Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in ...destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the 'protease web' is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules-such as cytokines, chemokines, and growth factors, among others-regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation.
Background:
In recurrent urinary tract infections (UTIs) usual prophylactic antibiotic regimes do not change the long-term risk of recurrence. Our aim was to evaluate the efficacy of D-mannose in the ...treatment and prophylaxis of recurrent UTIs.
Methods:
In this randomized cross-over trial female patients were eligible for the study if they had an acute symptomatic UTI and three or more recurrent UTIs during the preceding 12 months. Suitable patients were randomly assigned to antibiotic treatment with trimethoprim/sulfamethoxazole or to a regimen of oral D-mannose 1 g 3 times a day, every 8 hours for 2 weeks, and subsequently 1 g twice a day for 22 weeks. They received the other intervention in the second phase of the study, with no further antibiotic prophylaxis. The primary endpoint was evaluation of the elapsed time to recurrence; secondary endpoints were evaluation of bladder pain (VASp) and urinary urgency (VASu).
Results:
The results for quantitative variables were expressed as mean values and SD as they were all normally distributed (Shapiro–Wilk test). In total, 60 patients aged between 22 and 54 years (mean 42 years) were included. Mean time to UTI recurrence was 52.7 days with antibiotic treatment, and 200 days with oral D-mannose (p < 0.0001).
Conclusions:
Mean VASp, VASu score, and average numbers of 24-hour voidings decreased significantly. D-mannose appeared to be a safe and effective treatment for recurrent UTIs in adult women. A significant difference was observed in the proportion of women remaining infection free versus antibiotic treatment.
During the last decades, an increasing number of predators were found to use specific prey pheromones as chemical cues. Beyond its ecological relevance, this knowledge has practical applications on ...insect conservation and pest control. In this study, we present first evidence that two species of the family Dasytidae (Coleoptera) Aplocnemus brevis Rosenhauer and A. raymondi Sainte-Claire Deville use the sex pheromone of the pine bast scale Matsucoccus feytaudi Ducasse (Hemiptera: Matsucoccidae) as kairomone to locate this prey. The feeding habits and biology of Aplocnemus species are practically unknown. In the laboratory, the adults of Aplocnemus sp. accepted M. feytaudi egg masses as food source as well as other diets. Females represented more than 90% of Aplocnemus sp. attracted to the pheromone lures. We believe that females use this olfactory cue to locate suitable places for oviposition and that larvae are the predators of Matsucoccus. This study further demonstrates that the response to the kairomone elicited short prey searching times, about 23% of the individuals appeared less than 12 min after lure exposure, being consistent with the hypothesis of prey specialization. Habitat and geographical distribution predict an ancestral association of A. brevis with M. feytaudi and of A. raymondi with M. pini. Nevertheless, a recent prey shift of A. raymondi to the invasive M. feytaudi in Corsica is in progress.
This paper presents a novel mathematical model for the transmission network expansion planning problem. Main idea is to consider phase-shifter (PS) transformers as a new element of the transmission ...system expansion together with other traditional components such as transmission lines and conventional transformers. In this way, PS are added in order to redistribute active power flows in the system and, consequently, to diminish the total investment costs due to new transmission lines. Proposed mathematical model presents the structure of a mixed-integer nonlinear programming (MINLP) problem and is based on the standard DC model. In this paper, there is also applied a specialized genetic algorithm aimed at optimizing the allocation of candidate components in the network. Results obtained from computational simulations carried out with IEEE-24 bus system show an outstanding performance of the proposed methodology and model, indicating the technical viability of using these nonconventional devices during the planning process.
Cisplatin is an antineoplastic agent widely used, and no effective treatments capable of preventing cisplatin-induced ototoxicity and neurotoxicity in humans have yet been identified. This study ...evaluated the effect of the anti-inflammatory annexin A1 (AnxA1)-derived peptide Ac2–26 in a cisplatin-induced ototoxicity model. Wistar rats received intraperitoneal injections of cisplatin (10 mg/kg/day) for 3 days to induce hearing loss, and Ac2–26 (1 mg/kg) was administered 15 min before cisplatin administration. Control animals received an equal volume of saline. Hearing thresholds were measured by distortion product otoacoustic emissions (DPOAE) before and after treatments. Pharmacological treatment with Ac2–26 protected against cisplatin-induced hearing loss, as evidenced by DPOAE results showing similar signal–noise ratios between the control and Ac2–26-treated groups. These otoprotective effects of Ac2–26 were associated with an increased number of ganglion neurons compared with the untreated cisplatin group. Additionally, Ac2–26 treatment produced reduced immunoreactivity on cleaved caspase 3 and phosphorylated ERK levels in the ganglion neurons, compared to the untreated group, supporting the neuroprotective effects of the Ac2–26. Our results suggest that Ac2–26 has a substantial otoprotective effect in this cisplatin-induced ototoxicity model mediated by neuroprotection and the regulation of the ERK pathway.
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•Administration of cisplatin in rats resulted in significant distortion product otoacoustic emissions (DPOAE) decrease.•Ac2–26 protects against cisplatin-induced-hearing loss showed by 100% retention of the DPOAE in the 3–8 kHz frequencies.•Ac2–26 treatment decreases neuronal loss in the inner ear ganglions after cisplatin administration.•Neuroprotective effect of Ac2–26 is associated with downregulation of ERK activation in neurons.
Background The American College of Cardiology's Guidelines Applied in Practice (GAP) initiative for acute myocardial infarction (AMI) has been shown to increase the use of guideline-based therapies ...and improve outcomes in patients with AMI. It is unknown whether hospitals that are more successful in using the standard discharge contract—a key component of GAP that emphasizes guideline-based medications, lifestyle modification, and follow-up planning—experience a proportionally greater improvement in patient outcomes. Methods Medicare patients treated for AMI in all 33 participating GAP hospitals in Michigan were enrolled. We aggregated the hospitals into 3 tertiles based on the rates of discharge contract use: 0% to 8.4% (tertile 1), >8.4% to 38.0% (tertile 2), and >38.0% to 61.1% (tertile 3). We analyzed 1-year follow-up mortality both pre- and post-GAP and compared the mortality decline post-GAP with discharge contract use according to tertile. Results There were 1368 patients in the baseline (pre-GAP) cohort and 1489 patients in the post-GAP cohort. After GAP implementation, mortality at 1 year decreased by 1.2% ( P = .71), 1.2% ( P = .68), and 6.0% ( P = .03) for tertiles 1, 2, and 3, respectively. After multivariate adjustment, discharge contract use was significantly associated with decreased 1-year mortality in tertile 2 (odds ratio 0.43, 95% CI 0.22-0.84) and tertile 3 (odds ratio 0.45, 95% CI 0.27-0.75). Conclusions Increased hospital utilization of the standard discharge contract as part of the GAP program is associated with decreased 1-year mortality in Medicare patient populations with AMI. Hospital efforts to promote adherence to guideline-based care tools such as the discharge contract used in GAP may result in mortality reductions for their patient populations at 1 year.
Background Nailfold capillaroscopy (NC) can predict progression to systemic sclerosis (SSc) in patients diagnosed with primary Raynaud's phenomenon (RP). The occurrence of puffy fingers (PuFi) in ...patients with RP and positive antinuclear antibodies (ANA) has been associated to NC SSc-like lesions. The coexistence of these three factors has been recently proposed as criterium for very early SSc diagnosis. Objectives In this study we have explored the NC features in patients with PuFi in a 1-year NC registry from our unit. Methods Data were retrospectively collected from clinical records and from systematized NC evaluation sheets, which include a semiquantitative scoring, classification into established patterns of lesions, and description of coincidental macroscopic alterations. Data are shown as incidence rates. Statistical analysis was done with Chi-Square, Fisher's test and multivariate analysis. Results 136 cases were included in the analysis. NC was considered pathologic in 73 cases (54% of the cohort, rising to 60% in RP+ patients, p 0.036). PuFi were present in 20% of all patients. A higher incidence of pathologic NC studies was observed in the PuFi+ group (78%, p 0.002). NC lesions in this subgroup of patients were classified as SSc-like (13 p), non-SSc CTD-like (7 p), and non-immmune vasculopathy (2 p). There was coexistence with RP in 20 PuFi+ cases, but it did not increase either the risk of having a pathologic NC study (81% in double positive patients vs 83% in PuFi+ without RP) or the appearance of a SSc-like NC pattern in the subgroup. The occurrence of PuFi showed a strong association with + ANA (77% vs 54% in PuFi- patients, p 0.029). Moreover, the presence of both traits strongly predicted NC alterations, which appeared in 0.9% of double negative cases, 73% of ANA+ patients alone, and 90% of double positive cases. Patients with PuFi were diagnosed with primary RP (3 p), SSc (11 p), mixed connective tissue disease (CTD) (1 p), dermato/polymiositis (4 p), and non-classifiable CTD (6 p), while no PuFi+ cases were found in primary Sjögren's syndrome, lupus, rheumatoid arthritis, vasculitis, or antiphospholipid syndrome. No specific microscopic features were associated to PuFi. Conclusions In summary, in this cohort we have observed a high incidence of NC alterations in association with PuFi. Our findings support the relevance of PuFi as a CTD-associated trait, as recently underscored by the new EUSTAR proposed criteria for SSc classification. In addition, the appearance of ANA together with PuFi in our patients strongly predicted NC lesions, even in the absence of RP. Also of interest, PuFi were not exclusive of a SSc-like pattern of NC lesions. We suggest that NC should be performed in any patients presenting with a CTD-like scenario and swollen hands or PuFi, even in the absence of RP, because findings are likely to help characterize their syndrome. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3024
Brown spider (Loxosceles genus) venom causes necrotic lesions often accompanied by fever, hemolysis, thrombocytopenia, and acute renal failure. Using mice exposed to Loxosceles intermedia venom, we ...aimed to show whether the venom directly induces renal damage. The experimental groups were composed of 50 mice as controls and 50 mice that received the venom. Light microscopic analysis of renal biopsy specimens showed alterations including hyalinization of proximal and distal tubules, erythrocytes in Bowman's space, glomerular collapse, tubule epithelial cell blebs and vacuoles, interstitial edema, and deposition of eosinophilic material in the tubule lumen. Electron microscopic findings indicated changes including glomerular epithelial and endothelial cell cytotoxicity as well as disorders of the basement membrane. Tubule alterations include epithelial cell cytotoxicity with cytoplasmic membrane blebs, mitochondrial changes, increase in smooth endoplasmic reticulum, presence of autophagosomes, and deposits of amorphous material in the tubules. We also found that the venom caused azotemia with elevation of blood urea levels but did not decrease C3 complement concentration or cause hemolysis in vivo. Confocal microscopy with antibodies against venom proteins showed direct binding of toxins to renal structures, confirmed by competition assays. Double-staining immunofluorescence reactions with antibodies against type IV collagen or laminin, antibodies to venom toxins, and fluorescent cytochemistry with DAPI revealed deposition of toxins in glomerular and tubule epithelial cells and in renal basement membranes. Two-dimensional electrophoresis showed venom rich in low molecular mass and cationic toxins. By immunoblotting with antibodies to venom toxins on renal extracts from venom-treated mice, we detected a renal binding toxin at 30 kD. The data provide experimental evidence that L. intermedia venom is directly involved in nephrotoxicity.
We present two cases of
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in returning travelers from Central America successfully treated with miltefosine. The couple presented with ulcerative skin lesions nonresponsive to antibiotics. Skin ...biopsy with polymerase chain reaction (PCR) revealed
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To prevent the development of mucosal disease and avoid the inconvenience of parental therapy, we treated both patients with oral miltefosine. We suggest that miltefosine represents an important therapeutic alternative in the treatment of cutaneous lesions caused by
and in preventing mucosal involvement.
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