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671.
It has been reported that insulin eyedrops are useful preparations for delivering insulin systemically. In order to determine the individual contribution of insulin absorption through the conjunctiva and nasal mucosa, experiments were carried out with and without the puncta occluded, while insulin plus absorption enhancer was instilled into the eye. Blood samples were collected at various time points for blood glucose and plasma insulin determinations. It was found that approximately 28-34% of insulin was absorbed via the conjunctiva and 66-72% through nasal mucosa. The blood glucose was lowered significantly more in rabbits with the puncta opened than in those with the puncta occluded.  相似文献   
672.
Reproductive Toxicity of Tricresyl Phosphate in a ContinuousBreeding Protocol in Swiss (CD-I) Mice. CHAPIN, R. E., GEORGE,J. D., AND LAMB, J. C. IV. (1988). Fundam. Appl. Toxi-col. 10,344-354. The effects of a mixture of tricresyl phosphate isomerson reproductive performance in Swiss (CD-I) mice were evaluatedusing a continuous breeding protocol. Tricresyl phosphate (TCP)was mixed into the feed at 0, 0.05, 0.1, and 0.2% by weight.Although the fertility index was not changed in the animalsconsuming the high-concentration feed, the number of littersper pair decreased in a dose-related fashion, and the proportionof pups born alive, and their weight, was significantly decreasedin the high-dose group. A crossover mating trial found impairedfertility in both males and females exposed to 0.2% TCP, witha greater effect in females. Histopathology of the Fo pairsrevealed dose-related seminiferous tubule atrophy, and decreasedtestis and epididymal weights in the high-dose males, whilethe female reproductive tract showed no histopathologic changes.There were dose-related changes in the adrenals of both sexes,and body weight was depressed in both sexes at the highest concentration.The last litter born in the 98-day breeding phase was rearedto age 74 days and then mated within the control and two ofthe treatment groups (0.0,0.05, and 0.1 % TCP; there were toofew offspring in the 0.2% group). There was a decrease in thefertility index in the 0.1% TCP group, and a decreased proportionof liveborn and number of liveborn pups per litter. In the F,males at necropsy, sperm concentration and morphology were normalat termination, although motility was decreased in both the0.05% and the 0.1% groups compared to controls. These data showthat TCP impaired fertility in both sexes of mice in the Fogeneration and affected sperm motility at even the lowest dosein F, males.  相似文献   
673.
    
Titanium implants are commonly used in the field of dentistry for prosthetics such as crowns, bridges, and dentures. For successful therapy, an implant must bind to the surrounding bone in a process known as osseointegration. The objective for this ongoing study is to determine the potential of different implant surface coatings in providing the formation of hydroxyapatite (HA). The coatings include titanium nitride (TiN), silicon dioxide (SiO2), and quaternized titanium nitride (QTiN). The controls were a sodium hydroxide treated group, which functioned as a positive control, and an uncoated titanium group. Each coated disc was submerged in simulated body fluid (SBF), replenished every 48 h, over a period of 28 days. Each coating successfully developed a layer of HA, which was calculated through mass comparisons and observed using scanning electron microscopy (SEM) and energy dispersive analysis x-rays (EDX). Among these coatings, the quaternized titanium nitride coating seemed to have a better yield of HA. Further studies to expand the data concerning this experiment are underway.  相似文献   
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675.
    
Combination chemotherapy is often employed to improve therapeutic efficacies of drugs. However, traditional combination regimens often utilize drugs at or near-their maximum tolerated doses (MTDs), elevating the risk of dose-related toxicity and impeding their clinical success. Further, high doses of adjuvant or neoadjuvant chemotherapies can cause myeloablation, which compromises the immune response and hinders the efficacy of chemotherapy as well as accompanying treatments such as immunotherapy. Clinical outcomes can be improved if chemotherapy combinations are designed to reduce the overall doses without compromising their therapeutic efficacy. To this end, we investigated a combination of camptothecin (CPT) with doxorubicin (DOX) as a low-dose treatment option for breast cancer. DOX-CPT combinations were synergistic in several breast cancer cell lines in vitro and one particular ratio displayed extremely high synergy on human triple negative breast cancer cells (MDA-MB-231). This combination led to excellent long-term survival of mice bearing MDA-MB-231 tumors at doses roughly five-fold lower than the reported MTD values of its constituent drugs. Impact of low dose DOX-CPT treatment on local tumor immune environment was assessed in immunocompetent mice bearing breast cancer (4T1) tumors. The combination was not only superior in inhibiting the disease progression compared to individual drugs, but it also generated a more favorable antitumor immunogenic response. Engineering DOX and CPT ratios to manifest synergy enables treatment at doses much lower than their MTDs, which could ultimately facilitate their translation into the clinic as a promising combination for breast cancer treatment.  相似文献   
676.
    
Background: Underage drinking remains a pressing issue on college campuses across the United States. Though the most common form of addressing underage alcohol use on campuses is through deterrence-based policies, evidence suggests deterrence-based methods are ineffective and may produce negative outcomes. Objectives: Using dyadic data, the objective of this study is to use a friendship-informed perspective on deterrence theory to examine how an individual's and his/her friend's perceptions of sanction certainty relate to self-reported underage alcohol use. Results: Using multilevel mixed models which fall under the actor-partner interdependence modeling class, results demonstrate that respondents who perceive high levels of sanction certainty drink and heavily use alcohol more frequently than those who perceive low levels of sanction certainty. Additionally, those who have friends who perceive high levels of sanction certainty tend to drink at young ages significantly more frequently and in more dangerous patterns than those who have friends who perceive a low sanction certainty. The dyad members' levels of sanction certainty do not interact in relation to alcohol use. Conclusions: The significant relationships of the friends' sanction certainty support the notion of friendship-based deterrence. However, the consistent positive direction of all sanction certainty measures is the opposite of what deterrence theory hypothesizes. As such, it appears that deterrence is not only ineffective at stopping underage alcohol use on college campuses, but may be harmful due to increased rates of both drinking and high-risk drinking.  相似文献   
677.
    
BackgroundA clinical ability to describe the response trajectory of patients receiving preventive migraine treatment could expedite and improve therapeutic management decisions. This post hoc analysis of the PROMISE-2 study evaluated the consistency and predictive power of Month 1 treatment response on later response in patients with chronic migraine.MethodsPROMISE-2 was a double-blind, placebo-controlled trial that randomized adults with chronic migraine to eptinezumab 100 mg, 300 mg, or placebo administered IV every 12 weeks for up to 24 weeks (2 infusions over 6 study months). Migraine responder rates (MRRs) were calculated from monthly migraine days over 4-week intervals compared with baseline. Patients were grouped by MRR during Month 1 (< 25%, 25–< 50%, 50–< 75%, and ≥ 75%), with the number of subsequent study months (Months 2–6) with ≥50% and ≥ 75% MRR calculated in each subgroup. A similar analysis was conducted using Patient Global Impression of Change (PGIC) rating to define Month 1 subgroups (very much improved, much improved, minimally improved, and no change/worse) and rates of very much improved or much improved PGIC during Months 2–6.ResultsIn the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, 194/356 (54.5%), 212/350 (60.6%), and 132/366 (36.1%) patients were ≥ 50% migraine responders during Month 1. More eptinezumab-treated patients were ≥ 75% migraine responders (100 mg, 110/356 [30.9%]; 300 mg, 129/350 [36.9%]; placebo, 57/366 [15.6%]) and more placebo-treated patients were < 25% migraine responders (eptinezumab 100 mg, 103/356 [28.9%]; 300 mg, 80/350 [22.9%]; placebo, 153/366 [41.8%]). Among patients who achieved ≥75% migraine response in Month 1, more than one-third attained ≥75% migraine response for all 5 subsequent study months and more than two-thirds achieved ≥75% migraine response for ≥3 months. More than two-thirds of those in the very much improved (PGIC) subgroup at Month 1 were much or very much improved for all 5 subsequent months.ConclusionsIn this post hoc analysis of data from PROMISE-2, more eptinezumab-treated than placebo-treated patients were early (Month 1) responders, and most early responders went on to achieve a high level of response for at least half of the 24-week treatment period. Potential for later response in early non-responders was also observed.Trial registrationClinicalTrials.gov identifier: {\"type\":\"clinical-trial\",\"attrs\":{\"text\":\"NCT02974153\",\"term_id\":\"NCT02974153\"}}NCT02974153; registered November 23, 2016.  相似文献   
678.
679.
    
Magnetoencephalography (MEG) and EEG have identified poststimulus low frequency and 40 Hz steady‐state auditory encoding abnormalities in schizophrenia (SZ). Negative findings have also appeared. To identify factors contributing to these inconsistencies, healthy control (HC) and SZ group differences were examined in MEG and EEG source space and EEG sensor space, with better group differentiation hypothesized for source than sensor measures given greater predictive utility for source measures. Fifty‐five HC and 41 chronic SZ were presented 500 Hz sinusoidal stimuli modulated at 40 Hz during simultaneous whole‐head MEG and EEG. MEG and EEG source models using left and right superior temporal gyrus (STG) dipoles estimated trial‐to‐trial phase similarity and percent change from prestimulus baseline. Group differences in poststimulus low‐frequency activity and 40 Hz steady‐state response were evaluated. Several EEG sensor analysis strategies were also examined. Poststimulus low‐frequency group differences were observed across all methods. Given an age‐related decrease in left STG 40 Hz steady‐state activity in HC (HC > SZ), 40 Hz steady‐state group differences were evident only in younger participants' source measures. Findings thus indicated that optimal data collection and analysis methods depend on the auditory encoding measure of interest. In addition, whereas results indicated that HC and SZ auditory encoding low‐frequency group differences are generally comparable across modality and analysis strategy (and thus not dependent on obtaining construct‐valid measures of left and right auditory cortex activity), 40 Hz steady‐state group‐difference findings are much more dependent on analysis strategy, with 40 Hz steady‐state source‐space findings providing the best group differentiation.  相似文献   
680.
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