Contribution of pneumolysin and autolysin to the pathogenesis of experimental pneumococcal endophthalmitis

PURPOSE: To determine the contribution of pneumolysin and autolysin, two putative pneumococcal virulence proteins, to the pathogenesis of Streptococcus pneumoniae endophthalmitis. METHODS: Endophthalmitis was established in Lewis rats by intravitreal injection of pneumococcal strains at an inoculum of 10 organisms. The virulence of three closely related type 2 S. pneumoniae strains were compared: a pneumolysin-deficient derivative (PLN-A), an autolysin-deficient derivative (AL-6), and their isogenic wild-type parent (D 39). Clinical and histologic inflammation scores were compared 24 hours and 48 hours after inoculation. RESULTS: Eyes infected with PLN-A and AL-6 strains showed less anterior segment inflammation clinically at 24 hours than did eyes infected with the wild-type strain. Histologic examination at 24 hours showed significantly less corneal infiltration and vitritis and more relative preservation of retinal tissue in eyes infected with PLN-A and AL-6 strains than in eyes infected with the wild-type strain. At 48 hours, no observable differences between PLN-A and wild-type strains were present clinically or histologically. Histologically, however, the AL-6 strain caused less retinal damage than did the wild-type strain. CONCLUSIONS: Intraocular infection with pneumolysin-deficient S. pneumoniae results in less severe tissue damage in the first 24 hours of disease compared with infection with pneumolysin-producing S. pneumoniae. Autolysin-deficient S. pneumoniae shows a similar degree of attenuated virulence. Pneumolysin and autolysin may contribute to the early pathogenesis of pneumococcal endophthalmitis.     

The impact of ocular blood flow in glaucoma

Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.     

Study of the prolonged release of theopylline from polymeric matrices based on grafted chitosan with acrylamide

The aim of this work was to study the performance of chitosan (CB) grafted with acrylamide (CB-g-A) as prolonged drug release matrix as compared with unmodified chitosan. A non-pH dependent swelling behaviour for the matrix tablets based on grafted chitosan was observed. The overlaping between degree of swelling measured by weighing (DSw) and measured by increase of diameter (DSd) up to 240 minutes showed that the swelling process could be isotropic. The non-pH dependent swelling behaviour of these matrices could be explained by the partial substitution of amine groups of the chitosan chain by acrylamide. The grafting reaction provides an ionizable amine group by a neutral amide group which make the matrix non pH-dependent. On the contrary, the matrix tablet based on chitosan showed a pH dependent swelling behaviour where the swelling process could be anisotropic. The higher degree of erosion and swelling of the formulation based on CB-g-A600 (%G = 600) compared with the formulation based on chitosan and CB-g-A418 (%G = 418) could explain the higher fraction of theopylline released. For all formulations studied in this work, the amount of theopylline released from the matrix tablets was found to be controlled by a combination of the diffusion process and relaxation of the polymeric structure. These results match with the controlled swelling behaviour and low degree of erosion observed for these systems.     

NoiseChem: an European Commission research project on the effects of exposure to noise and industrial chemicals on hearing and balance

Exposure to multiple physical and chemical agents is common in occupational environments but workplace hazards and occupational safety criteria for combined exposures are lacking. NoiseChem is an European Commission research project examining the effects of exposure to noise and chemicals on hearing and balance. Partners in Sweden, Finland, France, Denmark, UK and Poland with expert guidance from partners in the USA will examine workers and study the mechanisms of action in animals to determine the levels of risk associated with joint exposure to noise and solvents. This paper briefly outlines the project details.     

Sports injury experiences from the Western Australian Sports Injury Cohort Study

OBJECTIVE: The Western Australian Sports Injury Study is the first prospective cohort study of sports injuries sustained during community-level sports participation in Australia. METHODS: The players were nonprofessional/non-elite participants of hockey, Australian football, basketball and netball from metropolitan Perth. Players completed a baseline questionnaire relating to their sports injury history, training practices, protective equipment use, demographic profile, general health and lifestyle factors. Sports participation and injury experiences were monitored by monthly telephone surveys over two consecutive five-month winter sporting seasons during 1997 and 1998. RESULTS: Of the 1,512 players recruited into the initial cohort, 966 (i.e. 64%) responded to at least 700% of the callback surveys over the two-year follow-up. Across all sports, the injury incidence rate was 16.1 injuries/ 1,000 exposure hours (both games and training). Injury rates were highest in Australian football and lowest in netball. Lower limb injuries were twice as common as those to the upper limb (67% vs. 31%). Three-quarters of injured players sought treatment from a health care practitioner. CONCLUSIONS AND IMPLICATIONS: This is the first longitudinal study of injuries to community-based sports participants in Australia. Compared with elite sports participants, the risk of injury is relatively low. The results provide valuable direction for the design and conduct of further aetiological studies.     

NoiseChem: An European Commission research project on the effects of exposure to noise and industrial chemicals on hearing and balance

Exposure to multiple physical and chemical agents is common in occupational environments but workplace hazards and occupational safety criteria for combined exposures is lacking. NoiseChem is an European Commission research project examining the effects of exposure to noise and chemicals on hearing and balance. Partners in Sweden, Finland, France, Denmark, UK and Poland with expert guidance from partners in USA will examine workers and study the mechanisms of action in animals to determine the levels of risk associated with joint exposure to noise and solvents. This paper briefly outlines the project details.     

Occupational exposure to insecticides and their effects on the auditory system

The objective of this investigation was to study the effects of occupational exposure to organophosphates and pyrethroid insecticides on the central auditory system. The study group consisted of 98 workers exposed to insecticides and 54 non-exposed workers. Data on work history, medical history, present diseases, occupational and non-occupational exposure to noise or chemicals and lifestyle factors were obtained through an interview. Central auditory system functions were assessed through frequency patterns and duration patterns testing. Fifty-six percent of the exposed workers had hearing dysfunction at the central level and its relative risk was 7.58 for the group with exposure to insecticides (95% CI 2.9- 19.8) when compared to the non-exposed group. The group exposed to insecticides and noise had a relative risk for central disorders of 6.5 (95% CI 2.2-20.0) when compared to the non-exposed group and 9.8 (95% CI 1.4-64.5) when compared to the group exposed only to noise. The finding suggests that exposure to organophosphates and pyrethroid products can induce damage to central auditory system. Further research is needed on the ototoxic mechanisms of these chemicals, and on hearing loss prevention measurements that are applicable and adequate to such risks and populations.     

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E2 on the pharmacology and physiology of propagated action potentials

1. We have studied the effects of prostaglandin E(2) (PGE(2)) on action potential propagation in the isolated, desheathed vagus and saphenous nerves of rats using an extracellular grease gap recording method. 2. PGE(2) evoked a small depolarization of vagus nerves but had no effect on the stimulation threshold, size or latency of either the A wave (corresponding to conduction in A fibres) or the C wave (corresponding to conduction in C fibres) of the compound action potential (CAP) recorded from either vagus or saphenous nerves. 3. Lidocaine (0.01 - 10 mM) reduced all components of the CAP of both vagus and saphenous nerves. PGE(2) had no significant effect on the sensitivity of any component of the CAP to lidocaine. 4. Tetrodotoxin (TTX, 10 microM) blocked completely both the A wave and the C wave of the CAP in either vagus or saphenous nerves. 5. In saphenous nerve preparations the A wave was blocked by lower concentrations of TTX than the C wave or any component of the CAP in vagus nerve preparations which suggests that somatosensory A fibres express a different sub-type of TTX-sensitive voltage-gated sodium channel (VGSC) than somatosensory C-fibres or visceral sensory fibres. 6. Chemical activation of VGSCs with veratridine (10 or 50 microM) induced a depolarization in either nerve. The depolarization induced by 50 microM veratridine was blocked by 10 microM TTX. 7. Although TTX-insensitive VGSCs are expressed by some vagal and some somatosensory neurones they do not appear to be expressed functionally in the axons.     

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

1 We investigated the effects of prolonged exposure to copper (Cu(2+)) on vascular functioning of isolated rat aorta. 2 Aortic rings were exposed to CuSO(4) (3-24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu(2+). 3 Exposure to 2 micro M Cu(2+) in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 micro M PE by 30% (P<0.05) and impaired the relaxant response to 3 micro M ACh or 1 micro M A23187 (ACh, from 65.7+/-7.1 to 6.2+/-1.1%, n=8; A23187, from 74.6+/-8.2 to 12.0+/-0.8%, n=6; P<0.01 for both). Cu(2+) exposure did not affect the relaxant response to NO-donors. 4 Impairment of vasorelaxation appeared 3 h after incubation with 2 micro M Cu(2+) and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2+/-6.4%, n=10, P<0.01 vs Cu(2+) alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. 5 Twenty-four hour-exposure to 2 micro M Cu(2+) did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8+/-1.1 to 18.9+/-2.9 ng mg(-1) wet weight, n=8; P<0.01. 6 Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu(2+) impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. British Journal of Pharmacology (2002) 136, 1185-1193