Model Of Conjunctivitis Research Articles

Expression of β Defensins in Ocular Surface Tissue of Experimentally Developed Allergic Conjunctivitis Mouse Model

To investigate the expression of beta-defensin in the ocular surface of a mouse experimental allergic conjunctivitis (EAC) model. Mouse beta-defensin (mBD)-1 and -2 mRNA expressed in conjunctival tissue of both the EAC and the control group were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. mBD-1 and mBD-2 mRNA expressed in cornea, limbus, and conjunctival epithelium of the EAC and the control group were also analyzed using a laser-assisted microdissection technique and the RT-PCR method. There was no significant difference in the amount of mBD-1 between the EAC and the control group. However, the EAC group had significantly less mBD-2 (0.23 +/- 0.15 x 10(4) copy/microl) than the control group (3.61 +/- 4.87 x 10(4) copy/microl) (P < 0.01, Mann-Whitney U test). mBD-1 mRNA was positive for all examined tissue in both groups. The expression of mBD-2 mRNA in the EAC group was definitely positive for the corneal and conjunctival epithelium and negative for the limbus. mBD-2 mRNA was expressed significantly less in the EAC model than in the control. Analysis by site in the ocular surface tissue revealed that this reduction was caused by the diminished expression of mBD-2 in the limbus.

Transglutaminase 2 in inflammation

Many reports have shown that the expression of transglutaminase 2 (TG 2) is increased in inflammatory diseases. Although during the last several decades multiple physiological roles for TG 2 have been demonstrated in various cell types, its role in the inflammatory process is not yet clear. TG 2 is a crosslinking enzyme that is widely used in many biological systems for tissue stabilization purposes and immediate defense against injury or infection. Aberrant activation of TG 2 activity in tissues contributes to a variety of diseases including neurodegenerative diseases, autoimmune diseases, and cancers. In most cases, TG 2 appears to form an inappropriate protein aggregate that may be cytotoxic enough to trigger inflammation and/or apoptosis. In some cases, such as celiac disease and rheumatoid arthritis, TG 2 is also associated with the pathogenic progression, as well as in the generation of autoantibodies. Recently, we discovered that increased TG 2 activity triggers NF-kappaB activation without I-kappaBalpha kinase signaling. TG 2 induces the polymerization of I-kappaBalpha rather than stimulating I-kappaBalpha kinase. This polymerization of I-kappaB results in the direct activation of NF-kappaB in various cell lines. We also found that TG inhibition reverses NF-kappaB activation. Interestingly, this coincides with the reversal of inflammation in conjunctivitis models by treatment with TG 2 inhibitors. Here, I introduce a new role for TG 2 as a signal modulator, which may suggest a new paradigm for the inflammatory process.

A PEPTIDE WITH ANTI-TRANSGLUTAMINASE ACTIVITY DECREASES LIPOPOLYSACCHARIDE-INDUCED LUNG INFLAMMATION IN MICE

Octapeptide R2 (KVLDGQDP), which has anti-transglutaminas (TGase) activity, decreases inflammation in allergic conjunctivitis model in guinea pigs. The authors examined the effect of R2 on lipopolysaccharide (LPS)-induced lung injury in BALB/c mice. R2 inhalation significantly decreased neutrophil count and cytokine mRNA expression in the lungs of LPS (25 mg/kg)-treated mice (P < .05). It also showed a tendency for decreased tumor necrosis factor (TNF)-α–immunoreactive protein in lung homogenates and significantly decreased TNF-α–immunoreactive protein in the serum of LPS-injected mice (P < .05). These results indicate that TGase may be a new therapeutic target in LPS-induced lung inflammation.

Mast cell hyperplasia induced by multiple challenge with cedar pollen in sensitised guinea pigs

Because immediate allergic symptoms are aggravated by repetitive antigen challenges in a guinea pig model of Japanese cedar pollen-induced conjunctivitis, we determined whether conjunctival mast cells are different in number between the acute and chronic stages. Sensitised guinea pigs were challenged by dropping a pollen suspension into their eyes once a week. Conjunctival tissue sections were stained with toluidine blue. Ophthalmic lavage was performed to assay for mast cell mediators. At the 20th and 40th challenges, the number of mast cells increased by 4- to 5-fold compared with the 1st challenge. Although mast cell degranulation was insignificant 10 min after the 1st challenge, the 20th and 40th challenges produced significant degranulation. After multiple challenges, the amount of histamine and tryptase-like activity in the lavage fluid was dramatically increased. Increased mast cells are associated with aggravated symptoms. Mast cell mediators may be involved in pathogenesis at the chronic stage.

Comparison of Topical Dexamethasone and Topical FK506 Treatment for the Experimental Allergic Conjunctivitis Model in Balb/c Mice

To evaluate the efficacy of topical dexamethasone and topical FK506 treatment on allergic inflammation in conjunctiva, we performed a comparative study using a mouse experimental allergic conjunctivitis model. The experimental allergic conjunctivitis model was developed by ovalbumin (OVA) instillation after OVA sensitization by intraperitoneal application of a mixed solution of OVA and aluminum hydroxide. The Balb/c mice of the experimental allergic conjunctivitis model were divided into three groups, depending on whether or not they received topical treatment and which type of treatment they received. The allergy group comprised six mice without topical treatment; the dexamethasone (Dx) group comprised six mice receiving topical 0.1% dexamethasone ointment treatment; and the FK506 (FK) group comprised six mice receiving topical 0.1% FK506 ointment treatment. The negative control group comprised six mice with neither sensitization nor topical treatment. For the histological examination, frozen sections of the eyelids, eyeballs, and lacrimal glands were stained with acid Giemsa stain or, in the immunohistochemical method, with alkaline phosphatase-antialkaline phosphatase (APAAP), for CD4. Densities of eosinophils and CD4-positive lymphocytes in the conjunctival tissue were counted. Productive C epsilon gene expression in the conjunctival tissue, including the lacrimal gland, was also evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). In the histological study, the cell density of eosinophils infiltrating into subconjunctival tissues was 66.3 +/- 34.7 cells/mm(2) (mean +/- SD) for the allergy group, 2.5 +/- 4.2 cells/mm(2) for the Dx group, 4.2 +/- 8.6 cells/mm(2) for the FK group, and 3.7 +/- 7.6 cells/mm(2) for the negative control group. The cell density of CD4-positive cells infiltrating into subconjuctival tissues was 145.9 +/- 66.4 cells/mm(2) for the allergy group, 10.0 +/- 12.9 cells/mm(2) for the Dx group, 10.1 +/- 15.5 cells/mm(2) for the FK group, and 21.7 +/- 17.8 cells/mm(2) for the negative control group. The allergy group showed significant differences in the density of eosinophils and CD4-positive cells compared with those of the Dx (P < 0.0001) and FK (P < 0.0001) groups. In the RT-PCR study, the expression of productive C epsilon gene was positive in the Dx group, but negative in the allergy group, the FK group, and the negative control group. Topical Dx and FK506 treatments were both efficacious in suppressing eosinophil and lymphocyte infiltration into subconjunctival tissue in the mouse experimental allergic conjunctivitis model. However, the influence of their IgE productive mechanisms seemed to differ, causing different efficacy of productive C epsilon gene expression in the conjunctival tissue.

Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection

A large body of evidence suggests that corneal allograft rejection is mediated by a type 1 Th cell response and that deviation toward type 2 immunity favors graft survival. However, clinical observations indicate that patients with severe ocular allergies have increased risk of corneal allograft rejection. We used a mouse model of atopic conjunctivitis to evaluate the effects of Th2 immune deviation on corneal allograft survival and possible mechanisms of graft rejection. Our results reveal the following novel findings: 1) atopic conjunctivitis promotes systemic Th2 immune responses to corneal graft donor alloantigens; 2) corneal allografts in atopic host eyes have an increased incidence and swifter tempo of rejection; 3) increased rejection is associated with alterations in systemic T cell-mediated responses to donor alloantigens; and 4) corneal allograft rejection in atopic hosts does not require the direct involvement of infiltrating eosinophils.

Rapid Corneal Allograft Rejection with TH2 Cell Involvement in a Model of Atopic Conjunctivitis

Mice injected with single or multiple doses of soluble alloantigen extracts (SAE) derived from H-2b cells failed to develop thymus dependent cell-mediated immunity (CMI) upon subsequent immunization with EL-4 (H-2b) tumor allograft. By contrast, the humoral response was only slightly affected. Nevertheless, the mice rejected the tumor allograft with no sign of enhancement. Suppression of cell-mediated immunity (SCMI) was obtained with SAE prepared from either tumor or spleen cells and was shown to be specific, i.e., SAE derived from sources histoincompatible with the allografted cells had no effect. The best conditions used to demonstrate specific SCMI were the following: (A) the alloantigen must be soluble; (B) the SAE must be administered prior to tumor inoculation; (C) multiple injections of SAE were more effective than single injection; (D) it was best observed with suboptimal tumor dose inoculums. Mice treated with a single dose of SAE showed appreciable blocking activity in their serum prior to tumor inoculation. Blocking, however, was not detected in the serum of mice injected with multiple injections of soluble alloantigen. These findings offered possible mechanisms for SCMI (afferent and/or central blocking).We conclude from these results that SAE preferentially suppress the formation of T-cytotoxic cells but not the T-helper cells. This preferential effect is discussed in view of its importance in promoting graft survival.

Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 2. 6,6-Dimethylbicyclo[3.1.1]heptane derivatives.

In an earlier paper, we reported that novel prostaglandin D(2) (PGD(2)) receptor antagonists having the bicyclo[2.2.1]heptane ring system as a prostaglandin skeleton were a potent new class of antiallergic agents and suppressed various allergic inflammatory responses such as those observed in conjunctivitis and asthma models. In the present study, we synthesized PGD(2) receptor antagonists having the 6,6-dimethylbicyclo[3.1.1]heptane ring system. These derivatives have the amide moiety, in contrast to those with the bicyclo[2.2.1]heptane ring system, which have the sulfonamide group. The derivatives having the 6,6-dimethylbicyclo[3.1.1]heptane ring also exhibited strong activity in PGD(2) receptor binding and cAMP formation assays. In in vivo assays such as allergic rhinitis, conjunctivitis, and asthma models, these series of derivatives showed excellent pharmacological profiles. In particular, compound 45 also effectively suppressed eosinophil infiltration in allergic rhinitis and asthma models. This compound (45, S-5751) is now being developed as a promising alternative antiallergic drug candidate.

Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 1. Bicyclo[2.2.1]heptane derivatives.

Novel prostaglandin D(2) (PGD(2)) receptor antagonists were synthesized as a potential new class of antiallergic agents having a bicyclo[2.2.1]heptane ring system with sulfonamide groups. Some of them exhibit extremely potent antagonism of the PGD(2) receptor in radioligand binding and cAMP formation assays with IC(50) values below 50 nM and much less antagonism of TXA(2) and PGI(2) receptors. These potent PGD(2) receptor antagonists, when given orally, dramatically suppress various allergic inflammatory responses such as increased vascular permeability in allergic rhinitis, conjunctivitis, and asthma models. The excellent pharmacological profiles of PGD(2) receptor antagonists, originally synthesized in our laboratories, are of potentially great clinical significance. This study also provides experimental evidence suggesting that PGD(2) plays an important role in the pathogenesis of allergic diseases.

Multiple cedar pollen challenge diminishes involvement of histamine in allergic conjunctivitis of Guinea pigs.

It has been reported that antihistamines do not fully modify symptoms of allergic conjunctivitis in clinical settings, suggesting that histamine is not the only contributor to symptom generation in the disease. However, in the majority of experimental allergic conjunctivitis models, antihistamines are very effective in the reduction of symptoms. In the present study, we used our recently developed guinea pig model of allergic conjunctivitis and evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by multiple antigen challenges. Guinea pigs were sensitized by intraperitoneal injection of Japanese cedar pollen extracts adsorbed on aluminum hydroxide gel, and then challenged by dropping a pollen suspension without the adjuvant on each eye once a week until the 15th challenge. The magnitude of the conjunctivitis intensity score (CIS), itch-associated scratching response and albumin leakage were found to increase with repeated challenges. At the 1st-3rd challenges, histamine H(1) receptor antagonist, mepyramine (10 mg/kg, p.o.), strongly reduced all these symptoms. However, symptoms at the 5th-15th challenges were not inhibited by mepyramine. On the other hand, a nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (10 mg/kg, i.v.), potently inhibited the increase of CIS and albumin leakage at the 15th challenge. In conclusion, histamine involvement in the induction of conjunctivitis symptoms in our model was diminished by multiple antigen challenges. The allergic conjunctivitis at the chronic stage is partly mediated by nitric oxide (NO) derived from NOSs that may be activated by mediators other than histamine. The histamine-independent allergic conjunctivitis may be useful for analyzing mechanisms underlying chronic conjunctivitis.

Immunosuppressive Effect of Cholera Toxin B on Allergic Conjunctivitis Model in Guinea Pig

Purpose: To investigate the new method of immunotherapy using cholera toxin B (CTB) in experimental allergic conjunctivitis. Methods: We used 21 white Hartley guinea pigs. The animals were sensitized by intraperitoneal injection of ovalbumin (100 μg/mL) and albumin hydroxide (5 mg/mL) repeated after an interval of 2 weeks. One week after the second injection, conjunctivitis was induced by topical instillation of ovalbumin (5 mg/mL). The animals were divided into two groups, CTB group and control group. The CTB group underwent pretreatment of topical instillation of CTB (4μg/30 mL) and ovalbumin (10 μg/30 mL), three times a day for 3 days, 1 week before the intraperitoneal injection. The control group did not undergo the pretreatment. Clinical examination was performed at 0.5, 6, and 24 hours after the development of conjunctivitis. Histological examination was performed at 6 and 24 hours. Results: Both groups developed palpebral and bulbar edema with hyperemia 30 minutes after instillation of ovalbumin. The allergic reaction score was significantly less in the CTB group than in the control group (Mann-Whitney U-test: P < .01). The clinical reactions subsided after 6 hours. The CTB group showed less eosinophilic infiltration in the conjunctiva and the limbus, particularly in the conjunctival epithelium, than the control group at 6 and 24 hours. Conclusion: Pretreatment with topical CTB and antigen suppresses clinical and histological findings in experimentally induced allergic conjunctivitis.

Immunosuppressive Effect of Cholera Toxin B on Allergic Conjunctivitis Model in the Guinea Pig

Purpose: To investigate the immunosuppressive effects of mucosal immune therapy in experimental allergic conjunctivitis. Method: We used 11 white Hartrey guinea pigs divided into two groups. Six animals (treated group) received pretreatment with topical instillation of cholera toxin B (4 μg/30 ml) and ovalbumin (10 μg/30 ml). The other group of 5 animals served as control. All the animals received intra-abdominal injection of ovalbumin (100 g/mL) and aluminum hydroxide (5 mg/mL) repeated twice 2 weeks apart. Allergic conjunctivitis was induced by topical instillation of ovalbumin solution (5 mg/mL) 1 week after the above procedure. Result: Both groups developed palpebral and bulbar edema with hyperemia 30 minutes after instillation. The allergic reaction was significantly less in score in the treated than in the control group (Mann–Whitney U-test: P < .01). The clinical findings subsided after 6 hours. The treated group showed less eosinophilic infiltration in the conjunctiva and the limbus, particularly in the conjunctival epithelium, than in the control group at 6 and 24 hours. Conclusion: Pretreatment with topical cholera toxin B and antigen suppresses clinical and histological findings in experimentally induced allergic conjunctivitis.

Anti VLA-4 monoclonal antibody inhibits eosinophil infiltration in allergic conjunctivitis model of guinea pig

Purpose. To determine the contribution of very late activation antigen-4 (VLA-4) molecule to eosinophil infiltration into the conjunctiva in an actively sensitized allergic conjunctivitis model of guinea pig, effects of a monoclonal antibody against VLA-4 was examined in vivo. Methods. A rat anti-mouse VLA-4 mAb (PS 2. 3), which cross-reacts with guinea pig VLA-4, inhibited the adhesion and transmigration of guinea pig eosinophils to /through human umbilical vein endothelial cells (HUVEC) in vitro. Hartley guinea pigs were actively sensitized by intraperitoneal injection of ovalbumin with aluminum hydroxide. Two weeks later, 2.5% ovalbumin was dropped into the eye for the antigen challenge. In the treatment group, 4 mg/kg (body weight) of the anti VLA-4 mAb (PS2·3), and in the control group, the same amount of a control Ab was intraperitoneally injected respectively at 4 hours before the antigen challenge. From both groups, the eyelids and eyeballs were excised at 2, 4, 10, and 24 hours after the antigen challenge, fixed, stained with Hansel solution and the number of the infiltrating eosinophils in the conjunctiva was counted. Results. In the control group, infiltration of eosinophils to the conjunctiva increased with time, peaked at 12 hours, and then gradually decreased until 24 hours after the antigen challenge. In the anti VLA4-mAb treated group, eosinophil infiltration was almost completely inhibited at least until 24 hours after the antigen challenge. Conclusion. VLA-4 molecule was elucidated to play a critical roll in the eosinophil infiltration in experimentally-induced allergic conjunctivitis model of guinea pig.

Allergic conjunctivitis and uveitis models: reappraisal with some marketed drugs.

The purpose of this study was to assess the activity of some marketed products in ocular non-immune and immune type I hypersensitivity reactions, and during intra-ocular type III hypersensitivity. In order to compare these activities, we improved and validated three different models of ocular allergic reaction already known for their ability to reproduce allergic conjunctivitis or uveitis. Allergic conjunctivitis was induced by ocular immediate hypersensitivity after instillation of compound 48/80 in the rat, or an active anaphylaxis reaction with ovalbumin immunisation and challenge in the guinea pig. Uveitis was induced by a reverse passive anaphylaxis reaction using intra-vitreal rabbit anti-bovine IgG anti-serum sensitisation and intravenous bovine gamma-globulin challenge in the rabbit. Clinical scores and blood-tissue permeability indices were studied. Using the same schedule of ocular instillation, the effects of Livostin (levocabastine 0.05%), Almide (lodoxamide 0.1%), Opticrom (sodium cromoglycate 2%), Ocufen (flurbiprofen 0.03%), Acular (ketorolac 0.5%) and 0.3% chlorpheniramine maleate were compared to positive and negative controls. We demonstrated the potent activity of chlorpheniramine maleate 0.3% and Livostin in both allergic conjunctivitis models. Significant activity was also evidenced with Almide, which was only active in the non-immune allergy model, while Opticrom was definitely not active in these models. In the uveitis model, Acular and Ocufen are active and potent drugs, while Livostin and Almide were not active. These results are discussed with respect to the models used and the mediators involved.

Preclinical Efficacy of Emedastine, a Potent, Selective Histamine H1 Antagonist for Topical Ocular Use

Emedastine [1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)- benzimidazole difumarate] was evaluated for topical ocular anti-histaminic activity in histamine and antigen stimulated conjunctivitis models. Concentration-dependent inhibition of histamine induced vascular permeability changes occurring in the conjunctiva was observed when the time interval between topical ocular administration and histamine challenge ranged from 1 min to 8 hr. The calculated ED50 values obtained using intervals of 1 min, 30 min, 2, 4 and 8 hr were 0.0002%, 0.000035%, 0.0029%, 0.019% and 0.19%, w/v, respectively. Comparisons of relative potency 30 min post dosing between emedastine and other anti-histamines demonstrated that emedastine is equipotent to ketotifen, and 7, 7, 10, 10, 100, 357, 3333, and 5813 times more potent than brompheniramine, chlorpheniramine, clemastine, pyrilamine, levocabastine, pheniramine, diphenhydramine, and antazoline, respectively. Emedastine (0.1%) failed to significantly attenuate either serotonin or platelet-activating-factor induced vascular permeability changes indicating high selectivity for the histamine H1 receptor. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of emedastine 5 min or 30 min prior to antigen challenge (ED50s 0.0046% and 0.00022%, respectively). These data clearly indicate that emedastine has potential as a topical ocular anti-histamine for treating allergic conjunctivitis.

Reproducible model of a bacterial conjunctivitis

To test the efficiency of antimicrobial substances on bacterial conjunctivitis under standardized conditions a reproducible model is needed. As there are no data in the literature concerning this topic we have developed a model of bacterial conjunctivitis in the rabbit eye. Instillation of a suspension of Haemophilus influenzae, Staphylococcus epidermidis or Staphylococcus aureus into the cul-de-sac did not result in any effect. Thus, standardized techniques of conjunctival incision were used additionally. A follow-up was done for a period of 2 weeks (degree of conjunctival hyperemia, microbiology). Radial incision of the conjunctiva with injection of an S. aureus suspension (50 microliters of ATCC 29213; 1.35 x 10(8) cells) was done mimicking a branch injury. This resulted in a purulent conjunctivitis over a period of 1 week and disappeared within 14 days. The swabs were negative on day 7. This is the first model establishing a reproducible purulent conjunctivitis in the rabbit. Using this model antimicrobial substances may be tested under standardized conditions.

Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus-specific 57-kD protein.

Recurrent or persistent infections with Chlamydia trachomatis are thought to provide the antigenic stimulus for the chronic inflammation associated with blinding trachoma. We used the guinea pig model of inclusion conjunctivitis to identify chlamydial antigens that may be involved in this deleterious immune response. We purified from chlamydial elementary bodies a genus-specific 57-kD protein that elicited an ocular hypersensitivity response when placed topically onto the conjunctiva of ocular immune guinea pigs. This response was characterized by a predominantly mononuclear macrophage and lymphocyte cellular infiltrate of the submucosal epithelium. The clinical and histological findings were consistent with those of a delayed hypersensitivity response. These data demonstrated that the 57-kD chlamydial protein was a potent stimulator of ocular delayed hypersensitivity. Our findings may be critical to understanding the pathogenesis of the debilitating chlamydial diseases associated with chronic inflammation, such as trachoma and many urogenital syndromes.

Bactériophages et bactériocines du genre Listeria

Since the discovery of the first Listeria bacteriophage by Schultz in 1945, more than 219 phages were isolated for L. monocytogenes, L. invanovii, L. innocua, L. seeligeri and L. welshimeri. To date, no phage for L. murrayi and L. grayi is described in the literature. Unless two phages found by Jasińska in a water sample, all the other phages, when the origin is mentioned, were isolated from lysogenic strains, with or without induction. Electron microscopic examination of 55 Listeria phages revealed that two L. innocua phages belonged to the Myoviridae family (tail with contractile sheath) whereas the 53 other phages of L. monocytogenes, L. ivanovii and L. innocua belonged to the Siphoviridae family (tail without contractile sheath). According to the length of the tail, phages of this second group were divided into three species (species 2685, 2671 and 2389). DNA/DNA hybridizations, performed with the method of Southern, after digestion of the DNAs with Eco RI, pointed out three genomic groups: one corresponded to a single phage of Myoviridae and the two others included phages of the Siphoviridae species 2671 and 2685, thus demonstrating a good correlation between ultrastructure and DNA relatedness. Serology of Listeria phages remained unclear. Host range studies showed that these phages are genus specific and allowed to type 34% to 80% Listeria strains. Phage typing of Listeria strains isolated during listeriosis epidemics and cross infections in nursery proved to be useful in order to elucidate epidemiology of this disease. Listeria phages were used to detect Listeria strains in various samples by phage fluorescent antiphage staining system and phage titer increase test. Some phages seem to induce prophylaxis against listeriosis when tested in animal listeric pneumonia and conjunctivitis models. The possible role of phages in the virulence of L. monocytogenes needs further investigations. Bacteriocins of Listeria, called monocins, were first described by Sword and Pickett in 1961. Monocins isolated by Hamon and Péron were resistant to trypsin, inactivated at 50 degrees C and at pH 4,5 and sedimented at low speed, suggesting that these bacteriocins might be in fact defective phages. This was confirmed by Bradley and Dewar by electron microscopic study. Host range of monocins included Listeria, Staphylococcus and Bacillus.

Enteropathogenic Escherichia coli diarrhea in hospitalized children in Bangladesh.

The role of enteropathogenic Escherichia coli (EPEC) was evaluated in a group of children with endemic diarrhea admitted to Dhaka Shishu Hospital in Dacca, Bangladesh. EPEC was detected in fecal samples of 23% of 104 cases and 8% of 74 concurrent control children. The most commonly isolated EPEC strains were serogroups O20a, O20c:K61; O20a, O20b:K84; O26:K60; and O18a, O18c:K77. Except for O26:K60, these groups had not been reported from Bangladesh. On testing for enterotoxin production, only two strains (serogroups O26:K60, O18a, and O18c:K77) were enterotoxigenic. None was enteroinvasive as tested in the guinea pig conjunctivitis model. Our study supports the concept that EPEC may be an important cause of endemic diarrhea in Bangladesh.

Intermittent vs continuous steroid administration. Efficacy in experimental conjunctivitis.

The development of techniques for the continuous administration of drugs to the eye raises the question of whether a conjunctivitis can be controlled by continuous low rates of steroid release, or whether large, intermittent doses of steroid, as provided by eyedrops, are necessary. Efficacy of the two modes of drug administration was evaluated in a conjunctivitis model produced in immunized rabbits by daily topical ocular challenge with antigen. The acetates of hydrocortisone and prednisolone were released from a drug delivery system inserted in the cul-de-sac of the eye or were provided in eyedrops. The model was sufficiently sensitive to differentiate between the effectiveness of hydrocortisone and prednisolone. The continuous delivery of either steroid from the drug delivery system was as efficacious, or more so, than the corresponding steroid dose given as eyedrops.