ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Chewing Gum Headaches

Aspartame, a popular dietetic sweetener, may provoke headache in some susceptible individuals. Herein, we describe three cases of young women with migraine who reported their headaches could be provoked by chewing sugarless gum containing aspartame.     

Management of intraabdominal testicle during laparoscopic hernia repair

A 22-year-old man who had previously undergone work-up for right cryptorchidism and been diagnosed as having right testicular absence was referred for repair of a right inguinal hernia. A laparoscopic approach was chosen for this patient, and at the time of laparoscopic herniorrhaphy, a small intraabdominal testicle was visualized and removed laparoscopically.Laparoscopy has served as an excellent procedure for locating intraabdominal testes and planning the most appropriate treatment for many cryptorchid patients. Until recently, atrophic testes located within the abdominal cavity through use of a laparoscope were removed via an open technique. Advances in laparoscopy now enable detection and definitive treatment for these patients without the need for large, more painful incisions.The laparoscopic approach to this patient enabled diagnosis and management of his cryptorchidism and provided a means for repair of his hernia.     

The aging thyroid. I. A description of lesions and an analysis of their age and sex distribution

Two types of follicular change in the thyroid are described. The first represents an involutional change in which colloid cysts (macrofollicles) are often found. The second represents a hyperplastic-dysplastic (microfollicular) lesion. Two types of change in calcitonin (C) cells are also described, one of which may represent an involutional process, although this is not certain. The second is a hyperplastic (micronodular) lesion, but without evidence of dysplasia. An infiltration of lymphocytes is also commonly encountered. Only about 15% of cases after age 60 are free of the follicular and lymphoid lesions. Both the macro- and microfollicular lesions show a statistically significant increase with age, as do the lymphoid lesion and its derivative Hashimoto's thyroiditis. C cell micronodules also appear to increase with age, but there are too few such cases for a reliable statistical analysis. An analysis of combinations of the follicular and lymphoid lesions show a particularly frequent association of the microfollicular and lymphoid lesions. Evidence is presented suggesting that many microfollicular lesions may represent clones of mutated cells, and that the lymphocytes may be targeted to these microfollicles. Lymphocytes were rarely found in association with C cell micronodules. Within individual thyroids there is considerable variation in the proportion of each lesion when combinations are present. Thus with advancing age there is an increasing heterogeneity of thyroid structure that may confound attempts to correlate structural and physiological changes with age.     

What we know about the genetics of asthma at the beginning of the 21st century

Summary The understanding of the genetic controls that lead to the development of asthma is essential to its proper diagnosis and management. As we enter the 21 st century, the goals of genetic research in asthma and allergies will be to: 1) identify genetic factors, 2) define environmental cofactors, 3) characterize how genes and the environment work together to cause disease, 4) develop treatment and prevention measures, including drugs designed for the individual's genetic make-up.