Study on development and tissue permeation of different formulations of Fasudil.

OBJECTIVE: The study is intended to formulate Fasudil loaded vesicular system for application in the management of angina. MATERIALS AND METHODS: Fasudil was made into a complex with phospholipid, and other different formulations were made, including Fasudil solution, liposomal form, and Fasudil loaded into the gel. A drug characterization study was conducted and noted. Drug release was quantified and analyzed and, finally, inoculated in Sprague-Dawley rats. These rats underwent anginal induction, and each formulation's effect on angina was evaluated. RESULTS: Drug solution (F-Phos) and F-Phos-Lipo (liposomal dispersion form of the drug) have shown that more than half percent of them have been released within 1.5 hours, and the rapid release occurred from liposomal dispersion in the first hour. The study determined the viscosity of the different formulations, which was significantly (p<0.05) higher than the theoretical sum of the viscosity of each formulation. The study found that the F-Phos-Lipo+P-407HMS formulation is the most effective as its application has the minimum infarct area percentage compared to the other formulations and can also reduce creatine kinase levels significantly as compared to the different formulations (p<0.05). CONCLUSIONS: The study concluded that the typical gel formulation (liposomal Fasudil dispersed in hydroxypropyl methylcellulose solution, which is added to blank poloxamer 407) had been shown to have significantly anti-anginal properties, including easy administration, its application on the infarct area percentage and subsequently its pharmacological effect on the cardiac tissue.

In silico elucidation of plausible anti-obesity activity by Withaferin-A compound targeting alpha-amylase.

OBJECTIVE: The study aimed to evaluate the Withaferin-A against the drug target α-amylase, revealing its plausible mode of action and molecular-level interactions essential for this specific target inhibitory potential computational approach. MATERIALS AND METHODS: In this scenario, we used computational methods, including docking, molecular dynamics simulation, and model-building simulations, to elucidate the atomic-level details responsible for the inhibitory potential of Withaferin-A derived from W. somnifera. The studio visualizer software was used for the visualization of ligands, structures of the receptor, bond length, and rendering of the image. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics of phytochemicals were investigated. Crystal structure of protein receptors and ligands were generated. Semi-flexible docking was done using Autodock software. Docking was performed using the Lamarckian Genetic Algorithm (LGA). Molecular descriptors were evaluated, and the pharmacological properties of the phytochemicals were explored. Molecular dynamic simulations were analyzed at the atomic level. All the simulations were conducted under the same temperature, pressure, and volume circumstances over the simulated time scale. RESULTS: Withaferin-A has shown a strong binding affinity towards α-amylase as demonstrated with -9.79 Kcal/mol with 66.61 estimated nanomolecular IC50 value for plausible anti-obesity activity. Molecular-level relationships and knowledge obtained from this study indicate solid interactions with TYR59, ASP197, and HIS299 residues which are of high importance for future works related to computational screening of target-specific α-amylase inhibitors. The results from the analysis have revealed potential molecular-level interactions useful for further designing/discovering novel α-amylase inhibitors. CONCLUSIONS: The framework of the studied phytochemicals enables the rapid development of subsequent modifications that could result in more lead-like compounds with better inhibitory efficacy and selectivity for α-amylase.

SARS-CoV-2 and Plasmodium falciparum common immunodominant regions may explain low COVID-19 incidence in the malaria-endemic belt.

Coronavirus disease 2019 (COVID-19) has caused significant morbidity and mortality and new cases are on the rise globally, yet malaria-endemic areas report statistically significant lower incidences. We identified potential shared targets for an immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by immune determinants' shared identities with P. falciparum using the Immune Epitope Database and Analysis Resource Immune 9.0 browser tool. Probable cross-reactivity is suggested through HLA-A∗02:01 and subsequent CD8+ T-cell activation. The apparent immunodominant epitope conservation between SARS-CoV-2 (N and open reading frame (ORF) 1ab) and P. falciparum thrombospondin-related anonymous protein (TRAP) may underlie the low COVID-19 incidence in the malaria-endemic zone by providing immunity against virus infection to those previously infected with Plasmodium. Additionally, we hypothesize that the shared epitopes which lie within antigens that aid in the establishment of the P. falciparum erythrocyte invasion may be an alternative route for SARS-CoV-2 via the erythrocyte CD147 receptor, although this remains to be proven.

Individuals with a Rh-positive but not Rh-negative blood group are more vulnerable to SARS-CoV-2 infection: demographics and trend study on COVID-19 cases in Sudan.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Sudan, several haematological studies were conducted to study the ABO blood group distribution among the population, in which the O blood group was dominant followed by the A blood group. However, there is no systematic study into any correlation between COVID-19 and the population's blood group types, therefore we have intended to study the possible effect of blood group on the acquisition of SARS-CoV-2 infection. A questionnaire-based case-control study was carried out on 557 individuals with COVID-19 in Sudan; factors such as age, blood group, previous malaria infection, history of ailments such as diabetes, hypertension and symptoms suffered were also considered and analysed. More women were infected than men, and individuals between 25 and 35 years were the most affected age group. O Rhesus-positive (O+) blood group was the least affected by the disease while A Rhesus-positive (A+) individuals were the most vulnerable. Fatigue, fever and loss of smell were the major symptoms among the patients, but 13% of SARS-COV-2-positive individuals remained asymptomatic. As the Sudan population is largely constituted of O Rhesus-positive inhabitants (approximately 50%) these results might explain the relatively lower COVID-19 incidence in the country.

Seroprevalence of rubella among pregnant women in Khartoum state, Sudan.

Rubella vaccine is not included in the Sudanese national immunization programme, and data on prevalence of rubella among women of childbearing age are inadequate. The objective of this cross-sectional study was to determine the seroprevalence of rubella among pregnant women in Khartoum state, Sudan. A total of 500 pregnant women who visited 7 antenatal clinics from November 2008 to March 2009 were examined for the presence of rubella IgG antibodies using ELISA. Rubella IgG antibodies were detected in 95.1% (95% Cl: 93.2%-97.0%) of women. This seroprevalence was significantly associated with education level, but not with age, residence area, occupation or parity. We presume this high seroprevalence indicates a high circulation of wild rubella virus in Khartoum state. Similar studies in other Sudanese states would be important for informing a decision to introduce rubella vaccine to Sudan.

Study on some factors affecting survivability of airborne fungi.

The aim of the present study was to investigate the effect of some air pollutants and meteorological parameters on the survivability of airborne fungi. Fungi were collected by using a slit impactor sampler calibrated to draw 20 L/min, for 3 min. Nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), particulate matter (PM), relative humidity (RH %), temperature (T °C) and wind speed (WS) were also measured. Air samples were taken during the period from March 2006 to February 2007. Fungal concentrations ranged between 45 and 451 CFU/m(3) with an annual mean concentration of 216 CFU/m(3). The lowest fungal concentration was found in the summer, however the highest one was found in the autumn. NO(2,) SO(2) and PM averaged 83.66 µg/m(3), 67.01 µg/m(3), and 237.69 µg/m(3), respectively. T °C was positively and negatively correlated with Aspergillus (P = 0.000) and Penicillium (P = 0.007), respectively. RH% was positively correlated with total fungi (P = 0.001), Aspergillus (P = 0.002) and Cladosporium (P = 0.047). Multiple regression analysis showed that T °C and RH% were the most predicted variants. Non-significant correlations were found between fungal concentrations and air pollutants. Meteorological parameters were the critical factors affecting fungal survivability.

Efficacies of artesunate plus either sulfadoxine-pyrimethamine or amodiaquine, for the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan.

Artemisinin-based combination therapy (ACT) is increasingly being adopted as the first-line treatment for malaria in sub-Saharan Africa. In September-November 2005, in New Halfa, eastern Sudan, the efficacy of artesunate-sulfadoxine-pyrimethamine (AS-SP) for the treatment of uncomplicated, Plasmodium falciparum was compared with that of artesunate-amodiaquine (AS-AQ). The artesunate was given at 4 mg/kg. day on days 0-2, with either a single dose of SP (25 mg sulfadoxine/kg) given on day 0, or AQ, at 10 mg/kg. day, given on days 0-2. Eighty-two of the patients treated (40 given AS-SP and 42 given AS-AQ) completed the 28 days of follow-up. On day 3 all the patients were afebrile and only one patient, in the AS-AQ group, was still parasitaemic. AS-SP appeared slightly more efficacious than AS-AQ but the differences were not statistically significant. Only one patient (2.5%) given AS-SP but four (9.5%) of those given AS-AQ were initially considered to be late treatment and parasitological failures, with all other patients showing an adequate treatment response. The PCR-corrected frequencies of cure were 97.5% for AS-SP and 95.2% for AS-AQ (P>0.05). No gametocytaemias were observed during the follow-up and, although mild adverse effects (nausea, vomiting, abdominal pain, dizziness and/or rash) were detected in 14 patients, they occurred at the same frequency in each treatment arm. It therefore appears that the AS-SP and AS-AQ combinations were both effective and safe for the treatment of uncomplicated, P. falciparum malaria in eastern Sudan.

Analysis of fibronectin expression in the bilharzial granulomas and of laminin in the transformed urothelium in schistosoma haematobium infested patients.

UNLABELLED: The bilharzial granulomas and urothelial transformation are common findings in Schistosoma haematobium infested patients. We hypothesize that the distribution of extrinsic (fibronectin, FN) and intrinsic basement membrane (BM) proteins (laminin, LN) is altered during the evolution of these lesions. METHODS: To test this hypothesis, 70 cystectomy specimens, entailing variable associations of normal and dysplastic urothelium (all cases), and bilharzial granulomas were examined for FN and LN protein expression. RESULTS: The biharzial granulomas were formed of admixture of CD3+T cells, CD68+histiocytes and CD220B cells. The CD3+T cells and and CD68+histiocytes were the predominant cell populations. Increased deposition of FN occurred with the evolution from cellular (loose fibrillary network, 20 cases) to fibrocellualr (dense fibrillary network, 30 cases) to fibrotic (tight conglomerates, 20 cases) granulomas. Alternatively, BM staining for LN was linear and continuous underlying normal and metaplastic urothelium. In dysplastic urothelium (20 cases), it showed breaks in continuity. CONCLUSIONS: Alterations of FN and LN occur during the development of the bilharzial granuloma and urothelial transformation.

Efficacies of chloroquine, sulfadoxine-pyrimethamine and quinine in the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan.

The efficacies of several antimalarial drugs in the treatment of uncomplicated Plasmodium falciparum malaria were compared, during an open, randomized trial, in New Halfa, eastern Sudan. The 96 patients who completed the 28 days of follow-up were treated with chloroquine (N = 26), sulfadoxine-pyrimethamine (N = 38) or quinine (N = 32). No treatment failures were observed among the patients given sulfadoxine-pyrimethamine. Only 23.1% of the patients given chloroquine showed adequate clinical response, however, the rest showing early (15.4%) or, more frequently, late (61.5%) treatment failure. In terms of parasitological failure, 54.1% of the patients given chloroquine showed early RI resistance, 7.7% showed late RI, and 15.1% showed RIII. Most (90.6%) of the patients treated with quinine had adequate treatment responses, the rest having late treatment failures (and late RI). The frequency of treatment failure was significantly higher, however, among the patients given chloroquine than in the quinine-treatment arm. The present results and those of earlier investigations indicate that the problem of chloroquine resistance is worsening in eastern Sudan, and that the use of chloroquine as the first-line drug for the treatment of uncomplicated malaria in this area is now compromised. The response to quinine may also be faltering.

Factors affecting variations in exposure to infections by Leishmania donovani in eastern Sudan.

A cross-sectional survey was carried out in Gedaref state, eastern Sudan to investigate the prevalence of positive leishmanin skin tests and environmental factors related to Leishmania donovani infection. A total of 3835 people living in 11 villages in 3 regions were screened. Soil types and tree densities were determined in 33 villages inhabited by 44 different tribes. The highest rates of positive skin tests were in Rahad region (33.9%), Atbara (21.6%) and Gedaref (10.6%), with an average of 21.1% for the state. Risk of infection by L. donovani varied significantly between different tribes. Higher densities of Acacia and Balanites spp. trees were in Masaleet villages, suggesting that the relatively high risk of L. donovani exposure in this tribe is due to environmental factors.

Characterization of two antagonistic strains of Rahnella aquatilis isolated from soil in Egypt.

In an attempt to obtain biological control agents for controlling bacterial spot of cucumber, over 250 bacterial strains were isolated from agricultural soil samples, collected from different localities in Giza Governorate (Egypt) and screened for in vitro antibiosis towards Xanthomonas campestris. Only 2 strains showed antagonistic activity. They and their culture filtrates restricted the growth of a number of G- and G(+)-indicator bacteria. On Chrome Azurol S agar, both strains exhibited a marked siderophore production. Biolog plates identified these strains as Rahnella aquatilis. Their characteristics were studied and compared with literature data on R. aquatilis. This antagonistic bacterium has not been previously isolated in Egypt.

Factors affecting variations in exposure to infections by Leishmania donovani in eastern Sudan

A cross-sectional survey was carried out in Gedaref state, eastern Sudan to investigate the prevalence of positive leishmanin skin tests and environmental factors related to Leishmania donovani infection. A total of 3835 people living in 11 villages in 3 regions were screened. Soil types and tree densities were determined in 33 villages inhabited by 44 different tribes. The highest rates of positive skin tests were in Rahad region [33.9%], Atbara [21.6%] and Gedaref [10.6%], with an average of 21.1% for the state. Risk of infection by L. donovani varied significantly between different tribes. Higher densities of Acacia and Balanites spp. trees were in Masaleet villages, suggesting that the relatively high risk of L. donovani exposure in this tribe is due to environmental factors

A comparison of the physicochemical and immunological properties of the plant gum exudates of Acacia senegal (gum arabic) and Acacia seyal (gum tahla).

The physiochemical and immunological properties of three Sudanese gum arabic samples and four gum tahla samples (two Sudanese, one West African and one Tanzanian--Acacia seyal var. seyal) were compared. The optical rotation (ca -30 degrees) and rhamnose (12-14%), arabinose (24-29%), galactose (36-42%), glucuronic acid (16-17%), nitrogen (0.327-0.365%) and protein (2.16-2.41%) contents of the gum arabic samples were consistent with the FAO (1990) specification for Acacia gum. In contrast the gum tahla samples had positive [alpha]D values (+45 degrees to +54 degrees), lower rhamnose (3-4%) and higher arabinose (41-45%) contents and lower nitrogen (0.147-0.175%), and hence protein (0.97-1.15%), contents. All of the gum arabic samples precipitated with beta-glucosyl Yariv reagent and hence were shown to contain arabinogalactan-protein(s) (AGPs), whereas in all but one of the gum tahla samples AGPs were not detected. The strong interaction of gum tahla with a monoclonal antibody known to recognize arabinose residues present in AGPs and arabinogalactans (AGs) was consistent with the observed higher levels of arabinose present in the gum tahla samples relative to the gum arabic samples. The data presented confirm that there are a number of physicochemical and structural differences between gum arabic (A. senegal gum) and gum tahla (A. seyal gum), and that a quick and simple immunological technique (immunodot blots) using an antiAGP/AG monoclonal antibody (MAC 207) could be used to screen for the presence of gum tahla in gum arabic consignments.

Risk of thrombocytopenia in the infants of mothers with idiopathic thrombocytopenia.

Twenty-nine of 27,662 pregnant women had autoimmune thrombocytopenia at the time of delivery at King Khalid University Hospital over 6 years starting June 1986. Twenty-six had idiopathic thrombocytopenic purpura (ITP), gave birth to 33 infants, of which 22 were by spontaneous vaginal delivery, eight by lower segment cesarean section, and two by forceps. Fourteen (44%) of the 32 living infants had platelets less than 150 x 10(9)/L and four (12.5%) had severe thrombocytopenia (platelets less than 50 x 10(9)/L). The mothers' platelets of less than 50 x 10(9)/L at delivery were found to be predictive of thrombocytopenia in their infants (P < 0.027), compared with mothers' platelet of more than 50 x 10(9)/L. Maternal treatment with prednisone did not seem to have significant effect on infants' platelets (P < 0.89). All infants with severe thrombocytopenia (less than 50 x 10(9)/L) at birth had ultrasound done and were found to be normal. We conclude that: (1) steroid given to pregnant women with ITP does not increase infants' platelet counts, (2) severe thrombocytopenia in the mothers (platelet counts less than 50 x 10(9)/L) is highly predictive of thrombocytopenia in their infants; (3) cesarean section should be limited to the mother with severe thrombocytopenia if fetal scalp platelets are less than 50 x 10(9)/L.