Ficus platyphylla alleviates seizure severity and neurobehavioral comorbidities in pentylenetetrazole-kindled rats via modulation of oxidative stress.

PTZ kindling induces oxidative stress, neuronal cell degeneration, and neurobehavioral alterations in rodents that mimic neuropsychiatric comorbidities of epilepsy, which could be initiated or aggravated by some antiepileptic drugs. Here, we investigated the effects of the methanol extract of Ficus platyphylla (FP) on severity scores for seizures, neuronal cell degeneration, and neurobehavioral alterations in rats kindled with pentylenetetrazole (PTZ) and probed the involvement of oxidative stress in these ameliorative effects of FP. FP (50 and 100 mg/kg, p.o.) ameliorated seizure severity, neuronal cell degeneration, depressive behaviors, cognitive dysfunctions, and oxidative stress in rats kindled with PTZ (42.5 mg/kg, i.p.). The findings from this study give additional insights into the potential values of FP in the treatment of persistent epilepsy and major neuropsychiatric comorbidities via modulation of oxidative stress.

Four-year follow-up of outcomes of the hybrid epicardial-endocardial ablation: A single-center experience.

BACKGROUND: The CONVERGE trial demonstrated that hybrid epicardial and endocardial ablation was more effective than catheter ablation for the treatment of persistent atrial fibrillation (AF) at 1 year. Long-term real-world outcome data are scarce. OBJECTIVE: We described a single-center experience by evaluating the long-term effectiveness and safety of hybrid epicardial-endocardial ablation. METHODS: This is a retrospective single-center study. Patients were followed up to 4 years. The primary end point was the rate of AF recurrence up to 4 years postablation. Secondary end points included reduction in antiarrhythmic therapy use, the effect of the ligament of Marshall removal, epicardial posterior wall, 3-dimensional mapping during epicardial ablation, and left atrial appendage exclusion as adjunct intraoperative interventions for AF recurrence. RESULTS: Of the 170 patients, 86.5% had persistent AF and 13.5% had long-standing persistent AF. AF-free survival was 87.6% at 1 year, 76.9% at 2 years, 70.4% at 3 years, and 59.3% at 4 years. Antiarrhythmic drug use was 87.6% at baseline and reduced to 21%, 20.6%, 18%, and 14.1% at year 1, 2, 3, and 4, respectively (P < .01 for all). Three-dimensional epicardial mapping showed a significant reduction in combined recurrence from 42% to 25% over 4 years of follow-up (P = .023). Ligament of Marshall and left atrial appendage exclusion showed numerical reduction in AF recurrence from 35% to 26% (P = .49) and from 44% to 30% (P = .07). CONCLUSION: The hybrid convergent procedure reduces AF recurrence and the need for antiarrhythmic drugs and, while maintaining a good safety profile, for the treatment of persistent and long-standing persistent AF.

RELATIONSHIP BETWEEN SICKLE CELL NEPHROPATHY AND SOME BIOCHEMICAL MARKERS OF HAEMOLYSIS AMONGST PATIENTS WITH SICKLE CELL ANAEMIA IN KANO, NORTHWESTERN NIGERIA.

Introduction: Advancements in the care of patients with sickle cell anaemia have led to significant improvement in survival with many patients reaching adulthood. As they age, long-term complications of the disease manifest in them, notable amongst which is nephropathy which is one of the leading causes of morbidity and mortality in them. There is limited information about sickle cell nephropathy and some biochemical markers of haemolysis that can detect it early in our setting. This study aimed to determine the relationship between some indirect markers of haemolysis and sickle cell nephropathy. Methodology: The study was a descriptive cross-sectional one where 204 adolescent and adult patients with sickle cell anaemia attending the clinic of AKTH Kano were recruited. An interviewer-administered questionnaire was utilized. Blood samples were taken for determination of serum bilirubin, LDH, and reticulocyte count. Spot urine was used to quantitatively determine albumin to creatinine ratio. Data collated was analyzed using SPSS version 22.0. P-value <0.05 was considered significant. Result: Two hundred and four (204) participants were enrolled in to the study. Their mean age was 19.6±5years. Females were the majority 131/204 (64.2%). The median (IQR) serum lactate dehydrogenase, bilirubin, direct bilirubin, and reticulocyte count were 607.0(487.3-758.5) U/L, 54.5(37.0-119.0) umol/L, 16.0(11.3-29.0) umol/L and 4.0(3.0-8.4%) respectively. Sickle cell nephropathy was found in 29/204 (14.2%). There were positive significant associations between sickle cell nephropathy with raised serum bilirubin and serum lactate dehydrogenase (p-value = 0.02 and 0.032 respectively). Conclusion: Sickle cell nephropathy is common amongst patients with sickle cell anaemia and raised serum bilirubin and lactate dehydrogenase are predictors of sickle cell nephropathy.

Synthesis, biological evaluation, and computational studies of N-benzyl pyridinium-curcumin derivatives as potent AChE inhibitors with antioxidant activity.

A library of N-benzylpyridinium-based compounds, 7a-j and 8a-j, was designed and synthesised as potential acetylcholinesterase) AChE (inhibitors. An in vitro assay for the synthesised compounds showed that most compounds had significant AChE inhibitory activities at the nanomolar and submicromolar levels. The benzyl (8a) and fluoro (8b) derivatives were the most active, with IC50 values ≤56 nM. Compound 7f, which had a benzyl moiety, showed the highest potency among all the target compounds, with an IC50 value of 7.5 ± 0.19 nM against AChE, which was higher than that of the activities of tacrine (IC50 = 30 ± 0.2 nM) and donepezil (IC50 = 14 ± 0.12 nM). Compounds with vanillin moieties exhibited antioxidant activity. Among the tested compounds, four derivatives (7f, 7 g, 8f, and 8 g) exhibited superior AChE inhibitory activity, with Ki values of 6-16 nM, which were potent in the same range as the approved drug, donepezil. These compounds showed moderate antioxidant activities, as indicated by the results of the ABTS assay.

Exclusive breastfeeding knowledge and practice among nursing mothers in selected healthcare facilities in Kaduna Metropolis, Nigeria.

Background: Exclusive breast feeding (EBF) in the first six months of life is recognized as an indispensable component of survival, physical and mental development of children. Despite the enormous benefits of EBF, only 39% of infants less than 6 months of age are exclusively breastfed globally. Objectives: This study assessed EBF knowledge, practice and associated factors among nursing mothers attending health facilities in Kaduna metropolis. Methods: Descriptive and cross-sectional study carried out with the aid of a structured questionnaire at the Barau Dikko Teaching Hospital and Gwamna Awwal General Hospital in Kaduna. The participants were recruited by simple random sampling technique with the assistance of trained research assistants for four consecutive weeks in each of the hospital. Data were analysed using SPSS version 16. Results: Majority of the participants were in the age range of 21-30 years. Their main source of information on breastfeeding was from ante-natal clinics (78.3%). Most (86.6%) of the participants had a good knowledge and awareness about EBF, 69.1% of them initiated breastfeeding immediately after birth (within an hour) and 70% of the participants practiced EBF. Insufficient milk, belief that infants require extra fluid, fear of alteration in the breast figure, cultural practice and societal beliefs were identified as the most common barriers to the practice of EBF. Conclusions: Findings from this study showed that most of the participants had a very good knowledge of EBF and are practicing it.

Comparison of Radiation Exposure Among Interventional Echocardiographers, Interventional Cardiologists, and Sonographers During Percutaneous Structural Heart Interventions.

Importance: Transesophageal echocardiography during percutaneous left atrial appendage closure (LAAO) and transcatheter edge-to-edge mitral valve repair (TEER) require an interventional echocardiographer to stand near the radiation source and patient, the primary source of scatter radiation. Despite previous work demonstrating high radiation exposure for interventional cardiologists performing percutaneous coronary and structural heart interventions, similar data for interventional echocardiographers are lacking. Objective: To assess whether interventional echocardiographers are exposed to greater radiation doses than interventional cardiologists and sonographers during structural heart procedures. Design, Setting, and Participants: In this single-center cross-sectional study, radiation doses were collected from interventional echocardiographers, interventional cardiologists, and sonographers at a quaternary care center during 30 sequential LAAO and 30 sequential TEER procedures from July 1, 2016, to January 31, 2018. Participants and study personnel were blinded to radiation doses through data analysis (January 1, 2020, to October 12, 2021). Exposures: Occupation defined as interventional echocardiographers, interventional cardiologists, and sonographers. Main Outcomes and Measures: Measured personal dose equivalents per case were recorded using real-time radiation dosimeters. Results: A total of 60 (30 TEER and 30 LAAO) procedures were performed in 60 patients (mean [SD] age, 79 [8] years; 32 [53.3%] male) with a high cardiovascular risk factor burden. The median radiation dose per case was higher for interventional echocardiographers (10.6 µSv; IQR, 4.2-22.4 µSv) than for interventional cardiologists (2.1 µSv; IQR, 0.2-8.3 µSv; P < .001). During TEER, interventional echocardiographers received a median radiation dose of 10.5 µSv (IQR, 3.1-20.5 µSv), which was higher than the median radiation dose received by interventional cardiologists (0.9 µSv; IQR, 0.1-12.2 µSv; P < .001). During LAAO procedures, the median radiation dose was 10.6 µSv (IQR, 5.8-24.1 µSv) among interventional echocardiographers and 3.5 (IQR, 1.3-6.3 µSv) among interventional cardiologists (P < .001). Compared with interventional echocardiographers, sonographers exhibited low median radiation doses during both LAAO (0.2 µSv; IQR, 0.0-1.6 µSv; P < .001) and TEER (0.0 µSv; IQR, 0.0-0.1 µSv; P < .001). Conclusions and Relevance: In this cross-sectional study, interventional echocardiographers were exposed to higher radiation doses than interventional cardiologists during LAAO and TEER procedures, whereas sonographers demonstrated comparatively lower radiation doses. Higher radiation doses indicate a previously underappreciated occupational risk faced by interventional echocardiographers, which has implications for the rapidly expanding structural heart team.

Binary and Ternary Complexes of Cucurbit[8]uril with Tryptophan, Phenylalanine, and Tyrosine: A Computational Study.

Selective binding of amino acids, peptides, and proteins by synthetic molecules and elucidation of the geometry and dynamics of the resulting complexes and their strengths are active areas of contemporary research. In recent work, we analyzed via molecular dynamics (MD) simulations the complexes formed between cucurbit[7]uril (CB7) and three aromatic amino acids: tryptophan (W), phenylalanine (F), and tyrosine (Y). Herein, we continue this line of research by performing MD simulations lasting 100 ns to investigate the formation, stabilities, binding modes, dynamics, and specific host-guest noncovalent interactions contributing to the formation of the binary (1:1) and ternary (2:1) complexes in aqueous solution between W, F, and Y amino acids and cucurbit[8]uril (CB8). All complexes were found to be stable, with the binding in each complex dominated by one mode (except for the F-CB8 complex, which had two) characterized by encapsulation of the aromatic side chains of the amino acids within the cavity of CB8 and the exclusion of their ammonium and carboxylate groups. Using the molecular mechanics/Poisson-Boltzmann surface area method to estimate the individual contributions to the overall free energies of binding, results revealed that the key role is played by the amino acid side chains in stabilizing the complexes through their favorable van der Waals interactions with the CB8 cavity and the importance of favorable electrostatic interactions between the carbonyl portal of CB8 and the ammonium group of the amino acid. Visual analysis of structures of the ternary complexes indicated the presence of π-π stacking between the aromatic side chains of the included amino acids. The insights provided by this work may be of value for further efforts aiming to employ the recognition properties of CB8 toward amino acids in applications requiring more elaborate recognition of short peptides and proteins.

New Insights Into the Anticonvulsant Effects of Essential Oil From Melissa officinalis L. (Lemon Balm).

Melissa officinalis L. is used in traditional European and Iranian folk medicines to treat a plethora of neurological diseases including epilepsy. We utilized the in vitro and in vivo models of epilepsy to probe the anticonvulsant potentials of essential oil from M. officinalis (MO) to gain insight into the scientific basis for its applications in traditional medicine for the management of convulsive disorders. MO was evaluated for effects on maximal electroshock (MES) and pentylenetetrazole (PTZ) -induced seizures in mice, on 4-aminopyridine (4-AP)-brain slice model of epilepsy and sustained repetitive firing of current clamped neurons; and its ameliorative effects were examined on seizure severity, anxiety, depression, cognitive dysfunction, oxidative stress and neuronal cell loss in PTZ-kindled rats. MO reversibly blocked spontaneous ictal-like discharges in the 4-AP-brain slice model of epilepsy and secondary spikes from sustained repetitive firing, suggesting anticonvulsant effects and voltage-gated sodium channel blockade. MO protected mice from PTZ- and MES-induced seizures and mortality, and ameliorated seizure severity, fear-avoidance, depressive-like behavior, cognitive deficits, oxidative stress and neuronal cell loss in PTZ-kindled rats. The findings warrant further study for the potential use of MO and/or its constituent(s) as adjunctive therapy for epileptic patients.

Effects of dietary Mitracarpus scaber leaves extract on growth, physiological, antioxidants, and mucosal immune profiles of North African catfish, Clarias gariepinus, and resistance against Edwardsiella tarda infection.

This study evaluated the effect of Mitracarpus scaber leaves extract (MSLE) as a dietary supplement on growth performance, physiological, antioxidants, and mucosal immune profiles of North African catfish, Clarias gariepinus, and resistance to Edwardsiella tarda infection. Four isonitrogenous diets containing 0, 2, 4, or 6 MSLE g/kg were fed to North African catfish fingerlings (n = 240; mean weight = 5.80 g) for 56 days. After the feeding trial, 10 fish from each experimental tank were intraperitoneally injected with E. tarda (ATCC 15,947; 1.0 × 108 CFU/mL) while clinical signs and mortalities were observed for 14 days. The results show that North African catfish fed dietary MSLE had better growth performance, physiological antioxidants, and mucosal immune profiles than when fed a control diet. The best growth, physiological, antioxidant, and mucosal immune response profiles were noticed in the fish fed diet containing 6 MSLE g/kg. Furthermore, fish fed 6 MSLE g/kg diet had a higher survival rate after E. tarda infection. These results indicated that supplementation of MSLE at 6 g/kg improves growth, physiological, antioxidant, and mucosal immune profiles, and promotes resistance of North African catfish.

Esophageal cancer epidemiology, diagnosis, and management in Sudan - A review.

INTRODUCTION: In Sudan, cancer a common health challenge, is the leading cause of death after malaria and viral pneumonia. The aim of the review is to determine the risk factors associated with esophageal cancer (EC) among Sudanese population. METHODS: All published online data concerning EC epidemiology, diagnosis, and management in Sudan were studied. RESULTS: The prevalence of EC in Sudan is ranked fourth among cancer types in males and fifth in females. The squamous cell carcinoma is more predominant than adenocarcinoma. The dietary, dysplasia and teeth loss, cigarette smoking, age, sex, GERD, genetic and environmental interactions remain a risk for developing EC in clinical practice. A significant challenge for treatment is that most of EC patients were often diagnosed in advanced stages due to the lack of early clinical symptoms. Management of EC depends on patient fitness and tumor stage, endoscopic removal was used for early tumors, while chemotherapy, chemo-radiotherapy, surgical resection, or combinations of these were used for advanced tumors. Despite improvements in the management and treatment of EC patients, the general outcome remains very poor. Furthermore, using molecular techniques to better understand the etiology of EC, it may assist in identifying complicated and critical issues and improve therapy towards a new treatment strategy. CONCLUSION: The remarkable factors associated with EC among Sudanese are geographical variation, environmental factors, ethnic differences, dietary and social habits.

Ecdysteroids from the Stem Bark of Vitex doniana Sweet (Lamiaceae; ex. Verbenaceae): A Geographically Variable African Medicinal Species.

Vitex doniana Sweet is an African medicinal species that is prescribed as an aqueous bark extract to be applied topically or orally to achieve anti-infective outcomes. In select regions it is also taken orally as an antimalarial agent. The aim of the current study was to explore the biological properties of V. doniana and isolated compounds in the context of pathogenic bacteria and the protozoan parasite Plasmodium falciparum. Three compounds were isolated and assigned by nuclear magnetic resonance spectroscopy as ecdysteroids: (1) 20-hydroxyecdysone, (2) turkesterone, and (3) ajugasterone C. Interestingly, two of these compounds had not previously been identified in V. doniana, providing evidence of chemical variability between regions. The bark extract and three ecdysteroids were screened for activity against a panel of pathogenic bacteria associated with skin, stomach and urinary tract infections, and the protozoan parasite P. falciparum. The crude extract of the bark inhibited all bacterial strains with MIC values of 125-250 µg.mL-1. The three isolated compounds demonstrated less activity with MIC values of 500-1000 µg.mL-1. Furthermore, no activity was observed against P. falciparum at the screening concentration of 4.8 µg.mL-1. Nevertheless, we present a hypothesis for the possible mechanism for symptomatic relief of malarial fever, which may involve reduction of prostaglandin E(1) & E(2) activity in the hypothalamus via modulation of the monoaminergic system. While further studies are required to identify all antimicrobial agents within this plant species and to determine the cytotoxicity of each of these compounds, these data suggest that the traditional application of this species as an antiseptic is valid.

COVID-19 in Sudan: Response towards control and prevention.

No abstract provided.

Encapsulation of ionic liquids inside cucurbiturils.

Cucurbit[n]urils (CBn, n = 6-8) serve as molecular receptors for imidazolium-based ionic liquids (ILs) in aqueous solution. The amphiphilic nature of 1-alkyl-3-methylimidazolium guests (Cnmim), with a cationic imidazolium residue and a hydrophobic alkyl chain, enabled their complexation with CBn through a combination of the hydrophobic effect and ion-dipole interactions. 1H NMR experiments revealed that the cavity of CBn can host the hydrophobic chain of the ILs, while one of the carbonyl rims served as a docking site for the imidazolium ring. The structure of the complexes was further analyzed by molecular dynamics (MD) simulations, which indicated that the cavity of CB6 can accommodate up to 5 carbon atoms, while the larger cavity of CB7 and CB8 can encapsulate longer alkyl chains in folded conformations. Isothermal titration calorimetry (ITC) experiments provided up to micromolar affinity of ILs to CBn in aqueous solution, which was independently quantified by indicator displacement titrations.

Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies.

The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS), and metoprolol succinate (MS) are reported. The research is, partly, based upon the utilization of computational tools: in this case, molecular dynamics simulations (MDs) and the response surface method (RSM) in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and xanthan gum (XG)) to drug ratio (P/D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG/LCS as well as XG and high molecular weight chitosan (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favorable complex is formed when LCS is used at 15% (w/w) and, importantly, the interaction between XG and LCS is more favorable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P/D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P/D ratios ≥2.6:1. Results obtained from in vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS/XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface, which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode, allowing full tablet hydration and a uniform drug distribution in the swollen tablet.

Comparative diagnosis of pregnancy wastage in cows at slaughter using pregnancy specific protein-B and post slaughter inspection diagnostic procedures.

Slaughter of pregnant animals is a common abattoir practice. This study was designed to compare the diagnostic capacity of pregnancy specific protein-B (PSPB) with post slaughter inspection (PSI) procedures in detecting cows pregnant at slaughter. Blood was collected from cows presenteded for slaughter at an abattoir. The uteri were examined post slaughter for the presence or absence of a foetus. Recovered foetuses were aged using crown-rump length to estimate the stage of pregnancy. Of the 361 cows examined, 72 (19.9 %) were diagnosed pregnant using the PSPB procedure, while 32 (8.9 %) were diagnosed pregnant using PSI diagnosis. Furthermore, with PSI there was a lack of pregnancy diagnosis in 42 (11.6 %) cows detected pregnant using PSPB procedure, and two (0.6 %) cows detected pregnant using PSI were not detected to be pregnant using PSPB diagnosis. Validity of the diagnostic procedures indicated that sensitivity and specificity of the PSPB was 93.8 % and 87.2 %, respectively, while with the PSI diagnosis there was a sensitivity and specificity of 41.7 % and 99.3 %, respectively. The PSPB diagnosis, had an excellent predictive value (AUC - 0.92; p < 0.001; 95 % CI - 0.856 to 0.981). Most of the pregnancy wastage (n = 22; 68.8 %) diagnosed using the PSI method were in the second trimester. The results of this study indicate that PSPB is reliable and a more sensitive diagnostic method than PSI . It is therefore recommended that the PSPB test be incorporated in routine screening for pregnancy status of cows before slaughter.

Effect of Protonation State and N-Acetylation of Chitosan on Its Interaction with Xanthan Gum: A Molecular Dynamics Simulation Study.

Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was ≤50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect.

Structure-activity relationship of novel series of 1,5-disubstituted tetrazoles as cyclooxygenase-2 inhibitors: Design, synthesis, bioassay screening and molecular docking studies.

A novel class of modified 1,5-disubstituted tetrazoles was designed and synthesized, their biological activity as cyclooxygenases inhibitors was screened, and their molecular docking studies were performed. The structural modifications of the first category included the 4-methylsulfonyl phenyl at C-1 of the central moiety and the linkers (-OH, -CH2OH, -CH2CH2OH) with different lengths at the para position of the N-1 phenyl group. For the second category, the 4-methylsulfonyl phenyl group at C-1 was replaced with 4-aminosulfonyl phenyl. While for the third category, a methylene unit was inserted between the C-1 of the tetrazole central ring and the 4-(methylsulfonyl)phenyl group, keeping the same linkers of various extensions at the para position of the N-1 phenyl group. Among the screened compounds, tetrazole 4i showed the best inhibition potency and selectivity values for both COX-2 enzyme (IC50=3µM, SI>67) and COX-1 isoenzyme (IC50>200µM). Compounds 4e, 4h, and 4i, which have the highest inhibition potency toward COX-2 were selected for the molecular docking studies to verify their inhibition and selectivity for COX-2 over COX-1 with their modified structure. The obtained theoretical studies are in agreement with the in vitro bioassay screening results, which supports the importance of the structural modifications for our studied compounds.