Does silicon protect against aluminium toxicity in dialysis patients?
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Aluminum↗
Biomedical subjects
M Yaqoob
Publications and source records attributed to M Yaqoob.
Purification and characterisation of B2 bradykinin receptor from rat uterus.
A B2 bradykinin (BK) receptor was solubilised and partially purified from rat uterine membranes by a combination of ammonium sulphate precipitation, desalting on Sephadex G-50, and hydroxyapatite and wheat germ agglutinin affinity chromatography. The partially purified BK receptor, enriched 1,500-fold, was then cross-linked to 125I-Tyr0-BK using disuccinimidyl suberate and purified to homogeneity as a single protein species on two-dimensional gel electrophoresis with a molecular mass of 81 kDa. This molecular size was in agreement with the value of 80-120 kDa estimated from Sephacryl 300 size exclusion column chromatography of the B2 receptor. The partially purified and the crude solubilised B2 BK receptor from rat uterus showed similar affinities for BK and the BK analogues iodo-Tyr0-Bk, D-Phe7-BK, and des-Arg9-BK, indicating that the ligand binding specificity of the receptor had been retained during the purification procedures. The biochemical properties of the solubilised B2 BK receptor correspond to those of a hydrophobic acidic glycoprotein (isoelectric focusing gave a value of 4.5-4.7) that binds specifically to wheat germ agglutinin but has no affinity for either concanavalin A or lentil lectin, suggesting the absence of terminal mannose or glucose residues.
Animals↗
Occupational hydrocarbon exposure and diabetic nephropathy.
Exposure to hydrocarbons has been implicated in the pathogenesis of glomerulonephritis but its role in the development of diabetic nephropathy remains unknown. Three groups of patients with Type 1 diabetes of over 10 years duration were studied. Group 1 comprised 45 patients (23 F) with no diabetic nephropathy (urinary albumin excretion (AER) < 30 mg 24 h-1), group 2 comprised 37 patients (17 F) with incipient diabetic nephropathy (AER between 30-300 mg 24 h-1), and group 3 comprised 31 patients (15 F) with overt diabetic nephropathy (AER > 300 mg 24 h-1). The groups were comparable for age, sex, duration of diabetes, recent glycaemic control, social class, and residential area. Patients were assessed blindly by a validated questionnaire and interview for hydrocarbon exposure, consumption of tobacco, analgesic agents, and alcohol. Exposure scores to hydrocarbons derived from the questionnaire were significantly higher in patients with incipient and overt diabetic nephropathy with smoking adjusted odds ratios of 3.6 and 5.2, respectively. The consumption of alcohol, analgesic agents, tobacco, and smoking habits were similar in the three groups. In conclusion, hydrocarbon exposure may be a key environmental factor in the development of diabetic nephropathy in patients with Type 1 diabetes.
Adult↗
Occupational factors and renal disease.
The male-to-female ratio of patients requiring dialysis treatment commonly approaches 2:1. It is proposed that environmental factors, particularly occupational exposure to hydrocarbons, may account for the excess number of male patients. The term "hydrocarbon" refers to the aliphatic, alicyclic, aromatic, and halogenated hydrocarbons (carbon tetrachloride, chloroform); glycols (ethylene glycol, diethylene glycol, dioxane, glycerol); and organic solvents. Hydrocarbons commonly find use as solvents in industrial manufacturing practices because of their lipid solubility. Hydrocarbons have long been known to be neurotoxicants, affecting both peripheral and central nervous systems. Although benzene and its derivative have a known association with uroepithelial tumors, there is now a considerable body of evidence suggesting a possible role for hydrocarbon exposure in the development of non-neoplastic renal diseases. This article presents an epidemiological case for such an association and critically reviews the literature.
Case-Control Studies↗
Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis.
Tubular damage is a recognized feature of both overt diabetic nephropathy and glomerulonephritis. However, the pattern and mechanism of tubular damage in the two clinical settings remain unclear. Two groups of patients with macroalbuminuria (albuminuria > 300 mg/day) were studied. Group 1 comprised 41 patients with biopsy proven primary glomerulonephritis and group 2 comprised 28 patients with clinical diabetic nephropathy due to insulin dependent diabetes mellitus. Serum creatinine, creatinine clearance, glomerular proteinuria (albuminuria and transferrinuria), markers of tubular damage such as urinary excretion of lysosomal enzyme (N-acetyl glucosaminidase), brush border enzymes (leucine aminopeptidase and gamma-glutamyl transferase) and retinol binding protein (tubular protein) were measured. Both groups were comparable in serum creatinine, creatinine clearance, glomerular proteinuria and excretion of N-acetyl-glucosaminidase. However, a significantly higher degree of tubular brush border enzymuria and a lower level of tubular proteinuria were seen in group 1 than in group 2. In group 1, albuminuria correlated to tubular enzymuria and tubular proteinuria. However, there was no correlation in diabetic patients between parameters of glomerular and tubular damage or dysfunction. The data presented suggested that the pattern of tubulopathy is different in patients with comparable degree of macroalbuminuria due to diabetic nephropathy and glomerulonephritis. Moreover, in diabetic nephropathy contrary to glomerulonephritis, markers of tubular damage are unrelated to glomerular proteinuria. This may suggest different mechanisms of tubular damage in the two clinical settings. We recommended that in all patients with proteinuria, particularly those with diabetic nephropathy, markers of renal tubular damage may be useful in monitoring the course of their disease.
Acetylglucosaminidase↗
Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis.
It has been proposed that renal tubular damage and chronic hydrocarbon exposure are causally related to progression of renal failure in primary glomerulonephritis. We examined the relationship between hydrocarbon exposure and morphological parameters of tubulointerstitial damage in 59 patients with biopsy-proven primary glomerulonephritis (proliferative, n = 52; membranous, n = 7). From a mean follow-up period of 6 years patients were divided into two groups (GP) according to the presence or absence of progressive renal failure (GP 1, n = 24 with progressive renal failure) and (GP 2, n = 35 without progressive renal failure). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood-pressure control. Patients were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Biopsy cylinders were blindly assessed retrospectively for relative interstitial volume of the renal cortex by the point-counting method. In addition an assessment was made of the degree of fibrosis and chronic inflammatory cellular infiltrate. Hydrocarbon exposure score derived from the questionnaire until the time of renal biopsy correlated both with interstitial volume (r = 0.55; P < 0.001) and serum creatinine (r = 0.46; P < 0.001). Moreover, interstitial volume also correlated with serum creatinine (r = 0.63; P < 0.001). Chronic hydrocarbon exposure scores and relative interstitial volume in the renal cortex at the time of renal biopsy was significantly higher in GP 1 than GP 2 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Evidence of oxidant injury and tubular damage in early diabetic nephropathy.
Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.
Adult↗
Human urinary intestinal alkaline phosphatase as an indicator of S3-segment-specific alterations in incipient diabetic nephropathy.
Urinary enzymes were determined in a controlled study including 28 type I diabetes mellitus patients. Fifteen patients had persistent microalbuminuria and were compared to 13 normoalbuminuric patients with comparable age and sex distribution. All patients had normal renal function as measured by serum creatinine. Human intestinal alkaline phosphatase (hIAP), a specific marker of the proximal tubular S3 segment, was elevated in the urine of microalbuminuric patients while human tissue non-specific alkaline phosphatase (hTNAP), indicating effects mainly at the S1-S2 segments, was not. Urinary hIAP was correlated with serum glycated haemoglobin. These results suggest that tubular alterations are present at an early stage of diabetic nephropathy, especially at the S3 segment, and that hIAP may have promise as an early marker.
Acetylglucosaminidase↗
Association of solubilized bradykinin B2 receptors with G-proteins.
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Adenosine Diphosphate↗
Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus.
1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hydrocarbon exposure and tubular damage: additional factors in the progression of renal failure in primary glomerulonephritis.
To investigate the role of hydrocarbon exposure in the progression of glomerulonephritis, 68 patients (12 female) with biopsy-proven primary glomerulonephritis (60 proliferative cases, 8 membranous) were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Serum creatinine, proteinuria, and urinary excretion of markers of renal tubular damage were measured. Patients were assessed for evidence of progressive renal failure (PRF) (defined as persistent rise of serum creatinine > 50 mumol/l above the baseline) during a mean follow up period of 5 years. Patients were divided according to the presence or absence of PRF, (group 1, n = 29, with PRF) and (group 2, n = 39, without PRF). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood pressure control. The derived chronic hydrocarbon exposure scores were significantly higher in group 1 than 2 (p < 0.001). Moreover, hydrocarbon exposure score since the diagnosis of glomerulonephritis was significantly higher in group 1 than 2 (p < 0.001). In group 1, 73% of patients continued to be exposed to hydrocarbons at their work site after the diagnosis of glomerulonephritis, compared to only 13% in group 2 (p < 0.001). At renal biopsy, group 1 had a significantly higher mean serum creatinine than group 2 but the degree of proteinuria and proportion of patients with hypertension were similar. During follow-up serum creatinine rose significantly in group 1 but not in group 2. In group 2, proteinuria fell significantly during follow-up but remained unchanged in group 1. A higher proportion of patients from group 1 developed hypertension requiring antihypertensive drugs (84% vs. 28%; p < 0.001). Urinary marker secretion data indicated a possible association between tubular damage and renal impairment. These results suggest that chronic hydrocarbon exposure and renal tubular damage are important additional risk factors in the progression of primary glomerulonephritis.
Acetylglucosaminidase↗
Early child health in Lahore, Pakistan: II. Inbreeding.
The prevalence of consanguineous marriages was studied in 940 families belonging to four different socio-economic groups in and around Lahore, Pakistan. The births occurring in these families from September 1984 to March 1987 were also investigated for birth defects. The overall prevalence of consanguineous marriages was 46%. The first cousin marriages were most common (67%), followed by the marriages between second cousins, 19%. The prevalence of consanguineous marriages was clearly associated with the socio-economic status of the study groups; 50% of the marriages was related in the periurban slum, 49% in the village, 44% in the urban slum and 31% in the upper middle class. The birth defects were also more prevalent in the poorer areas, being highest in the periurban slum (17.7%) followed by the urban slum (15.6%) and then the village (14.8%) and lowest in the upper middle class (12.3%). Although, the frequency of both consanguinity and birth defects were related with the socio-economic levels of the study groups, there was no association between inbreeding and birth defects. Perhaps, deleterious recessive genes for birth defects have been "bred out", because of continuous inbreeding over generations in this population. There was a significant predilection of major birth defects in boys without clear sex linkage. The conclusion is that the rate of consanguineous marriages was high, especially in the poorer areas, but the relationship between consanguineous marriages and birth defects was little or none. However, other child health indicators may be affected by consanguineous marriages.
Adult↗
Early child health in Lahore, Pakistan: IX. Perinatal events.
In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12-31% for boys and 12-25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (< -2SDS, odds ratio 5.5) and length of gestation (< 37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (< -2SDS, odds ratio 2.0) and weight for length (< -2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23-35% had height < -2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well.
Adolescent↗
Early child health in Lahore, Pakistan: XI. Growth.
This work gives growth reference values at birth to 24 months of age for Pakistan based on upper middle class infants. Growth rate reference values are also included and they are given for various interval lengths. The growth was differently affected in infants living in three poorer areas; the stunting incidence at 24 months of age was 63% in periurban slum, 54% in the village and 26% in the urban slum. Less differences could be seen between the areas in weight for length. There was an age dependency in the incidence of reduced growth; a normal length gain was seen at birth to about six months of age, but they were highly reduced at 6 to 18 months of age. The weight gain was to some degree reduced during the first 12 months of life, followed by a catch-up growth period. The seasonal influence was also age dependent; weight was highly affected during the summer at birth to 24 months of age, but not in the winter. The seasonal effect in length was marginal at birth to 6 months, little at 6 to 12 months (although, constant below the normal) and large at 12 to 24 months of age. We did not see any seasonality of growth in the reference group. The incidence of reduced growth reflects the socio-economic differences in one restricted geographic area, i.e., in the city of Lahore, Pakistan.
Age Factors↗
Early child health in Lahore, Pakistan: XII. Milestones.
Psychomotor development was assessed in 1476 infants from four different levels of urbanization in and around Lahore, Pakistan. Development was assessed monthly at birth to 24 months of age by using a set of 10 milestones selected from the Denver Developmental Screening Test and the Developmental Screening Inventory. The psychomotor development of children in the upper middle (Um) class was consistent with reference population groups in Europe and North America, hence this group was used as control. There was significant delay in the psychomotor development of infants belonging to the poorer areas compared to the Um class. There was no sex difference in the development of the milestones in any study area, except for girls in the Um class who were earlier for about one month than boys in talking. Infants in the poorer areas were, on average about 3 months, delayed in their walking and fine motor activity (building a tower of 3 cubes) in comparison with the Um class. Observed disturbance in psychomotor development at an early age may affect the abilities and achievements in later life.
Child Development↗
Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.
Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.
Aluminum↗
Renal impairment with chronic hydrocarbon exposure.
Occupational hydrocarbon exposure is believed by some investigators to play an important role in the development of several non-neoplastic renal diseases. In view of the continuing debate in this area of nephrology we adopted a cross-sectional approach by investigating the prevalence of clinical or sub-clinical renal dysfunction in subjects chronically exposed to hydrocarbons at their work site. Three groups of healthy men working in different and separate areas of a major car manufacturing plant in the North-west of England participated in the study. Group 1 comprised 112 paint sprayers with exposure to paint-based hydrocarbons, group 2 comprised 101 volunteers working in the transmission area of the plant with exposure to petroleum-based mineral oils, and group 3 comprised 92 automated press operators with minimal background exposure to lubricants who acted as internal controls. Early markers of renal dysfunction such as serum creatinine, urinary total protein, albumin, transferrin, retinol binding protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion were measured. Upper reference values of the parameters measured were derived from 105 comparable laboratory based controls with no occupational exposure to hydrocarbons or heavy metals. Group 1 had a significantly higher prevalence of elevated serum creatinine than the other groups and a higher prevalence of abnormal urinary total protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion than groups 2 and 3. Group 2 had normal serum creatinine but a significantly higher prevalence of abnormal urinary total protein, transferrin, retinol binding protein, N-acetyl-glucosaminidase, and leucine-amino-peptidase excretion than group 3. Serum albumin was similar in all groups. There was some clustering of abnormal findings but the markers of renal dysfunction used in the study identified 37 individuals in group 1 and 31 subjects in group 2 with at least one abnormal parameter, compared to only five individuals in internal controls. This difference between the two target groups and group 3 was highly significant (p < 0.001). Subjects with chronic paint exposure had renal impairment and tubular dysfunction. Tubular dysfunction was also prominent with petroleum oil exposure. We therefore conclude that chronic hydrocarbon exposure may be associated with clinical and sub-clinical renal dysfunction. We advocate careful monitoring of workers exposure to hydrocarbons and for more effective preventive measures.
Adult↗
Omani experience with a heterogeneous group of kidney transplant recipients over a 10-year period.
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Developing Countries↗