Mucosal Vaccination Shapes the Expression of Salivary Antibodies and Establishment of CD8+ T‐Cells

Background: Mucosal vaccination for preventing periodontitis shows promising results. However, various administration routes and adjuvants may have a substantial role in the efficacy of the vaccination. The aim of the study is to compare different modes of mucosal vaccination with whole‐cell Porphyromonas gingivalis and to test the role of various adjuvants as potential modifiers of this process. Methods: Mucosal vaccine was administered through oral or nasal routes to BALB/C mice. The tested adjuvants included Escherichia coli cholera toxin, E. coli labile toxin (LT), and unmethylated CpG dinucleotide (CpG). Control mice were vaccinated subcutaneously. Saliva and serum were collected; anti–P. gingivalis salivary immunoglobulin A (IgA) and serum IgG were quantified. A quantitative enzyme‐linked immunosorbent assay to measure anti–P. gingivalis IgA levels was established. In addition, cells were extracted from head and neck lymph nodes, and the relative CD8⁺ cells were quantified using flow cytometry. Results: All mucosal vaccination modes induced anti–P. gingivalis salivary IgA but not anti–P. gingivalis serum IgG. Subcutaneous vaccination induced both salivary IgA and serum IgG against P. gingivalis. Mucosal vaccination also induced greater establishment of CD8⁺ cells compared to the subcutaneous vaccination. Oral mucosal vaccinations with LT or CpG were the most efficient for salivary IgA expression and CD8 cell establishment in lymph nodes. Conclusions: Oral and nasal mucosal vaccination induced a local host response with little systemic effect. The use of CpG or LT as adjuvants with the oral mucosal vaccination was the most efficient vaccination mode in the present mouse model.     

Clinical significance of isolated mega cisterna magna

Objective The prevalence and clinical significance of isolated mega cisterna magna in both fetuses and adults is not yet well defined. It is therefore difficult to provide reliable parental counseling in cases of a fetal sonographic diagnosis of this anomaly. The aim of the present study was to, determine the cognitive profile of adults with isolated mega cisterna magna. Methods We reviewed 19,301 consecutive CT/MRI of the brain. Isolated mega cisterna magna was observed in 49 cases. A battery of neuropsychological tests was performed in 18 adults with this anomaly and in 18 controls who had no brain anomaly on CT/MRI. Results Subjects with isolated mega cisterna magna had a lower performance on memory tasks [RAVLT saving score (0.8 ± 0.2 vs. 1.02 ± 0.2, P = 0.003)] and verbal fluency [phonemic fluency (9.4 ± 4.5 vs. 13.6 ± 5.3, P = 0.02), semantic fluency (19.8 ± 5.8 vs. 24.4 ± 7.5, P = 0.05)]. They did not differ from controls in regard to the Raven similarity tests indicating that this brain anomaly is not associated with impairment of general cognitive abilities. Conclusion Adults with isolated mega cisterna have an overall normal cognitive functioning but may score inferior to controls on some parameters of memory and verbal fluency. Although application of adult cases to the fetuses is not well established, this information might be of value in parental counseling in cases of a fetus with this anomaly.     

Evaluation of endothelial function in women with polycystic ovary syndrome

Objectives

Previous studies have suggested that vascular reactivity may be altered in women with polycystic ovary syndrome (PCOS). We sought to evaluate the vascular reactivity specifically the endothelial function (EF) in women with PCOS and to study the effect of metformin on their EF.

Study design

Thirty-one women diagnosed with PCOS and 33 healthy controls underwent evaluation of EF using a post-ischemia reactive hyperemia technique (Endo-PAT). EF was quantitatively determined as the ratio between the arterial pulse wave amplitude following a 5 min arterial occlusion in the forearm to the pre-occlusion value. Oral metformin 850 mg bid was administered to PCOS patients. After 3 months of treatment EF was reassessed using the same technique.

Results

The average endothelial function was 1.48 ± 0.32 in the PCOS group versus 2.00 ± 0.51 in the controls (P < 0.001). There were no significant changes in the EF among the 18 patients who were treated with metformin, EF index pre- and post-treatment was 1.42 versus 1.43, respectively.

Conclusions

Endothelial dysfunction is more likely to occur among PCOS patients than in healthy controls. These preliminary results suggest that metformin treatment for 3 months in PCOS patients does not improve endothelial function.     

Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials

The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations.     

The role of physical status versus mental status in predicting the quality of life of patients with lumbar disk herniation

Purpose: To explore the role of physical status versus mental status in predicting the quality of life (QOL) of patients with lumbar disk herniation (LDH).

Method: In this correlative study 51 patients with LDH were recruited in their conservative stage of treatment. After profiling their physical status, all participants reported about pain level (according to VAS), pain perception using the Pain Catastrophizing Scale (PCS), and disability level (according to Oswestry Low Back Pain Disability Questionnaire). Their mental status was evaluated using the Spielberger’s State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI-II). Their QOL was evaluated by the World Health Organization Quality of Life Questionnaire, brief version (WHOQOL-BREF).

Results: Physical status/disability level correlated with anxiety and depression. While Physical status predicted physical QOL, mental status, and mainly anxiety and depression were the significant predictors of psychological, social, and environmental QOL.

Conclusions: Mental status may play a significant role in reducing most QOL domains among patients with LDH. The evaluation and intervention process should consider both physical and mental status and their relation to the person's QOL. Since QOL is a major parameter in determining intervention type and success this elaborated perspective may contribute to the intervention planning and outcomes.

• Implications for rehabilitaion

• A significant mental distress may accompany the physical disability of patients with LDH.

• The role of this mental distress in reducing the QOL of patients with LDH may be greater than that of their physical disability.

• The evaluation and intervention for patients with LDH should refer to both physical and mental status and explore their impacts on quality of life in order to elevate intervention success.

     

Modeling phasic insulin release: immediate and time-dependent effects of glucose

The cellular and molecular mechanisms of insulin secretion are being intensively investigated, yet most researchers are seemingly unaware of the complexity of the dynamic regulation of the secretion. In this article, we summarize studies of the physiology of insulin secretion performed over several decades. The insulin response of perifused islets of rats, perfused rat pancreas, or that of a human, to a square-wave glucose stimulus is biphasic, a transient first-phase response of 4- to 10-min duration followed by a gradual rise in secretion rates (second-phase response). Several hypotheses have been proposed to account for the phasic nature of insulin secretion; they are briefly discussed in this review. We have favored the hypothesis that nutrient stimulators such as glucose, in addition to a primary and almost immediate secretory signal, with time induce both stimulatory and inhibitory messages in the beta-cell, and those messages modulate the primary insulinogenic signal. Indeed, studies in the rat pancreas and in humans have demonstrated that short stimulations with glucose generate a state of refractoriness of the insulin secretion, which we have termed time-dependent inhibition (TDI). Nonnutrient secretagogues such as arginine induce strong TDI independent of the duration of stimulation. Once the agent is removed, TDI persists for a considerable period. In contrast, prolonged stimulations with glucose (and other nutrients) lead to the amplification of the insulin response to subsequent stimuli; this can be demonstrated in the perfused rat pancreas, in perifused islets from several rodents, and in humans. We have termed this stimulatory signal time-dependent potentiation (TDP). The generation of TDP requires higher glucose concentrations and prolonged stimulation; the effect is retained for some time after cessation of the stimulus. Of major interest is the observation that, while the acute insulin response to glucose is severely reduced in glucose-intolerant animals and humans, TDP seems to be intact. The cellular mechanisms of TDI and TDP are poorly understood, but data reviewed here suggest that they are distinct from those that lead to the acute insulin response to stimuli. A model is proposed whereby the magnitude and kinetics of the insulin response to a given stimulus reflect the balance between TDP and TDI. Researchers studying the cellular and molecular mechanisms of insulin release are urged to take into consideration these complex and opposing factors which regulate insulin secretion.     

Domain swapping in a COOH-terminal fragment of platelet factor 4 generates potent angiogenesis inhibitors

A few peptide residues in structurally important locations often determine biological functions of proteins implicated in the regulation of angiogenesis. We have shown recently that the short COOH-terminal segment PF-4(47-70) derived from platelet factor 4 (PF-4) is the smallest sequence that conserves potent antiangiogenic activity in vitro and in vivo. Here we show that modified COOH-terminal PF-4 peptides containing the sequence ELR (or related DLR), a critical domain present in proangiogenic chemokines, surprisingly elicit several times greater antiangiogenic potential than the original peptide. The modified peptides inhibit binding of iodinated vascular endothelial growth factor and fibroblast growth factor 2 to endothelial cell receptors, endothelial cell proliferation, migration, and microvessel assembly in the rat aortic ring model at lower doses than PF-4(47-70). On the differentiated chick chorioallantoic membrane, topical application of 40 micro g of modified peptides potently reduces capillary angiogenesis induced by vascular endothelial growth factor(165), a dose where peptide PF-4(47-70) was inactive. Established intracranial glioma in nude mice decreased significantly in size when treated locally with a total dose of 250 micro g of peptide PF-4(47-70)DLR (n = 10) compared with the same dose of the original PF-4(47-70) peptide (n = 10) or controls (n = 30). Tailored PF-4 peptides represent a new class of antiangiogenic agents with a defined mode of action and a strong in vivo activity.