This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41 days post-infection and were evaluated after 10 days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4 mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV\'s potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV\'s mechanisms of action and its clinical application in managing toxoplasmosis.

OBJECTIVE: Tacrolimus is an effective immunosuppressant commonly used post-transplantation and in certain autoimmune diseases. However, its long-term administration is associated with renal fibrosis through transforming growth factor-beta/suppressor of mother against decapentaplegic (TGF-β/Smad) signaling that could be partly attributed to endothelial dysfunction alongside decreased nitric oxide (NO) release. Our study aimed to investigate the prospective renal anti-fibrotic effect of enhanced NO production by nebivolol against tacrolimus-stimulated TGF-β1/Smad3 signaling.
METHODS: To illustrate the proposed mechanism of nebivolol, Nω-nitro-L-arginine methyl ester (L-NAME); nitric oxide synthase inhibitor; was co-administered with nebivolol. Rats were treated for 30 days as control, tacrolimus, tacrolimus/nebivolol, tacrolimus/L-NAME, and tacrolimus/nebivolol/L-NAME groups.
RESULTS: Our results revealed that renal NO content was reduced in tacrolimus-treated rats, while treatment with tacrolimus/nebivolol enhanced NO content via up-regulated endothelial nitric oxide synthase (eNOS), but down-regulated inducible nitric oxide synthase (iNOS) expression. That participated in the inhibition of TGF-β1/Smad3 signaling induced by tacrolimus, where the addition of L-NAME abolished the defensive effects of nebivolol. Subsequently, the deposition of collagen I and alpha-smooth muscle actin (α-SMA) was retarded by nebivolol, emphasized by reduced Masson\'s trichrome staining. In accordance, there was a strong negative correlation between eNOS and both TGF-β1 and collagen I protein expression. The protective effects of nebivolol were further confirmed by the improvement in kidney function biomarkers and histological features.
CONCLUSIONS: It can be suggested that treatment with nebivolol along with tacrolimus could effectively suppress renal TGF-β1/Smad3 fibrotic signaling via the enhancement of endothelial NO production, thus curbing renal fibrosis development.

Asymmetric reduction of 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-one (NEB-7) into 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-ol (NEB-8) is the crucial step for synthesis of liposoluble β1 receptor blocker nebivolol. Four efficient and stereoselective alcohol dehydrogenases were identified, enabling the stereoselective synthesis of all enantiomers of NEB-8 at a substrate loading of 137 g·L-1 with ee values of >99% and high space-time yields. This study provides novel biocatalysts for the efficient synthesis of nebivolol precursors and uncovers the molecular basis for enantioselectivity manipulation by parametrization of Prelog\'s rule.

Sepsis is a potential fetal organ destruction brought on through an overzealous immunologic reaction to infection, causing severe inflammation, septic shock, and damage to different organs. Although there has been progress in the identification and controlling of clinical sepsis, the fatality rates are still significant. This study, for the first time, intended to examine the possible ameliorative impact of Nebivolol, a β1-adrenergic antagonist antihypertensive drug, against nephrotoxicity resulted from cecal ligation and puncture (CLP)-induced sepsis in rats, on molecular basis. Sixty male Wistar albino rats were chosen. Oxidative stress indicators and biochemical markers of kidney activity were evaluated. Inflammatory mediators, fibrosis- and apoptosis-related proteins and gene expressions were investigated. Moreover, renal histopathological investigation was performed. CLP-induced nephrotoxicity characterized by markedly elevated serum levels of creatinine, blood urea nitrogen, uric acid, and renal malondialdhyde. On the other hand, it decreased serum total protein level, renal superoxide dismutase activity and reduced glutathione level. Additionally, it significantly elevated the renal inflammatory mediators (tumor necrosis factor-alpha, ilnerlukin (IL)-6, and IL-1β) and Caspase-3 protein, reduced IL-10 level, amplified the expression of transforming growth factor-beta 1 (TGF-β1), p-Smad2/3 and alpha-smooth-muscle actin proteins, downregulated the B cell lymphoma-2 (Bcl-2) gene and elevated the transcription of Bcl-2-associated X-protein (Bax), p53 and Nuclear factor-kappa B (NF-κB) genes. Furtheremor, kidney tissues exhibited significant histopathological changes with CLP. On the contrary, Nebivolol significantly improved all these biochemical changes and enhanced the histopathological alterations obtained by CLP. This research showed, for the first time, that Nebivolol effectively mitigated the CLP-induced kidney dysfunction via its antioxidant, antifibrotic and anti-apoptotic activity through modulation of oxidative stress, TGF-β/NF-κB and TGF-β/Smad/p53 signaling pathways.

UNASSIGNED: To describe the clinical characteristics and treatment adherence in European adult hypertensive patients starting treatment with the extemporaneous combination of nebivolol and ramipril (NR-EXC).
UNASSIGNED: Retrospective database analysis of patients receiving NR-EXC treatment across five European countries (Italy, Germany, France, Poland, Hungary) over a period ranging from 3 to 9 years (until 30 June 2020) according to data availability for the different data sources. Patient demographics, comorbidities, and treatment adherence were evaluated.
UNASSIGNED: We identified 592,472 patients starting NR-EXC. Most of them were over 60 years of age, with ramipril most commonly prescribed at 5 mg (from 30.0 to 57.2% of patients across the databases). Notable comorbidities included diabetes (19.2%) and dyslipidemia (18.2%). The study population was also highly subjected to polytherapy with antithrombotics, lipid-lowering agents, and other lowering blood pressure agents as the most co-prescribed medications, as resulted from Italian database. Up to 59% of the patients did not request a cardiologic visit during the study period. Adherence to therapy was low in 56.3% of the patients, and it was high only in 11.1% of them.
UNASSIGNED: The combination of nebivolol and ramipril is frequently prescribed in Europe, but adherence to treatment is suboptimal. The transition to a single pill combination could enhance treatment adherence and streamline regimens, potentially leading to significant benefits. Improved adherence not only correlates with better blood pressure control but also reduces the risk of cardiovascular events, underscoring the importance of this development.

New oral tablets of nebivolol have been developed aiming to improve, by cyclodextrin (CD) complexation, its low solubility/dissolution properties-the main reason behind its poor/variable oral bioavailability. Phase-solubility studies, performed using βCD and highly-soluble βCD-derivatives, indicated sulfobutylether-βCD (SBEβCD) as the best solubilizing/complexing agent. Solid drug-SBEβCD systems were prepared by different methods and characterized for solid-state and dissolution properties. The coevaporated product was chosen for tablet development since it provided the highest dissolution rate (100% increase in dissolved drug at 10 min) and almost complete drug amorphization/complexation. The developed tablets reached the goal, allowing us to achieve 100% dissolved drug at 60 min, compared to 66% and 64% obtained, respectively, with a reference tablet without CD and a commercial tablet. However, the percentage dissolved after 10 min from such tablets was only 10% higher than the reference. This was ascribed to the potential binding/compacting abilities of SBEβCD, reflected in the greater hardness and longer disintegration times of the new tablets than the reference (7.64 vs. 1.06 min). A capsule formulation with the same composition of nebivolol-SBEβCD tablets showed about a 90% increase in dissolved drug after 5 min compared to the reference tablet, and reached 100% dissolved drug after only 20 min.

UNASSIGNED: To explore real-life use of the extemporaneous combination of nebivolol and valsartan (NV-EXC) in adult hypertensive patients in Europe.
UNASSIGNED: Retrospective analysis of patients starting NV-EXC treatment conducted using prescription databases in Italy, Germany, Hungary, and Poland. The selection period during which study patients were identified covered a time span ranging from 3 to 9 years (until 30 June 2020) according to availability of the different data sources. Patient demographics, clinical information, and treatment adherence, measured by proportion of days covered, were evaluated. Additionally, the potential eligibility of Italian patients for the single pill combination (SPC) of nebivolol and valsartan over a one-year period was estimated.
UNASSIGNED: The study included 170,682 patients initiating NV-EXC across the databases. Most patients were females (from 51 to 60%) and primarily aged over 60 years. Few patients received prescriptions of both available dosages of valsartan (80 and 160 mg) during follow-up (from 3.2 to 8.5%). Common comorbidities included dyslipidemia (19.2%) and diabetes (19.1%). Around 59.5% of patients did not require cardiologic visits during the study period. Adherence to NV-EXC, as indicated by the Italian database, was low in 53.3% of patients, with only 16.1% showing high adherence. The Italian database revealed 680 prevalent NV-EXC users in 2019, estimating a potential 30,222 adult patients eligible for the nebivolol/valsartan SPC.
UNASSIGNED: The combination of nebivolol and valsartan is frequently prescribed for hypertension, but adherence remains a challenge. A potential nebivolol/valsartan SPC holds promise in enhancing adherence and optimizing therapeutic outcomes for hypertension management.

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Recently, nanomaterials have attracted a lot of attention due to their potential as effective fluorescent nano-sensor probes. They were distinguishing substitutes for other luminescent techniques, such as fluorescent dyes and luminous derivatization, because of their affordability, environmental friendliness, and special photocatalytic properties. In the suggested work, a straightforward method was used to create boron and nitrogen carbon dots (B@CDs) with a good quantum yield value of 31.15 % utilizing boric acid and di-sodium EDTA. For the purpose of characterizing QDs, a variety of instruments were employed, such as transmission electron microscopy, fluorescence spectroscopy, X-ray FTIR, and UV-VIS spectroscopy. Nebivolol (NEB) is a cardiovascular medication used globally to treat congestive heart failure and hypertension, is in the meantime. For this reason, a brand-new, environmentally friendly analytical technique was created to determine the amount of human plasma, uniformity test, and commercial nebivolol (NEB) tablets. After gradually adding NEB, the response of B@CQDs was enhanced at 438 nm (excitation at 371 nm). The calibration graph ranged between 20 and 500 ng mL-1 with a quantification limit (LOQ) of 2.50 ng mL-1 and a detection limit (LOD) of 0.82 ng mL-1.

Despite substantial progress in understanding the complex pathophysiology, hypertension remains a serious public health challenge affecting over 1.2 billion adults aged 30-79 years worldwide. Appropriate knowledge of the different pharmaceutical classes of antihypertensive agents and an understanding of the characteristics of individual molecules are essential to optimize clinical outcomes in patients with hypertension. We conducted a computer-assisted web interviewing (CAWI) quantitative survey in Italy, Poland, and Turkey to investigate physicians\' prescriptions, knowledge, and perceptions of antihypertensive drugs with a focus on β-blockers, to assess antihypertensive usage patterns and the reasons underlying prescription choices. The survey findings show that β-blockers retain a pivotal role in the management of hypertension and are prescribed more often for patients with cardiovascular comorbidities than for patients with diabetic comorbidities. In all three countries, nebivolol is the only β-blocker among the ones analyzed which is consistently prescribed to 20% or more of patients and is overall the most prescribed one for the population with comorbid diabetes. In terms of specific β-blockers\' features, this study revealed knowledge gaps that underline the need for educational activities focused on the differences among β-blockers, which are important in choosing the most suitable agent for individualized antihypertensive therapy.