China
Africa
Explore chapters and articles related to this topic
Antimetabolites
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Gemcitabine (GemzarTM) is similar in structure to cytarabine, except that the hydroxy group at the 2′-position of the N1-sugar moiety has been replaced with two fluorine atoms (Figure 3.11). Intracellularly, it is metabolized to biologically active diphosphate and triphosphate nucleosides that are responsible for inhibiting DNA synthesis and inducing apoptosis. It is used alone intravenously in elderly patients or for palliative treatment or in combination with cisplatin as first-line treatment for locally advanced or metastatic non-small-cell lung cancer. It is also used in locally advanced or metastatic pancreatic cancer. In the UK, it is recommended by NICE for the first-line treatment of locally advanced or metastatic non-small-cell lung (as monotherapy or in combination with cisplatin), pancreatic, bladder (with cisplatin), epithelial ovarian (with carboplatin), and breast (with paclitaxel) cancers.
Garlic
Published in Robert E.C. Wildman, Richard S. Bruno, Handbook of Nutraceuticals and Functional Foods, 2019
Sharon A. Ross, Craig S. Charron
A few studies have documented that garlic can inhibit platelet aggregation in vivo. Steiner and Lin235 provided evidence that consumption of AGE reduced epinephrine and collagen-induced platelet aggregation, although it failed to influence adenosine diphosphate-induced aggregation. Their studies also provided evidence that platelet adhesion to fibrinogen could be suppressed by consumption of this garlic supplement. In a study with 23 subjects who had consumed 5 mL of AGE daily for 13 weeks, AGE did inhibit adenosine diphosphate-induced aggregation.236 Finally, DAS, a constituent of garlic oil, induced a reduction in adenosine-induced platelet aggregation in women with type 2 diabetes mellitus.237
Bone Microcirculation
Published in John H. Barker, Gary L. Anderson, Michael D. Menger, Clinically Applied Microcirculation Research, 2019
Regulation of bone blood flow by O2 has not been studied sufficiently to decide if its mechanism differs from that in other tissues. While the existence of paired veins and arteries is well established, the degree to which they extend to arterioles and venules that could exhibit counter-current diffusion of O2 is not known for bone. In other tissues, smooth muscle cell hypoxia is accentuated in a counter-current environment, and mitochondrial support for contraction diminishes. As a result, the cell relaxes, allowing “reactive hyperemia” to develop.40,45 In bone, one product of metabolism, adenosine diphosphate (ADP), has been shown to induce vasodilation.42 Studies from other tissues suggest alternatives to this negative-feedback metabolic regulatory mechanism by which hypoxia stimulates arteriolar dilation.
The PEARL study: a prospective two-group pilot PrEP promotion intervention for cisgender female sex workers living in Baltimore, MD, U.S.
Published in AIDS Care, 2021
D. Pelaez, N. P. Weicker, J. Glick, J. V. Mesenburg, A. Wilson, H. Kirkpatrick, E. Clouse, S. G. Sherman
PEARL consisted of baseline, 3-, and 6-month study visits, each of which included a survey, bloodwork, case management services, and compensation for control and intervention participants. Baseline visits were the most intensive and lasted approximately 2 h. The audio computer-assisted self-interview (A-CASI) survey lasted 45–60 min. Survey items, informed by the literature and our prior research, included: socio-demographics and structural vulnerabilities; health service access and utilization; HIV/STI history and risk behaviors; PrEP use, interest, barriers, and facilitators; sex work history; sexual and physical violence; arrest and prison history; stigma; police encounters; social support; resilience; and mental health history (Decker et al., 2017; Sherman et al., 2019). A whole blood sample was collected at baseline and both follow-up visits for tenofovir diphosphate testing through dried blood spot and plasma, conducted at the Hopkins’ Clinical Pharmacology Analytical Laboratory. At the last study visit, intervention participants were invited to participate in a 45-minute qualitative interview led by an experienced ethnographer to discuss PrEP and the acceptability of study content and delivery. These interviews gauged participants’ exposure to and perceptions of novel intervention components (e.g., mHealth, small group sessions, PNs).
An overview of ProTide technology and its implications to drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Michaela Serpi, Fabrizio Pertusati
A ProTide is a cyclic or acyclic nucleoside aryl phosphate (or phosphonate) masked with an amino acid ester promoiety linked via P–N bond (Figure 1). Such prodrug is capable to cross the cell membrane by passive diffusion and therefore it does not require a membrane transporter [15]. Intracellularly, the ProTide is activated [16–18] (Figure 1) by a carboxylic-ester hydrolase or carboxypeptidase-type enzyme which mediated the hydrolysis of the carboxylic ester of the amino acid leading to intermediate (I). The ester cleavage is followed by an internal nucleophilic attack of the acid residue on the phosphorus atom, displacing the aryloxy group and giving the transient formation of the putative five-membered cyclic intermediate (II). The first experimental evidence of the formation of this cyclic intermediate has been recently reported [19]. This cyclic anhydride is rapidly hydrolyzed to the corresponding aminoacyl phosphor(n)amidate (III) which undergoes P–N bond cleavage, either mediated by an enzyme with phosphoramidase activity or spontaneous hydrolysis to eventually release the phosphorylated parent drug (P-NA). The nucleoside monophosph(on)ate generated then undergoes two successive phosphorylations to generate the active species (PPP-NA) (Figure 1). In some cases, the monophosphate or the diphosphate species might as well have biological activity [20,21].
Recent approaches to gout drug discovery: an update
Published in Expert Opinion on Drug Discovery, 2020
Naoyuki Otani, Motoshi Ouchi, Hideo Kudo, Shuichi Tsuruoka, Ichiro Hisatome, Naohiko Anzai
Enhanced ATP degradation in cells leads to adenosine diphosphate (ADP) or AMP accumulation, which accelerates purine degradation converting to urate. Alcohol consumption promotes ATP conversion to AMP, resulting in an increased urate production [8]. Urate excretion into the urine may also be reduced due to the dehydration and metabolic acidosis associated with alcohol consumption. It has been observed that excessive intake of fructose may cause not only fatty liver and insulin resistance, but also increased urate levels. Fructose is rapidly phosphorylated in the liver, but inorganic phosphorus decreases with ATP consumption. Thus, ATP re-synthesis using inorganic phosphorus is reduced, but AMP deaminase activity, normally suppressed by inorganic phosphorus, is increased, accelerating AMP degradation through IMP and increasing urate levels. Even in an ischemic state, ATP degradation is accelerated, and urate production is increased. Furthermore, urate production increases when bone marrow cells are in a hyperproliferative state, such as in hemolytic anemia or myeloproliferative diseases, and large quantities of nucleotides are released due to tumor cell destruction during chemotherapy, resulting in increased serum urate levels.