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1.
Ann Surg Open ; 3(1): e133, 2022 Mar.
Article in English | MEDLINE | ID: mdl-37600100

ABSTRACT

Objective: The aims of this study were to describe the process of integrating 2 established training programs, Nontechnical skills for surgeons, and a traditional essential surgical skills course and to measure the impact of this integrated course on the behaviors of interprofessional surgical teams in Rwandan district hospitals. Background: Surgical errors and resulting adverse events are due to variability in both technical and nontechnical surgical skills. Providing technical and nontechnical skills training to the perioperative team may enhance the learning of both of these skills and promote safe intraoperative patient care. Methods: A quality improvement framework guided the process of integrating essential surgical skills and nontechnical skills into a single training program for surgical teams. The resulting 2-day training program was delivered to 68-person teams from 17 hospitals. Nontechnical skills for surgeons was taught through didactics and in the operating room, where preoperative briefing, intraoperative interactions, and postoperative debriefing were used as essential and nontechnical skills teaching moments. Postcourse surveys, follow-up interviews, focus groups, and direct observation of participants in the operating room were conducted to assess how participants implemented the knowledge and skills from the training into practice. Results: Ninety-seven percent of the participants reported that they were satisfied with the course. Follow-up participant interviews and focus groups reported that the course helped them to improve their preoperative planning, intraoperative communication, decision-making, and postoperative debriefing. Conclusions: It is possible to implement an integrated essential surgical skills and nontechnical skills training course. Integrating nontechnical skills into essential surgical skills courses may enhance learning of these skills.

2.
J Gastrointest Cancer ; 53(3): 520-527, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34019238

ABSTRACT

PURPOSE: Gastric cancer is endemic in the so-called stomach cancer region comprising Rwanda, Burundi, South Western Uganda, and eastern Kivu province of Democratic Republic of Congo, but its outcomes in that region are under investigated. The purpose of this study was to describe the short-term outcomes (in-hospital mortality rate, length of hospital stay, 3-, 6-, 12-, and 24-month survival rates) in patients treated for gastric cancer in Rwanda. METHODS: We retrospectively reviewed the data collected from records of patients who consulted Kigali University Teaching Hospital (CHUK) over a period of 10 years from September 2007 to August 2016. We followed patients before and after discharge for survival data. Baseline demographic data studied using descriptive statistics, whereas Kaplan-Meier model and univariate Cox regression were used for survival analysis. RESULTS: Among 199 patients enrolled in this study, 92 (46%) were males and 107 (54%) females. The age was ranging between 24 and 93 years with a mean age of 55.4. The mean symptom duration was 15 months. Many patients had advanced disease, 62.3% with distant metastases on presentation. Treatment with curative intent was offered for only 19.9% of patients. The in-hospital mortality rate was 13.3%. The 3-, 6-, 12-, and 24-month survival rate was 52%, 40.5%, 28%, and 23.4%, respectively. The overall survival rate was 7 months. CONCLUSION: Rwanda records a high number of delayed consultations and advanced disease at the time of presentation in patients with gastric cancer. This cancer is associated with poor outcomes as evidenced by high hospital mortality rates and short post discharge survival.


Subject(s)
Stomach Neoplasms , Adult , Aftercare , Aged , Aged, 80 and over , Female , Hospitals, Teaching , Humans , I-kappa B Kinase , Male , Middle Aged , Patient Discharge , Retrospective Studies , Rwanda/epidemiology , Stomach Neoplasms/epidemiology , Stomach Neoplasms/therapy , Universities , Young Adult
3.
Front Physiol ; 12: 709804, 2021.
Article in English | MEDLINE | ID: mdl-34588992

ABSTRACT

Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.

4.
J Surg Educ ; 78(6): 1985-1992, 2021.
Article in English | MEDLINE | ID: mdl-34183277

ABSTRACT

OBJECTIVE: The primary objective was to describe the level of surgical trainee autonomy during non-trauma emergency laparotomy (NTEL) operations in Rwanda and South Africa. The secondary objective was to identify potential associations between trainee autonomy, and patient mortality and reoperation. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, observational study of NTEL operations at 3 teaching hospitals in South Africa and Rwanda over a 1-year period from September 1, 2017 to August 31, 2018. The study included 543 NTEL operations performed by the acute care and general surgery services on adults over the age of 18 years. RESULTS: Surgical trainees led 3-quarters of NTEL operations and, of these, 72% were performed autonomously in Rwanda and South Africa. Notably, trainee autonomy was not significantly associated with reoperation or mortality. CONCLUSIONS: Trainees were able to gain autonomous surgical experience without impacting mortality or reoperation outcomes, while still providing surgical support in a high-demand setting.


Subject(s)
Hospitals, Teaching , Laparotomy , Adult , Humans , Middle Aged , Prospective Studies , Rwanda , South Africa
5.
Int J Surg Case Rep ; 80: 105679, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33636407

ABSTRACT

INTRODUCTION AND IMPORTANCE: Abdominal actinomycetoma is a rare and often a missed diagnosis by most of clinicians due to its rarity and different clinical presentations. It is caused by Actinomyces speces which are gram positive bacilli and normal commensal inhabitants of the human bronchial and gastrointestinal tracts. A.Israelli is responsible for disease in humans once the mucosal barrier is broken. CASE PRESENTATION: This case report presents an adult female patient who consulted for a localized abdominal wall mass of 3 weeks duration and the clinical exam was in favor of an abdominal wall abscess, but later found to be an actinomycotoma of the colon invading the abdominal wall and forming an abdominal wall abscess. Transverse colectomy and drainage of abscess was done and she improved well. CLINICAL DISCUSSION: Actinomycosis is common in the tropical and subtropical area. However, this is the first case reported in Rwanda and prompt surgical treatment and antibiotherapy have led to a good clinical outcome. CONCLUSION: Abdominal actinomycetoma should be considered as a differential diagnosis of any abdominal wall mass for patients with known risk factors and surgery and antibiotics are the only curative treatment.

6.
J Toxicol Environ Health A ; 84(9): 357-388, 2021 05 03.
Article in English | MEDLINE | ID: mdl-33380269

ABSTRACT

This dermal study tested the potential toxicity of grade 3 (G3) and 4 (G4) organophosphate-containing aircraft engine oils in both new (G3-N, G4-N) and used states (G3-U, G4-U) to alter esterase activities in blood, brain and liver tissues, clinical chemistry parameters, and electrophysiology of hippocampal neurons. A 300 µl volume of undiluted oil was applied in Hill Top Chamber Systems®, then attached to fur-free test sites on backs of male and female Sprague Dawley rats for 6 hr/day, 5 days/week for 21 days. Recovery rats received similar treatments and kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxicity. In brain, both versions of G3 and G4 significantly decreased (32-41%) female acetylcholinesterase (AChE) activity while in males only G3-N and G4-N reduced (33%) AChE activity. Oils did not markedly affect AChE in liver, regardless of gender. In whole blood, G3-U decreased female AChE (29%) which persisted during recovery (32%). G4-N significantly lowered (29%) butyrylcholinesterase (BChE) in male plasma, but this effect was resolved during recovery. For clinical chemistry indices, only globulin levels in female plasma significantly increased following G3-N or G4-N exposure. Preliminary electrophysiology data suggested that effects of both versions of G3 and G4 on hippocampal function may be gender dependent. Aircraft maintenance workers may be at risk if precautions are not taken to minimize long-term aircraft oil exposure.


Subject(s)
Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Environmental Pollutants/adverse effects , Enzymes/blood , Oils/adverse effects , Aircraft , Animals , Blood/drug effects , Brain/drug effects , Brain/enzymology , Female , Liver/drug effects , Liver/enzymology , Male , Plasma/drug effects , Rats , Rats, Sprague-Dawley , Time Factors
7.
World J Surg ; 45(3): 668-677, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33225391

ABSTRACT

BACKGROUND: Emergency conditions requiring exploratory laparotomy (EL) can be challenging. The objective of this study is to describe indications, outcomes, and risk factors for perioperative mortality (POMR) after non-trauma EL. METHODS: This was a prospective study of patients undergoing non-trauma EL at four hospitals in Rwanda, South Africa, and the USA. Multivariate logistic regression was used to determine factors associated with POMR. RESULTS: Over one year, there were 632 EL with the most common indications appendicitis (n = 133, 21%), peptic ulcer disease (PUD) (n = 101, 16%), and hernia (n = 74, 12%). In Rwanda, the most common indications were appendicitis (n = 41, 19%) and hernia (n = 37, 17%); in South Africa appendicitis (n = 91, 28%) and PUD (n = 60, 19%); and in the USA, PUD (n = 16, 19%) and adhesions from small bowel obstruction (n = 16, 19%). POMR was 11%, with no difference between countries (Rwanda 7%, South Africa 12%, US 16%, p = 0.173). Risk factors associated with increased odds of POMR included typhoid intestinal perforation (adjusted odds ratio (aOR): 16.48; 95% confidence interval (CI): 4.31, 62.98; p value < 0.001), mesenteric ischemia (aOR: 13.77, 95% CI: 4.21, 45.08, p value < 0.001), cancer (aOR: 5.84, 95% CI: 2.43, 14.05, p value < 0.001), other diagnoses (aOR: 3.97, 95% CI: 3.03, 5.20, p value < 0.001), high ASA score (score ≥ 3) (aOR: 3.95, 95% CI: 3.03, 5.15, p value < 0.001), peptic ulcer disease (aOR: 2.82, 95% CI: 1.64, 4.85, p value < 0.001), age > 60 years (aOR: 2.32, 95% CI: 1.41, 3.83, p value = 0.001), and ICU admission (aOR: 2.23, 95% CI: 1.24, 3.99, p value = 0.007). Surgery in the US was associated with decreased odds of POMR (aOR: 0.41, 95% CI: 0.21, 0.80, p value = 0.009). CONCLUSIONS: Indications for EL vary between countries and POMR is high. Differences in mortality were associated with patient and disease characteristics with certain diagnoses associated with increased risk of mortality. Understanding the risk factors and outcomes for patients with EL can assist providers in judicious patient selection, both for patient counselling and resource allocation.


Subject(s)
Emergencies , Laparotomy , Humans , Middle Aged , Prospective Studies , Risk Factors , Rwanda/epidemiology , South Africa/epidemiology
8.
Adv Med Educ Pract ; 11: 825-832, 2020.
Article in English | MEDLINE | ID: mdl-33177911

ABSTRACT

INTRODUCTION: Teaching of human anatomy has undergone significant changes in the past three decades. At the University of Rwanda, anatomy is being taught using team-based learning (TBL). While student-generated multiple choice questions (MCQs) stimulate deeper thinking on a given topic, their impact on anatomy learning is not known. This study aimed to find out the impact of student-generated MCQs on the current anatomy teaching method at the University of Rwanda. METHODS: In this comparative interventional study, two similar chapters on anatomy were selected; one was taught using TBL while for the other one, in addition to TBL, students were encouraged to set MCQs while studying. Pre- and post-test scores were analyzed using SPSS 23 and the Student's t-test was used to compare the mean scores obtained. RESULTS: Thirty-one medical students were recruited. Pre-test mean scores were 25.10 and 25.19 out of 50 for chapters 1 and 2, respectively. Although the students' post-test scores improved after teaching for each chapter, the improvement was much greater for chapter 2 than for chapter 1, with mean scores of 39.97 and 32.45 out of 50, respectively (P<0.05). Despite such improvement, almost half of the students found that setting MCQs was not easy. CONCLUSION: This study found that student-generated MCQs can be used as a simple and cost-effective tool to enhance TBL of anatomy.

9.
World J Surg ; 44(11): 3651-3657, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32700110

ABSTRACT

BACKGROUND: Sepsis is common in surgical patients, and its presence influences the outcomes in those to undergo surgery. Factors such as advanced age, presence of comorbidities and many other conditions increase mortality in surgical patients with sepsis. The sequential organ failure assessment (SOFA) score simplified into qSOFA helps to define sepsis and to identify patients who are likely to die from it. Sepsis in surgery is under investigated in low- and middle-income countries and so are the factors for mortality in that specific surgical population. Our aim was to develop a prognostic tool accurate in predicting outcomes in surgical patients with sepsis who present at University Teaching Hospitals of Kigali (CHUK) and Butare (CHUB) and in other centers with limited resources METHODS: This was a prospective cohort study conducted over a period of 1 year from February 2018 to January 2019. The surgical patients with sepsis recruited in the first 6 months at CHUK served as the derivation cohort and those recruited in the next 6 months from both CHUK and CHUB served as the validation cohort. The Kigali surgical sepsis (KiSS) score was derived, and to determine its accuracy in predicting mortality, we measured sensitivity, specificity and area under receiver operator characteristic (AUROC) curve. We then compared this with qSOFA score. RESULTS: A total of 288 patients were recruited with 144 in each cohort. The mean age was 36.5, and median age was 32.6. The mean length of hospital stay (LoHS) was 22.9 days. The overall intensive care unit (ICU) admission rate was 51.4%, and the surgical sepsis-related hospital mortality rate was 21.7%. Factors associated with surgical sepsis-related hospital mortality were age above 55 years (p = 0.034), presence of comorbidities (p = 0.069), hypotension (p = 0.014), tachycardia (p = 0.061), tachypnea (p = 0.028), decreased level of consciousness (p = 0.021), presence of GIT perforation (p = 0.026) and number of impaired organ function (p = 0.035). A predictive score (KiSS score) consisting of six parameters was derived from these factors and compared to qSOFA score. The sensitivity of KiSS score in predicting mortality was 73% (vs 52% for qSOFA), and the specificity was 97% (vs 87% for qSOFA). The predictive validity for hospital mortality was assessed by AUROC curve, and it was 0.939 (95% CI, p < 0.001) for KiSS and 0.684 (95% CI, p < 0.001) for qSOFA. CONCLUSION: The KiSS score was effective in predicting surgical sepsis-related hospital mortality in low-resource setting. The KiSS score showed an added advantage of stratifying septic surgical patients to be operated on into those with good, variable and poor prognosis.


Subject(s)
Organ Dysfunction Scores , Postoperative Complications/diagnosis , Sepsis , Adult , Hospital Mortality , Humans , Intensive Care Units , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Retrospective Studies , Rwanda , Sepsis/diagnosis , Sepsis/epidemiology
10.
Curr Res Toxicol ; 1: 12-24, 2020 Jun 10.
Article in English | MEDLINE | ID: mdl-34345833

ABSTRACT

There is little data available for the toxicity of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if grade 3 (G3) and 4 (G4) aircraft engine oils in their new states (G3-N and G4-N) and their used versions (G3-U and G4-U) have the potential to induce toxicity via dermal application. Male and female Sprague Dawley rats were dermally exposed to water (control), new and used versions of G3 and G4 oils to determine the oil sub-chronic toxicity potentials. A volume of 300 µL of undiluted oil was applied to the pad of the Hill Top Chamber System©. Then the chamber was attached to a fur-free test site located at the back of the rat for 6 h/day for 5 consecutive days/week for 21 days (15 total exposures). Recovery rats also received similar treatments and were kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxic effects. Both G3 and G4 oils had a significant impact on the weight of male and female reproductive organs: testes weights for recovery rats exposed to G3-N significantly decreased (12%) relative to controls; G3-N and G3-U decreased uterus weights by 23% and 29%, respectively; G4-N decreased uterus weights by 32% but were resolved at the end of the recovery period; G4-N increased the weight of the adrenals and spleen for females by 34% and 27%, respectively, during the recovery period. G3 and G4 induced more changes in female blood indices than in those for males. Of all versions of oils, G4-N induced the most changes in profiles of female blood. G4-N significantly decreased the white blood cells, lymphocytes, neutrophils, eosinophils and increased the mean platelet volumes. Interestingly, males were not affected by exposure to G4-N oil. While G3-N decreased the white blood cells and lymphocytes for females it slightly increased those for males. In summary, G3 and G4 oils impacted the weights for male and reproductive organs. This study highlights the health risks that aircraft maintenance workers may be exposed to if precautions are not taken to minimize exposure to these oils.

11.
Toxicol Rep ; 6: 1246-1252, 2019.
Article in English | MEDLINE | ID: mdl-31799125

ABSTRACT

There is little data available on toxicity levels of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if new engine oils and their used versions have the potential to induce dermal irritation. Twelve male New Zealand White rabbits (Oryctolagus cuniculus, 19 weeks old) were used to determine the acute dermal toxicity potential of four aircraft turbine oils including MIL-PRF-7808 Grades 3 and 4 and MIL-PRF-23699 Grade 5 High Thermal Stability (HTS) and a Grade 5 experimental aircraft engine oil in their unused and used or laboratory stressed states. Five fur-free test sites (6 cm2 each) located lateral to the midline of the back were treated with two undiluted (0.5 ml) new engine oils and their used versions. The fifth site received reverse osmosis deionized (RODI) water as a control. Each treatment was repeated 3 times (3 rabbits/oil type). Each oil was tested under both semi-occluded and occluded conditions. The 4 h exposure was followed by gauze plus wrappings removal, and gentle cleaning of sites prior to scoring for erythema and edema at 0.5-1, 24, 48 and 72 h post exposure based on Draize (1959). E-collars were placed on each animal for at least 72 h to prevent ingestion of the test substance and/or gauze and wrappings and/or disturbance of site recovery. Additional observations were made on days 7, 10 and 14 to determine recovery. Exposure to both used and new oils produced dermal irritation consisting of no more than very slight to well-defined erythema and very slight edema. The calculated Primary Dermal Irritation Index (PDII) indicated that all the oils were slightly irritating (means ranged from 0.42 to 1.08). Although the PDII values for new oils and their used versions were not significantly different from each other, they were all statistically higher (p < 0.05) than those obtained for the control regardless of the type of occlusion binding applied. The used oils under semi-occlusion conditions yielded larger size effects (Cohen's d) relative to their unused versions suggesting an enhancement in irritation when the oil is aging. Grade 4 in the used state yielded the largest size effect which was d = 5.9 versus 2.6 for its unused version. The slight dermal irritation resulting from four hours of exposure to oils raises concerns about the magnitude of impact related to prolonged and/or repeated exposure.

12.
Trauma Surg Acute Care Open ; 4(1): e000332, 2019.
Article in English | MEDLINE | ID: mdl-31423464

ABSTRACT

BACKGROUND: Acute care surgery (ACS) encompasses trauma, critical care, and emergency general surgery. Due to high volumes of emergency surgery, an ACS service was developed at a referral hospital in Rwanda. The aim of this study was to evaluate the epidemiology of ACS and understand the impact of an ACS service on patient outcomes. METHODS: This is a retrospective observational study of ACS patients before and after introduction of an ACS service. χ2 test and Wilcoxon rank-sum test were used to describe the epidemiology and compare outcomes before (pre-ACS)) and after (post-ACS) implementation of the ACS service. RESULTS: Data were available for 120 patients before ACS and 102 patients after ACS. Diagnoses included: intestinal obstruction (n=80, 36%), trauma (n=38, 17%), appendicitis (n=31, 14%), and soft tissue infection (n=17, 8%) with no difference between groups. The most common operation was midline laparotomy (n=138, 62%) with no difference between groups (p=0.910). High American Society of Anesthesiologists (ASA) score (ASA ≥3) (11% vs. 40%, p<0.001) was more common after ACS. There was no difference in intensive care unit admission (8% vs. 8%, p=0.894), unplanned reoperation (22% vs. 13%, p=0.082), or mortality (10% vs. 11%, p=0.848). The median length of hospital stay was longer (11 days vs. 7 days, p<0.001) before ACS. CONCLUSIONS: An ACS service can be implemented in a low-resource setting. In Rwanda, ACS patients are young with few comorbidities, but high rates of mortality and morbidity. In spite of more patients who are critically ill in the post-ACS period, implementation of an ACS service resulted in decreased length of hospital stay with no difference in morbidity and mortality. LEVEL OF EVIDENCE: Prognostic and epidemiologic study type, level III.

13.
Chem Res Toxicol ; 32(2): 265-284, 2019 02 18.
Article in English | MEDLINE | ID: mdl-30604967

ABSTRACT

Previously, we demonstrated that treatment of rats with myo-inositol plus ethanolamine (ME) elevated brain ethanolamine plasmalogens (PE-Pls) and protected against phosphine-induced oxidative stress. Here we tested the hypothesis that ME treatment elevates PE-Pls in a neuro-2A (N2A) cell culture system and protects against hydrogen peroxide (H2O2)-induced oxidative stress, and we assessed the effects of treatments using myo-inositol with or without (+/-) ethanolamine on ethanolamine phospholipids (PLs) and cell viability following H2O2 exposure. Cells were treated with equimolar amounts (500 µM) of myo-inositol, ethanolamine (Etn), or their combination (ME) for 24 h, followed by an additional 24 h exposure to 650 µM H2O2. NMR analyses evaluated the treatment effects on Etn PLs, while LC-MS/MS analyses assessed the molecular species of Etn PLs preferentially affected by ME and H2O2 treatments, especially PE-Pls and their degradation byproducts-lysophosphatidylethanolamine (LPE) and glycerophosphoethanolamine (GPE). Only ME influenced the cellular levels of PLs. ME yielded a 3-fold increase in PE-Pls and phosphatidylethanolamine (PE) ( p < 0.001) and a preferential 60% increase in PE-Pls containing saturated and monounsaturated fatty acids (SFA+MUFA), while polyunsaturated fatty acid (PUFA) species increased by only 10%. Exposing cells to 650 µM H2O2 caused a significant cell death (56% viability), a 27% decrease in PE-Pls, a 201% increase in PUFA-rich LPE, and a ca. 3-fold increase in GPE. H2O2 had no impact on PE, suggesting that LPE and GPE were primarily the byproducts of PE-Pls (not PE) degradation. Surprisingly, ME pretreatment ameliorated H2O2 effects and significantly increased cell survival to 80% ( p < 0.05). Cellular PE-Pls levels prior to H2O2 treatment were highly correlated ( R2 = 0.95) with cell survival, suggesting a relationship between PE-Pls and cell protection. Data suggest that a preferential increase in PE-Pls containing SFA+MUFA species may protect cells from oxidative stress. Such studies aid in our understanding of the neuroprotective mechanisms that may be associated with plasmalogens and the relevance of these phospholipids to neurodegenerative diseases/disorders.


Subject(s)
Ethanolamine/pharmacology , Inositol/pharmacology , Oxidative Stress/drug effects , Plasmalogens/metabolism , Animals , Cell Line , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Ethanolamine/chemistry , Hydrogen Peroxide/toxicity , Inositol/chemistry , Mice , Plasmalogens/analysis , Tandem Mass Spectrometry
14.
Toxicol Mech Methods ; 29(1): 53-59, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30084267

ABSTRACT

Environments combining JP-8 jet fuel exposure with heightened ambient noise may accelerate hearing loss induced by noise. To reduce animal use and facilitate kinetic modeling of this military aviation fuel, tissue-specific parameters are required, including water, protein, and lipid content. However, tissues involved in hearing, including cochlea, brainstem, frontal, and temporal lobe, have not been characterized before. Therefore, water content was determined by lyophilization of rat auditory tissues and the protein of the freeze dried remainder was quantified using a bicinchoninic acid assay. Lipids were extracted from fresh-frozen rat auditory tissues and separated into neutral lipids, free fatty acids, neutral phospholipids, and acidic phospholipids using solid phase extraction. Phospholipid fractions were confirmed by 31 P nuclear magnetic resonance analysis showing distinct phospholipid profiles. Lipid content in reference tissues, such as kidney and adipose, confirmed literature values. For the first time, lipid content in the rat auditory pathway was determined showing that total lipid content was lowest in cochlea and highest in brainstem compared with frontal and temporal lobes. Auditory tissues displayed distinct lipid fraction profiles. The information on water, protein, and lipid composition is necessary to validate algorithms used in mathematical models and predict partitioning of chemicals of future interest into these tissues. This research may reduce the use of animals to measure partition coefficients for prospective physiological models.


Subject(s)
Auditory Pathways/chemistry , Lipids/analysis , Models, Theoretical , Proteins/analysis , Water/analysis , Animal Testing Alternatives , Animals , Male , Rats, Inbred F344 , Rats, Sprague-Dawley
15.
J Med Entomol ; 54(6): 1674-1683, 2017 11 07.
Article in English | MEDLINE | ID: mdl-28968911

ABSTRACT

The main malaria vectors in sub-Saharan Africa, the Anopheles gambiae (Giles; Diptera: Culicidae), normally breed in clean water sources. However, evidence suggests an on-going adaptation of Anopheline species to polluted breeding habitats in urban settings. This study aimed at understanding the adaptation to breeding in water bodies with different qualities, in five selected mosquito breeding sites in urban Accra, Ghana. The study sites were also evaluated for the WHO water-quality parameters as a measure of pollution, and insecticide residues. Field mosquitoes were evaluated for five genes; CYP6P3, CYP4H19, CYP4H24, GSTD1-4, and ABCC11-associated with insecticide detoxification-using quantitative RT-PCR, as well as Mono-oxygenase, Alpha Esterase, Glutathione S-transferase, and insensitive acetylcholinesterase (AChE) using biochemical enzyme assays. The lab-reared, insecticide susceptible An. gambiae Kisumu strain was bred in the most polluted water source for 10 generations and evaluated for the same genes and enzymes. The results revealed that the fold expression of the genes was higher in the larvae compared with the adults. The results also suggest that detoxification enzymes could be involved in the adaptation of An. gambiae to polluted breeding sites. Correlation analysis revealed a highly positive significant correlation between calcium levels and all five genes (P < 0.05). Stepwise linear regression to understand which of the variables predicted the expression of the genes revealed that sulphate was responsible for ABCC11 and CYP4H24, alkalinity for GSTD1-4, and calcium for CYP4H19 and CYP6P3. The detailed genetic basis of this adaptation need to be further investigated. A further understanding of this adaptation may provide outlooks for controlling malaria and other disease vectors adapted to polluted breeding water sources.


Subject(s)
Adaptation, Biological , Anopheles/enzymology , Mosquito Vectors/enzymology , Water Pollution , Animals , Anopheles/genetics , Female , Gene Expression , Inactivation, Metabolic , Malaria/transmission , Mosquito Vectors/genetics , Water Quality
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