A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in P. falciparum Malaria.

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant P. falciparum strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against P. knowlesi and P. cynomolgi. In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in P. falciparum revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189 in vitro and in vivo, its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.

Role of chest radiograph in predicting the need for ventilator support in COVID-19 patients.

Background: COVID-19 disease, a pandemic for more than two years, has major morbidity and mortality related to pulmonary involvement. Chest radiography is the main imaging tool for critically ill patients. As the availability of arterial blood gas analysis is limited in the Level I and II healthcare centres, which are major partners in providing healthcare in resource-limited times, we planned the present study. Objectives: To assess the role of chest radiography in predicting the need for oxygen/ventilator support in critically ill COVID-19 patients. Methods: This hospital-based, retrospective study included 135 patients who needed oxygen/ventilator support and had optimal-quality chest radiographs at admission. All the chest X-rays were evaluated and a severity score was calculated on a predesigned pro forma. Statistical evaluation of the data obtained was done using appropriate tools and methods. Results: Males outnumbered females, with a mean age of 54.35 ± 14.49 years. More than 72% of patients included in our study needed ventilator support while the rest needed oxygen support. There was a significant statistical correlation between the chest radiograph severity score and SPO2 /PaO2 levels in our study. Using a cut-off value >8 for the chest radiograph severity score in predicting the need for ventilator support in a Covid-19 patient, the sensitivity, specificity and accuracy was 85.7%, 92.5% and 89.5%, respectively. Conclusion: Chest radiography remains the mainstay of imaging in critically ill COVID-19 patients when they are on multiple life-support systems. Though arterial blood gas analysis is the gold standard tool for assessing the need for oxygen/ventilator support in these patients, the severity score obtained from the initial chest radiograph at the time of admission may also be used as a screening tool. Chest radiography may predict the need for oxygen/ventilator support, allowing time for patients to be moved to an appropriate-level healthcare centre, thus limiting morbidity and mortality.

Polyphenolic enriched extract of Cassia glauca Lamk, improves streptozotocin-induced type-1 diabetes linked with partial insulin resistance in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally Cassia glauca (CG) has been used to treat diabetes. AIM OF THE STUDY: The study was undertaken to evaluate anti-diabetic and antioxidant activity of polyphenolic enriched extract of CG in standardized streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The effect of ethanol (CGE) and water (CGW) extracts of CG (200 and 400mg/kg) treatment were evaluated in STZ (50mg/kg, iv) induced diabetic rats. On 10th day, oral glucose tolerance test and degree of insulin resistance was calculated. On 13th day, insulin tolerance test was performed to know the peripheral utilization of glucose. On 15th day, blood glucose, lipid profiles and endogenous antioxidant levels were estimated. In addition, the effects on oral glucose/sucrose tolerance test in normal rats. Further, HPLC fingerprinting profile of CGE and simultaneous quantification of biomarkers were carried out. RESULTS: Supplementation with CGE and CGW significantly reduced STZ-induced deleterious effects and improved glucose tolerance, and insulin tolerance. In addition, supplementation also decreased oxidative stress by improving endogenous antioxidant levels. Furthermore, administration significantly improves sucrose tolerance suggesting that extract possess inhibition of α-glucosidase enzyme. Further, HPLC studies revealed that CGE contains three bioactive polyphenolic compounds viz., rutin (0.10±0.01mg/g), luteolin-7-glucoside (0.06±0.01mg/g) and isorhoifolin (0.7±0.05mg/g). CONCLUSION: Observed beneficial outcome of CG might be attributed to the presence of polyphenolic compounds and mediated by interacting with multiple targets of diabetes and oxidative stress. Taken together, this study provided the scientific evidence for the traditional use of CG.

Amniotic membrane transplantation (AMT) without the use of sutures/fibrin glue.

INTRODUCTION: Amniotic membrane transplantation (AMT) has been used for a wide variety of ocular surface problems. Current techniques for the AMT involve suturing of the graft or patch over the ocular surface or use of fibrin glue. OBJECTIVE: To describe a new sutureless technique of amniotic membrane transplantation (AMT) without the use of sutures/fibrin glue. MATERIALS AND METHODS: Amniotic membrane transplantation as overlay or patch was done in fourteen eyes of eight patients with severe dry eye due to Stevens Johnson syndrome for ocular surface reconstruction, promotion of epithelization, reduction of inflammation and symptomatic relief from dry eye. In this new technique of amniotic membrane transplantation, we mount the amniotic membrane with its epithelial side up on a conformer and place it on the ocular surface without applying any sutures. CONCLUSION: In all the fourteen eyes of eight patients operated at our centre, the amniotic membrane take up was satisfactory, with significant reduction of inflammation and symptomatic relief from dry eye. This is a simple, fast effective technique with surgical outcomes comparable to amniotic membrane transplantation using sutures/ fibrin glue.

Long-term change in intraocular pressure after extracapsular cataract extraction with posterior chamber intraocular lens implantation versus phacoemulsification with posterior chamber intraocular lens implantation in Indians.

PURPOSE: The purpose of the study is to evaluate the long-term changes in intraocular pressure (IOP) after extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens (PCIOL) implantation versus phacoemulsification with PCIOL implantation in otherwise normal cataract patients in India. MATERIALS AND METHODS: The study was conducted in the Department of Ophthalmology, King George's Medical College, Lucknow between August 2000 and August 2001. One hundred and seventeen eyes of 115 patients were included in the study. 84 patients were randomly selected for ECCE with PCIOL implantation (ECCE group) and 31 patients were selected for phacoemulsification with PCIOL implantation (Phaco group). IOP was measured pre-operatively and post-operatively, from the 1(st) month to the 12(th) month. Statistical significance was indicated by P > 0.05. RESULTS: There was a mean fall in IOP of 2.70 mm Hg (19.74%) in the ECCE group and 2.74 mm Hg (20.57%) in the phaco group. The decrease in the mean post-operative IOP from baseline was statistically significant (P > 0.01) at the end of 2 months in both groups. There was no statistically significant difference in post-operative IOP at any visit between groups (P < 0.05, all post-operative visits). After 4(th) monthpost-operatively, the IOP was mostly stable, but it was significantly lower than the pre-operative IOP. CONCLUSION: Significant IOP reduction may be expected after cataract surgery with either ECCE or phacoemulsification with IOL implantation. The lowering of IOP became statistically significant at about 2 months post-operatively, but became almost stable after the 4(th) month.

Corneal stromal pseudohypopyon in a pseudophakic patient.

BACKGROUND: Corneal stromal pseudohypopyon is a rare entity. CASE: A 65-year-old female developed a suture abscess in her pseudophakic right eye, three years after conventional extra-capsular cataract extraction with posterior chamber intraocular lens implantation. Pusfrom the suture abscess tracked down the corneal stromal layers and formed a pus level leading to the appearance of a corneal intra-stromal pseudo-hypopyon. CONCLUSION: This case is unique due to its unusual clinical presentation and highlights the fact that corneal pseudo hypopyon may occur without any associated anterior chamber hypopyon or Descemet's detachment.

A study of peripheral T-Lymphocytes in alopecia areata.

Estimation of peripheral T-lymphocytes (active and total) was carried out in 100 cases of alopecia areata as per method described by Boyam (1977) and West et al (1978). Clinically patients were divided in two groups, alopecia areata circumscribed (group I) and severe alopecia areata (group II). Thirty healthy subjects served as controls. Decrease in percentage of both active and total E-RFC was observed in 70% cases. The decrease was more significant in group II.

The predictive value of the relative lens position in primary angle-closure glaucoma.

The relative lens position has been considered to be an important determinant in primary angle-closure glaucoma, but its predictive value needs to be assessed. Therefore, in this tertiary-care center-based case-control study, 70 cases and an equal number of controls were investigated to analyze this association. It was found that, after controlling for age, sex, and refractive error, the relative lens position and anterior chamber depth had a strong association with the disease in separate logit models (P < .01). The predictability of the separate logit models with the relative lens position and anterior chamber depth was found to be statistically significant (-2 x maximized logarithmic likelihood, 93.94 and 19.39, respectively, P < .01). Because the relative lens position represents a composite measure from a set of variables, it can be used as a significant predictive alternative to anterior chamber depth in the genesis of this disease.

Anterior chamber depth and lens thickness in primary angle-closure glaucoma: a case-control study.

Anterior chamber depth and lens thickness have been considered as important biometric determinants in primary angle-closure glaucoma (PACG). In a tertiary care centre-based case-control study, 70 patients and equal number of controls were investigated to analyse the strength of association and predictability of anterior chamber depth (ACD) and lens thickness (LT) in the disease. Mean (+/- S.D.) ACD and LT in the cases and the controls were found to be 2.28 +/- 0.19, 2.87 +/- 0.10; 4.57 +/- 0.34 and 4.13 +/- 0.19 mm respectively. Two sample t test demonstrated statistically significant difference in the ACD and LT between the cases and the controls (Difference being -0.59, 0.44; 95% confidence interval of the difference: -0.64, -0.53 and 0.34, 0.53 respectively, P < 0.01). Logistic regression analysis demonstrated statistically significant protective effect of ACD over PACG (P < 0.01). The odds ratio corresponding to an increase of 0.01 mm in ACD and LT were computed as 0.83 and 1.11 respectively.

Mast cell reactivity in lymphoma: a preliminary communication.

Fifty nodes of Hodgkin's disease, 50 of non-Hodgkin's lymphoma and 20 of reactive hyperplasia revealed varying degree of mast cell reactivity. It was maximum in reactive lymph nodes, sinuses and interfollicular areas being infiltrated more than zones. The number of mast cells was more in nodular sclerosis variety of Hodgkin's disease than other Rye-subtypes, and more in Hodgkin's group than non-Hodgkin's, out of the latter, the diffuse histiocytic lymphoma revealed higher number. Analysis of a larger series and follow-up of these patients are indicated to establish the possible reactionary nature of mast cell reactivity in lymphomas, and the prognostic bearing, if any.

Mast cell in leprosy.

Mast cell distribution in the affected skin and in the apparently normal skin at least 10 cm away from the lesion was studied in 250 leprosy patients. These cells were found and were more numerous in the apparently normal skin of established cases of leprosy as well amongst indeterminate group. Absence of mast cells was conspicuous in 16.7% LL, 41.7% BB, 40.9% BT, and 68.0% TT lesions. It is suggested that mast cells might play a role in the early stages of the disease and in postreactional connective tissue proliferation.

Pattern of paediatric ocular problems in north India.

In this study, 3,490 children were examined to know the pattern of ocular problems in children in this part of the country. It showed that heritable diseases were quite prevalent, i.e., 41.49%. In this group refractive error, nasolacrimal duct block, and primary squint were most common, while in the non-heritable group various types of conjunctivitis, trauma, foreign bodies, blepharitis and nutritional diseases were most prevalent.

Alteration in glutathione metabolism during cataract progression.

Human cataractous lenses obtained from eye relief camp showed decreased levels of sulphydryl and glutathione. Significant depletion in activities of glutathione reductase, glutathione peroxidase and glucose-6-phosphate dehydrogenase was also encountered. These findings indicated an impairment in glutathione metabolism of the mature cataractous lenses as compared to immature lenses, and oxidative stress could be considered as a primary event in this process.