Physostigmine is a cholinesterase inhibitor belonging to the carbamate class. It is also referred to as an indirectly acting cholinomimetic because, by inhibiting acetylcholinesterase, it potentiates responses to endogenous acetylcholine, which is released from cholinergic nerve endings in the central nervous system and periphery. Physostigmine is a water-soluble tertiary amine, which, unlike quaternary amine carbamates, can enter the central nervous system.

Carbachol is a structural analog of acetylcholine and has agonist activity at muscarinic and nicotinic cholinergic receptors. It is like acetylcholine in being a quaternary amine and having a positive charge at all pH values. A major difference from acetylcholine is that carbachol is not hydrolyzed by cholinesterases. Carbachol can also modulate cholinergic neurotransmission by stimulating prejunctional cholinergic receptors, which augment (nicotinic) or attenuate (muscarinic) the release of acetylcholine.

Dipivefrine is a member of a class of pharmaceutical agents known as prodrugs. Dipivefrine is not active itself but is biotransformed in the body to epinephrine. It is used in the treatment of open-angle and secondary glaucoma.

Timolol is a non-selective, beta adrenoceptor antagonist at beta-1 and beta-2 adrenoceptors. It lacks the partial agonist and local anesthetic properties that some drugs in this class have. It is most commonly used to treat glaucoma and cardiovascular diseases. Timolol is moderately lipophilic. Absorption of timolol after topical application to the eye is significant and can produce systemic side effects.

Isoflurophate is a long acting cholinesterase inhibitor and potent miotic. It works as an indirect acting parasympathomimetic agent to reduce intraocular pressure. Also known as diisopropyl phosphofluoridate (Dyflos), it is an irreversible organophosphate cholinesterase inhibitor. It and its analogues were studied extensively during the Second World War as substances that could be employed as war gases because of their volatility and rapid absorption from the lungs. Due to its toxicity it is only used in the treatment of patients with open angle glaucoma or other chronic glaucomas which are not controlled with other less toxic short acting agents.

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C1q is the first subcomponent of the classical complement pathway that can interact with a range of biochemically and structurally diverse self and nonself ligands. The globular domain of C1q (gC1q), which is the ligand-recognition domain, is a heterotrimeric structure composed of the C-terminal regions of A (ghA), B (ghB), and C (ghC) chains. The expression and functional characterization of ghA, ghB, and ghC modules have revealed that each chain has specific and differential binding properties toward C1q ligands. It is largely considered that C1q-ligand interactions are ionic in nature; however, the complementary ligand-binding sites on C1q and the mechanisms of interactions are still unclear. To identify the residues on the gC1q domain that are likely to be involved in ligand recognition, we have generated a number of substitution mutants of ghA, ghB, and ghC modules and examined their interactions with three selected ligands: IgG1, C-reactive protein (CRP), and pentraxin 3 (PTX3). Our results suggest that charged residues belonging to the apex of the gC1q heterotrimer (with participation of all three chains) as well as the side of the ghB are crucial for C1q binding to these ligands, and their contribution to each interaction is different. It is likely that a set of charged residues from the gC1q surface participate via different ionic and hydrogen bonds with corresponding residues from the ligand, instead of forming separate binding sites. Thus, a recently proposed model suggesting the rotation of the gC1q domain upon ligand recognition may be extended to C1q interaction with CRP and PTX3 in addition to IgG1.

C-reactive protein (CRP) is not an acute-phase protein in mice, and therefore, mice are widely used to investigate the functions of human CRP. It has been shown that CRP protects mice from pneumococcal infection, and an active complement system is required for full protection. In this study, we assessed the contribution of CRP's ability of activating the classical pathway of complement in the protection of mice from lethal infection with virulent Streptococcus pneumoniae type 3. We used two CRP mutants, Y175A and K114A. The Y175A CRP does not bind C1q and does not activate complement in human serum. The K114A CRP binds C1q and activates complement more efficiently than wild-type CRP. Passively administered, both CRP mutants and the wild-type CRP protected mice from infection equally. Infected mice injected with wild-type or mutant CRP had reduced bacteremia, resulting in lower mortality and increased longevity compared with mice that did not receive CRP. Thus, the protection of mice was independent of CRP-mediated activation of the classical pathway of complement. To confirm that human CRP does not differentiate between human and mouse complement, we analyzed the binding of human CRP to mouse C1q. Surprisingly, CRP did not react with mouse C1q, although both mutant and wild-type CRP activated mouse C3, indicating species specificity of CRP-C1q interaction. We conclude that the mouse is an unfit animal for exploring CRP-mediated activation of the classical complement pathway, and that the characteristic of CRP to activate the classical complement pathway has no role in protecting mice from infection.

Rats lesioned shortly after birth with 6-hydroxydopamine are posed as a near-ideal model of severe Parkinson's disease, because of the non-lethality of the procedure, near-total destruction of nigrostriatal dopaminergic fibers, near-total dopamine (DA)-denervation of striatum, reproducibility of effect, and relative absence of overt behavioral effects - there is no aphasia, no adipsia, and no change in motor activity. In vivo microdialysis findings reinforce the utility of the animal model, clearly demonstrating L-DOPA beneficial actions without an increase in hydroxyl radical production.

Mast cells often are found in a perivascular location but especially in mucosae, where they may response to various stimuli. They typically associate with immediate hypersensitive responses and are likely to play a critical role in host defense. In this chapter, a common airway pathogen, Moraxella catarrhalis, and a commensal bacterium, Neiserria cinerea, are used to illustrate activation of human mast cells. A human mast cell line (HMC-1) derived from a patient with mast cell leukemia was activated with varying concentrations of heat-killed bacteria. Active aggregation of bacteria over mast cell surfaces was detected by scanning electron microscopy. The activation of mast cells was analyzed by nuclear factor-kappaB (NF-kappaB) activation and cytokine production in culture supernatants. Both M. catarrhalis and N. cinerea induce mast cell activation and the secretion of two key inflammatory cytokines, interleukin-6 and MCP-1. This is accompanied by NF-kappaB activation. Direct bacterial contact with mast cells appears to be essential for this activation because neither cell-free bacterial supernatants nor bacterial lipopolysaccharide induce cytokine secretion.