Inhibition of serum and transforming growth factor beta (TGF-β1)-induced DNA synthesis in confluent airway smooth muscle by heparin

1. Airway remodelling occurs in asthma and involves an increase in airway smooth muscle mass through cell proliferation and hypertrophy. Increased eosinophil density in the airways is a feature of asthma. Eosinophils exhibiting activation in the airways of asthmatics also exhibit increased expression of transforming growth factor beta (TGF-β1). We have examined the capacity of TGF-β1 and epidermal growth factor (EGF) to influence airway smooth muscle division and the effect of heparin on TGF-β1, EGF and serum-induced smooth muscle DNA synthesis in confluent airway smooth muscle cells (ASMC) as an indication of entry into S phase preceding mitogenesis.
2. ASMC were obtained from cell populations growing out from explanted bovine trachealis muscle sections. Cell division was monitored in sparse plated cells by direct cell counting following nuclear staining. Cell DNA synthesis in confluent cells was monitored by uptake of [³H]-thymidine.
3. TGF-β1 (100 pM) inhibited FBS (10%)-induced smooth muscle division in sparsely plated cells (40%). TGF-β1 (100 pM) increased cell DNA synthesis (200%) in confluent cells in the presence of bovine serum albumin (BSA, 0.25%). EGF (0.7 nM) also increased airway smooth muscle DNA synthesis (69%) in the presence of BSA (0.25%). The facilitatory effect of TGF-β1 was observed between 1–100 pM, while that of EGF was observed between 20–200 pM.
4. Heparin inhibited serum and TGF-β1-induced DNA synthesis in confluent ASMC (55%), consistent with our previous observation of inhibition of division in sparsely populated ASMC (Kilfeather et al., 1995a). This action of heparin was observed between concentrations of 1–100 μg ml⁻¹. Heparin did not inhibit DNA synthesis in response to EGF. An anti-mitogenic effect of heparin was also observed against responses to combined exposure to TGF-β1 and EGF.
5. There was a clear inhibitory effect of heparin in absolute terms against serum-induced division in cells plated at 10, 20 and 45×10³ cells cm⁻². The inhibitory effect of heparin was also observed at a plating density of 45,000 cells cm⁻² when responses to serum were expressed as fold-stimulation of basal DNA synthesis.
6. These findings demonstrate a potential role of TGF-β1, EGF and heparin-related molecules in regulation of airway smooth muscle division.

     

Medical mortality in an emergency department in Nigeria: the transition is obvious!

IntroductionThe emergency department (ED), a major entry point into the hospital, provides an insight to the type of cases seen, the quality of care and mortality spectrum in a health institution. We aim to identify the spectrum of medical causes of mortality in our ED, the demographic pattern and duration of stay before death.MethodThis is a retrospective study that looked at medical mortality in the ED from January 2004 to December 2009. We obtained data on the demographics and causes of death from the medical records and case notes of the deceased.ResultsA total of 16587 patients were admitted during the period under review, of these 1262 (7.61%) died in the ED. The male to female ratio was 1.58:1.0 [772 males (61.2%), and 489 females (38.8%)]. Mortality was highest among the 20–45 years age range, followed by 46–65 years, >65 years and < 20 years in decreasing frequency [589(46.7%), 421(33.4%), 186 (14.8%) and 66(5.2%) respectively]. The three most common causes of death were stroke 315(25%), HIV related illnesses 126(10.0%), and heart failure 123(9.7%). Most deaths occurred less than 24hours of admission, 550(43.6%), followed by one day (36.0%) and two days (10.8%) post admissions respectively.ConclusionThe commonest cause of death in the ED was stroke. The burden of death was highest in the younger age group, with most occurring less than 24 hours of admission.     

Characterization of a Novel Thermostable Nuclease Homolog (NucM) in a Highly Divergent Staphylococcus aureus Clade

A thermostable nuclease homologue (Nuc_M) in an animal-associated divergent clade of Staphylococcus aureus in sub-Saharan Africa has a highly divergent nucleotide sequence compared to those of the classical nuc1 and nuc2 genes of S. aureus. Its deduced amino acid sequences, tertiary structures, and nuclease activities, however, are similar.     

Intestinal ameliorative effects of traditional Ogi-tutu,Vernonia amygdalina and Psidium guajava in mice infected with Vibrio cholera

BackgroundCholera, a severe acute watery diarrhea caused by Vibrio cholerae is endemic in Nigeria with most cases occurring in the rural areas. In South West Nigeria, some individuals resort to alternative treatments such as Ogi-tutu, Psidium guajava and Vernonia amygdalina during infections. The effectiveness of these alternatives in the prevention and treatment of V. cholerae infection requires experimental investigation.ObjectiveThis study was designed to investigate the ameliorative effects of Ogi-tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae.MethodsPreliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup diffusion assay. For ameliorative effects, adult mice were inoculated with 100 µl (106 cells) of Vibrio cholerae and dosed at 0 h (immediate prevention) and 4 h (treatment of infection) and their intestines were histopathologically evaluated.ResultsThe histopathological changes were the same irrespective of the treated groups, but the lesions varied in extent and severity. The ameliorative effects in decreasing order were V. amygdalina > P. guajava > Ogi-tutu.ConclusionV. amygdalina gave the best ameliorative effects in the prevention and treatment of V. cholerae infection.     

Correlation of serum PSA and Gleason score in Nigerian men with prostate cancer

Objective  Prostate cancer is an important cause of morbidity and mortality worldwide. While the predisposing factors are not fully understood, African descent is an important risk factor, and prostate cancer has become the number-one cancer in Nigerian men. This was a retrospective study of the correlation between serum prostate specific antigen (PSA) and Gleason grade and score in patients of Nigerian descent. Patients and Methods  The University College Hospital (UCH) Ibadan Cancer Registry was used to identify and quantify the incidence of prostate cancers occurring between 1998 and 2000. The histological slides of appropriate cases were reviewed to confirm the Gleason grade and score. The serum PSA values were retrieved from the patients' case notes and laboratory files. The data obtained were subjected to statistical analysis to look for associations and correlations. Results  The study included 67 men with prostate adenocarcinoma and PSA measurements who were diagnosed and treated at the UCH Ibadan between January 1998 and December 2000. There was a positive correlation between serum PSA and Gleason grade, as well as between serum PSA and Gleason score in our cohort of Nigerian African men with prostate cancer. PSA levels were significantly lower in patients with stage B disease than in patients with stage D disease. Conclusion  Serum PSA is significantly higher in metastatic than in localized disease. Further studies are necessary to determine biomarkers that complement serum PSA and the Gleason grading system in the prognostication of prostate cancer in African patients.     

Interventions for treating oral mucositis for patients with cancer receiving treatment

Background: Treatment of cancer is increasingly effective but associated with short and long‐term side effects. Oral side effects, including oral mucositis (mouth ulceration), remain a major source of illness despite the use of a variety of agents to treat them. Objectives: To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy or radiotherapy or both. Search strategy: Computerized searches of Cochrane Oral Health Group’s Trials Register; Cochrane Pain, Palliative and Supportive Care Group’s Trials Register; CENTRAL; MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. Date of the most recent searches June 2006: CENTRAL (The Cochrane Library 2006, Issue 2). Selection criteria: All randomized controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy or radiotherapy or both. Outcomes were oral mucositis, time to heal mucositis, oral pain, duration of pain control, dysphagia, systemic infection, amount of analgesia, length of hospitalization, cost and quality of life. Data collection and analysis: Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomization, blindness and withdrawals. Quality assessment was carried out on these three criteria. The Cochrane Oral Health Group statistical guidelines were followed and risk ratio (RR) values calculated using fixed effect models. Main results: Twenty‐six trials involving 1353 patients satisfied the inclusion criteria. Four agents, each in single trials, were found to be effective for improving (allopurinol RR 3.33, 95% confidence interval (CI) 1.06 to 10.49; granulocyte macrophage‐colony stimulating factor RR 4.23, 95% CI 1.35 to 13.24; immunoglobulin RR 1.81, 95% CI 1.24 to 2.65; human placentral extract RR 4.50, 95% CI 2.29 to 8.86) or eradicating mucositis (allopurinol RR 19.00, 95% CI 1.17 to 307.63). Three of these trials were rated as at moderate risk of bias and one as at high risk of bias. The following agents were not found to be effective: benzydamine HCl, sucralfate, tetrachlorodecaoxide, chlorhexidine and ‘magic’ (lidocaine solution, diphenhydramine hydrochloride and aluminum hydroxide suspension). Six trials compared the time to heal and mucositis was found to heal more quickly with two interventions: granulocyte macrophage‐colony stimulating factor when compared to povidone iodine, with mean difference ?3.5 days (95% CI ?4.1 to ?2.9) and allopurinol compared to placebo, with mean difference ?4.5 days (95% CI ?5.8 to ?3.2). Three trials compared patient controlled analgesia (PCA) to the continuous infusion method for controlling pain. There was no evidence of a difference, however, less opiate was used per hour for PCA, and the duration of pain was shorter. One trial demonstrated that pharmacokinetically based analgesia (PKPCA) reduced pain compared with PCA: however, more opiate was used with PKPCA. Authors’ conclusions: There is weak and unreliable evidence that allopurinol mouthwash, granulocyte macrophage‐colony stimulating factor, immunoglobulin or human placental extract improve or eradicate mucositis. There is no evidence that patient controlled analgesia (PCA) is better than continuous infusion method for controlling pain, however, less opiate was used per hour, and duration of pain was shorter, for PCA. Further, well designed, placebo‐controlled trials assessing the effectiveness of allopurinol mouthwash, granulocyte macrophage‐colony stimulating factor, immunoglobulin, human placental extract, other interventions investigated in this review and new interventions for treating mucositis are needed.     

E2RIA系统误差的分析

目的通过分析放射免疫测定(RIA)血清雌二醇(E2)的系统误差,提高测定的准确度.方法用回收实验、溶血和类似物干扰实验及方法比较实验进行系统误差分析.结果回收实验加入浓度100pg/ml回收率101.6%,加入浓度360pg/ml回收率104.3ng/ml.溶血干扰实验平均百分干扰值为-23.36%;类似物干扰实验干扰值雌二醇0.19%,雌酮13.1%,孕酮0.11%,睾酮0.45%.125I-RIA和3H-RIA方法比较实验结果Y(125I-RIA)=16.84+1.11X(3H-RIA),t=11.75,p＜0.05.结论125I-RIA测定血清雌二醇准确度高,标本溶血和雌酮影响测定结果,两种测定方法存在系统误差.     

Pneumonia and pneumonitis in childhood malignancy

We conducted a survey over a 21-year period of the incidence and risk of occurrence of episodes of pneumonia and pneumonitis in children treated for solid tumours and leukaemia. One hundred episodes occurred amongst 219 patients, seven of which were associated with death. Focal opacification on the chest radiograph was more common than diffuse opacification. Patients with leukaemia had a significantly higher rate of occurrence of pneumonia and pneumonitis during the periods of induction and maintenance compared with the off-treatment period, and during the relapse period compared with the period of maintenance. Patients with solid tumours had a significantly higher rate of occurrence during treatment compared to the off-treatment period. The rate of occurrence on treatment was the same in patients with solid tumours and acute leukaemia. Children with malignancy have a high incidence of pneumonia and pneumonitis and death is rare if the patient does not have terminal malignant disease.