Study of P wave dispersion in patients with paroxysmal atrial fibrillation and its role in prediction of atrial fibrillation recurrence.

BACKGROUND: It has been known that increased P wave duration and P wave dispersion reflect prolongation of intra-atrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses, which are well-known electrophysiologic characteristics in patients with atrial arrhythmias and especially paroxysmal atrial fibrillation. The objective of this study was assessment of P wave dispersion value in cases with paroxysmal atrial fibrillation and its role in predicting recurrence. RESULTS: Forty-eight patients with documented paroxysmal AF were subjected to clinical evaluation, electrocardiogram and routine Doppler echocardiogram. We found that a statistically significant association was detected between P wave dispersion and older age, diabetic and hypertensive cases with positive correlation also detected with left atrial dimension (LAD), left ventricle size and diastolic dysfunction grade. Mean corrected P wave dispersion and corrected QT interval were higher among cases using sotalol, ca channel blockers, among cases using nitrates and among cases with Morris index > 0.04. Higher mean value of corrected QT was associated with biphasic P v1 shape. Old age, female sex, P wave dispersion and QT wave dispersion are statistically significant predictors of PAF recurrence. CONCLUSION: P wave dispersion in patients with paroxysmal atrial fibrillation was strongly correlated to older age, diabetic and hypertensive patients and also with left atrial dimension (LAD), left ventricle size and diastolic dysfunction grade. Also, mean corrected P wave dispersion can predict atrial fibrillation recurrence in patients with Morris index > 0.04, old age, female sex, and QT wave dispersion.

Superior semicircular canal dehiscence: a radiological and clinical study.

Aim: to assess radiologically the prevalence of SSCD with its clinical presentations and its relationship with age. Methods: a prospective cohort study carried out on 200 consecutive patients (400 temporal bones). Radiological evaluation was performed using High Resolution Computed Tomography (HRCT) with measurement of thickness of bone covering superior semicircular canal (SCC), height and diameter of SSC. Results: Two hundred patients (400 temporal bones) were involved. The mean thickness ± SD, the mean diameter ± SD and the mean height ± SD were 1.38 ± 0.80 mm, 0.94 ± 0.26 mm and 10.91 ± 2.39 mm respectively. The prevalence of SSCD and predehiscence were 1% and 14% respectively. The commonest symptom encountered was autophony (48.3%). When the SSC thickness, diameter and height were compared with the age of patients, statistically significant differences were detected. The highest diameter, lowest height and lowest thickness were found in patients aged from 54 to 72 years. Thickness of bony layer covering SSC was found to be the most validated measurement for differentiation between cases with positive and negative symptoms with the highest sensitivity and specificity. Conclusion: The prevalence of SSCD and predehiscence varied among the studies. Autophony is the commonest symptom usually encountered. The condition is acquired rather than congenital. The thickness of bone covering SCC is the most validated measurement in differentiation between cases with positive and negative symptoms.

Heatwaves in Peninsular Malaysia: a spatiotemporal analysis.

One of the direct and unavoidable consequences of global warming-induced rising temperatures is the more recurrent and severe heatwaves. In recent years, even countries like Malaysia seldom had some mild to severe heatwaves. As the Earth's average temperature continues to rise, heatwaves in Malaysia will undoubtedly worsen in the future. It is crucial to characterize and monitor heat events across time to effectively prepare for and implement preventative actions to lessen heatwave's social and economic effects. This study proposes heatwave-related indices that take into account both daily maximum (Tmax) and daily lowest (Tmin) temperatures to evaluate shifts in heatwave features in Peninsular Malaysia (PM). Daily ERA5 temperature dataset with a geographical resolution of 0.25° for the period 1950-2022 was used to analyze the changes in the frequency and severity of heat waves across PM, while the LandScan gridded population data from 2000 to 2020 was used to calculate the affected population to the heatwaves. This study also utilized Sen's slope for trend analysis of heatwave characteristics, which separates multi-decadal oscillatory fluctuations from secular trends. The findings demonstrated that the geographical pattern of heatwaves in PM could be reconstructed if daily Tmax is more than the 95th percentile for 3 or more days. The data indicated that the southwest was more prone to severe heatwaves. The PM experienced more heatwaves after 2000 than before. Overall, the heatwave-affected area in PM has increased by 8.98 km2/decade and its duration by 1.54 days/decade. The highest population affected was located in the central south region of PM. These findings provide valuable insights into the heatwaves pattern and impact.

Selecting the optimal gridded climate dataset for Nigeria using advanced time series similarity algorithms.

Choosing a suitable gridded climate dataset is a significant challenge in hydro-climatic research, particularly in areas lacking long-term, reliable, and dense records. This study used the most common method (Perkins skill score (PSS)) with two advanced time series similarity algorithms, short time series distance (STS), and cross-correlation distance (CCD), for the first time to evaluate, compare, and rank five gridded climate datasets, namely, Climate Research Unit (CRU), TERRA Climate (TERRA), Climate Prediction Center (CPC), European Reanalysis V.5 (ERA5), and Climatologies at high resolution for Earth's land surface areas (CHELSA), according to their ability to replicate the in situ rainfall and temperature data in Nigeria. The performance of the methods was evaluated by comparing the ranking obtained using compromise programming (CP) based on four statistical criteria in replicating in situ rainfall, maximum temperature, and minimum temperature at 26 locations distributed over Nigeria. Both methods identified CRU as Nigeria's best-gridded climate dataset, followed by CHELSA, TERRA, ERA5, and CPC. The integrated STS values using the group decision-making method for CRU rainfall, maximum and minimum temperatures were 17, 10.1, and 20.8, respectively, while CDD values for those variables were 17.7, 11, and 12.2, respectively. The CP based on conventional statistical metrics supported the results obtained using STS and CCD. CRU's Pbias was between 0.5 and 1; KGE ranged from 0.5 to 0.9; NSE ranged from 0.3 to 0.8; and NRMSE between - 30 and 68.2, which were much better than the other products. The findings establish STS and CCD's ability to evaluate the performance of climate data by avoiding the complex and time-consuming multi-criteria decision algorithms based on multiple statistical metrics.

Comprehensive chemical profiling of Bassia indica Wight. aerial parts extract using UPLC-ESI-MS/MS, and its antiparasitic activity in Trichinella spiralis infected mice: in silico supported in vivo study.

BACKGROUND: Trichinellosis is a public health threat infected both animals and humans as a result of eating undercooked meat. It caused by Trichinella spiralis that has widespread drug resistance and even developed many sophisticated strategies for their survival, this increases the demand in searching for new anthelmintic drugs from natural source. METHODS: Our objectives were to test the in vitro and in vivo anthelmintic activity of Bassia indica BuOH frac., and to characterize its chemical composition using UPLC-ESI-MS/MS. Besides an in silico molecular docking study with the prediction of the PreADMET properties. RESULTS: In vitro investigation of B. indica BuOH frac., showed severe destruction of the adult worm and larvae, marked cuticle swelling, areas with vesicles, blebs and loss of annulations. This was assured via in vivo study, which revealed a significant reduction (P < 0.05) in the mean adult worm count with efficacy of 47.8% along with a significant decrease (P < 0.001) in the mean larval count per gram muscle with efficacy 80.7%. Histopathological examinations of the small intestine and muscular sections showed marked improvement. In addition, immunohistochemical findings demonstrated that B. indica BuOH frac. depressed the proinflammatory cytokines expressions of TNF-α, which was obviously upregulated by T. spiralis. Precise chemical investigation of the BuOH frac. using UPLC-ESI-MS/MS resulted in the identification of 13 oleanolic type triterpenoid saponins; oleanolic acid 3-O-6´-O-methyl-ß-D-glucurono-pyranoside (1), chikusetsusaponin-IVa (2) and its methyl ester (3), chikusetsusaponin IV (4) and its methyl ester (5), momordin-Ic (6) and its methyl ester (7), betavulgaroside-I (8), -II (9) -IV (10), -X (11), licorice-saponin-C2 (12) and -J2 (13). In addition, 6 more phenolics were identified as syringaresinol (14), 3,4-di-O-caffeoylquinic acid (15), 3-O-caffeoyl-4-O-dihydrocaffeoylquinic acid (16), 3,4-di-O-caffeoylquinic acid butyl ester (17), 3,5-di-O-galloyl-4-O-digalloylquinic acid (18) and quercetin 3-O-(6´´-feruloyl)-sophoroside (19). The auspicious anthelmintic activity was further ascertained using in silico molecular docking approach that targeted certain protein receptors (ß-tubulin monomer, tumor necrosis factor alpha (TNF-α), cysteine protease (Ts-CF1), calreticulin protein (Ts-CRT)), all the docked compounds (1-19) fit into the binding site of the active pocket with binding affinities noteworthy than albendazole. In addition, ADMET properties, drug score and drug likeness were predicted for all compounds.

Projection of temperature extremes of Egypt using CMIP6 GCMs under multiple shared socioeconomic pathways.

Global warming has amplified the frequency of temperature extremes, especially in hot dry countries, which could have serious consequences for the natural and built environments. Egypt is one of the hot desert climate regions that are more susceptible to climate change and associated hazards. This study attempted to project the changes in temperature extremes for three Shared Socioeconomic Pathways (SSPs), namely, SSP1-2.6, SSP2-4.5, and SSP5-8.5 and two future periods (early future: 2020-2059 and late future: 2060-2099) by using daily maximum (Tmax) and minimum temperature (Tmin) of general circulation model (GCMs) of Coupled Model Inter-comparison Project phase 6 (CMIP6). The findings showed that most temperature extreme indices would increase especially by the end of the century. In the late future, the change in the mean Tmin (4.3 °C) was projected to be higher than the mean Tmax (3.7 °C). Annual maximum Tmax, temperature above 95th percentile of Tmax, and the number of hot days above 40 °C and 45 °C were projected to increase in the range 3.0‒5.4 °C, 1.5‒4.8 °C, 20‒95 days, and 10‒52 days, respectively. In contrast, the annual minimum of Tmin, temperature below the 5th percentile, and the annual percentage of cold nights were projected to change in the range of 2.95‒5.0 °C, 1.4‒3.6 °C, and - 0.1‒0.1%, respectively. In all the cases, the lowest changes would be for SSP1-2.6 in the early period and the greatest changes for SSP5-8.5 in the late period. The study indicates that the country is likely to experience a rise in hot extremes and a decline in cold extremes. Therefore, Egypt should take long-term adaptation plans to build social resiliency to rising hot extremes.

Thermal bioclimatic indicators over Southeast Asia: present status and future projection using CMIP6.

Mapping potential changes in bioclimatic characteristics are critical for planning mitigation goals and climate change adaptation. Assessment of such changes is particularly important for Southeast Asia (SEA) - home to global largest ecological diversity. Twenty-three global climate models (GCMs) of Coupled Model Intercomparison Project Phase 6 (CMIP6) were used in this study to evaluate changes in 11 thermal bioclimatic indicators over SEA for two shared socioeconomic pathways (SSPs), 2-4.5 and 5-8.5. Spatial changes in the ensemble mean, 5th, and 95th percentile of each indicator for near (2020-2059) and far (2060-2099) periods were examined in order to understand temporal changes and associated uncertainty. The results indicated large spatial heterogeneity and temporal variability in projected changes of bioclimatic indicators. A higher change was projected for mainland SEA in the far future and less in maritime region during the near future. At the same time, uncertainty in the projected bioclimatic indices was higher for mainland than maritime SEA. Analysis of mean multi-model ensemble revealed a change in mean temperature ranged from - 0.71 to 3.23 °C in near and from 0.00 to 4.07 °C in far futures. The diurnal temperature range was projected to reduce over most of SEA (ranging from - 1.1 to - 2.0 °C), while isothermality is likely to decrease from - 1.1 to - 4.6%. A decrease in isothermality along with narrowing of seasonality indicated a possible shift in climate, particularly in the north of mainland SEA. Maximum temperature in the warmest month/quarter was projected to increase a little more than the coldest month/quarter and the mean temperature in the driest month to increase more than the wettest month. This would cause an increase in the annual temperature range in the future.

Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The food and drug administration approved many drugs to treat diabetes mellitus, but those drugs do not have a noticeable effect on weight management. Recently, glucagon-like peptide 1 agonist known as Cotadutide serve as a potent drug in treating type 2 diabetes by reducing blood glucose levels and body weight indices. This study aimed to explore the safety and efficacy of Cotadutide as a treatment for type 2 diabetes individuals. METHODS: A comprehensive literature search was done on different databases, including PubMed, Scopus, Web of Science, and Cochrane Library to capture all relevant articles using an established search strategy. The inclusion criteria were randomized controlled trials that assessed the safety and efficacy of Cotadutide versus placebo or any anti-diabetes drugs in patients with type 2 diabetes mellitus and a BMI between 22 kg/m2 and 40 kg/m2. We conducted the analysis using Revman software version 5.4. RESULTS: We found 663 relevant articles. From which nine studies were included and subjected to qualitative analysis and eight for quantitative analysis. The pooled effect showed that Cotadutide was better than placebo in reducing body weight (kg) (Mean difference (MD) = 3.31, p < 0.00001), glycated hemoglobin (HbA1c) (MD = 0.68, p > 0.00001), glucose area under the plasma concentration curve (AUC [0-4 h]) (MD = 30.15, p < 0.00001), and fasting plasma glucose over time (mg/dl) (MD = 31.31, p < 0.00001). CONCLUSION: Cotadutide is safe and effective in reducing plasma glucose levels, HbA1c and body weight in individuals with type 2 diabetes. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD: CRD42021257670 ).

Effectuation of loading a natural acetyl carnosine derivative within a promising cross-linked cyclodextrin spongey-like nanospheres on Physicochemical characterization and release behavior.

This study centered on the ability of the cross-linked nano-sponge system to load the drug and to improve its physicochemical and dissolution properties. A spectrophotometric method was used to determine the wavelength of maximum absorbance of the drug. The ultrasonic-assisted synthesis method was used for nano-sponge preparation. Solution-state interactions, encapsulation efficiency and production yield, and in-vitro release were also investigated. Nano-sponges were characterized by Transmission Electron-Microscopy (TEM), Scanning Electron-Microscopy (SEM), Fourier Transform-Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and X-Ray Diffractometry (X-RD) studies. The maximum absorption wavelength of N-acetyl-L-carnosine was found to be at 210 nm. Solution-state interaction studies revealed a bathochromic shift. The production yield of nano-sponges ranged from 59.58% to 72.54%. In-vitro release study showed a sustained drug release for 228 hours. TEM images showed regular spherical shapes and sizes of nano-sponges. Their average particle size ranged from 28 nm to 79.2 nm. DSC data documented the drug-polymer interactions. FT-IR determined the presence of functional groups. X-RD showed the physicochemical characteristics of nano-sponges. Proving successful development of N-acetyl-L-carnosine polymeric nano-sponge system with a suitable drug delivery over an extended period beside a noticeable improvement in the physicochemical characterization.

The potential chemo preventive effect of ursolic acid isolated from Paulownia tomentosa, against N-diethylnitrosamine: initiated and promoted hepatocarcinogenesis.

The present study discusses the isolation of ursolic acid from the chloroform extract of Paulownia tomentosa (Thunb) Steud fruits and its cytotoxic effect has been assessed in-vitro was performed in different cells lines (A-549, MCF-7, HepG2) and in-vivo using N-diethylnitrosamine. The obtained results revealed that ursolic acid showed significant cytotoxic activity on MCF-7 and HepG2 cell lines in comparison to Doxorubicin as a reference drug. Moreover, we have assessed the inhibitory effects of Paulownia tomentosa fruit chloroform extract and the isolated ursolic acid on hepatocarcinogenesis was carried out for the first time using N-diethylnitrosamine, where the group treated with ursolic acid given orally after 8 weeks of cancer induction showed the most significant results in comparison to the chloroform extract. The effect of ursolic acid on intoxicated rats caused significant restoration of most of the normal hepatocytes architecture with regular dark nuclei and the group treated with Paulownia tomentosa fruits showed remarkable results with improvement in biochemical analysis.

Erector spinae plane block for postoperative analgesia in patients undergoing total abdominal hysterectomy: a randomized controlled study original study.

Background: Abdominal hysterectomy is associated with marked postoperative pain and morbidity, but effective postoperative analgesia provides early recovery and ambulation. Aim: We intended to assess the efficacy of bilateral erector spinae plane block (ESPB) on postoperative analgesia in females undergoing abdominal hysterectomy under general anesthesia. Settings and Design: The design was a prospective, randomized, controlled, single-blind clinical study. Patients and Methods: Sixty patients with American Society of Anesthesiologists (ASA) physical status classes Ι to ΙΙΙ were scheduled for elective abdominal hysterectomy under general anesthesia, patients were randomly allocated into two equal groups. ESPB patients received ultrasound-guided ESPB at T9 vertebrae level with 20 ml bupivacaine 0.5%. Control group patients did not receive a block. Total fentanyl consumption in the first 24 h and visual analogue scale (VAS) score for pain were evaluated postoperatively. Unpaired Student's t-tests, chi-square tests, and Z tests were used to compare groups. Results: No significant differences were recorded between the groups regarding age, weight, ASA physical status, or surgery duration, Total fentanyl consumption in the first 24 h was significantly higher in the control group than the ESPB group (P=0.003; 485±20.39 mcg vs 445±67.49 mcg, respectively), VAS for pain was significantly higher in the control group for the first 12 h postoperatively. Conclusions: Bilateral ESPB provided effective postoperative analgesia and markedly decreased postoperative fentanyl consumption in patients undergoing an abdominal hysterectomy.

Impact of serum soluble programed death ligand 1 on end of treatment metabolic response of diffuse large B cell lymphoma patients.

Programmed death ligand-1 (PD-L1) plays an important role in the immune evasion of cancer cells and, in turn, can influence the outcome of many malignancies. The serum soluble PD-L1 (sPD-L1) levels were measured in diffuse large B cell lymphoma (DLBCL) patients at diagnosis and at end of treatment. Their impact on end of treatment metabolic response was analyzed. Serum sPD-L1 level was significantly elevated in DLBCL patients at diagnosis than in controls (P < 0.001). Also, serum sPD-L1 level at diagnosis was significantly higher than that at end of treatment (P < 0.001). Patients who achieved partial response (PR) had significantly higher serum sPD-L1 level at end of treatment than controls (P < 0.001). In contrast, all patients especially those who achieved complete response (CR) had insignificantly different serum sPD-L1 level at end of treatment than controls (P = 0.354 and P = 0.090, respectively). There was a significant difference between serum sPD-L1 level at diagnosis and that at end of treatment in patients who achieved PR and CR (P = 0.023 and P < 0.001, respectively). On univariate analysis, presence of comorbidities, Ann Arbor stage IV, high serum sPD-L1 level at diagnosis and high serum sPD-L1 level at end of treatment were significantly associated with achievement of PR (P = 0.018 and P = 0.043, P = 0.045 and P < 0.001, respectively). On multivariate analysis, serum sPD-L1 levels at diagnosis and at end of treatment were still influencing metabolic response significantly (P = 0.014 and P = 0.007, respectively). Serum sPD-L1 is a predictor for metabolic response to immunochemotherapy in DLBCL patients.

Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses.

The high propensity of influenza viruses to develop resistance to antiviral drugs necessitates the continuing search for new therapeutics. Peanut skins, which are low-value byproducts of the peanut industry, are known to contain high levels of polyphenols. In this study, we investigated the antiviral activity of ethanol extracts of peanut skins against various influenza viruses using cell-based assays. Extracts with a higher polyphenol content exhibited higher antiviral activities, suggesting that the active components are the polyphenols. An extract prepared from roasted peanut skins effectively inhibited the replication of influenza virus A/WSN/33 with a half maximal inhibitory concentration of 1.3 µg/mL. Plaque assay results suggested that the extract inhibits the early replication stages of the influenza virus. It demonstrated activity against both influenza type A and type B viruses. Notably, the extract exhibited a potent activity against a clinical isolate of the 2009 H1N1 pandemic, which had reduced sensitivity to oseltamivir. Moreover, a combination of peanut skin extract with the anti-influenza drugs, oseltamivir and amantadine, synergistically increased their antiviral activity. These data demonstrate the potential application of peanut skin extract in the development of new therapeutic options for influenza management.

Efficiency of the leaves and fruits of Aegle marmelos methanol extract (L.) Correa and their relative hepatotoxicity induced by CCL4 and identification of their active constituents by using LC/MS/MS.

The methanol extracts of both leaves and fruits (MEL & MEF) of A. marmelos (L.) Correa (family Rutaceae) were analyzed by using analytical method based on liquid chromatography-tandem mass spectrometry (LC/MS/MS). The objective of this study was to identify the active constituents of (MEL & MEF) of A. marmelos. Six, alkaloids namely aeglemarmelosine, marmesiline aegelinoside, shahidine, anhydromarmeline and N-2-methoxy-2-(4-methoxyphenyl) ethylcinnamide and two flavonoids, rutin and kaempferol-3-O-rutinoside in leaves were identified. Two alkaloids marmesiline and shahidine in the methanol extracts of fruits, also have been identified. Moreover, the efficiency of extracts was performed for measuring the reducing hepatotoxicity effect induced by carbon tetrachloride (CCl4) in mice. Accordingly, several biochemical parameters were performed such as lipid profile in serum, liver functions enzyme activities, glycolytic enzyme activities. In addition, LDH and SDH were investigated. The results obtained demonstrated, significant increase in lipid profile, liver function biomarkers in addition to glycolytic enzyme activities in CCl4-induced hepatotoxicity. Histopathological examination confirmed the biochemical results. Treatment of intoxicated mice with (MEL & MEF) of A. marmelos showed amelioration signs in biochemical findings as well as at cellular level. It could be concluded that both MEL & MEF can be used clinically for their potential effect as a hepatoprotective that normalized liver function biomarkers, hepatic architecture and restore physiologically status of the body against CCl4 intoxication.

Cytotoxic new furoquinoline alkaloid isolated from Ammi majus L. growing in Egypt.

Two alkaloids of the furoquinoline-type were isolated from Ammi majus L.; a new one and was identified as 4-hydro-7-hydroxy-8-methoxyfuroquinoline (1), and the other was isolated for the second time from nature and was identified as 4-hydro-7-hydroxy-8-prenyloxyfuroquinoline (2). The structures of the isolated compounds were established and confirmed by 1D and 2D NMR spectroscopy including 1H, 13C NMR, COSY, HSQC and HMBC, while the exact masses were confirmed by HRESI/MS. The cytotoxic activity of the isolated compounds (1 and 2) was evaluated against HepG-2, PC-3, A-549 and MCF-7 and the obtained results suggested selective antiproliferative and cytotoxic effects, with IC50 = 230.2 and 326.5 µM against HepG-2 and MCF-7, respectively, for compound (1). While, compound (2) recorded IC50 = 234.2 µM against MCF-7.

Burden of Diarrhea in the Eastern Mediterranean Region, 1990-2013: Findings from the Global Burden of Disease Study 2013.

Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.

Therapeutic role of a synthesized calcium phosphate nanocomposite material on hepatocarcinogenesis in rats.

Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade. With this in mind, this study was designed to evaluate the therapeutic effects of a synthesized tricalcium phosphate nanocomposite material (nano-TCP) on hepatocarcinoma in a rat model, as initiated with diethylnitrosamine (DEN) and promoted with phenobarbital (PB). Hepatocarcinoma was induced with intraperitoneal injections of DEN (50 mg·(kg body mass)(-1)) 3 times a week for 2 weeks. Three weeks after the last dose of DEN, the rats received PB (0.05 %, w/v) in their drinking water for a further 6 weeks. Nano-TCP (100 mg·(kg body mass)(-1)) was administered intraperitoneally 3 times per week to rats with HCC. At the end of the experimental period, liver samples were collected from all animals for biochemical and histopathological analysis. The degree of DNA fragmentation was analyzed, in addition to immune status, by measuring the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The activities of the most important free-radical scavengers of the antioxidant defense system as well as malondialdehyde (MDA) content and liver enzymes were measured. The levels of hepatic heat shock protein-70 (HSP-70), caspase-3, and metalloproteinase-9 were also measured as markers for inflammation and apoptosis. Histopathological examination of liver tissue was performed. The results revealed the potent efficacy of nano-TCP in repairing the fragmented DNA and ameliorating most of the investigated parameters by significant elevation in the levels of hepatic alanine aminotransferase (ALT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. On the other hand, there was a significant decrease in hepatic gamma-glutamyl transpeptidase (γ-GT), MDA, IL-2, IFN-γ, TNF-α, matrix metalloproteinase-9 (MMP-9), HSP-70, and caspase-3 levels upon treatment. The findings form histopathological examination of the liver tissues agreed with the biochemical results and confirmed the difference between the control and treatment groups. In conclusion, nano-TCP succeeded in treating hepatocarcinoma efficiently, and presents a new hope for patients to get safe, fast, and effective treatment.

Two new cytotoxic furoquinoline alkaloids isolated from Aegle marmelos (Linn.) Correa.

Two new cytotoxic furoquinoline alkaloids were isolated from the leaves of Aegle marmelos (Linn.) Correa; one from the total alkaloidal fraction (acid/base shake-out method) of the CHCl3 extract and identified as 7,8-dihydroxy-4-hydrofuroquinoline and named trivially as Aegelbine-A. The other new alkaloid isolated from the pet. ether extract and identified as 4-hydro-7-hydroxy-8-prenyloxyfuroquinoline and named trivially as Aegelbine-B, together with a known alkaloid; aegeline and a known phenolic acid; ρ-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and HR-ESI/MS. The cytotoxic activity of the isolated compounds was evaluated in vitro against HepG-2, PC3, A549 and MCF-7 cell lines. The obtained results revealed promising activity with structure-based relationship which is discussed briefly.

Transdermal delivery of vancomycin hydrochloride using combination of nano-ethosomes and iontophoresis: in vitro and in vivo study.

This study aimed to evaluate transdermal delivery of vancomycin hydrochloride using the combination of ethosomes as an encapsulating vesicle and iontophoresis. Ethosomes were prepared and evaluated in terms of electrochemical stability. Cathodal iontophoresis of negatively charged ethosomes and anodal iontophoresis of free drug solution and positively charged vesicles were conducted. The effect of current mode, density, concentration of drug and ionic strength was studied. In vivo study was performed by inducing mediastinitis in Sprague-Dawley rats using methicillin-resistant Staphylococcus aureus as infected pathogen, the mean bacterial count was compared between groups of rats, one of the treated groups received drug intramuscularly while the other group received vancomycin using iontophoretic delivery of optimized ethosomal formula. Ethosomes showed efficient electrochemical stability, cathodal iontophoresis of negatively charged vesicle (F2) showed maximum transdermal flux (550 µg/cm(2)/h) compared to free drug solution and other ethosomal formulae, transdermal flux was reduced by altering current mode from continuous to ON/OFF mode, reducing current density and by using normal saline as drug solvent; on the other hand, flux was potentiated by increasing drug concentration from 25 to 75 mg/ml. In vivo study revealed that there was a significant difference in terms of bacterial count between untreated and treated groups, while there was no statistically significant difference between the I.M. vancomycin treatment and treatment conducted by iontophoretic delivery of vancomycin encapsulated in ethosomal formula. Combination between ethosomes and iontophoresis had succeeded in delivering vancomycin transdermally.