Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. Perturbation of ...glutathione-dependent antioxidant defense and adenosine deaminase (ADA)/xanthine oxidase (XO) signaling has been implicated in the pathogenesis of cardiometabolic disorders. We thus, hypothesized that depletion of glutathione contents and upregulation of ADA/XO are involved in codeine-induced glucolipid deregulation. The present study also investigated whether or not codeine administration would induce genotoxicity and apoptosis in cardiac and renal tissues.
Male New Zealand rabbits received per os distilled water or codeine, either in low dose (4 mg/kg) or high dose (10 mg/kg) for 6 weeks.
Codeine treatment led to reduced absolute and relative cardiac and renal mass independent of body weight change, increased blood glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C), as well as increased atherogenic indices and triglyceride-glucose index (TyG). Codeine administration significantly increased markers of cardiac and renal injury, as well as impaired cardiorenal functions. Codeine treatment also resulted in increased cardiac and renal malondialdehyde, Advanced Glycation Endproducts (AGE) and 8-hydroxydeoxyguanosine (8-OH-dG), and myeloperoxidase (MPO), ADA, XO, and caspase 3 activities. These observations were accompanied by impaired activities of cardiac and renal proton pumps.
Findings of this study demonstrate that upregulation of ADA/XO and caspase 3 signaling are, at least partly, contributory to the glucolipid deregulation and cardiorenal injury induced by codeine.
The objective of this study was to evaluate the effect of in ovo feeding cysteine, lysine or their combinations on the perinatal and post-hatch physiological responses of broiler embryos exposed to ...heat stress during incubation. A total of two thousand fertile eggs of broiler breeders (Ross 308) flock (at 38 weeks of age) were used for this study. In the first 10 days, the eggs were incubated using the conventional protocol of relative humidity and temperature of 55% and 37.8°C respectively. From day ten onward, the temperature was increased to 39.6°C for 6 h per day. On day 17.5, 1,500 eggs with the evidence of living embryos were randomly selected and assigned to 6 treatments having five replicates of 50 eggs each. The treatments were: un-injected eggs (UI), eggs injected with only 0.5 ml distilled water (DW), 3.5 mg/egg cysteine (CY), 2mg/egg lysine (LY), 3.4 mg cysteine+2 mg lysine (CLH) and 1.7 mg cysteine+1 mg lysine (CLL). On day 21, the hatchability, anatomical characteristics, chick quality and the antioxidant status of the chicks were evaluated. During the post-hatch phase, data were collected on the haematology, biochemical parameters, growth performance and intestinal morphology of the birds. The results revealed that the hatchability of CY chicks was higher (
p
< 0.05) than in the other treatments, while the lowest values were recorded in CLH. The hatching muscle of the chicks of CLL was similar to those of CY but higher (
p
< 0.05) than the others. The MDA of DW and UI chickens was similar and higher than birds in the other treatment groups. The serum SOD of CLL birds was comparable to that of CY but higher than the values recorded in the other treatments. The final weights of CLL chickens were similar to those of LY but significantly higher (
p
< 0.05) than those of the other treatments. The duodenal villus heights of the birds of CLL were higher than those of the other treatment groups, whereas the villus height of the birds of CLH was higher than those of UI, DW and CY. Overall,
in ovo
feeding of cysteine alone improved the hatchability of thermally-challenged broiler embryos. In contrast, a low-dose mixture of cysteine plus lysine improved the post-hatch growth performance.
Myofibroblasts are crucial to the pathogenesis of tissue fibrosis. Their formation of stress fibers results in the release of myocardin-related transcription factor (MRTF), a transcriptional ...coactivator of serum response factor (SRF). MRTF-A ( Mkl1 )-deficient mice are protected from lung fibrosis. We hypothesized that the SRF/MRTF pathway inhibitor CCG-203971 would modulate myofibroblast function in vitro and limit lung fibrosis in vivo . Normal and idiopathic pulmonary fibrosis lung fibroblasts were treated with/without CCG-203971 (N-4-chlorophenyl-1-3-(2-furanyl)benzoyl-3-piperidine carboxamide) and/or Fas-activating antibody in the presence/absence of transforming growth factor (TGF)-β1, and apoptosis was assessed. In vivo studies examined the effect of therapeutically administered CCG-203971 on lung fibrosis in two distinct murine models of fibrosis induced by bleomycin or targeted type II alveolar epithelial injury. In vitro , CCG-203971 prevented nuclear localization of MRTF-A; increased the apoptotic susceptibility of normal and idiopathic pulmonary fibrosis fibroblasts; blocked TGF-β1–induced myofibroblast differentiation; and inhibited TGF-β1–induced expression of fibronectin, X-linked inhibitor of apoptosis, and plasminogen activator inhibitor-1. TGF-β1 did not protect fibroblasts or myofibroblasts from apoptosis in the presence of CCG-203971. In vivo , CCG-203971 significantly reduced lung collagen content in both murine models while decreasing alveolar plasminogen activator inhibitor-1 and promoting myofibroblast apoptosis. These data support a central role of the SRF/MRTF pathway in the pathobiology of lung fibrosis and suggest that its inhibition can help resolve lung fibrosis by promoting fibroblast apoptosis.
Anthocleista vogelii (Planch) is used in folk medicine in conditions related to inflammation and oxidative stress. This suggests that some of its constituents could possess ability to reduce ...oxidative damage to cells and ameliorate inflammatory conditions which are two prominent features in the brain of a person suffering from Alzheimer’s disease.
The leaf extracts were investigated for their bioactive constituents in our quest for novel compounds for the management of Alzheimer’s disease.
Anthocleista vogelii crude leaf extract obtained from 80% methanol was successively partitioned with n-hexane, dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol. This gave four solvent fractions of the crude extract. These fractions and isolated compound were subjected to acetylcholinesterase (AChE) inhibitory activity test using the microplate assay method. The structure of the isolated compound was determined using spectroscopic methods (1D and 2D NMR, and MS).
The results of the acetylcholinesterase inhibitory assay revealed that n-BuOH and ethyl acetate fractions had the best activity with IC50 of 564.58 and 727.63 µg/mL respectively. Activity directed fractionation of each of these fractions led to the isolation of the same compound identified as a C-glucosylflavone; isovitexin-7-O-methyl ether (swertisin). This rare C-glucosylflavone co-exist as two rotamers and exhibited duplication of NMR signals. It is reported from this plant for the first time. Swertisin displayed better acetylcholinesterase inhibitory activity with IC50 of 32.09 µg/mL than physostigmine (eserine) with IC50 of 56.09 µg/mL used as a standard.
This study reports isolation and characterization of a rare C-glycosylflavone; isovitexin-7-O-methyl ether (swertisin). Isolated compound exhibited duplication of NMR signals and better acetylcholinesterase inhibitory activity than eserine used as a standard. The activity exhibited by this compound suggests that it could be useful in the management of Alzheimer’s disease.
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► Tribological properties of MoN/Cu coatings assessed. ► Residual stresses directly affect coating adhesion and wear resistance. ► Copper addition weakens adhesion and increases wear.
Ceramic thin ...film coatings, such as MoN/Cu, are attractive for engine applications due to their low friction, high hardness and high wear resistance. However, there is a need to establish a reliable connection between the deposition parameters of the thin film and its tribological performance. In this study, two coating compositions, MoN and MoN with Cu were deposited on H-13 tool steel substrates in order to correlate compositional variables that result from processing to their respective tribological properties. The efficacy of the coating in protecting surfaces is highly dependent on its adhesion to the substrate and its tribological properties. Residual stresses resulting from the coating deposition were evaluated using an X-ray microprobe. Scratch testing was performed to measure the coating adhesion energy, and the wear rate was determined using a ball-on-flat contact configuration on a high frequency reciprocating test rig. It was observed that coatings with lower copper content performed better in the wear test and exhibited higher coating adhesion energy. A primary wear damage mechanism was coating removal by delamination and spallation, which is related to the adhesion energy. Since coating processing variables determine the structure and properties, and hence affect the tribological properties of these MoN based coatings, these parameters can be used to optimize coating composition for enhanced tribological performance.
Hypertension (HT) prevalence, Uncontrolled Blood Pressure (UBP), morbidity and mortality are highest in Sub-Saharan Africa (SSA). Correlating pathophysiology of HT to pharmaco-therapy with ...antihypertensive drugs (AHD) may bring amelioration. Aims:To review peculiarities of HT in SSA, UBP causes, diagnostic modalities, AHD use, rationality and efficacy.
14 published therapeutic audits in 4 SSA nations on Google Scholar or PUBMED, (total n = 6496 patients) were evaluated. Calcium Channel blockers (CCB) amlodipine, and thiazide diuretics (TD), hydrochlorothiazide (HCTZ) were the commonest AHD. Thiazide Like Diuretics (TLD) were underutilized. The % of patients on AHD were: 1 drug 5.4–55%; 2 drugs 37–82%; >/ = 3 drugs 6–50.3%. 2-drug combinations were: ACEI/ARB + TD (42%); CCB + TD (36.8%); ACEI + CCB (15.8%) of studies. Triple/quadruple therapy included Methyldopa (MTD) with ACEI + CCB or TD. The (%) attaining BP < 140/< 90 mmHg, ranged from 29 to 53.6%, median, 44%. The co-morbidities, range and median were: Diabetes Mellitus (DM): 9.8–64%, 19.2%; Chronic Kidney Disease (CKD): 5.7–7.5%, 6.9%, and Coronary artery Disease (CAD): 0.9–2.6%, 2.3%. ACEI + CCB ± TD were the preferred AHD for comorbidities.
Therapeutic inertia; Non-compliance; co-morbidities; refractory HT; ignorance; substandard AHD; contribute to UBP. Studies relating 24 hour ABPM to complications and mortality in SSA hypertensives; and impact of different AHD classes on ABPM, are needed. Study of ACEI + alpha-1 blockers + TLD on 24 hour ABPM and personalized care, are required.
Marek's disease (MD) is caused by oncogenic MD virus serotype 1 (MDV1) and is characterized by lymphoproliferative lesions resulting in high morbidity and mortality in chickens. Despite being ...ubiquitous on poultry farms, there is a dearth of information on its molecular characteristics in Nigeria. This study aimed at characterizing three virulence genes (Meq, pp38, and vIL-8) of MDV1 from chickens in Ogun state, Nigeria. Blood, feather quill, and tumour samples of chickens from different commercial poultry farms in Ogun State were pooled, spotted on 107 FTA cards, and screened for MDV1 by polymerase chain reaction (PCR). Phylogenetic analysis was carried out to compare Nigerian MDV1 Meq, pp38, and vIL-8 genes sequences with the published references. Thirteen samples were MDV1-positive and the Meq, as well as pp38, and vIL-8 genes from the different samples were 100% identical. The Meq genes contained 339 amino acids (aa) with three PPPP motifs in the transactivation domain and two interruptions of the PPPP motifs due to proline-to-arginine substitutions at positions 176 and 217 resulting in a 20.88% proline composition. Phylogenetic analysis revealed that the Meq gene clustered with strains from Egypt and very virulent ATE2539 strain from Hungary. Mutations were observed in the pp38 protein (at positions 107 and 109) and vIL-8 protein (at positions 4 and 31). Based on the molecular analysis of the three genes, the results indicate the presence of MDV1 with virulence signatures; therefore, further studies on in vivo pathotyping of Nigerian MDV1 from all states should be performed.
RESEARCH HIGHLIGHTS
Meq, pp38 and vIL-8 genes were 100% identical between Nigerian MDV strains.
Proline content in Nigerian meq gene was 20.88% with two PPPP motifs interruptions.
Meq, pp38 and vIL-8 genes of Nigerian MDV were similar to Egyptian and Indian strains.
Suppressed glucose metabolism, elevated fatty acid metabolism and lipid deposition within myocardial cells are the key pathological features of diabetic cardiomyopathy. Studies have associated ...cadmium exposure with metabolic disturbances.
To examine the effects of cadmium exposure on cardiac glucose homeostasis and lipid accumulation in male Wistar rats.
Male Wistar rats were treated for 21 days as (n
= 5): Control, cadmium chloride Cd5 (5 mg/kg, p.o.), cadmium chloride Cd30 (30 mg/kg, p.o).
The fasting serum insulin level in this study decreased significantly. Pyruvate and hexokinase activity reduced significantly in the Cd5 group while no significant change in lactate and glycogen levels. The activity of pyruvate dehydrogenase enzyme significantly increased with an increasing dosage of cadmium. The free fatty acid, total cholesterol and triglyceride levels in the heart increased significantly with increasing dosage of cadmium when compared with the control. Lipoprotein lipase activity in the heart showed no difference in the Cd5 group but a reduction in the activity in the Cd30 group was observed.
This study indicates that cadmium exposure interferes with cardiac substrate handling resulting in impaired glucometabolic regulation and lipid accumulation which could reduce cardiac efficiency.
Convolutional neural networks (CNNs) assume pivotal roles in aiding clinicians in diagnosis and treatment decisions. The rapid evolution of imaging technology has established three-dimensional (3D) ...CNNs as a formidable framework for delineating organs and anomalies in medical images. The prominence of 3D CNN frameworks is steadily growing within medical image segmentation and classification. Thus, our proposition entails a comprehensive review, encapsulating diverse 3D CNN algorithms for the segmentation of medical image anomalies and organs.
This study systematically presents an exhaustive review of recent 3D CNN methodologies. Rigorous screening of abstracts and titles were carried out to establish their relevance. Research papers disseminated across academic repositories were meticulously chosen, analyzed, and appraised against specific criteria. Insights into the realm of anomalies and organ segmentation were derived, encompassing details such as network architecture and achieved accuracies.
This paper offers an all-encompassing analysis, unveiling the prevailing trends in 3D CNN segmentation. In-depth elucidations encompass essential insights, constraints, observations, and avenues for future exploration. A discerning examination indicates the preponderance of the encoder-decoder network in segmentation tasks. The encoder-decoder framework affords a coherent methodology for the segmentation of medical images.
The findings of this study are poised to find application in clinical diagnosis and therapeutic interventions. Despite inherent limitations, CNN algorithms showcase commendable accuracy levels, solidifying their potential in medical image segmentation and classification endeavors.
Holdup in flighted rotary dryers can be classified according to its loading state as either over, under or at design load. The loading state influences the effectiveness of particle to gas heat and ...mass transfer as well as the residence time of solids through the dryer. As such, accurate estimation of the design load is critical to the analysis of performance and the optimal design of flighted rotary dryers. In this paper design load experiments carried out in a horizontal, pilot scale flighted rotary dryer at different experimental conditions are described. The design load experiments involved analysis of multiple photographs of the cross sectional area of the solids in the front end of the dryer, at increasing loading conditions. Subsequently, the design load was estimated using conventional criteria based on the saturation of material in the cascading or unloading flights. The study examined both free flowing and cohesive solids with cohesion being controlled through the addition of low volatility fluid to the solids (dynamic angle of repose ranged from 44.7° to 62.3°). The effect of drum rotational speed was also examined (2.5rpm–4.5rpm). In order to select an appropriate geometrically derived design load model, comparison with existing design load models from the literature was undertaken. The proportion of airborne to flight borne solids within the drum was characterised through a combination of photographic analysis coupled with Computational Fluid Dynamics (CFD) simulation. In particular, solid volume fractions of the airborne solids with solid flow rate ranging from 0.703kg/s to 0.134kg/s were characterised using a CFD technique based on the Eulerian–Eulerian approach. The suitability of using geometric models of flight unloading to predict design loading in flighted rotary dryers is discussed. A modified version of Baker's (1988) design load model is proposed.
► Flighted rotary dryer design loading is experimentally determined. ► The effect of rotational speeds and dynamic repose angles is described. ► Image analysis is used to quantify the saturation of the airborne solids at design conditions. ► CFD simulation is coupled with image analysis to quantify flight unloading. ► A geometric flight unloading model is presented to model design conditions.
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