Camel Milk: Potential Utility as an Adjunctive Therapy to Peg-IFN/RBV in HCV-4 Infected Patients in Egypt.

The present prospective study aims to investigate the potential therapeutic effect and the underlying mechanisms of drinking camel milk for 60 days as an adjunctive therapy to the standard treatment PEG/RBV. Twenty-five hepatitis C virus (HCV)-infected Egyptian patients, with mild to moderate parenchymal affection to mild cirrhosis were enrolled in this study after proper history taking and clinical examination. Their biomarkers were evaluated before and after the addition of camel milk. The improving effect of camel milk was reflected on the marked inhibition of the serum levels of the proinflammatory markers, viz., tumor necrosis factor-α, monocyte chemotactic protein-1, hyaluronic acid, and TGF-ß1, besides PCR, AST, ALT, GGT, bilirubin, prothrombin time, INR, and alpha-fetoprotein. In addition, camel milk elevated significantly (P < 0.001) the serum levels of albumin, the antiapoptotic protein BCL-2, the total antioxidant capacity, interleukin-10, and vitamin D. In conclusion, our study revealed a regulatory function of camel milk on multiple parameters of inflammatory mediators, immunomodulators, antiapoptosis, and antioxidants, giving insight into the potential therapeutic benefit underlying the anti-HCV actions of camel milk. The limitations of the current study include the small sample size recruited and the failure to test it on cohorts with severe stages of hepatitis; like Child-Pugh stage C, and hepatocellular carcinoma.

An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database.

OBJECTIVES: This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). METHODS: Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. RESULTS: Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. CONCLUSIONS: This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

The antimicrobial ß-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1α, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFα (4.4-times) and TGFß1 (3.2-times) compared to controls (p < 0.05). Further, HEPC and HIF-1α levels were also increased (8.8- and 3.6-times control levels), while EPO levels were decreased (77.8%) from control levels. After 12 weeks of antibiotic therapy, all septic AKI patients showed significant improvement of the altered markers of kidney dysfunction. In line with significant reductions in serum TNFα and TGFß1 (25.5% and 26.2%, respectively), HEPC and HIF-1α levels were significantly decreased (31.6% and 19.3%), and EPO levels increased (1.9-fold) compared to pretreatment values. There was a significant positive correlation between HEPC levels and kidney function markers (SCr and BUN), inflammatory TNFα and TGFß1 and serum HIF-1α and pAKT in septic AKI patients before and after treatment. Based on the results here, we conclude that HEPC, EPO and HIF-1α are involved in the pathogenesis of sepsis-induced AKI and confirm the dominating effects of inflammatory determinants over hypoxia-related complications.

Cord blood fibroblast growth factor-10 as a possible predictor of bronchopulmonary dysplasia in preterm infants.

OBJECTIVE: To evaluate fibroblast growth factor-10 (FGF-10) levels in cord blood as a possible predictor of the subsequent development of bronchopulmonary dysplasia (BPD) in preterm infants. PATIENTS AND METHODS: A total of 269 preterm (≤32 weeks gestation) infants (76 infants developed BPD and 193 had no BPD) were enrolled. FGF-10 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Preterm infants who subsequently developed BPD had significantly lower cord serum levels of FGF-10 than those who did not (p < 0.001). Cord blood levels of FGF-10 were significantly lower in infants with severe BPD than those with moderate or mild disease (p < 0.001). Logistic regression analysis demonstrated that low cord blood FGF-10 level was independently associated with the subsequent risk of BPD (OR = 0.978 [95 % CI: 0.959 - 0.997]; p = 0.02). CONCLUSION: Low cord blood FGF-10 levels may predict the subsequent development of BPD in preterm infants.

Circulating IL-6, IL-17 and vitamin D in hepatocellular carcinoma: potential biomarkers for a more favorable prognosis?

Hepatitis C virus (HCV) infects primarily hepatocytes, leads to development of fibrosis and/or cirrhosis of the liver and is a significant factor for developing hepatocellular carcinoma (HCC). Evidence indicates that liver fibrosis contains uncontrolled inflammation as a part of its etiology. Normal cell-mediated immunity plays a central role in the mechanisms involved in viral clearance/persistence in the liver. In this context, cytokines modulate the immune system and exert direct anti-viral activity. To this end, this study investigated potential associations of serum IL-17 and IL-6 with exacerbation of hepatic damage in chronic HCV patients to determine their utility as prognostic markers for potential development of HCC. Chronic HCV-patients were recruited, divided into groups according to degree of liver damage, i.e. patients with peri-hepatic fibrosis, hepatic cirrhosis, or HCC, and had their blood collected for analysis of liver function and serum IL-6 and IL-17 levels. Interestingly, increases in serum IL-17 levels in the study groups were associated with aggravation of the clinical state from HCV to cirrhosis and then to HCC. Serum IL-6 levels followed a similar pattern. The association of both cytokines with progressive exacerbation of the initial HCV-induced liver damage was further confirmed by correlation analysis that revealed positive correlations between HCV RNA titer and IL-17 (+0.951, p < 0.05) and IL-6 (+0.85, p < 0.05). A receiver operating characteristics (ROC) analysis revealed their beneficial addition as promising biomarkers for a better prognostic profile of HCC. Interestingly, a significant progressive decline in the active vitamin D status was noted in all three clinical states, and these too were associated with progressive liver disease. This study confirms the necessity of adding screening for IL-6 and IL-17 and vitamin D to that of the classic marker AFP for patients with HCV and cirrhosis to hopefully permit clinicians to initiate measures that ultimately might mitigate/delay development of HCC in these infected patients.

Impact of congenital heart disease on brain development in newborn infants.

OBJECTIVE: To assess brain development and brain injury in neonates with cyanotic and acyanotic congenital heart disease (CHD). METHODS: The study included 52 term infants with CHD who were divided into two groups: Cyanotic (n=21) and acyanotic (n=31). Fifteen healthy neonates of matched age and sex were enrolled in the study as controls. Three-dimensional proton magnetic resonance spectroscopic imaging and diffusion tensor imaging were used to assess brain development and injury. We calculated the ratio of N-acetylaspartate (NAA) to choline (which increases with maturation), average diffusivity (which decreases with maturation), fractional anisotropy of white matter (which increases with maturation), and the ratio of lactate to choline (which increases with brain injury). RESULTS: As compared with control neonates, those with CHD had significant decrease in NAA/choline ratio (P<0.001), significant increase in lactate/choline ratio (P<0.0001), significant increase in average diffusivity (P<0.0001), and significant decrease of white matter fractional anisotropy (P<0.001). Neonates with cyanotic CHD had significant less brain development and more brain injury than those with acyanotic CHD (P<0.05). CONCLUSIONS: Newborn infants with cyanotic and acyanotic CHD are at high risk of brain injury and impaired brain maturity.

The effect of chemical inactivation of bovine viral diarrhea virus with beta-propiolactone and binary ethyleneimine on plasma proteins and coagulation factors.

In the present study chemical inactivation of bovine viral diarrhea virus (BVDV), as a substitute of hepatitis C virus was studied in human plasma pool. Beta-propiolactone (BPL), binary ethyleneimine (BEI) and chlorhexidine (CHX) were assessed. Treatment of virus-spiked human plasma with 0.025% BPL reduced virus infectivity titer to undetectable levels within 2 h, whereas BEI treatment (1 mM) showed a slower kinetic of inactivation, attaining a complete virus inactivation within 8 h of incubation. In contrast, CHX treatment at the adopted dose level (0.41mM) showed a limited virucidal capacity with a residual live virus titer after 24 h. BPL and BEI treatments reduced the recovery of labile plasma coagulation factors activity (V and VIII), while the activity of other coagulation factors (VII, IX and XI) was mildly decreased. Agarose gel electrophoresis of plasma proteins showed that albumin concentration is not affected, while gamma-globulin is slightly reduced by BPL and BEI treatment. Plasma fibrinogen level was modestly reduced by BPL treatment, while it remained unchanged by BEI treatment. This demonstrates the potential and safety use of BPL and BEI in BVDV inactivation in human plasma pool without affecting significantly the coagulant activity of important blood coagulation factors and the levels of plasma major protein fractions.