Evaluation of cardiac indices using M-mode echocardiography after administration of metoclopramide and ondansetron in donkeys (Equus asinus): an experimental study.

The aim of the present study was to evaluate cardiac indices using M-mode echocardiography after the administration of metoclopramide and ondansetron in donkeys. For this purpose, 10 apparently healthy Egyptian Baladi donkeys (Equus asinus) were used in a crossover prospective study. Two trials were conducted with the administration of metoclopramide hydrochloride anhydrous at a dose of 0.25 mg Kg-1 and ondansetron hydrochloride sodium at a dose of 0.15 mg Kg-1. The control group (placebo) received a total volume of 50 mL of isotonic saline at 0.9%. An echocardiographic examination was performed using a Digital Color Doppler Ultrasound System equipped with a 2-3.9 MHz phased array sector scanner transducer. In general, the fractional shortening (FS%) was significantly affected by the time for metoclopramide (p = 0.031) and ondansetron (p = 0.047) compared with those of placebo, with treatment with metoclopramide provoking significantly higher percentages of FS% at T60 (p = 0.009) and T90 (p = 0.028) compared with those for ondansetron and placebo. The interaction of time x treatment also showed a statistically significant alteration of FS% (p < 0.05), while the values returned to the basal line at T240. Metoclopramide induced a significant decrease in E-point to septal separation (EPSS) at T90 (p = 0.005), and T240 (p = 0.007) compared with ondansetron and placebo. The time x treatment interaction also showed a significant (p < 0.05) variation in EPSS, with values returning to the basal line at T300. Mitral valve opening velocity (DE SLP) values were significantly affected by time (p = 0.004) in the metoclopramide group compared with those of ondansetron and placebo. Administration of metoclopramide and ondansetron provoked significant alterations of DE SLP at T60 (p = 0.039), T120 (p = 0.036), and T300 (p = 0.005) compared with placebo. In conclusion, caution should be exercised when administering both treatments, especially to animals with suspected cardiac problems.

Noninvasive identification of molecular biomarkers of hepatocellular carcinoma in HCV-Egyptian patients.

BACKGROUND: This study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender. METHODS: The expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases. RESULTS: The baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1. CONCLUSIONS: Overall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP.

Natural inhibitors for acetylcholinesterase and autophagy modulators as effective antagonists for tau and ß-amyloid in Alzheimer's rat model.

Background: Phytochemicals have amazing biological effects in relation to age-related illnesses and are increasingly being studied in clinical trials. The goal of this study was to examine the effectiveness of the aqueous extracts of Rosmarinus officinalis L. (Rosemary) and Crocus sativus L. (Saffron) and their combinations as tau and ß-amyloid antagonists in an Alzheimer's rat model. Methods: AlCl3 and D-galactose (150 & 300 mg/kg) were used to create the Alzheimer's neuroinflammation rat model. The animals were subsequently given the two extracts and their combinations (500 mg/kg) along 15 days. The cognitive impairment, oxidative stress, tau & amyloid neuroproteins, acetylcholine, acetylcholinesterase neurotransmitters, proinflammatory cytokines, LC3 as an autophagy marker, computational analysis, and morphological alterations were all assessed. Results: When compared to the conventional donepezil and normal groups, the treated groups showed a significant improvement in all calculated parameters. The cortex and hippocampus have a better morphological appearance. In silico analysis found that these extracts may have an affinity for and impede the activity of some proteins thought to be essential regulators of disease progression. Conclusion: Rosemary and Saffron extracts by the power of their constituents were able to alleviate the neurotoxicity of AlCl3 & D-galactose and regulate the natural autophagy process.

Clinical Association of CD44 Expression with Proliferative Activity and Apoptotic State in Egyptian Patients Suffering from Ulcerative Colitis and Colorectal Carcinoma.

BACKGROUND AND AIM: Cancer stem cell markers were thoroughly investigated as a promising strategy for the prediction of patient outcome and therapeutic response. The prospective role of CD44 cell adhesion molecule in tumorigenic potential and its association with the proliferative activity and apoptotic status of Egyptian patients with ulcerative colitis (UC) and colorectal cancer (CRC) were investigated in this study. MATERIAL AND METHOD: Flow cytometric analyses of CD44, DNA cell cycle, and apoptosis identified by Annexin V/PI were performed on colonic tissue specimens obtained from 44 CRC patients, 36 UC patients, and 30 controls. RESULTS: The CRC patients showed overexpression of CD44 marker (p < 0.0001) in comparison with UC and control groups. Regression analysis identified CD44 marker as an independent predictor for tumor staging and grading (p < 0.0001) of CRC patients. The CD44 expression was positively correlated with tumor stage (r = 0.656), tumor grade (r = 0.645), and the proliferative activity of DNA cell cycle (S phase, r = 0.396). However, CD44 expression was negatively correlated with early apoptosis (r = - 0.525). CONCLUSION: According to our findings, there was a significant and  positive association between CD44 dysregulated expression and S phase of DNA cell cycle but a negative association with early apoptosis in CRC patients, suggesting CD44 role in apoptosis suppression reducing the tumor growth reserve.

Levels of Schistosoma mansoni Circulating Antigen in Chronic Hepatitis C Patients with Different Stages of Liver Fibrosis.

The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (µg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 µg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease.

Immunoglobulin e, interleukin-18 and interleukin-12 in patients with atopic dermatitis: correlation with disease activity.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Immunological/inflammatory reactions are reported to play a role in AD but their role in disease activity has not been fully investigated. This study was done to investigate the role of immunoglobulin E (IgE), interleukin (IL)-18 and IL-12 in AD patients with different disease severities. MATERIALS AND METHODS: Sera from 50 AD infants with varying levels of disease activity according to the scoring index of atopic dermatitis (SCORAD) index and 30 age-matched healthy controls were evaluated for serum levels of IgE, IL-18 and IL-12/p40. RESULTS: Serum analysis showed higher levels of IgE, IL-18 or IL-12/p40 in AD patients compared with controls. Interestingly, not only was there an increased number of subjects positive for IgE, IL-18 or IL-12/p40, but also the levels of these parameters were higher among AD patients whose SCORAD scores were higher. In addition, a significant correlation was observed between the levels of these parameters and SCORAD scores. CONCLUSION: These findings support an association between IgE, IL-18 or IL-12/p40 and AD. The stronger response observed in serum samples from patients with higher SCORAD scores suggest that IgE, IL-18 and IL-12/p40 may be useful in evaluating the progression of AD and in elucidating the mechanisms of disease pathogenesis.

Genetic polymorphisms of NFκB1 -94 del/ins ATTG, NFκB1A 2758 A>G and SUMO rs237025 G>A in psoriasis.

BACKGROUND: Nuclear factor-κB (NF-κB) and small ubiquitin-like modifier (SUMO4) are key transcription factors involved in the regulation of immune responses and apoptosis. The aim of this study is to test for the association of NF-κB and SUMO gene polymorphisms with the susceptibility and severity of psoriasis among Saudi cases. SUBJECTS AND METHODS: This is a case controlled study including 85 Saudi psoriasis patients in addition to 92 matched healthy unrelated controls from the same locality. For all participants, DNA was analyzed by PCR for characterization of NF-κB1 -94 del/ins ATTG, NF-κB IA 2758 A>G and SUMO rs237025 G>A gene polymorphisms. RESULTS: Compared to controls, psoriasis patients showed a non-significant difference for all frequencies of genotypes and alleles of NF-κB1 ins/del, NF-κB1A A>G and SUMO4 G>A polymorphisms (p>0.05). However, cases with the plaque type had significantly higher frequency of the SUMO4 A allele carriage (GA+AA genoytpes) than the guttate type (78.6% vs. 21.4%, p=0.02). The PASI score was also significantly higher among cases with the NF-κB1A AA genotype than other cases (p=0.00). CONCLUSION: Genetic polymorphisms of NF-κB1-94 ins/del ATTG, NF-κB IA 2758 A>G and SUMO4 rs237025 G>A were not associated with the susceptibility to psoriasis vulgaris in Saudi patients. However, it might be associated with the expressivity of the disease in terms of its clinical type and severity.

The impact of environmental and agricultural pollutants on the prevalence of allergic diseases in people from Qassim, KSA.

BACKGROUND: There are multiple environmental factors that influence a sensitized (IgE antibody positive) patient's predisposition to manifest allergic symptoms following allergen exposure. The majority of allergens are known to induce morbidity with chronic symptoms such as rhinitis, pruritis, dermatitis and urticaria. AIM: To study the impact of environmental and agricultural pollutants with different pollens on the immunological, hematological and biochemical markers and to determine the prevalence of sensitization to allergens among exposed individuals as well as to identify the eliciting allergens. SUBJECTS AND METHODS: Ninety six highly exposed individuals to environmental and agricultural pollution in addition to 20 as controls were selected. A solid phase enzyme-linked immunosorbent assay and the EUROLINE test kit were used for the quantitative determination of total IgE concentration and semi-quantitative in vitro assay of human IgE antibodies to some of the inhalant, ingestant and contactant allergens in serum samples, respectively. Percentage and absolute eosinophil counts and biochemical parameters were analyzed. RESULTS: Thirteen (13.5%) out of the 96 studied highly exposed subjects were manifesting allergic symptoms. Higher significant total serum IgE levels and absolute eosinophil counts in groups 1 and 3 of the highly exposed individuals compared to the control group were found (p1=0.00, p3=0.001 and p1=0.016, p3=0.028, respectively). Higher sensitization with inhalant Timothy grass, Aspergillus fumigatus, Der. Farinae and Olive; ingestant Egg yolk, Mango, Strawberry and Codfish and with contactant Latex/plastic and Crude oil was found in the studied groups compared with the controls. CONCLUSION: The present data suggest that the highly exposed subjects to pollution are at high risk of developing an allergy. For the screening of those with suspected allergen sensitization, the determination of specific IgE antibodies is a suitable marker of type I allergy.

Immunodetection of Fasciola gigantica circulating antigen in sera of infected individuals for laboratory diagnosis of human fascioliasis.

Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC = 0.961, P < 0.0001) for discriminating Fasciola-infected and noninfected individuals. The developed assay showed high degrees of sensitivity, specificity, and efficiency (>93%), and a significant correlation (r = 0.715, P < 0.0001) between antigen level and parasite egg count was shown. In conclusion, a 27-kDa Fasciola antigen was identified in sera of F. gigantica-infected individuals. A highly sensitive and specific Fasciola antigen detection assay, FgCA-27 ELISA, was developed for laboratory diagnosis of human fascioliasis.

ACE I/D and eNOS E298D gene polymorphisms in Saudi subjects with hypertension.

BACKGROUND: Hypertension has a multifactorial background based on genetic and environmental interactive factors. OBJECTIVES: We aimed to test for the association of the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) gene polymorphisms with hypertension. SUBJECTS AND METHODS: Participants included 120 Saudi patients with hypertension and 250 normal healthy controls. For all participants, DNA was processed for characterization of ACE I/D and eNOS E298D gene polymorphisms. RESULTS: Hypertensive cases showed a significantly higher frequency of the ACE mutant D allele carriage (98.3% vs. 92.4%, p = 0.028, OR = 4.8). Cases with hypertension associated with diabetes and obesity showed 100% mutant D allele carriage. Regarding the eNOS E298D polymorphism, the frequency of the mutant D allele carriage was only observed to be higher among cases with hypertension associated with diabetes and obesity, in comparison with controls, yet not reaching statistical significance (41.2% vs. 34%, p > 0.05). CONCLUSIONS: There is increased frequency of ACE and eNOS mutant allele carriage among Saudi patients affected with hypertension, particularly if accompanied by obesity and diabetes.

Association of MTHFR C677T and A1298C gene polymorphisms with hypertension.

OBJECTIVES: To check for the association of genetic polymorphisms related to the methylenetetrahydrofolate reductase (MTHFR) gene namely C677T and A1298C with hypertension in Saudi affected subjects from Qassim region. SUBJECTS AND METHODS: Participants included 123 Saudi hypertensive cases (83 males and 40 females) in addition to 250 (142 males and 108 females) unrelated healthy controls from the same locality. Their age mean ±SD was 50.93 ± 15.43 years. For all subjects, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T and A1298C gene polymorphisms RESULTS: Total cases showed significantly higher carriage rate for the mutant allele 677T compared to controls (40.7% vs. 26%, OR=1.9, 95% CI= 1.2-3.1) with a lower frequency of the wild type 677CC genotype (59.3% vs. 74%, p=0.004). The same was observed among cases-subgroups of hypertension associated with obesity with a notably higher odds ratio (OR=2.6, 95% CI=1.3-5.01, p=0.004). Total cases showed also significantly higher frequency of mutant 1298 C allele carriage rate compared to controls (59.3% vs. 42.4%, OR=1.98, 95% CI= 1.3-3.1) with a lower frequency of the normal AA genotype (40.7% vs. 57.6%, p=0.003). The same was observed among cases-subgroups of hypertension associated with both diabetes and obesity and among cases of hypertension with obesity, also with higher odds ratio (OR=2.6 and 2.2 respectively). CONCLUSION: This work showed that genetic polymorphisms related to the MTHFR gene are associated with the risk of hypertension particularly when accompanied with obesity and diabetes among Saudi subjects.

CYP2J2 -50 G/T and ADRB2 G46A gene polymorphisms in Saudi subjects with hypertension.

BACKGROUND: Hypertension is a result of complex factors including multiple genetic polymorphisms. OBJECTIVE: This study aims to check for the association of genetic polymorphisms of the cytochrome P450 2J2 (CYP 2J2) and beta-2-adrenergic receptor (ADRB2) genes with hypertension among Saudi subjects. SUBJECTS AND METHODS: This study included 116 cases with documented hypertension of at least 1 year duration. Their data were compared to that of 250 unrelated healthy nonhypertensive subjects from the same locality. For all participants, DNA was extracted and analyzed using real time polymerase chain reaction technique for the identification of genotypic and allelic variants of the CYP2J2 -50 G/T and ADRB2 G46A genes. RESULTS: Hypertensive cases showed a significantly higher frequency of mutant CYP2J2 -50 T allele carriage (TT and GT genotypes) compared with controls (odds ratio [OR]=3.7, p=0.0003). The same was observed among subgroups of hypertension associated with diabetes and obesity (OR=3.6, p=0.007) and cases with isolated hypertension (OR=8.4, p=0.0002). On the other hand, hypertensive cases, whether being isolated or associated with obesity and/or diabetes, showed a nonsignificant difference from controls in relation to all genotypic variants related to the ADRB2 G46A polymorphism (p>0.05). CONCLUSION: This study showed positive association of CYP2J2 gene polymorphism with hypertension among Saudi cases.

Frequency of thrombophilic genetic polymorphisms among Saudi subjects compared with other populations.

Thrombophilic mutations increase the tendency toward thromboembolic disease. The aim of this study was to estimate the prevalence of the genetic variants related to thrombophilia among Saudis compared with other populations. Real-time polymerase chain reaction (PCR) genotyping was carried out to determine the polymorphic variants of factor V Leiden 1695G/A, prothrombin 20210G/A, plasmin activator inhibitor 1 4G/5G, methylene tetrahydrofolate reductase (MTHFR) 677C/T, MTHFR 1298A/C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) among a representative sample of healthy Saudi subjects. Carraige rate for each of the mutant variants of factor V Leiden (FVL) and FII genes constituted 2% of the surveyed subjects giving an allele frequency of 0.01, homozygous forms of plasminogen activator inhibitor-1 (PAI-1) gene 4G/4G, MTHFR 677TT, 1298CC, and ACE DD were present among 7.7, 2.55, 7, and 51.8% of subjects with a mutant allele frequency of 0.4, 0.19, 0.29, and 0.73, respectively. This study showed that the Saudi population has a peculiar pattern regarding thrombophilic mutations that might warrant additional considerations for prophylaxis.

Association of Blood Lead level with Elevated Blood Pressure in Hypertensive Patients.

BACKGROUND: Lead is a metal with many important industrial uses. The relationship between lead exposure and the rise of blood pressure has received a great deal of attention as it was implicated that the mortality from cardiovascular diseases might be reduced by lowering lead levels in the environment. OBJECTIVES: The study was to investigate the correlation between the blood lead (B-Pb) levels and the values of blood pressure in hypertensive patients. Moreover, the plasma activities of angiotensin converting enzyme (ACE), plasma levels of nitric oxide (NO), total antioxidants (TAOX) and malondialdehyde (MDA) were estimated to investigate the correlations between the measured parameters and B-Pb levels in hypertensive patients. METHODS: Fifty-five hypertensive patients were compared with fifty-three age and sex matched control group. The B-Pb levels were detected by flame atomic absorption spectrometry. The plasma levels of ACE activities, NO, TAOX and MDA were measured by colorimetric methods. RESULTS: In the hypertensive patients, B-Pb levels were significantly higher than controls. Concomitantly, the plasma levels of ACE activities and MDA were significantly increased while the plasma levels of NO and TAOX were significantly reduced in the hypertensive patients in comparison with controls. There were significant positive correlations between B-Pb and each of MDA, and systolic as well as diastolic blood pressure. Conversely, a significant negative correlation was found between B-Pb and NO. CONCLUSIONS: Our study indicated that a positive relationship exists between blood pressure and B-Pb levels. The increased B-Pb levels were associated with oxidative stress. Moreover, The B-Pb level was negatively correlated with NO and this may clarify the implication of Pb as leading risk factor for the cardiovascular diseases and hypertension. These findings provide support for continued efforts to reduce lead concentration in the population at Qassim region.

Vitamin D status among population of Qassim Region, Saudi Arabia.

OBJECTIVES: The objectives of this study were to assess serum 25OHD level among healthy Saudi population of Qassim region, besides socio-demographic characters, dietary habits, sun exposure and common symptoms of vitamin D deficiency were also evaluated. SUBJECTS AND METHODS: One hundred and eighty healthy males and females subjects above the age of 18 years were randomly selected from five primary health care centers of Qassim region. A predesigned structured questionnaire was administered by the doctor working in Primary Health Care Center and blood sample was obtained for measuring vitamin D (serum 25 OHD) level. Vitamin D sufficiency was defined as serum level of 25 OHD 30ng/ml or above. A level ranging 20 to 29 ng/ml was considered as vitamin D insufficiency, whereas below 20ng/ml as vitamin D deficiency. RESULTS: Out of 180 study participants, 51(28.3%) subjects were vitamin D deficient, 71 (39.4%) were vitamin insufficient and 58 (32.2%) had normal vitamin D level. Commonest symptom of vitamin D deficiency was bone pain (20%) and fatigue (11.1%). CONCLUSION: Vitamin D inadequacy is a major public health problem in Saudi population. The prevalence of vitamin D deficiency/insufficiency among healthy Saudi population residing in Qassim region is 67.8%. If the issue is not urgently addressed it could lead to serious health consequences.