Catecholamines Inhibit Gastric Epithelial [RGM-1] Cell Proliferation via Beta Adrenoceptors

Catecholamines have been implicated in the modulation of normal cell growth, exerting inhibitory or excitatory control depending on the cell type. However, there is a dearth of information on the role of adrenergic mediators in gastric cell proliferation. In the present study, the effects of adrenaline (ADR) and noradrenaline (NOR) on mucosal cell growth and the cell cycle were evaluated in vitro using a normal rat gastric mucosal cell line RGM-1. Cell proliferation was assessed using [3H]-thymidine incorporation and cell cycle patterns were determined by DNA labeling with propidium iodide and flow cytometric quantification. The expressions of adrenoceptors in RGM-1 were determined by Western blot. ADR (0.01 - 10microM) and NOR (0.01 - 10microM) inhibited the growth of RGM-1 cells in a concentration-dependent manner. Pre-treatment of cells with ADR and NOR also inhibited the proliferation stimulated by epidermal growth factor (EGF). Neither phentolamine (non-selective alpha-adrenergic blocker), methoxamine (alpha1-selective agonist) nor clonidine (alpha2-selective agonist) significantly affected the inhibition of cell proliferation produced by ADR and NOR. Propranolol (non-selective beta-adrenergic blocker) and butoxamine (selective beta2-adrenergic blocker) significantly (but not totally) reversed the inhibitory action of ADR on cell proliferation. Furthermore, procaterol (selective beta-2 agonist) but not dobutamine (selective beta-1 agonist) had effects similar to those produced by ADR and NOR. Exposure of RGM-1 cells to both ADR and NOR caused significant inhibition of the G1 - S cycle progression as evidenced by the higher percentage of the G0/G1 phase and a decreased S- phase. This effect was blocked by pre-treatment with propranolol but not phentolamine These results indicate that catecholamines inhibit the proliferation of RGM-1 cells probably partly through beta-2 receptors. ©Physiological Society of Nigeria.published_or_final_versio

Gastric Mucosa Re-epithelisation, Oxidative Stress and Apoptosis During Healing of Acetic Acid-Induced Ulceration in Thyroxine Treatment and Thyroidectomy on Rats

We had earlier reported that thyroxine treatment accelerates gastric ulcer healing while thyroidectomy delayed the processes of healing. Thus, this research was carried out to gain more insight about the mechanisms by which thyroxine affect ulcer healing. Male albino rats (160 – 200g) were used. They were divided into four groups viz: control, thyroidectomised, thyroidectomised with thyroxine treatment (100μg/kg/day) and Sham operated animals treated with thyroxine. After 35 days of drug treatment and surgery, ulcer was induced in stomach of animals using acetic acid method. Animals were sacrificed on days 3, 7 and 10 post ulcer induction for ulcer healing assessment. Healing was observed by measuring ulcer depth and width, lipid peroxidation and DNA fragmentation during healing. Result showed that by day 10, thyroxine treatment significantly decreased the ulcer width and depth by 69.3 ± 1.5% and 65.7 ± 1.4% (p< 0.01) respectively while thyroidectomy significantly reduced by (34.1 ± 0.5%) and (35.6 ± 7.5%) (p< 0.05) compared with control (40.5 ± 2.2%) and (53.9 ± 1.6%). Thyroxine treated animals had highest reduction in lipid peroxidation (57.0 ± 0.5% [p< 0.001]) and the least reduction in thyroidectomised animals (15.7 ± 1.6% [p< 0.05]) as compared with control (19.6 ± 1.6%). DNA fragmentation was low in all groups by day 3, but by day 10 the higher DNA fragmentation in thyroxine treated animal supports the rapid reduction in ulcer dimensions recorded. In conclusion, thyroxine treatment accelerated gastric ulcer healing by accelerating mucosa re-epithelization, reduction of lipid peroxidation and apoptotic mechanism.Keywords: Ulcer Healing; Thyroxine; Lipid peroxidation; Apoptosi

Antioxidant And Anti-Inflammatory Properties Of A Flavonoid Fraction From The Leaves Of Voacanga Africana

In this study we used several models for evaluation of probable anti-inflammatory and anti-nociceptive effects of the flavonoid fraction of the leaves of Voacanga Africana, using mice and rats. The extract (50 - 150mg/kg, p.o) inhibited, in a dose-related manner, carrageenan induced paw oedema in rats. The extract caused a significant inhibition of the cotton-pellet granuloma. Vascular permeability induced by acetic-acid in the peritoneum of the animals was equally inhibited. The extract also exhibited significant analgesic action in acetic acid- induced pain in mice. There was reduction of writhings induced by acetic acid. In the formalin test, the extract caused inhibition of the neurogenic (first phase) and inflammatory phase (second phase) of formalin-induced pain. The extract also produced anti-nociception in the animals, as assessed by the tail flick, hot-plate and limb-withdrawal tests. These findings suggest that the leaf extract of Voacanga Africana has potent anti-imfiammatory and anti-nociceptive action. Key words: Voacanga africana; anti-inflammatory and anti-nociceptive activities. Nigerian Journal of Physiological Sciences Vol.19(1&2) 2004: 69-7

Effect of zinc treatment on intestinal motility in experimentally induced diarrhea in rats

Zinc supplementation is a critical new intervention for treating diarrheal episodes in children. Recent studies suggest that administration of zinc along with new low osmolarity oral rehydration solutions / salts (ORS) can reduce the duration and severity of diarrheal episodes for up to three months. Several mechanisms of action of zinc has been proposed, however there is dearth of information about the effect of zinc on intestinal motility during diarrhea. Male albino Wistar rats (80-100g) were used. The effect of different doses of zinc sulphate (25, 50, 100, 150mg/Kg) on the number of wet faeces was investigated. Intestinal motility during castor oil induced diarrhea was assessed using activated charcoal meal and the mechanisms of action of zinc sulphate on motility were investigated. The effective dose of zinc sulphate (100mg/Kg) significantly reduced (p< 0.001) the number of wet faeces (3.0 ± 0.00) compared with control (6.8 ± 0.25) during diarrhea. This antidiarrheal effect of zinc was abolished by propranolol and nifedipine. Zinc sulphate significantly reduced (p< 0.05) intestinal transit time (60.7 ± 7.13%) compared with control (85.7 ± 2.35%). It is concluded that zinc sulphate reduces the frequency of wet faeces output and intestinal motility during diarrhea via activation of β adrenergic receptor and L-type Ca2+ channel.Keywords: Diarrhea, Zinc, Intestinal motility, Adrenergic receptor, Calcium channel

Antioxidative action of manganese treatment in delayed healing of acetic acid-induced ulceration in rat stomach

Background: The role of manganese in disease treatment such as diabetes, arthritis and osteoporosis has been well documented. Unhealed or delayed gastric ulcer is an experimental model mimicking recurrent peptic ulcer of which information is lacking. This study sought to examine the role of manganese during delayed gastric ulcer healing and its probable mechanism. Methods: 75 male wistar rats (150-170g) were divided into 5 groups of 15 rats each; Groups 1 was delayed untreated ulcerated animals while II, III, IV and V received 100mg/kg Manganese, 50mg/kg Manganese, 40 mg/kg Cimetidine and 100mg/kg Vitamin E respectively. Ulcer was induced by serosa application of 30% acetic acid and by day 5 post-induction, ulcer was delayed by continuous subcutaneous administration of 2mg/kg indomethacin (once daily) for 14 days simultaneously. Body weights of experimental animals were monitored daily, haematological studies; stomach ulcer score, biochemical and histological analysis were assessed by days 3, 7 and 14 indomethacin and drug treatment after quick decapitation. Data were expressed as Mean + SEM, analysed using one-way ANOVA while p=0.05 was considered statistically significant. Results: The percentage healing rates in Manganese (50mg/kg and 100mg/kg respectively) significantly increased on days 3 (76.5% and 42.9%), 7 (97.3% and 75.5%) and 14 (100% and 97.5%). Haematological data revealed increased circulating blood cells in the Manganese and Vitamin E treated groups compared with ulcerated untreated groups. Manganese treatment reduced gastric inflammation and lipid peroxidation (malodiadehyde, MDA) with a concomitant increase in superoxide dismutase and nitric oxide levels of gastric tissue homogenate compared with other treatment groups. Histological evaluations of gastric tissue from the manganese treated groups revealed healing compared with other treatment groups which further buttressed biochemical analysis. Conclusion: Manganese probably exerts its gastro-protective property on delayed ulcer by promoting increased antioxidant levels in experimental animals which probably mitigated the effect of continuous indomethacin injection.Keywords: Manganese, delayed ulcers, anti-inflammatory and antioxidative activitie

Profile and professional expectations of medical students in Mozambique: a longitudinal study

<p>Abstract</p> <p>Introduction</p> <p>This paper compares the socioeconomic profile of medical students registered at the Faculty of Medicine of Universidade Eduardo Mondlane (FM-UEM), Maputo, for the years 1998/99 and 2007/08.</p> <p>Case study</p> <p>The objective is to describe the medical students' social and geographical origins, expectations and perceived difficulties regarding their education and professional future. Data were collected through questionnaires administered to all medical students.</p> <p>Discussion and evaluation</p> <p>The response rate in 1998/99 was 51% (227/441) and 50% in 2007/08 (484/968).</p> <p>The main results reflect a doubling of the number of students enrolled for medical studies at the FM-UEM, associated with improved student performance (as reflected by failure rates). Nevertheless, satisfaction with the training received remains low and, now as before, students still identify lack of access to books or learning technology and inadequate teacher preparedness as major problems.</p> <p>Conclusions</p> <p>There is a high level of commitment to public sector service. However, students, as future doctors, have very high salary expectations that will not be met by current public sector salary scales. This is reflected in an increasing degree of orientation to double sector employment after graduation.</p

The training and professional expectations of medical students in Angola, Guinea-Bissau and Mozambique

<p>Abstract</p> <p>Background</p> <p>The purpose of this paper is to describe and analyze the professional expectations of medical students during the 2007-2008 academic year at the public medical schools of Angola, Guinea-Bissau and Mozambique, and to identify their social and geographical origins, their professional expectations and difficulties relating to their education and professional future.</p> <p>Methods</p> <p>Data were collected through a standardised questionnaire applied to all medical students registered during the 2007-2008 academic year.</p> <p>Results</p> <p>Students decide to study medicine at an early age. Relatives and friends seem to have an especially important influence in encouraging, reinforcing and promoting the desire to be a doctor.</p> <p>The degree of feminization of the student population differs among the different countries.</p> <p>Although most medical students are from outside the capital cities, expectations of getting into medical school are already associated with migration from the periphery to the capital city, even before entering medical education.</p> <p>Academic performance is poor. This seems to be related to difficulties in accessing materials, finances and insufficient high school preparation.</p> <p>Medical students recognize the public sector demand but their expectations are to combine public sector practice with private work, in order to improve their earnings. Salary expectations of students vary between the three countries.</p> <p>Approximately 75% want to train as hospital specialists and to follow a hospital-based career. A significant proportion is unsure about their future area of specialization, which for many students is equated with migration to study abroad.</p> <p>Conclusions</p> <p>Medical education is an important national investment, but the returns obtained are not as efficient as expected. Investments in high-school preparation, tutoring, and infrastructure are likely to have a significant impact on the success rate of medical schools. Special attention should be given to the socialization of students and the role model status of their teachers.</p> <p>In countries with scarce medical resources, the hospital orientation of students' expectations is understandable, although it should be associated with the development of skills to coordinate hospital work with the network of peripheral facilities. Developing a local postgraduate training capacity for doctors might be an important strategy to help retain medical doctors in the home country.</p

Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

Kolaviron is a mixture of bioflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-B and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assay, and reporter assay. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the proinflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IB/NF-B signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/ antioxidant response element (ARE) pathway. RNAi experiments revealed that Nrf2 is need for the anti-inflammatory effect of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders

Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

<p>Abstract</p> <p>Background</p> <p>Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1.</p> <p>Methods</p> <p>We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively.</p> <p>For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry.</p> <p>Results</p> <p>We initially found that CD4⁺T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4⁺T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4⁺T cells are more activated under HTLV-1 plus HIV co-infection.</p> <p>Conclusion</p> <p>Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4⁺T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700