Liver health is a key determinant of cardiovascular risk (CVR). Hepatic fibrosis is the shared common result of chronic hepatitis, irrespective of aetiology. Fibrosis profoundly distorts liver tissue architecture and perturbs hepatic physiology, dictates the course of chronic liver disease and is increasingly recognized as a CVR factor. The relative weights of pre-diabetes and hepatic fibrosis as risk factors for major adverse cardiac events (MACE) in patients with HCV remain an open issue. Sasso and Colleagues answered this research question by treating approximately half of 770 HCV positive pre-diabetic patients with direct antiviral agents (DAAs), while the rest served as historical controls. Data have shown that achieving HCV clearance with DAAs was associated with a 60% reduced risk of MACE, thereby implying that this antiviral strategy is recommended in HCV positive pre-diabetic patients, regardless of the severity of liver disease and concurrent CVR factors. This study paves the way for additional studies addressing the molecular patho-mechanisms and changes in the clinical spectrum involved in cardio-metabolic protection following HCV eradication in patients with pre-diabetes. 相似文献
Evidence of pre-operative resting state functional magnetic resonance (RS-fMRI) validation by correlating it with clinical pre-operative status in brain tumor patients is scarce. Our aim was to validate the functional relevance of RS-fMRI by investigating the association between RS-fMRI and pre-operative motor and language function performance in patients with brain tumor.
Materials and methods
Sixty-nine patients with brain tumors were prospectively recruited. Patients with tumors near precentral gyrus (n?=?49) underwent assessment for apparent (paresis) and subtle (finger tapping) deficits. Patients with left frontal tumors in the vicinity of the inferior frontal gyrus (n?=?29) underwent assessment for gross (aphasia) and mild language (phonological verbal fluency) deficits. RS-fMRI results were extracted by spatial independent component analysis (ICA).
Results
Motor group: paretic patients showed significantly (P?=?0.01) decreased BOLD signal in ipsilesional precentral gyrus when compared to contralesional one. Significantly (P?<?0.01) lower BOLD signal was also observed in ipsilesional precentral gyrus of paretics when compared with the non-paretics. In asymptomatic patients, a strong positive correlation (r?=?0.68, P?<?0.01) between ipsilesional motor cortex BOLD signal and contralesional finger tapping performance was observed. Language group: patients with aphasia showed significantly (P?=?0.01) decreased RS-fMRI BOLD signal in left BA 44 when compared with non- aphasics. In asymptomatic patients, a strong positive correlation (r?=?0.72, P?<?0.01) between BA 44 BOLD signal and phonological fluency performance was observed.
Conclusions
Our results showed that RS-fMRI BOLD signal of motor and language networks were significantly affected by the tumors implying the usefulness of the method for assessment of the underlying functions in brain tumors patients. 相似文献
Introduction: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system.
Areas covered: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms.
Expert opinion: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure–activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production. 相似文献
Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe3O4 nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day–1 (compared to 0.58 ± 0.02 day–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy. 相似文献
The Hoffmann (H) reflex is elicited by electrical stimulation of a mixed nerve and is used to measure the excitability of the spindle-motoneuron synapse. Recent investigations have indicated a positive correlation between increases in bite force and H-reflex facilitation. However, these investigations did not examine the H-reflex in detail or the possible role of periodontal mechanoreceptors (PMRs) in this facilitation. The current investigation was performed to determine whether PMRs play a role in H-reflex facilitation during tooth clench (TC). The H-reflex was elicited in the soleus muscle of human subjects while bite level was maintained at rest (0 N), 40 N, 80 N and maximal TC. The front teeth that contributed to the (40 N and 80 N) bite force were then locally anaesthetised (LA), and the protocol was repeated. The current data suggest that the effect of TC on the H-reflex amplitude in the human limb muscles is variable from one subject to the next. Statistical analysis has shown that the H-reflex was significantly smaller during the rest condition than during the 80 N bite (p<0.05) in both non-LA and LA conditions. Since LA did not alter the response, our results do not support that the PMRs play a major role in the facilitation of distal muscle activity. 相似文献
Abstract Experiments were done to learn whether or not the blastogenic responsiveness of peripheral blood mononuclear cells (PBM) from 34 patients to mitogens and homogenates of a panel of periodontal bacteria differs significantly from that of cells from 16 normal individuals. Groups of control individuals and patients with juvenile (JP), rapidly progressive (RP) and adult periodontitis (AP) were formed. Blastogenic responsiveness was assessed after 72 and 120 h incubation by measuring the uptake of radioactive precursor into DNA. Bacterial preparations and mitogens used as stimulators included Bacteroides melaninogemcus (BMEL), Capnocytophaga (CAPNO), Fusobacterium nucleatum (FUSO), Actinomyces viscosus (AVIS), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). When the data were calculated as Stimulation Index (E/C), responsiveness of cells from patients with AP and JP was enhanced relative to that of cells from normal control subjects, but the enhancement was not statistically significant. In contrast, responsiveness of cells from RP patients to FUSO and AVIS was significantly suppressed. Except in the case of AP cells activated with PHA, mitogenic responsiveness of all patient cells was significantly suppressed. When responsiveness was calculated as E minus C, these differences between patient and control cells disappeared except for suppression of the level of blastogenesis by AP and RP cells exposed to AVIS. After 120 h incubation, unstimulated cultures of AP cells incorporated significantly less, and RP cells significantly more, radioactivity than did unstimulated cultures from normal individuals indicating an abnormal autologous mixed lymphocyte reaction. Cells were harvested and tested from a group of AP patients before, during and following periodontal therapy. PBM responsiveness to horaogenates of CAPNO did not change significantly during therapy, but responsiveness to all of the other bacterial preparations including autologous plaque increased following initial therapy. Values for AVIS, FUSO, and PLAQ were statistically significant. Responsiveness to the bacterial preparations either remained at the enhanced levels or increased to even greater levels following completion of therapy, except in the case of autologous plaque, where the values had begun to return toward pretreatment levels. In addition, responsiveness to PWM and PHA dropped to about one-half the pretreatment values and responsiveness of unstimtilated cultures increased significantly to levels observed in cultures of ceils from normal donors. 相似文献
The objective of this study was to determine the effects of induced periapical abscesses on pregnant rats.
Design
In 1/2 of the animals (n = 16), the pulps of the maxillary right molars were exposed to the oral environment, which resulted in a periapical abscess. The other 1/2 (n = 16) were sham-operated. 1/2 of the animals of both groups became pregnant 2 weeks later. The pregnancy duration, and weight and number of pups were assessed at delivery. Serum, liver and uterine horn samples were taken from all animals at euthanasia and serum IL-6, endothelin-1, TNF-α, IL-10, cortisol and insulin were determined by ELISA. Liver concentrations of IL-6, CRP and IL-6 and uterine horn concentrations of IL-6, vascular endothelial growth factor (VEGF), TNF-α, IL-10 and IL-1-β were assessed by ELISA. Blood glucose concentrations were determined using a glucometer. Outcome variables were compared by factorial ANOVA, a post hoc Tukey test, and Pearson’s correlation test.
Results
Pregnant rats with periapical abscesses had a significantly longer pregnancy and delivered pups with a significantly higher birthweight (p < 0.05). They had significantly higher concentrations of IL-6, VEGF, IL-1-β, and IL-10 within the uterine horn and IL-6, CRP and TNF-α within the liver (p < 0.01). Blood glucose and serum TNF-α, IL-6, endothelin-1, IL-10, and insulin concentrations were significantly higher in the pregnant animals with pulpal abscesses (p < 0.01).
Conclusion
The significant increase in serum TNF-α, taken together with significant increases in blood glucose and serum insulin concentrations, suggest that animals with induced periapical abscesses developed insulin resistance, which significantly affected their pregnancy outcomes. 相似文献
BACKGROUND, AIMS: The aim of this study was to evaluate antibody responses against Porphyromonas gingivalis (P. gingivalis) infection in early-onset periodontitis (EOP) patients to elucidate further the host-parasite interactions in the pathogenesis of EOP. METHOD: 16 P. gingivalis-infected EOP and 20 adult periodontitis (AP) patients, and 18 periodontally healthy subjects (HS) participated in this study. Serum immunoglobulin G (IgG) antibody levels and avidities against extracted P. gingivalis whole cells were measured. The components of P. gingivalis outer membrane antigens (OMA) reacting to patients' sera were analysed from the molecular weights by Western blotting. Serum antibody levels against P. gingivalis lipopolysaccharide (LPS) were also measured. The ability of the patients' sera to block interleukin-1beta (IL-1beta) production by human mononuclear cells in response to P. gingivalis LPS was examined. RESULTS: Antibody levels were positively correlated with antibody avidities in both EOP and AP patients (r=0.91, r=0.72, p<0.0005, respectively), while not significantly so in HS (r=0.09). There was variability in the antigen recognition of P. gingivalis OMA in EOP and AP patients. Smear and 53-kDa protein were more frequently recognized by sera of EOP and AP patients rather than that of HS (p<0.05). The smear was partly diminished by absorption with P. gingivalis LPS, indicating the smear antigen was partly composed of LPS. There was high correlation between antibody levels against P. gingivalis whole-cell extracts and LPS in EOP and AP patients (r=0.81, p=0.0002, r=0.87, p<0.0001, respectively), while not significant in HS (r=0.22). The sera of EOP and AP patients with high IgG titre to P. gingivalis LPS blocked IL-1beta production more effectively than that of the patients with low IgG titre to P. gingivalis LPS. CONCLUSIONS: These results indicate that EOP patients' antibody response against P. gingivalis infection does not differ significantly from that of AP patients. The person-to-person heterogeneous antibody production against P. gingivalis LPS could contribute to our understanding of the relationship between the defensive ability of EOP patients and their chronic infection with this pathogen. 相似文献