Tahia H. Saleem

Interleukins -6, -8 and -10 and tumor necrosis factor-alpha and its soluble receptor I in human milk at different periods of lactation

Abstract In the present study, levels of interleukins (IL-), IL-10, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) and soluble TNF-receptor I (sTNF-RI) were measured in the whey (aqueous phase) of 55 breast milk samples of lactating mothers. These milk samples were classified according to periods of lactation into: colostrum, transitional milk and mature milk. In addition, the levels of IL-10, sTNF-RI and IL-8 were measured in milk specimens from ten lactating mothers had pre-term babies and from nine lactating allergic mothers. The levels of IL-10, sTNF-RI, IL-6, IL-8 and TNF-α were detected in all milk samples at different periods of lactation. The levels of these cytokines in colostrum were significantly higher than transitional milk. In mature milk, the levels of IL-6 and IL-8, were significantly lower while the levels of IL-10 and TNF-α were significantly higher than their levels in transitional milk. The levels of IL-6, IL-8, TNF-α and sTNF-RI at the first 6 months of lactation were positively correlated between each other. TNF−α in colostrum was negatively correlated with TNF-α in mature milk. Non significant changes in the levels of IL-10, IL-8 and sTNF-RI were found between full term and pre-term milk and between breast milk of allergic and non-allergic mothers except IL-8 levels were significantly higher in the allergic group. The changes of pro- and anti-inflammatory cytokines at different periods of lactation may reflect the change in the immune system of the breast and alteration in the needs of the newborn for these cytokines. The chemoattractant cytokine, IL-8, was significantly elevated in mature milk of allergic mothers. The gestational age at delivery may nothave any effect on the breast milk levels of cytokines. The parity and socioeconomic conditions should be considered in such kind of study.

Study of surfactant level in cases of primary atrophic rhinitis.

The surfactant system of the nose was examined biochemically in control cases and compared to cases of primary atrophic rhinitis. The study group included 25 cases with primary atrophic rhinitis compared to 10 normal volunteers. Biochemical analysis of the nasal aspirate in these cases revealed the presence of phospholipids constituting surfactant with phosphatidylcholine constituting 75.35 per cent of the total phospholipids. Biochemical analysis of the nasal aspirate in cases with primary atrophic rhinitis revealed a significant decrease in the total phospholipids compared to normal cases and also a significant change in the phospholipid profile. Thus significant biochemical changes in the surfactant system of the nose is an evident and early finding in cases of primary atrophic rhinitis. This suggests a possible role for surfactant deficiency in the aetiopathogenesis of cases of primary atrophic rhinitis.

Surfactant Protein D, Soluble Intercellular Adhesion Molecule-1 and High-Sensitivity C-Reactive Protein as Biomarkers of Chronic Obstructive Pulmonary Disease

Objective: The aim of this study was to estimate the serum levels of surfactant protein D (SP-D), soluble intercellular adhesion molecule-1 (sICAM-1), and high-sensitivity C-reactive protein (hs-CRP) in patients with chronic obstructive pulmonary disease (COPD) and to assess the correlation of these indices with COPD severity. Subjects and Methods: This analytic cross-sectional study was carried out on 64 COPD male patients, and 26 apparently healthy age-matched males as a control. Chest X-ray, spirometry and arterial blood gases were done for only COPD patients. Serum levels of SP-D, sICAM-1 and hs-CRP were determined by enzyme-linked immunosorbent assay in both patient and control groups. Results: The serum levels of SP-D, sICAM-1 and hs-CRP were significantly higher in COPD patients than controls (p < 0.001 for each). Also, these biomarkers were significantly higher in stages III and IV compared to either stage I or II (p < 0.01 for each). SP-D was significantly positively correlated with sICAM-1 and hs-CRP (r = 515, p < 0.001; r = 501, p < 0.001, respectively) and negatively correlated with PaO2 (r = -0.651, p < 0.001) and all parameters of spirometry.Conclusion: SP-D, sICAM and hs-CRP were significantly higher in COPD patients in comparison with controls. Moreover, SP-D, sICAM-1, and hs-CRP were significantly negatively correlated with FEV1%. Accordingly, estimation of these biochemical indices may be used as biomarkers for assessment of COPD severity.

In vivo evaluation of a novel albumin-binding prodrug of doxorubicin in an orthotopic mouse model of prostate cancer (LNCaP).

PSA, which is overexpressed in prostate carcinoma, represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. In this study, we report on the in vivo antitumor efficacy of an efficacious albumin-binding prodrug of doxorubicin (PSA9) that incorporates p-aminobenzyloxycarbonyl (PABC) as a self-immolative spacer in addition to the heptapeptide, Arg-Ser-Ser-Tyr-Tyr-Ser-Leu, which serves as a substrate for PSA. The prodrug is cleaved very efficiently by PSA releasing H-Ser-Leu-PABC-doxorubicin and subsequently doxorubicin in PSA-positive cell lysates and prostate tumor homogenates as the final cleavage product. PSA9 at 3 × 6 mg kg−1 doxorubicin equivalents (intravenous) was compared with conventional doxorubicin at equitoxic doses (at 3 × 3 mg kg−1; intravenous) in an orthotopic mouse model of prostate cancer using LNCaP lentiviral luciferase-neomycin cells transduced with luciferase. Whereas doxorubicin did not show any efficacy against the primary tumor or metastases, the prodrug reduced the primary tumor by 30–50% and circulating PSA levels, and in addition, showed a pronounced reduction in lung and bone metastases by ∼77% and ∼96%, respectively, and a positive trend regarding the activity against liver and lymph-node metastases compared with control and doxorubicin-treated animals. The incorporation of PABC as a self-immolative spacer together with a PSA substrate demonstrates superior antitumor effects over doxorubicin attributed to an efficient cleavage by PSA releasing doxorubicin as the final active agent in prostate tumor homogenates. Using this approach for developing effective prodrugs against prostate cancer, is worthy of further preclinical optimization.

Possible Protective Effects of Quercetin and Sodium Gluconate Against Colon Cancer Induction by Dimethylhydrazine in Mice.

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

The antitumor activity of a lactosaminated albumin conjugate of doxorubicin in a chemically induced hepatocellular carcinoma rat model compared to sorafenib

BACKGROUND Worldwide, consistent survival benefit for chemotherapy in hepatocellular carcinoma (HCC) is a golden goal for concerned researchers. Nexavar® (sorafenib) is the only approved agent that achieved touchable successes in this regard. Thus, there is a pressing medical need for new promising drugs to improve HCC therapy. AIMS our designed lactosaminated albumin conjugate of doxorubicin (L-HSA-DOXO) that rapidly and preferentially accumulates in the liver is compared, for the first time at its MTD, with doxorubicin and sorafenib, not only for antitumor efficacy but also for overall survival. METHODS HCC was induced in male Wistar rats with N-nitrosodiethylamine added to drinking water (100mg/L) for 8 weeks. Endpoints were antitumor efficacy, tolerability and overall survival. RESULTS L-HSA-DOXO proved to be superior at least over doxorubicin in the majority of assessed endpoints. Circulating AFP-L3% was diminished in L-HSA-DOXO (14.5%) and sorafenib (18.4%) groups compared to DENA (31.1%) and doxorubicin (29.5%) groups. This superiority was further confirmed by Western blot analyses of some novel HCC biomarkers. Survival study reinforced consistent benefits of both L-HSA-DOXO and sorafenib. CONCLUSIONS L-HSA-DOXO shows at least comparable activity to sorafenib which clinically achieves only ∼3 months overall survival benefit. Combination of these two agents could act beneficially or synergistically via two different modes of action to fight HCC.

Time-dependent Morphological and Biochemical Changes following Cutaneous Thermal Burn Injury and Their Modulation by Copper Nicotinate Complex: An Animal Model

Background: Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). Objectives: To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. Materials and Methods: An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. Results: High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Conclusions: Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Increased circulating ANG II and TNF-α represents important risk factors in obese saudi adults with hypertension irrespective of diabetic status and BMI.

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk.

Prevalence of Lactose Intolerance in Primary School Children in Qena Governorate, Egypt

Most people are born with the ability to digest lactose. Approximately 75% of the general population loses this ability, to some extent, going into adulthood (adult hypolactasia), while others retain such ability. The aim of the present study was to determine the prevalence of lactose intolerance, and its correlation with gastrointestinal symptoms, in primary school children aged 6-12 years in Qena Governorate, Egypt. A cross-sectional study was carried out on 300 school children with clinical suspicion of lactose intolerance. Biological and clinical data were obtained from children’s parents or guardians. The history of diarrheal attacks especially following ingestion of milk or dairy products, as well as the incidence of diabetes in the children or family history of such diseases was also obtained. The children were instructed to maintain a low fiber diet without lactose for 48 hours prior to the day of examination. After 12 hours of fasting lactose tolerance test was carried out. The data obtained revealed that 74% of the participants in the study were intolerant to lactose. However, only 56.8% of lactose-intolerant children had positive clinical history of abdominal pain, abdominal distension or diarrheal attacks following ingestion of milk or dairy products. The prevalence of lactose intolerance in the studied cohort increased with age. Such genetically determined intolerance was 58% at 6-7 years of age and increased to 90% by the age of 11-12.

Clinical and biochemical study of D-serine metabolism among schizophrenia patients

Background Schizophrenia is a typical N-methyl-d-aspartate receptor (NMDA-R) hypofunction disorder. Decreased d-serine (d-Ser) levels in the periphery occur in schizophrenia and may reflect decreased availability of d-Ser to activate NMDA-R in the brain. Objective The objective of this study was to investigate the role of d-Ser metabolism in the pathogenesis of schizophrenia via biochemical assays and correlates, the serum level of d-Ser, d-serine racemase (SR) (responsible for its formation from l-serine [l-Ser]) and d-amino acid oxidase (DAAO) (responsible for its catabolism), among different clinical types of schizophrenia patients. Patients and methods This cross-sectional case–control study was carried out on 100 patients and 50 controls. They were recruited from the outpatients’ psychiatric unit of the Neuropsychiatric Department of Assiut University Hospital, Upper Egypt. The type of schizophrenia was determined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), while the severity of schizophrenia was determined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Serum d-Ser levels were estimated using high-performance liquid chromatography (HPLC), while serum SR and DAAO were measured using commercially available enzyme-linked immunosorbent assay kits. Results There were significantly lower mean serum levels of d-Ser and SR and significantly higher mean serum levels of DAAO (P-value <0.01 for each) among schizophrenia patients when compared with the control group. Paranoid schizophrenia had the highest frequency, with a significantly lower serum levels of d-Ser and SR in the residual type and significantly higher serum levels of DAAO in undifferentiated and catatonic types. Combined receiver-operating characteristic curve for serum d-Ser, SR and DAAO indicated that the best serum level cutoff points at which schizophrenia manifestations started to appear were ≤ 61.4 mg/L for d-Ser, ≤ 15.5 pg/mL for SR and >35.6 pg/mL for DAAO. Conclusion The present study confirms that disturbed d-Ser metabolism could be implicated in the pathogenesis of schizophrenia.