Biosynthesis of scarab beetle pheromones

Chemical communication in scarab beetles (Coleoptera: Scarabaeidae) is achieved with a wide variety of pheromones, but one typical structure is the gamma-lactone having a long unsaturated hydrocarbon chain. Several species utilize (R, Z)-5-(-)-(oct-1-enyl)-oxacyclopentan-2-one (buibuilactone), (R, Z)-5-(-)-(dec-1-enyl)-oxacyclopentan-2-one and (S, Z)-5-(+)-(dec-1-enyl)-oxacyclopentan-2-one [(R)-japonilure and (S)-japonilure]. Using deuterated precursors, we have demonstrated that these compounds are biosynthesized from fatty acids. (9, 10-d4)-Palmitic acid, (9,10-d4)-stearic acid, (9,10-d2)-palmitoleic acid, (9,10-d2)-oleic acid, (9,10-d2)-8-hydroxypalmitoleic acid and (9,10-d2)-8-hydroxyoleic acid were readily incorporated by female Anomala cuprea into the pheromone molecules, while (Z)-(5, 6-d2)-5-dodecenoic acid and (Z)-(5,6-d2)-5-tetradecenoic acid were not. Therefore, the reaction pathway starts from saturated fatty acids, involves their desaturation, followed by 8-hydroxylation, chain shortening and cyclization. The products obtained from racemic (9,10-d2)-8-hydroxypalmitoleic acid and (9,10-d2)-8-hydroxyoleic acid were also racemic, implying that the steps following hydroxylation were not stereospecific. Perdeuterated palmitic acid was applied to disclose the mechanism of the unique hydroxylation reaction. Retention of all deuterium atoms implied that this reaction was a direct process mediated by a specific fatty acid hydroxylase, and preceding desaturation or epoxidation was not involved.     

Physical and functional interactions between the herpes simplex virus UL15 and UL28 DNA cleavage and packaging proteins

Herpes simplex virus (HSV) DNA is cleaved from concatemers and packaged into capsids in infected cell nuclei. This process requires seven viral proteins, including UL15 and UL28. UL15 expressed alone displays a nuclear localization, while UL28 remains cytoplasmic. Coexpression with UL15 enables UL28 to enter nuclei, suggesting an interaction between the two proteins. Additionally, UL28 copurified with UL15 from HSV-infected cells after ion-exchange and DNA affinity chromatography, and the complex sedimented as a 1:1 heterodimer upon sucrose gradient centrifugation. These findings are evidence of a physical interaction of UL15 and UL28 and a functional role for UL15 in directing UL28 to the nucleus.     

A survey of seroprevalence of human papillomavirus types 16, 18 and 33 among children

The importance and natural history of HPV infections in childhood is incompletely understood. We performed a survey for presence of serum antibodies to HPV capsids among 1031 children aged 0 to 13 years, resident in Stockholm, Sweden. The HPV seroprevalence among these children was 3.0% for HPV16, 0.6% for HPV18 and 2.7% for HPV33. By comparison, among simultaneously analyzed positive control panels comprising women with CIN or healthy women with type-specific cervical HPV DNA, seroprevalence of HPV 16, 18 and 33 was 69%, 58% and 63% respectively. The results suggest that HPV infection in childhood is not common.     

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.     

Age-dependent tetrahydrothiophenium ion formation in young children and adults receiving high-dose busulfan

Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan elimination is the formation of a tetrahydrothiophenium ion (THT+) in a glutathione S-transferase-catalyzed reaction. We present computer simulations that demonstrate that the ratio of the AUC of THT+ to that of busulfan over 6 h [(AUC(THT+)/AUC(BU))(0-->6)] is highly correlated (r2 = 0.805) with the determinants of THT+ formation and is virtually independent of the determinants of its elimination (r2 = 0.0201). We compared (AUC(THT+)/AUC(BU))(0-->6) determined in 14 children (0.5-4 years) to that of 11 adults (12-54 years) and found a 1.5-fold elevation in the area ratio (P = 0.0098) and a similarly significant increase in busulfan apparent oral clearance expressed relative to body surface area (P = 0.042). The only common explanation for the elevated busulfan apparent oral clearance and (AUC(THT+)/AUC(BU))(0-->6) is an enhanced ability of children to metabolize busulfan through glutathione conjugation.     

Do disease specific characteristics add to the explanation of mobility limitations in patients with different chronic diseases? A study in The Netherlands

STUDY OBJECTIVES: To determine whether disease specific characteristics, reflecting clinical disease severity, add to the explanation of mobility limitations in patients with specific chronic diseases. DESIGN AND SETTING: Cross sectional study of survey data from community dwelling elderly people, aged 55-85 years, in the Netherlands. PARTICIPANTS AND METHODS: The additional explanation of mobility limitations by disease specific characteristics was examined by logistic regression analyses on data from 2830 community dwelling elderly people. MAIN RESULTS: In the total sample, chronic non-specific lung disease, cardiac disease, peripheral atherosclerosis, diabetes mellitus, stroke, arthritis and cancer (the index diseases), were all independently associated with mobility limitations. Adjusted for age, sex, comorbidity, and medical treatment disease specific characteristics that explain the association between disease and mobility mostly reflect decreased endurance capacity (shortness of breath and disturbed night rest in chronic non-specific lung disease, angina pectoris and congestive heart failure in cardiac disease), or are directly related to mobility function (stiffness and lower body complaints in arthritis). For atherosclerosis and diabetes mellitus, disease specific characteristics did not add to the explanation of mobility limitations. CONCLUSIONS: The results provide evidence that, to obtain more detailed information about the differential impact of chronic diseases on mobility, disease specific characteristics are important to take into account.     

Topical fluorides: efficacy, administration, and safety

Fluoride's role in decreasing dental caries has been recognized for decades. The professional fluoride treatment has recently been augmented with home-use fluoride products. The introduction of many attractive products makes it difficult for dental professionals to know which are effective. Both professional and home-use products are described, as are proven techniques for their use. Recognition of fluoride toxicity, and its prevention and treatment, are also discussed.     

High prevalence of adynamic bone disease diagnosed by biochemical markers in a wide sample of the European CAPD population

BACKGROUND: Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. METHODS: In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. RESULTS: In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. CONCLUSION: A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.