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Purpose: To evaluate demographics and outcomes of patients with recurrent corneal erosions related to trauma and epithelial and Bowman layer disorders., Design: Retrospective case series., Methods: setting: Wills Eye Institute, Philadelphia, Pennsylvania. study population: Two hundred seventy-two eyes (230 patients) presenting between 2008 and 2011 with recurrent corneal erosions related to trauma and epithelial and Bowman layer disorders. procedure: Conservative management, diamond burr polishing, excimer laser phototherapeutic keratectomy (PTK), and epithelial debridement alone. main outcome measure: Recurrence of erosions, more than 6 weeks after commencing treatment., Results: Mean age was 46.5 ± 14.6 (2-85) years. Female subjects accounted for 53% of patients and 18.3% had bilateral involvement. Etiology included epithelial basement membrane dystrophy in 52.9% (144/272) and trauma in 25.7% (70/272). One hundred sixty-six eyes with more than a single visit were initially managed conservatively, 68 of 166 (40.9%) had diamond burr polishing, 7 of 166 (4.2%) had PTK, and 4 of 166 (2.4%) had epithelial debridement alone. Many eyes had >6 weeks follow-up: 120 of 166 (72.3%) after conservative management, 54 of 68 (79.4%) after diamond burr polishing, 7 of 7 (100%) after PTK, and 4 of 4 (100%) after epithelial debridement. Percentage of eyes with recurrence was 56.7% (68/120) after conservative management, 14.8% (8/54) after diamond burr polishing, and 28.6% (2/7) after PTK. Rate of recurrence (eye-years) was 0.74, 0.19, and 0.23 with conservative management, diamond burr polishing, and PTK, respectively. Mild haze was seen in 22.2% of eyes (12 eyes) after diamond burr polishing and 28.6% (2 eyes) after PTK., Conclusion: Recurrent corneal erosions are most commonly associated with epithelial basement membrane dystrophy. Patients are generally initially managed conservatively, with recurrence in more than half of eyes. Diamond burr polishing is the most common surgical intervention and is effective in a majority of eyes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To identify the most common corneal transplant procedures, indications, coexisting ocular diseases, and outcomes in elderly patients, and to compare younger geriatric patients with super-geriatric patients., Design: Retrospective case series., Methods: Data of all patients 65 years old and older who underwent corneal transplantation at Wills Eye Institute from April 2007 to January 2013, and were followed up for at least 1 year, were collected. Two hundred seventy-one eyes of 253 patients were divided into 2 groups according to the age of the patient., Results: Group I (65-79 years old) included 181 eyes and Group II (80 years and older) included 90 eyes. The most common indication was Fuchs endothelial dystrophy, with 78 eyes (43%) in Group I and 34 eyes (38%) in Group II. In Group I, 93 Descemet stripping endothelial keratoplasty (DSEK) (51%), 84 penetrating keratoplasty (PK) (46%), and 4 keratoprosthesis procedures(2%) were performed; in Group II, 37 DSEK (41%), 51 PK (57%), and 2 keratoprosthesis procedures (2%) were performed. Graft survival rate at last visit was 90% for Group I and 88% for Group II. Rejection occurred in 18 Group I eyes (10%) and 7 Group II eyes (8%) (P = .562)., Conclusion: Endothelial abnormalities were more common indications and keratoconus was a less common indication for surgery in the elderly. Fuchs dystrophy was the leading indication for surgery in both super-geriatric and younger geriatric patients. Graft survival rate was slightly higher in the younger geriatric age group but was not statistically significant. In the elderly, there is an increased prevalence of both glaucoma and retinal diseases that can affect the visual outcomes after corneal transplantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In this study, the biopolymeric fraction BOS 2000 from Boswellia serrata was evaluated for its potential ability as adjuvants on the immune responses to ovalbumin (OVA) in mice. Balb/c mice were immunized subcutaneously with OVA 100 μg alone or with OVA 100 μg dissolved in saline containing alum (200 μg) or BOS 2000 (10, 20, 40 and 80 μg) on Days 1 and 15. Two weeks later, OVA specific antibodies in serum; concanavalin A (Con A), OVA stimulated splenocyte proliferation, CD4/CD8/CD80/CD86 analysis in spleen cells and its estimation of cytokines (IL-2 and IFN gamma) from cell culture supernatant were measured. OVA specific IgG, IgG1 and IgG2a antibody levels in serum were significantly enhanced by BOS 2000 (80 μg) compared with OVA control group. Moreover, the adjuvant effect of BOS 2000 (80 μg) on the OVA-specific IgG, IgG1, and IgG2a antibody responses to OVA in mice were more significant than those of alum. BOS 2000 significantly enhanced the Con A and OVA induced splenocyte proliferation in the OVA immunized mice especially at a dose of 80 μg (p<0.001). However, no significant differences were observed among the OVA group and OVA/alum group. At a dose of 80 μg (p<0.001), there was a significant increase in the CD4/CD8 and CD80/CD86 analysis in spleen cells and cytokine (IL-2 and IFN-gamma) profile in the spleen cell culture supernatant was observed. In conclusion, BOS 2000 seems to be a promising balanced Th1 and Th2 directing immunological adjuvants which can enhance the immunogenicity of vaccine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In order to explore the possible role of macrophages and other necessary immune competent (T and B) cells in the modulation of immune responses, an attempt was made to study the immunomodulatory effect of an irridoid glycoside (RLJ-NE-299A) isolated from the roots of Picrorhiza kurroa. Both in vitro and in vivo studies were used to evaluate the effect of RLJ-NE-299A on humoral, cellular, and phagocytic activity of macrophages. The data obtained in the present study showed that RLJ-NE-299A significantly increased sheep red blood cell (SRBC) and induced antibody (IgM and IgG) titer and delayed type hypersensitivity (DTH) reaction in mice. Besides augmenting the humoral and cell-mediated immune response, it induced macrophage phagocytosis and stimulated cytokine-induced macrophage activation and nitric oxide (NO) production, which resulted in a high degree of protection against Candida albicans and Salmonella typhimurium infections. Flow cytometric analysis indicated the enhanced expression of co-stimulatory surface molecules CD80 and CD86. The ability of RLJ-NE-299A to upregulate these cell surface antigens involved in antigen presentation may provide an explanation for the increased T-cell mediated immunity involving macrophages. Taken together this in vitro and in vivo preclinical data suggests that RLJ-NE-299A acts as an effective immunomodulator specifically to improve macrophage function during infections. The effects of this agent on these cells at concentrations relevant to in vivo therapy support its immunopharmacologic application to modify cellular immunity., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The acylated analogs of picroside-II were synthesized and tested for immune-adjuvant activity in the presence of weak antigen ovalbumin found to stimulate anti-OVA IgG titer, neutralizing antibody (IgG1 and IgG2a) titer as well as the production of soluble mediators of a Th1 response (IL-2 and IFN-γ) and Th2 response (IL-4) and proliferation of T lymphocytes sub-sets (CD4/CD8). Furthermore, these modified analogs of picroside-II were able to elicit a substantial increase in anti-OVA IgG when compared with OVA alone. These results support the use of acylated analogs particularly PK-II-3 and PK-II-4 as potent enhancer of antigen-specific Th1 and Th2 immune responses and thus are promising immune-adjuvant candidate for vaccines., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

This study was taken up to see the effect of Withanolide A (WS-1), a compound isolated from Withania somnifera root extract on chronic stress-induced alterations on T lymphocyte subset distribution and corresponding cytokine secretion patterns in experimental Swiss albino mice. Stress disturbs the homeostatic state of the organism and brings about behavioral, endocrine and immunological changes. The chronic suppression induced by stress depresses the immune functioning and increases susceptibility to diseases. Oral administration of WS-1 once daily at the graded doses of 0.25, 0.5, 1 and 2 mg/kg p.o. caused significant recovery of stress-induced depleted T cell population causing an increase in the expression of IL-2 and IFN-gamma (a signature cytokine of Th1 helper cells) and a decrease in the concentration of corticosterone in stressed experimental animals. It also reversed the restraint stress-induced increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase(AST) and hepatic lipid peroxidation (LP) levels and improved the restraint stress-induced decrease in hepatic glutathione (GSH), and glycogen levels, thus showing the significant antistress potential of the test drug.

An immunopharmacological profile of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one (P-I) has been investigated using in vitro and in vivo models representing various features of Type I allergy. P-I prevented compound 48/80-mediated histamine release from rat peritoneal mast cells. A promising anti-inflammatory activity of P-I was evident in active paw anaphylaxis (mice) and carragenan-induced paw edema (rat). P-I inhibited eosonophil accumulation and eosinophil peroxidase activity in bronchoalveolar lavage fluid from ovalbumin challenged balb/c mice: in these animals blood levels of IL-5, and CD4+ T cells also remained attenuated. A promising bronchorelaxant effect of P-I was observed in histamine-contracted guinea pig tracheal chain via its antagonism to H1 receptor. These findings were compared with some known compounds (ketotifen, cetirizine and promethazine). The anti-histaminic, anti-inflammatory and bronchorelaxant activities of P-I has been discussed in context with its potential profile as an anti-allergic and anti-asthmatic agent.

Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component. In search of a potent vaccine adjuvant, the water-soluble biopolymeric fraction BOS 2000 from Boswellia serrata was evaluated for desired activity. We investigated the ability of BOS 2000 to enhance HBsAg specific immune responses. The effect was determined in the form of protective anti-HBsAg titers, neutralizing antibodies (IgG1 and IgG2a), spleen cell lymphocyte proliferation by using MTT assay, Th1 (IFN-gamma and TNF-alpha) and Th2 (IL-4) cytokines as well as T-lymphocyte subsets (CD4/CD8) and intracellular cytokines (IFN-gamma/IL-4), these responses were highest in BOS 2000 immunized mice. Alum induced only a modest enhancement of antibody responses. Reducing the dose of adjuvant by 18.1-fold in comparison to alum, total IgG and its subtypes (IgG1 and IgG2a) antibodies titer in serum was significantly enhanced. Analysis of HBsAg specific cytokines revealed that alum was associated with a predominantly IL-4 response. In contrast, BOS 2000 was associated with production of both IFN-gamma and IL-4. We conclude that BOS 2000 is a potent enhancer of antigen-specific Th1 and Th2 immune responses in comparison to alum with Th2 limitation and is a promising adjuvant for vaccine applications.

Alum has been in use since long as an adjuvant for vaccines. However, its use as a vaccine adjuvant offers limitation in supporting cell mediated response. Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported for its immunostimulatory activity, has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with alum, antigen-specific immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with RLJ-NE-299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably the expression of Th1 cytokines IL-2, IL-12, IFN-gamma, TNF alpha and Th2 cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1 (Th2) subtypes increased profoundly in blood sera of mice immunized with HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential to increase both cell mediated and humoral immune responses and is capable of sustaining the total antigen-specific antibody response. Besides, the RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and CD8 cells populations, which may have important implications for vaccination against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312-40 microg) containing vaccine antigen (HBsAg) were well tolerated with optimum T cell response at 2.5 microg/ml. Not only this, the adjuvant was also able to induce cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines upregulation, which enabled mice to overcome the unresponsiveness to antigen HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice population. The study presents evidence that the HPLC standardized fraction RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the improved immune status against HBsAg, and may also prove useful adjuvant candidate with other vaccine antigens, too.

In the last three decades, numerous biopolymeric fractions have been isolated from medicinal plants and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulatory effects. The biopolymeric fraction RLJ-NE-205 was isolated and purified from the rhizomes of Picrorhiza kurroa. We evaluated the effects of biopolymeric fraction RLJ-NE-205 from P. kurroa on the in vivo immune function of the mouse. Balb/c mice were treated with the biopolymeric fraction RLJ-NE-205 (12.5, 25 and 50 mg/kg body weight) for 14 days with sheep red blood cells (SRBC) as an antigen. Haemagglutination antibody (HA) titre, plaque forming cell (PFC) assay, delayed type hypersensitivity (DTH) reaction, phagocytic index, proliferation of lymphocytes, analysis of cytokines in serum and CD4/CD8 population in spleen (determined by flowcytometry) were studied. At the dose of 50 mg/kg, significant increases in the proliferation of lymphocytes (p<0.001) and cytokine levels (IL-4 and IFN-gamma) in serum (p<0.001) were observed. A dose dependent increase was demonstrated in HA titre (p<0.05), DTH (p<0.01), PFC (p<0.05), phagocytic index (p<0.05) and CD4/CD8 (p<0.01) population. This suggests that the biopolymeric fraction RLJ-NE-205 improves the immune system and might be regarded as a biological response modifier.

Stress has been associated with reports of both greater severity and prolongation of diseases in patients with the infectious origin as well as other immune-mediated diseases. Withania somnifera, an Indian medicinal plant used widely in the treatment of many clinical conditions in India, was investigated for its anti-stress properties using BALB/c mice subjected to chronic stress. The study aimed to investigate chronic stress-induced alterations on Th1 lymphocyte subset distribution and corresponding cytokine secretion patterns. Oral administration of chemically standardized and identified aqueous fraction of W. somnifera root (WS) at the graded doses of 25, 50, 100 and 200 mg/kg p.o. caused significant increase in the stress-induced depleted T-cell population and increased the expression of Th1 cytokines in chronically stressed mice.