Fibrogenic/Angiogenic Linker for Non-Invasive Assessment of Hepatic Fibrosis Staging in Chronic Hepatitis C Among Egyptian Patients.

Background and rationale for the study. Liver biopsy is the golden standard for staging liver fibrosis, but it may be accompanied by complications. Because of this complication, the aim of this study is to evaluate a simple noninvasive score to assess hepatic fibrosis in chronic hepatitis C genotype 4 patients which is very may have an important in diagnosis and therapeutic decision. This score [HA vascular (HAV) score] is a combination of direct markers [hyaluronic acid (HA) and vascular endothelial growth factor (VEGF)] and indirect markers [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)]. RESULTS: Samples were collected from 220 patients (F0-F4): an estimated group (n = 120) and a validated group (n = 100). HA and VEGF levels, HCV RNA, liver function tests, platelet counts were assayed, Fibroscan was done and liver biopsy was taken and the stage of liver fibrosis and the grade of inflammatory activity was calculated according to Metavir score system. HA vascular (HAV) score = -35.1 + 0.14 (HA) (ng/L) + 0.03 (VEGF) (pg/mL) + (-6.7) [AAR (AST/ALT ratio)]. The HAV score produced areas under curve of 0.979 and 0.994 for significant (F2-F4) and advanced fibrosis (F3-F4) (cut off = 0.583 and 6.3, respectively). Surprisingly, the validation study of this score gave very good values of AUCs i.e. 0.990, 0.996 and 0.995 for significant, advanced and liver cirrhosis. CONCLUSIONS: Our developed score can not only help to assess liver fibrosis staging effectively but also avoid the invasiveness and the limitations of liver biopsy in Egyptian hepatitis C virus patients.

Smart chitosan nanogel for targeted doxorubicin delivery, ensuring precise release, and minimizing side effects in Ehrlich ascites carcinoma-bearing mice.

In recent decades, bio-polymeric nanogels have become a forefront in medical research as innovative in-vivo drug carriers. This study introduces a pH-sensitive chitosan nanoparticles/P(N-Isopropylacrylamide-co-Acrylic acid) nanogel (CSNPs/P(NIPAm-co-AAc)), making significant advancements. The nanogel effectively encapsulated doxorubicin hydrochloride (Dx. HCl), a model drug, within its compartments through electrostatic binding. Comparing nano chitosan (CSNPs) before and after integrating copolymerized P(NIPAm-co-AAc), highlighting an improved and adaptable nanogel structure with responsive behaviors. The intraperitoneal delivery of Dx-loaded nanogel (Dx@N.gel) to Ehrlich ascites carcinoma (Eh)-bearing mice at doses equivalent to 1.5 and 3 mg/kg of Dx per day for 14 days exhibited superiority over the administration of free Dx. Dx@N.gel demonstrated heightened anticancer activity, significantly improving mean survival rates in Eh mice. The nanogel's multifaceted defense mechanism mitigated oxidative stress, inhibited lipid peroxidation, and curbed nitric oxide formation induced by free Dx. It effectively countered hepatic DNA deterioration, normalized elevated liver and cardiac enzyme levels, and ameliorated renal complications. This pH-responsive CSNPs/P(NIPAm-co-AAc) nanogel loaded with Dx represents a paradigm shift in antitumor drug delivery. Its efficacy and ability to minimize side effects, contrasting sharply with those of free Dx, offer a promising future where potent cancer therapies seamlessly align with patient well-being.

Discriminant function based on parameters of hyaluronic acid metabolism and nitric oxide to differentiate metastatic from non-metastatic colorectal cancer patients.

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. Because there is currently no useful serological marker for metastatic colorectal cancer, the search for simple biomarkers for colorectal cancer diagnosis and prognosis is needed. Hyaluronic acid level was determined by ELISA; in addition to its degrading enzymes, degradation products and nitric oxide were determined by standard techniques in 185 CRC patients with and without metastases. Statistical analyses were performed by logistic regression and receiver-operating characteristic (ROC) curves. The multivariate discriminate analysis (MDA) selects a function based on absolute values of six biochemical markers; score = [-0.62 (numerical constant) + hyaluronic acid (pg/l) × 0.002 + hyaluronidase (mg N-acetyl glucosamine/ml/18 h) × 0.009-ß-glucuronidase (µmol/ml/min) × 0.07 + N-acetyl-ß-D-glucosaminidase (µmol/ml/min) × 0.019-glucuronic acid (µg/dl) × 0.001 + nitric oxide (µmol/l) × 0.01]. The selected MDA function correctly classified 92% of the metastatic CRC patients at a discriminate cut-off score = 0.24 (i.e., less than 0.24 indicated patients with non-metastatic colon cancer, and greater than 0.24 indicated patients with metastatic colon cancer with high degrees of sensitivity (100%) and specificity (93%)). The positive predictive and negative predictive values were also high (81% and 85%, respectively). Colorectal cancer patients can be simply and efficiently classified into metastatic or non-metastatic using their MDA score.

Occupational exposure to gasoline in gasoline station male attendants promotes M1 polarization in macrophages.

Several studies have reported the toxicological implications of exposure to petroleum hydrocarbon fumes in animal models. There is little documentation on the effect of such exposure on oxidative stress levels and immune response. To our knowledge, no documentation of M1 polarization in macrophages in gasoline station male attendants. Therefore, this study aimed to evaluate the harmful effects of gasoline vapors in 62 male attendants (16-70 years) compared to 29 age- and sex-matched-unexposed controls. The attendants were recruited from Damietta governorate gasoline stations. Gasoline exposure induced a significant increase in tumor necrosis factor-α (TNF-α) level (p < 0.05) as well as a slight but non-significant increase in the activity of acidic mammalian chitinase (AMCase) (p > 0.05). Further TNF-α/AMCase ratio was significantly increased (p < 0.01) in sera of the attendants when compared to those of the healthy controls. Also, the total leucocytic and lymphocytic counts were significantly increased (p < 0.01 and p < 0.001, respectively). On contrary, neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) were significantly decreased (p < 0.05 and p < 0.001, respectively). In addition, significant reduction in hemoglobin (Hb) concentration, plasma glutathione reduced form (GSH), and catalase, as well as superoxide dismutase (SOD) activities in red blood cells were observed in the exposed attendants. As a result, malondialdehyde (MDA), nitric oxide (NO) levels, and NO/AMCase ratio were significantly increased (p < 0.05). In conclusion, this study inferred that prolonged gasoline exposure can mediate immune activation, especially M1 macrophages polarization, possibly via oxidative stress-mediated mechanism.

Diagnostic performance of extrinsic apoptosis pathway in hepatitis C virus patients: apoptosis fibrosis crosstalk.

BACKGROUND/AIM: Liver fibrosis assessment and evaluation of disease severity in hepatitis C virus (HCV) patients provides useful information for therapeutic decisions. Chronic HCV infection is associated with increased levels of peripheral T cell apoptosis. The aim was to study whether peripheral blood T lymphocyte apoptosis markers may contribute to clinical progression, and develop a simple index based on combination of apoptosis and routine biomarkers for accurate evaluation of fibrosis stages in HCV patients. PATIENTS AND METHODS: Peripheral blood T lymphocytes were isolated from 72 patients with hepatitis C virus and 25 healthy control individuals. Serum samples were collected at time of liver biopsy. Liver fibrosis was tested in biopsies using the Metavair score system. Stepwise linear discriminate analysis and area under receiver-operating characteristic curves were utilized to produce a predictive score comprising significant apoptosis biomarkers. RESULTS: A novel score named apoptosis fibrosis index (AFI) was created on the basis of a combination of CD8/Annexin, albumin and platelets. The multivariate discriminate analysis selected a score based on absolute values of the three biochemical markers; score = 5.8 + 0.008×CD8/Annexin-V (%) - 1.4×Albumin (g/dl) - 0.001×Platelet count (10/L), where 5.8 considered numerical constant. AFI produce an area under the curve of one for significant fibrosis, 0.80 for advanced fibrosis, and 0.889 for cirrhosis. CONCLUSION: Apoptosis biomarkers in HCV patients were associated with liver fibrosis. AFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage and may decrease the need for liver biopsy in hepatitis C virus Egyptian patients.

Adverse effects of energy drink on rat pancreas and the therapeutic role of each of bone marrow mesenchymal stem cells and Nigella Sativa oil.

BACKGROUND: Energy drinks have been observed to threaten public health leading to many medical problems. Bone marrow-derived mesenchymal stem cells (BMSCs) have broad prospects in tissue regeneration. Nigella Sativa (NS) possess great therapeutic properties for the treatment of a wide range of diseases. MATERIALS AND METHODS: Forty adult male albino rats were divided into: control group and treated group. The treated group was further subdivided into: energy drink subgroup 2a, BMSCs-injected subgroup 2b, NS-injected subgroup 2c. Histological, immunohistochemical and biochemical assessment was performed. RESULTS: Administration of energy drink revealed that it adversely affected the pancreatic cytoarchitecture. BMSCs and NS have been similarly observed to significantly ameliorate the histological, biochemical and immunohistochemical changes induced by energy drink. CONCLUSIONS: The extent of pancreatic regeneration, exerted by each of BMSCs and NS oil, is nearly similar but the effect of BMSCs is more superior; however, NS could be privileged to BMSCs as a line of treatment being easily accessible and of lower cost.

Noninvasive estimation of liver fibrosis in biopsy-proven hepatitis C virus-infected patients: angiogenic fibrogenic link.

BACKGROUND/AIM: The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decisions. This study aimed to develop and evaluate a predictive score named the angiogenic index (Angio-Index) for liver fibrosis staging and to compare Angio-Index by King, Gotebörg University Cirrhosis Index, Lok, FIB-4, and aspartate aminotranferase/alanine aminotranferase scores in hepatitis C virus-infected patients. PATIENTS AND METHODS: Serum levels of angiopoietin-2, basic fibroblast growth factor, hepatocyte growth factor, and endostatin were assayed using an enzyme-linked immunosorbent assay in 122 HCV patients represented in two sets (estimation group and validation group). Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were utilized to produce a predictive score comprising significant angiogenic biomarkers. RESULTS: A novel score named the Angio-Index score was created on the basis of a combination of angiopoietin-2, basic fibroblast growth factor, hepatocyte growth factor, and endostatin. Angio-Index produces an AUC of 0.90 for significant fibrosis, 0.865 for advanced fibrosis, and 0.857 for cirrhosis. The Angio-Index score correctly classified 71% of the significant fibrosis (F2-F4) with a sensitivity of 93% and a specificity of 91%. The Angio-Index had a similar AUC in the validation study. The above six scores showed lower AUCs than Angio-Index. CONCLUSION: Whereas liver biopsy is invasive, costly, and associated with complications, Angio-Index is simple, noninvasive, and more accurate; it may decrease the need for liver biopsy in Egyptian patients.

Discriminant function based on hyaluronic acid and its degrading enzymes and degradation products for differentiating cirrhotic from non-cirrhotic liver diseased patients in chronic HCV infection.

BACKGROUND/AIMS: The invasive liver biopsy is still considered the gold standard for assessing patients with chronic hepatitis C (CHC). Our aim was to determine the operating characteristics of a non-invasive index based on blood biomarkers for the prediction of cirrhosis in CHC patients. METHODS: Hyaluronic acid level was determined by radioimmuno-assay and its degrading enzymes and degradation products were determined by standard techniques in 153 patients with CHC with and without liver cirrhosis. Statistical analyses were performed by logistic regression, and receiver-operating characteristic (ROC) curves. RESULTS: The multivariate discriminant analysis (MDA) selected a function based on absolute values of five biochemical markers; Score=[1.63+Hyaluronic acid (microg/l)x0.001+N-acetyl-beta-d-glucosaminidase (micromol/ml/min)x0.02+glucuronic acid (microg/dl)x0.015+glucosamine (microg/dl)x0.006+AST/ALT ratiox0.04]. The selected MDA function correctly classified 96% of the cirrhotic patients at a discriminant cut-off score=2.5 (i.e. less than 2.5 indicated CHC without liver cirrhosis and greater than 2.5 indicated liver cirrhosis) with high degrees of sensitivity (95%) and specificity (97%). The positive predictive and negative predictive values were also high (95% and 97%, respectively). CONCLUSION: A patient with CHC can be simply and efficiently classified into cirrhotic or non-cirrhotic liver diseased patient using his or her MDA score.

The effect of daylength and level of feeding on serum prolactin in growing lambs.

Twenty-four castrated male lambs initially maintained on a photoperiod of 12 h light:12 h dark were allocated to a factorial experiment with two daylengths (8 h L: 16 h D or 16 h L: 8 h D) and two levels of feeding (restricted or ad libitum). Blood samples were taken every 4 h for 24 h during the introductory period and after 24, 51 and 79 days of treatment. There were highly significant positive effects of daylength and level of feeding on serum prolactin: mean concentrations increased from a mean of 38 plus or minus 1 ng/ml during the introductory period until at day 79 they were: 8L: 16D (restricted diet), 81 ng/ml; (food ad libitum), 167 ng/ml; 16L:8D (restricted diet), 262 ng/ml; (food ad libitum), 262 ng/ml (S.E. of treatment mean plus or minus 4). Long daylength and feeding ad libitum also significantly increased growth rate.

Assessment of certain neutrophil receptors, opsonophagocytosis and soluble intercellular adhesion molecule-1 (ICAM-1) following thermal injury.

Polymorphonuclear leukocytes (PMLs) play a key role in host defense, and phagocyte dysfunction has been associated with increased susceptibility to infections in patients with thermal injury. Intercellular adhesion molecule-1 (ICAM-1) plays a role in leukocyte accumulation and extravasation. Therefore, the aim of the present study was to assess the PMLs expression of opsonin receptors: Fc gamma RIII, CR1 and CR3; opsonophagocytosis of PMLs and plasma soluble ICAM-1. Flow cytometric analysis (FCM) was used to study PMLs expression of IgG Fc-receptor III (Fc gamma RIII) as well as the complement receptors CR1 (receptor for C3b) and CR3 (receptor for C3bi) in 23 patients with large burns. Analysis of PML complement- and immunoglobulin-mediated phagocytosis of Candida albicans were performed in parallel using the phagocytic index. Plasma sICAM-1 was determined using ELISA. This study revealed a significant increase, with variable degrees, in CR1 and CR3-dependent fluorescence, complement-mediated phagocytosis of C. albicans and plasma sIGAM-1 that started at day 2 and remained for about 20 days before normalization. In contrast, Fc gamma RIII-dependent fluorescence and Ig-mediated phagocytosis were significantly decreased versus the control values. These results demonstrate significant changes of PMLs opsonin receptors expression and opsonophagocytosis documenting systemic activator of PMLs after large burns. In addition, elevation of plasma sICAM-1 may enhance the harmful effect of neutrophil activation through leukocyte accumulation and extravasation through endothelial damage in skin and in lung.

Role of hyaluronic acid, its degrading enzymes, degradation products, and ferritin in the assessment of fibrosis stage in Egyptian patients with chronic hepatitis C.

BACKGROUND/AIMS: Liver biopsy is considered a gold standard for fibrosis staging, but it has a high risk of morbidity. Therefore, there is an interest in developing noninvasive markers for the prediction of liver fibrosis stages. METHODS: Hyaluronic acid, ferritin, N-acetyl-ß-D-glucosaminidase, ß-glucuronidase, glucosamine, aspartate transaminase, and alanine transaminase were assayed in 210 individuals with chronic hepatitis C infection. Statistical analysis was carried out by logistic regression and receiver-operating characteristic curves. RESULTS: The best linear combination of only significant blood markers was used for the determination of the fibrosis discriminant score; score=[1.64 (numerical constant)-0.002×hyaluronic acid (pg/l)-2.68×ß-glucuronidase (µmol/ml/min)-0.026×glucosamine (µg/dl)-0.001×ferritin-0.033 (ng/ml)×aspartate transaminase/alanine transaminase]. The selected fibrosis discriminant score function correctly classified 81% of patients with severe liver fibrosis at a discriminant cut-off score=0.55 (i.e. less than 0.55 indicated mild liver fibrosis and greater than 0.55 indicated severe liver fibrosis), with a sensitivity of 100% and a specificity of 73%. CONCLUSION: A simple fibrosis index can be useful to select hepatitis C virus-infected patients with a very low risk of significant fibrosis in whom the protocol of liver biopsies may be avoided.

Development of a novel metastatic breast cancer score based on hyaluronic acid metabolism.

Tumor metastasis involves the dissemination of malignant cells into the basement membrane, and the vascular system contributes to the circulating pool of these markers. In this context, our aim has been focused on the development of a non-invasive score based on degradation of the backbone of glycosaminoglycans of the extracellular matrix; namely hyaluronic acid (HA), for the assessment of metastasis in patients with breast cancer. HA level was determined by enzyme-linked immunosorbent assay; CA 15.3 was determined by microparticle enzyme immunoassay; hyaluronidase, N-acetyl-ß-D-glucosaminidase, ß-glucuronidase, glucuronic acid, and glucosamine were assayed by standard colorimetric techniques in 217 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver-operating characteristic analysis curves. The multivariate discriminant analysis selects a score based on absolute values of the six biochemical markers: metastatic breast cancer score (MBCS) = [1.04 (Numerical constant) + 0.003 × CA 15.3 (U/l) + 0.001 × HA (ng/ml) + 0.004 × hyaluronidase (mg N-acetyl-ß-D-glucosamine/ml/18 h) + 0.001 × N-acetyl-ß-D-glucosaminidase (µmol/ml/min) + 0.026 × glucuronic acid (ng/ml) + 0.003 × glucosamine (µg/dl)]. This function correctly classified 87 % of metastatic breast cancer at cut-off value = 0.85 (i.e., great than 0.85 indicates patients with metastatic breast cancer and less than 0.85 indicates patients with non-metastatic breast cancer). MBCS is a novel, non-invasive, and simple score which can be applied to discriminate patients with metastatic breast cancer.

Specific gravity measurements of lamb carcass joints.

10 Ossimi lamb carcasses were used to determine the specific gravity values of different joint cuts. The correlation coefficients were established between the specific gravities of these joints and the percentages of fat and muscle in the rib saddle joint. It was found that the gravity of different carcass sections was significantly related to the muscle and fat percentages in the rib saddle joint. The results indicate that the specific gravity values of carcass sections can be utilized for a practical estimate and assessment of carcass components.