Alternative route for erythropoietin ocular administration

Purpose

This study aimed to find an alternative route for erythropoietin (EPO) ocular administration because of its neuroprotective and neuroregenerative known properties. Ocular penetration of EPO after subconjunctival injection was assessed, and potential side-effects on the haematocrit for a 28-day period were also evaluated.

Methods

Wistar Hannover female albino rats (n?=?42) divided into seven groups of six were used. One group (n?=?6) served as control. Six groups (n?=?36) received 1,000 UI of EPO through the subconjunctival route in one of the eyes. According to the group, animals were humanely killed at 12 h (n?=?6), 24 h (n?=?6), 36 h (n?=?6), 48 h (n?=?6), and 60 h (n?=?6), after EPO administration, in a total of 30 animals. Enucleation of both eyes was performed, and EPO protein distribution in the rat’s retina was analyzed by immunohistochemistry. Another group of animals (n?=?6) was used to collect blood samples and perform haematocrit analysis at 0, 7, 14, 21, and 28 days after unilateral EPO subconjunctival administration.

Results

The evaluation of EPO expression in the animals' retinas after subconjunctival administration yielded a strong immunostaining signal. Among the retina’s layers, EPO expression was more evident in the RGC layer 24 h after the administration, and was still present on that layer till the end of the study (60 h). When administered subconjunctivally EPO reached several neuronal cells, in all retinal layers. The subconjunctival EPO administration did not cause significant changes in the haematocrit values over a 28-day period.

Conclusion

In this study, it was demonstrated that EPO reached the retinal ganglion cell layers when administered subconjunctivally. EPO reached the retina 24 h after the subconjunctival administration, and was still present 60 h after the administration. Furthermore, it was also proved that EPO subconjunctival administration did not cause any haematopoietic significant side-effects. The subconjunctival route was shown to be a promising alternative for EPO ocular delivery.     

ORIGINAL ARTICLE: Female Genital Tract Secretions Inhibit Herpes Simplex Virus Infection: Correlation with Soluble Mucosal Immune Mediators and Impact of Hormonal Contraception

Citation Shust GF, Cho S, Kim M, Madan RP, Guzman EM, Pollack M, Epstein J, Cohen HW, Keller MJ, Herold BC. Female genital tract secretions inhibit herpes simplex virus infection: correlation with soluble mucosal immune mediators and impact of hormonal contraception. Am J Reprod Immunol 2010; 63: 110–119 Problem Female genital tract secretions inhibit herpes simplex virus (HSV) infection, however, the intra‐ and inter‐subject variability, contribution of specific mediators, and impact of reproductive hormones have not been defined. Method of study Cervicovaginal lavage (CVL) (n = 89) obtained from nine cyclers and seven women on hormonal contraception (HC), who completed between three and eight weekly visits, were examined for anti‐herpes simplex virus activity and concentrations of mediators. Results The CVL inhibited HSV infection by a mean value of approximately 57% during the follicular or luteal phase, but only by 36% in hormonal contraceptive users. Human neutrophil peptides 1–3 (HNP1‐3) (P = 0.03), IL‐8 (P = 0.003), lactoferrin (P = 0.005), lysozyme (P = 0.003), IgA (P = 0.002), and IgG (P = 0.02) correlated with antiviral activity. Intra‐subject and inter‐subject variability was observed, suggesting that factors other than hormones contribute to innate defense. Conclusion Endogenous antimicrobial activity may provide a biomarker of healthy mucosal immunity and may be reduced in the setting of HC. However, larger prospective studies are needed.     

Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam

Purpose

Benzodiazepines are the drugs of choice in the treatment of alcohol withdrawal syndrome (AWS). Recent data have shown that baclofen may reduce AWS symptoms. At present, no comparative studies between baclofen and any benzodiazepine used in AWS treatment are available. Accordingly, the present study was designed to compare efficacy, tolerability and safety of baclofen versus diazepam in the treatment of AWS.

Subjects and methods

Thirty-seven patients with AWS were enrolled in the study and randomly divided into 2 groups. Baclofen (30 mg/day for 10 consecutive days) was orally administered to 18 patients (15 males, 3 females; median age: 46.5 years). Diazepam (0.5-0.75 mg/kg/day for 6 consecutive days, tapering the dose by 25% daily from day 7 to day 10) was orally administered to 19 patients (17 men, 2 women; median age: 42.0 years). The Clinical Institute Withdrawal Assessment (CIWA-Ar) was used to evaluate physical symptoms of AWS.

Results

Both baclofen and diazepam significantly decreased CIWA-Ar score, without significant differences between the 2 treatments. When CIWA-Ar subscales for sweating, tremors, anxiety and agitation were evaluated singly, treatment with baclofen and diazepam resulted in a significant decrease in sweating, tremors and anxiety score, without significant differences between the 2 drug treatments. Both treatments decreased the agitation score, although diazepam was slightly more rapid than baclofen.

Conclusion

The efficacy of baclofen in treatment of uncomplicated AWS is comparable to that of the “gold standard” diazepam. These results suggest that baclofen may be considered as a new drug for treatment of uncomplicated AWS.     

Evaluation of classical complement pathway activation in rheumatoid arthritis: measurement of C1q-C4 complexes as novel activation products

OBJECTIVE: Novel activation products that are stable and minimally susceptible to in vitro artefacts have recently been described in the classical complement pathway. The present study assessed circulating levels of these products, i.e., covalent complexes between the recognition molecule of the classical pathway (C1q) and activated C4, in plasma samples from patients with rheumatoid arthritis (RA) to establish the relationship between these levels and the clinical and immunologic parameters in these patients. METHODS: C1q-C4 levels were measured in plasma samples from 41 patients with active RA and 43 patients with inactive RA. These levels were related to other complement activation products and to disease activity according to the Disease Activity Score in 28 joints (DAS28), using Spearman's rank correlations. RESULTS: C1q-C4 plasma levels were significantly higher in patients with active RA as compared with patients with RA in clinical remission (median 3.3 arbitrary units [AU], range 0.4-13.4 versus 1.7 AU, range 0.2-5.5; P=0.0001), suggesting that activation of the classical complement pathway reflects disease activity. This was supported by a significant correlation between C1q-C4 levels and the DAS28 (r=0.398, P=0.0002). Levels of other complement activation products, such as activated C4 (C4b/c), were also significantly elevated in patients with active disease compared with patients with inactive disease (P=0.03), and were correlated with C1q-C4 levels (r=0.329, P=0.002). Levels of C1q-C4 complexes were higher in synovial fluid samples than in plasma samples from the 4 patients tested. CONCLUSION: Systemic complement activation via the classical pathway in patients with RA correlates with disease activity. These results indicate that C1q-C4 complexes may be used as a biomarker for RA.     

Memory abilities in children with subtypes of dyscalculia

This study examines (a) mathematical skills of 2 subgroups of children with developmental dyscalculia (DD)—1 group with DD only and a second group with DD plus reading disorders (RDD)—and (b) analyzes the memory skills of both groups of children. Fifty 11- and 12-year-old children were selected from public schools in Guadalajara, Mexico. Seventeen children had DD only, 13 had RDD, and 20 were normal controls. Testing included 10 calculation and 6 memory subtests taken from the Evaluacion Neuropsicologica Infantil (Matute, Rosselli, Ardila, & Ostrosky, in press). Results indicated that children with DD and children with RDD show a similar pattern of mathematical impairment. Both subgroups had significantly lower scores than the control group in working memory tasks. In addition, the RDD group had significantly lower scores than the control group in visual learning and semantic memory. Although the RDD group scored lower than the DD group in most memory tests, this difference did not reach significance. Working memory tests (digits backwards and sentence repetition) appeared to be the best predictors of mathematical test scores and may represent a major cognitive defect in children with specific defects in mathematics.     

In Vitro Synthesis of Triglycerides and Cholesterol in Human Gallbladder Mucosa

Triglyceride and sterol synthesis was investigated in vitro in the gallbladder mucosa from control subjects and patients with acalculous cholesterolosis. The incorporation rate of ¹⁴C-acetate was 1.6 ± 0.2 nmol/g/h into cholesterol (sum of squalene, methyl sterols, and cholesterol) and 5.7 ± 0.8 nmol/g/h into triglycerides. The rates were significantly correlated with each other (r = 0.667). The conversion of ³H-mevalonate into cholesterol (49 ± 10 nmol/g/h) and triglycerides (4.7 ± 1.2 nmol/g/h) indicated a high activity in the postmevalonate cholesterol synthesis and an active shunt pathway of mevalonate metabolism. The synthesis rates of cholesterol, triglycerides, and sterol esters were closely interrelated, were unaltered in cholesterolosis, and were not correlated with the serum, biliary, and mucosal lipid concentrations. Thus, despite marked lipid accumulation the lipid synthesis proceeds effectively in the gallbladder mucosa with cholesterolosis.     

In-traffic air pollution exposure and CC16, blood coagulation, and inflammation markers in healthy adults

Background: Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic.Objectives: The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers.Methods: Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM_2.5), PM ≤ 10 µm in diameter (PM₁₀), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters.Results: We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated.Conclusions: Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.     

Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists

Introduction  

Several studies have demonstrated that perioperative hemodynamic optimization has the ability to improve postoperative outcome in high-risk surgical patients. All of these studies aimed at optimizing cardiac output and/or oxygen delivery in the perioperative period. We conducted a survey with the American Society of Anesthesiologists (ASA) and the European Society of Anaesthesiology (ESA) to assess current hemodynamic management practices in patients undergoing high-risk surgery in Europe and in the United States.