Efficacy of clofibrate on severe neonatal jaundice associated with glucose-6-phosphate dehydrogenase deficiency (a randomized clinical trial)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency may cause severe hyperbilirubinemia with bilirubin encephalopathy unless intervention is initiated. The aim of this study was to assess the efficacy of clofibrate in full term G6PD deficient neonates with jaundice. A randomized clinical trial study was performed in two groups of full-term G6PD deficient jaundiced neonates (clofibrate treated group, n = 21; control group, n = 19). Infants in the clofibrate group received a single oral dose of 100 mg/kg clofibrate, whereas control group received nothing. Both groups were treated with phototherapy. Serum total and direct bilirubin levels were measured at the onset of treatments, 16, 24 and 48 hours later. On enrollment, the mean total serum bilirubin (TSB) level in the clofibrate treated group was 18.40 +/- 2.41 and in the control group was 17.49 +/- 1.03 (p = 0.401). At 16, 24 and 48 hours of treatment, the mean TSB in the clofibrate group were 15.2 +/- 1.9, 12.6 +/- 2.4, and 10.1 +/- 2.4 and in the control group were 16.5 +/- 1.2, 13.3 +/- 2.2 and 11.4 +/- 2.4, respectively (p = 0.047). At 48 hours, 7 (33%) cases in the clofibrate group and one (5%) case in the control group were discharged with a TSB < 10 mg/dl (p = 0.031). No side effects were observed on serial examinations during hospitalization, or on the 1st and 7th days after discharge. The results show that clofibrate induces a faster decline in serum total bilirubin level, a shorter duration of phototherapy, and hospitalization with no side effects in full-term G6PD deficient neonates with jaundice.     

Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF) and possible role of oxidative stress

Hormesis, a biphasic dose–response phenomenon, which is characterized by stimulation of an end point at a low‐dose and inhibition at a high‐dose. In the present study we used human lungs fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) in hormetic effects of non coplanar PCB 101. Results from 3‐(4,5‐dime‐thylthiazol‐2‐yl)‐2,5‐diphenyltetrazo‐lium bromide (MTT) assay indicated that PCB101 at lower concentrations (10^?5 to 10^?1 μg mL^?1) stimulated HELF cell proliferation and inhibited at high concentrations (1, 5, 10, and 20 μg mL^?1) in a dose‐ and time‐dependent manner. Reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) (except 48 h) showed a significant increase at higher concentrations of PCB 101 than those at the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase (GSH‐Px) exhibited decreasing trends in dose and time dependent manner. Lipid peroxidation assay resulted in a significant increase (P < 0.05) of MDA level in PCB 101‐treated HELF cells compared with controls, suggesting that OS plays a key role in PCB 101‐induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB 101 exposure compared to lower concentrations. Overall, we found that HELF cell proliferation was higher at low ROS level and vice versa, which revealed activation of cell signaling‐mediated hormetic mechanisms. The results suggested that PCB 101 has hormetic effects to HELF cells and these were associated with oxidative stress. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1385–1392, 2015.     

IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by Th2 cells. It down-regulates the proinflammatory response and modulates hepatic fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell response and has many antiviral properties. Data concerning the Th-1/Th-2 balance in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity. Our results showed that spontaneous IL-10 was undetectable in patients with CH-C, HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The presence of IL-12p40 was associated with HCV level of viremia and serum AST. Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40 was unrelated to liver histology or fibrosis. We concluded that in the Egyptian patients an augmentation of IL-12p40 and a suppression of IL-10 are both found. Whether this pattern is related to HCV genotype 4, or to the presence of schistosomiasis would need to be further investigated.     

Ultrasonic energy. Effects on vascular function and integrity

BACKGROUND. Ultrasonic energy transmitted via flexible wire probes provides a new means of ablating atherosclerotic plaque. We studied the effects of ultrasonic energy (20 kHz) delivered via a ball-tipped wire probe on arterial vasomotor behavior in rabbit thoracic aortas in a perfused whole-vessel model. METHODS AND RESULTS. After precontraction with phenylephrine (10(-5) M) or KCl (60 mM), the effects of ultrasonic energy (0.7-5.5 W x 60 seconds, 42-330 J) on arterial vasomotor behavior were measured using long-axis ultrasonic vessel imaging of the proximal (ultrasonic probe-treated) and distal (untreated) control segments. The efficacy of plaque ablation at these same probe-tip power outputs was evaluated in atherosclerotic, human cadaver iliofemoral arteries. Ultrasonic energy caused dose (energy)-dependent relaxation in rabbit aortas after precontraction with phenylephrine in arteries with endothelium (n = 8) and without endothelium (n = 8) (p less than 0.001 versus ultrasound treated at power outputs of 2.9 and 5.5 W). There was no difference in the relaxation dose responses between endothelialized and endothelially denuded segments (p = NS). Ultrasonic energy also caused significant relaxation (67 +/- 8%) after voltage-dependent precontraction with 60 mM KCl. Temperature measurements revealed less than 1 degrees C warming of the vessel wall during as long as 2 minutes of treatment at a power output of 5.5 W. Pathological examination showed no smooth muscle injury at (moderate) power outputs that caused arterial relaxation. At probe-tip power outputs of 2.9-5.5 W, ultrasonic energy recanalized two of two totally occluded cadaveric iliofemoral vessel segments. The ultrasonic ablation catheter was also demonstrated to cause arterial relaxation in a recanalized canine femoral artery in vivo. CONCLUSIONS. Ultrasonic energy delivered via a flexible-wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. At moderate power outputs, this relaxation response does not appear to be due to thermal effects or irreversible smooth muscle cell injury. This vasorelaxant effect of ultrasonic energy is also apparent in vivo, at doses that effectively ablate atherosclerotic plaque, and may improve the safety of arterial recanalization using ultrasonic energy.     

Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury

AIM: Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells. The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue. METHODS AND RESULTS: The authors developed a double transgenic mouse model with doxycycline induced human IL-8 expression restricted to intestinal epithelial cells. Doxycycline treatment of double transgenic mice for three days resulted in a 50-fold increase in the caecal IL-8 concentration and influx of neutrophils into the lamina propria. Although neutrophils entered the paracellular space between epithelial cells, complete transepithelial migration was not observed. Doxycycline treatment also increased the water content of the caecal and colonic stool, indicating dysfunctional water transport. However, the transmural electrical resistance was not decreased. Neutrophils recruited to the intestinal epithelium did not show evidence of degranulation and the epithelium remained intact as judged by histology. CONCLUSIONS: This conditional transgenic model of chemokine expression provides evidence that acute induction of IL-8 in the intestinal epithelium is sufficient to trigger neutrophil recruitment to the lamina propria, but additional activation signals are needed for full activation and degranulation of neutrophils, mucosal injury, and complete transepithelial migration.