-
European Review For Medical and... Dec 2023We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function.
OBJECTIVE
We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function.
PATIENTS AND METHODS
A retrospective study was conducted by enrolling sixty elderly patients who underwent femoral head replacement (FHR) under IA in our hospital from August 2019 to August 2020. The patients were divided into two groups according to the random number table method. In the control group (CG) (30 patients), 5 mg of ephedrine was administered sedately when patients developed hypotension (20% below basal blood pressure). In the research group (RG) (30 cases), 2 μg/(kg·h) of methoxamine hydrochloride was given as a constant-rate pump before anesthesia, and 1 mg of methoxamine hydrochloride was administered intraoperatively if hypotension occurred. The hemodynamic [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)], myocardial injury indexes [cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), fatty acid binding protein (FABP), plasma amino-terminal brain natriuretic peptide precursor (NT-proBNP)], cardiac function indexes [systemic vascular resistance (SVR), stroke volume (SV), net percentage ejection time (ET)] were observed before anesthesia (T1), at the end of surgery (T2), and 6 h after surgery (T3) in both groups. The Bruggemann Comfort Score (BCS) and Visual Analog Scale (VAS) scores at T3, 12 h postoperatively (T4) and 24 h postoperatively (T5) in both groups were observed, and the incidence of adverse reactions to intralesional anesthesia in both groups was counted.
RESULTS
SBP, DBP and HR at T2 were lower than those at T1 in both groups, and SBP, DBP and HR at T3 were higher than those at T2, and SBP, DBP and HR at T2 and T3 in the RG were higher than those in the CG (p<0.05). In both groups, cTnⅠ, CK-MB and FABP were higher at T2 and T3 than at T1, higher at T3 than at T2, and NT-proBNP was higher at T2 than at T1 and T3, and lower in the RG than in the CG (p<0.05). In both groups, SVR and SV at time point T2 were lower than at time point T1 and ET was higher than at time point T1, SVR and SV at time point T3 were higher than at time point T2 and ET was lower than at time point T2, SVR and SV in the RG were higher than in the CG and ET was lower than in the CG (p<0.05). VAS scores were higher in both groups at T4 and T5 than at T3, and lower in the RG than in the CG (p<0.05).
CONCLUSIONS
Methoxamine can effectively reduce the risk of hypotension in geriatric endotracheal anesthesia, which can reduce myocardial injury and stabilize cardiac function in patients.
Topics: Humans; Aged; Methoxamine; Retrospective Studies; Hemodynamics; Anesthesia; Creatine Kinase, MB Form; Fatty Acid-Binding Proteins; Hypotension
PubMed: 38164838
DOI: 10.26355/eurrev_202312_34773 -
Drugs Jan 2024A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication.
METHODS
Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters.
RESULTS
Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months.
CONCLUSION
The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months.
TRIAL REGISTRY
ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.
Topics: Humans; Travoprost; Glaucoma, Open-Angle; Intraocular Pressure; Timolol; Antihypertensive Agents; Cloprostenol; Ocular Hypertension; Glaucoma; Ophthalmic Solutions; Double-Blind Method; Treatment Outcome
PubMed: 38060092
DOI: 10.1007/s40265-023-01973-7 -
Reproductive Biology and Endocrinology... Mar 2024Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy.
BACKGROUND
Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy.
METHODS
Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage.
RESULTS
Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25).
CONCLUSIONS
The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.
Topics: Humans; Pregnancy; Female; Breast Neoplasms; Pregnancy Complications, Neoplastic; Prognosis; Parturition; Azides; Propanolamines
PubMed: 38532462
DOI: 10.1186/s12958-024-01206-w -
International Journal of Molecular... Aug 2023Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are...
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are the main causes of morbi-mortality in COPD and, in particular, hypertension and heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link has currently been established between the onset of COPD, elevated blood pressure (BP) and systemic vascular impairment (endothelial dysfunction). Thus, we aimed to characterize BP and vascular function and remodeling in a rat model of exacerbated emphysema focusing on the role of sympathetic hyperactivity. Emphysema was induced in male Wistar rats by four weekly pulmonary instillations of elastase (4UI) and exacerbation by a single dose of lipopolysaccharides (LPS). Five weeks following the last instillation, in vivo and ex vivo cardiac and vascular functions were investigated. Exacerbated emphysema induced cardiac dysfunction (HFpEF) and a BP increase in this COPD model. We observed vasomotor changes and hypotrophic remodeling of the aorta without endothelial dysfunction. Indeed, changes in contractile and vasorelaxant properties, though endothelium-dependent, were pro-relaxant and NO-independent. A β1-receptor antagonist (bisoprolol) prevented HFpEF and vascular adaptations, while the effect on BP increase was partial. Endothelial dysfunction would not trigger hypertension and HFpEF in COPD. Vascular changes appeared as an adaptation to the increased BP. The preventing effect of bisoprolol revealed a pivotal role of sympathetic hyperactivation in BP elevation. The mechanistic link between HFpEF, cardiac sympathetic activation and BP deserves further studies in this exacerbated-emphysema model, as well as in COPD patients.
Topics: Male; Rats; Animals; Pulmonary Emphysema; Bisoprolol; Heart Failure; Blood Pressure; Rats, Wistar; Stroke Volume; Hypertension; Pulmonary Disease, Chronic Obstructive; Emphysema
PubMed: 37628790
DOI: 10.3390/ijms241612609 -
Journal of Dairy Science Apr 2024Fat in the form of cracked rapeseed and 3-nitrooxypropanol (3-NOP, market as Bovaer) were fed alone or in combination to 4 Danish Holstein multicannulated dairy cows,...
Fat in the form of cracked rapeseed and 3-nitrooxypropanol (3-NOP, market as Bovaer) were fed alone or in combination to 4 Danish Holstein multicannulated dairy cows, with the objective to investigate effects on gas exchange, dry matter intake (DMI), nutrient digestion, and nutrient metabolism. The study design was a 4 × 4 Latin square with a 2 × 2 factorial treatment arrangement with 2 levels of fat supplementation; 33 g of crude fat per kg of dry matter (DM) or 64 g of crude fat per kg of DM for low and high fat diets, respectively, and 2 levels of 3-NOP; 0 mg/kg DM or 80 mg/kg DM. In total, 4 diets were formulated: low fat (LF), high fat (HF), 3-NOP and low fat (3LF), and 3-NOP and high fat (3HF). Cows were fed ad libitum and milked twice daily. The adaptation period lasted 11 d, followed by 5 d with 12 diurnal sampling times of digesta and ruminal fluid. Thereafter, gas exchange was measured for 5 d in respiration chambers. Chromic oxide and titanium dioxide were used as external flow markers to determine intestinal nutrient flow. No interactions between fat supplementation and 3-NOP were observed for methane yield (g/kg DM), total-tract digestibility of nutrients or total volatile fatty acid (VFA) concentration in the rumen. Methane yield (g/kg DMI) was decreased by 24% when cows were fed 3-NOP. In addition, 3-NOP increased carbon dioxide and hydrogen yield (g/kg DM) by 6% and 3,500%, respectively. However, carbon dioxide production was decreased when expressed on a daily basis. Fat supplementation did not affect methane yield but tended to reduce methane in percent of gross energy intake. A decrease (11%) in DMI was observed, when cows were fed 3-NOP. Likely, the lower DMI mediated a lower passage rate causing the tendency to higher rumen and total-tract neutral detergent fiber digestibility, when the cows were fed 3-NOP. Total VFA concentrations in the rumen were negatively affected both by 3-NOP and fat supplementation. Furthermore, 3-NOP caused a shift in the VFA fermentation profile, with decreased acetate proportion and increased butyrate proportion, whereas propionate proportion was unaffected. Increased concentrations of the alcohols methanol, ethanol, propanol, butanol, and 2-butanol were observed in the ruminal fluid when cows were fed 3-NOP. These changes in rumen metabolites indicate partial re-direction of hydrogen into other hydrogen sinks, when methanogenesis is inhibited by 3-NOP. In conclusion, fat supplementation did not reduce methane yield, whereas 3-NOP reduced methane yield, irrespective of fat level. However, the concentration of 3-NOP and diet composition and resulting desired mitigation effect must be considered before implementation. The observed reduction in DMI with 80 mg 3-NOP/kg DM was intriguing and may indicate that a lower dose should be applied in a Northern European context; however, the mechanism behind needs further investigation.
Topics: Female; Cattle; Animals; Lactation; Brassica napus; Digestion; Rumen; Hydrogen; Carbon Dioxide; Dietary Fiber; Milk; Nutrients; Diet; Propanols; Fatty Acids, Volatile; Fermentation; Methane
PubMed: 37863291
DOI: 10.3168/jds.2023-23743 -
Adipocyte Dec 2023Oil Red O (ORO) staining is a commonly used experimental technique to detect lipid content in cells or tissues. Freshly prepared ORO in 60% isopropanol is the most...
Oil Red O (ORO) staining is a commonly used experimental technique to detect lipid content in cells or tissues. Freshly prepared ORO in 60% isopropanol is the most widely used method at present. However, isopropanol is volatile and harmful to the human body. It will also affect the interpretation of the results due to the formation of crystals and non-specific diffuse staining. In this paper, by screening and validation, we report a salicylic acid ethanol solution (containing 50% ethanol, 5%-10% salicylic acid) for the preparation of ORO solution, which has a better staining effect on lipid staining in cells and tissues, with a clean background and short dyeing time. What's more, this ORO solution is non-toxic, convenient to prepare, and can be stored for a long time. Therefore, it is reliable, easy to operate, and can be widely popularized and applied in laboratories.
Topics: Humans; Salicylic Acid; Ethanol; 2-Propanol; Staining and Labeling; Lipids
PubMed: 36779587
DOI: 10.1080/21623945.2023.2179334 -
Journal of Dairy Science Jan 2024The objective of the present study was to investigate the effect of individual and combined use of dietary fat, nitrate, and 3-nitrooxypropanol (3-NOP) on dairy cows'...
The objective of the present study was to investigate the effect of individual and combined use of dietary fat, nitrate, and 3-nitrooxypropanol (3-NOP) on dairy cows' enteric methane (CH) emission and production performance. Twenty-four primiparous and 24 multiparous Danish Holstein cows (111 ± 44.6 d in milk; mean ± standard deviation) were included in an incomplete 8 × 8 Latin square design with six 21-d periods. Dietary treatments were organized in a 2 × 2 × 2 factorial arrangement aiming for 2 levels of FAT (30 or 63 g of crude fat/kg of dry matter [DM]; LF or HF, respectively), 2 levels of NITRATE (0 or 10 g of nitrate/kg of DM; UREA or NIT, respectively), and 2 levels of 3-NOP (0 or 80 mg/kg DM; BLANK or NOP, respectively). Treatments were included in ad libitum-fed partial mixed rations in bins that automatically measured feed intake and eating behavior. Additional concentrate was offered as bait in GreenFeed units used for measurement of gas emission. For total DM intake (DMI), a FAT × NITRATE interaction showed that DMI, across parities and levels of 3-NOP, was unaffected by separate fat supplementation, but reduced by nitrate with 4.6% and synergistically decreased (significant 2-way interaction) with 13.0% when fat and nitrate were combined. Additionally, 3-NOP decreased DMI by 13.4% and the combination of 3-NOP with fat and nitrate decreased DMI in an additive way (no significant 3-way interaction). The decreasing effects on DMI were more pronounced in multiparous cows than in primiparous cows. For treatments with largest reductions in DMI, eating behavior was altered toward more frequent, but smaller meals, a slower eating rate and increased attempts to visit unassigned feed bins. Energy-corrected milk (ECM) yield increased by 6.3% with fat supplementation, whereas ECM yield did not differ among diets including nitrate (FAT × NITRATE interaction). Cows supplemented with 3-NOP had 9.0% lower ECM yield than cows fed no 3-NOP. Based on three 2-way interactions including FAT, NITRATE, and 3-NOP, the combined use of the additives resulted in antagonistic effects on CH reduction. A 6% to 7% reduction in CH yield (CH/kg of DMI) could be ascribed to the effect of fat, a 12% to 13% reduction could be ascribed to the effect of nitrate and an 18% to 23% reduction could be ascribed to the effect of 3-NOP. Hence, no combinations of additives resulted in CH yield-reductions that were greater than what was obtained by separate supplementation of the most potent additive within the combination. The CH yield reduction potential of additives was similar between parities. Increased apparent total-tract digestibility of organic matter (OM) in cows fed combinations including nitrate or 3-NOP was a result of a NITRATE × 3-NOP interaction. Apparent total-tract digestibility of OM was also increased by fat supplementation. These increases reflected observed decreases in DMI. In conclusion, combined use of fat, nitrate, and 3-NOP in all combinations did not result in CH reductions that were greater than separate supplementation of the most potent additive within the combination (3-NOP > nitrate > fat). Additionally, separate supplementation of some additives and combined use of all additives reduced DMI.
Topics: Female; Cattle; Animals; Milk; Nitrates; Lactation; Dietary Fats; Methane; Diet; Eating; Animal Feed; Rumen; Zea mays; Propanols
PubMed: 37690719
DOI: 10.3168/jds.2023-23420 -
Cancer Biology & Therapy Dec 2024Chronic stress can induce stress-related hormones; norepinephrine (NE) is considered to have the highest potential in cancer. NE can stimulate the expression of...
BACKGROUND
Chronic stress can induce stress-related hormones; norepinephrine (NE) is considered to have the highest potential in cancer. NE can stimulate the expression of hypoxia-inducible factor-1α (HIF-1α), which is associated with vascular endothelial growth factor (VEGF) secretion and tumor angiogenesis. However, the underlying mechanisms are poorly understood.
METHODS
Tumor-bearing mice were subjected to chronic restraint stress and treated with normal saline, human monoclonal VEGF-A neutralizing antibody bevacizumab, or β-adrenergic receptor (β-AR) antagonist (propranolol). Tumor growth and vessel density were also evaluated. Human colorectal adenocarcinoma cells were treated with NE, propranolol, or the inhibitor of transforming growth factor-β (TGF-β) receptor Type I kinase (Ly2157299) . TGF-β1 in mouse serum and cell culture supernatants was quantified using ELISA. The expression of HIF-1α was measured using Real time-PCR and western blotting. Cell migration and invasion were tested.
RESULTS
Chronic restraint stress attenuated the efficacy of bevacizumab and promoted tumor growth and angiogenesis in a colorectal tumor model. Propranolol blocked this effect and inhibited TGF-β1 elevation caused by chronic restraint stress or NE. NE upregulated HIF-1α expression, which was reversed by propranolol or Ly2157299. Propranolol and Ly2157199 blocked NE-stimulated cancer cell migration and invasion.
CONCLUSIONS
Our results demonstrate the effect of NE on tumor angiogenesis and the critical role of TGF-β1 signaling during this process. In addition, β-AR/TGF-β1 signaling/HIF-1α/VEGF is a potential signaling pathway. This study also indicates that psychosocial stress might be a risk factor which weakens the efficacy of anti-angiogenic therapy.
Topics: Animals; Colorectal Neoplasms; Humans; Neovascularization, Pathologic; Mice; Transforming Growth Factor beta1; Hypoxia-Inducible Factor 1, alpha Subunit; Signal Transduction; Bevacizumab; Propranolol; Cell Line, Tumor; Vascular Endothelial Growth Factor A; Male; Cell Movement; Norepinephrine; Stress, Psychological; Adrenergic beta-Antagonists; Angiogenesis; Pyrazoles; Quinolines
PubMed: 38857055
DOI: 10.1080/15384047.2024.2366451 -
The American Journal of Tropical... Jul 2023Alcohol-based hand rub (ABHR) is an effective hand hygiene measure to mitigate and prevent infectious disease transmission in healthcare facilities (HCFs); however,...
Alcohol-based hand rub (ABHR) is an effective hand hygiene measure to mitigate and prevent infectious disease transmission in healthcare facilities (HCFs); however, availability and affordability in low- and middle-income countries are limited. We sought to establish centralized local production of ABHR using a district-wide approach to increase provider access at all public HCFs in Kabarole and Kasese Districts in Western Uganda. Partner organizations worked with district governments to adapt and implement the WHO protocol for local ABHR production at the district scale. These groups identified and upgraded sites for ABHR production and storage to ensure recommended security, ventilation, and air conditioning. District governments selected technicians for training on ABHR production. Raw materials were sourced within Uganda. Alcohol-based hand rub underwent internal quality control by the production officer and external quality control (EQC) by a trained district health inspector before distribution to HCFs. We assessed ABHR production and demand from March 2019 to December 2020. All ABHR batches (N = 316) met protocol standards (alcohol concentration: 75.0-85.0%) with a mean of 79.9% (range: 78.5-80.5%). Internal quality control measurements (mean alcohol concentration: 80.0%, range: 79.5-81.0%) matched EQC measurements (mean: 79.8%, range: 78.0-80.0%). Production units supplied ABHR to 127 HCFs in Kasese District (100%) and 31 HCFs in Kabarole District (56%); 94% of HCFs were small (dispensary or next higher level). This district-wide production met quality standards and supplied ABHR to many HCFs where facility-level production would be unfeasible. Low- and middle-income countries may consider district models to expand ABHR production and supply to smaller HCFs.
Topics: Humans; Hand Disinfection; Ethanol; Hand Hygiene; 2-Propanol; Delivery of Health Care; World Health Organization
PubMed: 37188343
DOI: 10.4269/ajtmh.22-0554 -
Foods (Basel, Switzerland) Sep 2023Direct iodization in fish sauce, soy sauce, and seasoning sauces plays a crucial role in optimizing the iodine intake of Thailand's people. However, determining the...
Direct iodization in fish sauce, soy sauce, and seasoning sauces plays a crucial role in optimizing the iodine intake of Thailand's people. However, determining the iodine content to ensure that these sauces meet the standard of Thailand's Food and Drug Administration (FDA) is challenging. In this study, all local laboratories equipped with inductively coupled plasma-mass spectrometry (ICP-MS) and with experience in iodine analysis by any analytical method were invited to participate in a hands-on training workshop and two rounds of interlaboratory comparison. The aim was to improve laboratory performance and assess the potential for iodine monitoring for mandatory direct-iodized sauces. All target laboratories participated in this study. The hands-on training workshop harmonized the analytical method and increased the capacity of participating laboratories. Most laboratories (7/8) achieved satisfactory performance for six test samples based on interlaboratory comparison. Samples were extracted by tetramethylammonium hydroxide (TMAH), with the presence of 6% 2-propanol, 0.01% triton X-100, internal standard, and iodine determination in direct-iodized sauces by ICP-MS. The reproducibility standard deviation (), after the removal of outlier results for iodine content, was 7-22% iodine at a level of 0.03-4.81 mg/L. Moreover, the Thai FDA's judgment range for official control activities should expand the range of 2-3 mg per 1 L (ppm) by at least 22%.
PubMed: 37761222
DOI: 10.3390/foods12183513