Tyloxapol Research Articles

Learning Curve in Posterior Segment Ophthalmic Diagnostic Endoscopy: Implications for Budding Enthusiasts and Fellows-In-Training

ABSTRACT Purpose To elucidate the learning curve for posterior segment diagnostic endoscopy (DE) based on the results of a self-trained (ST) and a supervised (SUP) vitreoretinal surgeon. Methods Retrospective review of medical records of DE performed between 2017 and 2023 by one ST and one SUP vitreoretinal surgeon at a tertiary eye care institute. Data were collected and the serial number of cases was plotted against the time taken for the procedure. A comparative regression plot was created for both the surgeons to know the slope of the learning curve. The start time was noted as that of attachment of the endoscope and the stop time was noted as the end of diagnostic evaluation. Procedures were divided into blocks of 10 cases each and the time taken for the procedures was calculated. Results Total of 106 eyes (58 by ST surgeon and 48 by SUP surgeon) were included. For ST surgeon, the time taken for the surgery correlated inversely (reduced sequentially) with the serial number of the case till the 20th case (correlation coefficient = −0.5, p = .01), for SUP surgeon, the time taken for the surgery correlated inversely with the serial number of the case till the 10th case (correlation coefficient = −0.9, p = <0.0001) and then stabilized. Neither of the groups had any adverse events. Conclusion About 20 cases for a self-trained and about 10 cases for a supervised vitreoretinal surgeon are required to get stable with DE. These observations have implications in creating a training module for DE with appropriate number of training cases.

Histopathological and Antioxidant Effects of Bromelain on Kidney Tissue of Tyloxapol-Induced Hyperlipidemic Rats

This study was designed to investigate the nephroprotective effect of Bromelain against oxidative stress induced by Tyloxopol-induced hyperlipidemia in rats. Rats (n=6) were divided into three groups. I: Control (C) Group: No treatment was given and only distilled water was given; II: Tyloxapol (TX) Group: Group receiving Tyloxapol (400 mg/kg, i.p); III: Tyloxapol + Bromelain (TX+BR) Group: Group receiving Tyloxapol (400 mg/kg, i.p.) and group receiving Bromelain (250 mg/kg, o.d.) for 18 days. As a result of Tyloxapol administration, oxidative stress parameters SOD and CAT levels decreased, while MDA levels increased. In addition, histopathologic variations were detected in kidney sections. On the other hand, lipid peroxidation decreased and most of the studied parameters improved with combined administration (TX+BR group). According to the results obtained, bromelain may be a potent and alternative agent with protective effect for further studies.

Tyloxapol and nanoliposomes induce selective delivery of 5‐fluorouracil into hepatic tissues via VLDL/LDL‐mediated pathway

AbstractThis study aimed to enhance the hepatic targeting of 5‐fluorouracil (5‐FU) by tyloxapol (TYL) and nanoliposomes to promote drug efficacy and safety. The lipophilicity of 5‐FU was increased by cholesterol conjugation (5‐FUC). Nanoliposomes were prepared, characterized, and loaded with 5‐FU and 5‐FUC and injected into TYL‐treated male Wistar albino rats. After 4 h, LDL and hepatic homogenate were isolated, and the concentrations of 5‐FU and 5‐FUC were investigated in both specimens. The pharmacokinetic parameters of 5‐FU‐ and 5‐FUC‐loaded liposomes were also investigated. The present results revealed that the prepared liposomes have a nanoscale size, negative zeta potential, and prolonged drug release. TYL injection significantly elevated the plasma levels of nonhigh‐density lipoproteins, triacylglycerol (TAG), and total cholesterol (TC). The isolated LDL nanoparticles had a nanosized homogenous vesicle structure and a negative zeta potential. 5‐FUC‐loaded liposomes and TYL augmented 5‐FUC loading into LDL and hepatic tissues compared to that for 5‐FU. Moreover, the present results indicated that 5‐FUC‐loaded liposomes significantly improved the Cmax, Tmax, AUC, MRT, and t1/2 compared to those for the 5‐FUC solution and 5‐FU‐loaded liposomes. This study concluded that the triple approach of a lipophilic shift, nanoliposomes, and TYL is promising for enhancing drug bioavailability, LDL loading, and selective hepatic drug targeting.Practical Applications: 5‐Fluorouracil (5‐FU) is a hydrophilic anticancer medicine that elicits multiple side effects due to high doses, short half‐life, and nonspecific tissue distribution. In this study, 5‐FU was shifted into a lipophilic form (5‐FUC) by cholesterol conjugation. The 5‐FUC was loaded into a nanoliposome. Rats were injected with tyloxapol (TYL) to induce a temporary hyperlipidemia that produces a lipophilic milieu. The hyperlipidemia was confirmed physically by plasma milky appearance and biochemically by marked elevation of non‐HDL lipoproteins. Hyperlipidemia promotes 5‐FUC loading into VLDL‐LDL in vivo. The 5‐FUC level was determined in isolated LDL and liver tissues using HPLC analysis. The lipophilic shift, liposomal loading, and TYL improve pharmacokinetic parameters and bioavailability of 5‐FU with sustained action and hepatic targeting. This study opens a new avenue for endogenous drugs loading into lipoproteins as an approach for selective hepatic drug targeting.

Digeda-4 decoction and its disassembled prescriptions improve dyslipidemia and apoptosis by regulating AMPK/SIRT1 pathway on tyloxapol-induced nonalcoholic fatty liver disease in mice

Ethnopharmacological relevanceNonalcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and the leading cause of chronic liver disease worldwide. Digeda-4 decoction (DGD-4) is a commonly prescribed Mongolian herbal drug for treating acute and chronic liver injury and fatty liver. However, the mechanisms underlying the improvement of dislipidemia and liver injury via treatment with DGD-4 remain unclear. Disassembling a prescription is an effective approach to studying the effects and mechanisms underlying Mongolian medicine prescriptions. By disassembling a prescription, it is feasible to discover effective combinations of individual herbs to optimize a given prescription. Accordingly, we disassembled DGD-4 into two groups: the single Lomatogonium rotatum (L.) Fries ex Nym (LR) (DGD-1) and non-LR (DGD-3). Aim of this studyTo study whether DGD-4 and its disassembled prescriptions have protective effects against tyloxapol (TY)-induced NAFLD and to explore the underlying mechanisms of action and compatibility of prescriptions. Material and methodsNAFLD mice were developed by TY induction. Biochemical horizontal analyses, enzyme-linked immunosorbent assay, and liver histological staining were performed to explore the protective effects of DGD-4 and its disassembled prescriptions DGD-3 and DGD-1. Furthermore, we performed immunohistochemical analyses and Western blotting to further explore the expression of target proteins. ResultsDGD-4 and its disassembled prescriptions could inhibit TY-induced dislipidemia and liver injury. In addition, DGD-4 and its disassembled prescriptions increased the levels of p-AMPKα and p-ACC, but decreased the levels of SREBP1c, SCD-1, SREBP-2, and HMGCS1 proteins. The activation of lipid metabolic pathways SIRT1, PGC-1α, and PPARα improved lipid accumulation in the liver. Moreover, DGD-4 could inhibit hepatocyte apoptosis and treat TY-induced liver injury by upregulating the Bcl-2 expression, downregulating the expression of Bax, caspase-3, caspase-8, and the ratio of Bax/Bcl-2, and positively regulating the imbalance of oxidative stress (OxS) markers (such as superoxide dismutase [SOD], catalase [CAT], malondialdehyde [MDA], and myeloperoxidase [MPO]). DGD-1 was superior to DGD-3 in regulating lipid synthesis-related proteins such as SREBP1c, SCD-1, SREBP-2, and HMGCS1. DGD-3 significantly affected the expression of lipid metabolic proteins SIRT1, PGC-1α, PPARα, apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, and the regulation of Bax/Bcl-2 ratio. However, DGD-1 showed no regulatory effects on Bax and Bcl-2 proteins. ConclusionThis study demonstrates the protective effects of DGD-4 in the TY-induced NAFLD mice through a mechanism involving improvement of dyslipidemia and apoptosis by regulating the AMPK/SIRT1 pathway. Although the Monarch drug DGD-1 reduces lipid accumulation and DGD-3 inhibits apoptosis and protects the liver from injury, DGD-4 can be more effective overall as a therapy when compared to DGD-1 and DGD-3.

Employing Semi-Supervised and Supervised Learning to Discover False Online Ratings

Today's modern industry and trade, internet evaluations matter a lot. Buying web items is often influenced by the opinions of other customers. Because of this, unscrupulous folks or organisations attempt to rig customer evaluations to their personal advantage. Using a lodging rating database, this research examines the performance of semi-supervised (SSVD) and supervised (SVD) word extraction methods for detecting false ratings.

Corosolic Acid Attenuates Hepatic Lipid Accumulation and Inflammatory Response via AMPK/SREBPs and NF-B/MAPK Signaling Pathways.

Corosolic acid (CA) is the main active component of Lagetstroemia speciosa and has been known to serve as several different pharmacological effects, such as antidiabetic, anti-oxidant, and anticancer effects. In this study, effects of CA on the hepatic lipid accumulation were examined using HepG2 cells and tyloxapol (TY)-induced hyperlipidemia ICR mice. CA significantly inhibited hepatic lipid accumulation via inhibition of SREBPs, and its target genes FAS, SCD1, and HMGCR transcription in HepG2 cells. These effects were mediated through activation of AMPK, and these effects were all abolished in the presence of compound C (CC, an AMPK inhibitor). In addition, CA clearly alleviated serum ALT, AST, TG, TC, low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) levels, and obviously attenuated TY-induced liver steatosis and inflammation. Moreover, CA significantly upregulated AMPK, ACC, LKB1 phosphorylation, and significantly inhibited lipin1, SREBPs, TNF-, F4/80, caspase-1 expression, NF-B translocation, and MAPK activation in TY-induced hyperlipidemia mice. Our results suggest that CA is a potent antihyperlipidemia and antihepatic steatosis agent and the mechanism involved both lipogenesis and cholesterol synthesis and inflammation response inhibition via AMPK/SREBPs and NF-B/MAPK signaling pathways.

Impact Of Prehabilitation In Oncology Via Exercise - Breast Cancer: The Improve-B Study

The manifold benefits of exercise during and after breast cancer therapy are well investigated and lead international agencies to recommend exercise for breast cancer patients and survivors (Schmitz, 2010). However, there is still a knowledge gap regarding the efficacy of prehabilitative exercise for patients undergoing breast cancer surgery. PURPOSE: Investigate the effects of exercise before surgery (prehabilitation), on the health perception and functional capability of women after surgery. METHODS: 33 sedentary breast cancer patients scheduled for breast cancer surgery were randomized to either a partly supervised (SE), a home based (HE) resistance exercise groups or a usual care group (UC), each consisting of 11 patients. The patients were assessed before the intervention, immediately before surgery, before and after adjuvant treatment. The data were analyzed via linear Mixed-Effect-Models, questionnaire scales were standardized to the pooled pretest standard deviation. The reported results are the incremental effects in the intervention groups compared to the UC at the post-surgical follow up. RESULTS: The interim results showed superior functional fitness for both exercise groups, with an incremental increase in the 6min walk distance of 123.5 meter (95%-CI= 41.8 - 206.1) in the HE and 113.0 meter (95%-CI= 27.3 - 198.7) in the SE. The gain of grip strength in the dominant hand surpassed the gain in the UC by 7.0kg (95%-CI= 3.6 - 10.4) in the HE and 5.4kg (95%-CI= 3.4 - 7.3) in the SE. In the non-dominant hand the strength gains were lower with 3.2kg (95%-CI= -0.15 - 6.6) in the HE and 3.1kg (95%-CI= -0.5 - 6.7) in the SE. Both exercise groups showed superior improvements in quality of life compared to the UC. With large effects of β= 1.34 (95%-CI= 0.18 - 2.50) in the HE and β= 2.60 (95%-CI= 1.31 - 3.89) in the SE in role function, and β= 0.49 (95%-CI= -0.29 - 1.27) in the HE and β= 1.54 (95%-CI= 0.66 - 2.42) in the SE, in physical function measures. CONCLUSION: These results support the implementation of a brief prehabilitative exercise intervention and display the multidimensional effects of exercise on functional, as well as psychological health parameters.

Supervised physiotherapy leads to a better return to physical activity after anterior cruciate ligament reconstruction.

The main goal of rehabilitation after anterior cruciate ligament reconstruction (ACLR) is to return to functional and sports activity at a preinjury level. The aim of this study was to assess the influence of supervised (SU) versus non-supervised (NS) rehabilitation protocols after ACLR on the return to sports activity and quality of life of amateur athletes. The study included a total of 50 patients after ACLR, with 25 in the SU group and 25 in the NS group. No significant differences were observed between the two groups with regard to age, sex, or BMI. Two different ACLR techniques were used: hamstring graft and bone patellar tendon bone. The patients were examined preoperatively and 12 months postoperatively. Outcomes were evaluated utilizing the Kujala Scale, Tegner Scale, the Knee injury and Osteoarthritis Outcome Score (KOOS), the Functional Movement Screen (FMS), and range of motion. Patients from the SU group participated in rehabilitation sessions with a physiotherapist with an average of 48 meetings. Those in the NS attended six meetings with the physiotherapist. At final follow-up, patients from both groups demonstrated a higher level of functional and sports activity and had a better quality of life 12 months after ACLR. Patients from the supervised group returned to a significantly higher level of sports activity (Tegner Scale: SU=6, NS=5, P=0.003) and reported significantly better quality of life 12 months after ACLR (KOOS QOL: SU=90, NS=74; P<0.001). Supervised, controlled physiotherapy results in higher activity levels and better quality of life in amateur athletes 12 months after ACLR.

A 5-Year Follow-Up of The Benefits of an Exercise Training Program in Liver Recipients Transplanted Due to Familial Amyloidotic Polyneuropathy.

Supervised (SE) and home-based exercise (HBE) training regimes are effective on reconditioning patients with familial amyloidotic polyneuropathy (FAP) after liver transplantation, but research of the long-term retention of the benefits attained in patients with FAP has not yet been conducted. In this 5-year follow-up study, we aimed to determine whether the exercise training gains in body composition, physical activity, and function promoted by a 24-week SE or HBE training regimes are retained in patients with FAP who resume normal activity. Sixteen liver-transplanted patients with FAP were reassessed for body composition (dual X-ray absorptiometry), physical activity (questionnaire), and function (handgrip strength and 6-minute walk test). Total body fat increased with both exercise regimes during follow-up ( P < .05; η2 = 0.432-0.625) as well as femoral neck bone density ( P = .048; η2 = 0.119). However, gains in upper limbs muscle quality during follow-up ( P < .001; η2 = 0.597) were only found in the SE group ( P = .042; η2 = 0.245). Both exercise regimes showed retaining aptitudes in walking capacity ( P < .05; η2 = 0.329-0.460) and muscle mass ( P = .05; η2 = 0.245). Still, none could retain the physical activity levels. Long-term resumption of normal activity following a 24-week SE or HBE regime in patients with FAP resulted in loss of exercise induced increases in physical activity but counterweighted postoperative losses in bone mineral density and substantially retained the benefits in walking capacity, muscle mass, and quality, in particular, in the SE group.

Effects of a Supervised versus an Unsupervised Combined Balance and Strength Training Program on Balance and Muscle Power in Healthy Older Adults: A Randomized Controlled Trial

Background: Losses in lower extremity muscle strength/power, muscle mass and deficits in static and particularly dynamic balance due to aging are associated with impaired functional performance and an increased fall risk. It has been shown that the combination of balance and strength training (BST) mitigates these age-related deficits. However, it is unresolved whether supervised versus unsupervised BST is equally effective in improving muscle power and balance in older adults. Objective: This study examined the impact of a 12-week BST program followed by 12 weeks of detraining on measures of balance and muscle power in healthy older adults enrolled in supervised (SUP) or unsupervised (UNSUP) training. Methods: Sixty-six older adults (men: 25, women: 41; age 73 ± 4 years) were randomly assigned to a SUP group (2/week supervised training, 1/week unsupervised training; n = 22), an UNSUP group (3/week unsupervised training; n = 22) or a passive control group (CON; n = 22). Static (i.e., Romberg Test) and dynamic (i.e., 10-meter walk test) steady-state, proactive (i.e., Timed Up and Go Test, Functional Reach Test), and reactive balance (e.g., Push and Release Test), as well as lower extremity muscle power (i.e., Chair Stand Test; Stair Ascent and Descent Test) were tested before and after the active training phase as well as after detraining. Results: Adherence rates to training were 92% for SUP and 97% for UNSUP. BST resulted in significant group × time interactions. Post hoc analyses showed, among others, significant training-related improvements for the Romberg Test, stride velocity, Timed Up and Go Test, and Chair Stand Test in favor of the SUP group. Following detraining, significantly enhanced performances (compared to baseline) were still present in 13 variables for the SUP group and in 10 variables for the UNSUP group. Conclusion: Twelve weeks of BST proved to be safe (no training-related injuries) and feasible (high attendance rates of >90%). Deficits of balance and lower extremity muscle power can be mitigated by BST in healthy older adults. Additionally, supervised as compared to unsupervised BST was more effective. Thus, it is recommended to counteract intrinsic fall risk factors by applying supervised BST programs for older adults.

Ophthalmic Vehicles Containing Polymer-Solubilized Tropicamide: “In Vitro/In Vivo” Evaluation

ABSTRACTCommercial 1.0% aqueous tropicamide (TR) eyedrops are buffered to pH 4.4–5.0 to produce sufficiently stable solutions of the weakly basic, poorly soluble drug. These acidic solutions, however, are irritants and may induce copious lachrimation, thus reducing the drug bioavailability. The aim of the present study was to evaluate some solubilizing agents for the preparation of 1.0% TR ophthalmic solutions adjusted at physiologically compatible pH, potentially showing increased eye tolerance, activity, and stability when compared with standard commercial eyedrops. The tested solubilizers were two non-ionic surfactants—Tyloxapol (TY) and Cremophor EL (CR)—and one polymer, Pluronic P85 (PL). Four stable 1% TR formulations, containing 3% TY, 7.5% CR, 15% PL, or 5% CR + 10% PL were submitted to mydriatic activity tests in rabbits. They improved to a small but statistically significant extent the AUC for mydriatic effect of TR in the test animals when compared with commercial 1.0% TR eyedrops.

TYLOXAPOL CONFERS DURABLE PROTECTION AGAINST HYPEROXIC LUNG INJURY IN THE RAT

We tested the hypothesis that the nonlipid components of Exosurf, tyloxapol (TY), and cetyl alcohol (CA), protect against hyperoxic lung injury by induction of the animals' endogenous antioxidant defenses. Adult rats were intratracheally instilled with escalating doses of TY and CA (n=20) or TY alone (n=32) and immediately exposed to 100% oxygen. Intratracheal instillation of TY alone or in combination with CA protected against lethal hyperoxic injury in the rat in a dose-dependent fashion. To assess the effects of timing, rats were instilled with TY plus CA 24 hours before (n=6) and 24 hours after (n=6) exposure to 100% oxygen, with time to death determined. Rats were also instilled with TY alone at 0 hour (n=6), 48 hours (n=3), 96 hours (n=3), and 186 hours (n=4) prior to exposure to 100% oxygen. Lungs were assayed for superoxide dismutase, glutathione peroxidase, and catalase activities. Finally, the pharmacokinetics of TY in the rat lung were determined by instilling radiolabelled TY intratracheally. TY has a prolonged half-life in the rat lung, and protection against lethal hyperoxic injury was achieved by a single intratracheal dose delivered up to 186 hours prior to injury. Antioxidant enzymes were not induced in protected animals. We conclude that TY provides durable protection against hyperoxic lung injury without induction of antioxidant enzymes. It is present in the lung for sufficient duration to invoke a direct mechanism of protection, possibly as a radical scavenger. These findings raise the prospect of a therapeutic application for TY as prophylaxis in patients at risk for oxygen toxicity and adult respiratory distress syndrome.

THE INFLUENCE OF DIRECT SUPERVISION OF RESISTANCE TRAINING ON PHYSICAL PERFORMANCE AND HORMONAL RESPONSES.

934 This study compared changes in performance, body composition, and hormonal responses after 12 wks of supervised (SUP) or unsupervised (UNSUP), periodized heavy resistance training. Twenty-two, moderately trained men (24±4 yrs) were tested for maximal (1RM) squat and bench press (BP) strength, lower body power output, BP local muscular endurance, body composition, and resting serum [testosterone] and [cortisol] at wk 0, and after 1 and 12 wks of training. Test-retest reliability coefficients were ≥ 0.95. Subjects were randomly assigned (2:1 experimental vs. control) to either SUP (n=14) in which training was supervised by a personal trainer or UNSUP (n=8) in which subjects trained without professional supervision. Groups performed identical linear periodized resistance training programs consisting of preparatory (10-12RM), hypertrophy (8-10RM), strength (5-8RM), and peaking phases (3-6RM) using free-weight and variable-resistance machine exercises. Squat and BP 1RM, mean and peak power output, absolute local muscular endurance, and fat mass increased significantly (p≤0.05) while [cortisol] decreased significantly in both groups following training. FFM,% body fat, and testosterone to cortisol ratio (T/C) increased significantly in SUP following training. Change(Wk 0 to Wk 12) in squat and BP 1RM, absolute local muscular endurance, and FFM were significantly greater in SUP than UNSUP. During training, mean resistance (kg/set) was significantly greater in SUP than UNSUP at wks 8 and 10 for the squat, and wks 7 to 12 for BP. Results indicate that maximal strength, absolute local muscular endurance, FFM, and T/C increase significantly greater following 12 wks of periodized heavy resistance training supervised by a personal trainer than in unsupervised training.

Alevaire as an adjunct for preventing pulmonary complications after thoracotomy; a comparative study of 200 cases.

Alevaire as an adjunct for preventing pulmonary complications after thoracotomy; a comparative study of 200 cases.