Influence of nimodipine combined with ulinastatin on neurological function and inflammatory reaction in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVE: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Overall, 90 patients with CVS after SAH who were admitted to our hospital were enrolled in this study and randomly divided into research and control groups (n = 45 for both groups). On the basis of conventional therapy, patients in the control group were injected with ulinastatin and those in the research group were injected with ulinastatin+nimodipine through an intravenous drip for 7 days with the others the same as those of the control group. RESULTS: Blood flow velocity in all cerebral arteries was lower in the research group than in the control group after treatment (P < 0.05). Calcitonin gene-related peptide and nitric oxide levels were higher in the research group than in the control group after treatment (P < 0.05). Endothelin levels were lower in the research group than in the control group (P < 0.05). The total effective rate was higher in the research group than in the control group (P < 0.05). Glasgow Coma Scale scores were higher in the research group than in the control group (P < 0.05). CONCLUSION: The drug combination of nimodipine and ulinastatin improved blood flow and neurological function in patients with CVS after SAH and enhanced the therapeutic efficacy; the underlying mechanism may be associated with the regulation of vascular endothelial dilatation function and the inhibition of relevant inflammatory factors' expression.

Traditional Chinese medicine for septic patients undergoing ulinastatin therapy: A meta-analysis.

PURPOSE: This study aimed to assess the efficacy of traditional Chinese medicine (TCM) in septic patients treated with ulinastatin. METHODS: PubMed, EmBase, and the Cochrane library were searched up to January 2021 to identify randomized controlled trials. The weight mean difference (WMD) and relative risk (RR) with 95% confidence intervals were used with the random-effects model. RESULTS: Twenty-three randomized controlled trials with 1903 septic patients were included. TCM significantly reduced the APACHE II score (WMD: -5.18; P < .001), interleukin-6 (WMD: -63.00; P < .001), tumor necrosis factor-α (WMD: -8.86; P < .001), c-reactive protein (WMD: -9.47; P < .001), mechanical ventilation duration (WMD: -3.98; P < .001), intensive care unit stay (WMD: -4.18; P < .001), procalcitonin (WMD: -0.53; P < .001), lipopolysaccharide (WMD: -9.69; P < .001), B-type natriuretic peptide (WMD: -159.87; P < .001), creatine kinase isoenzyme MB (WMD: -45.67; P < .001), cardiac troponin I (WMD: -0.66; P < .001), and all-cause mortality risk (RR: 0.55; P < .001). CONCLUSIONS: TCM lowers inflammation levels and reduces the risk of all-cause mortality for septic patients.

Protective effect of rhubarb combined with ulinastatin for patients with sepsis.

BACKGROUND: Sepsis is the leading cause of death in critically ill patients. Ulinastatin (UTI), a protease inhibitor, and rhubarb, used as a traditional Chinese medication, are proved to be effective in treating sepsis, but the effect of the combination therapy of these two drugs on sepsis remains unclear. This study aimed to investigate the effect of the combination treatment of UTI and rhubarb on sepsis patients. METHODS: A total of 75 septic patients were randomly divided into control group, UTI group, Rhubarb group, and UTI plus Rhubarb group. Clinical data and score of Acute Physiology and Chronic Health Evaluation II (APACHE II) were collected; lymphocyte subtypes in the peripheral blood were analyzed before and after the 5-day treatment in the Intensive Care Unit. RESULTS: All the therapeutic interventions (UTI alone, rhubarb alone, or UTI plus rhubarb) significantly reduced the levels of C-Reactive protein, white blood cell density, lactic acid, and APACH II scores, and elevated the levels of CD4/CD8, but only UTI plus rhubarb treatment obviously decreased the level of procalcitonin. CONCLUSION: This study suggested that the combination of UTI and rhubarb may be a promising therapeutic scheme to ameliorate sepsis.

Tamarind Trypsin Inhibitor in Chitosan-Whey Protein Nanoparticles Reduces Fasting Blood Glucose Levels without Compromising Insulinemia: A Preclinical Study.

In vivo studies show the benefits of the trypsin inhibitor isolated from tamarind (Tamarindusindica L.) (TTI) seeds in satiety and obesity. In the present study, TTI nanoencapsulation (ECW) was performed to potentialize the effect of TTI and allow a controlled release in the stomach. The impact on glycemia, insulin, and lipid profile was evaluated in Wistar rats overfed with a high glycemic index diet (HGLI). Characterization of the nanoparticles and in vitro stability in simulated gastrointestinal conditions, monitored by antitrypsin activity and HPLC, was performed. ECW and empty nanoparticles (CW) were administered by gavage, using 12.5 and 10.0 mg/kg, respectively. Both nanoformulations presented a spherical shape and smooth surface, with an average diameter of 117.4 nm (24.1) for ECW and 123.9 nm (11.3) for CW. ECW maintained the antitrypsin activity (95.5%) in the gastric phase, while TTI was completely hydrolyzed. In Wistar rats, the nanoformulations significantly reduced glycemia and HOMA IR, and ECW increased HDL-c compared to CW (p < 0.05).Pancreas histopathology of animals treated with ECW suggested an onset of tissue repair. Thenanoencapsulation provided TTI protection, gradual release in the desired condition, and improvement of biochemical parameters related to carbohydrate metabolism disorders,without compromising insulinemia.

Rhubarb combined with trypsin inhibitor for severe acute pancreatitis: A systematic review and meta-analysis.

The objective of this study is to evaluate the efficacy and safety of rhubarb combined with trypsin inhibitor for severe acute pancreatitis (SAP). This meta-analysis was performed in accordance with the Transparent Reporting of Systematic Reviews and Meta-analysis protocol (PRISMA-P) and Cochrane Handbook. Relevant studies from inception to 2016 were searched through 7 related databases. The Cochrane Library was searched to assess the bias of the included trials. Data were analysed with Review Manager 5.3 software. A total of 16 randomized controlled trials (RCTs) involving 912 participants with SAP were included in this meta-analysis. The result showed that when compared with trypsin inhibitor used alone, rhubarb combined with trypsin inhibitor showed intensive effects on decreasing mortality, increasing overall efficacy, shorting length of hospitalization, reducing abdominal pain relief time, and decreasing the level of serum amylase. There was no serious adverse event reported in these RCTs. It should be noted that potential publication bias was observed. This meta-analysis demonstrated that rhubarb combined with trypsin inhibitor could be an effective and safe treatment for patients with SAP. However, the small sample size and poor quality of these RCTs should be noted. And more rigorously designed, multicentre, large-scale worldwide trials with more practitioners and higher quality are required.

Xuebijing combined with ulinastation benefits patients with sepsis: A meta-analysis.

BACKGROUND: The potential benefits and possible risks associated with Xuebijing when combined with ulinastatin for sepsis treatment are not fully understood. METHODS: Databases, such as PubMed, Web of Science, CNKI, WanFang and VIP, were searched to collect randomized, controlled trials. Studies were screened, data were extracted, and the methodological quality was assessed by two reviewers independently. A meta-analysis was carried out with Stata 11.0 software. RESULTS: A total of 16 studies involving 1192 participants were enrolled for meta-analysis based on the inclusion and exclusion criteria. The results showed that compared with the group using routine therapies and the group using a single administration of either ulinastatin or Xuebijing, the trial group using Xuebijing combined with ulinastatin was significantly superior in the following aspects: mortality (RR = 0. 54,95% CI (0. 41, 0. 70, P = .000), 7 d APACHE II (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), duration of mechanical ventilation (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), average length of time in the intensive care unit (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), incidence of multiple organ dysfunction syndromes (RR = 0. 54, 95% CI (0.41, 0. 70, P = .000), interleukin-6 (SMD = -1.36,95%CI (-2.46, -0.27), P = .000), lipopolysaccharide (SMD = -9.92, 95%CI (-11.7, -7.90), P = .006), and procalcitonin (SMD = -0.30, 95%CI (-0.34, -0.26), P = .012). CONCLUSIONS: Our results found that Xuebijing when combined with ulinastatin was superior to both routine therapies and the single administration of either ulinastatin or Xuebijing. This finding provides a new therapeutic option for the treatment of sepsis.

Therapeutic effect of ulinastatin on pulmonary fibrosis via downregulation of TGF­ß1, TNF­α and NF­κB.

Pulmonary fibrosis is a chronic, progressive, lethal lung disease characterized by alveolar cell necrosis and dysplasia of interstitial fibrotic tissue, resulting in loss of lung function and eventual respiratory failure. Previously, glucocorticoid drugs were used to treat this lung disorder. However, positive responses were recorded in less than half of treated patients and the cytotoxicity caused by high dosage treatment is still a concern. The present study investigated whether ulinastatin, a typical urinary trypsin inhibitor that mitigates numerous inflammatory responses, could be a treatment option for lung fibrosis. The results demonstrated that ulinastatin had the ability to ameliorate interstitial fibrosis and alveolar exudates and to protect against lung diseases induced by smoke, irradiation or silica particles. The mechanism of ulinastatin resulted in the downregulation of inflammatory cascades: Transforming growth factor­ß1, tumor necrosis factor­α and nuclear factor­κB, as demonstrated by western blotting and ELISA. Ulinastatin treatment with a high dose (100,000 U/kg body weight/day) resulted in an attenuated inflammatory response, and inhibited fibrosis formation in lungs, suggesting that ulinastatin may become a part of a clinical therapeutic strategy.

Autodigestion by migrated trypsin is a major factor in small intestinal ischemia-reperfusion injury.

BACKGROUND: The pathophysiological role of pancreatic digestive hydrolases in intestinal ischemia-reperfusion (I/R) injury is still not clear. Here, we studied whether ischemia-induced injury to the small intestine can be explained by the autodigestion hypothesis. MATERIALS AND METHODS: Mesenteric I/R was induced in rats by superior mesenteric artery occlusion (90 min) and reopening (120 min). Thirty minutes before superior mesenteric artery occlusion, aprotinin (14.7 mg/kg), orlistat (5 mg/kg), and their combination or α1-proteinase inhibitor (60 mg/kg) were injected into the lumen of the small intestine. Systemic and vital parameters, intestinal microcirculation, and mucosal barrier function were monitored during the observation phase; markers of small intestinal injury, as well as trypsin-, chymotrypsin-, elastase-, and lipase-like activities in intestinal effluates were assessed at the end. RESULTS: The pattern of small intestinal injury correlated inversely with the local alterations in microvascular tissue perfusion and corresponded with the intestinal distribution of trypsin-like activity. Aprotinin almost completely inhibited trypsin-like activity (P < 0.05) and significantly reduced intestinal tissue injury. Combined with orlistat, it also increased the postischemic blood pressure (P < 0.05) but not the intestinal barrier function. Macroscopic as well as the histologic alterations were decreased by α1-proteinase inhibitor, which significantly improved postischemic blood pressure (P < 0.05). CONCLUSIONS: The I/R-induced pattern of small intestinal injury is likely to result from both local differences in tissue ischemia and the digestive activity of migrated pancreatic trypsin. Therefore, administration of aprotinin and orlistat into ischemic small intestines may be a therapeutic option in patients with a poor diagnosis.

Oral Cancer Chernoprevention: Current Status and Future Direction.

The aim of this study is to review the current status of cancer chemoprevention and its effectiveness in treatment of oral premalignant lesions and prevention of their progression to oral cancer. The challenges encountered in the different oral cancer chemoprevention clinical trials, including lack of surrogate endpoints, reversal of histologic premalignant changes as study endpoints, tobacco use, human papillomavirus, delivery system, adverse effects and risk of bias in clinical studies, are presented.

Anti-tumoral effects of a trypsin inhibitor derived from buckwheat in vitro and in vivo.

Native buckwheat, a common component of food products and medicine, has been observed to inhibit cancer cell proliferation in vitro. The aim of the present study was to evaluate the in vitro and in vivo anti-tumoral effects of recombinant buckwheat trypsin inhibitor (rBTI) on hepatic cancer cells and the mechanism of apoptosis involved. Apoptosis in the H22 cell line induced by rBTI was identified using MTT assays, DNA electrophoresis, flow cytometry, morphological observation of the nuclei, measurement of cytochrome C and assessment of caspase activation. It was identified that rBTI decreases cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies and DNA fragmentation. rBTI-induced apoptosis occurred in association with mitochondrial dysfunction, leading to the release of cytochrome C from the mitochondria to the cytosol, as well as the activation of caspase-3, -8 and -9. In conclusion, the results of the present study suggested that rBTI specifically inhibited the growth of the H22 hepatic carcinoma cell line in vitro and in vivo in a concentration-dependent and time-dependent manner, while there were minimal effects on the 7702 normal liver cell line. In addition, rBTI­induced apoptosis in H22 cells was, at least in part, mediated by a mitochondrial pathway via caspase-9.

Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels.

OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30-60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated.

In vivo efficacy of anuran trypsin inhibitory peptides against staphylococcal skin infection and the impact of peptide cyclization.

Staphylococcus aureus is a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weak in vitro inhibitory activities against S. aureus, but several had strong antibacterial activities against S. aureus in an in vivo murine wound infection model. pYR, an immunomodulatory peptide from Rana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg(-1). Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

Beneficial effects of trypsin inhibitors derived from a spider venom peptide in L-arginine-induced severe acute pancreatitis in mice.

HWTI is a 55-residue protein isolated from the venom of the spider Ornithoctonus huwena. It is a potent trypsin inhibitor and a moderate voltage-gated potassium channel blocker. Here, we designed and expressed two HWTI mutants, HWTI-mut1 and HWTI-mut2, in which the potassium channel inhibitory activity was reduced while the trypsin inhibitory activity of the wild type form (approximately 5 EPU/mg) was retained. Animal studies showed that these mutants were less toxic than HWTI. The effects of HWTI and HWTI-mut1 were examined in a mouse model of acute pancreatitis induced by intraperitoneal injection of a large dose of L-arginine (4 mg/kg, twice). Serum amylase and serum lipase activities were assessed, and pathological sections of the pancreas were examined. Treatment with HWTI and HWTI-mut1 significantly reduced serum amylase and lipase levels in a dose dependent manner. Compared with the control group, at 4 mg/kg, HWTI significantly reduced serum amylase level by 47% and serum lipase level by 73%, while HWTI-mut1 significantly reduced serum amylase level by 59% and serum lipase level by 72%. Moreover, HWTI and HWTI-mut1 effectively protected the pancreas from acinar cell damage and inflammatory cell infiltration. The trypsin inhibitory potency and lower neurotoxicity of HWTI-mut1 suggest that it could potentially be developed as a drug for the treatment of acute pancreatitis with few side effects.

Ulinastatin as a neuroprotective and anti-inflammatory agent in infant piglets model undergoing surgery on hypothermic low-flow cardiopulmonary bypass.

OBJECTIVE: Infants are potentially more susceptible to brain injury mediated via cell death attributed to cardiopulmonary bypass (CPB) especially with prolonged hypothermic low flow (HLF). We hypothesized that a human urinary protease inhibitor (ulinastatin), by its anti-inflammatory effect, would reduce central nervous system (CNS) injury during HLF. METHODS: Fifteen general-type infant piglets were randomized to ulinastatin group (group U, n = 5), control group (group C, n = 5), and sham operation group (group S, n = 5). Routine CPB was established after median thoracotomy in group U and C under anesthesia. When the temperature of infant piglets dropped down to 25 °C, low-flow CPB (50 ml·kg(-1) ·min(-1) ) was instituted. After 120 min of aortic cross-clamping and 20- to 30-min rewarming, the aortic cross-clamp was removed and finally the piglet was weaned from CPB. Five thousand units per killogram of ulinastatin and equivalently normal saline were, respectively, given at the beginning of and at aortic declamping in group U and group C. group S just received sham median thoracotomy. Venous blood samples were taken immediately after anesthesia induction in all three groups, 5- and 120-min post CPB in both group U and C, respectively; plasma markers of inflammation and CNS injury were compared. Pathology results of hippocampus were observed by light microscopy. RESULTS: Statistically significant differences between group C and U were noted in the expression of inflammatory markers such as IL-10, TNF-α and neuron-specific enolase at 120-min post CPB. Brain injuries were observed in both groups (index cases and controls) and were milder in group U. CONCLUSIONS: In our study, HLF CPB on infant piglets resulted in brain injury, and ulinastatin might reduce the extent of such injury.

Effect of hyperbaric oxygen and ulinastatin on plasma endotoxin, soluble CD14, endotoxin-neutralizing capacity and cytokines in acute necrotizing pancreatitis.

BACKGROUND: We sought to study the effect of a combination therapy comprised of hyperbaric oxygen (HBO) and ulinastatin on the plasma levels of endotoxin, soluble CD14 (sCD14), endotoxin neutralizing capacity (ENC) and cytokines in acute necrotizing pancreatitis (ANP) in rats. METHODS: We randomly allocated 90 Sprague-Dawley rats into 6 groups: group 1 (ordinary control), group 2 (sham operation), group 3 (ANP), group 4 (ANP with HBO), group 5 (ANP with ulinastatin) and group 6 (ANP with HBO and ulinastatin). We induced ANP by retrograde injection of 3.5% sodium taurocholate (2.5 mL/kg) via the pancreatic duct. Five minutes after induction, animals in groups 5 and 6 were infused with ulinastatin (20 000 U/kg) via the portal vein. Thirty minutes after induction, animals in groups 4 and 6 received HBO therapy. We collected samples 3, 6 and 10 hours after induction of ANP. RESULTS: We found that the plasma level of endotoxin in group 3 was significantly higher than in group 4 (3, 6 h, both p < 0.001), group 5 (3 h, p < 0.001; 6 h, p = 0.014) and group 6 (both p < 0.001). The level of plasma sCD14 in group 3 was significantly higher than in group 4 (3, 6 h, both p < 0.001), group 5 (3, 6 h, both p = 0.001) and group 6 (3 h, p < 0.001; 6 h, p = 0.001). The plasma endotoxin and sCD14 levels in group 6 were significantly lower than in groups 4 and 5. The plasma ENC level in group 6 was significantly higher than in groups 3, 4 and 5 (p < 0.001). The ENC level in groups 4 and 5 were higher than in group 3, but there was no significant difference. The plasma level of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in group 6 were significantly lower than in groups 3, 4 and 5 (p < 0.001). The TNF-alpha and IL-6 levels in groups 4 and 5 were lower than in group 3, but there was no significant difference. CONCLUSION: The use of an early combination therapy of HBO and ulinastatin was more effective than either therapy alone in the treatment of ANP.

Antitrypsin activity of extracts from Ecballium elaterium seeds.

The antitrypsin activity of extracts obtained from two different seed types of Ecballium elaterium, was tested in vitro. The presence of trypsin inhibitors in three chromatographed samples for each extract, showed a strong and specific antitrypsin activity.

[Clinical trial with a new immunomodulatory strategy: treatment of severe sepsis with Ulinastatin and Maipuxin].

OBJECTIVE: To evaluate the efficacy of treatment of severe sepsis by combining anti-inflammatory and immune-enhancing agents. METHODS: Multiple-center, prospective, randomized, controlled designs. Cases were from surgical or general ICU of 26 university teaching hospitals. Totally, 433 adult patients developing severe sepsis with Marshall score 5-20 were enrolled. Patients received either standard treatment based on SSC direction (as group control), or additional Ulinastatin (urinary trypsin inhibitor) 300 K units per day+thymosin alpha1 (Maipuxin) 1.6 mg per day for 7 days (as treatment group 1, adopted in the first trial), or double dosage of the above agents (as treatment group 2, adopted in the second trial). The outcome of 28 and 90 days, APACHEII and Marshall score, monocyte HLA-DR/CD14+ at several points until 28 days, and the lengths of ICU stay, antibiotics usage and mechanical ventilation were determinated. RESULTS: In the first trial (91 cases), there was no significant difference in variables between treatment group 1 and control at 28 days. In the second trial (342 cases), the mortality of treatment group 2 decreased from 38.32% to 25.14% (P=0.0088), compared with group control at 28 days, and from 52.10% to 37.14% (P=0.0054) on 90 days. APACHEIIalso decreased from 14.32 to 12.70 (P=0.0384) and monocyte HLA-DR/CD14+ increased from 40.13% to 51.65% (P=0.0092) on 28 days in treatment group 2. Other variables had no significant differences between two groups. CONCLUSION: Treatment by the combining anti-inflammatory and immune enhancing agents can significantly improve the outcome of severe sepsis. The efficacy of this therapy seems to be dose dependent on.

Induction of apoptosis by buckwheat trypsin inhibitor in chronic myeloid leukemia K562 cells.

Buckwheat is an ancient and specialty grain in China. Due to its unique chemical and bio-activity components, buckwheat has been found to have many uses in food products and medicine. However, very little is known about the toxicity of protease inhibitors from buckwheat. Here, the possible effects of a recombinant buckwheat trypsin inhibitor (rBTI) on the induction of apoptosis of the human K562 cell line were investigated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays and flow cytometric analysis. MTT assay showed that rBTI could specifically inhibit the growth of K562 cells in a dose-dependent manner, but there were minimal effects on normal human peripheral blood mononuclear cells (PBMCs). Furthermore, comparison the effects of rBTI on K562 cells with those of negative control (BSA and the complex of BSA and rBTI) revealed that rBTI was highly toxic to K562 cells, and BSA hardly had any inhibition on proliferation in K562 cells. The analysis of flow cytometric indicated that the apoptosis of K562 cells were 31.0%, 32.8%, 35.3% and 52.1% after treated by rBTI in range of 12.5-100 microg/ml, respectively. The results suggested that rBTI can induce apoptosis of K562 cells and that it might be a potential protein drug of the trypsin inhibitor family.

Chronicles in drug discovery.

Chronicles in Drug Discovery features special interest reports on advances in drug discovery and development. This month we focus on the progress of the ongoing search for safe and effective chemopreventive agents. Chemoprevention is a strategy to decrease the risk of developing cancer by using agents that prevent or abrogate carcinogenic processes. Bowman- Birk inhibitor concentrate, budesonide, NCX-4016 and statins are all undergoing investigation in the clinical setting as potential chemopreventive agents for head and neck, lung, colon and breast cancers, respectively.