Sp Garg

Endogenous cortisol profile in patients with central serous chorioretinopathy

AIM To study the endogenous cortisol levels in patients with central serous chorioretinopathy (CSCR). METHODS Endogenous cortisol levels in urine and plasma were determined in 30 patients with acute CSCR and compared with 30 age and sex matched controls. RESULTS The mean values of the 8 am plasma cortisol (29.97 μg/dl v 18.76 μg/dl), 11 pm plasma cortisol (22.03 μg/dl v 13.06 μg/dl), and 24 hour urine cortisol (11.01 mg/24 h v 7.39 mg/24 h) revealed significantly higher values in the patient group (p<0.001). CONCLUSIONS Increased levels of endogenous cortisol are present in patients with CSCR.

Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations

BackgroundThe Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen. The complete AMA1 protein is comprised of three domains where domain I exhibits high sequence polymorphism and is thus named as the hyper-variable region (HVR). The present study describes the extent of genetic polymorphism and natural selection at domain I of the ama1 gene among Indian P. falciparum isolates.MethodsThe part of the ama 1 gene covering domain I was PCR amplified and sequenced from 157 P. falciparum isolates collected from five different geographical regions of India. Statistical and phylogenetic analyses of the sequences were done using DnaSP ver. 4. 10. 9 and MEGA version 3.0 packages.ResultsA total of 57 AMA1 haplotypes were observed among 157 isolates sequenced. Forty-six of these 57 haplotypes are being reported here for the first time. The parasites collected from the high malaria transmission areas (Assam, Orissa, and Andaman and Nicobar Islands) showed more haplotypes (H) and nucleotide diversity π as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian P. falciparum subpopulations indicated moderate level of genetic differentiation and limited gene flow (Fixation index ranging from 0.048 to 0.13) between populations. The difference between rates of non-synonymous and synonymous mutations, Tajimas D and McDonald-Kreitman test statistics suggested that the diversity at domain I of the AMA1 antigen is due to positive natural selection. The minimum recombination events were also high indicating the possible role of recombination in generating AMA1 allelic diversity.ConclusionThe level of genetic diversity and diversifying selection were higher in Assam, Orissa, and Andaman and Nicobar Islands populations as compared to Uttar Pradesh and Goa. The amounts of gene flow among these populations were moderate. The data reported here will be valuable for the development of AMA1-based malaria vaccine.

Prospective evaluation of intravitreal triamcinolone acetonide injection in macular edema associated with retinal vascular disorders

Purpose To evaluate the effect of intravitreal triamcinolone acetonide on visual acuity and macular thickness using optical coherence tomography (OCT) in macular edema associated with various retinal vascular disorders. Methods This prospective nonrandomized clinical interventional study included 81 eyes (76 patients) comprised of Group I, 57 eyes (51 patients) with diabetic macular edema; Group II, 10 eyes (10 patients) with branch retinal vein occlusion; and Group III, 13 eyes (13 patients) with central retinal vein occlusion. All eyes received an intravitreal injection of 4 mg triamcinolone acetonide (with the solvent) in the operation theater under sterile conditions. Results Mean preinjection central macular thickness was 531.84±132 μm in Group I, 458.4±149 μm in Group II, and 750.81±148 μm in Group III. All groups showed a statistically significant decrease in mean central macular thickness at 1 month (300.7±119 μM in Group I, 218.2±99 μm in Group II, and 210.5 ±56 μm in Group III) and 3 months (253.19±109 μm in Group I, 187±47 μm in Group II, and 182±50 μm in Group III) after injection (p<0.05). Mean follow-up was 22±2.4 weeks. Mean visual acuity increased in all three groups (preoperative visual acuity in Group I, 1.2±0.4 logMAR units; Group II, 1.24±0.5 logMAR units; Group III, 1.1 ±0.4 logMAR units; 1 month postinjection in Group I, 0.88±0.3 logMAR units; Group II, 0.67±0.3 logMAR units; Group III, 0.86±0.4 logMAR units; 3 months postinjection in Group I, 0.84±0.4 logMAR units; Group II, 0.59±0.3 logMAR units; Group III, 0.82±0.5 logMAR units) (p<0.05). Forty-one eyes completed 6 months and 20 eyes completed 9 months follow-up. Twelve of 20 (41%) eyes in Group I, 2/6 (33%) eyes in Group II, 3/6 (50%) eyes in Group III, and 8/15 (53%) eyes in Group I, 1/3 (33%) eyes in Group II, and 2/2 (100%) eyes in Group III developed recurrence of macular edema with worsening of visual acuity at 6 and 9 months, respectively. Thirty-three (40.7%) eyes developed IOP elevation (at least one reading > 24 mmHg). One eye developed infective endophthalmitis. Conclusions Intravitreal injection of triamcinolone acetonide may be considered as an effective treatment for reducing macular thickening due to diffuse diabetic macular edema, venous occlusion associated macular edema, and may result in increase in visual acuity at least in the short term. Further follow-up and analysis is required to demonstrate its long-term efficacy.

Immunological responses to a 39.8 kDa Plasmodium vivax tryptophan-rich antigen (PvTRAg39.8) among humans

Tryptophan-rich protein from P. yoelii called PypAg3 had shown protection in a murine model. We describe here its P. vivax orthologue named PvTRAg39.8 which is expressed during schizont stages of the parasite. The transcription initiation site was mapped to the -41 nucleotide position from the first AUG codon and thus established the ORF of PvTRAg39.8 which codes for a 322aa long protein. The sequence of this protein is highly conserved among the P. vivax isolates. Recombinant PvTRAg39.8 was expressed in E. coli, purified to electrophoretic homogeneity, and used for immunological studies. A majority of P. vivax-exposed individuals (90%, n=50) contained antibodies against the recombinant PvTRAg39.8. There was a switching of immunoglobulin isotypes against this antigen from IgG1 to IgG4 among individuals from the acute phase of P. vivax infection to convalescence. The PBMCs of 80% of the total 20 P. vivax-exposed individuals showed proliferation when stimulated with this antigen. The cytokine pattern produced by the PBMCs of the P. vivax-exposed individuals, after stimulation with this antigen, indicated a mixed type of immune response with a distinct bias towards the Th2 anti-inflammatory profile. Because of its high natural immunogenicity, conserved nature, and the protective properties of its P. yoelii counterpart, this protein may be a potential candidate for developing the immunotherapeutic reagents.

Congenital porphyria with necrotizing scleritis in a 9‐year‐old child

Porphyria is a rare metabolic disorder that is characterized by the accumulation of photosensitive, toxic intermediates of the heme metabolic pathway in various organs of the body including the skin, eye and neural tissue. Porphyria as a potential cause for bilateral necrotizing scleritis in children is very infrequently emphasized in literature, probably due to the relatively rare occurrence and lack of well‐documented cases. A case of a 9‐year‐old child with congenital porphyria who had developed necrotizing scleral ulceration in both eyes in addition to severe cutaneous hypersensitivity and facial disfigurement is herein presented.

Plasmodium vivax tryptophan-rich antigen PvTRAg33.5 contains alpha helical structure and multidomain architecture.

Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion.

Cytomegalovirus retinitis in a patient with non-Hodgkin's lymphoma: a diagnostic dilemma.

Purpose Patients with lymphoma can rarely develop cytomegalovirus (CMV) retinitis. Clinically it is difficult to distinguish from intraocular lymphoma. Also, in such cases the CD4+ count may be high. The authors report a rare case of bilateral CMV retinitis in a patient with non-Hodgkins lymphoma with high CD4+ counts. Methods Observational case report with review of literature. Results CMV retinitis was clinically suspected due to the presence of large areas of retinal necrosis and hemorrhages in one eye and a demarcation line with white mottled retina in the other eye. Other differential diagnoses considered were intraocular lymphomatous infiltration and acute retinal necrosis due to herpes group of viruses. The diagnosis of CMV retinitis was confirmed by polymerase chain reaction performed on vitreous sample. Conclusions CMV retinitis can develop in cases of lymphoma despite high CD4+ counts. An early diagnosis can be established by performing PCR on vitreous biopsy.

Psychological Factors in the Etiopathogenesis of Central Serous Chorioretinopathy

Central serous chorioretinopathy (CSCR) has been associated with a number of psychological factors. We evaluated the psychological profile in 30 patients with acute CSCR and 30 age controls. CSCR patients had a higher proneness to stress, whereas no difference in psychological coping resources and degree of depression were found. We conclude that proneness to stress might predispose patients to acute CSCR.

Antioxidants: Basis concepts in relation to the eye.

Antioxidants are a small group of substances that protect living cells from the destructive consequences of powerful oxidizing intermediates that can be formed from oxygen. Situations in which pro-oxidant mechanisms within the body are more active than the antioxidant mechanisms (oxidative stress) predispose and contribute to the pathogenesis of several ailments in various organs of the body. In the eye, pro-oxidant factors have been blamed for the causation of diseases such as age related macular degeneration and senile cataract. The role of pro-oxidants in the genesis of certain diseases is well established however, the effectivity of antioxidants provided to the body by dietary supplementation is inconclusive. In this article we provide a review on the basic concepts of antioxidant-pro-oxidant interaction in relation to its effects on the eye.

Intraocular live cysticercus larva.

Ocular cysticercosis is one of the most common parasitic infections of the eye in humans. Although the adult pork tapeworm, Taenia solium, resides in the lumen of the intestine, the only structural element of an adult worm is usually found within a tissue cyst in the eye, its adenexa, or other places in the body with a single invaginated scolex. An unusual case is described in which a 13- to 14-mm live cysticercus larva was found, removed from the eye, and confirmed by histopathologic examination.