Development and Leaf Consumption by Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) Reared on Leaves of Agroenergy Crops.

Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) is a polyphagous pest that threatens more than 24 species of crop plants including those used for biodiesel production such as Ricinus communis (castor bean), Jatropha curcas (Barbados nut), and Aleurites fordii (tung oil tree). The development and leaf consumption by S. cosmioides reared on leaves of these three species were studied under controlled laboratory conditions. The egg-to-adult development time of S. cosmioides was shortest when reared on castor bean leaves and longest when reared on tung oil tree leaves. Larvae reared on castor bean and Barbados nut leaves had seven instars, whereas those reared on tung oil tree leaves had eight. Females originating from larvae reared on castor bean and Barbados nut leaves showed greater fecundity than did females originating from larvae reared on tung oil tree leaves. Insects fed on castor bean leaves had shorter life spans than those fed on tung oil tree and Barbados nut leaves although the oviposition period did not differ significantly. The intrinsic and finite rates of increase were highest for females reared on castor bean leaves. Total leaf consumption was highest for larvae reared on tung oil tree leaves and lowest for those reared on Barbados nut leaves. We conclude that castor bean is a more appropriate host plant for the development of S. cosmioides than are Barbados nut and tung oil tree.

Results of a randomized, dose-ranging trial of etoricoxib in patients with osteoarthritis.

OBJECTIVES: To evaluate the clinical efficacy and tolerability of etoricoxib in the treatment of osteoarthritis (OA) of the knee and define the clinically active dose range for further clinical trials. METHODS: This two-part, randomized, double-blind, placebo- and active comparator-controlled trial was conducted in 617 adults with knee OA. In Part 1 (6 weeks), patients received placebo, etoricoxib 5, 10, 30, 60 or 90 mg q.d. In Part 2 (8 weeks), patients received etoricoxib 30, 60 or 90 mg q.d. or diclofenac 50 mg t.i.d., predetermined at Part 1 allocation. Efficacy and safety were evaluated. Primary efficacy end-points were the Western Ontario and McMaster's University Osteoarthritis Index (WOMAC) Pain subscale, Patient Global Assessment of Response to Therapy, and Investigator Global Assessment of Disease Status. RESULTS: At 6 weeks, etoricoxib 5, 10, 30, 60 and 90 mg each demonstrated clinical efficacy superior to placebo. Maximal efficacy was seen with 60 mg. In Part 2, etoricoxib 30, 60 and 90 mg were generally similar to diclofenac. Patients receiving etoricoxib 30, 60 or 90 mg in Parts I and II had sustained effects over 14 weeks. All treatments were well tolerated. CONCLUSIONS: Etoricoxib 60 mg once daily showed maximal efficacy in treating OA in this study. Etoricoxib 5-90 mg once daily was generally well tolerated in OA patients for up to 14 weeks.

Montelukast, a leukotriene receptor antagonist, in combination with loratadine, a histamine receptor antagonist, in the treatment of chronic asthma.

BACKGROUND: Montelukast sodium, a potent, oral, specific leukotriene-receptor antagonist, has demonstrated clinical efficacy in the treatment of chronic asthma. Loratadine, a selective histamine type 1 (H(1))-receptor antagonist, has demonstrated antiallergic properties. Leukotriene-receptor antagonists given concomitantly with H(1)-receptor antagonists have been shown to have additive effects in the prevention of bronchospasm in antigen-challenge models. OBJECTIVE: To determine whether montelukast plus loratadine provides improved efficacy to montelukast alone in the treatment of chronic asthma. METHODS: The efficacy of montelukast alone vs montelukast-loratadine was studied in a 10-week, multicenter, randomized, double-blind, 2 x 2 crossover study. After a 2-week placebo run-in period, patients received montelukast sodium (10 mg) plus loratadine (20 mg), or montelukast sodium (10 mg) plus placebo once daily for 2 weeks. After a 2-week placebo washout period, patients were crossed over to receive 2 weeks of the other active treatment regimen, followed by another 2-week placebo washout period. RESULTS: Montelukast given concomitantly with loratadine caused significant improvement in percentage of change from baseline in forced expiratory volume in 1 second (FEV(1)) compared with montelukast alone (13.86% vs 9.72%; P =.001). The average additional effect of loratadine (least square mean difference in percentage of change from baseline in FEV(1)) was 4.15% (95% confidence interval, 1.65%-6.65%). Key secondary end points (mean daily beta-agonist use, daytime and nighttime symptom scores, morning and evening peak expiratory flow rate, and the Patient Global Evaluation) all showed significant improvement with montelukast-loratadine (P<.05). CONCLUSION: Montelukast-loratadine significantly improved end points of asthma control during a 2-week treatment period.

The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia.

BACKGROUND: Data suggest that androgenetic alopecia is a process dependent on dihydrotestosterone (DHT) and type 2 5alpha-reductase. Finasteride is a type 2 5alpha-reductase inhibitor that has been shown to slow further hair loss and improve hair growth in men with androgenetic alopecia. OBJECTIVE: We attempted to determine the effect of finasteride on scalp skin and serum androgens. METHODS: Men with androgenetic alopecia (N = 249) underwent scalp biopsies before and after receiving 0.01, 0.05, 0.2, 1, or 5 mg daily of finasteride or placebo for 42 days. RESULTS: Scalp skin DHT levels declined significantly by 13.0% with placebo and by 14.9%, 61.6%, 56. 5%, 64.1%, and 69.4% with 0.01, 0.05, 0.2, 1, and 5 mg doses of finasteride, respectively. Serum DHT levels declined significantly (P <.001) by 49.5%, 68.6%, 71.4%, and 72.2% in the 0.05, 0.2, 1, and 5 mg finasteride treatment groups, respectively. CONCLUSION: In this study, doses of finasteride as low as 0.2 mg per day maximally decreased both scalp skin and serum DHT levels. These data support the rationale used to conduct clinical trials in men with male pattern hair loss at doses of finasteride between 0.2 and 5 mg.

MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen.

Two isozymes (types 1 and 2) of 5alpha-reductase (5alphaR; EC 1.3.99.5), with differential tissue distribution, catalyze the reduction of testosterone (T) to dihydrotestosterone (DHT) in humans. This study examined sequentially increasing oral doses of MK-386 (4,7beta-dimethyl-4-aza-5alpha-cholestan-3-one), an azasteroid that specifically inhibits the human 5alphaR1 isozyme in vitro. Finasteride, a selective inhibitor of 5alphaR2, was included for comparison. One hundred men were evaluated in a double blind, randomized, placebo-controlled, sequential, increasing dose, parallel group trial. Ten to 20 subjects received MK-386, and 2 to 5 received placebo in each of 6 panels. In 1 panel, 10 subjects received finasteride (5 mg), and 5 received placebo. Treatments were given once daily for 14 days, except in 1 panel in which MK-386 was administered 10 mg twice daily for comparison to 20 mg daily. Serum, sebum, and semen DHT concentrations and serum and sebum T concentrations were measured before and after treatment. The mean changes from baseline on day 14 for serum DHT after placebo and 0.1, 0.5, 5, 20, and 50 mg MK-386 were 6.9%, 4.6%, -2.7%, -1.2%, -14.1% (P < 0.05 vs. placebo), and -22.2% (P < 0.05 vs. placebo), respectively. No significant alterations in serum T were observed after any dose of MK-386. Serum DHT fell 65.8% from the baseline 14 days after finasteride treatment (P < 0.05 vs. placebo). The mean changes from baseline on day 14 in sebum DHT were 5.0%, 3.0%, -25.4% (P < 0.05 vs. placebo), -30.1% (P < 0.05 vs. placebo), and -49.1% (P < 0.05 vs. placebo) for the placebo and 0.5, 5, 20, and 50 mg MK-386 groups, respectively. Finasteride also reduced sebum DHT, but to a lesser extent (- 14.9%; P < 0.05 vs. placebo). Reciprocal increases in sebum T concentration were noted at doses of 5 mg or more of MK-386, but not with finasteride. The mean reduction in semen DHT with 5 mg finasteride was approximately 88% (P < 0.01 vs. placebo); no significant change in semen DHT was noted with 20 or 50 mg MK-386. Serum 3alpha-androstanediol glucuronide values were also reduced after the 20- and 50-mg MK-386 treatments in parallel with the changes in serum DHT. No meaningful changes were observed in serum LH after MK-386 treatment. MK-386 was generally well tolerated by all subjects; reversible aspartate aminotransferase/alanine aminotransferase elevations were observed in two subjects at the 50-mg dose. The differential responses in serum, sebum, and semen DHT concentrations associated with MK-386 and finasteride treatments are consistent with those changes anticipated for selective inhibitors of the human 5alphaR isozymes. Dose-dependent suppression of sebum DHT by a 5alphaR1 inhibitor suggests the potential utility of such compounds in the treatment of acne.

Effective services for homeless substance abusers.

A heterogeneous and representative sample of 323 homeless individuals in the metropolitan-Denver area with alcohol or other substance abuse problems received a comprehensive array of substance-abuse treatment services. Following treatment, these individuals showed dramatic improvement on average in their (a) levels of alcohol and drug use, (b) housing status, (c) physical and mental health, (d) employment, and (e) quality of life. Those who received more service improved more than those who received less service. These improvements are attributable, at least partly, to the treatment rather than to alternative hypotheses such as spontaneous remission. However, the rate of improvement generally slowed during the six-month follow-up period. A random half of the clients received intensive case management in addition to the other services. Case management marginally increased clients' contacts with addictions counselors, but had little effect on the level of other services received or on the tailoring of services to client needs. As a result, case management also had little, if any, effect on outcomes.

The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness.

The effects of the 5 alpha-reductase inhibitor, finasteride, on scalp skin testosterone (T) and dihydrotestosterone (DHT) levels were studied in patients with male pattern baldness. In a double blind study, male patients undergoing hair transplantation were treated with oral finasteride (5 mg/day) or placebo for 28 days. Scalp skin biopsies were obtained before and after treatment for measurement of T and DHT by high pressure liquid chromatography-RIA. In 10 male subjects studied at baseline, mean (+/- SEM) DHT levels were significantly higher in bald (7.37 +/- 1.24 pmol/g) compared to hair-containing (4.20 +/- 0.65 pmol/g) scalp, whereas there was no difference in mean T levels at baseline. In bald scalp from 8 patients treated with finasteride, the mean DHT concentration decreased from 6.40 +/- 1.07 pmol/g at baseline to 3.62 +/- 0.38 pmol/g on day 28. Scalp T levels increased in 6 of 8 subjects treated with finasteride. Finasteride decreased the mean serum DHT concentration from 1.36 +/- 0.18 nmol/L (n = 8) at baseline to 0.46 +/- 0.10 nmol/L on day 28 and had no effect on serum T. There were no significant changes in scalp or serum T or DHT in placebo-treated patients. In this study, male subjects treated with 5 mg/day finasteride for 4 weeks had significantly decreased concentrations of DHT in bald scalp, resulting in a mean level similar to the baseline levels found in hair-containing scalp.