BackgroundThe Centers for Disease Control and Prevention (CDC) issued an update on hepatitis C virus (HCV) testing approach, in which it omitted the use of recombinant immunoblot assay (RIBA) in the diagnostic algorithm and recommended that future studies are needed to evaluate the performance of HCV testing without RIBA. As Egypt has the highest prevalence of HCV worldwide, we aimed to evaluate the value of RIBA in HCV testing in a high prevalence population. Our objective was to clarify whether enzyme linked immunosorbent assay (ELISA) anti-HCV signal-to-cutoff (S/CO) ratios were able to discriminate true positive from false positive anti-HCV antibody status and to evaluate the role of RIBA in solving this problem which may lead to a redefined strategy for diagnosis of HCV infection. Our second objective was to elucidate the effects of different HCV peptides of both structural and non-structural proteins on the humoral immune response to HCV infection. MethodsThe current study drew results from 167 individuals divided into three groups: Group I: included 77 HCV antibody positive (ELISA) high risk health care workers (HCW), Group II: included 56 presumably uninfected individuals who showed normal liver enzymes, negative HCV RNA and were asymptomatic. Their ELISA HCV antibody S/C ratio ranged from 0.9 to <5. Group III: included 34 patients enrolled from outpatient clinics of Ain Shams Hospital with persistent viral replication, elevated liver enzymes, and chronic HCV related liver disease. All study participants were assessed for the presence of anti-HCV antibodies by 3rd generation ELISA which was confirmed by RIBA.ResultsInterpreting the results of both ELISA and RIBA together, false positive results were highly significantly increased in HCW when compared with the other two groups. Indeterminate and false negative results were only found in the presumably uninfected group. For differentiated antibody responses by RIBA, chronic HCV cases had the highest frequency of positive antibody response to core peptides while the presumably uninfected group had the lowest. Antibody response to E2 was found less frequently in chronic cases than Core 1, Core 2 and NS3. The specific antibody response to the different HCV peptides showed the same distribution of frequencies in both chronic HCV cases and the presumably uninfected individuals with the chronic cases having the highest frequencies. This distribution was different from the HCW. The most evident difference was the reaction towards NS3 which was the highest antibody producing peptide in chronic HCV and presumably uninfected individuals whereas in HCW Core1 was the highest.ConclusionThe HCV antibody immunoblot assay (RIBA) is still necessary for the detection of false positive cases which can occur quite frequently in countries of high prevalence as Egypt. Indeterminate RIBA results indicate a waning antibody response in elderly individuals who recovered from previous or distant HCV infection.
Inflammatory pathway and disruption in glutamate homeostasis join at the level of the glia, resulting in various neurological disorders. In vitro studies have provided evidence that membrane proteins connexions (Cxs) are involved in glutamate release, meanwhile, excitatory amino-acid transporters (EAATs) are crucial for glutamate reuptake (clearance). Moreover, pannexin-1 (Panx-1) activation is more detrimental to neurons. Their expression patterns during inflammation and the impacts of IκB kinase (IKK) inhibition, morphine, and galantamine on the inflammatory-associated glutamate imbalance remain elusive.To investigate this, rats were injected with saline or lipopolysaccharide.Thereafter, vehicles, morphine, galantamine, and BAY-117082 were administered in different groups of animals. Subsequently, electroencephalography, enzyme-linked immunosorbent assay, western blot, and histopathological examinations were carried out and various indicators of inflammation and glutamate level were determined. Parallel analysis of Cxs, Panx-1, and EAAts in the brain was performed. Our findings strengthen the concept that unregulated expressions of Cxs, Panx-1, and EAATs contribute to glutamate accumulation and neuronal cell loss. Nuclear factor-kB (NF-κB) pathway can significantly contribute to glutamate homeostasis via modulating Cxs, Panx-1, and EAATs expressions. BAY-117082, via inhibition of IkK, promoted the antiinflammatory effects of morphine as well as galantamine. We concluded that NF-κB is an important component of reshaping the expressions of Cxs, panx-1, and EAATs and the development of glutamate-induced neuronal degeneration.
Introduction Type 1 diabetes is a major cause of cardiovascular death; diabetic cardiomyopathy (DCM) is the most important cause of mortality among diabetic patients. There is an increasing body of evidence that the most important inducer of DCM is microvascular injury. The aim of this study is to establish a potential relationship between low frequency/high frequency (LF/HF) ratio and DCM and to set a possible predictive cutoff of LF:HF ratio for early detection of DCM. Methods 75 type 1 diabetic patients together with 75 controls were assessed using tissue Doppler imaging for left ventricular (LV) and right ventricular (RV) diastolic function, and heart rate variability (HRV) indices including LF/HF ratio. Type 1 diabetic patients were also assessed for parameters of glycemic and lipid profile control. Results Cases showed a statistically significant increase in LF/HF ratio compared to controls reflecting reduced HRV. Also, LV and RV diastolic function were reduced in cases compared to controls, there was a significant correlation between LV E/E’ ratio (ratio of early transmitral velocity and average early mitral annular and basal septal velocities) and LF/HF ratio. LF/HF ratio was able to predict LV diastolic dysfunction as expressed by the LV E/E’ ratio with a sensitivity of 96%. Conclusion HRV indices notably LF/HF ratio seem to be an early and sensitive predictor of DCM, the latter finding not only underlines the role of microvascular injury in the induction of DCM but might help also for the early detection and reversal of it.
Background and objectives Inflammatory pathway and dysregulation of glutamate level are connected at the level of the glia, leading to numerous neurological disorders. In vitro models have revealed that the channel connexions (Cxs) are implied in glutamate release, while excitatory amino‐acid transporters (EAATs) are crucial for glutamate re‐uptake. Additionally, pannexin‐1 (Panx‐1) is involved in glutamate induced neuronal degeneration. However, the pattern of their expressions during inflammation and the effects of nuclear factor‐kappa B (NF‐κB) inhibition on the inflammatory‐ induced glutamate imbalance remain unknown. The aim of the study was to explore the roles of Cxs, Panx‐1 and EAATS on glutamate induced neurotoxicity, and to clarify the relationship between NK‐FB activation and the expressions of Cxs, Panx‐1 and EAATS in lipopolysaccharide‐induced neuroinflammation. Hypothesis we hypothesized that NF‐κB may be involved in the development of glutamate neurotoxicity via regulating the expressions of Cxs, Panx‐1 and EAATS on the activated glia cells. Material & Methods To study this, 30 male albino rats were injected with saline or lipopolysaccharide. Subsequently, LPS challenged rats were treated with either vehicle or BAY‐117082 (an inhibitor of IκB Kinase (IKK)). Thereafter, reverse transcription polymerase chain reaction (RT‐PCR), western blot, enzyme‐linked immunosorbent assay (ELISA), and immune‐histological analysis were carried out to assess the glia activity, NFKB activation, and glutamate level. Concomitantly, measurement of Cxs, Panx‐1, and EAAts expressions in the brain was conducted. The electroencephalography (EEG) was used to record the neuronal activity. The present study was conducted following the FASEB Statement of Principles for the use of Animals in research and Education, and was approved by the Institutional Animal Care Committee (CU Ш F 55 17). Results Our results confirm the previous in‐ vitro findings that paradoxical changes in the expressions of Cxs, Panx‐1, and EAATs may participate significantly in glutamate accumulation and subsequent neurotoxicity. Nuclear factor‐kB (NF‐κB) pathway significantly impacted the glutamate balance via regulating the expressions of Cxs, Panx‐1, and EAATs. BAY‐117082 ameliorated gliosis and provided a neuroprotection. Figure 1. Conclusion We concluded that NF‐κB is a critical key player in the remodeling of Cxs, panx‐1, and EAATs expressions and the initiation of glutamate toxicity.
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