Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

The pathogenesis of atherosclerosis: a perspective for the 1990s

https://www.cell.com/cell/pdf/S0092-8674(00)80949-6.pdf

Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199201233260406?articleTools=true

The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

/pdf/inositol-trisphosphate-and-diacylglycerol-as-second-4drzjsg27y.pdf

Inositol trisphosphate and diacylglycerol as second messengers.

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Mechanism of the cross tachyphylaxis between piperine and capsaicin in rat atria: Involvement of calcitonin gene-related peptide (CGRP)

Release of calcitonin gene-related peptide (CGRP) from perivascular nerves in the rat mesenteric artery

Pharmacokinetics of glufosinate

PURPOSE
To investigate the effects of 1% atropine eye drops on the choroidal thickness and structure of amblyopic and fellow eyes in children with hyperopic anisometropic amblyopia.


METHODS
This study included 16 children with hypermetropic anisometropic amblyopia. All patients received 1% atropine eye drops in both eyes twice a day for 7 days. In the subfoveal choroidal region, choroidal thickness, total choroidal area, luminal area, and stromal area were measured quantitatively using swept-source optical coherence tomography. The choroidal parameters of the amblyopic and fellow eyes were compared between the baseline and atropine conditions.


RESULTS
There were no significant differences in all choroidal parameters of the amblyopic eye between baseline and atropine conditions. However, the subfoveal choroidal thickness in the fellow eye was significantly higher for the atropine condition than the baseline condition. This change was accompanied by a significant increase in both the luminal and stromal areas of the choroid. The median differences of subfoveal choroidal thickness between the conditions were larger for the fellow eye (6.46%) than the amblyopic eye (0.26%).


CONCLUSIONS
The choroidal structural change induced by 1% atropine instillation was smaller for the amblyopic eye than the fellow eye in children with hyperopic anisometropic amblyopia. Mechanisms of choroidal thickness changes could be inhibited in amblyopic eyes. [J Pediatr Ophthalmol Strabismus. 20XX;XX(X):XX-XX.].

Changes in Choroidal Thickness and Structure Induced by 1% Atropine Instillation in Children With Hyperopic Anisometropic Amblyopia.

The tachykinins are a family of naturally occuring bioactive peptides, which share the common C-terminal amino acid sequence, Phe-X-Gly-Leu-Met-NH2 (Fig.1) and exhibit a wide spectrum of biological actions such as smooth muscle contraction, sialogogic action and hypotension (Ersparmer, 1981). Until recently, substance P (SP)(X=Phe) has been the only known tachykinin shown to be present in the mammalian tissues. The accumulating evidence suggest that SP is a neurotransmitter or neuromodulator in the central and peripheral nervous systems (Otsuka and Konishi, 1975; Pernow, 1983). We have recently determined the amino acid sequences of two additional and novel tachykinins (X=Va1), neurokinin A (NKA) and neurokinin B (NKB), which are remarkably similar to kassinin (Kimura et al., 1983). The identical peptides were independently reported and named differently; NKA as neuromedin L or substance K (Maggio et al., 1983; Minamino et al., 1984; Nawa et al., 1983) and NKB as neuromedin K (Kangawa et al., 1983). Pharmacologically, it was revealed that both neurokinins (NKs) possess the typical tachykinin activities and SP-E type ligand characteristics using peripheral tissues (Hunter and Maggio, 1984; Kimura et al., 1984; Nawa et al., 1984) and central nervous tissues (Buch et al., 1984; Mantyh et al., 1984; Quirion and Pilapil, 1984; Torrens et al., 1984). Electrophysiologically, it was found that both NKA and NKB have potent excitatory actions on neurons in the isolated spinal cord of neuborn rat (Matsuto et al., 1984). Moreover, we and others have shown using radioimmunoassay system that NKA and NKB are distributed unevenly in rat central nervous system (Kanazawa et al., 1984; Minamino et al., 1984). Especially, considerable amounts of NKs were found in the spinal cord and localized predominantly in the dorsal horn (Ogawa et al., 1985). Furthermore, the nucleotide sequences of two different SP precursors isolated from bovine striatum have been reported; one contains each copy of SP and NKA (substance K) while the other contains only substance P (Nawa et al., 1983). It was suggested that NKA (SK) may be coreleased with SP from the common precursor and serves as a second type of the endogenous tachykinin in mammalian tissue. These lines of evidence strongly suggested that NKs may act as neurotransmitters or neuromodulators like SP in mammalian central nervous system, especially, in the spinal cord.

Katsutoshi Goto

Papers

Mechanism of the cross tachyphylaxis between piperine and capsaicin in rat atria: Involvement of calcitonin gene-related peptide (CGRP)

Release of calcitonin gene-related peptide (CGRP) from perivascular nerves in the rat mesenteric artery

Pharmacokinetics of glufosinate

Changes in Choroidal Thickness and Structure Induced by 1% Atropine Instillation in Children With Hyperopic Anisometropic Amblyopia.

The Mammalian Tachykinins and Their Receptors: Structure-Activity Relationship of the Mammalian Tachykinins