Potential of Three Ethnomedicinal Plants as Antisickling Agents.

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicines. The potential of aqueous extracts of Cajanus cajan leaf and seed, Zanthoxylum zanthoxyloides leaf, and Carica papaya leaf in sickle cell disease management was investigated in vitro using freshly prepared 2% sodium metabisulfite for sickling induction. The results indicated that the percentage of sickled cells, which was initially 91.6% in the control, was reduced to 29.3%, 41.7%, 32.8%, 38.2%, 47.6%, in the presence of hydroxyurea, C. cajan seed, C. cajan leaf, Z. zanthoxyloides leaf, and C. papaya leaf extracts, respectively, where the rate of polymerization inhibition was 6.5, 5.9, 8.0, 6.6, and 6.0 (×10-2) accordingly. It was also found that the RBC resistance to hemolysis was increased in the presence of the tested agents as indicated by the reduction of the percentage of hemolyzed cells from 100% to 0%. The phytochemical screening results indicated the presence of important phytochemicals including tannins, saponins, alkaloids, flavonoids, and glycosides in all the plant extracts. Finally, gas chromatography-mass spectrometry analysis showed the presence of important secondary metabolites in the plants. These results suggest that the plant extracts have some potential to be used as alternative antisickling therapy to hydroxyurea in SCD management.

Identification of Coq11, a new coenzyme Q biosynthetic protein in the CoQ-synthome in Saccharomyces cerevisiae.

Coenzyme Q (Q or ubiquinone) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail and is required for mitochondrial electron transport. In the yeast Saccharomyces cerevisiae, Q is synthesized by the products of 11 known genes, COQ1-COQ9, YAH1, and ARH1. The function of some of the Coq proteins remains unknown, and several steps in the Q biosynthetic pathway are not fully characterized. Several of the Coq proteins are associated in a macromolecular complex on the matrix face of the inner mitochondrial membrane, and this complex is required for efficient Q synthesis. Here, we further characterize this complex via immunoblotting and proteomic analysis of tandem affinity-purified tagged Coq proteins. We show that Coq8, a putative kinase required for the stability of the Q biosynthetic complex, is associated with a Coq6-containing complex. Additionally Q6 and late stage Q biosynthetic intermediates were also found to co-purify with the complex. A mitochondrial protein of unknown function, encoded by the YLR290C open reading frame, is also identified as a constituent of the complex and is shown to be required for efficient de novo Q biosynthesis. Given its effect on Q synthesis and its association with the biosynthetic complex, we propose that the open reading frame YLR290C be designated COQ11.

A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae.

Coenzyme Qn (ubiquinone or Qn) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1-coq9 mutants have defects in Q biosynthesis, lack Q6, are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q2, Q3, Q10, or demethoxy-Q3 in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C. crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q6 in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain.

Specific detection of the Old World screwworm fly, Chrysomya bezziana, in bulk fly trap catches using real-time PCR.

The Old World screwworm fly (OWS), Chrysomya bezziana Villeneuve (Diptera: Calliphoridae), is a myiasis-causing blowfly of major concern for both animals and humans. Surveillance traps are used in several countries for early detection of incursions and to monitor control strategies. Examination of surveillance trap catches is time-consuming and is complicated by the presence of morphologically similar flies that are difficult to differentiate from Ch. bezziana, especially when the condition of specimens is poor. A molecular-based method to confirm or refute the presence of Ch. bezziana in trap catches would greatly simplify monitoring programmes. A species-specific real-time polymerase chain reaction (PCR) assay was designed to target the ribosomal DNA internal transcribed spacer 1 (rDNA ITS1) of Ch. bezziana. The assay uses both species-specific primers and an OWS-specific Taqman((R)) MGB probe. Specificity was confirmed against morphologically similar and related Chrysomya and Cochliomyia species. An optimal extraction protocol was developed to process trap catches of up to 1000 flies and the assay is sensitive enough to detect one Ch. bezziana in a sample of 1000 non-target species. Blind testing of 29 trap catches from Australia and Malaysia detected Ch. bezziana with 100% accuracy. The probability of detecting OWS in a trap catch of 50 000 flies when the OWS population prevalence is low (one in 1000 flies) is 63.6% for one extraction. For three extractions (3000 flies), the probability of detection increases to 95.5%. The real-time PCR assay, used in conjunction with morphology, will greatly increase screening capabilities in surveillance areas where OWS prevalence is low.

MRI and clinical findings in patients with ankylosing spondylitis eligible for anti-tumour necrosis factor therapy after a short course of etoricoxib.

OBJECTIVE: To describe and assess the response to short-term etoricoxib as shown by MRI and clinical variables in patients with ankylosing spondylitis (AS) selected for eligibility for anti-tumour necrosis factor therapy. METHODS: In a 6-week open-label study, 22 patients with AS and eligible for biological therapy were treated with 90 mg of etoricoxib daily. Clinical and laboratory parameters were obtained and MRI of the sacroiliac joints and the lower thoracic and lumbar spine performed at baseline and at week 6. The primary end point was the proportion of patients fulfilling the SpondyloArthritis international Society (ASAS) response criteria for biological therapies (ASASBIO) while secondary end points included the change in MRI-determined bone lesions. RESULTS: Eight of 20 completers improved enough to meet the ASASBIO response criteria and most clinical variables improved significantly. Fifteen patients had a total of 63 MRI-detectable lesions; overall, 13/60 lesions with paired scans either resolved completely or improved, while five lesions worsened or appeared during treatment. CONCLUSION: Etoricoxib is an effective symptomatic treatment for patients with AS; however, its effect on MRI-detected lesions is small. Further studies are needed to determine the effect of etoricoxib on MRI-determined bone oedema.

Does the use of tumour necrosis factor antagonist therapy in poor prognosis, undifferentiated arthritis prevent progression to rheumatoid arthritis?

OBJECTIVES: To evaluate the ability of tumour necrosis factor (TNF) antagonist therapy to produce remission and prevent progression to rheumatoid arthritis (RA) in patients with poor prognosis undifferentiated inflammatory arthritis (UA). METHODS: Patients with UA of <12 months' duration and having relapsed after a single parenteral corticosteroid injection were recruited into a double-blind, placebo-controlled trial of infliximab or placebo monotherapy administered at weeks 0, 2, 6 and 14. Methotrexate was added at week 14 if no clinical response (raised C-reactive protein (CRP) and clinical synovitis) was achieved. Standard outcomes were collected at baseline, infusion visits and weeks 26 and 52. The primary outcome was clinical remission at week 26. RESULTS: 17 patients were randomised (10 infliximab, 7 placebo) all with poor prognostic features. At week 14, the infliximab group had greater improvements in CRP and Health Assessment Questionnaire (HAQ) but by week 26 there was just a trend favouring infliximab for early morning stiffness, tender joint score, swollen joint score and HAQ; there was no significant difference in 28 joint count Disease Activity Score between the two groups. Furthermore, only three patients were in clinical remission (two infliximab, one placebo). By week 52, 100% patients in the infliximab group and 71% (5/7) patients in the placebo group had developed RA. CONCLUSIONS: In poor prognosis UA, a short course of TNF antagonist therapy provided modest short-term relief but did not prevent the development of RA. Patients with UA with a poor prognosis relapsing after corticosteroid have a high risk of evolving to RA and are suitable candidates for interventional treatment.

Exercise training-induced hypervolemia in the horse.

The purpose of this study was to determine if a chronic hypervolemia would accompany endurance exercise training in the horse. Six mature previously inactive horses were utilized for this study. During the 5-wk experiment, five of the horses were trained for 14 d on a treadmill ergometer at a constant treadmill speed of 5.6 km X hr-1 and a constant grade of 12.5% for graduated lengths of time. One horse was trained by lunging at a trotting pace in a round pen. Following training, plasma volume increased by 4.7 1 (29.1%, P less than 0.05). Although the rate of daily water intake did not change during the training period, 24-h urine output decreased by an average of 3.5 1 X d-1 (-24.5%, P less than 0.05). Resting glomerular filtration rate and the rate of sodium clearance were not altered by training. However, urea, potassium, and osmotic clearance were decreased by training (P less than 0.05) while free water clearance was increased (P less than 0.05). Resting plasma aldosterone and arginine vasopressin concentrations were not altered by training. Plasma potassium concentration was significantly decreased (P less than 0.05) following the 2 wk of training. These data would appear to suggest that renal control mechanisms affecting water reabsorption via the re-absorption of urea and osmotically active substances other than sodium provide the primary route for the training-induced hypervolemia seen in horses.

Measuring coping in breast cancer.

The emotional distress associated with breast cancer varies between individual women. These variations may be accounted for by differences in cognitive and behavioural coping responses to diagnosis. This study has attempted to develop a reliable, situation-specific approach to the measurement of coping responses in women with breast cancer. It has adapted a general coping questionnaire and modified an interview-based schedule for coping with cancer. The strengths and weaknesses of the interview and self-report methods of assessment are highlighted. Consistent results from these complementary approaches have been obtained. Both indicate the extensive use of cognitive avoidance and positive reappraisal. It has been shown that the majority of patients use a wide repertoire of coping responses which challenges the notion of mutually exclusive coping styles. These measures may be employed to examine the relationship between women's thoughts and behaviours in response to the diagnosis and treatment of breast cancer and subsequent psychological outcome.

Molecular epidemiological characterization of respiratory isolates of Moraxella catarrhalis in a pediatric intensive care unit.

A perceived increase in the number of isolates of Moraxella catarrhalis from the respiratory secretions of patients intubated in the pediatric intensive care unit prompted a review of the clinical profiles of such patients and restriction enzyme analysis of the strains involved. Over two months, of 192 patients admitted to the unit, 154 were intubated. Of the 46 for whom endotracheal tube specimens were submitted to the laboratory, M catarrhalis was isolated in 12. M catarrhalis was not felt to be a significant respiratory pathogen by the attending medical staff in any of the patients from whom it was isolated. In only two patients (17%) could nosocomial acquisition be firmly invoked. Restriction enzyme analysis of the 12 strains ruled out the presence of an epidemic strain. Isolation of M catarrhalis from intubated children does not necessarily imply pathogenicity nor an outbreak situation.

Availability and Use of Contraceptive Implants in Jamaica: Results of a Review of Medical Records and a Survey of Reproductive Healthcare Providers in Six Public Health Centres / Disponibilidad y uso de los implantes anticonceptivos en Jamaica: resultados de una revisión de las historias clínicas y una encuesta de los proveedores de salud reproductiva en seis centros de salud pública

ABSTRACT Objective: The prevalence of sub-dermal contraceptive implant use in Jamaica is low, despite growing international acceptance of long-acting reversible contraception. This study assessed the availability, effectiveness, side-effects and utilization of sub-dermal contraceptive implants and described the characteristics of users over a one-year period. Methods: We reviewed the medical records of women aged 15-45 years who utilized contraceptive implant-related services at any of the six included public health centres in Jamaica during 2013, and surveyed 20 available reproductive healthcare providers. Results: In 2013, 738 women attended a Jamaican public health centre for contraceptive implant services: 493 (66.8%) for insertion, 202 (27.4%) for removal and 53 (7.2%) for follow-up visits (10 women had the same implant inserted and removed in 2013). The women's median age was 26.0 years, 24.3% were ≤ 18 years, and 85.9% had ≥ 1 child. Most women (68.5%) did not have documented side-effects; irregular bleeding, the most commonly documented side-effect, was recorded for 24%. Of the 493 women who had implants inserted, three (0.6%) were identified to be pregnant within three months of insertion. Among the 202 women who had implants removed, 11 (5.4%) experienced complications with removal. Reproductive healthcare providers highlighted the need for an expansion of contraceptive implant availability and provider training. Conclusion: Sub-dermal implants have few insertion complications and side-effects and are effective, but were underutilized in Jamaica. Increased implant availability and enhanced reproductive healthcare provider training may improve implant utilization and reduce unintended pregnancy rates in Jamaica.

RESUMEN Objetivo: La prevalencia del uso de implantes anticonceptivos subdérmicos en Jamaica es baja, a pesar de la creciente aceptación internacional de la anticoncepción reversible de acción prolongada. El presente estudio evalúa la disponibilidad, efectividad, efectos secundarios y utilización de los implantes anticonceptivos subdérmicos, y describe las características de los usuarios durante el período de un año. Métodos: Se revisaron las historias clínicas de mujeres de 15 a 45 años de edad, que utilizaron servicios relacionados con los implantes anticonceptivos en cualquiera de los seis centros de salud pública de Jamaica durante 2013, y se encuestaron 20 profesionales de salud reproductiva disponibles. Resultados: En 2013, 738 mujeres asistieron a un centro de salud pública de Jamaica para recibir servicios de implantes anticonceptivos: 493 (66.8%) para inserción, 202 (27.4%) para eliminación, y 53 (7.2%) para visitas de seguimiento (a 10 mujeres se les insertó y se les quitó el mismo implante en 2013). La edad promedio de las mujeres fue 26.0 años, 24.3% tenían ≤ 18 años, y el 85.9% tenían ≥ 1 niño. La mayoría de las mujeres (68.5%) no presentaban efectos secundarios documentados. El sangramiento irregular - el efecto secundario más comúnmente documentado - se registró en un 24%. De las 493 mujeres que tenían implantes insertados, se halló que tres (0.6%) resultaron embarazadas en el plazo de tres meses tras la inserción. De las 202 mujeres a las que se les había retirado el implante, 11 (5.4%) tuvieron complicaciones en el proceso de la eliminación. Los profesionales de la salud reproductiva destacaron la necesidad de expandir la disponibilidad de implantes anticonceptivos y la capacitación de proveedores. Conclusión: Los implantes subdérmicos presentan pocas complicaciones a la hora de su inserción, y tienen pocos efectos secundarios. Sin embargo, son subutilizados en Jamaica, a pesar de ser efectivos. Una mayor disponibilidad de implantes y una mejor capacitación de los profesionales de la salud reproductiva pueden mejorar la utilización de implantes y reducir las tasas de embarazos no intencionados en Jamaica.

Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study.

OBJECTIVE: To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis (AS) using MRI and DXA to monitor its impact on bone. METHODS: In this single centre study 42 subjects with active AS were treated with methotrexate and were randomly assigned, in a ratio of 2:1, to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks. The primary outcome was improvement in disease activity as shown by the BASDAI at week 30. MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density. RESULTS: Both therapeutic agents were well tolerated with no dropouts due to adverse events. A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 (p = 0.017) than in the placebo arm, but this was not maintained by week 30 (p = 0.195), 8 weeks after the last infusion, at which stage disease flares were reported by some subjects. MRI showed that the mean number of lesions resolving for each subject from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group (p = 0.016). CONCLUSIONS: Infliximab in combination with methotrexate was a safe and efficacious treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI. However, disease flares were reported 8 weeks after the last infusion, indicating that addition of methotrexate failed to extend the infliximab dosing interval.

Smallpox eradication: selected management issues.

The eradication of smallpox was dependent on the attainment of a high level of herd immunity during the consolidation and maintenance phases of the eradication program, after mass vaccination effort had reduced the incidence of the disease to a few endemic areas in the world. Immunity was possible through the immunization of susceptible population. Attainment of effective immunization in both large and small countries, with both concentrated and dispersed population settlement patterns, was dependent not only on improved vaccination technology, notably the widespread availability of heat-stable freeze-dried vaccine and the use of the bifurcated needle, but also on the way eradication programs were designed and implemented. This paper will outline important components of the smallpox eradication program, particularly, information management, personnel management, and material resources management. Although they were critical to the eventual success of the program, there has been little consolidated effort to review these management strategies. The paper, to a large extent, concentrates on the eradication programs of Bangladesh, India, and West Africa, given that these come to the forefront in terms of reviewing management strategies in the internationally available literature.

Ibuprofen-induced aseptic meningitis in rheumatoid arthritis.

OBJECTIVE: To report a case of aseptic meningitis related to ibuprofen ingestion. CASE SUMMARY: We discuss the case of a 56-year-old white man with a history of rheumatoid arthritis and hypertension who became confused, nauseated, and began to vomit within 2 hours of the ingestion of ibuprofen. A diagnosis of ibuprofen-induced aseptic meningitis was made based on the patient's physical and laboratory findings, the quick onset and resolution of symptoms, and his medical history. DISCUSSION: Ibuprofen-induced aseptic meningitis has been most frequently reported in patients with systemic lupus erythematosus. However, there have been reports of this reaction in patients with other underlying disease states. Various nonsteroidal antiinflammatory drugs have been reported to cause this reaction, but ibuprofen is the most common offending agent. A drug-related cause should be considered in any patient who presents with typical meningitis symptoms, such as fever, headache, and stiff neck, that occur within hours of ingesting a drug. CONCLUSIONS: Although persons with systemic lupus erythematosus appear to have an increased risk for this type of reaction, the development of signs and symptoms in other patients warrants the consideration of nonsteroidal antiinflammatory drugs as the cause of aseptic meningitis.