivity pattern. METHODS: This descriptive cross-sectional study was performed in the Departments of Medicine and Surgery, Khyber Teaching Hospital, Peshawar from April, 2011 to February, 2012. Specimens collected from ulcers of 131 patients were inoculated on Blood Agar and MacConkey Agar, and antibiotic sensitivity was tested using standard disc diffusion method. RESULTS: Out of 131, specimens from 120 patients yielded 176 bacteria. Sixty-six patients had monomicrobial infection while polymicrobial growth was obtained in 54 patients. Overall, Staphylococcus aureus (38.6%) was the most common isolate followed by Pseudomonas aeruginosa (27.3%). Staphylococcus aureus was most often sensitive to Moxifloxacin, Imipenem/Meropenem, Vancomycin and Linezolid while it showed varying sensitivity to Penicillins and Cephalosporins. 47.1% isolates of Staphylococcus aureus were resistant to Methicillin. Most of the gram negative rods were sensitive to Imipenem/Meropenem, Piperacillin-Tazobactam and Ticarcillin-Clavulanate. Majority of gram negative bacteria were found resistant to Cephalosporins and Moxifloxacin except Pseudomonas which showed variable sensitivity to Ceftriaxone, Ceftazidime and Moxifloxacin. CONCLUSIONS: Majority of isolates were found resistant to the commonly used antibiotics. Most commonly isolated bacterium, Staphylococcus aureus was most often sensitive to Moxifloxacin, Imipenem/Meropenem, Vancomycin and Linezolid, while majority isolated gram negative rods were sensitive to Imipenem/Meropenem, Piperacillin-Tazobactam and Ticarcillin-Clavulanate.

Uveitis in human immunodeficiency virus-infected persons with CD4+ T-lymphocyte count over 200 cells/mL.

BACKGROUND: Introduction of highly active antiretroviral therapy has altered the course of disease for persons infected with human immunodeficiency virus by elevating CD4+ T-lymphocyte levels. Changes in the spectrum of systemic diseases encountered in human immunodeficiency virus-positive individuals are reported in the general medical literature. DESIGN: Retrospective case series. PARTICIPANTS: Sixty-one individuals infected with human immunodeficiency virus, who presented with uveitis when the peripheral CD4+ T-lymphocyte count was over 200 cells/µL. METHODS: Standardized data collection at seven tertiary-referral inflammatory eye disease clinics. MAIN OUTCOME MEASURES: Standardization of Uveitis Nomenclature anatomic classification and descriptors, cause of uveitis, and visual acuity RESULTS: Peripheral CD4+ T cell counts varied between 207 and 1777 (median = 421) cells/µL at the time of diagnosis of uveitis. Uveitis was classified anatomically as anterior (47.5%), intermediate (6.6%), anterior/intermediate (16.4%), posterior (14.8%) and pan (14.8%). Specific causes of uveitis included infections (34.4%), with syphilis responsible for 16.4% of all cases, and defined immunological disorders (27.0%); no cause for the inflammation was identified in 34.4% of persons. Visual acuity was better than 6/15 in 66.7% and 6/60 or worse in 11.8% of 93 eyes at presentation, and better than 6/15 in 82.4% and 6/60 or worse in 8.8% of 34 eyes at 1 year of follow-up. CONCLUSIONS: Both infectious and non-infectious forms of uveitis occur in individuals who are infected with human immunodeficiency virus and have preserved or restored peripheral CD4+ T cell levels. Individuals who are human immunodeficiency virus-positive and present with uveitis should be evaluated in the same way all patients with uveitis are assessed.

Mitigation of photoreceptors abnormalities after low-level laser therapy and chia seeds supplementation in experimental diabetic retinopathy.

BACKGROUND: This study aimed to assess the effect of low-level laser therapy (LLLT) and chia seeds on the mitigation of photoreceptors abnormalities in experimental diabetic retinopathy (DR). MATERIALS AND METHODS: A total of 65 female Wistar rats, 5 rats were served as a control group and 60 rats were injected intraperitoneally with one dose of 55 mg/kg of streptozotocin (STZ) to induce DR after 6-8 weeks. The rats were divided into (n = 20 rats each): (a) DR group: did not receive any treatment, (b) DR+ LLLT group was exposed to 670-nm LLLT for 6 weeks (two sessions/week), and (c) DR+ LLLT+ chia seed group, in which rats were exposed to LLLT and administrated with 250 mg/kg/day of chia seeds flour for 2 weeks before STZ injection and continued to the end of the experiment. Blood glucose (BG) levels and retinal histological examination were employed after 1, 2, 4, and 6 weeks. RESULTS: The BG level in the DR group and the treated groups were significantly higher (P < 0.001) than in the control group after the four-time periods. Chia seeds group exhibited BG levels less than the DR and the DR+ LLLT groups after 6 weeks (P < 0.01). LLLT improved the degeneration of the photoreceptors after 6 weeks of treatment, while LLLT+ chia seeds supplementation showed early photoreceptors improvement after 2 weeks. CONCLUSION: The early improvement in the photoreceptors after LLLT+ chia seed may be attributed to the potent antioxidant properties of chia seeds. Therefore, the combination between LLLT and chia seeds should be employed to protect the retinal photoreceptors against DR.

Effect of L-Carnitine and/or Calf Thymus Gland Extract Supplementation on Immunity, Antioxidant, Duodenal Histomorphometric, Growth, and Economic Performance of Japanese Quail (Coturnix coturnix japonica).

This study aimed to evaluate the supplementation (of drinking water) effects of L-Carnitine (LC) and/or calf thymus extract (TE) on immunity, antioxidant, duodenal histomorphometric, growth, and economic performance of Japanese quail. Six hundred, one day old unsexed quail were divided into four groups, the control group (G1) received plain drinking water, while G2, G3, and G4 were supplemented with LC and/or TE, respectively. The treated groups recorded a significant (p < 0.05) improvement in the final body weight, weight gain, feed conversion ratio, phagocytic activity %, phagocytic index, lymphocytes %, and plasma glutathione level compared to the G1. On the other hand, these supplementations significantly lower the mortality rate %, heterophil %, H/L ratio and plasma malondialdehyde level of the supplemented groups relative to G1. The supplemented groups recorded a non-significant increase in duodenal histomorphometric parameters (villous height, villous width, surface area, and crypt depth) relative to G1. Generally, LC and/or TE improve the values of economic profile (total returns, net profit, total return/total costs %, etc.) in treated groups compared to the control one. In conclusion, L-carnitine supplementation was more effective than TE or their combination with TE in the immunological, anti-oxidative, growth, and economic performance.

Antioxidant Activity, Phenolic Profile, and Nephroprotective Potential of Anastatica hierochuntica Ethanolic and Aqueous Extracts against CCl4-Induced Nephrotoxicity in Rats.

Kaff-e-Maryam (Anastatica hierochuntica L.) is extensively used to treat a range of health problems, most notably to ease childbirth and alleviate reproductive system-related disorders. This study aimed to evaluate the effect of A. hierochuntica ethanolic (KEE), and aqueous (KAE) extracts on CCl4-induced oxidative stress and nephrotoxicity in rats using the biochemical markers for renal functions and antioxidant status as well as histopathological examinations of kidney tissue. A. hierochuntica contained 67.49 mg GAE g-1 of total phenolic compounds (TPC), 3.51 µg g-1 of total carotenoids (TC), and 49.78 and 17.45 mg QE g-1 of total flavonoids (TF) and total flavonols (TFL), respectively. It resulted in 128.71 µmol of TE g-1 of DPPH-RSA and 141.92 µmol of TE g-1 of ABTS-RSA. A. hierochuntica presented superior antioxidant activity by inhibiting linoleic acid radicals and chelating oxidation metals. The HPLC analysis resulted in 9 and 21 phenolic acids and 6 and 2 flavonoids in KEE and KAE with a predominance of sinapic and syringic acids, respectively. Intramuscular injection of vit. E + Se and oral administration of KEE, KAE, and KEE + KAE at 250 mg kg-1 body weight significantly restored serum creatinine, urea, K, total protein, and albumin levels. Additionally, they reduced malondialdehyde (MOD), restored reduced-glutathione (GSH), and enhanced superoxide dismutase (SOD) levels. KEE, KAE, and KEE + KAE protected the kidneys from CCl4-nephrotoxicity as they mainly attenuated induced oxidative stress. Total nephroprotection was about 83.27%, 97.62%, and 78.85% for KEE, KAE, and KEE + KAE, respectively. Both vit. E + Se and A. hierochuntica extracts attenuated the histopathological alteration in CCl4-treated rats. In conclusion, A. hierochuntica, especially KAE, has the potential capability to restore oxidative stability and improve kidney function after CCl4 acute kidney injury better than KEE. Therefore, A. hierochuntica has the potential to be a useful therapeutic agent in the treatment of drug-induced nephrotoxicity.

Low-Level Laser Therapy with 670 nm Alleviates Diabetic Retinopathy in an Experimental Model.

PURPOSE: To evaluate the effects of low-level laser therapy (LLLT) on the retina with diabetic retinopathy (DR). METHODS: Eight Wistar rats were used as a control group, and 64 rats were injected intraperitoneally with 55 mg/kg of streptozotocin to induce diabetes and served as a diabetic group. After the establishment of the DR, the rats were separated into (a) 32 rats with DR; did not receive any treatment, (b) 32 rats with DR were exposed to 670 nm LLLT for 6 successive weeks (2 sessions/week). The retinal protein was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, total antioxidant capacity (TAC), hydrogen peroxide (H2O2), and histological examination. RESULTS: LLLT improved retinal proteins such as neurofilament (NF) proteins (200 KDa, 160 KDa, and 86 KDa), neuron-specific enolase (NSE) (46 KDa). Moreover, the percentage changes in TAC were 46.8% (P < 0.001), 14.5% (P < 0.01), 4.8% and 1.6% (P > 0.05), and in H2O2, they were 30% (P < 0.001), 25% (P < 0.001), 20% (P < 0.01), and 5% (P > 0.05) after 1, 2, 4, and 6 weeks, compared with the control. DR displayed swelling and disorganization in the retinal ganglion cells (RGCs) and photoreceptors, congestion of the capillaries in the nerve fiber layer, thickening of the endothelial cells' capillaries, and edema of the outer segment of the photoreceptors layer. The improvement of the retinal structure was achieved after LLLT. CONCLUSION: LLLT could modulate retinal proteins such as NSE and NFs, improve the RGCs, photoreceptors, and reduce the oxidative stress that originated in the retina from diabetes-induced DR.

Gastroprotective Effects of Spirulina platensis, Golden Kiwifruit Flesh, and Golden Kiwifruit Peel Extracts Individually or in Combination against Indomethacin-Induced Gastric Ulcer in Rats.

This study was conducted to investigate the therapeutic effect of hydro-alcoholic extract of Spirulina platensis (SP), golden kiwifruit (Actinidia chinensis) flesh (KF), and golden kiwifruit peel (KP) individually or in combination (SFP) on indomethacin-induced gastric ulcer in rats. Negative control rats (GI) were orally administered distilled water in parallel with other treatments. The positive control rat group (GII) was administered 30 mg kg-1 indomethacin to induce gastric ulcers. The KF and KF extracts were used individually or together with SP in treating indomethacin-induced gastric ulcerated rat groups. Gastric ulcerated rat's groups GIII, GIV, GV, GVI, and GVII were orally administered at 30 mg kg-1 rat body weight as total phenolic content (TPC) equivalent from SP, KF, KP, SPF extracts, and Lansoprazole (30 mg kg-1, as reference drug) daily up to 14 days, respectively. The relevant biochemical parameters, antioxidant biomarkers, and histopathological examination were examined. Remarkably, treating rats with SP, KF, KP, and SFP extracts markedly reduced gastric juice and stomach volume expansion induced by indomethacin. The SP significantly retrieved the pH of gastric juice to a regular rate compared to GI. The ulcer index (UI) was significantly attenuated by SP, KF, KP, and SFP administration. The protection index percentage (PI %) was 80.79, 54.51, 66.08, 75.74, and 74.86% in GIII, GIV, GV, GVI, and GVII, respectively. The gastric mucin content was significantly better attenuated by 95.7 in GIII compared to its content in GI. Lansoprazole increased mucin content by 80.3%, which was considerably lower than SP and SFP. SP, KF, KP, SFP, and Lansoprazole improved the reform of gastric mucosal-increased secreted mucus by 95.6, 61.3, 64.8, 103.1, and 80.2% in GIII, GIV, GV, GVI, and GVII, respectively. Interestingly, SFP efficiently increased vit. B12 level by 46.0% compared to other treatments. While Lansoprazole administrating did not significantly attenuate vit. B12 level. The SP and SFP improved iron and Hemoglobin (HB) levels depending on treatment. SP, KF, KP, and SFP significantly decreased the malondialdehyde (MDA) and increased reduced glutathione (GSH) as well as superoxide dismutase (SOD) levels in blood and stomach tissues. The most potent effect was observed with SP, and SFP was even better than Lansoprazole. Histopathologically, treating rats with SP extract showed a marked reduction of gastric damage and severity changes induced by indomethacin. KP was much better than KF in lessening gastric histopathological damages caused by indomethacin. SFP significantly alleviates gastric histopathological alterations. The lansoprazole-treated group (GVII) greatly relieved the gastric histopathological changes and recorded mild focal necrosis and desquamation of the mucosa in addition to mild oedema in the serosal layer. In conclusion, the presented results proved the antiulcer potential of SP and A. chinensis extracts against an indomethacin-induced gastric ulcer in rats, which may be due to their antioxidant and anti-inflammation efficiency. Thus, these data suggested that SP, KF, KP, and SFP extracts as natural and safe alternatives have a gastroprotective potential against indomethacin-induced gastric ulceration. The antioxidative and anti-inflammatory properties are probable mechanisms.

The Role of Supportive Food Environments to Enable Healthier Choices When Eating Meals Prepared Outside the Home: Findings from Focus Groups of 18 to 30-Year-Olds.

Young adults are the highest consumers of food prepared outside home, which has been linked to weight gain. The aim of this qualitative research was to gather opinions from young adults about what influences their food choice when eating out and if they so desired, what might enable healthy choices. Thirty-one adults aged 18 to 30 years participated in four focus groups (females = 24). Predetermined questions were used to guide discussions which were audiotaped then transcribed. The content was organized into themes and sub-themes using NVivo software. Two broad groupings arose-personal behaviors and changes to physical and social food environments. For many, eating out was viewed as a special occasion so that healthy food was not a priority and despite understanding health consequences of poor diets this was not an immediate concern. Price discounts and menu-labelling were suggested and trust in credible organizations and peers' endorsement of meals and venues expressed. The role of smartphones in the modern food environment emerged as a tool to enable immediate access to many restaurants to order food and access reviews and social media as a source of persuasive food imagery. Current menu-labelling initiatives should continue, food pricing be explored and influence of smartphones on diet further researched. However, these findings may be limited by the high proportion of women and higher socioeconomic status and urban residence of many participants.

Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma.

PURPOSE: To investigate the role of interferon (IFN)-gamma in the pathogenesis of conjunctival squamous metaplasia in dry eye. METHODS: Experimental dry eye was created by subjecting C57BL/6 and IFN-gamma-knockout mice to desiccating environmental stress for 5 or 10 days. T-cell antigens and IFN-gamma were detected by immunohistochemistry. Goblet cells were counted in periodic acid Schiff (PAS)-stained sections. Expression of small, proline-rich protein (SPRR)-2 was evaluated by confocal microscopy. Tear IFN-gamma was measured by immunobead assay. RESULTS: Dry eye promoted migration of CD4+ T cells and IFN-gamma+ cells into goblet cell zones of the conjunctiva and increased the concentration of IFN-gamma in tears. This migration was accompanied by progressive goblet cell loss and an increase in SPRR-2 expression in the conjunctival epithelium. A significant inverse correlation was observed between the density of infiltrating CD4+ T cells and goblet cells. Dry eye had no effect on conjunctival goblet cell density in IFN-gamma-knockout mice; however, exogenous administration of IFN-gamma significantly decreased goblet cell density after 5 days. CONCLUSIONS: Conjunctival epithelial response to experimental dryness is related to the degree of CD4+ T-cell infiltration and the level of IFN-gamma production. These findings suggest that IFN-gamma plays a pivotal role in promoting conjunctival squamous metaplasia in dry eye, and they provide insight into the immune pathogenesis of keratoconjunctivitis sicca.

Influence of follicle size, methods of retrieval on oocytes yield and morphology in Egyptian Jennies ovaries with special reference to maturation rate in vitro.

UNLABELLED: This work was designed to evaluate the ovarian follicular development, oocytes morphology, methods of oocytes reterival, and the effect of different in vitro maturation (IVM) media on cumulus cell expansion and nuclear maturation of Jennies oocytes. Experiment 1, the number of small (<6 mm), medium (6 to 9 mm) and large size (>10 mm) ovarian follicles was recorded. Cumulus-oocyte-complexes (COCs) were reterived and classified into 4 Grades based on their cumulus-cells investment and the homogenous of the ooplasm. In Experiment 2, COCs were recovered by using 18-G, 20-G needle or slicing and scraping of ovarian follicles to determine the number and morphology of the recovered COCs. In Experiment 3, Grade A and B COCs were IVM in DMEM-HG, DMEM-LG, DMEM-F12, TCM199, TCM199-F12 or CR1aa media supplemented with 10% FCS+10 µg FSH/mL+10 IU hCG/mL+50 µg/mL gentamicin. Maturation was performed for 36 h at 38.5 °C under 5% CO2 in humidified air. After IVM, cumulus cell expansion and oocytes nuclear canfiguration were determined. An average of 6.40±0.26 follicles was recorded per Jenny ovary, representing 3.37±0.46, 1.89±0.14 and 1.14±0.16, for the small, medium and large size follicles, respectively. Oocyte recovery was higher (P<0.05) in large and medium size follicle than in the small one (62%, 60% and 45.1%, respectively). Small size follicles produced higher (P<0.05) percentage of Grade A COCs than large or medium size follicles. A higher number of oocytes was recovered by slincing and scraping of follicles (4.86±0.67), then aspiration of follicles using 18-G needle (3.14±0.36 COCs/ovary, P<0.05). Aspiration using 18-G needle or slicing and scraping of follicles using produced a significantly higher (P<0.05) percentage of Grade A COCs compared to aspiration of follicles using 20-G needle (56.6%, 46.7% and 32.0%, respectively, P<0.05). IVM of COCs in CR1aa and TCM 199-F12 media significantly increased (P<0.05) Grade 3 cumulus-cell expansion compared with TCM199, DMEM-F12, DMEM-LG and DMEM-HG (65.5% and 64.0%, 52.8%, 32.1%, 0.0% and 7.4%, respectively). The proportion of IVM oocytes reaching the M II stage was significantly higher (P<0.05) for oocytes matured in TCM199-F12 or CR1aa media than TCM199, DMEM-HG, DMEM-LG, DMEM-F12 (69.1% and 62.2%, 55.7%, 45.8%, 39.0% and 40.7%, respectively). The proportion of degenerated oocytes IVM in TCM199-F12 (10.3%), CR1aa (11.3%) or TCM199 (13.1%) was lower (P<0.05) than that matured in DMEM-HG, DMEM-LG or DMEM-F12 media (23.7%, 29.3% and 22.9%, respectively). CONCLUSION: Slicing and scraping or aspiration of follicles using 18-G needle increased the number and percentage of Grade A Jennies oocytes. TCM199-F12, CR1aa and TCM199 medi are more suitable for IVM of Jenny oocytes by promoting cumulus cells expansion and nuclear maturation to M II stage.

Cystoid macular edema without leakage secondary to nab-Paclitaxel (Abraxane): clinical experience with intravitreal bevacizumab.

PURPOSE: Cystoid macular edema (CME) is a rarely reported side effect of nanoparticle albumin bound (nab)-paclitaxel therapy-an antimitotic agent used for breast cancer. We describe a patient with bilateral CME secondary to Abraxane that was minimally responsive to intravitreal bevacizumab. To our knowledge, this is the first reported case of the use of intravitreal bevacizumab for this condition. A previous report has described the ineffectiveness of concurrent intravenous bevacizumab with Abraxane. This lack of efficacy and knowledge of the mechanism of paclitaxel may provide insights into the mechanisms of CME without angiographic leakage. METHODS: Retrospective, interventional case report of a patient with bilateral CME after starting Abraxane therapy for recurrent breast cancer treated with intravitreal bevacizumab (1.25 mg/0.05 mL) every 4 weeks. Records were reviewed for visual acuity and macular edema as assessed by spectral-domain optical coherence tomography (SD-OCT). RESULTS: A 73-year-old patient with recurrent, metastatic breast cancer presented with bilateral visual loss 3 months after nab-paclitaxel was initiated. Baseline visual acuities (VA) were 20/50 in the right eye (OD) and 20/80 in the left eye (OS). Fundus exam showed marked CME in both eyes (OU). Fluorescein angiography was notable for the marked absence of petalloid late-phase leakage characteristic of vascular, ischemic, and inflammatory causes of CME. SD-OCT showed marked cystoid spaces predominantly involving the outer and inner nuclear layers with central subfield thicknesses (CST) of 398 µm OD and 441 µm OS. Serial intravitreal bevacizumab injections (OD, 2 injections; OS, 3 injections) were administered on a 4-week basis with an improvement and stabilization of VA at 20/50 OD and 20/70 OS. However, CME on SD-OCT persisted with CST of 492 µm OD and 478 µm OS. CONCLUSIONS: The pathogenesis of CME without leakage is poorly understood; however, fluid accumulation in Muller cells due to toxicity has been proposed. The persistence of CME suggests that additional nonvascular endothelial growth factor-mediated mechanisms are involved. Improved understanding of the mechanisms underlying paclitaxel-associated CME is needed, especially in patients with limited systemic options for metastatic carcinoma.

Nocardia veterana endogenous endophthalmitis in a cardiac transplant patient.

BACKGROUND: Endogenous endophthalmitis secondary to Nocardia species is extremely rare but often portends a poor visual prognosis often owing to the advanced nature of disease at presentation and delay in diagnosis. Patients who are systemically immunosuppressed are at greatest risk and early suspicion of the role of this organism in patients with acute panuveitis is paramount. FINDINGS: A 66-year-old cardiac transplant patient on oral prednisone, Myfortic, and tacrolimus developed unilateral panuveitis with a focal white subretinal and retinal lesion. His past medical history was notable for Aspergillus pneumonia and cytomegalovirus retinitis in the contralateral eye 12 months prior. Aqueous humor sampling for eubacterial, eufungal, and viral PCR testing, as well as vitreous cultures for bacteria and fungi were unsuccessful in the identification of a causative organism. Progressive enlargement of the lesion was noted despite intravitreal foscarnet, vancomycin, ceftazidime, and voriconazole. A pars plana vitrectomy and retinal and subretinal biopsy led to the identification of Nocardia veterana, a recently identified Nocardia species. A combination of linezolid, meropenem, azithromycin, ceftriaxone, and intravitreal amikacin resulted in eradication of the infection. CONCLUSION: This is the first reported case of N. veterana endogenous endophthalmitis in an immunosuppressed patient. Pars plana vitrectomy with a subretinal biopsy was required to establish a diagnosis, as other testing including aqueous PCR and vitreous cultures were negative. The poor visual outcome in our patient highlights the importance of early consideration of Nocardia in the differential diagnosis of panuveitis with subretinal disease in the context of immunosuppression.

Retinal metastasis simulating cytomegalovirus retinitis.

A 62-year-old man with lung cancer presented with a 2-week history of decreased vision and clinical features of cytomegalovirus retinitis. The patient was empirically treated for viral retinitis, but microbiological testing of the vitreous fluid was negative. Based on the suspicion for retinal metastasis, the patient underwent pars plana vitrectomy with retinal biopsy. Surgical techniques included the use of a chandelier illumination to enable bimanual manipulation of the retinal tissue, creation a focal retinal detachment with a 41-gauge subretinal cannula, diathermy demarcation of the biopsy site, localized retinectomy with vertical scissors, endolaser, and long-acting gas tamponade. Histopathologic examination revealed sheets of tumor cells with pleomorphic nuclei and positive staining for cytokeratins consistent with metastatic adenocarcinoma. The patient subsequently underwent external beam radiation and was alive 10 months after presentation. This surgical technique may be valuable in select patients with retinal metastasis for diagnostic, therapeutic, and counseling purposes.

Imaging Retinal Vascular Changes in the Mouse Model of Oxygen-Induced Retinopathy.

PURPOSE: Oxygen-induced retinopathy in the mouse is the standard experimental model of retinopathy of prematurity. Assessment of the pathology involves in vitro analysis of retinal vaso-obliteration and retinal neovascularization. The authors studied the clinical features of oxygen-induced retinopathy in vivo using topical endoscopy fundus imaging (TEFI), in comparison to standard investigations, and evaluated a system for grading these features. METHODS: Postnatal day (P)7 mice were exposed to 75% oxygen for five days to induce retinopathy or maintained in room air as controls. Retinal vascular competence was graded against standard photographs by three masked graders. Retinal photographs were obtained at predetermined ages using TEFI. Postmortem, retinal vaso-obliteration was measured in whole mounts with labeled vasculature, and retinal neovascularization was quantified in hematoxylin- and eosin-stained ocular cross sections. RESULTS: Fundus photography by TEFI was possible from P15, when retinal vascular incompetence, including dilatation and tortuosity, was significant in mice with oxygen-induced retinopathy in comparison to controls. Vascular incompetence peaked in severity at P17 and persisted through P25. Comparison with in vitro analyses indicated that vascular changes were most severe after retinal avascularity had begun to decrease in area, and coincident with the maximum of retinal neovascularization. A weighted Fleiss-Cohen kappa indicated good intra- and interobserver agreement for a 5-point grading system. CONCLUSIONS: Topical endoscopy fundus imaging demonstrates retinal vascular incompetence in mice with oxygen-induced retinopathy. The technique complements standard postmortem analysis for following the course of the model. TRANSLATIONAL RELEVANCE: Topical endoscopy fundus imaging has application in the evaluation of novel biologic drugs for retinopathy of prematurity.

Chorioretinitis and panuveitis in an infant with systemic langerhans cell histiocytosis.

BACKGROUND: Panuveitis and chorioretinitis in infants with Langerhans cell histiocytosis are rare and fundus photographic documentation is lacking in the literature. METHODS: Case report with fundus photography. RESULTS: The authors report a case of an infant with disseminated Langerhans cell histiocytosis who presented with panuveitis in the right eye and chorioretinitis in left eye. Treatment with chemotherapy led to resolution of chorioretinal lesions; however, the visual prognosis remained guarded because of the macular involvement and amblyopia. CONCLUSION: The authors recommend examination of infants with Langerhans cell histiocytosis for chorioretinal involvement.

Repressors of androgen and progesterone receptor action.

Androgen and progesterone receptors (AR and PR) are two determining factors in gonadal differentiation that are highly expressed in developing and mature gonads. Loss of AR results in XY sex reversal and mutations causing reduced AR activity lead to varying degrees of defects in masculinization. Female PR knockout mice are infertile due to ovarian defects. While much has been discovered about positive regulation of these receptors by coactivators little is known about repression of the transcriptional activity of AR and PR in the presence of agonists. In this study we assessed the effect of SMRT and DAX-1 on AR and PR activity in the presence of both agonists and partial antagonists. We show that SMRT and DAX-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases. We demonstrate that endogenous agonist-bound PR and DAX-1 in T47D breast cancer cells and endogenous AR and DAX-1 in LNCaP prostate cancer cells can be coimmunoprecipitated suggesting that the interaction is physiological. Surprisingly, although DAX-1 represses partial antagonist activity of AR, it was ineffective in repressing partial antagonist induced activity of PR. In contrast to most reported repressors, the expression of DAX-1 is restricted. We found that although DAX-1 is expressed in normal human prostate, its expression is strongly reduced in benign prostatic hyperplasia suggesting that DAX-1 plays a role in limiting AR activity in prostate.