A transmission electron microscopical study of the tegument of Maritrema feliui (Digenea: Microphallidae)

The tegument of the microphallid digenean Maritrema feliui, examined by means of TEM, is described as a syncytial epithelium organised into two layers. The outer layer is an external anucleate, cytoplasmic region connected to a second region composed of nucleate perikarya (cytons) deeply embedded in the surrounding cortical parenchyma. The surface layer of the tegument is covered by a plasma membrane with many deep invaginations, which are apparently pinocytotic. This layer also bears numerous large, electron-dense spines of two types, which are intracellular and attached to the basal plasma membrane. Its cytoplasm is rich in free ribosomes, contains numerous mitochondria, disc-shaped granules frequently arranged in a rouleau, and several large, moderately electron-dense, membranous bodies. The subtegumentary perikarya and their nuclei, which are both flattened, are described in detail, as are their connections with the surface tegument. These perikarya appear to be the source of the disc-shaped granules and some of the other inclusions present in the surface layer. The main characteristics of the tegumental structure of M. feliui are commented upon in relation to the findings of previous publications and their suggested functions.     

Block of transmitter release by botulinum C1 action on syntaxin at the squid giant synapse

Electrophysiological, morphological, and biochemical approaches were combined to study the effect of the presynaptic injection of the light chain of botulinum toxin C1 into the squid giant synapse. Presynaptic injection was accompanied by synaptic block that occurred progressively as the toxin filled the presynaptic terminal. Neither the presynaptic action potential nor the Ca²⁺ currents in the presynaptic terminal were affected by the toxin. Biochemical analysis of syntaxin moiety in squid indicates that the light chain of botulinum toxin C1 lyses syntaxin in vitro, suggesting that this was the mechanism responsible for synaptic block. Ultrastructure of the injected synapses demonstrates an enormous increase in the number of presynaptic vesicles, suggesting that the release rather than the docking of vesicles is affected by biochemical lysing of the syntaxin molecule.     

Lymphocytotoxic antibodies in primary biliary cirrhosis

Sera of 30 patients with primary biliary cirrhosis (PBC) and 72 normal subjects matched for age and sex were examined for the presence of lymphocytotoxic antibodies (LCAs) against B and T cells at 4° C and 37° C. Patients were prospectively screened for: Sjögren's syndrome, scleroderma, Hashimoto's thyroiditis, and rheumatoid arthritis, in which LCAs have been described. Seventeen patients with PBC (56.6%) had LCAs against B cells as compared with only 11 of the 72 normal subjects (P<0.001). Five PBC patients (16.6%) also reacted against T cells as compared with none in control group (P<0.01). Clinical and biochemical features and the histological stage of PBC were similar in patients with and without LCA. Sjögren's syndrome was present in 13 patients—two with scleroderma and another with Hashimoto's thyroiditis. No patient had rheumatoid arthritis. The prevalence of LCAs was similar in PBC patients with or without autoimmune associated disease (54% vs 59%). We conclude that in PBC a high incidence of LCA is unrelated to the presence of an associated disease. LCA in PBC might be a nonspecific marker of an immune disorder.     

Low doses of insulin-like growth factor-I induce mitochondrial protection in aging rats

Serum IGF-I levels decline with age. We have recently reported that in aging rats the exogenous administration of IGF-I restores IGF-I circulating levels and age related-changes, improving glucose and lipid metabolisms, increasing testosterone levels and serum total antioxidant capability, and reducing oxidative damage in the brain and liver associated with a normalization of antioxidant enzyme activities. Understanding that mitochondria are one of the most important cellular targets of IGF-I, the aims of this study were to characterize mitochondrial dysfunction and study the effect of IGF-I therapy on mitochondria, leading to cellular protection in the following experimental groups: young controls, untreated old rats, and aging rats treated with IGF-I. Compared with young controls, untreated aging rats showed an increase of oxidative damage in isolated mitochondria with a mitochondrial dysfunction characterized by: depletion of membrane potential with increased proton leak rates and intramitochondrial free radical production, and a significant reduction of ATPase and complex IV activities. In addition, mitochondrial respiration from untreated aging rats was atractyloside insensitive, suggesting that the adenine nucleotide translocator was uncoupled. The adenine nucleotide translocator has been shown to be one of the most sensitive locations for pore opening. Accordingly, untreated aging rats showed a significant overexpression of the active fragment of caspases 3 and 9. IGF-I therapy corrected these parameters of mitochondrial dysfunction and reduced caspase activation. In conclusion, these results show that the cytoprotective effect of IGF-I is closely related to a mitochondrial protection, leading to reduce free radical production, oxidative damage, and apoptosis, and to increased ATP production.     

Differential Roles of Antimicrobials in the Acquisition of Drug Resistance through Activation of the SOS Response in Acinetobacter baumannii

The effect of antimicrobials on SOS-mediated mutagenesis induction depends on the bacterial species and the antimicrobial group. In this work, we studied the effect of different families of antimicrobial agents used in clinical therapy against Acinetobacter baumannii in the induction of mutagenesis in this multiresistant Gram-negative pathogen. The data showed that ciprofloxacin and tetracycline induce SOS-mediated mutagenesis, whereas colistin and meropenem, which are extensively used in clinical therapy, do not.     

Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles.     

Prophylaxis with Teicoplanin and Cefuroxime Reduces the Rate of Prosthetic Joint Infection after Primary Arthroplasty

The aim of this study was to compare the prosthetic joint infection (PJI) rate after total joint arthroplasty in two consecutive periods of treatment with different antibiotic prophylaxes: cefuroxime versus cefuroxime plus teicoplanin. We retrospectively reviewed 1,896 patients who underwent total hip arthroplasty or total knee arthroplasty between March 2010 and February 2013. From March 2010 to August 2011, patients received 1.5 g of cefuroxime during induction of anesthesia and another 1.5 g 2 h later (the C group). From September 2011, 800 mg of teicoplanin was added to cefuroxime (the CT group). Throughout the period studied, there were no variations in pre- or postoperative protocols. Univariate and multivariate analyses were performed to evaluate independent predictors of PJI. There were 995 (55.7%) patients in the C group and 791 (44.3%) in the CT group. Patients in the CT group had a significantly lower PJI rate than patients in the C group (1.26% versus 3.51%, P = 0.002). There were no infections due to Staphylococcus aureus in the CT group (0% versus 1.6% in the C group, P < 0.001). A stepwise forward Cox regression model identified male sex (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.09 to 7.18), a body mass index of ≥35 kg/m² (HR, 2.93; 95% CI, 1.37 to 6.27), the presence of lung disease (HR, 2.46; 95% CI, 1.17 to 5.15), and red blood cell transfusion (HR, 3.70; 95% CI, 1.89 to 7.23) to be independent variables associated with a higher risk of PJI. The addition of teicoplanin was associated with a lower risk of infection (HR, 0.35; 95% CI, 0.17 to 0.74). In conclusion, the addition of teicoplanin to cefuroxime during primary arthroplasty was associated with a significant reduction in the global PJI rate due to a reduction of infections caused by Gram-positive bacteria.     

Mitochondrial respiratory chain in brain homogenates: activities in different brain areas in patients with Alzheimer's disease

BACKGROUND AND AIMS: The potential influence of impaired oxidative metabolism in the modulation of manifestations in sporadic Alzheimer's disease (AD) has attracted much attention in the last 50 years. Unfortunately, many clinical and experimental results aiming at proving this hypothesis are still controversial. The aim was to study the enzymatic activities of respiratory chain (RC) complexes I through V in three brain areas of a group of patients with definite AD, and to compare the results with a group of normal brains. We simultaneously assessed the lipid peroxidation of the samples as a measure of free radical damage. METHODS: The specific activity of the individual complexes of the RC was measured spectrophotometrically, and the loss of cis-parinaric acid fluorescence was used to determine the chemical process of lipid peroxidation. RESULTS: We were not able to detect differences in any of the analyzed RC enzymatic activities, or in the level of lipid peroxidation between patients with AD and controls. Instead, differences were found in the number of mitochondria and in the intrinsic enzymatic activities of complexes III and IV in various brain areas. CONCLUSIONS: Spectrophotometric enzymatic analyses of respiratory complexes in brain homogenates do not support the primary contribution of mitochondrial RC dysfunction in the pathogenesis of AD.