Knowledge and attitude towards HIV/AIDS among Iranian students

BACKGROUND: Young people are of particular importance in state policies against Acquired Immunodeficiency Syndrome (AIDS). We intended to assess the knowledge and attitude of high school students regarding AIDS in Iran. METHODS: Through a cluster-sampling, 4641 students from 52 high schools in Tehran were assessed by anonymous questionnaires in February 2002. RESULTS: The students identified television as their most important source of information about AIDS. Only a few students answered all the knowledge questions correctly, and there were many misconceptions about the routes of transmission. Mosquito bites (33%), public swimming pools (21%), and public toilets (20%) were incorrectly identified as routes of transmission. 46% believed that Human Immunodeficiency Virus positive (HIV positive) students should not attend ordinary schools. Most of the students wanted to know more about AIDS. In this study knowledge level was associated with students' attitudes and discipline (p < 0.001). CONCLUSION: Although the knowledge level seems to be moderately high, misconceptions about the routes of transmission were common. There was a substantial intolerant attitude towards AIDS and HIV positive patients. We recommend that strategies for AIDS risk reduction in adolescents be developed in Iranian high schools

Basement Membrane Zone Collagens XV and XVIII/Proteoglycans Mediate Leukocyte Influx in Renal Ischemia/Reperfusion

Collagen type XV and XVIII are proteoglycans found in the basement membrane zones of endothelial and epithelial cells, and known for their cryptic anti-angiogenic domains named restin and endostatin, respectively. Mutations or deletions of these collagens are associated with eye, muscle and microvessel phenotypes. We now describe a novel role for these collagens, namely a supportive role in leukocyte recruitment. We subjected mice deficient in collagen XV or collagen XVIII, and their compound mutant, as well as the wild-type control mice to bilateral renal ischemia/reperfusion, and evaluated renal function, tubular injury, and neutrophil and macrophage influx at different time points after ischemia/reperfusion. Five days after ischemia/reperfusion, the collagen XV, collagen XVIII and the compound mutant mice showed diminished serum urea levels compared to wild-type mice (all

Proteoglycans modulate renal inflammation : studies on complement and leukocyte recruitment

Rol van proteoglycanen bij ontstaan nierschade De huidige behandeling van nierfalen is gebaseerd op het vervangen van de nier door dialyse of transplantatie. In beide gevallen blijft een verhoogd risico op nierfalen bestaan. Ontstekingsreacties spelen hierbij een grote rol. Azadeh Zaferani onderzocht mogelijkheden om deze ontstekingsreacties tegen te gaan. Daarbij richtte zij haar aandacht op de interactie tussen het aangeboren immuunsysteem (meer specifiek: het complementsysteem) en proteoglycanen. Dit zijn complexe glycoconjugaten die in ieder weefsel voorkomen op het celoppervlak en in de extracellulaire matrix. Zaferani laat zien hoe nierschade kan ontstaan door interactie tussen proteoglycanen en het complementsysteem. Daarnaast toont ze aan dat er een nieuwe rol is voor basaal membraan proteoglycanen bij het optreden van nierschade. Deze inzichten in moleculaire interacties kunnen helpen bij de ontwikkeling van nieuwe behandelingen. Voordat deze behandelingen er zijn, moet er echter nog veel nader onderzoek worden verricht. Current management of end stage renal disease is based on renal replacement therapy by dialysis or transplantation. Increasing occurrence of renal failure in both native and transplanted kidneys emerges the need for new therapies to stop the progression of the disease. Ischemia/reperfusion (I/R) injury and proteinuria have been shown to be major risk factors in the development of renal failure. Innate immunity plays an important role in the pathogenesis of renal diseases both in native and transplanted kidneys. The complement system forms a major humoral part of the innate immune system. Most of the complement factors interact with proteoglycans (PG) which thus represent docking platforms for complement activation both on cellular membranes and in the extracellular compartment. Therefore, this interaction might be a target for intervention. In this thesis we studied the contribution of proteoglycans in innate immune-derived renal injury in transplantation and native kidney diseases. Based on our findings, we propose a novel mechanism for proteinuria-derived tubular injury via PGs interaction with complement factors. We also showed a novel role for basement membrane PGs in I/R induced renal injury. It is clear that insight in the molecular interactions in renal diseases are important to allow the design of novel strategies for treatment. Our studies provide novel insights in the role of PGs in renal inflammation in relation to innate immune derived injuries. Further research is required to bring these findings closer to application.

Heparin/heparan sulphate interactions with complement-a possible target for reduction of renal function loss?

Current management of end-stage renal failure is based on renal replacement therapy by dialysis or transplantation. Increased occurrence of renal failure in both native and transplanted kidneys indicates a need for novel therapies to stop or limit the progression of the disease. Acute kidney injury and proteinuria are major risk factors in the development of renal failure. In this regard, innate immunity plays an important role in the pathogenesis of renal diseases in both native and transplanted kidneys. The complement system is a major humoral part of innate defense. Next to the well-known complement activators, quite a number of the complement factors react with proteoglycans (PGs) both on cellular membranes and in the extracellular compartment. Therefore, these interactions might serve as targets for intervention. In this review, the current knowledge of interactions between PGs and complement is reviewed, and additionally the options for interference in the progression of renal disease are discussed

Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate.

International audienceDuring proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope than properdin. Factor H was present on the urinary side of renal tubular cells in proteinuric, but not in normal renal tissues and colocalized with properdin in proteinuric kidneys. Factor H dose-dependently bound to proximal tubular epithelial cells (PTEC) in vitro. Preincubation of factor H with exogenous heparin and pretreatment of PTECs with heparitinase abolished the binding to PTECs. Surface plasmon resonance experiments showed high affinity of factor H for heparin and HS (K(D) values of 32 and 93 nm, respectively). Using a library of HS-like polysaccharides, we showed that chain length and high sulfation density are the most important determinants for glycosaminoglycan-factor H interaction and clearly differ from properdin-heparinoid interaction. Coincubation of properdin and factor H did not hamper HS/heparin binding of one another, indicating recognition of different nonoverlapping epitopes on HS/heparin by factor H and properdin. Finally we showed that certain low anticoagulant heparinoids can inhibit properdin binding to tubular HS, with a minor effect on factor H binding to tubular HS. As a result, these heparinoids can control the alternative complement pathway. In conclusion, factor H and properdin interact with different HS epitopes of PTECs. These interactions can be manipulated with some low anticoagulant heparinoids, which can be important for preventing complement-derived tubular injury in proteinuric renal diseases

MCP-1-induced monocyte migration is increased in the presence of immobilized heparin-albumin and glycosylated collagen XVIII.

<p><i>A:</i> MCP-1 dose dependently increased the migration of monocytes over a porous membrane. Immobilization of heparin-albumin, mimicking an artificial BM HSPG, promotes monocyte transmigration. Spontaneous migration over albumin-coated membrane in the absence of MCP-1 was set as 1 and the other values were calculated accordingly. The error bars represent SEM. <i>B:</i> Transmigration of monocytes towards MCP-1 (10 ng/ml) was increased in the presence of heparin-albumin and collagen XVIII with long GAG chains. Heparin-albumin increased the monocyte migration significantly compared to albumin coated membrane (p<0.01). N-terminal fragment of short collagen XVIII with long GAG chains promoted transmigration significantly compared to albumin and N-terminal fragment without GAG chain (both p<0.05). Relative to albumin, also the full-length short collagen XVIII promoted MCP-1-induced monocyte transmigration to some extent (not significant). Data is calculated relative to migration over albumin-coated membrane towards 10 ng/ml MCP-1. The error bars represent SEM. *: p<0.05, **: p<0.01.</p

Reduced macrophage/monocyte influx after renal I/R in double mutant mice for collagen XV and XVIII.

<p><i>A:</i> Immunofluorescent staining for collagen IV, XV and XVIII (green) and macrophages (red) in WT and double mutant mice at day 5 after I/R showed presence of collagen IV, XV and XVIII in peritubular capillaries (white arrows) in WT mice and accumulation of macrophage/monocytes around these capillaries. Less macrophage influx (in red) was observed in double mutant mice, also lacking collagen XV and XVIII signal (in green). The nuclei are stained in blue. Scale bars 20 µm. <i>B:</i> Immunofluorescent staining for macrophages (red) and nuclei (blue) in WT and double mutant sham operated mice at day 5 after I/R showed no macrophage/monocyte in renal tissues. Scale bars 20 µm. <i>C:</i> Number of macrophage/monocytes per HPF (High Power Field) at different timepoints after I/R. At day 5 significantly less macrophage/monocytes were observed in kidneys of <i>Col15a1^−/−×Col18a1^−/−</i> mice compared to WT (p<0.05). Data is presented as mean ± SEM. *: p<0.05.</p

Tubular damage is reduced in double mutant mice deficient of collagen XV and XVIII compared to the WT mice.

<p><i>A–D:</i> Paraffin-embedded sections stained with periodic acid Schiff's (PAS) reagent in sham operated WT(day 1; <i>A</i>), in sham-operated <i>Col15a1^−/−×Col18a1^−/−</i> compound mutant mice (day 1; <i>B</i>) and in WT (<i>C</i>) and <i>Col15a1^−/−×Col18a1^−/−</i> compound mutant mice (<i>D</i>) at day 5 after renal I/R. WT mice showed tubular casts, tubular widening and flattening, and loss of nuclei in tubular cells (black arrows). Such damage was not observed in double collagen mutant mice kidneys. Scale bars 50 µm. <i>E:</i> Percentage of tubular damage was determined at different time points after I/R (see methods) in the <i>Col15a1^−/−</i>, <i>Col18a1^−/−</i> and <i>Col15a1^−/−×Col18a1^−/−</i> double mutant mice compared to the WT controls (*: day 5 p<0.01 double mutant mice compare to WT). Data is presented as mean percentage ± SEM.</p