Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads.

Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: "cardiotonic steroids", "anti-inflammatory", "antiviral", "anticancer", "toad venom", "bufadienolides", and "poison chemical composition". Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms.

Structural modifications in Bermuda grass [Cynodon dactylon (L.) Pers.] ecotypes for adaptation to environmental heterogeneity.

Introduction: It is well known that different ecotypes adopt different mechanisms to survive under environmental stress conditions. In this regard, each ecotype showed different type of modifications for their existence in a specific habitat that reflects to their ecological success. Methods: Here, differently adapted ecotypes of Bermuda grass [Cynodon dactylon (L.) Pers.] were collected to evaluate their differential structural and functional modifications that are specific to cope with environmental stress conditions. The soil that adheres ecotypes roots were highly saline in case of DF-SD (Derawar Fort-Saline Desert), UL-HS (Ucchali Lake-Hyper Saline) and G-SSA (Gatwala-Saline Semiarid) ecotypes. Soils of S- HS (Sahianwala-Hyper Saline), S-SW (Sahianwala-Saline Wetland) and PA-RF (Pakka Anna-Reclaimed Field) were basic (pH 9 to 10). Soils of UL-HS and PA- HS (Pakka Anna-Hyper Saline), KKL-S (Kalar Kahar Lake-Saline), BG-NS (Botanic Garden-Non Saline) and G-SSA were rich in organic matter, and soil of BG-NS and DF-SD were rich in minerals. Anatomical modifications were performed by using the free hand sectioning technique and light microscopy. Results and Discussion: DF-SD is one of the best ecotypes which showed anatomical modifications to cope with environmental changes. These modifications included stem cross-sectional area and leaf sheath thickness that contribute towards water storage, vascular tissues for proficient translocation of solutes and trichomes that provide resistance to water loss. On the other hand, sclerification in root is the only notable modification in the Gatwala Saline Semiarid (G-SSA) ecotype from saline arid habitat where rainfall is not as low as in the Cholistan Desert. Two ecotypes from hyper-saline wetlands, UL-HS and KL-HS showed increased number and size of vascular tissue, central cavity and sclerification in stem which are important for solutes conduction, water loss and salts bulk movement, respectively. The ecotype from reclaimed site was not much different from its counterpart from hyper-saline dryland. Overall, anatomical modifications to maintain water conservation are key mechanisms that have been identified as mediating stress tolerance in C. dactylon ecotypes.

Nephrotic range proteinuria; does it predict lung involvement in patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder that is well known for its long term serious complications. Proteinuria whether micro or macroproteinuria is one of these complications. Many studies has related proteinuria to other complications of diabetes as retinopathy and cardiovascular disease of diabetes, while the lungs of diabetic patients which is the largest organ in the body with a large macro and microvascular bed, has not been related to this complication. AIM: The aim of the study was to find out whether proteinuria in diabetic patients can predict lung involvement. PATIENTS AND METHODS: A comparative cross sectional study in which we compared the lung function of 100 type 2 diabetic patients with proteinuria with that of 100 type 2 diabetic patients without proteinuria. Proteinuria is measured in a random sample by "urine protein/urine creatinine ratio". FEV1 and FVC were measured by spirometer. RESULTS: The results showed that patients with proteinuria had a high frequency of abnormal PFT (86%), while patients without proteinuria had a low frequency of abnormal PFT (11%).Also diabetic patients with proteinuria had lower FVC (72.9 ±â€¯6.5 vs. 88.2 ±â€¯8.2), than diabetic patients without proteinuria. CONCLUSIONS: We concluded that diabetes mellitus causes a significant impairment in pulmonary function test. This impairment is significantly related with proteinuria.

Retrospective analysis of nephritis response and renal outcome in a cohort of 928 Egyptian lupus nephritis patients: a university hospital experience.

Aim We aim to describe the pattern of response to treatment in a cohort of Egyptian lupus nephritis (LN) patients and to define variable prognostic factors. Methods We retrospectively analyzed records of 928 systemic lupus erythematosus (SLE) patients (898 females, 30 males) with biopsy-confirmed LN seen between 2006 and 2012 at Cairo University hospitals. Results Our study involved 928 SLE patients with a mean age of 26.25 ± 6.487 years, mean LN duration at time of renal biopsy 6.48 ± 4.27 months, mean SLEDAI 28.22 ± 11.7, and mean follow-up duration of 44.14 ± 17.34 months. Induction treatment achieved remission in 683 patients. Remission was achieved in all 32 patients with class II LN, compared to 651/896 (72.7%) patients in classes III, IV, and V. Induction by intravenous (IV) cyclophosphamide achieved response in 435/575 (75.7%) patients, while induction by mycophenolate mofetil (MMF) resulted in response in 216/321 (67.3%) patients ( p = 0.0068). Nephritic flares were least observed when MMF was used for maintenance (30/239 (12.6%) patients), compared to 71/365 patients (19.5%) ( p = 0.0266) when azathioprine (AZA) was used, and 22/79 patients (27.8%) ( p = 0.002) with IV cyclophosphamide. Class IV LN, high chronicity index, presence of crescents, and interstitial fibrosis in biopsies were all associated with chronic kidney disease (CKD) development eventually ( p < 0.001, p = 0.005, p = 0.012, and p = 0.031, respectively). By the end of the study duration, 305 (32.7%) patients had CKD. Logistic regression detected that high baseline serum creatinine, failure to achieve remission, hypertension, and nephritic flare were the main risk factors for poor renal outcome ( p < 0.001, p < 0.001, p = 0.004, and p < 0.001, respectively). The 5 years' mortality was 69 (7.4%) patients with sepsis being the main cause of death. Conclusion IV cyclophosphamide superseded as induction treatment, while MMF was the best maintenance treatment. High serum creatinine, hypertension, and nephritic flare were the main risk factors for poor renal outcome.

Oral Administration of Vitamin C, Cimetidine and Famotidine on Micronuclei Induced by Low Dose Radiation in Mouse Bone Marrow Cells.

BACKGROUND: In many studies, chemicals and natural materials were tested to reduce the harmful effects of radiation. It is known that Famotidine and vitamin C reduce DNA damage. OBJECTIVE: The aim of this study was to evaluate the radioprotective effect of vitamin C, Cimetidine and Famotidine on gamma-radiation-induced damage on mouse bone marrow. METHODS: Six-to-seven week male NMRI mice (28 g ±3) were randomly divided into fourteen groups: control, 2Gy irradiation, six group drugs without irradition (Famotidine, Cimetidine, vitaminC, Fam-Cim, Fam-Vit, Cim-Vit), six groups received drugs and 2Gy radiation with a 60Co |γ|-ray source at room temperature 22 ± 2 °C. The mice were killed 48 hours after irradiation by cervical dislocation. Slides were prepared from bone marrow cells and stained in May-Granwald and Giemsa. Finally, the cells were counted with microscope, frequencies of polychromatic erythrocyte (PCE), normochoromatic erythrocyte (NCE) and their micronuclated cell were recorded. PCE / PCE + NCE were calculated. RESULTS: There were significant differences of MNPCE/1000PCE, MNNCE/1000NCE and PCE/PCE+NCE among different groups with similar radiation doses (p≤0.01). Moreover, there were significant differences of MNPCE/1000PCE and PCE/PCE+NCE among different doses of radiation (p≤0.01). While considering MNNCE/1000NCE, there were no significant differences among silimar groups with radiation dose (p˃0.05). CONCLUSION: Oral administration of Famotidine, vitamin C and Cimetidine demonstrate reliable and similar radioprotective effects. Additionally, the protective effect of single use of these drugs was similar to the combination form. Thus, the oral use of combination, 48 hours after irradiation cannot induce more radioprotective effect.

High Salinity Induces Different Oxidative Stress and Antioxidant Responses in Maize Seedlings Organs.

Salinity negatively affects plant growth and causes significant crop yield losses world-wide. Maize is an economically important cereal crop affected by high salinity. In this study, maize seedlings were subjected to 75 mM and 150 mM NaCl, to emulate high soil salinity. Roots, mature leaves (basal leaf-pair 1,2) and young leaves (distal leaf-pair 3,4) were harvested after 3 weeks of sowing. Roots showed the highest reduction in biomass, followed by mature and young leaves in the salt-stressed plants. Concomitant with the pattern of growth reduction, roots accumulated the highest levels of Na(+) followed by mature and young leaves. High salinity induced oxidative stress in the roots and mature leaves, but to a lesser extent in younger leaves. The younger leaves showed increased electrolyte leakage (EL), malondialdehyde (MDA), and hydrogen peroxide (H2O2) concentrations only at 150 mM NaCl. Total antioxidant capacity (TAC) and polyphenol content increased with the increase in salinity levels in roots and mature leaves, but showed no changes in the young leaves. Under salinity stress, reduced ascorbate (ASC) and glutathione (GSH) content increased in roots, while total tocopherol levels increased specifically in the shoot tissues. Similarly, redox changes estimated by the ratio of redox couples (ASC/total ascorbate and GSH/total glutathione) showed significant decreases in the roots. Activities of enzymatic antioxidants, catalase (CAT, EC 1.11.1.6) and dehydroascorbate reductase (DHAR, EC 1.8.5.1), increased in all organs of salt-treated plants, while superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), glutathione-s-transferase (GST, EC 2.5.1.18) and glutathione reductase (GR, EC 1.6.4.2) increased specifically in the roots. Overall, these results suggest that Na(+) is retained and detoxified mainly in roots, and less stress impact is observed in mature and younger leaves. This study also indicates a possible role of ROS in the systemic signaling from roots to leaves, allowing leaves to activate their defense mechanisms for better protection against salt stress.

Prenatal diagnosis for thalassaemia in Egypt: what changed parents' attitude?

OBJECTIVES: To present the current status of the prenatal diagnosis services and results from the largest thalassaemia center in Egypt treating 3000 patients. Traditionally, prenatal diagnosis has not been successful in reducing the births of affected children in Egypt, because the majority of women undergoing prenatal diagnosis continued to have affected pregnancies. METHODS: Seventy-one pregnant mothers at risk for ß-thalassaemia underwent prenatal diagnosis by chorionic villus sampling (n=57) or amniocentesis (n=14) between 11 to 14 weeks of gestation. Molecular characterization of fetal DNA by reverse dot blot hybridization and polymerase chain reaction-amplification refractory mutation system techniques was conducted in all cases. RESULTS: Twenty-four women (33.8%) were found to have affected fetuses; 100% of these women opted to terminate the pregnancy. The change in attitude towards termination of pregnancy was related to in-depth counseling of the religious aspects towards prenatal diagnosis and termination of pregnancy. Forty-eight women (66.2%) with normal or carrier fetuses for ß-thal requested human leukocyte antigen typing of the fetal material to determine if the fetus was a human leukocyte antigen match for their existing thalassaemic siblings. CONCLUSION: This study demonstrates that prenatal diagnosis is feasible and acceptable in Egypt, a Muslim country, provided an in-depth discussion, which also addresses the religious considerations of prevention, is held with the couples.

Prenatal magnetic resonance imaging diagnosis of molar tooth sign at 17 to 18 weeks of gestation in two fetuses at risk for Joubert syndrome and related cerebellar disorders.

We report on the prenatal MRI diagnosis of Joubert syndrome and related cerebellar disorders (JSRD) in 2 unrelated fetuses at 17-18 weeks of gestation who were referred to us with history of siblings with JSRD and additional renal affection in the second case. Ultrasonography (US) showed non-specific cranial findings in both fetuses such as prominent cisterna magna and ventricular system as well as bilateral renal enlargement in the first case. MRI identified the molar tooth sign (MTS) and suggested a JSRD affection in both fetuses. The final suggested diagnosis for both cases was Joubert syndrome with intrafamilial variability in renal expression. This report describes the earliest prenatal detection of MTS. We include a discussion of the differential diagnosis of renal affection in conjunction with MTS and review the previously reported cases with prenatal MRI detection of MTS. The report emphasizes the role of MRI in the early specific prenatal diagnosis of JSRD through the recognition of MTS.

Evaluation of offline analysis of archived three-dimensional volume datasets in the diagnosis of fetal brain abnormalities.

OBJECTIVE: To retrospectively evaluate the reliability of offline manipulation of archived three-dimensional (3D) ultrasound volumes in the assessment of the normal fetal brain and the diagnosis of fetal brain abnormalities. METHODS: Seventy-nine 3D volume datasets, archived at the time of scanning, from women attending a tertiary center, were analyzed. They comprised 52 cases with brain abnormalities and 27 normal controls. Postnatal magnetic resonance imaging or postmortem examination confirmed the final diagnosis in all cases with brain anomalies. Offline analysis of the 79 anonymized 3D volume datasets was carried out by three fetal medicine experts, examiner one (E1), examiner two (E2) and examiner three (E3), using 4D View software. The experts were blinded to any prior diagnosis or history. Data were collected on a specially designed data sheet and entered into a specialized database for analysis. Results were compared between examiners, with the initial two-dimensional (2D) diagnosis and with the final definitive diagnosis by calculation of percentage agreement and kappa coefficients. RESULTS: Of the 52 cases with brain anomalies, the correct diagnosis was reached in 88.5% (46/52), 98.1% (51/52) and 92.3% (48/52) of cases on analysis of the 3D volumes by E1, E2 and E3, respectively, whereas only 82.7% (43/52) of cases were correctly diagnosed on the initial 2D examination when compared with the definitive diagnosis. Fetuses without brain anomalies were identified as such by the three experts with 100% agreement. There was good agreement between the initial 2D examination and the analysis of 3D volumes by each of the experts: 86.1% for E1 (κ = 0.7), 89.9% for E2 (κ = 0.79) and 88.6% for E3 (κ = 0.76). CONCLUSIONS: 3D volume datasets are an appropriate and reliable format for storing data from examination of the fetal brain. Offline analysis of 3D datasets is a reliable method that can be used to help in the assessment of brain anomalies and could be a useful adjunct to realtime 2D ultrasonography.

Evaluation of a newly developed ELISA against Widal, TUBEX-TF and Typhidot for typhoid fever surveillance.

INTRODUCTION: Typhoid fever is endemic in many parts of the world and represents a major cause of acute febrile illness (AFI). Rapid and accurate laboratory methods for diagnosis of this disease are needed for both patient care and surveillance situations. METHODOLOGY: Serum samples were collected from AFI patients and used to evaluate the performance of a newly developed ELISA assay that uses a mixture of somatic and flagellar antigens to detect the total antibody response against Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) infection. The levels of Ig isotype response (IgG, IgM and IgA) were also evaluated, and results were compared to those of TUBEX-TF and Typhidot commercial kits.  RESULTS: Of 234 culture-confirmed typhoid patients, the total Ig ELISA diagnosed 93% compared to 71% using Widal test. This sensitivity level (93%) is higher than that observed for the individual Ig ELISAs (IgG 75%; IgM 79%; IgA 57%) and the commercial tests TUBEX-TF (75%), Typhidot IgM (63%) and Typhidot IgG (28%). An agreement of 78% was achieved between the total Ig ELISA and Widal test. The average specificity of the ELISA was 96%. Using ELISA, up to 200 samples can be tested per run with cost per test at US$0.20. CONCLUSIONS: The developed ELISA shows superior sensitivity and specificity, when compared to Widal, TUBEX-TF and Typhidot assays, is more cost effective and allows higher throughput. This method is highly recommended for active surveillance studies or outbreak investigations of typhoid fever.

13-14-week fetal anatomy scan: a 5-year prospective study.

OBJECTIVES: To assess the potential value of an early (first-trimester) ultrasound examination in depicting fetal anomalies by transabdominal (TAS) and transvaginal (TVS) sonography, to compare it with the traditional mid-trimester anomaly ultrasound examination and to evaluate the degree of patient acceptance of early sonography by the transvaginal route. METHODS: In this prospective study over a 5-year period (January 2002 to January 2007) 2876 pregnant women underwent a 13-14-week ultrasound examination. The scan was performed by TAS at first and then, if a full fetal anatomical survey was not achieved, by TVS. A mid-trimester fetal anatomy scan was then performed in patients who had not dropped out, miscarried or undergone pregnancy termination (n = 2834). RESULTS: In the early scan, analyzable data for 2876 TAS and 1357 TVS examinations showed that TVS was significantly better in visualizing the cranium, spine, stomach, kidneys, bladder and upper and lower limbs (P < 0.001). Complete fetal anatomical surveys were achieved by TAS in 64% of cases versus 82% of the cases in which it was attempted by TVS (P < 0.001). Patient body mass index significantly affected the ability of the sonographer to achieve a complete anatomical survey by both TAS and TVS (P < 0.001 and P = 0.004, respectively). The duration of the scan was significantly longer using TVS. The heart and kidneys were not properly visualized in 42% and 27% of cases, respectively, at the 13-week scan compared with 1.6% and 0% at the mid-trimester scan. The total number of cases in which anomalies were detected was 31. At the first-trimester scan, anomalies were detected in 21 fetuses and in 14 of these cases the parents chose pregnancy termination. At the second-trimester scan, anomalies were detected in 17 fetuses: 10 new anomalous cases along with seven cases already detected in the first-trimester scan. CONCLUSION: Besides its importance in screening for chromosomal abnormalities, the early scan has great potential in visualizing with precision fetal anatomy. TVS can be used to compliment difficult TAS examinations; however, patients do not always agree to undergo TVS. The mid-trimester scan remains crucial for detailed fetal anatomical survey.

Isolation of cryptococcus, Candida, Aspergillus, Rhodotorula and nocardia from meningitis patients in egypt.

Meningitis occurs throughout Egypt and is largely attributed to bacterial pathogens, but there is little information on fungal etiologies of meningitis. We, therefore, investigated fungal infections among Egyptian patients with acute and subacute meningitis who tested negative for bacterial and viral agents. A total of 1000 cerebrospinal fluid (CSF) samples collected from nine governorates of Egypt during 1998-2002 were initially stained with Gram's, India ink, and lacto-phenol cotton-blue stains, and examined under light microscope to detect fungal elements. All CSF samples were cultured on brain heart infusion, Wickerham and Staib agar media for fungus isolation. CSF with suspected Cryptococcus neoformans infections were also tested by latex agglutination test for antigen detection. Species identification of selected isolates was carried out at the Mycotic Diseases Branch, CDC, Atlanta, Georgia, USA. Fungal agents were detected microscopically and by culture in 17 of 1000 (1.7%) CSF samples tested. Ten of 17 were identified as C. neoformans var grubii (serotype A), 4 as Candida albicans, and one each of Aspergillus candidus, Rhodotorula mucilaginosa (rubra) and Nocardia spp (actinomycetes). Out of the 17 cases with fungal CSF infection, 8 died (Cryptococcus-3, Candida-2, Aspergillus, Rhodotorula and Nocardia) and 2 suffered neurological sequelae. Of the 10 cryptococcal meningitis patients, 4 were HIV positive and one was diagnosed with lymphoma. To our knowledge, this is the first study on isolation of fungi other than Cryptococcus from CSF of Egyptian patients with acute/subacute meningitis. Consideration must now be given to cryptococcosis and candidiasis as potential etiologies of meningitis in Egypt.

Differentiation of tuberculous meningitis from acute bacterial meningitis using simple clinical and laboratory parameters.

Tuberculous meningitis (TBM) is still a major cause of serious illness in many parts of the world. The newer diagnostic tests and neuroimaging methods are unlikely to be available in many developing countries. We attempt to identify simple parameters for early diagnosis. A retrospective study was performed to compare the clinical and laboratory features of cultured-confirmed, TBM (134) and other bacterial meningitis (709). Features independently predictive of TBM were studied by multivariate logistic regression to develop a diagnostic rule. Six features were found predictive: length of clinical history >5 days, headache, total cerebrospinal fluid (CSF) white blood cell count of <1000/mm3, clear appearance of CSF, lymphocyte proportion of >30%, and protein content of >100 mg/dL. Application of 3 or more parameters revealed 93% sensitivity and 77% specificity. Applying this diagnostic rule can help in the early diagnosis of TBM, in both children and adults.

Intrapartum prediction of macrosomia: accuracy of abdominal circumference estimation.

OBJECTIVE: To evaluate the accuracy of abdominal circumference (AC) estimation of macrosomia early in labor and whether a cutoff value could be detected. DESIGN: A prospective clinical trial. SETTING: The Department of Obstetrics and Gynecology, Cairo University. PARTICIPANTS: One hundred pregnant females presenting in early labor with clinical impression of macrosomia were examined by ultrasound, and those babies with abdominal circumference more or equal to 35 cm were recruited for the study. INTERVENTIONS: Every woman was considered as her own control, and fetal weight was calculated using the formula of Shepard et al. The accuracy of abdominal circumference in prediction of macrosomia was evaluated using the Receiver operating characteristic curve. RESULTS: A cutoff value of AC > or =37 cm was found to have a sensitivity of 77%, a specificity of 75%, a positive likelihood ratio of 3.1 and a negative likelihood ratio of 0.3. CONCLUSION: Intrapartum ultrasonographic evaluation of abdominal circumference for suspected macrosomic babies in early labor is an easy, practical method that should be adopted in decision making.

Doppler study of the uterine artery in patients using an intrauterine contraceptive device.

A Doppler flow study of the uterine artery was performed using transvaginal sonography in 68 women, including 44 using an intrauterine contraceptive device (IUCD) and 24 control women who were not using any method of contraception. Both the pulsatility index (PI) and resistance index (RI) were significantly lower in women with IUCD-induced bleeding than in those without abnormal vaginal bleeding (p < 0.001) or in women not using any method of contraception (p < 0.001). No significant variations in PI and RI levels (p > 0.05) were found with the duration of IUCD application or the duration of IUCD-induced bleeding in patients using the device. Also, no significant changes in blood flow indices were demonstrated between women using the device without abnormal vaginal bleeding and the control group. These preliminary results suggest that some women are more prone to develop IUCD-induced bleeding than others, and this bleeding may be due to decreased vascular resistance in the uterine artery. Transvaginal Doppler study of the uterine artery may be a helpful technique to identify such women.