Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online‐Hemodiafiltration: A Hypothesis Generating Study

Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single‐center crossover study compared HFR and online‐hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8‐week run‐in period of high‐flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8‐week periods in the sequence: HFR/OLHDF/HFR/OLHDF. Relative to OLHDF, HFR was associated with greater indoxyl sulfate removal and lesser abnormalities in all other study variables, namely circulating interleukin‐6, tumor necrosis factor‐alpha, proportions of activated proinflammatory (CD14+CD16+, CD14++CD16+) monocytes, endothelial progenitor cells, apoptotic endothelial microparticles, vascular endothelial growth factor, vascular cellular adhesion molecule, angiopoietins 2 and 1, annexin V, and superoxide dismutase. Differences were significant (P < 0.05) in median values of 13/15 variables. Study period comparisons were generally consistent with dialysis technique comparisons, as were data from the subgroup completing all study periods (n = 9). Our investigation provides hypothesis‐generating results suggesting that compared with OLHDF, HFR improves protein‐bound toxin removal, inflammatory and endothelial status, and oxidative stress.     

Localization of the cannabinoid type‐1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus

Astroglial type‐1 cannabinoid (CB₁) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB₁ receptors. In particular, brain CB₁ receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB₁ receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB₁ receptor expression specifically in glial fibrillary acidic protein (GFAP)‐containing astrocytes (GFAP‐CB₁‐KO mice) and also generated genetic rescue mice to re‐express CB₁ receptors exclusively in astrocytes (GFAP‐CB₁‐RS). To better identify astroglial structures by immunoelectron microscopy, global CB₁ knock‐out (CB₁‐KO) mice and wild‐type (CB₁‐WT) littermates were intra‐hippocampally injected with an adeno‐associated virus expressing humanized renilla green fluorescent protein (hrGFP) under the control of human GFAP promoter to generate GFAPhrGFP‐CB₁‐KO and ‐WT mice, respectively. Furthermore, double immunogold (for CB₁) and immunoperoxidase (for GFAP or hrGFP) revealed that CB₁ receptors are present in astroglial mitochondria from different hippocampal regions of CB₁‐WT, GFAP‐CB₁‐RS and GFAPhrGFP‐CB₁‐WT mice. Only non‐specific gold particles were detected in mouse hippocampi lacking CB₁ receptors. Altogether, we demonstrated the existence of a precise molecular architecture of the CB₁ receptor in astrocytes that will have to be taken into account in evaluating the functional activity of cannabinergic signaling at the tripartite synapse.     

Rectal advancement flap for the treatment of complex cryptoglandular anal fistulas: a systematic review and meta-analysis

Purpose

Rectal advancement flap is an accepted approach for treating complex fistula-in-ano. However, a diversity of technical modifications have been described. The aim of this study was to evaluate recurrence and fecal continence rates after performing rectal advancement flaps depending upon flap thickness (full-thickness, partial-thickness, or mucosal flaps) and treatment of the fistulous tract (core-out or curettage).

Methods

Medline (PubMed, Ovid), the Cochrane Library database, and ClinicalTrials.gov were searched. Studies that involved patients with complex cryptoglandular fistulas who had been treated with rectal advancement flaps were included. The outcomes measured were recurrence and fecal continence. All of the statistical analyses were performed using Comprehensive Meta-Analysis software. A fixed model was used if there was no evidence of heterogeneity; otherwise, a random effects model was used.

Results

Twenty-six studies were included (1655 patients). The pooled rate of recurrence was 21%. Full-thickness flaps showed the best results concerning recurrence (7.4%), partial flaps revealed 19% and mucosal flaps 30.1%. Core-out and curettage had a similar recurrence (19 vs 21%). Regarding anal incontinence, the pooled rate was 13.3%. Mucosal- and partial-thickness flaps showed similar rates (9.3 vs 10.2%), while full-thickness flaps disturbed it in 20.4%. Most of these alterations were minor symptoms. Otherwise, core-out and curettage showed similar rates (14.3 vs 12%).

Conclusions

1. Full-thickness rectal advancement flaps offer better results regarding the recurrence than mucosal or partial flaps. 2. All flaps cause some incontinence, which increases with the thickness of the flap. 3. The results did not suggest differences in recurrence and incontinence between core-out and curettage.

     

Randomized, Crossover and Single-Dose Bioquivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 μg) in Healthy Female Volunteers

Despite the increase in the substitution of branded medicinal product with generic drugs, this is a controversial issue for some pharmacological groups (such as contraceptives).The aim of the present clinical trial was to assess the bioequivalence and tolerability of two oral formulations of desogestrel.Thirty-three healthy female volunteers participated in this randomized and two-way crossover study. During two separate experimental periods, with at least four weeks of washout period, women received a single oral dose of 75 μg of desogestrel from each of the formulations (test formulation and reference formulation). Desogestrel bioavailability was determined by the measurement of 3-ketodesogestrel plasma concentration.Pharmacokinetic parameters were comparable and the 90% CI for the ratio of C_max (96.14–114.53%) and AUC_0–t (105.73–123.83%) values for the test and reference formulations fell within the established regulatory interval (80–125%). Both formulations were also comparable in terms of tolerability.From the results of this study it can be concluded that test formulation (desogestrel 75 μg, Cyndea PHARMA S.L.) is bioequivalent to the reference formulation (Cerazet® 75 μg, Organon Española S.A.).     

Oral health and the symptoms of schizophrenia

The objectives of this study were to evaluate the oral health of a group of schizophrenic outpatients and a control group without psychiatric illness. The study also aimed to assess the influence of positive and negative symptomatology on oral health among outpatients with schizophrenia. The DMF-T Index (sum of decayed, missing and filled teeth) and the Community Periodontal Index of Treatment Needs (CPITN) were assessed in both groups. We evaluated the psychopathological state of the patient group using the Positive and Negative Syndrome Scale (PANSS). The schizophrenic patients had higher scores than the control group with respect to decayed teeth (4.39 vs. 0.72), missing teeth (5.66 vs. 1.50), the DMF-T index (13.51 vs. 7.8) and CPITN (2.32 vs. 1.04); and lower scores for filled teeth (3.53 vs. 5.54). The PANSS negative subscale score correlated positively with the oral health variables studied, whereas the PANSS positive subscale score correlated negatively and exclusively with the number of missing teeth. Age and smoking status affected oral health in both groups, but even when the influence of these factors was considered, the oral health of the patients was poorer than that of the control group.