Slavery and Empire: The Development of Slavery in the Natchez District, 1720-1820

“Slavery and Empire: The Development of Slavery in the Natchez District, 1720- 1820,” examines how slaves and colonists weathered the economic and political upheavals that rocked the Lower Mississippi Valley. The study focuses on the fitful— and often futile—efforts of the French, the English, the Spanish, and the Americans to establish plantation agriculture in Natchez and its environs, a district that emerged as the heart of the “Cotton Kingdom” in the decades following the American Revolution. Before American planters established their hegemony over Natchez, the town was a struggling outpost that changed hands three times over the course of the century. “Slavery and Empire” explores how enslaved Africans struggled to find their footing on this unstable ground. Slaves seized upon many weapons to claim their freedom. Some cast their lots with Indians hostile to their colonial masters, while others tested their chains in the courts. Slaveowners often found the field tilted against them; wars, regime changes, and an unstable economy conspired to place their mastery—not to mention their titles to land and slaves—on unsound footings. The pitched battles between slaves and their owners, along with the contests between colonial subjects and their countries, had a profound effect on a region that became the heart of the Deep South. As the French began to settle the Natchez District in the early 1720s, only seventy slaves worked in the fertile Natchez fields for their European masters. Sixty-four of these slaves were African, the rest were bound Native Americans. Over the next century, the slave numbers increased gradually and when Mississippi became a state in 1817, the first census taken shows a slave majority in all counties that the Americans carved out of the Natchez District. Yet Natchez experienced a very uneven development over the course of the century that bridged the first French attempt and American success in creating a slave society in the district. Although slave numbers multiplied, planters, imperial officials, and the enslaved sought every means to contest one another over measures of control and power in Natchez. These constant conflicts, coupled with economic crisis and imperial strive in the lower Mississippi Valley, made for a bumpy road to the pinnacle of planter power and the uncontested reign of King Cotton in the 1820s

The Many Faces of American Captivity and its Legal Matrix: A Review Essay

Reviewing: Alfred L. Brophy - University, Court, and Slave: Pro-Slavery Thought in Southern Colleges and Courts and the Coming of the Civil War; Paul Finkelman - Supreme Injustice: Slavery in the Nation’s Highest Court; William Kiser - Borderlands of Slavery: The Struggle over Captivity and Peonage in the American Southwes

Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems

Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD

L-dopa and dopamine-(R)-alpha-lipoic acid conjugates as multifunctional codrugs with antioxidant properties

A series of multifunctional codrugs (1-4), obtained by joining L-Dopa (LD) and dopamine (DA) with (R)-R-lipoic acid (LA), was synthesized and evaluated as potential codrugs with antioxidant and iron-chelating properties. These multifunctional molecules were synthesized to overcome the pro-oxidant effect associated with LD therapy. The physicochemical properties, together with the chemical and enzymatic stabilities of synthesized compounds, were evaluated in order to determine both their stability in aqueous medium and their sensitivity in undergoing enzymatic cleavage by rat and human plasma to regenerate the original drugs. The new compounds were tested for their radical scavenging activities, using a test involving the Fe (II)- H2O2-induced degradation of deoxyribose, and to evaluate peripheral markers of oxidative stress such as plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma. Furthermore, we showed the central effects of compounds 1 and 2 on spontaneous locomotor activity of rats in comparison with LD-treated animals. From the results obtained, compounds 1-4 appeared stable at a pH of 1.3 and in 7.4 buffered solution; in 80% human plasma they were turned into DA and LD. Codrugs 1-4 possess good lipophilicity (log P > 2 for all tested compounds). Compounds 1 and 2 seem to protect partially against the oxidative stress deriving from auto-oxidation and MAO-mediated metabolism of DA. This evidence, together with the “in vivo” dopaminergic activity and a sustained release of the parent drug in human plasma, allowed us to point out the potential advantages of using 1 and 2 rather than LD in treating pathologies such as Parkinson’s disease, characterized by an evident decrease of DA concentration in the brain

Codrugs linking L-Dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson’s Disease

A series of multifunctional codrugs (1-6) were synthesized to overcome the pro-oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an antioxidant effect superior to that of N-acetylcysteine (NAC). After intracerebroventricular injection of codrug 4, the levels of DA in the striatum were higher than those in LD-treated groups, indicating that this compound has a longer half-life in brain than LD

Lipid nanocarriers loaded with natural compounds: Potential new therapies for age related neurodegenerative diseases?

Article in pressAge related neurodegenerative disorders (ARND) are presented as the most debilitating and challenging diseases associated with the central nervous system. Despite the advent of active molecules with a positive role on neurodegenerative mechanisms, many of the current therapeutic strategies remain ineffective in treating or preventing ARND. Lipid nanocarriers have emerged as efficient delivery systems with the capability to cross biological barriers, especially the blood brain barrier (BBB). Also, when associated to natural compounds, lipid nanocarriers have demonstrated to be an interesting alternative to ARND therapies with multiple beneficial effects. This comprehensive review focus on state-of-the-art lipid based nanocarriers for the delivery of natural compounds targeting neurodegeneration. A critical analysis of published reports will be also provided giving indications to researchers about the most promising ARND nanotherapy strategies.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013. Marlene Lúcio acknowledges the exploratory project funded by FCT with the reference IF/00498/2012. Telma Soares acknowledges COMPETE 2020 “Programa Operacional Competitividade e internacionalização”info:eu-repo/semantics/publishedVersio