Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Bacteria and viruses are different classes of pathogens. Hence, the body uses different molecular "receptors" to detect them in order to mount an immune defense. Paradoxically, while the detection systems differ, the immune defenses the body employs to clear the system of viral or bacterial infection are much the same. So are the symptoms. Fighting off bacteria or viruses can produce the same fatigue, inflammation or hacking cough.

An article in Nature dated July 23, 2003, explains how microorganisms as disparate as viruses and bacteria can share such a common bottom line. It's titled "Identification of Lps2 as a key transducer of MyD88-independent TIR signaling." Its co-authors are immunologists at the Scripps Research Institute in La Jolla, Calif.

"The proximal reason for these similar symptoms," said the paper's senior author, Scripps Professor Bruce Beutler, "is a single protein." The molecule, called Trif or Tricam, associates with different receptors that detect a virus or bacterium on the surfaces of human cells. Trif helps turn these positive detections into immune reactions. Significantly, Trif is the top-most protein shared by the pathway that detects Gram-negative bacteria and most viruses.

"You could imagine that blocking this pathway would have a pretty strong anti-inflammatory effect in a diverse range of infectious diseases," said Beutler, who identified and cloned the Trif gene (called Lps2). He and his co-authors mapped the Lps2 mouse gene, which has a counterpart gene in humans. TLRs (Toll-like receptors) act as primary innate immune sensors, responding to specific molecules of microbial origin.

"This is the first time," Beutler observed, "that anyone has identified a protein that directly responds to the signals the innate immune system sends when it recognizes both bacteria and viruses. In addition, Trif could be a potential target for intervening in diseases in which the innate human system plays a role, as in sepsis. Innate immunity is essential for survival in a world filled with microbial pathogens because innate system cells are the body's first responders.

"Sepsis infection results from a runaway cascade of inflammation in response to a bacterial infection in which Trif is involved from the start. If drugs might be designed that could modulate the function of Trif," Beutler suggested, "they might help to improve the prognosis for sepsis.

"Two percent of all individuals admitted to a hospital suffer from sepsis," he added, "which is one of the top 10 causes of both infant and adult mortality in the U.S. In 1999, it directly inflicted more than 30,000 deaths. The prognosis for sepsis - the presence of pathogens or their toxins in blood or tissue - is dire. It can threaten many parts of the body, from bones to brains, and death from septic shock may come in a matter of hours."

Which Vitamin D Analogue Is Better In Treating Chronic Kidney Disease?

Dialysis patients taking a particular intravenous vitamin D formulation have a survival advantage over patients given an older and more commonly prescribed version of vitamin D. Led by a physician at Massachusetts General Hospital, a three-year study found that patients receiving the newer drug had a 16 percent greater chance of survival than those prescribed the older formulation.

This finding is reported in the New England Journal of Medicine (NEJM) dated July 31, 2003. The report is titled "Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy."

"Elevated calcium and phosphorus levels after therapy with injectable vitamin D for treating secondary hyperparathyroidism may accelerate vascular disease," the NEJM article pointed out. "It may hasten death in patients undergoing long-term hemodialysis. Paricalcitol [Zemplar, Abbott Laboratories] appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol [Calcitjex, Abbott Laboratories] the standard form of injectable vitamin D."

The 36-month patient follow-up period resulted in an 18 percent lower mortality rate for paricalcitol than calcitriol's 22.3 percent.

Secondary hyperparathyroidism is a common consequence of chronic kidney disease. It results from abnormal regulation of calcium and phosphate homeostasis. The disorder and its dramatic clinical consequences, are preventable. Early administration of calcium supplements or vitamin D attenuates the development and progression of hyperparathyroidism.

An accompanying editorial noted, "The approximately 8 percent greater representation of blacks in the paricalcitol group could be important because the population of black patients with chronic kidney disease is at increased risk for severe hyperparathyroidism as well as cardiovascular disease. Black patients' risk of hyperparathyroidism may reflect their well-documented low intake of dietary calcium and high intake of dietary phosphorus. This would set the stage for subtle degrees of overstimulation of the parathyroid gland, even before the onset of renal disease."

The editorial calls "strongly for a randomized, controlled clinical trial of vitamin D analogues in the management of this disease to determine precisely whether one vitamin D analogue is superior to another." It concludes: "Despite the intriguing findings of the current study, the data do not permit any claim that paricalcitol is superior in the management of chronic kidney disease."

Rats Treated With L-DOPA Respond To Electrical Stimuli Of Brain Synapses, Plus/Minus Dyskinesia

Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia (harmful involuntary movements). Neurologists at the University of Rome divided hemiparkinsonian rats treated chronically with L-DOPA into two groups. In response to the treatment, one cohort showed motor improvement without dyskinesia; the other developed debilitating dyskinesia. The co-authors report their findings in Nature Neuroscience for May 2003, under the title "Loss of bi-directional striatal synaptic plasticity in L-DOPA-induced dyskinesia." The paper then compared brain cortex synapses between the two rodent groups.

High-frequency stimulation induced long-term potentiation in both contingents of animals. Control and non-dyskinetic rodents showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not. The negative effect was prevented by activation of the D1 subclass of dopamine receptors.