Evaluation of mucoadhesive property and the effect of Boswellia carteri gum on intranasal vaccination against small ruminant morbillivirus infection (PPR)

ABSTRACT

A study was conducted to evaluate mucoadhesive property and immunomodulatory effect of phytogenic gums from Boswellia frereana, Boswellia carteri andCommiphora myrrha on intranasal Peste des petits ruminants (PPR) vaccination in goats and sheep in an ex-vivo and in-vivo situations. Plant gums were purified, dried and compressed into 500gm tablets. Modified shear stress measurement technique was used on freshly excised trachea and intestine tissues of goat to measure peak adhesion time. Forty eight animals (24 goats and 24 sheep) were divided into eight groups (of 3 goats and 3 sheep) and immunized intranasally with gum-vaccine combinations in two ratios (1:1, 1:2). Antibody against PPR virus was measured on day 14, 28, 42 and 56 post vaccination using H-based PPR bELISA. The peak adhesion time of the different gums was transient. PPR virus antibodies were detected in all immunized goats and sheep but not in unvaccinated control. The best percentage inhibition was recorded for Boswellia carteri-vaccine combination group at a ratio of 1:1. Administration of Boswellia carteri-PPR vaccine combination through intranasal or subcutaneous route, elicited similar antibody titre, implying that the intranasal route may be used as a non-invasive alternative delivery in PPR vaccination of small ruminants.     

The role of the macrophage in cutaneous leishmaniasis.

The investigation of the role of the macrophage in cutaneous leishmaniasis has been prompted by observations of the clinical behaviour of the infection. In contrast to the self-healing oriental sore, chronic leishmaniasis is characterized by persistent lesions and leishmania recidiva by lesions that flare up locally long after clinical healing. In both clinical types, the parasite is thought to be maintained inside the macrophages. It will be shown that the normal macrophages of mice and guinea-pigs are parasitized by L. tropica; the parasite is not killed by the macrophages but it multiplies within these cells. Incubation of the macrophages with rabbit or human anti-Leishmania sera on the other hand, leads to the attachment of specific immunoglobulins to the macrophage cell surface and consequently to the prevention of parasitization by L. tropica under the experimental conditions. The parasite appears to be immobilized at the macrophage cell surface. Normal rabbit or human sera did not interfere with parasitization. It is postulated that the parasite specifically immobilized at the cell surface might possibly be better exposed to and affected by the immune response than intracellular parasites. Furthermore, infected parasitized macrophages contribute to the immune response by processing soluble antigens from the intracellular parasites and presenting them on their surfaces, as seen by the greater affinity (higher dilution) of anti-Leishmania antibody for the cell membrane of infected macrophages than for normal macrophages.     

Regulation of epithelial cell cytokine responses by the alpha3beta1 integrin

Epithelial cells (EC) from various tissues can produce important cytokines and chemokines when stimulated by proinflammatory cytokines. These EC also receive signals from cell surface integrins, like the alpha3beta1 integrin, which is important in cell migration and wound healing of epithelial monolayers. However, little is known of the effect of integrin signals on cytokine responses by EC. Colonic Caco-2 cells treated with an anti-alpha3 integrin antibody prior to stimulation with the proinflammatory cytokine interleukin (IL)-1 yielded suppressed levels of mRNA and secreted IL-6, IL-8 and monocyte chemoattractant protein-1 as compared to cells treated with normal mouse immunoglobulin G. Lung A549 cells also showed a similar suppression of cytokine secretion. Likewise, treatment of the Caco-2 cells with the same antibody suppressed tumour necrosis factor-alpha-stimulated IL-6 secretion. Fab fragments of the anti-alpha3 integrin antibody did not induce the suppressive effect but did block the suppressive effect of the whole antibody suggesting that the effect of the antibody required cross-linking of the integrins. Finally, culture of the Caco-2 cells on laminin type 5 (the major ligand for this integrin) yielded depressed levels of IL-1-induced IL-6 secretion as compared to cells on laminin type 1. These data are the first indication that the alpha3beta1 integrin may cause a suppression of cytokine responses by EC which may be important in regulating the capacity of EC to respond during inflammation or wound healing.     

Preferential recognition of human myocardial antigens by T lymphocytes from rheumatic heart disease patients.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune sequelae of upper respiratory infections with group A streptococci (GAS). To gain a better understanding of the pathogenesis of these diseases, we examined the in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) from RHD patients to human myocardial proteins in a T-cell Western assay. A number of myocardial proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were recognized by PBMC from both patients and controls. However, PBMC from a significant percentage of RHD patients (40%) responded to a discrete band of myocardial proteins migrating with an apparent molecular mass of 50 to 54 kDa while none of the control subject PBMC responded to this protein band (P < or = 0.0001). To further investigate the link between infections with GAS and autoimmune carditis, we studied the proliferative responses of PBMC from patients and controls to myocardial proteins before and after in vitro stimulation of the cells with opsonized GAS isolated from ARF patients. Priming of PBMC with rheumatogenic GAS caused the percentage of RHD patients responding to the 50- to 54-kDa myocardial proteins to increase from 43 to 90% (P < or = 0.0284). By contrast, PBMC from control subjects failed to recognize the 50- to 54-kDa myocardial proteins even after stimulation with the opsonized streptococci (P < or = 0.0001). The assay sensitivity was increased from 40 to 90% after priming of a patient's cells with opsonized GAS, but the positive predictive value was 100% in both unprimed and primed cultures. Antibodies generated to partially purified 50- to 54-kDa myocardial proteins did not cross-react with either streptococcal homogenates, purified M protein, myosin, laminin, or vimentin, suggesting a lack of cross-reactivity at the humoral level. This study suggests that the 50- to 54-kDa myocardial proteins contain a putative antigen that is preferentially recognized by T cells from RHD patients and demonstrates that exposure to streptococcal antigens enhances the ability of patients to recognize these proteins.     

Hydatidosis in camels in Kuwait

Infection of indigenous camels, Camelus dromedarius, with hydatid cysts has been recorded for the first time in Kuwait. From February 1982 to April 1983, 293 camels slaughtered for human consumption were examined. The overall rate of infection was 39.6%: 18.5% in animals less than 6 years old, and between 40.1% and 45.2% in older animals. The infection rate in females (44.9%) was significantly higher than in males (24.7%). Females also showed higher susceptibility to infections in multiple organs (22.7%) than males (10.5%). The lung was the most predominant site infected (63.0%). Pulmonary cysts showed a higher fertility rate than hepatic cysts (71.7% vs 29.2%) and were smaller and more numerous. The high infection rate recorded for this animal is probably related to recent shifts in animal maintenance from the traditional free-grazing to the corralling system.     

Identification ofSchistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained fromS. haematobium-infected patients and sex- and agematched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples from 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84 000, 63 000, 57 000, 55 000, 40 000, 30 000, and 28 000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evok in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.     

CADASIL in Arabs: clinical and genetic findings

Background  

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs.     

Terminal deletion 6p23: a case report

We report on a girl with cleft lip and cleft palate, antimongoloid slant of the palpebral fissures, umbilical hernia, skeletal anomalies, partial syndactyly, hypertonia with increased deep tendon reflexes, psychomotor and growth retardation, and other congenital anomalies. Cytogenetic studies demonstrated a 46,XX,del(6)(qter----p23:) chromosome constitution.     

Serological evidence of dengue fever among refugees, Hargeysa, Somalia

Epidemics of a malaria-like illness affected several thousand residents of the Dam Camp, a refugee camp near Hargeysa in Somalia, during 1985, 1986, and 1987. The disease was characterized by fever, chills, sweats, headache, back and joint pains for as long as 10 days in some patients. Blood smears from acutely ill patients were negative for malaria. Of 28 acute and 10 convalescent sera tested by the indirect fluorescent antibody (IFA) and by the hemagglutination inhibition (HI) tests, all were negative for antibody to Rift Valley fever, Crimean-Congo hemorrhagic fever, Sindbis, Chikungunya, yellow fever, and Zika viruses. However, antibody reactive to dengue 2 virus was detected by the IFA test in 39% (15/38), and 11 of 29 (38%) of the same sera were antibody positive by the HI test. Also, IgG antibody reactive to dengue 2 was demonstrated in 60% (17/28) of the same sera by the enzyme immunoassay (EIA), and 14% (4/28) were positive for IgM antibody. Of ten patients for which acute and convalescent sera were available, two developed four fold or greater rises in antibody titer evidencing infection. These data suggested that dengue virus may have been the cause of the epidemic among the Dam Camp refugees.