Burden of mental disorders and unmet needs among street homeless people in Addis Ababa, Ethiopia

BACKGROUND: The impact of mental disorders among homeless people is likely to be substantial in low income countries because of underdeveloped social welfare and health systems. As a first step towards advocacy and provision of care, we conducted a study to determine the burden of psychotic disorders and associated unmet needs, as well as the prevalence of mental distress, suicidality, and alcohol use disorder among homeless people in Addis Ababa, the capital of Ethiopia. METHODS: A cross-sectional survey was conducted among street homeless adults. Trained community nurses screened for potential psychosis and administered standardized measures of mental distress, alcohol use disorder and suicidality. Psychiatric nurses then carried out confirmatory diagnostic interviews of psychosis and administered a locally adapted version of the Camberwell Assessment of Needs Short Appraisal Schedule. RESULTS: We assessed 217 street homeless adults, about 90% of whom had experienced some form of mental or alcohol use disorder: 41.0% had psychosis, 60.0% had hazardous or dependent alcohol use, and 14.8% reported attempting suicide in the previous month. Homeless people with psychosis had extensive unmet needs with 80% to 100% reporting unmet needs across 26 domains. Nearly 30% had physical disability (visual and sensory impairment and impaired mobility). Only 10.0% of those with psychosis had ever received treatment for their illness. Most had lived on the streets for over 2 years, and alcohol use disorder was positively associated with chronicity of homelessness. CONCLUSION: Psychoses and other mental and behavioural disorders affect most people who are street homeless in Addis Ababa. Any programme to improve the condition of homeless people should include treatment for mental and alcohol use disorders. The findings have significant implications for advocacy and intervention programmes, particularly in similar low income settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0138-x) contains supplementary material, which is available to authorized users

Thiol methyltransferase activity in inflammatory bowel disease

BackgroundLuminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes.AimsTo measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis.PatientsVenepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis.MethodsTMT activity was measured by high performance liquid chromatography with radioactive detection to measure (14)C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and (14)C S-adenosylmethionine.ResultsErythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (pConclusionsErythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile

Nitric oxide effect on colonocyte metabolism: co-action of sulfides and peroxide

Luminal levels of nitric oxide/nitrite are high in colitis. Whether nitric oxide is injurious or protective to human colonocytes is unknown and the role of nitric oxide in the genesis of colitis unclear. The aims were to establish whether nitric oxide was injurious to oxidation of substrates (n-butyrate and D-glucose) in isolated human and rat colonocytes both alone and in the presence of hydrogen sulfide and hydrogen peroxide, agents implicated in cell damage of colitis. Nitric oxide generation from S-nitrosoglutathione was measured by nitrite appearance. Colonocytes were isolated and incubated with [1-14C] butyrate or [6-14C] glucose and 2.6 microM nitric oxide, 1.5 mM sodium hydrogen sulfide or 2.5 mM hydrogen peroxide. Acyl-CoA esters were measured by high performance liquid chromatography, 14CO2 radiochemically and lactate/ketones by enzymic methods. Results indicate that nitric oxide very significantly (p < .001) reduced acyl-CoA formation but did not impair 14CO2 generation. Peroxide and sulfide with nitric oxide resulted in significant reduction (p < 0.01) of substrate oxidation to CO2. Sulfide significantly stimulated release of nitric oxide from S-nitrosoglutathione. The principal conclusion is that nitric oxide diminishes CoA metabolism in colonocytes. CoA depletion has been observed in chronic human colitis for which a biochemical explanation has been lacking. For acute injurious action in human colonocytes nitric oxide requires co-action of peroxide and sulfide to impair oxidation of substrates in cells. From current observations treatment of colitis should aim to reduce simultaneously nitric oxide, peroxide and sulfide generation in the colon

Colonic sulfide in pathogenesis and treatment of ulcerative colitis

A role for colonic sulfide in the pathogenesis and treatment of ulcerative colitis (UC) has emerged based on biochemical, microbiological, nutritional, toxicological, epidemiological, and therapeutic evidence. Metabolism of isolated colonic epithelial cells has indicated that the bacterial short-chain fatty acid n-butyrate maintains the epithelial barrier and that sulfides can inhibit oxidation of n-butyrate analogous to that observed in active UC. Sulfur for fermentation in the colon is essential for n-butyrate formation and sulfidogenesis aids disposal of colonic hydrogen produced by bacteria. The numbers of sulfate-reducing bacteria and sulfidogenesis is greater in UC than control cases. Sulfide is mainly detoxified by methylation in colonic epithelial cells and circulating red blood cells. The enzyme activity of sulfide methylation is higher in red blood cells of UC patients than control cases. Patients with UC ingest more protein and thereby sulfur amino acids than control subjects. Removing foods rich in sulfur amino acids (milk, eggs, cheese) has proven therapeutic benefits in UC. 5-Amino salicylic acid reduces fermentative production of hydrogen sulfide by colonic bacteria, and aminoglycosides, which inhibit sulfate-reducing bacteria, are of therapeutic benefit in active UC. Methyl-donating agents are a category of drugs of potential therapeutic use in UC. A correlation between sulfide production and mucosal immune responses in UC needs to be undertaken. Control of sulfidogenesis and sulfide detoxification may be important in the disease process of UC, although whether their roles is in an initiating or promoting capacity has yet to be determined.Roediger, W.E.W. ; Moore, J. ; Babidge, W

Methionine derivatives diminish sulphide damage to colonocytes - implications for ulcerative colitis.

BACKGROUND:Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes. AIMS:To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives. METHODS AND SUBJECTS:Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed. RESULTS:In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide. CONCLUSION:Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value

Sulfides impair short chain fatty acid beta-oxidation at acyl-CoA dehydrogenase level in colonocytes: Implications for ulcerative colitis

The disease process of ulcerative colitis (UC) is associated with a block in beta-oxidation of short chain fatty acid in colonic epithelial cells which can be reproduced by exposure of cells to sulfides. The aim of the current work was to assess the level in the beta-oxidation pathway at which sulfides might be inhibitory in human colonocytes. Isolated human colonocytes from cases without colitis (n = 12) were exposed to sulfide (1.5 mM) in the presence or absence of exogenous CoA and ATP. Short chain acyl-CoA esters were measured by a high performance liquid chromatographic assay. 14CO2 generation was measured from [1-14C]butyrate and [6-14C]glucose. 14CO2 from butyrate was significantly reduced (p < 0.001) by sulfide. When colonocytes were incubated with hydrogen sulfide in the presence of CoA and ATP, butyryl-CoA concentration was increased (p < 0.01), while crotonyl-CoA (p < 0.01) and acetyl-CoA (p < 0.01) concentrations were decreased. These results show that sulfides inhibit short chain acyl-CoA dehydrogenase. As oxidation of n-butyrate governs the epithelial barrier function of colonocytes the functional activity of short chain acyl-CoA dehydrogenase may be critical in maintaining colonic mucosal integrity. Maintaining the functional activity of dehydrogenases could be an important determinant in the expression of ulcerative colitis.Wendy Babidge, Susan Millard, William Roedige

Methionine derivatives diminish sulphide damage to colonocytes--implications for ulcerative colitis.

BACKGROUND: Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes. AIMS: To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives. METHODS AND SUBJECTS: Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed. RESULTS: In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide. CONCLUSION: Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value

Surgical Evidence – The Australian Safety and Efficacy Register of New Interventional Procedures – Surgical Experience

Guy Maddern, P. Middleton and W. Babidg