The Potential of Using Bisr Date Powder as a Novel Ingredient in Biscuits Made of Wheat Flour Only or Mixed with Barley.

An overproducing date fruit with limited industrial utilization leads to significant waste and losses, especially in the early stage of date maturity known as bisr. This study aimed to investigate the potential use of bisr date powder (BDP) at different concentrations (25%, 50%, and 100%) as a natural sweetener instead of sugar and barley flour as a source of dietary fiber, vitamins, and minerals instead of wheat flour (50%) in biscuit production over storage periods of 7, 14, and 21 days. The analysis revealed that the bisr Al-Khalas powder sample had a moisture content of 11.84%, ash content of 2.30%, and crude fiber content of 10.20%. Additionally, it had a low protein (2.50%) and fat (0.77%) content, with total carbohydrates at 82.59%. The gradual substitution of bisr Al-Khalas in biscuit production resulted in an increased moisture, ash, fat, protein, crude fiber, and iron content, as well as a decrease in total carbohydrate percentage. A chemical analysis of bisr Al-Khalas powder demonstrated high levels of antioxidants, with 248.49 mg gallic acid/g of phenolic compounds, 31.03 mg quercetin/g of flavonoids, and an antioxidant activity ranging from 42.30%, as shown by the DPPH test. The peroxide content was 0.009 mg equivalent/kg. Biscuit samples with different proportions of bisr Al-Khalas showed an improved resistance to oxidation compared to samples without bisr Al-Khalas, with increased resistance as the percentage of replacement increased during storage. Physical properties such as the diameter, height, and spread percentage, as well as organoleptic properties like color, flavor, aroma, and taste, were significantly enhanced with higher levels of bisr Al-Khalas in the mixture. Biscuit samples fortified with 100% pure bisr Al-Khalas powder were found to be less acceptable, while samples with a 25% substitution did not negatively impact sensory properties. In addition, acrylamide and hydroxymethylfurfural (HMF) were not detected in bisr powder and biscuit samples prepared at different concentrations (25%, 50%, and 100%). In conclusion, the study suggests that bisr Al-Khalas powder, an underutilized waste product, has the potential to add value to commercial biscuit production due to its high nutritional value and extended storage period resulting from its potent antioxidant activity.

Desosomes and desimicelles - a novel vesicular and micellar system for enhanced oral delivery of poorly soluble drug: Optimization of in vitro characteristics and in vivo performance.

This study introduces two innovative nanocarrier systems to improve oral drug delivery. Desosomes and desimicelles combine Deep eutectic solvent (DES) with vesicular or micellar nanosystems, respectively. These novel nanosystems integrate the DES solubilization potency for administering drugs with low aqueous solubility and the vesicular and micellar systems to bypass physiological barriers and improve poor drug bioavailability. Lornoxicam (LRX) is a BCS class II anti-inflammatory with limited aqueous solubility and rapid clearance. Desosomes and desimicelles were prepared and successfully optimized. The optimization depended on particle size, zetapotential, entrapment efficiency, and solubility. The optimized desosomes (LRX-DES-V) and desimicelles (LRX-DES-M) were pictured by transmission electron microscope. Differential scanning calorimetry (DSC) and FTIR analysis indicated the successful inclusion of LRX inside each system. Invitro LRX release profiles revealed controlled release of LRX-DES-V and LRX-DES-M, with more sustained release by the later one. In-vivo study, inflammation was induced using a carrageenan rat model, and the anti-inflammatory effect of LRX-pure, marketed product, traditional niosomes, LRX-DES-V & LRX-DES-M were determined using inhibition %, serum inflammatory cytokines, and histopathology. After 4 h of induction, LRX-DES-M (68.05%) showed a significant inhibition compared to LRX-DES-V (63.57%). LRX-DES-M also showed a better reduction in COX2, PGE2, and TNF-α (1.25-fold, 1.24-fold, and 1.36-fold inhibition), respectively, compared to LRX-DES-V. We can conclude that LRX-DES-V and LRX-DES-M showed better effects than all other groups and that LRX-DES-M might be more effective than LRX-DES-V.

Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.

The potential use of Indian rice flour or husk in fortification of pan bread: assessing bread's quality using sensory, physicochemical, and chemometric methods.

Hassawi rice is an Indica variety cultivated in Saudi Arabia with a higher nutritional value than the commercial Basmati rice varieties. The present study has investigated the feasibility of combining Hassawi rice flour (HRF) or husk (HRHF), an abundant byproduct, with wheat flour to produce nutritious economical pan bread. To achieve this aim, the physicochemical properties of HRF and HRHF were assessed using techniques such as UPLC-tandem MS, ICP-OES, and colorimeter. The proximate composition (moisture, crude fiber, and ash) and mineral contents of HRHF are significantly (p < 0.05) higher than HRF. On the other hand, the compounds p-coumaric acid, vanillic acid, γ- and δ-tocotrienols, and γ-oryzanol were unique to HRF. We further determined the changes in sensory, technological, and physicochemical properties of wheat flour bread substituted with 5%, 10%, and 15% of HRF or HRHF. The rheological tests showed that the addition of HRF and HRHF increased dough development and stability time. Further, substituting wheat flour for HRF and HRHF at levels higher than 10% affected sensory attributes, such as color, taste, odor, flavor, and appearance. These changes, however, were not always at a significant level. The causes of the differences in properties between control and fortified bread samples were investigated by chemometric methods. Samples of bread +HRF at 5 and 10% had comparable overall profiles to the control. On the other hand, bread +HRHF samples proved to retain higher concentrations of bioactive molecules compared to the control bread. Our findings shed light on the possible use of rice husk fibers in baking goods, notably pan bread. Furthermore, by integrating rice husk fibers into baked goods, we may boost their health benefits while also contributing to the long-term use of agricultural waste.

Impact of Modified Atmosphere Packaging Conditions on Quality of Dates: Experimental Study and Predictive Analysis Using Artificial Neural Networks.

Dates are highly perishable fruits, and maintaining their quality during storage is crucial. The current study aims to investigate the impact of storage conditions on the quality of dates (Khalas and Sukary cultivars) at the Tamer stage and predict their quality attributes during storage using artificial neural networks (ANN). The studied storage conditions were the modified atmosphere packing (MAP) gases (CO2, O2, and N), packaging materials, storage temperature, and storage time, and the evaluated quality attributes were moisture content, firmness, color parameters (L*, a*, b*, and ∆E), pH, water activity, total soluble solids, and microbial contamination. The findings demonstrated that the storage conditions significantly impacted (p < 0.05) the quality of the two stored date cultivars. The use of MAP with 20% CO2 + 80% N had a high potential to decrease the rate of color transformation and microbial growth of dates stored at 4 °C for both stored date cultivars. The developed ANN models efficiently predicted the quality changes of stored dates closely aligned with observed values under the different storage conditions, as evidenced by low Root Mean Square Error (RMSE) and Mean Absolute Percentage Error (MAPE) values. In addition, the reliability of the developed ANN models was further affirmed by the linear regression between predicted and measured values, which closely follow the 1:1 line, with R2 values ranging from 0.766 to 0.980, the ANN models demonstrate accurate estimating of fruit quality attributes. The study's findings contribute to food quality and supply chain management through the identification of optimal storage conditions and predicting the fruit quality during storage under different atmosphere conditions, thereby minimizing food waste and enhancing food safety.

The Bioactive Substances in Spent Black Tea and Arabic Coffee Could Improve the Nutritional Value and Extend the Shelf Life of Sponge Cake after Fortification.

The study aimed to evaluate the potential use of spent coffee powder (SCP) and spent tea powder (STP) as bioactive supplements for sponge cake. To achieve this aim, we initially compared the chemical properties of spent tea and coffee powders with those of their raw forms. Subsequently, three supplemented cake blends were prepared (1, 2, and 3% of SCP and STP) to test the effect of their addition on the chemophysical characteristics, sensory attributes, and shelf life of the final products. Our results indicated that spent tea and coffee are prospective materials for polyphenols. Spent tea powder could retain up to 72% (theaflavin trigallate), while spent coffee powder could retain up to 63.9% (1-caffeoylquinic acid) of the identified compounds compared to the raw materials. Furthermore, spent tea and coffee powders contained high levels of dietary fiber (18.95 and 31.65 g/100 g dry weight) and the elements potassium (254.6 and 1218.2 mg/100 g of DW), phosphorus (189.8 and 161.3 mg/100 g of DW), calcium (904.1 and 237.8 mg/100 g of DW), and magnesium (158.8 and 199.6 mg/100 g of DW). In addition, the fortified samples with SCP and STP significantly enhanced the nutritional values while retaining good sensory qualities compared to those of the control sample. Moreover, cakes fortified with the highest concentrations of SCP and STP (3%) showed a significant decrease in malondialdehyde content (MDA; 17.7 and 18.0 µg/g) and microbiological counts (2.4 and 2.5 log cfu/g) compared to the control cake after 14 days of storage. These findings suggest that incorporating SCP and STP into cakes not only enhances their nutritional value but also extends their shelf life. By utilizing these waste products, we can contribute to a more sustainable and ecofriendly food industry.

The Chemical, Rheological, and Sensorial Characteristics of Arabic Bread Prepared from Wheat-Orange Sweet Potatoes Flour or Peel.

The current study investigates the feasibility of preparing Arabic bread from wheat flour, sweet potato flour, or peeled sweet potatoes based on the nutritional values, technological characteristics, and sensory properties of the final products. First, we analyzed the proximate, elemental, total and individual phytochemical compositions of the raw materials and bread samples. The analysis showed that potassium, calcium, and phosphorus were higher in peels than pulp, in the same manner to the total phenolics, flavonoids, and anti-radical scavenging activities. Phenolic acids and flavonols were quantified, where p-coumaric, feruloyl-D-glucose, eucomic, gallic, and ferulic acids were measured as major phenolic acids in either peels or pulp flours, and their quantities were higher in the peels. Furthermore, we evaluated the effects of wheat substitution on the properties of the dough blends and their final bakery. The results indicated that the fortified samples' nutritional and rheological properties were significantly improved, while their sensory qualities were comparable to those of the control. Thereby, the fortified dough blends presented higher dough stabilities, indicating a wider range of applications. Additionally, after the heat treatment, the fortified breads maintained significantly higher total phenolic, flavonoid, anthocyanin, and carotenoid contents, and total antioxidant activities, implying their accessibility for humans upon consumption.

Exploring the potential of intranasally administered naturally occurring quercetin loaded into polymeric nanocapsules as a novel platform for the treatment of anxiety.

Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9 nm, polydispersity index of 0.466 ± 0.023, zeta potential of - 17.5 ± 0.01 mV, and encapsulation efficiency % of 92.5 ± 1.9%. In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. Behavioral testing demonstrated the superiority of QRC loaded polymeric nanocapsules administered intranasally compared to QRC dispersion administered both orally and intranasally. The prepared QRC loaded polymeric nanocapsules also demonstrated good safety profile with high tolerability.

Biological Activities of Grape Seed By-Products and Their Potential Use as Natural Sources of Food Additives in the Production of Balady Bread.

The biological function of bioactive compounds found in plant by-products has triggered expanded interest in recent years. This study aims to produce balady bread enriched with dietary fiber, mineral, and phenolic compounds by the addition of grape seeds powder (GSP) at different levels (5%, 10%, and 15% as a partial substitute for wheat flour). The results show that balady bread (Bb) and grape seed powder have ash contents of about 1.97% and 3.04%, lipid contents of 3.22% and 17.15%, protein contents of 11.16% and 12.10%, fiber contents of 1.06% and 44.90%, and carbohydrates contents of 56.52% and 29%, respectively. Moreover, grape seed powder contains a higher level of iron and zinc about 30.02 and 9.43 mg/kg than the Bb control sample which contains about 8.19 and 7.25 mg/kg respectively. The findings revealed that balady bread fortified with grape seed powder contains a high amount of total polyphenols content (TPC), total flavonoid content (TF), and antioxidant capacity. The farinograph test results showed that increasing the GSP concentration in the flour above 10% reduced dough development, stability, and farinograph quality number. The addition of GSP to wheat flour accelerated the dough's water absorption and mixing tolerance. Grape seed incorporation levels up to 10% (w/w) had no negative effect on dough rheological performance. The sensory evaluation of bread showed that samples that were enriched with grape seeds powder at up to 10% had good quality. Based on these findings, it is recommended to replace up to 10% GSP in the manufacturing of fortified balady bread with satisfactory physical and sensory characteristics and high TPC and antioxidant activity.

Prevalence and Amounts of Common Ingredients Found in Energy Drinks and Shots.

BACKGROUND: Energy drinks are one of the most popular packaged beverage products consumed within the United States (US). Energy drinks are considered a functional beverage, a category that also includes sports drinks and nutraceutical beverages. PURPOSE: The focus of the current study was to examine the nutrition fact panels of the top selling commercially available energy drink and energy shot products within the US to characterize common ingredient profiles to help establish a standard definition and ingredient profile of energy drinks and energy shots for consumers, health care practitioners, and researchers. METHODS: The top 75 commercially available energy drinks and shots were identified and compiled from multiple commercial retail websites as of September 2021. For the purpose of this study, an energy drink must have met the following criteria: (A) marketed as an energy drink; (B) purported to improve energy, focus, or alertness; (C) not sold as a dietary supplement (no supplement fact panels); (D) manufactured as a pre-packaged and ready-to-drink beverage; and (E) contains at least three of (1) caffeine, (2) B-vitamins, (3) sugar, (4) taurine, (5) creatine, (6) quercetin, (7) guarana, (8) ginseng, (9) coenzyme Q10, or (10) branched chain amino acids. Energy shots must have met similar criteria to be included: (A) marketed as an energy shot; (B) purported to improve energy, focus, or alertness; (C) sold as a dietary supplement; (D) manufactured as a pre-packaged beverage with a small volume (<3.5 mL); and (E) contains at least three of the ingredients stated above. RESULTS: Twenty energy shots and fifty-five energy drinks were included in this analysis. The number of ingredients per product (mean ± SD) was 18.2 ± 5.7, with 15 products containing proprietary blends with undisclosed ingredient amounts. The relative prevalence and average amounts of the top ingredients were as follows: caffeine (100%; 174.4 ± 81.1 mg), vitamin B6 (72%; 366.9 ± 648.1 percent daily value (%DV)), vitamin B3 (67%; 121.44 ± 69.9% DV), vitamin B12 (67%; 5244.5 ± 10,474.6% DV), vitamin B5 (37.3%; 113.6 ± 76.6% DV), and taurine (37.3%; amounts undisclosed). CONCLUSIONS: Our findings suggest a high prevalence of caffeine and B-vitamins in these energy products, with many of the formulations containing well above the recommended daily value of B-vitamins.

Nanostructured lipid carriers for enhanced in vitro and in vivo schistosomicidal activity of praziquantel: effect of charge.

WHO considers praziquantel (PZQ) as the drug of choice for treatment of Schistosoma mansoni infection but this requires high dose due to poor solubility and first pass metabolism. The aim of this work was to optimize nanostructured lipid carriers (NLCs) for enhanced PZQ oral delivery. The optimization involved testing the effect of surface charge of NLCs. NLCs comprised precirol ATO as solid lipid with oleic acid, Span 60 and Tween 80 as liquid components. Dicetyl phosphate and stearyl amine were the negative and positive charging agents, respectively. NLCs were prepared by microemulsification technique and were characterized. The schistosomicidal activity of PZQ loaded NLCs was monitored in vitro and in vivo using infected mice. PZQ showed high entrapment efficiency in all types of NLCs (ranged from 93.97 to 96.29%) with better PZQ loading in standard NLCs. This was clarified by thermal analysis which reflected displacement of PZQ by charging agents. In vitro schistosomicidal study revealed the superiority of PZQ loaded positively charged NLCs (LC50 and LC95 equal 0.147 and 0.193 µg/ml respectively) with traditional and negatively charged NLCs being inferior to simple PZQ solution after short incubation period. Scanning electron micrographs showed that PZQ loaded positively charged NLCs resulted in more intense ultrastructural changes in worms. The superiority of positively charged NLCs was confirmed by in vivo assessment as they showed better improvement in histopathological features of the liver of the infected mice compared with other formulations. The study introduced positively charged NLCs as promising carriers for oral delivery of PZQ.

A potent photoreactive general anesthetic with novel binding site selectivity for GABAA receptors.

The pentameric γ-aminobutyric acid type A receptors (GABAARs) are the major inhibitory ligand-gated ion channels in the central nervous system. They mediate diverse physiological functions, mutations in them are associated with mental disorders and they are the target of many drugs such as general anesthetics, anxiolytics and anti-convulsants. The five subunits of synaptic GABAARs are arranged around a central pore in the order ß-α-ß-α-γ. In the outer third of the transmembrane domain (TMD) drugs may bind to five homologous intersubunit binding sites. Etomidate binds between the pair of ß - α subunit interfaces (designated as ß+/α-) and R-mTFD-MPAB binds to an α+/ß- and an γ+/ß- subunit interface (a ß- selective ligand). Ligands that bind selectively to other homologous sites have not been characterized. We have synthesized a novel photolabel, (2,6-diisopropyl-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)methanol or pTFD-di-iPr-BnOH). It is a potent general anesthetic that positively modulates agonist and benzodiazepine binding. It enhances GABA-induced currents, shifting the GABA concentration-response curve to lower concentrations. Photolabeling-protection studies show that it has negligible affinity for the etomidate sites and high affinity for only one of the two R-mTFD-MPAB sites. Exploratory site-directed mutagenesis studies confirm the latter conclusions and hint that pTFD-di-iPr-BnOH may bind between the α+/ß- and α+/γ- subunits in the TMD, making it an α+ ligand. The latter α+/γ- site has not previously been implicated in ligand binding. Thus, pTFD-di-iPr-BnOH is a promising new photolabel that may open up a new pharmacology for synaptic GABAARs.

Hyaluronan biofilms reinforced with partially deacetylated chitin nanowhiskers: Extraction, fabrication, in-vitro and antibacterial properties of advanced nanocomposites.

Fabrication of nanocomposite biofilms with enhanced mechanical and antibacterial properties was successfully achieved from hyaluronan (HA) and partially deacetylated chitin nanowhiskers (ChNWs) by a casting-evaporation method. The hydrolysis process of chitin showed an important role in the dimensions, stability, and the crystallinity of extracted ChNWs in a time-dependent manner. The volume fraction of ChNWs nanofiller varying from (0.001 to 0.5) exhibited a great influence on the mechanical properties of the biofilms (young modulus, strength) was enhanced by the high load-bearing capacity of NWs compared with net HA film. The antibacterial activity of the nanocomposite biofilms exhibited significant bactericidal activity against different types of bacteria (-/+ gram). HA/ChNWs Nanocomposite biofilms did not show any toxicity against normal human dermal fibroblasts (NHDF) and human primary osteogenic sarcoma (Saos-2) cell lines. The new biofilms with unique properties like edibleness, environmental friendliness, high mechanical properties, antibacterial performance, and non-cytotoxicity that could be used in skin tissue regenerations, and drug delivery applications.

An unusual presentation of pleomorphic adenoma in a patient with thalassemia: A case report.

We report the first case of spontaneous infarction occurring in pleomorphic adenoma located in infratemporal fossa mimicking parapharyngeal abscess, including clinical presentation, workups, and surgical approach. The final diagnosis was confirmed on a histological basis. The combination of CT scan and MRI might be helpful in distinguishing neoplasia from abscess collection in this area. Surgical intervention is the treatment of choice.

Nuchal cord: impact of umbilical artery Doppler indices on intrapartum and neonatal outcomes: a prospective cohort study.

Background/objective: The purpose of this study is to investigate the use of a more biologic parameter for evaluation of the effect of nuchal cord tightness; the study of blood flow in the umbilical arteries of nuchal cord using Doppler ultrasonography. Methods: This prospective cohort study was conducted at Ain Shams University Maternity Hospital, Cairo, Egypt in the period between August 2015 and August 2017. Hundred primigravidas were recruited with nuchal cord diagnosed by Doppler ultrasonography; whereas the rest of the study population was included in the "Control group". Doppler velocimetry study was then performed on a free-floating loop of the umbilical cord and Doppler indices were calculated. Both groups were followed up during labor: intrapartum events, mode of delivery, and neonatal outcome were recorded. Results: Intrapartum fetal heart rate abnormalities were significantly more common in the nuchal cord group compared to the control group. The overall cardiotocography category was significantly more commonly reflecting abnormal fetal heart rate patterns in the nuchal cord group compared to the control group with 46.74% of the nuchal group patients falling within the "suspicious - pathological - need urgent intervention" categories. Intervention rate was significantly higher in the nuchal cord group than the control group (33.69 versus 21.84%). Moreover, incidence of intrapartum fetal heart rate abnormalities and intervention rate were significantly higher in the nuchal cord with abnormal Doppler subgroup compared to both nuchal cord with normal Doppler subgroup and the control group; with a calculated number needed to harm of 2.11. Conclusions: In view of these results, it might be concluded that umbilical cord tightness affecting fetal hemodynamics (expressed by changes in umbilical artery Doppler) might be a determinate factor affecting the intrapartum course.

Systematic Structure-Activity Studies on Selected 2-, 3-, and 4-Monosubstituted Synthetic Methcathinone Analogs as Monoamine Transporter Releasing Agents.

Methcathinone analogs are appearing on the clandestine market at a rate nearly out-pacing the ability of investigators to examine them on an individual basis. To formulate structure-activity relationship (SAR) generalities, we examined the releasing ability of several simple methcathinone analogs at the three monoamine transporters (i.e., the dopamine, norepinephrine, and serotonin transporters, DAT, NET, and SERT, respectively) using in vitro assay methods. The analogs included methcathinone and 14 other compounds monosubstituted at the 2-, 3-, or 4-position. In general, (a) the 2-substituted analogs were less potent than either the 3- or 4-substituted analogs, (b) the 3- and 4-substituted analogs were relatively similar in potency, (c) methcathinone was the most selective as a DAT-releasing agent, and (d) the 3- and 4-CF3 analogs were the least DAT-selective. For the 15 compounds, there was a significant correlation ( r > 0.9) between DAT and NET potency, suggesting relatively similar structure-activity relationships (at least for the compounds examined here). Several of the compounds have appeared on the clandestine market since our studies were initiated, and the present results provide new information on how they might act.

Protective effect of apocynin against gentamicin-induced nephrotoxicity in rats.

Gentamicin (GNT) is an aminoglycoside antibiotic used for treatment of serious infections, and the nephrotoxic adverse effect is one of the main therapeutic limitations. This study aimed to investigate the possible protective effect of apocynin (APO) on nephrotoxicity induced by GNT in rats. Twenty-four rats were allocated into three groups: control, GNT (100 mg/kg, intraperitoneally (i.p.)), and GNT plus APO (10 mg/kg, i.p.). All rats were killed at the end of the experiment, and then the blood, urine, and kidneys samples were taken. GNT-induced nephrotoxicity was manifested by a significant ( p < 0.05) increase in the weight of kidney, 24-h urine volume, renal somatic index (RSI), protein in urine, serum lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (BUN), renal Fas ligand (CD95), nitric oxide (NO), and malondialdehyde (MDA). Furthermore, a significant reduction in body weight, creatinine clearance (CCr), serum albumin, renal superoxide dismutase (SOD), and glutathione activities were detected when compared with the control rats. APO ameliorated the nephrotoxic effect and oxidative damage caused by GNT by improving tissue morphology and significantly decreasing 24-h urine volume, RSI, serum Cr, LDH and BUN, protein in urine, and renal content of MDA, CD95, and NO. Additionally, APO caused a significant elevation in renal SOD activity and CCr when compared with the GNT group. These results confirm that APO by its anti-inflammatory, antiapoptotic, and antioxidant effects can ameliorate GNT-induced nephrotoxicity.

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release.

Bupropion (1), an α-aminophenone uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET), is a widely prescribed antidepressant and smoking cessation aid. Cathinone (2), a structurally simpler α-aminophenone, is a substrate-type releasing agent at the same transporters and a recognized drug of abuse. Our goal was to identify the structural features of α-aminophenones that govern the mechanistic transition from uptake inhibition to substrate-induced release. Deconstructed analogues of 1 were synthesized and compared for their ability to interact with DAT, NET, and the serotonin transporter (SERT) using in vitro assay methods. Bulky amine substituents resulted in compounds that function as DAT uptake inhibitors but not release agents, whereas smaller amine substituents result in relatively nonselective releasing agents at DAT and NET. Our findings add to empirical evidence supporting distinct molecular determinants for α-aminophenone- (i.e., cathinone-) related agents acting as transporter inhibitors versus those acting as releasers.

CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value.

CD123 is the α-subunit of the interleukin-3 receptor; it represents a potential therapeutic target in systemic mastocytosis (SM) given its absent expression on normal/reactive mast cells (MCs) and aberrant expression on neoplastic MCs. We studied 58 SM patients to define CD123 expression patterns by immunohistochemistry and its clinical significance. Two hematopathologists independently scored bone marrow slides using predefined histologic parameters. In all, 23 patients had indolent SM (ISM), 10 aggressive SM (ASM), 23 SM with associated hematological neoplasm (SM-AHN) and 2 had mast cell leukemia (MCL). MC_CD123 expression was demonstrable in 37 (64%) cases; expression rates were 100%, 61%, 57% and 0% in ASM, ISM, SM-AHN and MCL, respectively (P=0.02). Focal proliferation of plasmacytoid dendritic cells (PDCs) around MC aggregates, suggesting a tumor-promoting role for PDCs, was noted in 44 (76%) cases, and was significantly higher in CD123-positive versus -negative cases (87% versus 50%, P=0.005). CD123 expression and its staining intensity had prognostic value in SM-chronic myelomonocytic leukemia and nonindolent SM patients, respectively. These observations suggest that targeting CD123 in SM may have direct (via MCs) and indirect (via PDCs) antitumor effects and clinical trials to that effect require laboratory correlative studies to address the observed target expression heterogeneity.

Hydrogen sulfide ameliorates cardiovascular dysfunction induced by cecal ligation and puncture in rats.

Hydrogen sulfide (H2S) is an endogenously produced gaseous messenger that participates in regulation of cardiovascular functions. This study evaluates the possible protective effect of H2S in cardiovascular dysfunction induced by cecal ligation and puncture (CLP) in rats. After 24 h of induction of CLP, heart rate (HR), mortality, cardiac and inflammation biomarkers (creatine kinase-MB (CK-MB) isozyme, cardiac troponin I (cTnI), C-reactive protein (CRP), and lactate dehydrogenase (LDH)), in vitro vascular reactivity, histopathological examination, and oxidative biomarkers (malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD)) were determined. CLP induced elevations in HR, mortality, serum CK-MB, cTnI, CRP, and LDH, in addition to impaired aortic contraction to potassium chloride and phenylephrine and relaxation to acetylcholine without affecting sodium nitroprusside responses. Moreover, CLP increased cardiac and aortic MDA and decreased SOD, without affecting GSH and caused a marked subserosal and interstitial inflammation in endocardium. Sodium hydrosulfide, but not the irreversible inhibitor of H2S synthesis dl-propargyl glycine, protected against CLP-induced changes in HR, mortality, cardiac and inflammatory biomarkers, oxidative stress, and myocardium histopathological changes without affecting vascular dysfunction. Our results confirm that H2S can attenuate CLP-induced cardiac, but not vascular, dysfunction possibly through its anti-inflammatory and antioxidant effects.