New York State Climate Impacts Assessment Chapter 05: Ecosystems.

The people of New York have long benefited from the state's diversity of ecosystems, which range from coastal shorelines and wetlands to extensive forests and mountaintop alpine habitat, and from lakes and rivers to greenspaces in heavily populated urban areas. These ecosystems provide key services such as food, water, forest products, flood prevention, carbon storage, climate moderation, recreational opportunities, and other cultural services. This chapter examines how changes in climatic conditions across the state are affecting different types of ecosystems and the services they provide, and considers likely future impacts of projected climate change.

Soil carbon sequestration in global working lands as a gateway for negative emission technologies.

The ongoing climate crisis merits an urgent need to devise management approaches and new technologies to reduce atmospheric greenhouse gas concentrations (GHG) in the near term. However, each year that GHG concentrations continue to rise, pressure mounts to develop and deploy atmospheric CO removal pathways as a complement to, and not replacement for, emissions reductions. Soil carbon sequestration (SCS) practices in working lands provide a low-tech and cost-effective means for removing CO from the atmosphere while also delivering co-benefits to people and ecosystems.

Binding of lopinavir to human alpha1-acid glycoprotein and serum albumin.

HIV protease inhibitors are an important component of highly active antiretroviral therapy used to treat pregnant women infected with HIV. They have a low placental transfer and are highly plasma protein bound. This study was carried out to determine the unbound fraction of lopinavir in cord blood, and to characterize the binding of lopinavir to alpha(1)-acid glycoprotein (AAG) and human serum albumin (HSA), and displacement by ritonavir.

Ibuprofen suppresses interleukin-1beta induction of pro-amyloidogenic alpha1-antichymotrypsin to ameliorate beta-amyloid (Abeta) pathology in Alzheimer's models.

Epidemiological and basic research suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) should protect against the most common forms of Alzheimer's disease (AD). Ibuprofen reduces amyloid (Abeta) pathology in some transgenic models, but the precise mechanisms remain unclear. Although some reports show select NSAIDs inhibit amyloid production in vitro, the possibility that in vivo suppression of amyloid pathology occurs independent of Abeta production has not been ruled out.

Pharmacokinetics of lamivudine in cats.

Objective: To characterize the pharmacokinetics of lamivudine (3TC) in cats.

Animals: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats.

Procedure: Cats were randomly alloted into 3 groups, and lamivudine (25 mg/kg) was administered i.

Pharmacokinetics of zidovudine in cats.

Objective: To characterize the pharmacokinetics of zidovudine (AZT) in cats.

Animals: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats.

Procedure: Cats were randomly alloted into 3 groups, and zidovudine (25 mg/kg) was administered i.

Pharmacokinetic evaluation of 3'-azido-2', 3'-dideoxyuridine-5'-O-valinate-hydrochloride as a prodrug of the anti-HIV nucleoside 3'-azido-2', 3'-dideoxyuridine.

3'-Azido-2', 3'-dideoxyuridine (AZDU, AzddU, CS-87) has been shown to have potent anti-HIV activity in vitro. However, the compound exhibits a relatively short half-life and incomplete oral bioavailability in humans. In an effort to improve the pharmacokinetic properties of AZDU, prodrug 3'-azido-2',3'-dideoxyuridine-5'-O-valinate hydrochloride (AZDU-VAL) was synthesized by the esterification of 5'-OH function in AZDU.

Simultaneous determination of 3'-azido-2',3'-dideoxyuridine and novel prodrugs in rat plasma by liquid chromatography.

3'-Azido-2',3'-dideoxyuridine (AZDU) is a nucleoside analog structurally similar to zidovudine (AZT) with proven activity against human immunodeficiency virus (HIV). The purpose of this study was to develop and validate a high-performance liquid chromatographic (HPLC) method to quantitatively determine AZDU and its novel prodrugs in rat plasma simultaneously. A reversed-phase gradient elution HPLC method was developed to quantitate AZDU and its prodrugs, N3-pivaloyloxymethyl-3'-azido-2',3'-dideoxyuridine (I), 5'-pivaloyloxymethyl-3'-azido-2',3'-dideoxyuridine (II), 5'-O-valinyl-3'-azido-2',3'-dideoxyuridine hydrochloride (III) and 5'-O-phenylalanyl-3'-azido-2',3'-dideoxyuridine hydrochloride (IV), in rat plasma.

Pharmacokinetics of imipenem in dogs.

Objective: To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro.

Animals: 6 adult dogs.

Procedure: A 3-way crossover design was used.

Characterization of selective estrogen receptor modulator (SERM) activity in two triarylethylene oxybutyric acids.

Previously we identified 4-[1-(4-hydroxyphenyl)-2-phenylbuten-1-yl]phenoxy-n-butyric acid (4HBA) and its des-hydroxy analog (BA) as potential selective estrogen receptor modulators (SERMs) in the ovariectomized (OVX) rat. The aim of the present study was to characterize comprehensively the effects of 4HBA and BA in both the OVX rat and in estrogen-responsive cells. Thus, 4HBA was found to be an estrogen antagonist with partial agonist efficacy in estrogen-responsive reporter gene and estrogen-dependent proliferation assays (MVLN cells and MCF-7 human breast cancer cells, respectively).

Identification of new triarylethylene oxyalkanoic acid analogues as bone selective estrogen mimetics.

Previously, the estrogen receptor (ER) ligand 4-[1-(p-hydroxyphenyl)-2-phenylethyl]phenoxyacetic acid (5) was found to have differential bone loss suppressive effects in the ovariectomized (OVX) rat approaching those of selective ER modulators (SERMs) such as tamoxifen. In an effort to improve efficacy, analogues of this compound were prepared which incorporated features designed to reduce polarity/ionizability. Thus, the acetic acid side chain of 5 was replaced by n-butanoic acid and 1H-tetrazol-4-ylmethyl moieties, to give 8 and 10, respectively.

Pharmacokinetics of bis(t-butyl-SATE)-AZTMP, a bispivaloylthioethyl prodrug for intracellular delivery of zidovudine monophosphate, in mice.

The pharmacokinetics of a bispivaloylthioethyl prodrug of zidovudine monophosphate (AZTMP), bis(t-butyl-SATE)-AZTMP, and intracellular conversion of the prodrug to AZTMP were characterized following intravenous (i.v.) and oral (p.

Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats.

Objective: To determine pharmacokinetics of troglitazone in healthy cats after i.v. and oral administration of a single dose of the drug.

Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships and pharmacokinetics.

Significant improvements in antiviral therapy have been realized over the past 10 years. Numerous nucleoside analogs, as well as prodrugs of active compounds, have been synthesized and tested for anti-HIV activity. In addition to the five nucleoside analogs currently used clinically for the treatment of HIV infection, a broad spectrum of anti-HIV nucleoside analogs (including 2',3'-dideoxynucleoside analogs, oxathiolanyl 2',3'-dideoxynucleoside analogs, dioxolanyl 2',3'-dideoxynucleoside analogs, carbocyclic 2',3'-dideoxynucleoside analogs and acyclic nucleoside analogs) and their prodrugs (including ester prodrugs, phospholipid prodrugs, dihydropyridine prodrugs, pronucleotides and dinucleotide analogs), targeted at HIV reverse transcriptase, are reviewed with focus on structure-activity relationships, cellular pharmacology and pharmacokinetics.

Simultaneous determination of zidovudine and its monophosphate in mouse plasma and peripheral red blood cells by high-performance liquid chromatography.

Novel prodrugs for the intracellular delivery of zidovudine monophosphate (AZTMP) have recently been designed. To investigate the bioconversion and pharmacokinetic profiles of these compounds, an analytical method for the simultaneous determination of zidovudine (AZT) and AZTMP in mouse plasma and peripheral red blood cells was developed. Mouse whole blood samples were treated with TBAHS, EDTA and NaH2PO4, and separated into plasma and red blood cell portions.

Age-related changes in protein binding of drugs: implications for therapy.

The plasma protein binding of drugs, particularly those that are highly bound, may have significant clinical implications. Although protein binding is a major determinant of drug action, it is only one of a myriad of factors that influence drug disposition. The extent of protein binding is a function of drug and protein concentrations, the affinity constant for the drug-protein interaction and the number of protein binding sites per class of binding site.

Preclinical investigation of L-FMAU as an anti-hepatitis B virus agent.

Preclinical aspects of a potent anti-hepatitis B virus (HBV) L-nucleoside, 1-(2-fluoro-5-methyl-beta-L-arabino-furanosyl)uracil (L-FMAU) are described. L-FMAU was prepared from L-ribose derivatives via either L-xylose or L-arabinose. L-FMAU shows potent antiviral activity against hepatitis B virus (EC50 5.

Pharmacokinetics of (-)-beta-D-dioxolane guanine and prodrug (-)-beta-D-2,6-diaminopurine dioxolane in rats and monkeys.

(-)-beta-D-Dioxolane guanine (DXG) is a nucleoside analog possessing potent activity against human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), and hepatitis B virus (HBV) in vitro. Owing to the limited aqueous solubility of DXG, (-)-beta-D-2,6-diaminopurine dioxolane (DAPD), a more water-soluble prodrug of DXG, is being developed for clinical use. The purpose of this study was to characterize the pharmacokinetics of DXG after administration of DXG and DAPD to rats and monkeys.

Pharmacokinetics of the antihyperglycemic agent metformin in cats.

Objective: To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.

Animals: 6 healthy adult ovariohysterectomized cats.

Procedure: In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally.

Pharmacokinetics of 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil in woodchucks.

1-(2-Fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU) is a nucleoside analog with potent in vitro activity against hepatitis B virus (HBV) and Epstein-Barr virus. The purpose of this study was to characterize the disposition of L-FMAU following oral and intravenous administration in the woodchuck animal model. The numerous similarities between woodchuck hepatitis virus and HBV infection justify the use of the woodchuck as an animal model for preclinical studies of anti-HBV agents in vivo.

Biotransformation and pharmacokinetics of prodrug 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine and its antiviral metabolite 9-(beta-D-1,3-dioxolan-4-yl)guanine in mice.

9-(beta-D-1,3-Dioxolan-4-yl)guanine (DXG) exhibits potent antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) in vitro. However, since DXG possesses limited aqueous solubility, a more water soluble prodrug of DXG, 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine (APD), was synthesized. The purpose of this study was to characterize the pharmacokinetics of APD and its antiviral metabolite DXG in mice.

Nonlinear pharmacokinetics of 5-fluorouracil in rats.

The effects of dose on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated following intravenous administration of 5-FU at 10, 50, and 100 mg/kg to adult male Sprague-Dawley rats. Six rats were studied at each dose level. The dose-normalized area under the curve (AUC) was significantly higher after administration of 100 mg/kg (1.

Lymphatic targeting of anti-HIV nucleosides: distribution of 2',3'-dideoxyinosine after intravenous and oral administration of dipalmitoylphosphatidyl prodrug in mice.

In the search for prodrugs of 2',3'-dideoxyinosine (ddI) with potential for improving the delivery of the nucleoside analogue to the lymphatic system, we synthesized dipalmitoylphosphatidyl-2',3'-dideoxyinosine (DPP-ddI) and its pharmacokinetics were investigated in mice. The disposition of ddI in plasma and lymph nodes was examined following intravenous and oral administration of parent nucleoside (100 mg/kg) and DPP-ddI (400 mg/kg, equivalent to 100 mg/kg of ddI). Concentrations of ddI were determined by HPLC.

High-performance liquid chromatographic determination of (-)-beta-D-2-aminopurine dioxolane and (-)-beta-D-2-amino-6-chloropurine dioxolane, and their metabolite (-)-beta-D-dioxolane guanine in monkey serum, urine and cerebrospinal fluid.

(-)-beta-D-2-Aminopurine dioxolane (APD), (-)-beta-D-2-amino-6-chloropurine dioxolane (ACPD) and dioxolane guanine (DXG) are nucleoside analogues possessing potent activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in vitro. APD and ACPD are metabolized in vivo to yield DXG. Reversed-phase HPLC analytical methodologies were developed for the simultaneous determination of APD and DXG, and for ACPD and DXG in monkey serum, urine and cerebrospinal fluid (CSF).