Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = –0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.     

Where do college students get health information? Believability and use of health information sources

This study aims to identify predictors of use of health information sources among U.S. college students. For this purpose, the Spring 2006 American College Health Association-National College Health Assessment (ACHA-NCHA) database of 94,806 students at 117 colleges and universities was used. Univariate and multivariable analyses of survey data were conducted. The four most believable sources of health information as indicated by survey respondents were health center medical staff, health educators, faculty or coursework, and parents. Health center medical staff, health educators, and faculty or coursework were underutilized in relation to their perceived believability, whereas parents were both used and believed at high frequencies. In general, older students, females, full time students, and Black and Hispanic students were more likely to use information from one of the four health sources. However, there was considerable subgroup variability, especially in the use of parents as a health information source. The authors conclude that information on use and believability of health information sources can help colleges to design more effective health information campaigns.     

Prevalence of cryptococcosis among HIV-infected patients in Yaounde, Cameroon

Background

Cryptococcus neoformans is encapsulated yeast which causes life-threatening infections in up to 40% of AIDS patients in Africa.

Objective

To investigate the prevalence of cryptococcosis among HIV infected patients in Yaounde.

Methods

In a hospital-based surveillance study of cryptococcosis, the colonization of Cerebrospinal Fluid (CSF), urine and blood sample by C. neoformans was evaluated by direct microscopic examination and culture techniques. Data obtained were then analyzed based on the medical records of the patients.

Results

Among the105 patients sampled for the study, the CD4 counts varied between 31 and 304 lymphocytes/mm³. Direct specimens examination (n= 294) in India ink preparations revealed polysaccharide capsule in 25 (8.5%) of the samples. Upon culture, 29 (9.86 %) samples were positive of C. neoformans (23 from the CSFs and 6 from the urine). All the positive samples were obtained from patients who were not on Antiretroviral Therapy (ART). Meningo-encephalitis symptoms were observed in 13 patients with C. neoformans in CSFs.

Conclusion

This study reveals that cryptococcosis is rife in AIDS patients in Yaounde. Therefore, to minimize the death toll, we recommend that its routine check should be integrated in the management of HIV/AIDS patients.     

Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in drug delivery

Cell-derived membrane vesicles (CMVs) are endogenous carriers transporting proteins and nucleic acids between cells. They appear to play an important role in many disease processes, most notably inflammation and cancer, where their efficient functional delivery of biological cargo seems to contribute to the disease progress. CMVs encompass a variety of submicron vesicular structures that include exosomes and shedding vesicles. The lipids, proteins, mRNA and microRNA (miRNA) delivered by these vesicles change the phenotype of the receiving cells. CMVs have created excitement in the drug delivery field, because they appear to have multiple advantages over current artificial drug delivery systems. Two approaches to exploit CMVs for delivery of exogenous therapeutic cargoes in vivo are currently considered. One approach is based on engineering of natural CMVs in order to target certain cell types using CMVs loaded with therapeutic compounds. In the second approach, essential characteristics of CMVs are being used to design nano-scaled drug delivery systems. Although a number of limiting factors in the clinical translation of the exciting research findings so far exist, both approaches are promising for the development of a potentially novel generation of drug carriers based on CMVs.     

Protection Efficacy of Multivalent Egg Yolk Immunoglobulin against Eimeria tenella Infection in Chickens

Background

To control avian coccidiosis with drug-independent strategy effectively and safely, multivalent hyperimmune egg yolk immunoglobulin (IgY) was prepared and its ability to protect against Eimeria tenella infection was evaluated.

Methods

Hens were orally immunized with live oocysts of 5 species of Eimeria for six times, antibody titers in serum and yolk were monitored by indirect enzyme-linked immunosorbent assay. The specific IgY was isolated, purified and lyophilized. IgY powder was orally administrated as dietary supplement in newly hatched chicks at various dosages. Birds were orally challenged with 10000 sporulated oocysts of E. tenella at 10 days of age, weighed and killed at 8 days post challenge, and the protective effect was assessed.

Results

The averge yeid of IgY was 9.2 mg/ml yolk, the antibody titer of IgY reached to 1:163840 per mg with the purity up to 98%. Chickens fed IgY resulted in reduced mortality, increased body weight gain (BWG), reduced oocyst shedding, reduced caecal lesion score and increased anti-coccidial index. In terms of BWG and caecal lesion, IgY significantly enhanced the resistance of bird at ≥ 0.05% of IgY in the diet when compared with the challenged control group (P<0.05). No significant difference was observed at dosage ≥ 0.5% and 1.0% when BWG and caecal lesion were compared with the sodium salinomycin control group, respectively (P>0.05).

Conclusion

Supplementing newly hatched chicks with Eimeria-specific IgY represents a promising strategy to prevent avian coccidiosis.     

Pharmacological characterization of the new histamine H4 receptor agonist VUF 8430

Background and purpose:

We compare the pharmacological profiles of a new histamine H₄ receptor agonist 2-(2-guanidinoethyl)isothiourea (VUF 8430) with that of a previously described H₄ receptor agonist, 4-methylhistamine.

Experimental approach:

Radioligand binding and functional assays were performed using histamine H₄ receptors expressed in mammalian cell lines. Compounds were also evaluated ex vivo in monocyte-derived dendritic cells endogenously expressing H₄ receptors and in vivo in anaesthetized rats for gastric acid secretion activity.

Key results:

Both VUF 8430 and 4-methylhistamine were full agonists at human H₄ receptors with lower affinity at rat and mouse H₄ receptors. Both compounds induced chemotaxis of monocyte-derived dendritic cells. VUF 8430 also showed reasonable affinity and was a full agonist at the H₃ receptor. Agmatine is a metabolite of arginine, structurally related to VUF 8430, and was a H₄ receptor agonist with micromolar affinity. At histamine H₃ receptors, agmatine was a full agonist, whereas 4-methylhistamine was an agonist only at high concentrations. Both VUF 8430 and agmatine were inactive at H₁ and H₂ receptors, whereas 4-methylhistamine is as active as histamine at H₂ receptors. In vivo, VUF 8430 only caused a weak secretion of gastric acid mediated by H₂ receptors, whereas 4-methylhistamine, dimaprit, histamine and amthamine, at equimolar doses, induced 2.5- to 6-fold higher output than VUF 8430.

Conclusions and implications:

Our results suggest complementary use of 4-methylhistamine and VUF 8430 as H₄ receptor agonists. Along with H₄ receptor antagonists, both agonists can serve as useful pharmacological tools in studies of histamine H₄ receptors.     

Dual modulation of urinary bladder activity and urine flow by prostanoid EP3 receptors in the conscious rat

Background and purpose:

Cyclooxygenase inhibitors function to reduce levels of prostaglandin E₂ (PGE₂) and are broadly efficacious in models of bladder overactivity. We therefore investigated a regulation of urinary bladder function in conscious rats by modulation of the EP₃ receptor for PGE₂.

Experimental approach:

The activity of the EP₃ receptor agonist GR63799X, and EP₃ receptor antagonists, CM9 and DG041, at recombinant EP₃ receptors was evaluated in vitro. In vivo, intraduodenal dosing during conscious, continuous-filling cystometry of spontaneously hypertensive rats was utilized to determine the urodynamic effect of EP₃ receptor modulation.

Key results:

GR63799X dose-dependently (0.001–1 mg·kg⁻¹) reduced bladder capacity, as indicated by a reduction in both the micturition interval and volume of urine per void. In contrast, CM9 (10 and 30 mg·kg⁻¹) and DG041 (30 mg·kg⁻¹) enhanced bladder capacity, as indicated by significantly longer micturition intervals and larger void volumes. CM9 and DG041 inhibited the responses to GR63799X supporting the in vivo activity of these pharmacological agents at the EP₃ receptor. In addition to its effect on bladder capacity, GR63799X increased endogenous urine production. Intra-arterial infusion of saline mimicked the enhancement of urine flow observed with GR63799X, and the response was inhibited by CM9.

Conclusions and implications:

These data support the EP₃ receptor as a modulator of urinary bladder activity in the conscious rat, and in addition, indicate a role for EP₃ receptor activity in regulating urine flow.