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The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a three component complex aimed at increasing the delivery efficiency and adding new avenues to its mechanism of action. This study focuses on pharmacokinetic studies of the isoniazid-sucrose–copper (II)-PEG-3350 complex. The assays include the Plasma Protein Binding Assay (85.8%), Caco-2 Permeability Assay (B→AP app , 0.13 × 10 −6 cm/s), Cytochrome P450 Inhibition Assay (i.e. CYP2B6, IC 50 = 7.26 μM), In vitro microsomal Stability Assay (t 1/2 NADPH-Dependent > 240 min), and HepG2 Cytotoxicity (no toxicity). The National Cancer Institute's 60 cell line panel is used to measure activity against cancer cells. The percent growth values averaged over all 60 cell lines indicates the complex has no anti-cancer activity, which also suggests a lack of general toxicity. It also provides data for the complexes specificity against Mycobacterium tuberculosis .

College athletic departments have a responsibility to provide a safe environment for student-athletes; however, most colleges do not have a crisis management plan that includes procedures for displaced student-athletes or alternate facilities to perform athletic events. Continuity of operations planning ensures athletic programs are equipped to maintain essential functions during, or shortly after, a disruption of operations due to possible hazards. Previous studies have identified a lack of emergency preparedness and continuity planning in college athletic departments. The purpose of this article is to illustrate in detail one approach to disaster planning for college athletic departments, namely the Federal Emergency Management Agency (FEMA) continuity of operations framework. By adhering to FEMA guidelines and promoting a best practices model, athletic programs can effectively plan to address potential hazards, as well as protect the organization's brand, image, and financial sustainability after a crisis event.

The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis.

In the first phase of this study, the binding of hydroxychloroquine to the copper(II) cation is examined using liquid chromatography-mass spectrometry (LC-MS), matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), Fourier transform-ion cyclotron resonance spectrometry (FT-ICR) and nuclear magnetic resonance ((1)H and (13)C NMR) in one and two dimensions. The data suggest the metal-ligand complex is a polarity adaptive molecule. In the second phase of the study, the complexes activity is tested against the National Cancer Institute's 60 cell line panel. Its anti-cancer activity is compared to quinine, Cu(II)-quinine and hydroxychloroquine. It serves as a base line for future anti-cancer complexes in which hydroxychloroquine is utilized for its ability to impact cell autophagy.

Bryostatin structures share a commonality of a central bryophan ring, but each differs due to two groups (R(1) and R(2)) that are attached to the bryophan ring via ester bonds. This research examines the impact that conditions such as UV light, acidic and basic conditions can have on the bryostatin structure in the presence of octanoic acid and water. Mass spectrometry (MS) measurements suggest that bryostatin can easily rearrange into various structures under natural conditions by reacting with carboxylates that are ubiquitous in nature. A second set of measurements suggest bryostatin can be hydrolyzed by water, a reaction that has significant implications in both medicinal applications and extraction procedures.

The bacterium responsible for causing tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis (XDR-TB) strains. In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, and LC–MS are used to study different aspects of the Copper–polyethylene glycol (PEG)–Amikacin complex. The Cu(II) cation and the aggregate formed by PEG serve as a carrier for the antibiotic. Several Cu–PEG–Amikacin complex variations were tested against NIH-NIAID cell lines containing both resistant and nonresistant strains of M. tuberculosis.

In recent years, the bacterium responsible for tuberculosis has been increasing its resistance to antibiotics resulting in new multidrug resistant Mycobacterium tuberculosis (MR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study we use several analytical techniques including NMR, FT-ICR, TOF-MS, LC-MS and UV/Vis to study the copper-capreomycin complex. The copper (II) cation is used as a carrier for the antibiotic capreomycin. Once this structure was studied using NMR, FT-ICR, and MALDI-TOF-MS, the NIH-NIAID tuberculosis cell line for several Tb strains (including antibiotic resistant strains) were tested against up to seven variations of the copper-capreomycin complex. Different variations of copper improved the efficacy of capreomycin against Tb up to 250 fold against drug resistant strains of Tb.

Iron chelators are being examined as a potential class of pharmaceutical agents to battle different types of cancer as well as iron overload diseases. In recent studies, iron binding species such as desferrioxamine, triapine, tachpyridine, Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using published chemical equilibrium values (stability constants, equilibrium constants), it is argued that an iron chelator cannot competitively remove iron from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a cancerous cell to die. This type of reaction (DFO(aq) + [Fe(2+,3+)-Hb] --[Fe(2+,3+)-DFO] + Hb) has been proposed in a number of published studies using circumstantial evidence. It is argued that iron chelators can potentially interact with iron from ferritin or iron that has precipitated or flocculated as oxyhydroxide under physiological pH's. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca(2+), Zn(2+) or K(+). A number of siderophores and natural products that have the ability to bind Fe(3+)/Fe(2+) as well as other cations are discussed in terms of their potential pharmaceutical activity as chelators. Chemical equilibria between cations and pharmaceutical agents, which are rarely quantitated in explaining medicinal mechanisms, are used to show that chelators can bind and remove iron and other cations from physiologically important systems required for cell survival and propagation.

In this computational study, geometric factors are calculated by applying semi-empirical methods (PM3) that support experimental evidence from this lab where bryostatins can bind trivalent iron with six Fe-O bonds forming an octahedral geometry. The geometric factors are calculated for all 20 structures (Fe3+ bound to bryostatin 1-20) as a neutral, monovalent, and divalent species. The average Fe-O bond distances and bond angles are compared to those of known marine and terrestrial siderophores. From these two data sets, we then examined other known marine natural products (MNPs) that can form a hexavalent complex with six Fe-O bonds and draw conclusions about their potential biological role as marine siderophores. This computational data indicates that Fe(III) strongly bonds to a host of MNPs, increasing their water solubility, contracting their structure, hence allowing transport through cell membranes more readily, and in some cases, stabilizing ester bonds that are susceptible to hydrolysis. It is argued that administering medicinally bryostatin, its analogs or other MNPs as a ferric complex, holds some fundamental chemical advantages compared to its administration as a neutral uncomplexed species.

A reflex are from the medial elbow ligaments to the forearm pronator muscles was shown to exist in the feline model. A single articular branch emerging from the median nerve and converging on the medial collateral ligament was identified and stimulated with supramaximal pulses of 100 microseconds duration at a rate of 10 pulses/s. Stimulation of the articular nerve elicited myoelectric activity in the flexor digitorum superficialis, flexor digitorum profundus, flexor carpi radialis, flexor carpi ulnaris, and pronator teres. Transection of the articular nerve between the electrodes and the median nerve resulted in the disappearance of any myoelectric activity in the muscles, thus confirming the afferent nature of the articular nerve. The mean time delay from the application of the stimulus to the corresponding myoelectric discharge ranged from 3.2 to 5.8 ms for the 5 muscles. The existence of a fast-acting reflex arc from the medial elbow ligaments to the forearm muscles both confirms the concept of ligamentomuscular protective synergy (shown to exist in the knee, shoulder, and ankle joints) and extends it to the elbow. This reflex arc has significant implications for both the planning of elbow surgery while preserving the neural supply of the ligaments and for the planning of postsurgical or conservative therapeutic rehabilitation modalities.

This study was designed to investigate dopaminergic mechanisms in the control of corticosteroid secretion. Eight rhesus monkeys received metoclopramide (200 micrograms/kg) or domperidone (200 and 400 micrograms/kg) with 5% dextrose (vehicle), or with dopamine (4 micrograms/kg/min) infusions begun 60 min before administration of the dopamine antagonist. Metoclopramide, in the presence of vehicle, increased plasma aldosterone concentrations from 4.8 +/- 0.6 ng/dl to a maximum of 36 +/- 4.7 ng/dl and PRL concentrations from 7.6 +/- 1.1 ng/ml to a maximum of 120.5 +/- 8.0 ng/ml. Administration of metoclopramide resulted in a rise in plasma 18-hydroxycorticosterone from 10.2 +/- 1.3 ng/dl to a maximum concentration of 49.6 +/- 4.5 ng/dl. Plasma concentrations of electrolytes, PRA, plasma cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxocorticosterone, were not altered by metoclopramide. Domperidone, in both doses, markedly increased plasma PRL concentrations but had no effect on plasma 18-OHB or aldosterone concentrations. Dopamine infusion inhibited the aldosterone response to metoclopramide and the prolactin response to metoclopramide and domperidone. The results of this investigation demonstrate that aldosterone responses to metoclopramide and prolactin responses to metoclopramide and domperidone are mediated by their antagonist activity at dopamine receptors.

In this perplexing case, a child with signs of apparent hip pain was treated for a sewing needle embedded in the sole of the foot. The diagnosis of foreign body easily could have been missed, because the external signs were minimal and the clinical findings indicated hip disease. However, the child's extreme distress seemed inconsistent with the initial normal findings. Only reexamination and looking beyond the obvious led to the diagnosis.