Comparing Effectiveness of Hyaluronic Acid-Chitosan Nanoparticles Encapsulation Versus Hyaluronic Acid Monotherapy in Osteoarthritis Rat Model: Microarray Screening for miR-140.

Osteoarthritis is a debilitating, progressive joint disease linked to lower quality of life and higher health care costs. This study compared hyaluronic acid-chitosan nanoparticle encapsulation to hyaluronic-acid monotherapy in a rat model of knee osteoarthritis. Four groups of 40 adult male albino rats were designed. Group (Gp) I: control; Gp II (osteoarthritis model): intra-articular injection of monoiodoacetate; Gp III (hyaluronic acid-treated): intra-articular injections of hyaluronic-acid on days 14 and 21 after monoiodoacetate injection; and Gp IV (hyaluronic acid-chitosan nanoparticle-treated): intra-articular injections of hyaluronic acid-chitosan nanoparticle on days 14 and 21 after monoiodoacetate injection. After 28 days, knee joints were examined using H&E, Safranin O, and immunohistochemistry for nuclear factor kappa beta (NF-κB), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase (MMP)-13. Quantification for gene expression of collagen-II, aggrecan, and micro-RNA-140; ELISA for interleukin (IL)-1ß and IL-8; and western blotting for IKBα and NF-κB was estimated. Osteoarthritis-knee joints showed a severe cartilage damage and synovial inflammation with increased NF-κB, iNOS, and MMP-13 immunostaining, decreased miR-140, collagen II, and aggrecan levels, and increased inflammatory markers' gene expressions. The hyaluronic acid-chitosan nanoparticle significantly improved knee joint structure and reduced inflammatory cytokines compared to hyaluronic acid monotherapy. Intra-articular injection of hyaluronic acid-chitosan nanoparticle encapsulation revealed a significant improvement in the knee joint structure compared to hyaluronic-acid in a rat model of osteoarthritis.

Role of trace elements in pityriasis Alba.

BACKGROUND: Pityriasis Alba (PA) is a common skin disorder affecting the children and it has multiple risk factors. OBJECTIVES: To assess the serum levels of trace elements (copper, zinc, and magnesium) and hemoglobin (Hb) level in patients with PA. METHOD: This is a case control study; 110 participants (55 cases and 55 controls) were recruited from pediatric dermatology and family medicine clinics, Cairo university hospitals. Patients were allocated into two groups, PA group (randomly selected male and female children age group (6-16) with PA lesions) and a matched control group. Full history was taken including sociodemographic data, present history of the lesions. Full general and dermatological examination was done. Blood samples were taken to asses iron and trace elements levels. The gained measures were analyzed by (SPSS) program version 22. RESULTS: This study showed that Hb levels, serum ferritin, copper, zinc and magnesium were significantly lower in PA group. There was statistically significant difference between both cases and controls regarding trace elements (copper, zinc, and magnesium) with (p value was 0.000, 0.000 and 0.003) respectively. Zinc deficiency increased the risk by more than 15 folds. Also, there was statistically significant difference between both groups regarding Hb levels and serum ferritin (p value was 0.000). The reduced Hb level increases the risk of PA by more than nine folds (OR 9.6) CONCLUSION: PA is associated with reduced levels of Hb, serum zinc, ferritin, copper and magnesium; sun exposure, skin phototype were found to be important risk factors for PA.

Modification of Diet in Renal Disease equation underestimates glomerular filtration rate in Egyptian kidney donors.

OBJECTIVES: Inulin clearance and radioisotope studies are the most accurate means of measuring glomerular filtration rates (GFRs). The Kidney Disease Outcomes Quality Initiative guidelines recommend estimating GFRs with the Modification of Diet in Renal Disease (MDRD) or the Cockcroft- Gault equation. We examined the accuracy of the MDRD equation and creatinine clearance based on 24-hour urine collection to predict GFRs in a group of healthy donors. MATERIALS AND METHODS: We examined the medical records of 100 kidney donors who had undergone 99mTc-diethylenetriamine-pentaacetic acid (DTPA) renal clearance and creatinine clearance measurements at the transplant outpatient clinic of Cairo University Hospital in Cairo, Egypt, between June 2002 and July 2006. GFR was predicted with the abbreviated MDRD formula. We examined significant differences, potential correlations, and agreements between GFR as predicted and as measured. RESULTS: The mean eGFRMDRD was 8.16% lower than the 99mTc-DTPA GFR (116.11 -/+ 25.44mL/min/1.73m2 vs 126.32 -/+ 24.21 mL/min/1.73 m2; difference range, -84 to +61 mL/min/1.73 m2; P = .002). Creatinine clearance was 13.14% higher than the 99mTc-DTPA GFR (142.90 -/+ 27.51 mL/min/1.73 m2; difference range, +65 to -60 mL/min/1.73 m2; P < .001). A significant positive correlation was observed when creatinine clearance and 99mTc-DTPA-measured GFR were compared (R=0.451; P = .000). No significant correlation was noted between eGFRMDRD and 99mTc-DTPA-measured GFRs (R=0.126; P = .211). A Bland-Altman analysis showed poor agreement between GFRMDRD and creatinine clearance on the one hand and measured GFR on the other. CONCLUSIONS: Neither the MDRD equation nor creatinine clearance is accurate in predicting GFRs in healthy donors.

The cellular selection between apoptosis and autophagy: roles of vitamin D, glucose and immune response in diabetic nephropathy.

BACKGROUND AND AIMS: Apoptosis, autophagy and cell cycle arrest are cellular responses to injury which are supposed to play fundamental roles in initiation and progression of diabetic nephropathy (DN). The aims of the present study is to shed light on the potential effects of vitamin D analog 22-oxacalcitriol (OCT) on different cell responses during DN, and the possible interplay between both glucose, immune system and vitamin D in determining the cell fate. METHOD: All rats were randomly allocated into one of three groups: control, vehicle-treated DN group and OCT-treated DN group. Eight weeks after induction of diabetes, the rats were killed. Fasting blood glucose levels, serum 25 (OH) D, renal functions, cytokines and gene expression of autophagy, apoptotic and cell cycle arrest markers were assessed. In addition, the histological assessment of renal architecture was done. RESULTS: OCT treatment remarkably improved the renal functions and albuminuria. The reductions in mesangial cell hypertrophy, extracellular matrix as well as cell loss were significantly associated with upregulation of pro-autophagy gene expressions and downregulation of both pro-apoptotic and G1-cell cycle arrest genes expression. The reno-protective effects of OCT treatment were associated with significant attenuation of the fasting blood glucose, serum IL-6, renal TLR-4 and IFN-g gene expression. CONCLUSION: Modulator effects of OCT on glucose and immune system play important roles in renal cell fate decision and chronic kidney disease progression.

Malondialdehyde; Lipid peroxidation plasma biomarker correlated with hepatic fibrosis in human Schistosoma mansoni infection.

Schistosomiasis is a debilitating parasitic disease, affects large number of host species. Currently affects 250-300 million people in tropic areas. Schistosoma pathogenic impact is hepatic periportal fibrosis; the parasite-induced inflammatory cellular activation promotes oxidative stress, resulting in lipid peroxidation (LPO), with subsequent increase in inflammatory mediators as malondialdehyde (MDA). This study was set up to reveal possible contribution of lipid peroxidation byproducts MDA in hepatic pathophysiology. Results displayed that MDA don't tend to change in relation with either age, nor hepatic transaminases AST & ALT, while exhibited a significant increase in MDA levels in human schistosomiasis versus control group P<0.0001 (Mn. ± St.dev. 7.77 ± 3.59, 1.21 ± 0.28 nmol/ml) respectively. Moreover; MDA plasma levels in Schistosoma infected group correlated significantly with two hepatic fibrosis parameters; (a) ultrasonography graded periportal fibrosis P< 0.0001. Levels of MDA in hepatic fibrosis grades 0, I, II, III in Schistosoma infected group were (Mn. ± St.dev. 2.8 ± 0.64, 4.3 ± 1.2, 9.3 ± 1.6 and 10.8 ± 1.3 nmol/ml) respectively, (b) serum Hyaluronic acid (HA) P<0.0001 (spearman r = 0.77) as a reliable hepatic fibrosis marker. This implies a considerable role of LPO byproducts in schistosomiasis pathogenicity, and proposing malondialdehyde as a biomarker for schistosomiasis morbidity.

Study of the effects of cyclooxygenase-2 inhibitor on the promotion of hepatic tumorigenesis in rats fed a high fat diet.

BACKGROUND/OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The highest prevalence of hepatitis is an important risk factor contributing to development of HCCs. However, an increasing number of cases are associated metabolic disease and steatohepatitis. Inflammation associated with many liver disease, seems to be a necessary pre-requisite for successful tumor initiation. Mechanisms that link high fat diet and inflammation initial stage of HCC are not completely understood. The present work was designed to investigate the effect of fat, through modulation of the insulin-like growth factors I and II (IGF-I and IGF-II), on the promotion of hepatocellular carcinoma, and the role of cyclooxygenase 2 (COX-2). METHODS: two main groups of rats were used: control and HCC groups. The HCC group was further sub-divide in to two subgroups, HCC fed with standard diet and HCC fed with high fat diet. The effects of celecoxib were also investigated in HCC fed with high fat diet. RESULTS: We found that high fat diet was associated with significant increases in COX2 and interleukin 6 (IL6) with significant promotion of HCC progression. The significant increase in IGF could contribute partially to the observed effects of high fat diet. In addition, celecoxib was found to significantly reduce HCC progression. CONCLUSIONS: We conclude that COX2 could play central role in high prevalence of HCC observed with high fat diet. Several triggering factors such as IGF and IL6, together with the direct modulation of fat metabolism could open several novel preventive strategies of celecoxib treatment, and could be useful biomarkers for assessment of its pharmacological effects.

Can we consider the right hepatic lobe size/albumin ratio a noninvasive predictor of oesophageal varices in hepatitis C virus-related liver cirrhotic Egyptian patients?

BACKGROUND: The current guidelines recommend the screening of all cirrhotic patients by endoscopy, but repeated endoscopic examinations are unpleasant for patients and have a high cost impact and burden on endoscopic units. The aim of this study is to evaluate the optimal liver lobe size/albumin ratio and to compare this ratio with spleen size, platelet count and platelet count/spleen diameter ratio as potential noninvasive predictors of oesophageal varices in hepatitis C virus (HCV)-related liver cirrhosis in Egyptian patients. METHODS: This prospective study included one hundred patients with HCV-related liver cirrhosis. All studied subjects underwent a detailed clinical examination, biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound. The platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio for all patients were calculated. RESULTS: The 4 predictors demonstrated a high statistically significant correlation with the presence and grade of oesophageal varices (P values<0.001). The platelet count/spleen diameter ratio had the highest accuracy, followed by the right liver lobe/albumin concentration ratio, spleen size and then platelet count. CONCLUSION: The use of the studied noninvasive predictors, especially the platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio, can help physicians by restricting the use of endoscopic screening only to patients presenting a high probability of oesophageal varices. This is especially useful in clinical settings where resources are limited and endoscopic facilities are not present in all areas. Such is the case in Egypt, where there is a large number of patients who require oesophageal screening for oesophageal varices.

Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection.

AIM: To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-four patients with chronic HCV infection were included in this study; 124 patients were non-cirrhotic, and 30 were cirrhotic. The following measurements were obtained in all patients: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin, prothrombin time and concentration, complete blood count, hepatitis B surface antigen (HBsAg), HCVAb, HCV-RNA by quantitative polymerase chain reaction, abdominal ultrasound and ultrasonic-guided liver biopsy. The following ratios, scores and indices were calculated and compared with the results of the histopathological examination: AST/ALT ratio (AAR), age platelet index (API), AST to platelet ratio index (APRI), cirrhosis discriminating score (CDS), Pohl score, Göteborg University Cirrhosis Index (GUCI). RESULTS: AAR, APRI, API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%, 79.2%, 76.6% and 80.5%, respectively); P values were: < 0.01, < 0.05, < 0.001 and < 0.001, respectively. Among the studied parameters, AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5, respectively. APRI, API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P < 0.001, < 0.001 and < 0.005, respectively), while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P > 0.05). In addition, we found significant correlations for the AAR, APRI, API, GUCI and Pohl score between the non-cirrhotic (F0, F1, F2, F3) and cirrhotic (F4) groups (P values: < 0.001, < 0.05, < 0.001, < 0.001 and < 0.005, respectively; CDS did not demonstrate significant correlation (P > 0.05). CONCLUSION: The use of AAR, APRI, API, GUCI and Pohl score measurements may decrease the need for liver biopsies in diagnosing cirrhosis, especially in Egypt, where resources are limited.

A comparative study between three noninvasive predictors of oesophageal varices in post hepatitis C virus liver cirrhosis in Egypt.

BACKGROUND AND AIM: The prevention of variceal bleeding is very important. The current guide lines recommend screening of all cirrhotic patients by endoscopy, to identify patients at risk of bleeding in whom prophylactic treatment should be started. Repeated endoscopic examinations are unpleasant for patients, and carry a high cost impact and burden on endoscopic units, while only 50% of cirrhotic patients have esophageal varices, 30% of whom have large varices. The aim of this study is to evaluate prospectively the spleen size, platelet count and platelet count/spleen diameter ratio as noninvasive predictors of oesophageal varices in post hepatitis C virus liver cirrhosis in Egypt. PATIENTS AND METHODS: One hundred patients with post hepatitis C virus liver cirrhosis were included in the study. All studied subjects underwent a detailed history taking, clinical examination, biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound. The platelet count to spleen diameter ratio was calculated. RESULTS: All the 3 predictors showed high statistically significant correlation with the presence, size and the grade of oesophageal varices (P < 0.01). Among the 3 noninvasive predictors the platelet count/spleen diameter ratio gave the highest accuracy (94%) at a cut-off value of 1326.58 followed by the spleen size (89%) at a cut-off value of 131.5 mm and lastly the platelet count (84%) at a cut-of value of 131000/mm3. CONCLUSION: The use of the three studied predictors in this study can help the physicians to restrict endoscopy to those who are highly suspected to have oesophageal varices.