A brief, highly selective history of acute phase proteins as indicators of infection, inflammation and injury.

There is an array of plasma protein alterations that occur in a wide variety of species, including humans in response to trauma, inflammation and infections, seemingly irrespective of etiologic agent. In numerous species, these plasma proteins are part of the innate immune response. In addition, it appears that a number of the plasma proteins in this array can be predictive of morbidity and/or mortality. We propose that based on historic use, selected acute phase proteins should be included in ongoing and future non-clinical and clinical studies to help us better understand disease progression in chronic, as well as acute diseases. In addition to assess if there is a relationship between vaccine-induced inflammation and degree of protection from live, attenuated or synthetic vaccines.

Celery Seed and Related Extracts with Antiarthritic, Antiulcer, and Antimicrobial Activities.

Celery preparations have been used extensively for several millennia as natural therapies for acute and chronic painful or inflammatory conditions. This chapter reviews some of the biological and chemical properties of various celery preparations that have been used as natural remedies. Many of these have varying activities and product qualities. A fully standardized celery preparation has been prepared known as an alcoholic extract of the seeds of a plant source derived from northern India. This is termed, Celery Seed Extract (CSE) and has been found to be at least as effective as aspirin, ibuprofen, and naproxen in suppressing arthritis in a model of polyarthritis. CSE can also reduce existing inflammation in rats. CSE has also been shown to provide analgesia in two model systems. CSE, in addition to acting as an analgesic and inflammatory agent, has been shown to protect against and/or reduce gastric irritation caused by NSAIDs, as well as act synergistically with them to reduce inflammation. The CSE was fractionated by organic solvent extractions, then subjected to column chromatography followed by HPLC and was characterized by mass spectrometry. This yielded a purified component that had specific inhibitory effects on Helicobacter pylori but was not active against Campylobacter jejuni or Escherichia coli. Additionally, toxicology studies did not reveal any clear signs of toxicity at doses relevant to human use. Also, unlike many dietary supplements, the available data suggest that CSE does not significantly affect the p450 enzyme systems and thus is less likely to alter the metabolism of drugs the individual may be taking. CSE may be a prototype of a natural product that can be used therapeutically to treat arthritis and other inflammatory diseases.

Is there a role for vitamin D in the treatment of chronic pain?

A brief survey of recent literature was conducted with regard to vitamin D and pain. There is evidence for and against a role for vitamin D in the treatment of chronic pain. The contradictory findings may have to do with study design or perhaps the type and intensity of pain. To answer the question whether there is a role for vitamin D in the treatment of chronic pain, larger and longer duration studies need to be conducted. The design should also be such to assess whether vitamin D might act to increase the effectiveness of existing analgesics and/or reduce the dose and duration of their use, thereby increasing safety.

Metabolic effects of infection on protein and energy status.

A review of some of the seminal studies of metabolism during various infections indicates that similar patterns of metabolic alterations occur during these illnesses. This patterned metabolic array occurs whether the infection is caused by a gram-positive or a gram-negative bacterium, a rickettsia or a virus, or is respiratory or systemic. In all instances, the previously healthy host responds to infection with cytokine-mediated alterations that appear to occur in proportion to the infectious challenge and to the likelihood of death. These alterations also can occur in the vaccinated host, if the infectious challenge is sufficiently great. Because of their widespread occurrence and seemingly ingrained status, these metabolic alterations may be presumed to be of survival benefit to the host. Whether this patterned array of metabolic sequelae is of benefit to the host, or even to the species, its widespread and systematic occurrence allows it to be of value in assessing the safety and efficacy of vaccines and drugs to prevent or treat a wide variety of infections. In this era of bioterrorism, wherein drugs and vaccines may have to be approved for human use without clinical trials and solely on the basis of animal data, these cytokine-mediated metabolic sequelae can aid in the rational selection of drug and vaccine candidates.

Hydroxyethyl starch in balanced electrolyte solution (Hextend)--pharmacokinetic and pharmacodynamic profiles in healthy volunteers.

UNLABELLED: Hextend is a new plasma volume expander containing 6% hydroxyethyl starch (HES) in a physiologically balanced medium of electrolytes, glucose, and lactate (weight average, molecular weight 670 kDa, molar substitution 0.75). This open-label study was designed to investigate the pharmacokinetic and pharmacodynamic profiles of Hextend in 21 healthy volunteers. We infused Hextend 10 ml/kg IV over 20 min and determined serum concentrations of HES at selected intervals over a 7-day period. Serum concentration-time curves indicated mixed pharmacokinetic behavior reflecting a two-compartment model in most subjects. The median serum half-life over 7 days was 38.2 h. The balanced formulation of the suspension medium did not seem to affect distribution, metabolism, or excretion of Hextend when compared with similar HES. Pharmacodynamic analysis demonstrated decreases in some plasma components compatible with the infusion of that volume of fluid and the duration of plasma volume expansion. Other plasma components remained unchanged, reflecting the benefit of a balanced electrolyte solution. Hemodilution was observed for 24--48 h after short-term infusion of Hextend. Some hemostatic indices showed moderate changes, and serum amylase demonstrated a temporary increase. Our study suggested that Hextend has pharmacokinetic and pharmacodynamic profiles that are similar to those of other HES. IMPLICATIONS: Hextend is a new plasma volume expander containing 6% hydroxyethyl starch in a physiologically balanced medium. This open-label volunteer study demonstrated that it has pharmacokinetic and pharmacodynamic profiles similar to those of established HES.