Study Objective: To report the use of a sustained Valsalva maneuver during deliberate hypotension in order to reduce the incidence of distal particle embolization during the neuroangiographic embolization of intracranial arteriovenous malformations (AVMs). Design: Retrospective case series. Patients: 54 cases were studied involving 46 unique patients (20 male, 26 female) seen between January 1, 2007 and December 31, 2008. All patients were ASA class II-III and were undergoing neuroangiographically-assisted embolization for intracranial AVMs. Intervention: Immediately prior to the injection of the embolic substance, each patient received a dose of nitroglycerin to lower their systolic blood pressure from baseline (112-146 mm Hg) to a target of 55 mm Hg. Next, mechanical ventilation was suspended and manual pressure was applied to the ventilation bag of the anesthesia circuit to maintain a constant airway pressure of 20 cm H2O. This simulated Valsalva maneuver was maintained for 15 seconds after the injection of the embolic material, at which point mechanical ventilation was resumed. Main Results: All patients tolerated the deliberate hypotension/Valsalva protocol well. 2 patients experienced a rupture of the AVM during the procedure. Conclusions: The distal embolization of the embolic material during intracranial AVM embolization is a potentially fatal complication of this procedure. Although our results represent a small case series, they suggest that the use of deliberate arterial hypotension in addition to a simulated Valsalva maneuver may enhance the safety and efficacy of intracranial AVM embolization. Further study, with rigorous control standards and monitoring, is warranted.
Aims: Depressive symptoms in children and adolescents are commonly treated with serotonin re-uptake inhibitors like fluoxetine. Astrocytes expressing different serotonin receptors (5-HTRs) and the serotonin transporter (5-HTT) are affected by fluoxetine administration. The study was conducted to revise whether fluoxetine treatment during postnatal brain development results in long-term changes of astroglia. Methodology: Thus, immunohistochemistry and real-time PCR analyses were performed at different postnatal periods in rats to investigate short- and long-term changes following by a 14-day administration with fluoxetine (5 mg/kg/BW s.c. once daily). Results: Fluoxetine-treatments from postnatal day (pd) 1-15, measured at pd 16, led to a significant reduction of GFAP gene (Gfap) in hippocampus and GFAP protein expression in the dentate gyrus and CA1 without changes at pd 90 compared to controls. Treatments from pd 21-35 resulted in a significant decrease of Gfap and protein (measured 24 hours after last injection) in striatum (putamen), frontal cortex and hippocampus. Contrary, if measured at day 90, the same treatment led to a significant increase in those regions. Later treatments from pd 50-64 did not result in significant changes in mRNA or in protein expression. Conclusion: This study revealed a fluoxetine-sensitive period of brain astrocyte development (i.e. periadolescence) that led to structural effects, which can even be detected in adulthood. These results might be relevant for psychopharmacological treatment in children and require continuative clinical studies.
Objectives: Chronic lymphocytic leukaemia (CLL) is associated with abnormalities of the B-Cell Receptor (BCR) signalling, including low responsiveness to antigenic stimulation and constitutive phosphorylation of several components of the signalling pathway. In B-cells, BCR-mediated signalling is regulated in part by the amount of membrane cholesterol. It was observed that Statins, pharmacological inhibitors of cholesterol synthesis, induce apoptosis of CLL cells in vitro and in vivo. Having previously reported that ectopic expression of CD5 in a B-cell line stimulated the transcription of genes involved in the synthesis of cholesterol, we investigated the expression and synthesis of cholesterol in CLL B-cells. Study Design & Methodology: Plasma membrane cholesterol in CLL cells was evaluated by staining with Filipin and Flow cytometry in 26 patients. CLL cells were cultured with Lovastatin and subG1 cells and Gumprecht’s shadows counted thereafter; surface expression of IgM, CD19 and CD5 was analysed. The expression of cholesterol synthesis genes was investigated in transcriptomic data from the MILE project (150 CLL and 110 controls). Results: We confirmed that leukemic B-cells contained more cholesterol in their plasma membranes than their normal counterparts. An enhanced expression of genes involved in the synthesis of cholesterol in CLL as compared to healthy controls was observed. Interestingly, among the 150 CLL patients analyzed, four cholesterol synthesis genes were activated in 65 “Ig-mutated” (M) in comparison to 69 “Ig-unmutated” (UM) CLLs. Leukemic cells cultured with Lovastatin exhibited a dose-response apoptosis, however surface IgM expression was unaffected and CD19 and CD5 were downregulated at highest concentrations only. Conclusions: High membrane cholesterol in CLL cells may explain their sensitivity to Statins, with a potential difference between UM- and M-CLL.
Aims: To determine menstrual pattern and disorder associated with it among female medical students. Study Design: Cross-sectional study. Place and Duration of Study: College of Medical Sciences, University of Maiduguri, Borno State, Nigeria between February – September 2010. Methodology: Self descriptive cross-sectional study was carried out among 169 Medical students (MBBS II-V) between the ages 19-46 years. Respondents were selected from each class using stratified random sampling method. Stratification was done according to their class. Questionnaires were designed and administered to the respondents to complete. Three researchers and two research assistances were on site to assist. Students were briefed on the objective of the study and duly completed questionnaires were collected and analyzed. Subjects who had primary amenorrhea and/or history of abdominal or pelvic surgery were not eligible for the study. The questionnaire included data such as; age of menarche, menstrual pattern, severity of pain (dysmenorrheal), marital status, effects of exercise, socioeconomic status, Body mass Index (BMI) and Diet. The method of observation involved personal interaction and questioning of respondent to find out if they had anything peculiar about their cycle. The number of days of menstrual flow on menarche and number of pads use per day were in the questionnaire. Results: It was observed that 148(87.6%) respondents had regular length of menstrual cycle, particularly in the age groups 20-22 and 23-26 years which recorded 39 and 43 respondents respectively. Irregular menstrual cycle was found in 21(12.4%) respondents, which showed its peak at the age group of 17-19(33.3%) years, between age groups. It was also observed that 118(69.8%) respondents had painful menstrual flow, out of which 71(60.2%) had mild pain, 30(29.7%) had moderate pain while 17(14.4%) had severe pain. Result of length of menstrual cycle between single and married respondents showed that, 20(71.4%) of single respondents had short menstrual length compared to 8(28.6%) married respondents of corresponding short menstrual length. It was revealed that in 148(87.6) respondents that had regular menstrual cycle type, 106(71.6%) menstrual flow was average, while in 31(21.0%), it was scanty and heavy in 11(7.4%) respondents. 10(47.6%) respondent had average irregular menstrual cycle, while 9(42.9%) and 2(9.5%) respondents had scanty and heavy irregular menstrual cycles The result showed no significant variation in frequency of menstrual cycle (p=0.5). 99(58.6%) of respondents did no physical exercise; while 70(41.4%) did at least 30 minutes exercise (p=0.38). 101(59.8%) respondents belong to high upper, 51(30.2%) in upper-middle and 17(10.0%) belonged to lower socioeconomic status (p=0.14). 135(80.0%) respondents had daily fast food habits, out of which 95(80.5%) had positive history of pain and 34(20.0%) had no daily fast food (P=0.80). 30(17.8) respondents were underweight, 120(71.0%) had average weight and 19(11.2%) respondents were overweight (p=0.20). Conclusion: Study has established mean age at menarche, menstrual pattern and menstrual disorder (pain) in relation to BMI, exercise and socioeconomic factor among female Medical Students of University of Maiduguri, Nigeria. The prevalence of dysmenorrhea was very high among the female medical students. Although further research is needed, as relationship between Menstrual cycle, obesity, diet and exercise are conflicting with other studies.
Aims: To review and analyse Australian general practitioner’s workforce data for the 2000 to 2010 period by comparing this to Australian population trends and to make informed recommendations about GP workforce planning. Study Design: Descriptive analysis of the available Australian government data on GP workforce and the Australian population between 2000 and 2010. Place and Duration of Study: Griffith University, Australia, between April and November 2011. Methodology: Australian GP workforce data for the 2000 to 2010 period was obtained from the Australian Department of Health and Ageing (DoHA) website and population data was obtained from the Australian Bureau of Statistics website. A descriptive analysis of workforce trends using variables of interests such as overseas trained GPs, gender, age, professional services during the 11 year period was compared to population trends data. A new GP Workforce Index ratio (GPWIR = No. of GPs <35yrs ÷ No. of GPs 35yrs to 64yrs of age) was derived from the data and calculated for each year of the study period. Results: The ratio of female to male GPs has increased by 35% and the percentage of overseas graduates has increased by nearly 35% in the 11 year period, an indication that the 0.12% number of GPs as a percentage of Australian population between 2000 and 2010 was only sustained by increasing the intake of foreign trained graduates. Vocationally registered GPs have increased by 20% in same period. The GP workforce index ratio (GPWIR) decreased from 0.223 in 2000 to 0.118 in 2007; this was followed by a slight increase from 0.120 in 2008 to 0.128 in 2010. Conclusion: The impact that an increase in the number of female GPs graduating from medical schools may have on the overall number of GP services available to the Australian population requires further study, since it was noted in the literature that female GPs are more likely to work part-time than male GPs. The GPWIR may be a useful indicator for evaluating the proportion of the <35yrs old GPs as a proportion of overall GP workforce. Lower GPWIR may be associated with GP workforce shortage. GPWIR increased in the last 3 years of the study corresponding with an improvement in GP supply. In this study, the GPWIR proved to be more effective in predicting overall National GP workforce shortage trend than the DoHA GP per Population ratio of 0.71:1000 (Primarily used for regional and rural workforce shortage prediction). The Department of Health and Ageing may need to keep supporting rural and remote migration of GPs and also maintain an increase in the number of students entering medical schools.
Aims: Pharmacological-challenge magnetic resonance imaging (phMRI) is powerful new tool enabling researchers to map the central effects of neuroactive drugs in vivo. To employ this technique pre-clinically, head movements and the stress of restraint are usually reduced by maintaining animals under general anaesthesia. However, interactions between the drug of interest and the anaesthetic employed may potentially confound data interpretation. NMDA receptor (NMDAR) antagonists used widely to mimic schizophrenia have recently been shown to interact with the anaesthetic halothane. It may be the case that neural and cerebrovascular responses to NMDAR antagonists are dependent on the types of anaesthetic used. Methodology: We compared the phMRI response to NMDAR antagonist ketamine in rats maintained under α-chloralose to those under isoflurane anaesthesia. A randomized placebo/vehicle controlled design was used in each of the anaesthetic groups. Results: Changes in the anaesthetic agent resulted in two very different profiles of activity. In the case of α-chloralose, positive activations in cortical and sub-cortical structures reflected a response which was similar to patterns seen in healthy human volunteers and metabolic maps of conscious rats. However, the use of isoflurane completely reversed such effects, causing widespread deactivations in the cortex and hippocampus. Conclusion: This study provides initial evidence for a drug-anesthetic interaction between ketamine and isoflurane that is very different from responses to α-chloralose-ketamine
Aims: The prognostic value of different clinical, echocardiographic and functional parameters was evaluated in clinically stable outpatients with heart failure due to idiopathic dilated cardiomyopathy (DCM). Study Design: Observational prospective study. Methodology: 56 patients suffering from idiopathic dilated cardiomyopathy in waiting list for heart transplantation (33 men and 23 women, mean age 56.4 years) and in clinical stable conditions for a minimum of 3 months underwent baseline clinical evaluation, echocardiogram, 6 minute walk test (6 MWT) and cardiopulmonary exercise test (CPET). They were followed for an average period of 26.5 months to assess event-free survival (death, heart transplantation). Results: During follow-up period 23 patients died, 21 for cardiovascular causes. 4 patients underwent heart transplantation. Age and sex were not related to survival. We found a significant predictive value for 6MWTD (at 1 year event-free survival was 53% for a distance <300 m), but not for VO2 peak or respectively anaerobic threshold (AT). At multivariate analysis using Cox-stepwise regression model NYHA class, 6MWTD, left ventricular ejection fraction and left ventricular end diastolic diameter were independent prognostic markers of survival. Conclusion: An advanced NYHA class, a higher LVEDD and a distance of < 300m at 6MWT are useful prognostic markers of event free survival in outpatients with stable DCM while CPET was not.
Aims: To determine the antibacterial effect of Oenothera rosea against Escherichia coli, Salmonella enteritidis and Vibrio cholerae. Study Design: In vitro antibacterial study. Place and Duration of Study: Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología and Departamento de Química, San Nicolás de los Garza, NL. México, from June 2010 to June 2011. Methodology: The antibacterial in vitro effect of methanol and aqueous extracts of the Mexican plant O. rosea against strains of E. coli, S. enteritidis and V. cholerae was evaluated in liquid medium by the colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Results: Methanol and aqueous extracts significantly inhibited growth of all bacterium strains tested. The methanol extract caused up to 55%, 66% and 87% growth against E. coli, S. enteritidis and V. cholerae, respectively, whereas the aqueous extract induced up to 54%, 69% and 88% bacterial growth inhibition, respectively. Methanol and aqueous vehicle controls did not alter bacterial growth. Conclusion: The observed antibacterial effect of O. rosea extracts may be of benefit as an adjuvant treatment of diseases caused by the studied enterobacteria.
Aim: Child abduction by one parent and their transport to a foreign country is increasing worldwide but has not received adequate scientific interest. When inter-marital relationships reach the point of break-up and divorce, one of the parents abducts his/her child/children. Method: Records of forty seven (47) cases of inter family abduction that took place in 2007 in Greece were obtained. The majority of cases concerned relocation of children in a foreign country. A special inventory was developed for data collection. This consisted of three distinctive parts, for the father, the mother, or the abducted child. Results: Results showed that a typical abductive mother is of non Greek nationality, more likely of having psychiatric symptoms, without indication of substance abuse and no signs of violent behavior. Abductive fathers are of Greek nationality, less likely of having psychiatric symptoms, no substance abuse, and tend to exhibit violent behavior. Legal resolution of these cases and repatriation takes very long adding to the child and family’s distress. Conclusions: Child abduction is associated with cases of dissolved marriages. Domestic violence is frequent. Child abduction cases takes on average 3.5 years to be resolved, a phenomenon that has obvious implications on the mental health of the children and the parents involved.
Aims: To elucidate if endothelial dysfunction is an early CV risk marker in obese men and women with prediabetes. Study Design: Cross-sectional study. Place and Duration of Study: Clinical Research Unit, Pennington Biomedical Research Center, Baton Rouge, LA. United States. Methodology: Overweight and obese status denotes an increasing adipose tissue burden which spills over into ectopic locations, including the visceral compartment, muscle and liver. Associated co-morbidities enhance cardiovascular (CV) risk. Endothelium which is the largest receptor-effector end-organ in our bodies, while responding to numerous physical and chemical stimuli maintains vascular homeostasis. Endothelial dysfunction (ED) is the initial perturbation, which precedes fatty streak known to initiate atherosclerosis: insidious process which often culminates as sudden catastrophic CV adverse event. Asymptomatic men and women; [n=42] coming in after an overnight fast had demographic, anthropometric, clinical chemistry and resting endothelial function [EF: increased test finger peripheral arterial tone (PAT) relative to control; expressed as relative hyperemia index (RHI)] assessments. Results: Adults with desirable weight [n=12] and overweight [n=8] state, had normal fasting plasma glucose [Mean(SD)]: FPG [91.1(4.5), 94.8(5.8) mg/dL], insulin [INS, 2.3(4.4), 3.1(4.8) µU/ml], insulin sensitivity by homeostasis model assessment [HOMA-IR, 0.62(1.2), 0.80(1.2)] and desirable resting clinic blood pressure [SBP/DBP, 118(12)/74(5), 118(13)/76(8) mmHg]. Obese adults [n=22] had prediabetes [FPG, 106.5(3.5) mg/dL], hyperinsulinemia [INS 18.0(5.2) µU/ml], insulin resistance [HOMA-IR 4.59(2.3)], prehypertension [PreHTN; SBP/DBP 127(13)/81(7) mmHg] and endothelial dysfunction [ED; reduced RHI 1.7(0.3) vs. 2.4(0.3); all p<0.05]. Age-adjusted RHI correlated with BMI [r=-0.53; p<0.001]; however, BMI-adjusted RHI was not correlated with age [r=-0.01; p=0.89]. Conclusion: Endothelial dysfunction reflective of cardiometabolic changes in obese adults can be an early risk marker for catastrophic CV events.
The present study intended to determine the drug resistance patterns of Mycobacterium tuberculosis isolates among human new tuberculosis cases from northeastern Sudan using conventional and molecular techniques. Of 100 mycobacterial isolates tested by proportion method, 6% and 2% were identified, respectively, as multi drug resistant-tuberculosis (MDR-TB) and non-multi drug resistant-rifampicin (non-MDR-RIF). A total of 8% was found resistant to rifampicin (RIF), 13% to isoniazid (INH), 34% to streptomycin (STM) and 12% to ethambutol (EMB). Mono-resistant were 0% for RIF, 1% INH, 18% STM and 3% ETH. The remaining 61% isolates were identified as sensitive. Resistance to pyrazinamide was evaluated conventionally for the first time in this country and was found as low as 1%. Molecularly, mutations of MDR-TB, RIF, INH, EMB and STM resistant isolates were detected in 66.7%, 87.5%, 76.9%, 66.7% and 17.6% of corresponding conventional findings, respectively. The genetic mutations were related to the following codons: rpoB 531 (71.4%) and rpoB 526 (28.6%) for RIF, katG 315 (90%) and mabA-inhA-15 (10%) for INH, embB 306 (66.7%) for EMB and rpsL (17.6%) for STM. The study showed that drug resistant tuberculosis increased steadily and provided potentially valuable information on resistant genes circulating in the community. The rapid solving of this problem can benefit both public health and patient management.
Aims: Evidence is increasing to indicate that individuals with mental illness may be at risk of premature death. We studied the prevalence of QTc prolongation, QT dispersion (QTd) and cardiac arrhythmias in patients on psychotropic drugs. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine and Department of Behavioral Sciences, University of Ilorin Teaching Hospital, Nigeria Between Januaryand June 2010. Methodology: One hundred and ninety-one consecutive patients on psychotropic medications with 121 controls were studied. All the subjects had detailed clinical examination and resting electrocardiogram (ECG) at 25mm/sec. QTc was determined using Bazett formula and QTd by subtracting shortest from longest QTc in 12-lead ECG. Results: Mean QTc of the patients (450±46msc) was longer (p=0.0001) than that of the controls (390±27msc) but mean QTd was similar (p=0.13) in both groups. QTc was prolonged in 68(35.6%) patients compared to 11(9.1%) controls, p=0.0001. LVH, arrhythmias and abnormal T-wave morphology occurred more (p=0.01, 0.01 and 0.001 respectively) in the patients than controls. Age, duration of treatment and total daily doses of antipsychotics were independent predictors of QTc. Cardiac arrhythmias were seen in 24.1% of the patients but none had ventricular arrhythmias. Conclusion: Psychotropic drug use is a risk factor for QTc prolongation and cardiac arrhythmias. We suggest periodic electrocardiography, discourage polypharmacy and recommend drug holiday in stable patients.
Aims: Our aim was to study the modulatory effect of a Unani herbal formulation Jawarish amla sada against cyclophosphamide-induced toxicity in tumour bearing mice. Study Design: Non randomized control study. Place and Duration of Study: The study was conducted at the Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi during 2008-10. Methodology: Study was conducted in Swiss albino mice divided in five groups (n=6). Animals were challenged with Ehrlich’s ascites tumour cells (1x106 cells). Cyclophosphamide (50 mg/kg body weight), an alkylating anticancer drug that especially affects humoral immune functions, was injected intraperitoneally in a single dose. The protective effect of Unani drug Jawarish amla sada (250 mg/kg body weight) was studied in tumour bearing animals treated with cyclophosphamide. Immune function assessment test such as plaque forming cell assay (PFC) and biochemical parameters such as activities of antioxidant enzymes and reduced glutathione were measured in mice. Results: Jawarish amla sada significantly modulated the immunosuppressive effect of cyclophosphamide as compared to the group treated with cyclophosphamide. Jawarish amla sada also protected activities of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase and significantly restored level of reduced glutathione in liver and kidney of tumour bearing mice exposed to cyclophosphamide. Similar protective effect of Jawarish amla sada was observed against elevated lipid peroxidation in these tissues. Conclusion: Jawarish amla sada showed potential to provide protection against toxic effects of cyclophosphamide in tumour bearing mice. The mechanism of action of the drug may be attributed to various antioxidants fortified in this herbal Unani formulation, which is used in the traditional system of medicine in Indian subcontinent against several liver ailments.
Aims: Insufficient exposure of students to neurosurgery and neuroradiology has often been a matter of concern in medical schools across USA, Canada, UK and Europe. When taking into account the high incidence and mortality from head injuries in the form of subarachnoid and intracranial haemorrhages, it becomes evident that core knowledge in basic neurosurgical imaging and diagnoses need to be an essential part of medical training. The aim of this pilot study was to investigate the level of basic neurosurgical knowledge with regard to image interpretation in interns who were in their first post-graduate year in New Zealand. Study Design: Clinical and educational research paper. Place and Duration of Study: Wellington, New Zealand from January 2011 to January 2012. Methodology: Fifty interns in their first postgraduate year were invited to complete a neurosurgical imaging questionnaire with images of common neurosurgical findings (obvious subarachnoid and intracranial haemorrhages) randomly mixed with normal studies. Five computerized tomography (CT) scan images were required to be matched to five diagnoses. Results: All respondents agreed to participate. The mean score for the all 50 interns was 40% (95% CI 37.3 - 42.4), with a range of 0 to 80%. Thirty-six interns (72%) had a score of less than 60% and thus failed to demonstrate basic competency on the examination. None of the interns scored a full 100%. Conclusion: This study suggests that only 28% of newly qualified New Zealand doctors were able to demonstrate a basic level of competence in the evaluation of neurosurgical imaging at the start of their internship. Improvement of the undergraduate neurosurgical curriculum is strongly suggested.
Of the approximately 9 million children under the age of 5 yr that die annually in developing nations, about 5.1 million will die from preventable infectious diseases. This disastrous human and economic loss is caused in large part by three types of acute diarrhea and attendant respiratory tract infections that are responsible for approximately 2.6 million of these deaths. Thus, enteric pathogens remain a major factor contributing to persistent poverty and poor health in developing nations. Novel mucosal vaccination strategies are emerging that can protect epithelial surfaces and therefore promise a simple, effective and safe interventional therapy to overcome the mortality generated by these debilitating infectious diseases. Before the full potential for mucosal vaccination against enteric diseases can be realized, the innate immune system must be strengthen by addressing secondary problems such as malnutrition, malabsorption and gastrointestinal tract impairment. Here we describe the major enteric pathogens responsible for childhood morbidity and mortality in developing and resource-limited countries. We also discuss the development of mucosal vaccination strategies that when combined with modern principles of nutritional therapy may help improve the health and socio-economic status of developing nations.
Over the past two decades, emerging data have found that YKL-40, a secreted glycoprotein, is elevated in a broad spectrum of human diseases including cancers, liver injury, asthma, diabetes, inflammatory diseases, and cardiac disorders. In breast cancer, increased serum levels of YKL-40 are correlated with cancer metastasis and short survival, suggesting that serum levels of YKL-40 serve as a cancer biomarker. YKL-40 has the ability to stimulate vascular endothelial cell activation and suppress mammary epithelial cell differentiation, the pathophysiological events associated with tumor angiogenesis and poor differentiation. Neutralization of YKL-40 via an anti-YKL-40 monoclonal antibody in animal trials demonstrates the ability of YKL-40 blockade to impede tumor angiogenesis and tumor growth, thus holding therapeutic promise for cancer therapy. Apart from these findings, substantial efforts are urgently required to decipher the key molecular mechanisms that mediate cancer metastasis and malignancy, which is expected to significantly offer translational value for breast cancer diagnosis, prognosis and therapy. This review discusses the current status of research on YKL-40’s expression, biophysiological and pathological activities and functional inhibition, which is instrumental for future clinical practice.
Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information about the various roles that metabolites have in rheumatoid arthritis. An extensive PubMed search is conducted to collect the relevant manuscripts. The metabolites are discussed in relation to rheumatoid arthritis. Subsequently, the metabolites are organized according to levels of system organization. In the last section an integrated pathway analysis of the metabolites conducted with Ingenuity Pathway Analysis software is presented. Literature search resulted in information about vitamins, eicosanoids, fatty acids, lipids, hormones and peptides. The metabolites could be related to metabolic processes, oxidative stress processes and inflammatory processes. Cell death, lipid metabolism and small molecule biochemistry were found by the pathway analysis to be the top functions, characterized by the metabolites arachidonic acid, ascorbic acid, beta-carotene, cholecalciferol, hydrocortisone, keratan sulfate, melatonin, palmitic acid and stearic acid. These nine metabolites are highly connected to a number of canonical pathways related to immune functions, the production of nitric oxygen and reactive oxygen species in macrophages and pathways involved in arthritis. This review indicates groups of metabolites that could be interesting for metabolomics studies related to rheumatoid arthritis. Circadian rhythms of metabolite levels are found to be important for understanding and treating rheumatoid arthritis. In addition, some key processes and pathways are found by integrating the metabolite data. This might offer new ideas for studies into the mechanism of and possible treatment options for rheumatoid arthritis.
