Administration Of Hydrochloride Research Articles

Comparative Study on the Effect of Different Modes of Administration of Ambroxol Hydrochloride in the Treatment of Pediatric Respiratory Diseases

Objective: To investigate the comparison of the effects of intravenous infusion of Ambroxol Hydrochloride and nebulized inhalation in the treatment of pediatric respiratory diseases. Methods: 188 children with respiratory diseases admitted to the pediatrics department of the hospital from September 2022 to March 2024 were selected as the study subjects, and were randomly divided into the control group (n = 41) and the observation group (n = 41) according to the random number table method. Both groups of patients were first treated with conventional treatment, and based on conventional treatment, the control group was treated with intravenous infusion of Ambroxol Hydrochloride, and the observation group was treated with nebulized inhalation of Ambroxol Hydrochloride. The general information, clinical symptom improvement time, oxygen therapy time, sputum aspiration frequency, hospitalization time, and the occurrence of adverse reactions were observed in the two groups. Results: The baseline data of the two groups of patients were not statistically significant (P > 0.05); the disappearance time of clinical symptoms such as cough, lung rales, and shortness of breath in the observation group was shorter than that in the control group (t = 8.739, t = 10.108, t = 19.448, P < 0.001); the time of oxygen therapy, number of sputum aspirations, and hospital stay of the patients in the observation group were significantly shorter than that of the control group (t = 10.593, t = 10.665, t = 14.673, all P < 0.001); the total incidence of adverse reactions in patients in the observation group (3/3.18%) was significantly lower than that in the control group (14/14.89%) (x2 = 7.825, P = 0.005 < 0.01). Conclusion: In the treatment of pediatric respiratory diseases with Ambroxol Hydrochloride, nebulized inhalation has better efficacy than intravenous drip, and can better improve the clinical symptoms and reduce the side effects in children.

Comparative Study on the Effect of Different Modes of Administration of Ambroxol Hydrochloride in the Treatment of Pediatric Respiratory Diseases

Objective: To investigate the comparison of the effects of intravenous infusion of Ambroxol Hydrochloride and nebulized inhalation in the treatment of pediatric respiratory diseases. Methods: 188 children with respiratory diseases admitted to the pediatrics department of the hospital from September 2022 to March 2024 were selected as the study subjects, and were randomly divided into the control group (n = 41) and the observation group (n = 41) according to the random number table method. Both groups of patients were first treated with conventional treatment, and based on conventional treatment, the control group was treated with intravenous infusion of Ambroxol Hydrochloride, and the observation group was treated with nebulized inhalation of Ambroxol Hydrochloride. The general information, clinical symptom improvement time, oxygen therapy time, sputum aspiration frequency, hospitalization time, and the occurrence of adverse reactions were observed in the two groups. Results: The baseline data of the two groups of patients were not statistically significant (P > 0.05); the disappearance time of clinical symptoms such as cough, lung rales, and shortness of breath in the observation group was shorter than that in the control group (t = 8.739, t = 10.108, t = 19.448, P < 0.001); the time of oxygen therapy, number of sputum aspirations, and hospital stay of the patients in the observation group were significantly shorter than that of the control group (t = 10.593, t = 10.665, t = 14.673, all P < 0.001); the total incidence of adverse reactions in patients in the observation group (3/3.18%) was significantly lower than that in the control group (14/14.89%) (x2 = 7.825, P = 0.005 < 0.01). Conclusion: In the treatment of pediatric respiratory diseases with Ambroxol Hydrochloride, nebulized inhalation has better efficacy than intravenous drip, and can better improve the clinical symptoms and reduce the side effects in children.

Sevoflurane-induced overexpression of extrasynaptic α5-GABAAR via the RhoA/ROCK2 pathway impairs cognitive function in aged mice.

Perioperative neurocognitive disorder (PND) is a serious neurologic complication in aged patients and might be associated with sevoflurane exposure. However, the specific pathogenesis is still unclear. The distribution of α5-GABAAR, a γ-aminobutyric acid type A receptor (GABAAR) subtype, at extrasynaptic sites is influenced by the anchor protein radixin, whose phosphorylation is regulated via the RhoA/ROCK2 signaling pathway and plays a crucial role in cognition. However, whether sevoflurane affects the ability of radixin phosphorylation to alter extrasynaptic receptor expression is unknown. Aged mice were exposed to sevoflurane to induce cognitive impairment. Both total proteins and membrane proteins were extracted for analysis. Cognitive function was evaluated using the Morris water maze and fear conditioning test. Western blotting was used to determine the expression of ROCK2 and the phosphorylation of radixin. Furthermore, the colocalization of p-radixin and α5-GABAAR was observed. To inhibit ROCK2 activity, either an adeno-associated virus (AAV) or fasudil hydrochloride was administered. Aged mice treated with sevoflurane exhibited significant cognitive impairment accompanied by increased membrane expression of α5-GABAAR. Moreover, the colocalization of α5-GABAAR and p-radixin increased after treatment with sevoflurane, and this change was accompanied by an increase in ROCK2 expression and radixin phosphorylation. Notably, inhibiting the RhoA/ROCK2 pathway significantly decreased the distribution of extrasynaptic α5-GABAAR and improved cognitive function. Sevoflurane activates the RhoA/ROCK2 pathway and increases the phosphorylation of radixin. Excess α5-GABAAR is anchored to extrasynaptic sites and impairs cognitive ability in aged mice. Fasudil hydrochloride administration improves cognitive function.

Quantifying Renal Changes: A Study of Area of Bowman's Space Following Prolonged Itopride Hydrochloride Exposure in Albino Rats

Objective: To see the effects of long-term administration of itopride hydrochloride on the histomorphology of kidney of the male Wistar albino rats.Study Design: A Laboratory based experimental study.Place and Duration of Study: The study was conducted at the Department of Anatomy, CMH Multan Institute of Medical Sciences Multan, Pakistan from September 2020 to March 2022.Methods: The study involved two groups: Group A served as the control, and Group B functioned as the experimental group. Each group consisted of 30 adult male albino rats. The animals of group A were administered 2ml/100g of distilled water by oral gavage along with a diet for laboratory rodents daily for 15 days. The animals of group B were given 4.4mg/kg of itopride hydrochloride dissolved in 2ml/100g body weight of distilled water by oral gavage three times a day for 15 days. The kidney was processed for paraffin embedding and stained with Periodic Acid Schiff (PAS). The area of Bowman's space was measured by linear micrometer after calibration with a stage micrometer and image J software. The student's t-test was utilized to assess potential differences between the two groups, with significance set at a p-value of ≤ 0.05.Result: The area of Bowman's space was significantly increased in the experimental group as compared to the control group (p= 0.045).Conclusion: Long-term Itopride Hydrochloride administration appears to influence the area of Bowman's Space in Wistar albino rats. How to cite this: Hashmi A, Syed H, Irfan A, Rabbani A, Mir A, Razzaq M. Quantifying Renal Changes: A Study of Area of Bowman's Space Following Prolonged Itopride Hydrochloride Exposure in Albino Rats. Life and Science. 2024; 5(2): 138-143. doi: http://doi.org/10.37185/LnS.1.1.539

The stereoselective pharmacokinetics of the desmethyl-phencynonate hydrochloride in beagle dogs.

The aim of this study was to investigate the chiral inversion and the stereoselective pharmacokinetic profiles of desmethyl-phencynonate hydrochloride after administration of the single isomer and its racemate to beagle dogs. A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was established for determination of the stereoisomers on chiral columns in beagle dog plasma, which met all the requirements. The chiral inversion in dogs of the desmethyl-phencynonate hydrochloride were studied after administration of the single isomer or the racemic modification. The stereoselective pharmacokinetic profiles of the desmethyl-phencynonate hydrochloride were studied by assays for simultaneous isomers after administration of the racemic modification. The results showed that the absorption of the R-configuration dosed as the single isomer was higher than it dosed as the racemic modification. The AUC(0-t), AUC(0-∞), and Cmax of the S-configuration were much higher than those of R-configuration after oral administration of the racemic desmethyl-phencynonate hydrochloride. The chiral inversion of desmethyl-phencynonate isomers could not occur in dogs after administration of the R-configuration.

Benzydamine hydrochloride: an overview on a well-established drug with news in mechanisms of action

Pain and inflammation are the consequences of sore throat, dental and oral procedures, infections, ulcers and head and neck chemotherapy/radiotherapy, and their management is of fundamental importance to avoid distress in patients. Benzydamine hydrochloride (HCl) is a topical indolic nonsteroidal anti-inflammatory drug, endowed with analgesic and anesthetic activity, and with antimicrobial (including both gram-positive and gram-negative bacteria) and antifungal properties (targeting Candida albicans and non-albicans strains), used in odontostomatology, otorhinolaryngology, and gynecology for its properties. This molecule has a lipophilic nature, showing high affinity with cell membranes and exhibiting membrane stabilization properties, resulting in local anesthesia, an effect related also to the interaction of the drug with cationic channels. In addition, benzydamine HCl is able to inhibit the production of pro-inflammatory cytokines, with consequent analgesia. Moreover, benzydamine HCl is able to inhibit leukocyte-endothelial interactions and platelet aggregation. Unlike other non-steroidal anti-inflammatory drugs, benzydamine HCl does not inhibit cyclooxygenase or lipoxygenase. Here we review the most updated clinical data available on benzydamine HCl local application as spray, mouthwash or gargling and evidence of its effectiveness in inflammatory and/or septic conditions in the otorhinolaryngology and odontostomatology settings, with particular reference to sore throat, oral inflammation, dental plaque, tonsillitis/tonsillectomy and chemo- or radiotherapy-induced oral mucositis. Novel formulations for oral administration of benzydamine HCl are also reviewed, including in situ gelling formulations to be sprayed onto the damaged oral mucosa. Finally, novel data on the potential role of benzydamine HCl in nociceptor excitability are introduced.

Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan.

In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.

Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease

Ethnopharmacological relevanceTrichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the “Gualou Xiebai” formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic “Jin-Guì-Yào-Lüe” for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). Aim of the studyThis study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. Materials and methodsA CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP (“HaiShi GuaLou” and “WanLou”) by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. ResultsTP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCβ], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCβ, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. ConclusionCynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

VARIOUS ASPECTS OF PERCUTANEOUS CORONARY INTERVENTIONS AS PREDICTORS OF DEATH IN MYOCARDIAL INFARCTION AND CORONARY MICROVASCULAR OBSTRUCTION (NO-REFLOW)

HighlightsThe review analyzed the role of various preoperative indicators as predictors of long-term mortality in patients with myocardial infarction and coronary microvascular obstruction (no-reflow) that developed during percutaneous coronary intervention. As a result of a multifactorial analysis, taking into account the confounders available for evaluation, we have found that predilation serves as an independent predictor of death within two years. AbstractAim. To evaluate the role of various aspects of percutaneous coronary interventions (PCI) as predictors of long-term death in myocardial infarction (MI) and coronary microvascular obstruction (CMVO, no-reflow).Methods. The unmatched case-control study included 232 patients with type 1 MI and CMVO developed during PCI. CMVO criteria were as follows: TIMI flow grade <3, Myocardial blush grade <2, ST segment resolution after PCI <70%. The “cases” group consisted of 54 (23.3%) patients who died within the next two years, the “controls” group consisted of 178 (76.7%) patients who survived. The analysis included the following indicators: predilation, high-pressure balloon post-dilation, vacuum assisted manual thromboaspiration, intra-aortic balloon pump, intracoronary administration of isosorbide dinitrate and verapamil hydrochloride, glycoprotein IIb/IIIa inhibitors and “potent” p2y12 inhibitors usage, bare-metal stents, stent implantation with exceeded rated burst pressure, 3 or more stents usage, PCI on more than one artery, the ratio of contrast agent volume to glomerular filtration rate (GFR) >3.0. A univariate comparative analysis of the groups regarding PCI aspects and potential confounders was performed (Mann-Whitney, Fisher). To control the confounders, a multivariate analysis was carried out (logistic regression).Results. Differences were obtained for the following indicators: “predilation” – in 51 (94%) patients in the “cases” group and in 139 (78%) in the “control” group, p-value = 0.005; “intra-aortic balloon pump” – in 9 (17%) and 7 (4%) patients respectively, p-value = 0.003; “the ratio of contrast agent volume to GFR >3.0” – in 26 (48%) and 48 (27%) patients, p-value = 0.005. Multivariate analysis revealed that only predilation was an independent predictor of death within two years – odds ratio 7.38 (95% confidence interval 1.70–49.04, p-value = 0.005).Conclusion. Predilation of the infarct-related coronary artery is an independent predictor of death within two years in MI patients who develop CMVO during PCI.

Histopathological changes in the spleen of rats exposed to N,N-dimethylhydrazine with the following protective input of Au/Ag/Fe

Colon cancer is one of the leading causes of cancer-related deaths worldwide. Despite the growing number of studies on nanoparticles of different metals, there is still a lack of reliable information about their ability to work together as a composition and their antitumor effects. It has been established that the regulation of genes encoding proteins of the Bcl-2 family changes in cancer. Bcl-2 family proteins can be a potential target in cancer diagnosis and have a prognostic value in treating cancer with chemotherapeutic drugs. The tumor microenvironment includes myeloid suppressor cells, tumor-associated neutrophils, and tumor-associated macrophages that promote cancer progression and are derived from splenic hematopoietic stem cells and progenitor cells. The work aimed to ascertain histological changes and expression of Bcl-2 family proteins in the spleen of rats with N,N-dimethylhydrazine-induced carcinogenesis followed by the protective administration of Au/Ag/Fe nanometal composition. The study was conducted on 72 outbred white male rats. Colon adenocarcinoma was modelled by N,N-dimethylhydrazine hydrochloride administration for 30 weeks. Animals received an aqueous dispersion of Au/Ag/Fe nanoparticles intragastrically once a day for 21 days at a dose of 0.842 mg Ag/0.0526 mg Fe/1.625 μg Au per 1 kg of rat body weight. Paraffin sections of the spleen were stained with hematoxylin and eosin. For immunohistochemical analysis, sections were stained with rabbit monoclonal antibodies to Bcl-2. Under conditions of 30-week exposure to N,N-dimethylhydrazine hydrochloride, blood circulation disorders, stasis, thrombosis, reduction in the size of white pulp lymphatic nodules and loss of their zonation were histologically proved in the rat's spleen. The development of sclerotic processes in the organ was noted. It was indicated that using metal nanoparticles under N,N-dimethylhydrazine hydrochloride-induced colon carcinogenesis leads to less evidenced morphological manifestations of structural changes in the spleen. Immunohistochemically, the expression of Bcl-2 protein in the white pulp of the spleen of animals subjected to correction was lower than in animals without the corrective effect of the composition of nanoparticle metals. Administration of the Au/Ag/Fe metal nanoparticle composition to intact white rats does not cause pathological changes in the spleen morphology. The structural components of the red and white pulp match the typical histological structure of the organ.

Suppression of hypoxia-induced CAV1 autophagic degradation enhances nanoalbumin-paclitaxel transcytosis and improves therapeutic activity in pancreatic cancer

Nanoalbumin-paclitaxel (nab-paclitaxel) is a standard chemotherapy for pancreatic cancer but has shown limited efficacy. However, the mechanism through which circulating nab-paclitaxel passes through the tumour vascular endothelium has not been determined. In our study, a new nonradioactive and highly sensitive method for analysing nab-paclitaxel transcytosis was established. Based on these methods, we found that hypoxia significantly enhanced the autophagic degradation of CAV1 and therefore attenuated caveolae-mediated nab-paclitaxel transcytosis across endothelial cells (ECs). In a proof-of-concept experiment, higher levels of CAV1, accompanied by lower levels of LC3B, were observed in the vascular endothelium of pancreatic cancer tissues collected from patients who showed a good response to nab-paclitaxel compared with those from patients who showed a poor response to nab-paclitaxel. Furthermore, both in vivo and in vitro studies confirmed that suppressing the autophagic degradation of CAV1 via EC-specific ATG5 knockdown or hydroxychloroquine sulfate (HCQ) treatment significantly enhanced nab-paclitaxel translocation across the endothelial barrier into pancreatic cancer cells and amplified the inhibitory effect of nab-paclitaxel on pancreatic tumour growth. The stimulation of CAV1 expression by EC-specific overexpression of exogenous CAV1 or administration of gemcitabine hydrochloride (GE) had the same effect. These results demonstrated that suppressing CAV1 autophagic degradation is a novel translatable strategy for enhancing nab-paclitaxel chemotherapeutic activity in the treatment of pancreatic cancer.

Иммунометаболический статус крыс при моно-КВЧ-терапии отека легких

In pulmonary oedema, the accumulation of tissue fluid in the interstitial spaces of the lungs as well as in the cavities of the alveoli prevents the respiratory system from performing the gas exchange function. The ineffectiveness of various therapeutic approaches proposed to combat SARS-CoV-2 justifies the search for new therapeutic agents. Extremely high frequency (EHF) therapy could be one of the alternative treatment methods. The purpose of this article was to evaluate the immunometabolic status of rats in mono-EHF therapy of pulmonary oedema. Materials and methods. The paper evaluated the concentration of circulating immune complexes in the blood serum and the activity of lactate dehydrogenase in the lung tissue at experimental pulmonary oedema and a course of EHF therapy. The study involved 60 rats divided into 3 groups (intact, control and experimental). In the control and experimental groups, pulmonary oedema was simulated by intraperitoneal administration of adrenaline hydrochloride. A 10-day EHF therapy course was given to the experimental group using the CEMTECH device (40−43 GHz, Russia) by targeting three acupuncture points. Results. Pulmonary oedema was shown to increase the level of circulating immune complexes in the blood and the activity of lactate dehydrogenase in the lung tissue. Exposure to EHF radiation restored the normal values of these parameters. EHF therapy proved to be a promising treatment and rehabilitation method for pulmonary oedema. The selected markers for assessing the immunometabolic status could serve as an addition to the traditional methods of diagnosing this pathology, including in experimental conditions.

Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis

Objective: To evaluate the protective effect of benzydamine hydrochloride against ethanol-induced oxidative stress and inflammation in RAW 264.7 macrophages. Methods: RAW 264.7 macrophages were treated with ethanol (100 mM) and benzydamine hydrochloride (7.5 μM). The inflammatory status was confirmed by measuring pro-(TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines through ELISA and RT-PCR assays. Reactive oxygen species generation and mitochondrial membrane potential were investigated to study the protective role of benzydamine hydrochloride against ethanol-induced oxidative stress. Apoptosis detection was also investigated using flow cytometry and acridine orange/ethidium bromide staining. Results: Benzydamine hydrochloride significantly decreased the secretion of TNF-α and IL-6, as well as the generation of reactive oxygen species inside the cells, thereby stabilizing the mitochondrial membrane potential and reducing DNA fragmentation. The ethanol-induced cellular necrosis was also reversed by the administration of benzydamine hydrochloride. Conclusions: Benzydamine hydrochloride ameliorates ethanol-induced cell apoptosis and inflammation in RAW macrophages.

Comparative pharmacokinetics of free doxorubicin and a liposomal formulation in cats following intravenous administration.

Doxorubicin, a potent chemotherapeutic agent used extensively in cancer treatment, displays complex pharmacokinetic behavior, especially across various formulations. With a rising incidence of cancer cases in cats, understanding the drug's pharmacokinetics in feline subjects remains a critical yet unexplored area. Hence, this study investigated the pharmacokinetic profile of doxorubicin after slow intravenous administration of doxorubicin hydrochloride (DOX·HCl) or doxorubicin hydrochloride pegylated liposome (DOX·HCl-PLI) in twelve cats at a single dose of 20 mg/m2. Blood samples collected at pretreatment time (0 h) and over 192 h were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The obtained pharmacokinetic parameters of doxorubicin revealed significant differences between the two formulations and were as follows: elimination half-life (T1/2λz) of 5.00 ± 3.20 h (DOX·HCl) and 17.62 ± 8.13 h (DOX·HCl-PLI), area under the concentration/time curve from 0 to last point (AUClast) of 0.67 ± 0.12 μg hr./mL (DOX·HCl) and 783.09 ± 267.29 μg hr./mL (DOX·HCl-PLI), and total body clearance (CL_obs) of 27098.58 ± 5205.19 mL/h/m2 (DOX·HCl) and 28.65 ± 11.09 mL/h/m2 (DOX·HCl-PLI). Additionally, differences were also detected in the apparent volume of distribution (Vz_obs) with 178.56 ± 71.89 L/m2 (DOX·HCl) and 0.64 ± 0.20 L/m2 (DOX·HCl-PLI), and the maximum plasma concentration (Cmax) with 2.25 ± 0.30 μg/mL (DOX·HCl) and 24.02 ± 5.45 μg/mL (DOX·HCl-PLI). Notably, low concentration of doxorubicinol, the metabolite of doxorubicin, was detected in plasma after administration of DOX·HCl, with even less present when DOX·HCl-PLI was administered. This investigation provides valuable insights into the distinct pharmacokinetic behaviors of DOX·HCl and DOX·HCl-PLI in cats, contributing essential groundwork for future studies and potential clinical applications in feline oncology.

Constipation anti-aging effects by dairy-based lactic acid bacteria.

Constipation, which refers to difficulties in defecation and infrequent bowel movement in emptying the gastrointestinal system that ultimately produces hardened fecal matters, is a health concern in livestock and aging animals. The present study aimed to evaluate the potential effects of dairy-isolated lactic acid bacteria (LAB) strains to alleviate constipation as an alternative therapeutic intervention for constipation treatment in the aging model. Rats were aged via daily subcutaneous injection of D-galactose (600 mg/body weight [kg]), prior to induction of constipation via oral administration of loperamide hydrochloride (5 mg/body weight [kg]). LAB strains (L. fermentum USM 4189 or L. plantarum USM 4187) were administered daily via oral gavage (1 × 10 Log CFU/day) while the control group received sterile saline. Aged rats as shown with shorter telomere lengths exhibited increased fecal bulk and soften fecal upon administration of LAB strains amid constipation as observed using the Bristol Stool Chart, accompanied by a higher fecal moisture content as compared to the control (p < 0.05). Fecal water-soluble metabolite profiles showed a reduced concentration of threonine upon administration of LAB strains compared to the control (p < 0.05). Histopathological analysis also showed that the administration of LAB strains contributed to a higher colonic goblet cell count as compared to the control (p < 0.05). The present study illustrates the potential of dairy-sourced LAB strains as probiotics to ameliorate the adverse effect of constipation amid aging, and as a potential dietary intervention strategy for dairy foods including yogurt and cheese.

PEO-b-PCL/Tween 80/cyclodextrin systems: from bioinspired fabrication to possible nasal administration of ropinirole hydrochloride.

In this study, we designed and developed systems composed of poly(ethylene-oxide)-b-poly(ε-caprolactone) block copolymers of different molecular weights and compositions, non-ionic surfactant, and cyclodextrins. The innovation of this study lies in the combination of these diverse biomaterials to create biomimetic and bioinspired drug delivery supramolecular structures. The systems were formed by the thin-film hydration method. Extensive physicochemical and morphological characterization was conducted using differential scanning calorimetry, light scattering techniques, microcalorimetry analysis, high-resolution ultrasound spectroscopy, surface tension measurements, fluorescence spectroscopy, cryogenic transmission electron microscopy images, and in vitro cytotoxicity evaluation. These innovative hybrid nanoparticles were found to be attractive candidates as drug delivery systems with unique properties by encompassing the physicochemical and thermotropic properties of both classes of materials. Subsequently, Ropinirole hydrochloride was used as a model drug for the purpose of this study. These systems showed a high RH content (%), and in vitro diffusion experiments revealed that more than 90% of the loading dose was released under pH and temperature conditions that simulate the conditions of the nasal cavity. Promising drug release performance was observed with all tested formulations, worth further investigation to explore both ex vivo permeation through the nasal mucosa and in vivo performance in an experimental animal model.

Аналіз виникнення післяопераційної когнітивної дисфункції в разі застосування морфіну гідрохлориду після ендопротезування кульшового суглоба під спінальною анестезією

Purpose - to analyze the state of cognitive function of patients according to the Mini Mental State Examination (MMSE) scale in points at different follow-up periods; to establish the relationship between the occurrence of postoperative cognitive dysfunction (POCD) and a single administration of morphine hydrochloride after hip arthroplasty under spinal anaesthesia in the early postoperative period Materials and methods. The study was conducted on the basis of the Vinnytsia City Clinical Hospital of Emergency Medical Care with the participation of 120 patients. All patients were operated on for a hip fracture - hip joint replacement under spinal anesthesia. All patients in the postoperative period were evaluated for pain intensity according to the visual analog scale (VAS). In the early postoperative period, patients received: a combination of paracetamol and dexketoprofen. In case of insufficient effectiveness of paracetamol and dexketoprofen, which was assessed as the impossibility of maintaining the pain level according to VAS no more than 4 points, morphine hydrochloride 10 mg was used. The MMSE scale was used as one of the main evaluation scales for the dynamics of POCD. In this part of the work, patients were divided into two main groups depending on the dynamics of the cognitive deficit, which was determined by the MMSE scale during the entire period of observation, which generally divided the patients into two groups: «Without negative dynamics of cognitive functions» (n=85) and «With negative dynamics of cognitive functions» (n=35). Statistical processing was carried out using StatPlus programs according to parametric and non-parametric criteria, differences were considered significant at p&lt;0.05. Results. On the 7th day after hip arthroplasty, the negative dynamics of cognitive function, compared to the data during hospitalization, remained in 68.6% of patients with morphine hydrochloride among them: in 41.6% of patients, mild cognitive disorders appeared in their absence at the stage of hospitalization, in 29.2% there was a transition from mild cognitive disorders to mild dementia and in another 29.2% - mild to moderate dementia (p=0.03). Conclusions. The obtained data indicate that 92.3% of patients who had cognitive impairment at the time of discharge from the hospital received morphine hydrochloride, which may indicate a negative effect of the use of this drug on the cognitive functions of patients with hip arthroplasty on the background of a hip fracture. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the patients was obtained for the research. No conflict of interests was declared by the authors.

Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model.

Introduction: As psychoneuroimmunology flourishes, there is compelling evidence that depression suppresses the anti-tumor immune response, promotes the progression of cancer, and inhibits the effectiveness of cancer immunotherapy. Recent studies have reported that antidepressants can not only alleviate the depressant condition of cancer patients, but also strengthen the anti-tumor immunity, thus suppressing tumors. Tumor necrosis factor receptor 2 (TNFR2) antagonistic antibodies (Anti-TNFR2) targeting tumor-infiltrating regulatory T cells (Tregs) has achieved great results in preclinical studies, and with a favorable toxicity profile than existing immunotherapies, and is expected to become a new generation of more effective treatment strategies. Understanding the effects of combination therapy with antidepressants and Anti-TNFR2 may help design new strategies for cancer immunotherapy. Methods: We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0-50 µM), ansofaxine hydrochloride (0-50 µM) and amitifadine hydrochloride (0-150 µM) to examine their effects on cell proliferation and apoptosis. We explored the antitumor effects of ansofaxine hydrochloride in combination with or without Anti-TNFR in subcutaneously transplanted CT26 cells in tumor-bearing mouse model. Antitumor effects were evaluated by tumor volume. NK cell, M1 macrophage cell, CD4+ T cell, CD8+ T cell, exhausted CD8+ T and regulatory T cell (Tregs) subtypes were measured by flow cytometry. 5-hydroxytryptamine, dopamine and norepinephrine levels were measured by ELISA. Results: Oral antidepression, ansofaxine hydrochloride, enhanced peripheral dopamine levels, promoted CD8+T cell proliferation, promoted intratumoral infiltration of M1 and NK cells, decreased the proportion of tumor-infiltrating exhausted CD8+T cells, and strengthened anti-tumor immunity, thereby inhibiting colon cancer growth. In combination therapy, oral administration of ansofaxine hydrochloride enhanced the efficacy of Anti-TNFR2, and produced long-term tumor control in with syngeneic colorectal tumor-bearing mice, which was attributable to the reduction in tumor-infiltrating Treg quantity and the recovery of CD8+ T cells function. Discussion: In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8+T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2.

The combination of astragalus injection and ambroxol hydrochloride in the adjuvant treatment of COPD: a systematic review and meta-analysis

Chronic obstructive pulmonary disease (COPD) is a severe condition that leads to premature mortality and places a significant financial burden on healthcare systems. An adjunctive therapy in COPD includes the simultaneous administration of astragalus injection and ambroxol hydrochloride. Despite its widespread use, the effectiveness of this combined approach in COPD treatment has not been systematically evaluated. Thus, we conducted a systematic review and meta-analysis to assess the efficacy of combining astragalus injection with ambroxol hydrochloride as an adjuvant treatment for COPD. Six electronic databases were used to search for relevant randomized controlled trials, and data analysis was conducted using Review Manager 5.4. A total of 14 randomized controlled trials were included, involving 1070 patients who met the criteria. The results of the meta-analysis indicated that the combination of astragalus injection with ambroxol hydrochloride as an adjuvant treatment can improve various clinical parameters in patients with COPD compared to conventional treatment alone. These parameters include the clinical effective rate (OR = 5.44, 95% CI 3.51–8.43, I2 = 0%), partial pressure of oxygen in artery (MD = 1.12, 95% CI 0.87–1.36, I2 = 5%), partial pressure of carbon dioxide in artery (MD = − 1.43, 95% CI − 1.65 to − 1.21, I2 = 0%), forced expiratory volume in one second (MD = 0.30, 95% CI 0.18–0.42, I2 = 0%), percentage of forced expiratory volume in one second (MD = 16.18, 95% CI 12.60–19.76, I2 = 82%), forced vital capacity (MD = 0.33, 95% CI 0.21–0.45, I2 = 36%), hemoglobin (MD = − 16.17, 95% CI − 20.84 to − 11.51, I2 = 29%), and the ratio of forced expiratory volume in one second to forced vital capacity (MD = 2.51, 95% CI − 0.05 to 5.06, I2 = 0%). The combination of astragalus injection and ambroxol hydrochloride could be a selection of COPD patients as an adjuvant treatment. However, further validation is required to evaluate the effectiveness of combining astragalus injection and ambroxol hydrochloride as an adjunctive treatment for patients with COPD.

Early locus coeruleus degeneration impairs the longevity of fear memory in APPswe/PS1dE9 mice

AbstractBackgroundThe locus coeruleus (LC), a brainstem noradrenergic nucleus is known to modulate cognitive functions and behaviour. LC is one the first sites of appearance of misfolded tau protein which later develops into neurofibrillary tangles. Hyperphosphorylated tau and amyloid β are best protein correlates of cognitive decline in Alzheimer’s disease (AD). In early onset AD, subtle cognitive deficits develop &lt;25 years before the patients develop dementia. Loss of LC neurons and its innervation has been found to be significantly associated with behavioural deficits observed during prodromal stage of AD. However, the extent and consequences of LC‐noradrenergic system degeneration during early stages of AD pathogenesis are still under investigation.MethodTo address this question, we have performed contextual fear conditioning (cFC) behavioural task to test fear memory in 2‐month‐old APPswe/PS1dE9 (APP/PS1) mice, a transgenic amyloidogenic model of AD. We further investigated the status of LC terminals and the distribution of β‐adrenoceptors (β‐AR) in the hippocampus using dopamine‐β‐hydroxylase (DBH), tyrosine hydroxylase (TH), and β‐AR immunohistochemistry respectively. Finally, we checked if stereotaxic delivery of β‐AR agonist to the hippocampus could rescue the impairments in long‐term fear memory.ResultOur study demonstrates that 2‐month‐old male but not female APP/PS1 mice exhibit impaired long‐term fear memory in cFC task. Immunohistochemical analysis of DBH and TH positive nerve terminals revealed loss of noradrenergic and dopaminergic terminals in male but not female APP/PS1 mice hippocampus. Further, male APP/PS1 mice were found to have low levels of β‐AR in the hippocampus and intra‐hippocampal administration of isoproterenol hydrochloride, a β‐AR agonist, immediately before cFC could restore long‐term contextual fear memory.ConclusionLC‐noradrenergic system degeneration displayed an inherent sex‐specific difference on longevity of fear memory with deficits occurring only in male APP/PS1 mice during early stages of AD.