The rule of five should not impede anti-parasitic drug development.

The "rule of 5" has become a mainstay of decision-making in the pharmaceutical industry as well as in nonindustrial (academic and institutional) drug development. However the authors of the original paper never intended for "double cutoffs" to preclude development of new drug leads for parasitic diseases

Identification of three stage-specific proteinases of Plasmodium falciparum.

We have identified and characterized three stage-specific proteinases of Plasmodium falciparum that are active at neutral pH. We analyzed ring-, trophozoite-, schizont-, and merozoite-stage parasites by gelatin substrate PAGE and characterized the identified proteinases with class-specific proteinase inhibitors. No proteinase activity was detected with rings. Trophozoites had a 28 kD proteinase that was inhibited by inhibitors of cysteine proteinases. Mature schizonts had a 35-40 kD proteinase that also was inhibited by cysteine proteinase inhibitors. Merozoite fractions had a 75 kD proteinase that was inhibited by serine proteinase inhibitors. The stage-specific activity of these proteinases and the correlation between the effects of proteinase inhibitors on the isolated enzymes with the effects of the inhibitors on whole parasites suggest potential critical functions for these proteinases in the life cycle of malaria parasites

The major neutral proteinase of Entamoeba histolytica.

FPLC anion-exchange and chromatofocusing chromatography were used to purify the major neutral proteinase from secretions of axenically cultured Entamoeba histolytica trophozoites. HM-1 strain trophozoites, which were more proteolytically active than the less virulent HK-9 strain, were used for purification of the enzyme. It is a thiol proteinase with a subunit Mr of approximately 56,000, a neutral pH optimum, and a pI of 6. The importance of this enzyme in extraintestinal amoebiasis is suggested by its ability to degrade a model of connective tissue extracellular matrix as well as purified fibronectin, laminin, and type I collagen. The enzyme caused a loss of adhesion of mammalian cells in culture, probably because of its ability to degrade anchoring proteins. Experiments with a peptide substrate and inhibitors indicated that the proteinase preferentially binds peptides with arginine at P-1. It is also a plasminogen activator, and could thus potentiate host proteinase systems

Antibiotics to improve recovery following tonsillectomy: a systematic review.

OBJECTIVE: To determine if antibiotics improve recovery following tonsillectomy. STUDY DESIGN: DATA SOURCES: Electronic databases Medline, Embase, and Cochrane Controlled Trials Register were searched using relevant search terms. Additional trials, if any, were retrieved by searching the references from all identified trials, reviews, correspondences, editorials, and conference proceedings. No language restriction was applied. STUDY SELECTION: Systematic review of trials in which antibiotic was administered as a study medication intraoperatively and/or postoperatively, in children or adults undergoing tonsillectomy or adenotonsillectomy. Only randomized, placebo-controlled, double-blind trials attaining preset quality scores were included. Outcomes analyzed: 1) pain, need for analgesia, fever, halitosis, and return to normal diet and activities; 2) secondary hemorrhage using 2 parameters-significant hemorrhage (ie, warranting readmission, blood transfusion, or return to theatre for hemostasis) and total hemorrhage; and 3) adverse events. RESULTS: Five trials met the eligibility criteria. Antibiotics significantly reduced the number of subjects manifesting fever (relative risk [RR]: 0.62, 95% confidence interval [CI]: 0.45, 0.85) and duration of halitosis (-1.94 [-3.57, -0.30] days), and marginally reduced the time taken to resume normal activity (-0.63 [-1.12, -0.14] days), but had no significant effect in reducing pain scores (-0.01 [-0.60, 0.57]) or need for analgesia. Similarly, there was no significant difference in the time taken to resume normal diet or incidence of significant and total hemorrhage, although data was underpowered to detect differences for these outcomes. In the antibiotic group 4 patients developed an adverse reaction (3 cases of rash and 1 case of oropharyngeal candidiasis), while in the control group 1 patient had an adverse reaction (rash). The RR of antibiotic-related adverse events was 2.45 (0.45, 13.31). CONCLUSION: Antibiotics appear to be effective in reducing some, but not all, morbid outcomes following tonsillectomy, and may increase the risk of adverse events. Further trials are needed to better define the role of antibiotics in facilitating post-tonsillectomy recovery. EBM RATING: A-1a