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C J Czura

Publications and source records attributed to C J Czura.

5 recordsLinked to original sources
PubMed2005

Autonomic neural regulation of immunity.

The 'cytokine theory of disease' states that an overproduction of cytokines can cause the clinical manifestations of disease. Much effort has been expended to determine how cytokines are regulated in normal health. Transcriptional, translational and other molecular control mechanisms protect the host from excessive cytokine production. A recent discovery revealed an unexpected pathway that inhibits macrophage cytokine production. The inflammatory reflex is a physiological pathway in which the autonomic nervous system detects the presence of inflammatory stimuli and modulates cytokine production. Afferent signals to the brain are transmitted via the vagus nerve, which activates a reflex response that culminates in efferent vagus nerve signalling. Termed the 'cholinergic anti-inflammatory pathway', efferent activity in the vagus nerve releases acetylcholine (ACh) in the vicinity of macrophages within the reticuloendothelial system. ACh can interact specifically with macrophage alpha7 subunits of nicotinic ACh receptors, leading to cellular deactivation and inhibition of cytokine release. This 'hard-wired' connection between the nervous and immune systems can be harnessed therapeutically in animal models of inflammatory disease, via direct electrical stimulation of the vagus nerve, or through the use of cholinergic agonists that specifically activate the macrophage alpha7 subunit of the ACh receptor. Autonomic dysfunction has been associated with human inflammatory diseases including rheumatoid arthritis, diabetes and sepsis; whether this dysfunction results from the inflammatory component of these diseases, or is actually an underlying cause, is now less clear. The description of the cholinergic anti-inflammatory now brings to the fore several new therapeutic strategies for inflammatory disease, and suggests that many of these diseases may actually be diseases of autonomic dysfunction.

Autonomic Nervous System↗
PubMed2001

Balloon blunt-tip trocar for laparoscopic cholecystectomy: improvement over the traditional Hasson and Veress needle methods.

BACKGROUND AND PURPOSE: Laparoscopic cholecystectomy (LC) is a routine procedure for most general surgeons, yet the technical aspects of gaining access to the peritoneal cavity continue to be quite diverse. We describe a prospective review of 180 LCs using three access techniques: open balloon blunt-tip trocar (BBTT), open Hasson (HA), and closed Veress needle (VN). We favor the BBTT because it is designed to avoid all sharp instrumentation and offers superior seal and mobility, as well as expeditious and easy abdominal access. PATIENTS AND METHODS: The techniques and devices were evaluated prospectively with regard to simplicity of access, leakage of carbon dioxide, access time, and complications. All patients underwent LC by one of two Board-certified surgeons. RESULTS: The mean time to insertion of the laparoscope for the BBTT (3.5 +/- 0.99 minutes) was significantly less than the insertion time for the VN technique (5.2 +/- 0.9 minutes, P < 0.05). The insertion time for the BBTT was also less than for the standard HA approach (4.25 +/- 1.0 minutes; P < 0.05). There were no visceral or vascular injuries noted, but CO2 leakage and subcutaneous insufflation of gas experienced in the standard HA and VN groups resulted in lengthened operative times. One patient in the BBTT group experienced a postoperative port-site herniation, which was repaired primarily without consequence. CONCLUSION: The BBTT is an established, safe alternative to blind access for LC. Our technique is simple and rapid and avoids most of the technical difficulties encountered by other open access devices. We believe this method provides surgeons with an option that is efficient and easier to perform than most other conventional open-access laparoscopic techniques.

Cholecystectomy, Laparoscopic↗
PubMed2001

Mind over immunity.

The central nervous system regulates the innate immune system by elaborating anti-inflammatory hormone cascades in response to bacterial products and immune mediators. We recently discovered that the central nervous system also responds via acetylcholine-mediated efferent signals carried through the vagus nerve. Nicotinic cholinergic receptors expressed on macrophages detect these signals and respond with a dampened cytokine response. Vagus nerve stimulators can mimic this response and can prevent lethal endotoxemia. This newly appreciated cholinergic anti-inflammatory pathway provides a neural substrate to study brain-immune interactions and might be harnessed for therapy of cytokine-mediated disease.

Acetylcholine↗
PubMed2001

Dual roles for HMGB1: DNA binding and cytokine.

Effective therapies against overwhelming Gram-negative bacteremia, or sepsis, have eluded successful development. The discovery that tumor necrosis factor (TNF), a host-derived inflammatory mediator, was both necessary and sufficient to recapitulate Gram-negative sepsis raised cautious optimism for developing a targeted therapeutic. However, the rapid kinetics of the TNF response to infection defined an extremely narrow window of opportunity during which anti-TNF therapeutics could be successfully administered. HMGB1 was previously studied as a DNA-binding protein involved in DNA replication, repair, and transcription; and as a membrane-associated protein that mediates neurite outgrowth. A decade-long search has culminated in our identification of HMGB1 as a late mediator of endotoxemia. HMGB1 is released by macrophages upon exposure to endotoxin, activates many other pro-inflammatory mediators, and is lethal to otherwise healthy animals. Elevated levels of HMGB1 are observed in the serum of patients with sepsis, and the highest levels were found in those patients that died. The delayed kinetics of HMGB1 release indicate that it may be useful to target this toxic cytokine in the development of future therapies.

Animals↗