Tumor Deposits in Stage III Colon Cancer: Correlation With Other Histopathologic Variables, Prognostic Value, and Risk Stratification-Time to Consider "N2c".

OBJECTIVES: National Comprehensive Cancer Network (NCCN) guidelines for stage III colon cancer define low-risk versus high-risk patients based on T (1 to 3 vs. 4) and N (1 vs. 2) status, with some variations in treatment. This study analyzes the impact of tumor deposits (TDs), T and N status, poor differentiation (PD), perineural invasion (PNI), and lymphovascular invasion (LVI) on survival. MATERIALS AND METHODS: A retrospective analysis (2010-2015) of the National Cancer Database of stage III colon cancer patients treated with both surgery and chemotherapy was conducted. Data was extracted on sex, race, age at diagnosis, Charlson-Deyo Score, histopathologic variables, and survival rates. Statistical analysis used the test of proportions, log-rank test for Kaplan-Meier curves, and Cox proportional hazard models. RESULTS: For the 42,901 patients analyzed, 5-year survival rates were similar for LNTD (59.8%) and LNTD (58.2%), but significantly worse for LNTD (41.5%) (P<0.001). The presence of LNTD was more often associated with T4 (36.9%), N2 (55.1%), PD (37.4%), PNI (34.5%), and LVI (69.1%), than LNTD or LNTD (P<0.001). The hazard ratios for each variable were: TD: 1.34; T4: 1.71; N2: 1.44; PD: 1.37; PNI: 1.11; LVI: 1.18. LN patients with ≥3 TD (N1c) had worse overall survival than those with 1 to 2 TD (P<0.01), but similar to ≥4 LNTD (N2) and 1 to 3 LNTD (N1a-b). In our model, 5-year survival ranged from 23.4% for high-risk to 78.1% for low-risk patients (P<0.001). CONCLUSION: This National Cancer Database (NCDB) analysis offers greater risk stratification and may prompt consideration of changes in American Joint Committee on Cancer (AJCC) classification (N2c, in addition to N1c) to reflect the different prognosis and guide management, as well as survivorship strategies, for TD stage III colon cancer patients.

Juvenile Papillomatosis (Swiss-Cheese Disease) of Breast in an Adult Male With Sequential Diagnoses of Ipsilateral Intraductal, Invasive, and Widely Metastatic Carcinoma: A Case Report and Review of the Disease in Males.

Juvenile papillomatosis of the breast (JPB, also known as Swiss cheese disease) is a rare ailment that typically afflicts young females, and presents as a mass-forming lesion. The lesional mass usually comprises multiple cysts and duct stasis, amid a variety of proliferative and nonproliferative epithelial changes. The proliferative changes include papillary hyperplasia, florid hyperplasia, and papillary apocrine hyperplasia. Concurrent carcinoma (either in situ or invasive) is present in approximately 10% of cases at presentation, and subsequent carcinoma (either in situ or invasive) is diagnosed in about 10% of patients. About 20% of patients have a strong family history of breast carcinoma. A total of 10 cases of JPB have been previously reported in males, both children and adults, only one of which, in a 33-year-old, was associated with invasive carcinoma. Here, another case of JPB in a 45-year-old male-one with subsequent sequential diagnoses of ipsilateral intraductal carcinoma, invasive carcinoma, and widely metastatic carcinoma over the course of 15 years-is reported.

Interactions of a Dopamine D1 Receptor Agonist with Glutamate NMDA Receptor Antagonists on the Volitional Consumption of Ethanol by the mHEP Rat.

Stimulation of the dopamine D1 receptor is reported to cause the phosphorylation of DARPP-32 at the thre34 position and activates the protein. If intracellular Ca2+ is increased, such as after activation of the glutamate NMDA receptor, calcineurin activity increases and the phosphates will be removed. This balance of phosphorylation control suggests that a D1 receptor agonist and a NMDA glutamate receptor antagonist should have additive or synergistic actions to increase activated DARPP-32 and consequent behavioral effects. This hypothesis was tested in a volitional consumption of ethanol model: the selectively bred Myers' high ethanol preferring (mHEP) rat. A 3-day baseline period was followed by 3-days of twice daily injections of drug(s) or vehicle(s) and then a 3-day post-treatment period. Vehicle, the D1 agonist SKF 38393, the non-competitive NMDA receptor antagonist memantine, or their combination were injected 2 h before and after lights out. The combination of 5.0 mg/kg SKF 38393 with either 3.0 or 10 mg/kg memantine did not produce an additive or synergistic effect. For example, 5.0 mg/kg SKF reduced consumption of ethanol by 27.3% and 10 mg/kg memantine by 39.8%. When combined, consumption declined by 48.2% and the proportion of ethanol solution to total fluids consumed declined by 17%. However, the consumption of food also declined by 36.6%. The latter result indicates that this dose combination had a non-specific effect. The combination of SKF 38393 with (+)-MK-801, another NMDA receptor antagonist, also failed to show an additive effect. The lack of additivity and specificity suggests that the hypothesis may not be correct for this in vivo model.  The interaction of these different receptor systems with intraneuronal signaling and behaviors needs to be studied further.

Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma.

BRCA1/BRCA2 mutations are common and the hallmarks of high-grade serous ovarian carcinoma. We found that MIR182, a negative BRCA1 regulator, is significantly overexpressed in high-grade serous ovarian carcinoma. To examine whether overexpression of MIR182 and its target genes, including BRCA1, HMGA2 (high-mobility group A2), FOXO3 and MTSS1, are associated with high-grade serous ovarian carcinoma tumor types and clinical outcome, we studied MIR182 by in situ hybridization and its target gene expression by immunohistochemistry in 117 cases of advanced ovarian cancer. We found that high-grade serous ovarian carcinoma had significantly higher MIR182 (P=0.0003) and HMGA2 (P=0.04) expression, and significantly lower BRCA1 (P<0.0001) and FOXO3 (P<0.001) expression than normal controls. MIR182 is significantly correlated with MTSS1 expression (r=0.31; P<0.001), whereas other target genes did not show a significant correlation with MIR182, indicating a complicated regulatory mechanisms of these genes in high-grade serous ovarian carcinoma. Among the examined MIR182 target genes, only HMGA2 was significantly associated with serous type carcinomas (P<0.01), ascites (P<0.01) and high death rate (P=0.02). FOXO3 expression was associated with lower-stage disease (P=0.04) and solid growth pattern (P=0.03). MIR182 expression is significantly higher in high-grade serous ovarian carcinoma than in fallopian tubes.

Incapacitated sexual violence involving alcohol among college women: the impact of a brief drinking intervention.

This study assessed the impact of a motivational interviewing (MI) brief alcohol intervention and prior victimization on alcohol-involved sexual victimization experiences. First-year female college students (N = 229) were randomly assigned to an intervention condition: MI, MI with feedback (MIFB), feedback (FB), and assessment only (AO). Findings indicate reduced alcohol use for all conditions and violence for MIFB, with interactions for prior victimization. The mechanism of change for reduced victimization was not reductions in alcohol use and mechanisms for this effectiveness remain somewhat convoluted. Tailoring of brief interventions addressing alcohol use and sexual violence, particularly for women with prior victimization, is critical.

Effects of the non-competitive NMDA receptor antagonist memantine on the volitional consumption of ethanol by alcohol-preferring rats.

Potent N-methyl-d-aspartate (NMDA) receptor antagonists decrease volitional consumption of ethanol by rats. This study examined the effects of memantine, a low-affinity, open channel NMDA antagonist, on volitional consumption of ethanol by alcohol-preferring rats and potential locomotor, sedative and hypothermic effects. Volitional consumption of ethanol in a 24-hr two-choice paradigm was determined for male Myers' high-ethanol-preferring (mHEP) rats. Effects of memantine (0.3, 1.0, 3.0 and 10.0 mg/kg, i.p., b.i.d. [twice daily] for 3 days) or vehicle on volitional consumption of ethanol, proportion of ethanol to total fluids consumed, total fluid intake and consumption of food were observed. Potential sedating and locomotor effects of memantine (10.0 mg/kg, i.p., b.i.d.) were determined using an elevated plus maze and an Auto-Track Opto-Varimex activity monitoring system. Rectal temperature was measured to determine if memantine (10.0 mg/kg, i.p.) produces a hypothermic effect. The results indicate that memantine dose-dependently decreased the amount of ethanol and proportion of ethanol to total fluids consumed daily, reaching 48% and 24%, respectively, at the highest dose. These effects did not appear to be anti-caloric. Memantine (10.0 mg/kg) partially reversed both the sedation and the reductions in locomotor activity induced by ethanol. This dose did, however, produce a small, partially reversible hypothermic effect. In conclusion, memantine may decrease ethanol consumption with fewer side effects than other NMDA receptor antagonists, such as phencyclidine (PCP), MK 801 and ketamine.

College students' responses to a 5/4 drinking question and maximum blood alcohol concentration calculated from a timeline followback questionnaire.

OBJECTIVE: Many surveys employed to study college drinking ask whether students have had a five-drink (for men) or four-drink (for women) episode in one sitting at least once during the previous 2 weeks to indicate risky or heavy episodic drinking. However, some researchers have questioned the predictive validity of the 5/4 measure. This study tested whether such students attained extremely high blood alcohol concentrations (BACs) during the previous 30 days. METHOD: Freshmen students were recruited by presentation of short screening surveys in the classroom or outside the student stores. Students who reported a risky drinking episode were invited to enroll in the study and were given a lengthy survey battery that included a computerized 30-day Timeline Followback recall of their drinking. The amount of alcohol consumed was used along with each subject's gender and weight to calculate an estimated BAC (eBAC) for each event and the maximum eBAC taken for this report. RESULTS: Fifty-five percent of the 953 students who completed the screening survey met criterion for enrollment, and 381 students entered the study. The average peak calculated eBAC was 233 mg/dl. Only 9.2% of subjects did not have an eBAC value at or above the threshold for a driving while intoxicated offense, 80 mg/dl. CONCLUSIONS: Students who report one recent risky drinking episode are very likely to have had at least one heavy drinking episode that generated a BAC in excess of the threshold for driving while intoxicated. Many report extremely high consumption levels. The 5/4 screening question is highly predictive of abusive drinking and can be used to identify students at severe risk for adverse events related to the consumption of alcohol.

Effect of DOV 102,677 on the volitional consumption of ethanol by Myers' high ethanol-preferring rat.

BACKGROUND: Inhibitors of monoamine neurotransmitter transporters are well established as antidepressants. However, the evidence that single (serotonin) or dual (serotonin-norepinephrine) neurotransmitter uptake inhibitors can treat ethanol abuse, either as a comorbidity with depression or as a separate entity, is inconsistent. Drugs that have, in addition, the ability to inhibit dopamine uptake may have an advantage in the treatment of alcohol abuse. Therefore, the inhibitor of norepinephrine, serotonin and dopamine uptake, DOV 102,677, was tested for its effects on the volitional consumption of ethanol by an ethanol-preferring rat strain. METHODS: Myers' high ethanol-preferring rats were screened by a 10-day, 3 to 30% step-up test and then given free access to the preferred concentration of ethanol in a 3-bottle choice task. Consumption of ethanol (g/kg), water, food, and body weight were measured daily during a 3-day predrug treatment period, a 3-day treatment period, and a 3-day posttreatment period. Additional Sprague-Dawley rats were observed for 24 hours for the behavioral effects of 2.0 mg/kg s.c. reserpine after a 30-minute pretreatment with different doses of DOV 102,677. RESULTS: The triple monoamine uptake inhibitor DOV 102,677 dose-dependently decreased the volitional consumption of ethanol by as much as 71.2% (20 mg/kg i.p., b.i.d.) over 3 days of administration. This effect carried over into the posttreatment period. Similarly, the proportion of ethanol to total fluids consumed declined by 66.2% (20 mg/kg s.c., b.i.d.), while food consumption and body weight were unaltered. In contrast, amperozide (2 mg/kg i.p., b.i.d.) suppressed the amount of ethanol consumed by 56%, while naltrexone (5 mg/kg i.p., b.i.d.) was without effect. DOV 102,677 (40 mg/kg s.c.) inhibited reserpine-induced akinesia and ptosis, but not hypothermia in Sprague-Dawley rats, consistent with its transient inhibition of serotonin transport, and more long-lived inhibition of norepinephrine and dopamine uptake. CONCLUSIONS: DOV 102,677 significantly decreased the volitional consumption of ethanol with minimal alterations in the intake of food or on body weight in an ethanol-preferring rat strain, suggesting that triple reuptake inhibitors may find utility in treating alcohol abuse.

Nicotine increases FosB expression within a subset of reward- and memory-related brain regions during both peri- and post-adolescence.

INTRODUCTION: Periadolescent nicotine exposure is associated with increased consumption and rewarding properties of abused drugs. In the case of peri- but not post-adolescent animals, these effects are persistent and last to adulthood, suggesting that early nicotine treatment may alter postnatal CNS development in ways that contribute to long-term problems with drug abuse. MATERIALS AND METHODS: To begin to identify brain regions that may be altered by developmental nicotine exposure, we have measured expression of a transcription factor, FosB, within a series of reward- and memory-related brain regions of Sprague-Dawley rats. RESULTS: FosB expression is known to acutely and cumulatively increase within a subset of brain regions, particularly nucleus accumbens, after exposure to many classes of abused drugs. Our results demonstrate that FosB is increased within nucleus accumbens and also the granule cell layer of hippocampal dentate gyrus after both peri- and post-adolescent nicotine exposure (0.4 mg kg(-1) day(-1) from days 34 to 43 and 60 to 69, respectively). In periadolescents, expression increases were detected 2 days after nicotine exposure, and persisted for weeks, through at least early adulthood at 80 days of age. In post-adolescents, expression increases persisted for at least 11 days to postnatal day 80. DISCUSSION: These findings demonstrate that nicotine treatment during both peri- and post-adolescence persistently alters activity of brain regions involved in reward and memory. CONCLUSION: Because this altered gene expression occurs after both peri- and post-adolescent treatment, it cannot be directly responsible for increased consumption and rewarding properties of abused drugs previously established to be distinctly associated with periadolescent nicotine exposure.

Periadolescent nicotine exposure produces sensitization to reinforcement by diazepam in the rat.

Epidemiologic studies establish a relationship between nicotine use by adolescents and a subsequent involvement with drugs of abuse in adulthood. Recent research implicates the periadolescent period as a crucial time in development, during which nicotine use produces persistent adaptations that serve to predispose an individual to substance use. The present investigation evaluated the effects of periadolescent nicotine priming on young adult sensitization to reinforcement by a drug of abuse. Nicotine (0.4 mg/kg, intraperitoneal), mecamylamine (2 mg/kg, subcutaneous), mecamylamine and nicotine, or saline was administered as a once-daily injection to periadolescent (postnatal days 35-44) Sprague-Dawley male rats. The effects of periadolescent nicotine priming on reinforcement parameters in the young adult animal (postnatal day 80) were measured by conditioning a place preference with diazepam (1 mg/kg, subcutaneous). Rats were tested for place conditioning in a drug-free state. In contrast to other periadolescent treatment groups, rats treated with only nicotine during periadolescence showed a heterologous sensitization to the subthreshold dose of diazepam utilized during conditioning. Pretreatment with mecamylamine before periadolescent nicotine priming prevented the enhanced response to diazepam observed in the young adult animal. Priming with nicotine during late adolescence (postnatal days 60-69) failed to sensitize the adult rats to diazepam. This study supports a relationship between periadolescent nicotine priming and the production of persistent, behavioral adaptations in the young adult animal.

The effect of oral consumption of perchlorate, alone and in combination with ethanol, on plasma thyroid hormone and brain catecholamine concentrations in the rat.

Literature has reported a controversy concerning the effects of the environmental pollutant perchlorate on pertinent physiological systems. However, no research to date has evaluated the effect of concomitant consumption of perchlorate and an additional environmental contaminant on physiological systems. The present preliminary investigation served to assess the effects of oral consumption of perchlorate, alone and in combination with ethanol, on thyroid hormone and brain catecholamine concentrations in female rats of gestational age. Forty, female Myers' high ethanol-preferring rats were randomly assigned to 1 of 7 groups that received: (1) deionized water, both bottles (2) deionized water and 10% ethanol (v/v), two separate bottles (3) 300 microg/l perchlorate solution in deionized water, both bottles (4) 300 microg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (5) 3000 microg/l perchlorate solution in deionized water, both bottles (6) 3000 microg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (7) 0.01% propylthiouracil solution in deionized water, both bottles. At cessation of the treatment period, plasma triiodothyronine (T3) and thyroxine (T4) levels were measured by radioimmunoassay and brain area concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine were measured by high performance liquid chromatography. Perchlorate consumption, alone and/or in combination with ethanol consumption, failed to produce significant alterations from control values for triiodothyronine, thyroxine, dopamine, DOPAC, or norepinephrine. The data suggest that the no-observed effect level of perchlorate consumption on thyroid hormone and brain catecholamine concentrations is above the 3000 microg/l concentration in the adult female rat.

Effects of a metabotropic, mglu5, glutamate receptor antagonist on ethanol consumption by genetic drinking rats.

AIMS: To compare the effect of an antagonist of the mGlu5 glutamate receptor, 2-methyl-6-(phenylethynyl)pyridine (MPEP) on a test for anxiety and on the volitional consumption of ethanol. METHODS: The test for anxiety was placement of a Sprague-Dawley rat for a 5 min observation period in an elevated plus-maze. Volitional consumption of ethanol in a two-choice paradigm was determined for male and female myers high ethanol-preferring rats after a 10-day 'step-up' test of 3-30% v/v ethanol vs water used to determine each rat's preferred concentration of ethanol. Each rat received a 4-day baseline period, 3-days of drug injection b.i.d., and a 4-day post-treatment period and then rotated to a different dose of drug or vehicle. RESULTS: The effects of MPEP on elevated plus-maze activity were not significant at doses up to 3.0 mg/kg subcutaneously 60 min. before observation. There was a dose-dependent, 0.3, 1.0, 3.0 mg/kg, decrease in consumption of preferred concentrations of ethanol, along with a decrease in the proportion of ethanol consumed to total fluids consumed. The 3.0 mg/kg b.i.d. dose of MPEP reduced consumption by 57%, proportion by 45%, and food intake by 10%. CONCLUSIONS: MPEP did not appear to have an anti-anxiety effect, but volitional drinking in a genetic model was reduced. The mGlu5 receptor may provide a target for drug action to reduce the consumption of ethanol.

Periadolescent nicotine exposure causes heterologous sensitization to cocaine reinforcement.

There is increasing concern that abuse of tobacco during periadolescence increases the potential for later abuse of other drugs. To test this hypothesis, Sprague-Dawley rats received once-daily injections of either water or 0.4 mg/kg nicotine from postnatal day 35 through 44. Beginning on postnatal day 80, animals were tested in a 12-day cocaine-induced conditioned place preference (CPP) paradigm. Prior nicotine treatment enhanced the dose-response to cocaine. CPP training with 3.0 mg/kg i.p. cocaine increased time in drug-paired chambers by 50% in control rats and 94% in nicotine-exposed animals. Thus, periadolescent nicotine exposure produced long-term sensitization to an indirect-acting dopamine agonist.

Effects of NMDA glutamate receptor antagonist drugs on the volitional consumption of ethanol by a genetic drinking rat.

The ability of drugs that reduce NMDA receptor activity on the volitional consumption of ethanol in the genetic drinking rat, mHEP line, was investigated. After the consumption of ethanol solutions and water by each male or female mHEP rat had stabilized on its preferred concentration, different doses of LY 274614, a competitive NMDA antagonist, MK 801, a non-competitive NMDA antagonist, (+)-HA-966 or ACPC (1-aminocyclopropane-1-carboxylic acid), antagonists of the glycine site were administered daily for three days. The dose of 3.0 mg/kg i.p. LY 274614 reduced the consumption of ethanol by 64% compared to the pre-treatment baseline, while 0.3 mg/kg of MK 801 reduced consumption by 44%, 20 mg/kg (+)-HA-966 reduced consumption by 47% and 300 mg/kg of ACPC reduced consumption by 30%. These doses of LY 274614 and MK 801 reduced the ability of Sprague-Dawley rats to walk on a rotorod. Effects of these drugs on food intake were small except for the 20 mg/kg dose of (+)-HA-966. Therefore, the drugs did not have an anti-caloric effect and manipulations of the glutamatergic system through NMDA receptors may modify the consumption of ethanol. This interaction should be explored further for its therapeutic potential and to better understand the control by central neuronal systems of the consumption of ethanol.

Lower fumonisin mycotoxin levels in the grain of Bt corn grown in the United States in 2000-2002.

Fumonisins were monitored in corn grain collected from Bt hybrids grown in 107 locations across the United States in 2000-2002. Bt corn hybrids contain the Cry1Ab protein from Bacillus thuringiensis that controls European corn borers and other stalk-boring pests. Fumonisin levels were frequently lower in grain from Bt hybrids grown in field trials under conditions of natural (FACT trials) or manual insect infestation (university trials). Over three years of FACT trials, there were 126/210 comparisons when fumonisin levels in grain from control hybrids were >2 ppm, exceeding U.S. FDA guidance levels of 2 ppm for human food. Grain from Bt hybrids was at or below 2 ppm of fumonisins for 58 of the 126 comparisons. The use of Bt hybrids can increase the percentage of corn grain that would be suitable for use in food and feed.

Conditioned taste aversion and the Myers' high-ethanol-preferring rat.

AIMS: Male and female Myers' high-ethanol-preferring (mHEP) rats were compared to outbred controls in a taste aversion paradigm. METHODS: Alcohol-naïve rats were adapted to a 2-h access to water. Each rat was given either 0.05% saccharin (w/v) or 7% ethanol (v/v) as a novel solution for 1 h, after which either 0.5 M LiCl, as the aversive stimulus, or NaCl, as the control, was injected intraperitoneally. Each rat was tested 48 h later by presentation of the same solution. RESULTS: After LiCl injections, saccharin consumption declined 21.6% in female Sprague-Dawley, 9.5% in female mHEP, 33.3% in male Wistar, and 38.3% in male mHEP rats. Ethanol consumption in these groups declined by 88.5, 30, 45 and 52%, respectively. These mHEP rats were then screened for 24-h alcohol consumption on a 10-day 3-30% ethanol vs water 'step-up' procedure. During the step-up procedure, only the male mHEP rats trained with ethanol for taste aversion drank less ethanol at the 3-5% concentrations than did rats trained with saccharin. The female mHEP rats did not learn an aversion to either saccharin or ethanol. CONCLUSIONS: The female mHEP rat consumes copious amounts of ethanol, but the basis for this consumption may be different from that of the male mHEP rat.

On the role of monoamine oxidase-A for the maintenance of the volitional consumption of ethanol in two different rat models.

It is hypothesized that although the overall metabolism of ethanol in the brain is very limited, a very small percentage of the brain tissue may carry out that little amount of metabolism. Specifically, hydrogen peroxide may be used as a co-substrate for the metabolism of ethanol to acetaldehyde by catalase and the action of monoamine oxidase in the monoaminergic neurons would supply the hydrogen peroxide. This production of acetaldehyde may result in the formation of novel metabolites that provide the rewarding stimulus for the consumption of ethanol. To test this hypothesis, a reversible inhibitor of the A-isoform of monoamine oxidase, BW A616U, was compared to irreversible inhibitors of one or both MAO-A and B isoenzymes. Doses of 12.5-75 mg/kg p.o. BW A616U reduced the behavioral effects, ptosis and catalepsy, due to monoamine depletion by 2.5 mg/kg reserpine, but these signs of monoamine depletion were evident 24 h after injection. In the cyanamide-induced drinking rat, 50 mg/kg BW A616U reduced consumption of ethanol by 37%. Phenylzine, an irreversible MAO-A and B inhibitor, reduced consumption of ethanol by 67%, but also food consumption; however, the intake of both increased during the post-treatment period. The MAO-B inhibitor, R(-)-deprenyl, was without effect. Both BW A616U, 50 mg/kg and 75 mg/kg, and 2.0 mg/kg i.p. clorgyline reduced the consumption of ethanol in the genetic drinking Myers high-ethanol preferring (mHEP) rat and reduced the proportion of ethanol consumed to total fluids by over 50%. Again, R(-)-deprenyl was without effect. Clorgyline also markedly reduced the intake of food during the 3-day treatment period, only. However, the consumption of ethanol remained depressed during the 4 days after either 75 mg/kg BW A616U or clorgyline. These data demonstrate that inhibition of MAO-A, but not MAO-B, reduces the volitional consumption of ethanol probably by preventing the formation of both biogenic aldehydes and acetaldehyde so that rewarding alkaloidal products cannot be formed.