The devastating effect of exposure to high irradiation dose on liver and the performance of synthesized nano-Hap in relieve the associated symptoms in rats.

Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction through a mechanism involving oxidative stress. This investigation studied the possible therapeutic effects of nano-HAp on hepatotoxicity in rats induced with gamma (γ) radiation. The study was carried out using 3 groups with 10 rats in each. Group 1 comprised the non-irradiated control rats, whereas the rats in groups 2 and 3 received a single dose of 10 Gy γ-radiation. The rats in group 3 were treated with nano-HAp [100 mg·(kg body mass)-1] once a week for 2 weeks starting the day after irradiation. The results showed that the rats exposed to γ-radiation had fragmented DNA, and significantly decreased levels of liver tissue enzymes such as paraoxonase 1, gamma glutamyl, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Pro-inflammatory factors such as interleukin (IL)-2, IL-6, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in tissue were significantly increased compared with the controls. Also, exposure to γ-radiation significantly decreased the activity of superoxide dismutase and glutathione oxidase and increased lipid peroxidation in liver tissue. These effects were accompanied by severe histopathological changes to the hepatocytes. Intravenous injection of nano-HAp after irradiation has significant therapeutic potential against irradiation-induced liver damage because the treatment with nano-HAp restored antioxidant activity in the liver, antagonized the significant changes in the levels of IL-2, IL-6, TNF-α, IFN-γ, and restored the tissue level of paraoxonase 1, gamma glutamyl, ALT, and AST. Administering nano-HAp seemed to relieve the pathological changes induced by γ-radiation. Based on these results, it could be concluded that nano-HAp may have a therapeutic effect against liver dysfunction induced by γ-radiation through antagonizing the generation of free radicals and enhancing the antioxidant defense mechanisms.

Therapeutic role of a synthesized calcium phosphate nanocomposite material on hepatocarcinogenesis in rats.

Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade. With this in mind, this study was designed to evaluate the therapeutic effects of a synthesized tricalcium phosphate nanocomposite material (nano-TCP) on hepatocarcinoma in a rat model, as initiated with diethylnitrosamine (DEN) and promoted with phenobarbital (PB). Hepatocarcinoma was induced with intraperitoneal injections of DEN (50 mg·(kg body mass)(-1)) 3 times a week for 2 weeks. Three weeks after the last dose of DEN, the rats received PB (0.05 %, w/v) in their drinking water for a further 6 weeks. Nano-TCP (100 mg·(kg body mass)(-1)) was administered intraperitoneally 3 times per week to rats with HCC. At the end of the experimental period, liver samples were collected from all animals for biochemical and histopathological analysis. The degree of DNA fragmentation was analyzed, in addition to immune status, by measuring the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The activities of the most important free-radical scavengers of the antioxidant defense system as well as malondialdehyde (MDA) content and liver enzymes were measured. The levels of hepatic heat shock protein-70 (HSP-70), caspase-3, and metalloproteinase-9 were also measured as markers for inflammation and apoptosis. Histopathological examination of liver tissue was performed. The results revealed the potent efficacy of nano-TCP in repairing the fragmented DNA and ameliorating most of the investigated parameters by significant elevation in the levels of hepatic alanine aminotransferase (ALT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. On the other hand, there was a significant decrease in hepatic gamma-glutamyl transpeptidase (γ-GT), MDA, IL-2, IFN-γ, TNF-α, matrix metalloproteinase-9 (MMP-9), HSP-70, and caspase-3 levels upon treatment. The findings form histopathological examination of the liver tissues agreed with the biochemical results and confirmed the difference between the control and treatment groups. In conclusion, nano-TCP succeeded in treating hepatocarcinoma efficiently, and presents a new hope for patients to get safe, fast, and effective treatment.

Efficiency of calcium phosphate composite nanoparticles in targeting Ehrlich carcinoma cells transplanted in mice.

The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC) was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Groups 1 and 2 were allocated as the EAC control. Groups 3 and 4 were injected once intratumorally (IT) by nano-calcium phosphate (nano-CaP). Groups 5 and 6 received once intraperitoneal injection (IP) of nano-CaP. Groups 7, 8, and 9 received nano-CaP (IP) weekly. Blood samples and thigh skeletal muscle were collected after three weeks from groups 1, 3, 5, and 7 and after four weeks from groups 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP) for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT), and gamma-aminobutyric acid (GABA) were measured. In serum, 8-Hydroxy-deoxyguanosine (8-OHDG), adenosine triphosphate (ATP), and vascular endothelial growth factor (VEGF) were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA). Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months.

Significance of Anti-C1q Antibodies in Patients with Systemic Lupus Erythematosus as A Marker of Disease Activity and Lupus Nephritis.

Anti-C1q autoantibodies have been proposed as a useful marker in SLE. This study aimed at measuring serum levels of anti-C1q antibodies in patients with SLE and investigates correlations of this level with the histopathological classes of renal biopsies and disease activity. The anti-C1q antibody level was measured in 30 females SLE patients and 20 controls. The activity of SLE disease was calculated according to the SLE disease activity index. A renal biopsy from patients with clinical manifestations of renal disease was obtained. There was a significant increase in the level of anti-C1q antibodies in SLE patients than controls and in patients with active LN than inactive LN (P<0.05). There were significant positive correlations between anti-C1q antibody level and SLEDAI & rSLEDAI scores and activity index score of renal biopsies. Anti-C1q antibodies showed higher diagnostic sensitivity and specificity than anti-dsDNA antibodies. In conclusion, anti-C1q antibodies are useful and sensitive non-invasive biomarker with high specificity in combination with anti-dsDNA antibodies for the diagnosis of renal disease activity.

Polymorphism of CYP1A1 gene and susceptibility to childhood acute lymphoblastic leukemia in Egypt.

The origin of acute lymphoblastic leukemia (ALL) may be explained by a combination of genetic susceptibility and environmental exposure. We aimed to study the frequency of CYP1A1 allelic variants in Egyptian patients with ALL, to evaluate their role in the development of ALL and to correlate these allelic variants with clinical and biological characteristics of the patients. Polymorphism of CYP1A1*2A, *2B and *4 alleles was examined in 186 Egyptian children with ALL and 200 normal individuals using polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP). A higher prevalence of the CYP1A1*4 allele was found in patients with ALL than in the normal population (19.4%vs. 10.0%, odds ratio [OR] = 2.160, 95% confidence interval [CI] = 1.200-3.89, p = 0.01), especially in the homozygous variant (OR = 6.6, 95% CI = 2.23-19.58, p = 0.001) and in male patients (p = 0.005), particularly those aged 2-10 years (OR = 5.214, 95% CI = 1.535-17.706, p = 0.008). CYP1A1*2A showed a significant difference between age groups (p = 0.046), with a higher incidence in the 10-17-year-old group (21.1%). Multivariate analysis showed that only the CYP1A1*4 allele remained as a probable independent risk factor for ALL development (OR = 2.250, 95% CI = 1.244-4.069; p = 0.007). Our results suggest that polymorphic variants in the CYP1A1*4 gene may increase the risk of childhood ALL, particularly in male patients aged 2-10 years.

Vascular endothelial growth factor in preterm infants with respiratory distress syndrome.

Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of morbidity and mortality in premature infants. An increasing evidence suggests that vascular endothelial growth factor (VEGF) may contribute to surfactant secretion and pulmonary maturation. This study determines cord blood VEGF levels in preterm infants and investigates its association with the development and severity of RDS. 50 preterm neonates and 10 healthy full term neonates were included in this study. All preterm neonates were subjected to full history taking, complete clinical examination, chest X-ray and laboratory investigations including arterial blood gases, CBC and C-reactive protein. Cord blood samples were obtained for determination of VEGF levels using ELISA. Cord blood VEGF level was significantly lower in preterm infants with RDS (7.76 +/- 2.28 in mild cases and 3.64 +/- 1.22 in severe cases) as compared to preterm infants without RDS (16.61 +/- 4.58) and controls (16.48 +/- 3.23) (p < 0.001). Infants with severe RDS especially those with small gestational age (GA), low birth weight (BW) and low APGAR score at 1 and 5 minutes had significantly lower cord blood VEGF level than those with mild RDS (p < 0.001). There was no significant effect on the level of VEGF regarding maternal use of antenatal steroids, premature rupture of membrane (PROM) and sex of newborn infants (P > 0.05). The sensitivity and specificity of cord blood VEGF test was 80% and 62% respectively with positive predictive value (PPV) of 80% and negative predictive value 56% at cutoff point of 10.02 ng/mL. It's concluded that cord blood VEGF elevation is associated with the absence of RDS, and that its level negatively correlates with the severity of the disease and duration on ventilation.