Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardioprotective actions of two bioflavonoids , quercetin and rutin , in experimental myocardial infarction in both normal and streptozotocin-induced type I diabetic rats

Objectives Revascularization therapy is the mainstay of treatment in the management of myocardial infarction in normal and diabetic patients. We attempted to evaluate the cardioprotective actions of quercetin and rutin in ischaemia–reperfusion-inducedmyocardial infarction in both normal and diabetic rats. Methods Myocardial infarct size was measured using the staining agent 2,3,5triphenyltetrazoliumchloride. Serum and tissue malondialdehyde levels, superoxide dismutase and catalase in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Key findings Results demonstrated the larger infarct size, enhanced lipid peroxidation, partial depletion of antioxidant enzymes and drastic drop in heart rate in diabetic hearts subjected to in-vivo ischaemia–reperfusion in comparison to normal rats subjected to ischaemia–reperfusion. Furthermore, quercetin and rutin significantly limit the infarct size in both normal and diabetic animals in a similar fashion. However, rutin offered complete cardioprotection at a dose of 10 mg/kg in terms of limiting infarct size. Both flavonoids could partially but significantly attenuate the lipid peroxidation. In addition, treatment has shown moderate improvement in heart rate in both normal and diabetic rats. Conclusions Our data suggest the possible cardioprotective effects of quercetin and rutin in ischaemia–reperfusion injury in both normal and diabetic rats, and that protectionmight be in part due to the attenuation of oxidative stress andmoderate increment in antioxidant reserves.
Geranylgeranylacetone preconditioning may attenuate heat‐induced inflammation and multiorgan dysfunction in rats

Objectives Geranylgeranylacetone, an acyclic isoprenoid, is a non‐toxic inducer of heat shock protein (HSP)70. HSP70 overproduction is associated with heat tolerance in rats. This study aimed to investigate whether geranylgeranylacetone preconditioning of rats reduced heat‐induced inflammation and multiple organ dysfunction.
Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL‐C). For ~50 years, HDL‐C has been considered as the atheroprotective ‘good’ cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL‐C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL‐C levels. Based on these data, the significance of HDL‐C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL‐C functionality, rather than HDL‐C concentration, is important for the CVD‐preventive qualities of HDL‐C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL‐C. Our survey indicates that HDL‐C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of anti‐inflammatory drugs to either prevent HDL‐C clearance or improve the function and production of HDL‐C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL‐C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD.
Neuroleptic discontinuation in the very stable schizophrenic patient: Relapse rates and serum neuroleptic levels

This double‐blind, placebo‐controlled study investigated the effect of discontinuation of maintenance neuroleptic medication in chronic, long‐stay schizophrenic patients who had been clinically stable for over 5 years. After 12 months, 75 per cent of the patients on placebo had relapsed as compared to 33 per cent on active medication and relapses in the placebo group occurred significantly earlier during the study; survival analysis revealed the differences to be statistically significant. No clear predictors of relapse could be identified, although patients who relapsed from either group were more likely to have had higher scores for anxiety symptoms and a lower serum prolactin level at baseline. It was concluded that even in older patients who have been chronically ill with prominent negative symptoms and living in a relatively undemanding environment on stable doses of neuroleptics, the risk of relapse remains unacceptably high after abrupt withdrawal of maintenance neuroleptic therapy.
Effects of ranolazine in a model of doxorubicin‐induced left ventricle diastolic dysfunction

Doxorubicin is a highly effective anticancer drug, but its clinical application is hampered by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of doxorubicin cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent later development of cardiotoxicity is warranted. Increased doxorubicin‐dependent ROS may explain, in part, Ca2+ and Na+ overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine, a selective blocker of late Na+ current, immediately after completing doxorubicin therapy, could affect diastolic dysfunction and interfere with the progression of functional decline.
D‐512, a novel dopamine D2/3 receptor agonist, demonstrates greater anti‐Parkinsonian efficacy than ropinirole in Parkinsonian rats

Symptoms of Parkinson's disease are commonly managed using selective dopamine D2/3 receptor agonists, including ropinirole. While D2/3 agonists are useful in early‐stage Parkinson's disease, they tend to lose efficacy in later disease stages and do not appear to modify disease progression. We have recently developed a novel ‘multifunctional’ compound, D‐512: a high‐affinity D2/3 receptor agonist with antioxidant and other neuroprotective properties that may limit Parkinson's disease progression. This study sought to compare the anti‐Parkinsonian properties of the clinically used compound, ropinirole, with those of the novel compound, D‐512.
Helicobacter pylori‐eradication therapy decreases the level of neutrophil‐derived oxidants in the ulcerous mucosa of the human stomach: Relationship between ulcer stage and mucosal oxidant level

Background: The purpose of the present study was to determine the effect of Helicobacter pylori eradication on the intensity of inflammation in the ulcerous mucosa by measuring the level of neutrophil‐associated oxidants and to understand the role of mucosal inflammation in ulcer relapse from the viewpoints of the scarring stage and the H. pylori‐infection status. The level of inflammation in the gastric mucosa after the eradication of H. pylori was examined using biopsy samples obtained from patients with gastric ulcers.
Metabolic profiling of murine plasma reveals eicosapentaenoic acid metabolites protecting against endothelial activation and atherosclerosis

Atherosclerosis results from a maladaptive inflammatory response initiated by the intramural retention of LDL in susceptible areas of the arterial vasculature. The ω‐3 polyunsaturated fatty acids (ω‐3) have protective effects in atherosclerosis; however, their molecular mechanism is still largely unknown. The present study used a metabolomic approach to reveal the atheroprotective metabolites of ω‐3 and investigate the underlying mechanisms.
Early intervention services

Early intervention services aim to provide effective and evidence-based care early in the course of psychotic disorder. The impetus for the development of such services has arisen from the recognition that generic mental health services do not always meet the needs of this patient group. In addition, research evidence suggests that delays in initiating effective treatment may lead to poorer outcomes. Several international efforts are under way in service development and in research programmes to evaluate effectiveness of service models. Early intervention encompasses several different strategies, including intervention in pre-psychotic and prodromal interventions to prevent transition to psychosis; community detection of untreated psychosis; and programmes to facilitate and consolidate recovery in established cases of psychosis. The evidence for such interventions is currently limited but several trials are already under way. This contribution discusses the components of early intervention and constituents of an early intervention programme, summarizes available evidence from services around the world, suggests some service models for early intervention, and recommends areas for future research.
Rubiarbonone C inhibits platelet‐derived growth factor‐induced proliferation and migration of vascular smooth muscle cells through the focal adhesion kinase, MAPK and STAT3 Tyr705 signalling pathways

The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet‐derived growth factor (PDGF) are important steps in cardiovascular diseases, including neointimal lesion formation, myocardial infarction and atherosclerosis. Here, we evaluated the rubiarbonone C‐mediated signalling pathways that regulate PDGF‐induced VSMC proliferation and migration.
Role of signalling molecules in behaviours mediated by the δ opioid receptor agonist SNC80

GPCRs exist in multiple conformations that can engage distinct signalling mechanisms which in turn may lead to diverse behavioural outputs. In rodent models, activation of the δ opioid receptor (δ‐receptor) has been shown to elicit antihyperalgesia, antidepressant‐like effects and convulsions. We recently showed that these δ‐receptor‐mediated behaviours are differentially regulated by the GTPase‐activating protein regulator of G protein signalling 4 (RGS4), which facilitates termination of G protein signalling. To further evaluate the signalling mechanisms underlying δ‐receptor‐mediated antihyperalgesia, antidepressant‐like effects and convulsions, we observed how changes in Gαo or arrestin proteins in vivo affected behaviours elicited by the δ‐receptor agonist SNC80 in mice.
Different contributions of chemokine N‐terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3

Chemokines and their receptors form an intricate interaction and signalling network that plays critical roles in various physiological and pathological cellular processes. The high promiscuity and apparent redundancy of this network makes probing individual chemokine/receptor interactions and functional effects, as well as targeting individual receptor axes for therapeutic applications, challenging. Despite poor sequence identity, the N‐terminal regions of chemokines, which play a key role in their activity and selectivity, contain several conserved features. Thus far little is known regarding the molecular basis of their interactions with typical and atypical chemokine receptors or the conservation of their contributions across chemokine‐receptor pairs.
The Role of PET Imaging in Solitary Pulmonary Nodules

The finding of a solitary pulmonary nodule is a common dilemma, because of the desire to avoid both a delay in initiating treatment of a lung cancer as well as the risks and morbidity of an invasive biopsy that may not be needed. Positron emission tomography (PET) imaging has great utility in directing management of many of these patients. However, appropriate selection of patients for this test, and appropriate interpretation of the results is crucial. Several situations can be defined in which PET imaging has little utility. Optimal use of PET requires a clear understanding of the strengths and limitations of this imaging modality.
Boosting phagocytosis and anti‐inflammatory phenotype in microglia mediates neuroprotection by PPARγ agonist MDG548 in Parkinson's disease models

Microglial phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). PPARγ agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548.
Short-Term Recovery After Subtotal and Total Abdominal Hysterectomy-A Randomized Clinical Trial

Although it is commonly believed that recovery from subtotal abdominal hysterectomy (SH) is associated with fewer complications and less pelvic organ dysfunction than total abdominal hysterectomy (TH), there is little data supporting this belief in the literature. Previous studies have found no difference in the postoperative recovery time between these procedures. Overall recovery after hysterectomy depends on treatment of postoperative physical symptoms and complications. Some studies have shown that recovery also depends on preoperative psychological well being and postoperative overall well being. The impact of these factors on the postoperative day-by-day recovery has not been investigated. This prospective randomized, controlled, open, multicenter study assessed possible differences between SH and TH in the day-by-day postoperative recovery, and also analyzed factors associated with postoperative recovery and sick leave. The study was conducted at 7 hospitals and 1 private gynecological clinic in Sweden between 1998 and 2004. The study subjects were 200 women who were scheduled for hysterectomy because of benign gynecological conditions. Of the 178 patients who completed the study, 94 were randomized to a SH group and 84 to a TH group. Assessment of day-by-day recovery of general well being was made using a patient diary with daily entries initiated at 1 week before surgery and continuing until the 35th postoperative day; the results were calculated on a visual analogue scale. Psychometric measurements included depression and anxiety; general psychological well being was also assessed. The primary study outcome measures were the associations between day-by-day recovery of general well being and duration of sick leave with mode of hysterectomy. The data showed no significant difference in the SH and TH groups for the day-by-day recovery of general well being in the preoperative and postoperative periods. A strong association was found between both postoperative day-by-day recovery of general well being and the duration of sick leave, with the occurrence of minor complications, but there was no significant association for major complications. The postoperative day-by-day recovery of general well being and duration of sick leave were strongly associated with the level of preoperative psychological well being. These findings show no difference in the speed of day-by-day recovery of general well being between the 2 procedures, but demonstrate an association between postoperative recovery of general well being and the duration of sick leave with preoperative psychological well being. Strong determinants for a prolonged sick leave include minor postoperative complications and a low preoperative level of psychological well being.
Reliability and Validity of the Pediatric Evaluation of Disability Inventory

The reliability and validity of the Pediatric Evaluation of Disability Inventory (PEDI) were investigated in a series of three studies: 1) intrarater reliability (n = 23), 2) interrespondent reliability (n = 1 7), and 3) concurrent validity with the Peabody Developmental Motor Scales (PDMS) (n = 25). In the intrarater reliability component of the study, parents were interviewed using the PEDI two times, with one week between interviews. Intraclass correlation coefficients (ICC) (3,1) were high for the summary scores for each domain and moderate to good for the content areas within each domain. Interrespondent reliability was investigated using parents and therapists as respondents. ICC (2,1) ranged from 0.18 to 0.94 for content areas within the domains, indicating varying degrees of reliability on the items. Those items that had inconsistent ratings between parents and therapists were ones typically not observed in the clinic setting. The results suggest that reliability is increased when the PEDI is administered to both the parent and the primary therapist, as their perceptions of the child differ on some of the PEDI items. Pearson correlation coefficients between subscale scores for the PDMS and the summary scores from each domain of the PEDI were moderate to high (r = 0.64–0.95), indicating that these tests measure similar aspects of the child's performance. The PDMS was more sensitive in identifying children as delayed, when using the criterion of 1.5 SD below the mean. In general, the findings support the PEDI as a reliable and valid assessment of functional performance in children with disabilities. (Pediatr Phys Ther 1996;8:15–24)
Evidence of thalamic gray matter loss in pediatric multiple sclerosis

Objective: We used voxel-based morphometry (VBM) to assess the pattern of regional gray matter (GM) loss in patients with pediatric multiple sclerosis (MS) and its relation with the Expanded Disability Status Scale (EDSS) score, disease duration, and the extent of T2 lesion load (LL). Methods: From 28 patients with pediatric relapsing-remitting MS (16 girls; mean age = 14.4 years, range = 7 to 16 years) and 21 matched controls, dual-echo and three-dimensional T1-weighted magnetization prepared rapid acquisition gradient echo sequences were acquired. T2 LL was measured using a local thresholding segmentation technique. Data were analyzed using an optimized VBM analysis and statistical parametric mapping. Results: In pediatric patients with MS, mean brain T2 LL was 7.8 mL ± 11.3. Intracranial volume did not differ between patients and controls. Compared to controls, patients with pediatric MS had significant GM loss in the thalamus, bilaterally, which was significantly correlated with T2 LL (r = −0.80 for the right thalamus, r = −0.74 for the left thalamus, p < 0.05, corrected for multiple comparisons). No correlation was found between thalamic GM loss, disease duration, and disability. Conclusions: In patients with pediatric multiple sclerosis (MS), differently from what happens in adult-onset MS, gray matter (GM) atrophy seems to involve the thalamus only, with sparing of the cortex and other deep GM nuclei. The correlation found between atrophy and T2 lesion load suggests transsynaptic and Wallerian degenerations as the most likely substrate of tissue loss in the thalamus of these patients. GLOSSARY: DT = diffusion tensor; EDSS = Expanded Disability Status Scale; FA = flip angle; FOV = field of view; LL = lesion load; GM = gray matter; ICV = intracranial volume; MP-RAGE = magnetization prepared rapid acquisition gradient echo;MS = multiple sclerosis; MT = magnetization transfer; NAWM = normal-appearing white matter; NBV = normalized brain volume; NGM = normalized GM; RR = relapsing-remitting; TE = echo time; TR = repetition time; TSE = turbo spin-echo; VBM = voxel-based morphometry.
CLINICOPATHOLOGIC STUDY OF A SNCA GENE DUPLICATION PATIENT WITH PARKINSON DISEASE AND DEMENTIA

There is evidence that α-synuclein gene ( SNCA ) point mutations and gene multiplications play a pivotal role in the development of Lewy bodies (LBs) and Lewy neuritic (LN) pathology. Dysregulation of the production/degradation of the α-synuclein protein, a major component of LBs and LNs, is speculated to result in its accumulation and produce the neuropathological features of SNCA -related neurodegeneration.1 The identification of SNCA multiplications in families with parkinsonism suggests that SNCA gene dosage may play a role in the onset of Parkinson disease (PD). 2 Most patients with SNCA triplication develop cognitive and autonomic dysfunction in early stage of the disease.3,4 However, three families with SNCA duplication have been reported with symptoms more reminiscent of typical PD.5,6 Interestingly, a recent study reported that one triplication (a Swedish-American pedigree) and one duplication pedigree have a common ancestor.7 As a common mechanism of multiplications, the area including the SNCA-MMRN1 locus could play a role in multiple copy numbers. Another multiplication family has been reported also to have the rearrangement change in the same region indicating the SNCA-MMRN1 locus may be fragile.2,5–7 With regard to clinical aspects, patients with SNCA duplication tend to have milder symptoms compared to those with triplication.5–7 The onset of disease in SNCA duplication patients occurs approximately 15 years later (50 years of age) than that of SNCA triplication families (35 years of age). These features suggest that differences in genetic copy numbers could influence the clinical features of PD. Recently, we identified two families of Japanese origin with SNCA duplications.8 One patient from Family B (named as B-1) developed severe parkinsonism and dementia. These findings indicate that SNCA duplication also causes PD with dementia (PDD). Three copies of the locus SNCA-MMRN1 were identified in the two duplication families. The length of …
A COMPARISON OF CENTRAL VENOUS PRESSURE CHANGES IN THE THIRD STAGE OF LABOUR FOLLOWING OXYTOCIC DRUGS AND DIAZEPAM

The changes in central venous pressure (CVP) in patients who received ergometrine, oxytocin, ergometrine with oxytocin (Syntometrine), or no oxytocic drug in the third stage of labour have been compared. The results showed that there was a significant rise in central venous pressure after the administration of ergometrine and Syntometrine. When diazepam was given late in the first stage of labour to a group of patients who received Syntometrine during the course of delivery the changes in CVP were not significantly different from those of the control group. In addition, the administration of oxytocin in the management of the third stage did not produce a significant rise in CVP. The volume of blood lost was significantly reduced in all subjects by the use of oxytocic drugs.