Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents

Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;mM. Significant neuroprotective effects towards MPPþ-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 mM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection

HIV seroprevalence and its effect on outcome of moderate to severe burn injuries: A Ugandan experience

\ud \ud HIV infection in a patient with burn injuries complicates the care of both the patient and the treating burn team. This study was conducted to establish the prevalence of HIV among burn patients in our setting and to compare the outcome of these patients who are HIV positive with those who are HIV negative. This was a prospective cohort study involving burn injury patients admitted to Mulago Hospital between November 2005 and February 2006. Patients were stratified into HIV positive (exposed) group and HIV-negative (unexposed) group. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software version 11.5. Of the 130 patients included in the study, 17 (13.1%) patients tested HIV positive and this formed the study (exposed) group. The remaining 113 patients (86.9%) formed the control (unexposed) group. In the HIV positive group, females outnumbered males by a ratio of 1.4:1 and the mean age was 28.4 ± 21.5 years (range 3 months-34 years). 64.7% of HIV positive patients reported to have risk factors for HIV infection. Of these, multiple sexual partners [Odds Ratio 8.44, 95% C.I. (3.87-143.23), P = 0.011] and alcoholism [Odds Ratio 8.34, 95% C.I. (5.76-17.82), P = 0.002] were found to be independently and significantly associated with increased risk to HIV infection. The mean CD4 count for HIV positive and HIV negative patients were 394 ± 328 cells/μL and 912 ± 234 cells/μL respectively which is statistically significant (P = 0.001). There was no difference in the bacteria cultured from the wounds of HIV positive and negative patients (P = 0.322). Patients with clinical signs of sepsis had lower CD4+ counts compared to patients without sepsis (P < 0.001). ). Skin grafting was carried out in 35.3% of HIV negative patients and 29.4% of HIV positive patients with no significant difference in skin graft take and the degree of healed burn on discharge was the same (P = 0.324). There was no significant difference in hospital stay between HIV positive and negative patients (P = 0.674). The overall mortality rate was 11.5%. Using multivariate logistic regression analysis, mortality rate was found to be independently and significantly related to the age of the patient, HIV positive with stigmata of AIDS, CD4 count, inhalation injury, %TBSA and severity of burn (p-value < 0.001). HIV infection is prevalent among burn injury patients in our setting and thus presents an occupational hazard to health care workers who care for these patients. All burn health care workers in this region need to practice universal precautions in order to reduce the risk of exposure to HIV infection and post-exposure prophylaxis should be emphasized. The outcome of burn injury in HIV infected patients is dependent upon multiple variables such as age of the patient, inhalation injury and %TBSA and not the HIV status alone

Topical haemostatic agents for skin wounds: a systematic review

Background: Various agents and techniques have been introduced to limit intra-operative blood loss from skin lesions. No uniformity regarding the type of haemostasis exists and this is generally based on the surgeon's preference. To study the effectiveness of haemostatic agents, standardized wounds like donor site wounds after split skin grafting (SSG) appear particularly suitable. Thus, we performed a systematic review to assess the effectiveness of haemostatic agents in donor site wounds. Methods. We searched all randomized clinical trials (RCTs) on haemostasis after SSG in Medline, Embase and the Cochrane Library until January 2011. Two reviewers independently assessed trial relevance and quality and performed data analysis. Primary endpoint was effectiveness regarding haemostasis. Secondary endpoints were wound healing, adverse effects, and costs. Results: Nine relevant RCTs with a fair methodological quality were found, comparing epinephrine, thrombin, fibrin sealant, alginate dressings, saline, and mineral oil. Epinephrine achieved haemostasis significantly faster than thrombin (difference up to 2.5 minutes), saline or mineral oil (up to 6.5 minutes). Fibrin sealant also resulted in an up to 1 minute quicker haemostasis than thrombin and up to 3 minutes quicker than placebo, but was not directly challenged against epinephrine. Adverse effects appeared negligible. Due to lack of clinical homogeneity, meta-analysis was impossible. Conclusion: According to best available evidence, epinephrine and fibrin sealant appear superior to achieve haemostasis when substantial topical blood loss is anticipated, particularly in case of (larger) SSGs and burn debridement

Pattern of childhood burn injuries and their management outcome at Bugando Medical Centre in Northwestern Tanzania

Burn injuries constitute a major public health problem and are the leading cause of childhood morbidity and mortality worldwide. There is paucity of published data on childhood burn injuries in Tanzania, particularly the study area. This study was conducted to describe the pattern of childhood burn injuries in our local setting and to evaluate their management outcome. A cross sectional study was conducted at Bugando Medical Centre (in Northwestern Tanzania) over a 3-year period from January 2008 to December 2010. Data was collected using a pre-tested coded questionnaire and statistical analyses performed using SPSS software version 15.0. A total of 342 burned children were studied. Males were mainly affected. Children aged = 2 were the majority accounting for 45.9% of cases. Intentional burn injuries due to child abuse were reported in 2.9% of cases. Scald was the most common type of burns (56.1%). The trunk was the most commonly involved body region (57.3%). Majority of patients (48.0%) sustained superficial burns. Eight (2.3%) patients were HIV positive. Most patients (89.8%) presented to the hospital later than 24 h. The rate of burn wound infection on admission and on 10th day were 32.4% and 39.8% respectively.Staphylococcus aureus were more common on admission wound swabs, with Pseudomonas aeruginosa becoming more evident after 10th day. MRSA was detected in 19.2% of Staphylococcus aureus. Conservative treatment was performed in 87.1% of cases. Surgical treatment mainly skin grafting (65.9%) was performed in 44 (12.9%) of patients. The overall average of the length of hospital stay (LOS) was 22.12 ± 16.62 days. Mortality rate was 11.7%. Using multivariate logistic regression analysis; age of the patient, type of burn, delayed presentation, clothing ignition, %TBSA and severity of burn were found to be significantly associated with LOS (P < 0.001), whereas mortality rate was found to be independently and significantly related to the age of the patient, type of burn, HIV positive with stigmata of AIDS, CD4 count, inhalation injury, %TBSA and severity of burn (P < 0.001). Childhood burn injuries still remain a menace in our environment with virtually unacceptable high morbidity and mortality. There is need for critical appraisal of the preventive measures and management principles currently being practiced

Comparison of Surface Swab Cultures and Quantitative Tissue Biopsy Cultures to Predict Sepsis in Burn Patients: A Prospective Study.

This study aimed at evaluating the possibility of predicting septicemia in burn patients by using wound surface and tissue culture techniques as well as blood cultures. Fifty patients with full-thickness burn wounds covering at least 10% of the total body surface area were included. Signs of septicemia were noted in 21 patients (42%) and 29 patients died (58%). The bacterial colonization of the burn wounds consisted mainly of Staphylococcus aureus and Pseudomonas aeruginosa. Sepsis was better correlated to quantitative burn tissue biopsy cultures than surface swab cultures but the time needed for processing limits its predictive and therapeutic value

HIV infection reduces skin graft survival in burn injuries: a prospective study

Impaired survival of skin grafts has been noted in human immunodeficiency virus (HIV) infected patients, but the reason is not known. Alterations in inflammatory response, which might be recorded as an imbalance in cytokine production, have been implicated. The aim of this study was to determine the impact of HIV infection in patients with burn injuries by comparison of split skin graft survival, T lymphocyte count and cytokine levels in HIV-infected and non HIV-infected patients in relation to healthy and HIV-infected nonburnt volunteers. Fifty-four patients with deep dermal burns were included. Fifteen patients' were HIV-infected. Thirteen healthy and 15 HIV-infected, volunteers were recruited as controls. The burnt surface area was traced on a transparent plastic sheet and converted to area. Graft survival on day of discharge/regraft for non HIV-infected patients was 69%, and in HIV-infected 22%, (p < 0.05). The median length of hospital stay for early excision among non HIV-infected patients was 21 (12-53) days and for HIV-infected, 41 days (p < 0.05). Serum protein levels in HIV-infected patients were elevated compared to non HIV-infected patients (p < 0.05). CD4+ Lymphocytes were depressed in HIV-infected volunteers and HIV-infected burn patients compared to healthy volunteers (p < 0.05). CD8+ lymphocytes were elevated in HIV-infected volunteers compared to non HIV-infected burn patients. Pro-inflammatory cytokine levels of Interleukin-2 (IL-2), Interteukin-6 (IL-6), Interferon-gama (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were depressed in HIV-infected volunteers compared to healthy volunteers and non HIV-infected burn patients. The pro-inflammatory cytokine IFN-gamma did not increase after burn injury in HIV-infected burns patients as did IL-2, IL-6 and TNF-alpha (p < 0.05). Antiinflammatory cytokine levels of IL-4 were elevated in HIV-infected volunteers compared to healthy volunteers and burn patients (p < 0.05). Conclusion: Graft survival after split skin grafting of burn wounds in HIV-infected patients is impaired and hospital stay is prolonged. HIV infection. result in immune dysregulation, which might be related to impaired skin graft survival. (C) 2003 The British Association of Plastic Surgeons. Published by Elsevier Ltd. ALL rights reserved

A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns

Introduction: Early excision and skin grafting has become the standard of good burn management, but it is associated with major blood loss. Aim: To determine the haemostatic effect of terlipressin compared with placebo. Material and methods: Fifty-one patients with bums of 10-20% total body surface area had early excision and split skin grafting of deep burns. The surface area of the bum wound and of the heated graft were measured by planimetry. The patients were randomly allocated to medication, either terlipressin or placebo. Blood loss and number of transfused units of blood were recorded. Results: Twenty-one patients received terlipressin, 13 received terlipressin late (cross-over) and 17 received placebo. Six out of 21 patients exposed to terlipressin were transfused with eleven units of packed red blood cells. Seven out of 13 patients crossed over from placebo to terlipressin (late terlipressin) were transfused with 17 units of blood. Eight out of 17 patients exposed to the placebo were transfused with 22 units of blood (P < 0.05). Graft healing was 1055 +/- 609 cm(2) out of 1452 +/- 1811 cm(2) in terlipressin and 914 +/- 633 cm(2) out of 1288 720 cm 2 in the placebo group (n.s.). Conclusion: Terlipressin reduced the need for blood transfusion by a factor of 2.5 compared to a placebo without impairment of graft healing

Poverty, life events and the risk for depression in Uganda.

BACKGROUND: Understanding the determinants of major depression in sub-Saharan Africa is important for planning effective intervention strategies. OBJECTIVE: To investigate the social and life-event determinants of major depressive disorder in the African sociocultural context of rural Uganda. METHODS: A cross-section survey was carried out in 14 districts in Uganda from 1 June 2003 to 30 October 2004. 4,660 randomly selected respondents (15 years and above) were interviewed. The primary outcome was the presence of 'probable major depressive disorder' (PMDD) as assessed by the Hopkins symptom checklist. RESULTS: The prevalence of PMDD was 29.3% (95% confidence interval, 28.0-30.6%). Factors independently associated with depression in both genders included: the ecological factor, district; age (increase with each age category after 35 years); indices of poverty and deprivation (no formal education, having no employment, broken family, and socioeconomic classes III-V). Only a few adverse life events, notably those suggestive of a disrupted family background (death of a father in females and death of a mother in males) were associated with increased risk. CONCLUSION: Socioeconomic and sociodemographic factors, operating at both ecological and the individual level are the strongest independent determinants of depression. Adverse life events were less strongly associated with depression in this sample

Queimaduras autoinfligidas: tentativa de suicídio

OBJETIVO: Analisar a incidência, características, conduta e taxa de mortalidade de pacientes com autolesão por queimaduras internados no Centro de Queimaduras de Brasília, Distrito Federal, Brasil. MÉTODOS: Os pacientes do estudo consistiram das vítimas de queimaduras consecutivamente internadas na Unidade de Queimados do Hospital Regional da Asa Norte, Brasília, Distrito Federal, Brasil, durante o período de fevereiro de 2008 e fevereiro de 2009. Os dados foram obtidos na admissão e foram registrados prospectivamente durante a internação. Os pacientes foram seguidos até a alta ou o óbito. RESULTADOS: No período do estudo, foram admitidos 15 casos de autolesão por queimaduras na Unidade de Queimados. A média de idade foi 38,0 ± 20,6 anos; 66,7% dos casos de autolesão por queimadura eram mulheres. Na maioria dos casos eram casadas, provedoras do lar, e pobres. O maior motivo foi conflito conjugal. A taxa de mortalidade foi 40%. A área média de superfície corporal queimada foi 38,7 ± 26,1%. O álcool foi usado por 66,7% dos pacientes como causa das queimaduras. A média de duração do tratamento foi 20,1 ± 14,8 dias. Pacientes com autoinjúria por queimadura apresentaram lesões mais extensas, permaneceram mais tempo no hospital e pior prognóstico. CONCLUSÃO: Pacientes com autolesão por queimaduras apresentaram média de idade mais elevada, maior superfície corporal queimada, maior período de internação, mais complicações infecciosas e maior taxa de letalidade do que os pacientes com queimaduras acidentais. Esses pacientes precisam de constante suporte psiquiátrico, o qual pode ser útil na prevenção de futuros episódios de autoagressão