The scarlet eye colour gene of the tephritid fruit fly: Bactrocera tryoni and the nature of two eye colour mutations

A homologue of the Drosophila melanogaster eye-colour gene, scarlet (st), has been isolated from the genome of the tephritid fruit fly, Bactrocera tryoni. The comparison of the B. tryoni and D. melanogaster scarlet gene shows 71.2% and 79.3% sequence identity at the DNA and the derived amino acid level, respectively. Two allelic eye-colour mutations of B. tryoni, orange-eyes and lemon-eyes, have been recovered and found to be colocalized with the st gene. The st gene sequence in the two mutant strains has been examined for DNA sequence changes and expression levels.     

Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea

BACKGROUND: Hypoglossal nerve stimulation has been demonstrated to relieve upper airway obstruction acutely, but its effect on obstructive sleep apnea is not known. OBJECTIVE: To determine the response in obstructive sleep apnea to electrical stimulation of the hypoglossal nerve. METHODS: Eight patients with obstructive sleep apnea were implanted with a device that stimulated the hypoglossal nerve unilaterally during inspiration. Sleep and breathing patterns were examined at baseline before implantation and after implantation at 1, 3, and 6 months and last follow-up. RESULTS: Unilateral hypoglossal nerve stimulation decreased the severity of obstructive sleep apnea throughout the entire study period. Specifically, stimulation significantly reduced the mean apnea-hypopnea indices in non-rapid eye movement (mean +/- SD episodes per hour, 52.0 +/- 20.4 for baseline nights and 22.6 +/- 12.1 for stimulation nights; P<.001) and rapid eye movement (48.2 +/- 30.5 and 16.6 +/- 17.1, respectively; P<.001) sleep and reduced the severity of oxyhemoglobin desaturations. With improvement in sleep apnea, a trend toward deeper stages of non-rapid eye movement sleep was observed. Moreover, all patients tolerated long-term stimulation at night and did not experience any adverse effects from stimulation. Even after completing the study protocol, the 3 patients who remained free from stimulator malfunction continued to use this device as primary treatment. CONCLUSION: The findings demonstrate the feasibility and therapeutic potential for hypoglossal nerve stimulation in obstructive sleep apnea.     

A reimbursable education service for patients with hepatitis C

OBJECTIVE: To describe a pharmacy's subcutaneous injection education service for patients with hepatitis C. PRACTICE PROBLEM: Obstacles identified in the delivery of the service included the need to increase the pharmacists' level of knowledge regarding hepatitis C, establish methods for consistent education and documentation of patient education sessions, and improve coordination of scheduling appointments, pharmacy workflow, and obtaining documentation from physicians for reimbursement. PRACTICE INNOVATION: In this pharmacist-coordinated hepatitis C education service, policies and procedures were developed and implemented to ensure uniform standards of patient care and to improve pharmacists' knowledge base, patient education, and documentation of services. A one-page, faxable treatment order form was designed to help streamline physician office documentation and workflow. A task flow sheet for each patient case was used to address additional scheduling and workflow issues. Third party payers were billed for every teaching session. RESULTS: After evaluating the service and implementing several improvements, coordination of patient care became more streamlined. From March 1997 through February 2000, 94 patients received care, with appointments lasting between 45 and 90 minutes. Reimbursement was obtained from third party payers for 19% (18/94) of the teaching sessions. When claims were rejected, patients were billed for the education service. CONCLUSION: Pharmacists have an opportunity to provide a reimbursable education service to patients with hepatitis C.     

COX-2 inhibitors compared and contrasted

Non-steroidal anti-inflammatory drugs (NSAIDs) are the principal drug treatments for inflammation, pain and fever. They act primarily by inhibiting prostaglandin (PG) synthesis but this can cause adverse events (AEs). Since the discovery of two PG synthesising enzymes, COX-1 and COX-2, and the substantial evidence that sparing COX-1 is advantageous for gastric safety, great interest has focused on selective COX-2 inhibitors. Much of the impetus has come from the most recently developed compounds celecoxib and rofecoxib, which have shown spectacular sales growth. However, the older drugs etodolac, nimesulide and meloxicam, made before COX-2 was discovered, are also COX-1-sparing and have good GI safety and therapeutic activities. These five compounds show similarities and differences that are discussed in relation to aspects that include their uses, efficacy, actions and safety.     

Health-related quality of life following podiatric surgery

This 6-month prospective study investigated the outcomes of foot surgery performed by Fellows of the Australian College of Podiatric Surgeons. The study recruited 140 patients who were treated for orthopedic, neurological, or integumentary diseases of the foot. The majority of subjects who underwent podiatric surgery experienced significant postoperative improvements in a range of health-related quality-of-life dimensions as measured by the disease-specific Foot Health Status Questionnaire (FHSQ) and the generic Short Form 36 (SF-36) questionnaire. Subjects reported a reduction in foot pain, increased levels of physical function, improved general foot health perception, and improved footwear-related quality of life. No significant adverse outcomes or unplanned re-admissions to the hospital were reported. This study demonstrates the advantage of assessing health-related quality of life as opposed to patient satisfaction.     

Increased efficacy of antileishmanial antisense phosphorothioate oligonucleotides in Leishmania amazonensis overexpressing ribonuclease H

Ribonuclease H (RNase H), an enzyme that cleaves an RNA sequence base-paired with a complementary DNA sequence, is proposed to be the mediator of antisense phosphorothioate oligonucleotide (S-oligo) lethality in a cell. To understand the role of RNase H in the killing of the parasitic protozoan Leishmania by antisense S-oligos, we expressed an episomal copy of the Trypanosoma brucei RNase H1 gene inside L. amazonensis promastigotes and amastigotes that constitutively express firefly luciferase. Our hypothesis was that S-oligo-directed degradation of target mRNA is facilitated in a cell that has higher RNase H activity. Increased inhibition of luciferase mRNA expression by anti-luciferase S-oligo and by anti-miniexon S-oligo in these stably transfected promastigotes overexpressing RNase H1 was correlated to the higher activity of RNase H in these cells. The efficiency of killing of the RNase H overexpressing amastigotes inside L. amazonensis-infected macrophages by anti-miniexon S-oligo was higher than in the control cells. Thus, RNase H appears to play an important role in the antisense S-oligo-mediated killing of Leishmania. Chemical modification of S-oligos that stimulate RNase H and/or co-treatment of cells with an activator of RNase H may be useful for developing an antisense approach against leishmaniasis. The transgenic Leishmania cells overexpressing RNase H should be a good model system for the antisense-mediated gene expression ablation studies in these parasites.     

Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats

N-acylhomoserine lactones (AHLs) are small, diffusible signalling molecules, employed by Gram-negative bacteria to coordinate gene expression with cell population density. Recent in vitro findings indicate that AHLs may function as virulence determinants per se, through modification of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels. In the present study, we assessed the influence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic effect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modification of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic effect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated. In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic effects of the LPS, 6 h after the onset of its infusion. Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an influence of bacterial quorum sensing signalling molecules on the host.     

Effects of the novel selective endothelin ET(A) receptor antagonist, SB 234551, on the cardiovascular responses to endotoxaemia in conscious rats

1. In conscious, freely moving, male, Long Evans rats, regional haemodynamic responses to exogenous endothelin-1 (ET-1; 25, 50 and 250 pmol kg(-1) i.v.) were assessed in the presence of vehicle, or the selective ET(A)-receptor antagonist, SB 234551. On the following day, the effects of SB 234551 on the haemodynamic responses to lipopolysaccharide (LPS) infusion (150 microg kg(-1) h(-1), i.v.) were determined. 2. When SB 234551 was given i.v. by primed infusion at a dose of 0.3 mg kg(-1) bolus, 0.3 mg kg(-1) h(-1) infusion, it caused selective inhibition of the vasoconstrictor effects of exogenous endothelin-1, whereas at a dose of 1 mg kg(-1), 1 mg kg(-1) h(-1), SB 234551 also inhibited some of the vasodilator effects of endothelin-1. 3. Infusion of LPS, in the presence of vehicle, caused a short-lived (1 - 2 h) hypotension, tachycardia, and vasodilatation in renal, superior mesenteric and hindquarters vascular beds. Thereafter, blood pressure, heart rate and mesenteric vascular conductance returned to baseline values, but renal vasodilatation persisted, and there was vasoconstriction in the hindquarters. 4. In the presence of SB 234551 (0.3 mg kg(-1), 0.3 mg kg(-1) h(-1)), the early (1 - 2 h) cardiovascular responses to LPS infusion were unaffected, but the subsequent recovery of mean arterial blood pressure was impaired, due to developing vasodilatation in the mesenteric and, to a lesser extent, hindquarters, vascular beds. SB 234551 had no effect on the renal haemodynamic responses to LPS infusion. 5. The results confirm an important, regionally-selective, vasoconstrictor role for endogenous endothelin in this model of endotoxaemia.     

The effects of pyridostigmine bromide on progressive ratio performance in male and female rats

Small doses of pyridostigmine bromide (PB) affect the acquisition and maintenance of food-maintained behavior in laboratory animals. The present experiment was designed to investigate the effects of this drug on food motivation. Male and female rats were trained to respond on a progressive-ratio schedule of reinforcement and treated with different doses of PB. PB dose-dependently decreased breaking points and response rates in male and female rats. Gender differences were not observed. The results indicate that decreased food motivation may be a factor that contributes to the behavioral effects of PB administration.     

p53 and K-ras mutations in lung cancers from former and never-smoking women

Somatic p53 mutations are common in lung cancer. Active cigarette smoking is positively correlated with the total frequency of p53 mutations and G:C to T:A transversions on the nontranscribed (DNA coding) strand. Mutational hotspots within the p53 gene, e.g., codon 157, have been identified for tobacco-related lung cancer, whereas these same mutations are found rarely in other cancers. Such data implicate specific p53 mutations as molecular markers of smoking. Because limited data exist concerning the p53 mutation frequency and spectra in ex-smokers and nonsmokers, we have analyzed p53 and K-ras mutations in 126 lung cancers from a population-based case-control study of nonsmoking (n = 117) or ex-smoking (n = 9) women from Missouri with quantitative assessments of exposure to environmental tobacco smoke. Mutations in the p53 gene were found in lung cancers from lifetime nonsmokers (19%) and ex-smokers (67%; odds ratio, 9.08; 95% confidence interval, 2.06-39.98). All deletions were found in tumors from patients who were either ex-smokers or nonsmokers exposed to passive smoking. The G:C to A:T transitions (11 of 28; 39%) were the most frequent p53 mutations found and clustered in tumors from lifetime nonsmokers without passive smoke exposure. The incidence of K-ras codon 12 or 13 mutations was 11% (14 of 115 analyzed) with no difference between long-term ex-smokers and nonsmokers. These and other results indicate that p53 mutations occur more commonly in smokers and ex-smokers than in never-smokers. Such comparisons provide additional evidence of genetic damage caused by tobacco smoke during lung carcinogenesis.