Background: Dolutegravir sodium (DTG), used to treat HIV, faces challenges in delivering effective therapeutic concentrations to the brain due to the blood-brain barrier (BBB). Nanostructured lipid carriers (NLCs) combined with in situ gels present a promising strategy for enhancing brain drug delivery via the intranasal route. Objective: To compare brain pharmacokinetics of DTGs delivered via NLC-loaded in situ gel intranasal administration with the conventional intravenous (IV) drug solution. Methods: 80 Wistar rats, which were divided into three groups: two groups consisting of 39 animals each and a control group with 2 animals. Rats were administered with a dose of 1.0 mg/kg of DTGs IV, and DTGs NLC-loaded in situ gel were administered intranasally. DTGs were determined in rats’ plasma and brain tissue by high-performance liquid chromatography (HPLC). Results: Intranasal administration produced significantly higher brain drug concentrations (Cmax 35344.8ng/ml) compared to the IV solution (Cmax 4536.85ng/ml). The area under the curve (AUC) for the intranasal formulation was twice that of the IV solution, indicating enhanced bioavailability. Furthermore, the intranasal route exhibited a faster onset (lower Tmax) and prolonged retention in brain tissue. The developed nanoformulation exhibited a Drug Targeting Efficiency (DTE) of 232.5% and a Drug Targeting Potential (DTP) of 57%, suggesting improved brain targeting efficiency. Conclusions: The DTGs-loaded NLC in situ gel shows superior brain pharmacokinetics compared to IV administration, highlighting its potential as an effective strategy for enhancing brain targeting.
العقم هو أحد المشاكل التي تواجه النساء والرجال. تعد السمنة واضطرابات مستوى الدهون، وكذلك مقاومة الأنسولين، من عوامل الخطر التي تسبب العقم، بالإضافة إلى العوامل الأخرى ذات الصلة. تهدف هذه الدراسة إلى معرفة تأثير السمنة واختلال توازن الدهون مع دراسة علاقة كل من ثنائي الببتيديل ببتيديز-4 وعامل نخر الورم-الفا لدى النساء المصابات بالعقم مقارنة بالنساء غير المصابات به، لتحديد مدى إمكانية اعتمادها كعوامل تشخي
... Show MoreIn the current study, new derivatives were synthesized by reaction of N-hydroxyphthalimide with chloro acetyl chloride in the presence of Et3N as a base to form 1,3-dioxoisoindolin-2-yl 2-chloroacetate (B1), which in turn enters several reactions with different amines where it interacts with primary amines to give 1,3-dioxoisoindolin-2-yl acetate derivatives (B2-B4) in basic medium, in the same way it interacts with these amines but with adding KNCS to form thiourea derivatives (B5-B7). It also reacts with diamines to give bis(azanediyl) derivatives (compounds B8-B10). The prepared derivatives were diagnosed using infrared FTIR and 1HNMR,13CNMR for some derivatives. Compounds B4, B5 and B9 were measured as corrosion inhibitors the inhibitio
... Show MoreObjectives. This study was carried out to quantitatively evaluate and compare the sealing ability of Endoflas by using differentobturation techniques. Materials and Methods. After 42 extracted primary maxillary incisors and canines were decoronated, theircanals were instrumented with K files of size ranging from #15 to #50. In accordance with the obturation technique, the sampleswere divided into three experimental groups, namely, group I: endodontic pressure syringe, group II: modified disposable syringe,and group III: reamer technique, and two control groups. Dye extraction method was used for leakage evaluation. Data wereanalyzed using one-way ANOVA and Dunnett’s T3 post hoc tests. The level of significance was set at p<0:05. Results.
... Show Morethis paper presents a novel method for solving nonlinear optimal conrol problems of regular type via its equivalent two points boundary value problems using the non-classical
An efficient modification and a novel technique combining the homotopy concept with Adomian decomposition method (ADM) to obtain an accurate analytical solution for Riccati matrix delay differential equation (RMDDE) is introduced in this paper . Both methods are very efficient and effective. The whole integral part of ADM is used instead of the integral part of homotopy technique. The major feature in current technique gives us a large convergence region of iterative approximate solutions .The results acquired by this technique give better approximations for a larger region as well as previously. Finally, the results conducted via suggesting an efficient and easy technique, and may be addressed to other non-linear problems.
Schools and artistic trends derive their themes from artistic styles and styles as methods followed by the artist to express his themes embodied in the values of artistic and plastic elements as symbols and signs that can be described according to the type of art school and the extent to which the artist is influenced in employing them as a goal to achieve the plastic achievement in the painting, and from those vocabulary (human beings nature Life) as encoded messages that have an appearance and an interior, the appearance of which are forms, colors, formats and distributions of space and their interior meanings and semantics embody attitudes, events and circumstances that stem from the social depth and daily life and derive their comp
... Show MoreRhythm is considered one of the creative concepts in the recent architectural thought; it has emerged clearly as a mean of creating the highest levels of creativity in architecture, especially in contemporary architectural movements. The importance of rhythm has emerged, especially, when the architecture , its beginnings concentrated on the principle of the links with poetic structures. Many architectural studies deal with concept of rhythm in architecture with different ways various according to the trend of each study, this show the importance of studying the concept of rhythm in the architectural field in general. This study try to focus on the utilization of rhythm as creative system in architecture of heritage and contemporary
... Show MorePurpose: The purpose of the study is to compare and evaluate Earnings Management in Tunisia and Iraq. Theoretical framework: Earnings Management is an important topic that has been studied by a significant number of researchers, as well as those who are interested in the accounting profession. Earnings Management has gotten a lot of attention from academics, professionals, and other interested parties in recent years (e.g. Kliestik et al., 2020; Rahman et al., 2021; Gamra &Ellouze, 2021) Design/methodology/approach: The sample includes ten banks listed on the Bourse of Tunisia and Iraq Stock Exchanges for the year 2017. We have used a model of Kothari et al., (2005) as a tool to measure Earnings Management in both mark
... Show MoreNewcastle Disease is one of the most important disease world wide distributions which invade the flock in different age resulting in large economic losses. This study aimed to evaluate the effect of treatment with 4 different concentrations (0.25, 0.5, 1.0 and 2.0 %) of Sodium deoxycholate (SDC) on the vaccinal virus (La Sota) using inoculation in the fragments of Chorioallantoic membrane. The treatment with each of the above 4 concentrations of SDC resulted in an increase in the Hemagglutination titer (HA) of the virus (28, 29.6, 211.6, 214.6) respectively as compared to the HA titer value for the untreated virus (26.6). No significant differences were noticed among all concentrations with regard to their effect on the HA titer, except
... Show Morebackground: human epidermal growth factor receptor-2 (her2/neu) is related to growth factor receptors with alkaline kinase activity and it is regarded as important prognostic and therapeutic factor that can depended on in breast cancer therapy. HER2/neu expression by immunohistochemistry (IHC) is submitted to a great in terob server inconsistency. Subsequently additional confirmatory tests for assessment of gene alterations and amplification status are needed for patients with early or metastatic breast cancer. In situ hybridization techniques and specifically Chromogenic in situ hybridization (CISH) was arise as a practical, cost-effective, and alternative to fluorescent in situ hybridization in testing for gene alterationAims of the study
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