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Bradley J Catalone Shendra R Miller Mary Lee Ferguson Dan Malamud Tina Kish-Catalone Nina J Thakkar Fred C Krebs Mary K Howett Brian Wigdahl 《Biomedicine & Pharmacotherapy》2005,59(8):430-437
C31G, which has potent activity against the human immunodeficiency virus type 1 (HIV-1) and an established record of safety in animal studies and human trials, is a microbicidal agent comprised of a buffered equimolar mixture of two amphoteric, surface-active agents: an alkyl amine oxide (C14AO) and an alkyl betaine (C16B). Studies of long-term in vitro exposure to C31G and its constituents have suggested that the components of C31G may contribute differentially to its toxicity and efficacy. In the present studies, in vitro assays of cytotoxicity and anti-HIV-1 activity demonstrated that C16B was slightly less cytotoxic compared to either C31G or C14AO, whereas the anti-HIV-1 activities of C31G and its individual constituents were similar. In the murine model of cervicovaginal microbicide toxicity, in vivo exposure to C14AO resulted in severe cervical inflammation followed by a delayed disruption of the columnar epithelium. In contrast, exposure to C16B caused severe cervical epithelial disruption and a secondary, less intense inflammatory response. These results demonstrate that (i) there are both mechanistic and temporal differences in toxicity associated with the components of C31G not necessarily predicted by in vitro assessments of cytotoxicity and (ii) contributions of each component to the anti-HIV-1 activity of C31G appear to be equal. In addition, these findings indicate that direct and indirect mechanisms of in vivo toxicity can be observed as separate but interrelated events. These results provide further insight into the activity of C31G, as well as mechanisms potentially associated with microbicide toxicity. 相似文献
3.
Summary Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic reactive microglia were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.Paper presented at the Erwin Riesch symposium on Lysosomal Disorders of the Nervous System, Berlin (Convenor, Prof. Cervos-Navarro); and as poster-talk at the 9th International Congress of Neuropathology, Vienna, September 1982 相似文献
4.
Olubusola Oladeji Chi Zhang Tiam Moradi Dharmesh Tarapore Andrew C Stokes Vukosi Marivate Moinina D Sengeh Elaine O Nsoesie 《JMIR Public Health and Surveillance》2021,7(4)
BackgroundThe prevalence of chronic conditions such as obesity, hypertension, and diabetes is increasing in African countries. Many chronic diseases have been linked to risk factors such as poor diet and physical inactivity. Data for these behavioral risk factors are usually obtained from surveys, which can be delayed by years. Behavioral data from digital sources, including social media and search engines, could be used for timely monitoring of behavioral risk factors.ObjectiveThe objective of our study was to propose the use of digital data from internet sources for monitoring changes in behavioral risk factors in Africa.MethodsWe obtained the adjusted volume of search queries submitted to Google for 108 terms related to diet, exercise, and disease from 2010 to 2016. We also obtained the obesity and overweight prevalence for 52 African countries from the World Health Organization (WHO) for the same period. Machine learning algorithms (ie, random forest, support vector machine, Bayes generalized linear model, gradient boosting, and an ensemble of the individual methods) were used to identify search terms and patterns that correlate with changes in obesity and overweight prevalence across Africa. Out-of-sample predictions were used to assess and validate the model performance.ResultsThe study included 52 African countries. In 2016, the WHO reported an overweight prevalence ranging from 20.9% (95% credible interval [CI] 17.1%-25.0%) to 66.8% (95% CI 62.4%-71.0%) and an obesity prevalence ranging from 4.5% (95% CI 2.9%-6.5%) to 32.5% (95% CI 27.2%-38.1%) in Africa. The highest obesity and overweight prevalence were noted in the northern and southern regions. Google searches for diet-, exercise-, and obesity-related terms explained 97.3% (root-mean-square error [RMSE] 1.15) of the variation in obesity prevalence across all 52 countries. Similarly, the search data explained 96.6% (RMSE 2.26) of the variation in the overweight prevalence. The search terms yoga, exercise, and gym were most correlated with changes in obesity and overweight prevalence in countries with the highest prevalence.ConclusionsInformation-seeking patterns for diet- and exercise-related terms could indicate changes in attitudes toward and engagement in risk factors or healthy behaviors. These trends could capture population changes in risk factor prevalence, inform digital and physical interventions, and supplement official data from surveys. 相似文献
5.
Courtney Pisano Renata Fabia Junxin Shi Krista Wheeler Sheila Giles Lisa Puett Dylan Stewart Susan Ziegfeld Jennifer Flint Jenna Miller Pablo Aguayo Emily C. Alberto Randall S. Burd Lisa Vitale Justin Klein Rajan K. Thakkar 《Burns : journal of the International Society for Burn Injuries》2021,47(3):545-550
BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study. 相似文献
6.
Holden W. Richards Junxin Shi Rajan K. Thakkar Sheila Giles Krista K. Wheeler Renata Fabia 《Burns : journal of the International Society for Burn Injuries》2021,47(2):322-326
BackgroundDespite the vast literature studying the opioid crisis, sparse data describe this in the pediatric burn population. This study sought to assess patient-level characteristics and their potential effects on opioid administration in nonsurgical pediatric burn inpatients.MethodsAdmitted burn patients from 2013 to 2018 with nonsurgical management at an American Burn Association (ABA) verified pediatric burn center were retrospectively identified. Morphine milligram equivalents by weight (MME/kg) per admission were evaluated through a multiple loglinear regression with race, sex, age, total body surface area burned (TBSA), and burn depth as predictors. Simple linear regression was used to evaluate the temporal trend of median opioid utilization.ResultsA total of 806 patients (55% White, 35% Black, 5% Hispanic, 5% Other) were included. In an adjusted analysis, no differences in opioid administration were seen by sex, burn degree, or for Blacks and Hispanics when compared with Whites. Increased MME/kg was associated with older age (10–18 years; p < 0.0001) and larger burns (>5% TBSA burned; p < 0.0001). From 2013 to 2018, median MME/kg per admission declined significantly (2013:0.21, 2018:0.09; p = 0.0103).ConclusionsNonsurgical burn patients who were older and presented with larger TBSA experienced marked increases in opioid utilization. Overall, opioid administration decreased over time. 相似文献
7.
Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method 总被引:2,自引:0,他引:2
Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations. 相似文献
8.
The goal of palliative care is the achievement of the best quality of life for patients and their families. Eyes are generally the first features of the face to be noticed. Loss of an eye is a traumatic event which has a crippling effect on the psychology of the patient. Several ocular and orbital disorders require surgical intervention that may result in ocular defects. An ocular prosthesis is fabricated to restore the structure, function, and cosmetics of the defects created by such conditions. Although an implant eye prosthesis has a superior outcome, due to economic factors it may not be a feasible option for all patients. Therefore, a custom-made ocular prosthesis is a good alternative. This case report presents a palliative treatment for a patient with an enucleated eye by fabricating a custom ocular prosthesis which improved his psychological, physical, social, functional, emotional and spiritual needs. 相似文献
9.
Husain M. Gheewala Snehajit Wagh Surajsinh A. Chauhan Sonam M. Devlekar Shruti Bhave Dharmesh J. Balsarkar 《The Indian journal of surgery》2017,79(3):254-255
Blunt abdominal trauma mostly results from motor vehicle accidents, recreational accidents, falls or assaults with commonly injured internal organs being the spleen, liver, retroperitoneum, small bowel, kidneys, bladder, colorectal, diaphragm and pancreas. Gastric rupture is quite uncommon. Isolated gastric perforations following blunt trauma to the abdomen are mostly seen in paediatric patients. It is uncommon in adult patients and even rarer is the occurrence of double gastric perforations. We report here with a case of isolated double gastric perforation in a 24-year-old male patient following vehicular accident. 相似文献
10.
Raymond F. Hamilton Zheqiong Wu Megha Thakkar Somenath Mitra 《Inhalation toxicology》2013,25(11-12):429-438
AbstractObjective: The toxicity of silver nanomaterials in various forms has been extensively evaluated, but the toxicity of silver nanocarbon composites is less well understood. Therefore, silver-carbon nanotube composites (Ag-MWCNT-COOH) and silver-graphene oxide composites (Ag-GO) were synthesized by microwave irradiation and evaluated in two in vitro cell models.Materials/Methods: Toxicity of silver nanosphere (Ag), Ag-MWCNT-COOH and Ag-GO were analyzed by MTS assay and LDH assay in primary C57BL/6 murine alveolar macrophages and human THP-1 cells. Activation of NLRP3 inflammasome by particle variants in these models was done by proxy using LPS co-culture and IL-1β release.Results: The results depended on the model, as the amount of Ag on the modified carbon resulted in slightly increased toxicity for the murine cells, but did not appear to affect toxicity in the human cell model. IL-1β release from carbon particle-exposures was decreased by the presence of Ag in both cell models. Suspensions of Ag-MWCNT-COOH, Ag-GO and Ag in artificial lysosomal fluid were prepared and ICP-MS was used to detect Ag ions concentration in three silver suspension/solutions. The amount of Ag ions released from Ag-MWCNT-COOH and Ag-GO were similar, which were both lower than that of Ag nanospheres.Conclusions: The results suggest the bioactivity of silver composites may be related to the amount of Ag ions released, which can be dependent on the cell model under investigation. 相似文献