Effect of Gastric Fluid Volume on the in Vitro Dissolution and in Vivo Absorption of BCS Class II Drugs: A Case Study with Nifedipine

Nifedipine is a BCS Class II drug used for treatment of hypertension and preterm labor. Large inter-patient variability in nifedipine absorption results in variable exposure among different patients. We conducted in vitro dissolution studies to compare nifedipine dissolution from immediate release (IR) capsules with different volumes of dissolution media. Results from dissolution studies were used to design a crossover study in healthy volunteers to evaluate the effect of coadministered water volume with nifedipine 10 mg IR capsules on nifedipine pharmacokinetics, especially absorption (Cmax, tmax, and AUC0-6). Dissolution studies demonstrated that larger gastric fluid volumes result in enhanced nifedipine dissolution from 10 mg IR cosolvent capsules (73 vs. 17% in 200 and 100 mL simulated gastric fluid, respectively, at 30 min). The pharmacokinetic crossover study in healthy volunteers (N = 6) did not show a significant effect of the water volume administered with the capsule (50 vs. 250 mL) on Cmax, tmax, or AUC0-6 of orally administered nifedipine IR capsules (10 mg). However, administration of large water volumes resulted in lower variability in nifedipine Cmax (47 vs. 70% for 250 and 50 mL, respectively). Administration of large water volumes with nifedipine 10 mg IR cosolvent capsules may reduce inter-individual variability in plasma exposure. Evaluation of similar effects in other BCS Class II drugs is recommended

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1,2. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 3. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 4-7. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 8. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, Kuwait, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. The recombination role is further supported by the high fidelity replication in swine influenza 9 and aggregation of single nucleotide polymorphisms in H5N1 clade 2.2 hemagglutinin 10

Differences in Neuropsychological Performance between Refugee and Non-Refugee Children in Palestine

Neuropsychological studies on refugee children are scarce, but there are even less in the case of Palestinian children. This work aims to study the neuropsychological performance of Palestinian refugee children in Palestine compared to other Palestinian children living outside refugee camps. A comprehensive Neuropsychological battery was administrated to 584 Palestinian school children (464 refugees and 120 non-refugees) aged 6, 7, and 8 years old. Results showed that non-refugee children outperformed refugee children in sustained attention, verbal comprehension, verbal memory, and visual memory. This study is the first to have performed a comprehensive neuropsychological assessment, based on a standardized and validated battery with the Palestinian refugee children. It supports professionals in their evaluation of neurodevelopment and neuropsychological alterations in refugee and non-refugee children in Palestine.Center for Development Cooperation Initiatives (Centro de Iniciativas de Cooperación al Desarrollo—CICODE), Granada University, Spain (Reference No. C14P11_9359

Nature as a treasure trove of potential anti-SARS-CoV drug leads:a structural/mechanistic rationale

The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (M(pro)). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates, viz. acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The evolution of H5N1 has attracted significant interest 1-4 due to linkages with avian 5,6 and human infections 7,8. The basic tenets of influenza genetics 9 attribute genetic drift to replication errors caused by a polymerase complex that lacks a proof reading function. However, recent analysis 10 of swine influenza genes identifies regions copied with absolute fidelity for more than 25 years. In addition, polymorphism tracing of clade 2.2 H5N1 single nucleotide polymorphisms identify concurrent acquisition 11 of the same polymorphism onto multiple genetic backgrounds in widely dispersed geographical locations. Here we show the aggregation of regional clade 2.2 polymorphisms from Germany, Egypt, and sub-Sahara Africa onto a human Nigerian H5N1 hemagglutinin (HA), implicating recombination in the dispersal and aggregation of single nucleotide polymorphisms from closely related genomes

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The rapid evolution of the H5N1 serotype of avian influenza has been explained by a mechanism involving the selection of single nucleotide polymorphisms generated by copy errors. The recent emergence of H5N1 Clade 2.2 in fifty countries, offered a unique opportunity to view the acquisition of new polymorphism in these evolving genomes. We analyzed the H5N1 hemagglutinin gene from a fatal human case from Nigeria in 2007. The newly emerged polymorphisms were present in diverse H5N1 isolates from the previous year. The aggregation of these polymorphisms from clade 2.2 sub-clades was not supported by recent random mutations, and was most easily explained by recombination between closely related sequences

Prevalence and characterization of plasmid-mediated quinolone resistance genes in Proteus species isolated from different patients

Proteus spp. are widely distributed opportunistic pathogens that can cause various human infections. A total of 361 clinical specimens were obtained from patients who were attending to different hospitals in El-Minia governorate, Egypt. Approximately 23 % of the samples belong to Proteus spp. isolates which were obtained from various clinical sources. After biochemical identification, 42.1 % of isolates were found to belong to Proteus vulgaris and 57.8 % to P. mirabilis. The urine samples collected from catheterized patients represented 32.6 % of all the clinical specimens, and the majority of the recorded isolates were Proteus spp. The antibacterial sensitivity of the Proteus spp. was examined using 16 different antibiotics from various families. The most effective antibiotics were Amikacin; Levofloxacin, and Meropenem, recording 68.6 %, 66.2 %, and 62.2 % of the isolates sensitivity to each of these antibiotics, respectively. Using the ureR-based PCR, 48 % of the isolates were identified as P. mirabilis. Moreover, the Qnr genes (i.e., qnrA, qnrB, qnrS, qnrD, and qnrC) and the aac (6')-Ib-cr gene had been identified in 40 % of P. mirabilis isolates. The aims of the study were to investigate the prevalence of Proteus spp. in El-Minia, Egypt; determine the antibacterial susceptibility pattern of these isolates, and characterize the PMQR genes in Proteus spp. Quinolone resistance in P. mirabilis isolates might have been brought on by mechanisms other than qnr and aac (6')-Ib genes. Finally, since Proteus spp. are widespread in the environment; healthcare facilities must uphold stringent sanitation standards to reduce the incidence of the nosocomial infections

On modeling two immune effectors two strain antigen interaction

In this paper we consider the fractional order model with two immune effectors interacting with two strain antigen. The systems may explain the recurrence of some diseases e.g. tuberculosis (TB). The stability of equilibrium points are studied. Numerical solutions of this model are given. Using integer order system the system oscillates. Using fractional order system the system converges to a stable internal equilibrium. Ulam-Hyers stability of the system has been studied

Mercury Materno-fetal Burden and Its Nutritional Impact

BACKGROUND: Mercury exists worldwide in food, water and air throwing its health hazards on all body systems. AIM: To show the influence of the presence of mercury in pregnant mothers’ blood on its level in the umbilical cord blood; and to display the relationship between the different foodstuff on the mercury levels in pregnant mothers' and umbilical cord blood. PATIENTS AND METHODS: This cross-sectional study was conducted on randomly chosen 113 pregnant mothers at the time of labour and on their newborns. Full history, sociodemographic data and food frequency questionnaire for dietary assessment were recorded. The Maternal and neonatal anthropometric measurements together with the Apgar scoring were also measured. Serum mercury levels in both mothers' and umbilical cord blood were measured using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: A high percentage of mothers (82.3%) were exposed to passive smoking. There was a statistically significant positive correlation between the maternal and fetal umbilical cord blood mercury levels (p = 0.002). There was an insignificant negative correlation between the maternal blood and fetal umbilical cord blood mercury levels on one side and each of the different foodstuff on the other side (fish, vegetables, fruits and proteins, for example, meat and legumes). An insignificant positive correlation was found between dairy products and of the maternal blood and umbilical cord blood mercury levels. CONCLUSION: The fetal umbilical cord blood mercury levels correlate positively with the maternal blood mercury. The different foodstuff can influence the maternal and umbilical cord blood mercury levels whether by increase or decrease. Strict measures should be taken to decrease environmental mercury contamination with attention to pregnant mothers