NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria.

Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA, comparable to artesunate and artemether.

Nitric oxide synthase dysfunction contributes to impaired cerebroarteriolar reactivity in experimental cerebral malaria.

Cerebrovascular dysfunction plays a key role in the pathogenesis of cerebral malaria. In experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA, cerebrovascular dysfunction characterized by vascular constriction, occlusion and damage results in impaired perfusion and reduced cerebral blood flow and oxygenation, and has been linked to low nitric oxide (NO) bioavailability. Here, we directly assessed cerebrovascular function in ECM using a novel cranial window method for intravital microscopy of the pial microcirculation and probed the role of NOS isoforms and phosphorylation patterns in the impaired vascular responses.

Bis(3,5-dimethyl-1H-pyrazole-κN)silver(I) hexa-fluorido-anti-monate.

The title compound, [Ag(C(5)H(8)N(2))(2)]SbF(6), contains an Ag(+) cation almost linearly bonded to two N atoms of dimethylpyrazole ligands [N-Ag-N = 176.54 (18)°]. The structure exhibits hydrogen bonding between the two dimethyl-pyrazole H atoms and two F atoms of one hexa-fluorido-anti-monate anion.

Outflow facility in mice with a targeted type I collagen mutation.

Purpose: Transgenic Col1a1(r/r) mice develop elevated intraocular pressure (IOP) with an open angle and progressive optic nerve axon loss. The present study was undertaken to evaluate aqueous outflow facility and its age dependence in these mice.

Methods: Homozygous B6;129S4-Col1a1(tm1Jae) mice and corresponding wild-type Col1a1(+/+) mice from 12 to 56 weeks of age were anesthetized, and IOP was measured with a microneedle.

Partitioning of the aqueous outflow in rat eyes.

Purpose: To determine the effect of molecular size on the drainage route of dextrans injected into the rat anterior chamber (AC).

Methods: Anesthetized adult rats received monocular AC injections of a mixture of 3-kDa dextran-cascade blue, 40-kDa dextran-Texas red, and 500-kDa dextran-FITC. After exsanguination of the rats 2, 4, 6, 12, 24, or 72 hours later, the eyes, facial lymph nodes, and cervical lymph nodes were isolated, and the total content of each dextran type was determined by spectrofluorometry.

Galanin acts at GalR1 receptors in spinal antinociception: synergy with morphine and AP-5.

The neuropeptide galanin (Gal) and its receptors (GalR1, GalR2, and GalR3) are expressed in spinal cord. We have characterized the pharmacology of the antinociceptive effects of intrathecally (i.t.