RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

Clinical presentation and outcome of retinoblastoma based on age at presentation: a review of 1450 children

To compare the clinical presentation and outcomes of retinoblastoma (RB) based on age at presentation. Retrospective comparative study of 1940 eyes of 1450 children with RB. Presentation of RB with enlarged eyeball and eyelid swelling (2% and < 1% in ≤ 1 year, 4% and 2% in > 1–2 years, 7% and 2% in > 2–3 years, and 12% and 4% in > 3 years; p < 0.0001 and p = 0.05, respectively) is more common with increasing age. Based on the 8th edition of American Joint Committee Classification, T1 is more common in children younger than 1 year (27%), while T4 is more common in children > 3 years of age (20%) (p < 0.0001). Kaplan–Meier (KM) estimate at 1 and 5 years for globe salvage was 64% and 58% in children ≤ 1 year of age versus 30% and 20% in children > 3 years, respectively [Hazard ratio (HR) = 2.48; p < 0.0001], and KM estimate at 1 and 5 years for life salvage was 99% and 97% in children ≤ 1 year of age versus 89% and 78% in children older than 3 years, respectively (HR = 7.65; p < 0.0001). Uncommon clinical features of RB including enlarged eyeball and eyelid swelling are more common with increasing age. Younger age at presentation with RB is associated with better prognosis including higher chances of life and globe salvage.     

Changing trend in the morphology of cataracts at a tertiary eye care centre in South India due to COVID-19-pandemic related national lockdown

Purpose:To study the changing trends in the morphology of cataracts at a tertiary eye care center in South India due to COVID-19 pandemic-related national lockdown.Methods:A retrospective study conducted at a tertiary eye care center in Andhra Pradesh state of South India, which included 1724 patients (1753 eyes) who underwent cataract surgery at our center during April 2019–July 2019 (1298 eyes of 1271 patients) and April 2020–July 2020 (455 eyes of 453 patients). Factors studied included preoperative lens status, associated phacodonesis or subluxation, pupil size, other eye lens status, associated retinal problems, glaucoma, and complications during surgery. Postoperative uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), corneal clarity, intraocular pressure (IOP), and disc status at postoperative day 1, 1 week, and 1-month visits were compared.Results:A significantly lower proportion of nuclear sclerosis (decreased from 83.2% in last year before lockdown to 55.2% during lockdown) and significantly higher proportions of mature, brown, or black cataract and phacomorphic, phacolytic, or Morgagnian cataract (increased from 15.5% in last year before lockdown to 43.8% during lockdown) were observed. The proportion of small-incision cataract surgery decreased significantly (from 63.2% to 57.4%), whereas the proportion of phacoemulsification increased significantly (from 35.9% to 41.5%) during lockdown as compared to last year. A significantly higher proportion of eyes with small pupils and association with retinal pathology were also observed during the lockdown.Conclusion:During the national lockdown, there was a shift from nuclear sclerosis grade toward mature, brown, black grade of cataracts. In addition, the proportion of small-incision cataract surgery decreased significantly whereas the proportion of phacoemulsification increased significantly during the lockdown. More number of cataracts with small pupils and associated retinal pathology were observed during the lockdown.     

Evaluation of leucocyte esterase reagent strip test for the rapid bedside diagnosis of spontaneous bacterial peritonitis

Background  

Spontaneous bacterial peritonitis (SBP) is a common serious complication of cirrhosis, and carries a high morbidity and mortality. Rapid diagnosis and prompt treatment of this condition may improve survival of such patients.     

Cytotoxicity and antibacterial activity of Sida rhombifolia (Malvaceae) grown in Bangladesh

The cytotoxicity and antibacterial activities of crude extracts from the leaves of Sida rhombifolia were investigated. The ethyl acetate extract showed potent cytotoxicity with LC50 values (5.41 ppm) comparable to the reference standard, gallic acid. All the extracts showed weak antibacterial activity against both Gram-positive and Gram-negative test organisms.     

A randomized masked pilot clinical trial to compare the efficacy of topical 1% voriconazole ophthalmic solution as monotherapy with combination therapy of topical 0.02% polyhexamethylene biguanide and 0.02% chlorhexidine in the treatment of Acanthamoeba keratitis

PurposeTo compare the efficacy of topical voriconazole 1% and the combination therapy of 0.02% polyhexamethylene biguanide (PHMB) and 0.02% chlorhexidine for the treatment of Acanthamoeba keratitis (AK).MethodsThis is a prospective, pilot, double-masked randomized comparative study. Twenty-three eyes of 23 patients with microbiologically (smear and/or growth on culture) confirmed AK were randomized to group BG (PHMB 0.02% and chlorhexidine 0.02%) or group VZ (voriconazole 1%). Primary outcome measure was change in geometric mean (GM) of the corneal ulcer size at final visit. Secondary outcome measures were change in visual acuity.ResultsOut of 71 patients with confirmed AK seen during study period, 23 patients were recruited and 18 patients completed minimum 2 weeks of treatment and further analyzed. Ten patients received BG, whereas eight received VZ. Median ulcer size measured as GM of infiltrate decreased from 5.7 mm (IQR, 5.3–6.5 mm) (p = 0.02) to 1 mm (IQR, 0–4.3 mm) in group BG and from 4.5 mm (IQR, 1.8–5.1 mm) (p < 0.05) to 0.7 mm (IQR, 0–1.6 mm) in VZ group. Median visual acuity improved from 1.79 (IQR, 1.48–2.78) to 1.10 (IQR, 0.48–1.79) in BG group (p = 0.02) and from 1.60 (IQR, 1.00–2.78) to 0.80 (IQR, 0.48–1.30) in VZ group (p = 0.18).ConclusionThese outcomes suggest that topical VZ as a monotherapy in AK treatment is effective and comparable to BG combination therapy but needs trials with larger sample size and longer follow-up to provide conclusive evidence.Subject terms: Corneal diseases, Parasitic infection     

Outcomes of Ahmed glaucoma valve implantation and risk factors for graft failure in eyes with Descemet’s stripping endothelial keratoplasty

International Ophthalmology - The aim of this study was to assess the efficacy of Ahmed glaucoma valve (AGV) in eyes with Descemet’s stripping endothelial keratoplasty (DSEK) and glaucoma and...     

The butanol fraction of guava (Psidium cattleianum Sabine) leaf extract suppresses MMP-2 and MMP-9 expression and activity through the suppression of the ERK1/2 MAPK signaling pathway

The leaf extract of guava (Psidium cattleianum Sabine) has traditionally been used for the treatment of diarrhea and diabetes in East Asia and other countries. Recently, the leaf extract has been employed in the therapy of cancer, bacterial infections, and inflammation in experimental models. However, the exact mechanisms of how guava leaf extract inhibits tumor metastasis and invasion are still unknown. In the present study, we investigated in detail the molecular mechanism(s) responsible for the potential antimetastatic and antiinvasive effects of the butanol fraction of guava leaf extract (GBF). Interestingly, we observed for the first time that GBF suppressed both matrix metalloproteinases (MMP)-9 and MMP-2 expression and activity in part through the downregulation of the ERK1/2 activation in lung cancer cells. Also, importantly, the major components of the GBF were identified as d-glucuronic acid, quercetin 3-glucuronide, loganin, and xanthyletin by LC-ESI-MS/MS. Collectively, our data indicate that the guava leaf could reduce the metastasis of lung cancer cells and therefore suggest that it could be advantageously used to control the metastatic process.