Relationship between level of circulating modified LDL and the extent of coronary artery disease in type 2 diabetic patients.

The impact of diabetes on health is due almost entirely to a series of complications that characterise the disease. It is associated with an increased incidence of macrovascular complications including coronary artery disease (CAD). The aim of the present study is to evaluate the possible relationship between the circulating levels of the modified derivatives of low-density lipoprotein (LDL) and the development of angiopathy in type 2 diabetic patients with CAD. The status of the antioxidant defences and the role of supplementation with antioxidant combinations are also studied in these patients. The study was conducted on three groups: group I (controls); group II (type 2 diabetic patients without complications--CAD[-]); and group III (including type 2 diabetic patients with stable CAD - CAD[+]). Patients in group III received adjunct treatment of antioxidant tablets for three months. The results of the present study clearly indicated that there was excessive exposure to oxidative stress in diabetic patients. The increase in free radicals was coupled with disturbance in free radical scavengers, particularly the glutathione system. The disturbance was more prominent in CAD(+) patients. The study has shown alteration in the lipid profile in diabetic groups, where the oxidised LDL (ox-LDL) levels were significantly higher than in control subjects. Diabetics with CAD had higher levels of ox-LDL than did patients without CAD. The intima/media thickness (IMT) of the carotid artery was within clinically accepted normal values if the ox-LDL level was below 100-110 u/L. Once the ox-LDL exceeded this range, IMT increased sharply with the increase in plasma ox-LDL. It seems that the level of ox-LDL should be kept below an upper limit of the 100-110 u/L range in order to avoid the serious atherosclerotic effects of this factor. The results demonstrate that plasma levels of ox-LDL correlate with the extent of coronary artery disease in type 2 diabetic patients and suggest that elevated levels of ox-LDL, can serve as an independent and significant predictor for future cardiac events in type 2 diabetic patients with CAD.

Embryopathy in experimental diabetic gestation: assessment of oxidative stress and antioxidant defence.

Maternal diabetes is associated with an increased rate of congenital fetal anomaly. In the present study, diabetes was induced by streptozotocin in female rats one week prior to conception and the embryos were examined during organogenesis. Experimental diabetes is associated with over-production of free radicals and disturbed antioxidant defence, particularly in malformed embryos. Oxidative stress is demonstrated by increased MDA accumulation and reduced glutathione levels. Despite large differences in the reduced/oxidised glutathione ratios during organogenesis in the control, diabetic non-malformed and malformed embryo groups, the half-cell redox potential was constant for each group during the experimental period. Calculated redox potentials indicated that although embryo cells from the control and diabetic mother groups were of the same chronological age, the stages of development were different. Increased oxidative stress in rat embryos was associated with increased glutathione peroxidases and glutathione-S-transferase activity. This may, in part, provide an explanation for the observed accumulation of oxidised glutathione in malformed embryos. Moreover, decreased levels of vitamin C and selenium were observed. Increased oxidative stress and perturbations in antioxidant defence contribute to the high incidence of congenital anomalies in experimental diabetic gestation.

Embryopathy in experimental diabetic gestation: assessment of PGE2 level, gene expression of cyclooxygenases and apoptosis.

The causes of, and predisposing conditions for, increased congenital anomalies in embryos of experimental diabetic gestation are not fully identified. In the present study, some possible factors involved in diabetes-induced embryopathy are explored. The concentration of PGE2, the gene expression of cyclooxygenases (COX-1 and COX-2) and level of apoptosis (measured by caspase-3 activity) are assessed during organogenesis in the embryos of streptozotocin-induced diabetic rats. The concentrations of PGE2 in the embryos of diabetic rats were lower than controls, with the lowest values in malformed embryos and their associated membranes (yolk sacs). The pattern of change in PGE2 was similar in the embryos of the control and diabetic groups, which showed a steady decline between days 9 and 11 of gestation. These changes in PGE2 were accompanied by a small decrease in COX-1 expression in all embryos and associated membranes during the same gestational period. Expression of COX-2, which was below normal in diabetic embryos, decreased between days 9 and 11 of gestation in all groups. In the membranes of non-malformed embryos, COX-2 expression peaked on day 10 of gestation. It was found that there was little or no detectable COX-2 expression in the membranes of malformed embryos on day 9 of gestation and although its expression was detectable on the following days it was much lower than in the other groups. Caspase-3 activity increased substantially between days 9 and 11 of gestation. Embryos from the experimentally diabetic group showed higher activity than did controls, with the largest increases in the malformed embryos. It would appear that COX-2 expression and PGE2 concentration (in both embryo and associated membranes) play a significant role in organ formation. The data presented here suggest that an unhealthy placenta may be instrumental in the development of malformed embryos.

Nitric oxide generation by peripheral blood cells in chronic renal failure.

Nitric oxide (NO), a labile free radical synthesised from L-arginine by the action of nitric oxide synthase (NOS), is said to be implicated in uraemic complications, such as infection and a tendency to bleed. In this study of NO production by peripheral blood cells, an increased level is seen in platelets from uraemic patients (both non-dialysed and haemodialysed) and a decreased level in leucocytes (neutrophils and monocytes). A negative correlation was noted between blood urea level and inducible NO in neutrophils and monocytes in uraemic patients not on dialysis. In contrast, haemodialysis appears to lead to an increase in inducible NO production in neutrophils and monocytes. Plasma NO levels were significantly increased in uraemic patients, compared with normal controls, and hemodialysis led to further increases. Superoxide dismutase (SOD) activity was significantly reduced in platelets, neutrophils and monocytes in the uraemic group. It is concluded that increased NO production by platelets may contribute to the bleeding tendency observed in uraemia, and high urea concentrations may contribute to the regulation of inducible NO production in leucocytes.

Studies on serum beta-glucuronidase activity and urinary tryptophan metabolites in human fascioliasis.

In the last few years, human fascioliasis has been reported more frequently from different parts of the world including Egypt. The present work aimed to study the ability of fascioliasis affected patients to metabolize tryptophan and to explore how this disease can affect the activity of the hydrolytic lysosomal enzyme beta-glucuronidase. Liver and kidney functions and complete blood pictures of the studied patients were considered. Eleven tryptophan metabolites together with 4-pyridoxic acid, the major metabolite of vitamin B6, were determined. Fascioliasis showed an abnormal pattern of tryptophan metabolism which resembled that described earlier by Kupke and Knapp and which indicated that those patients were suffering from vitamin B6 deficiency. This conclusion was proved by the decreased levels of 4-pyridoxic acid. Abnormally high levels of beta-glucuronidase were also encountered in the fascioliasis cases which points to the liver damage caused by the fluke.

Effect of some xenobiotics on kynurenine hydrolase and kynurenine aminotransferase of mouse liver.

The effects of some xenobiotics on the activity of the B6-dependent kynurenine hydrolase (KH) and kynurenine aminotransferase (KATE) in mouse liver, were investigated. Polychlorinated biphenyl (Aroclor 1254) (400mg/kg/day x4) markedly decreased the activity of both enzymes. Benzo(a)pyrene (BP) and 3-methylcholanthrene (3-MC) (40mg/Kg/day x1) as well as phenobarbital (PB) (75mg/kg/day x3) did not alter the activity of KH, while that of KATE was mildy reduced. The response of the two enzymes to treatment with chlorpromazine (CPZ) (5mg/Kg/day x5) were opposite with marked elevation of KH and inhibition of KATE activities. Treatment with B-naphthoflavone (B-NF) (80mg/Kg/day x2), Pyrazole (200mg/Kg/day x1) or indole (400mg/kg/day x1) produce no change in the activity of either enzyme. It, seems therefore, that Aroclor (1254) and chlorpromazine may cause disordered kynurenine metabolism through alterations in the activities of its metabolizing enzymes. This, in turn, might affect nicotinamide adenine dinucleotide biosynthesis and/or the accumulation of some tryptophan metabolites suspected of being carcinogenic or co-carcinogenic.

Urinary alpha-naphthyl acetate esterases: a preliminary screening test for bladder cancer.

The urinary activities of alpha-naphthyl acetate esterases were measured for groups of bilharzial and nonbilharzial patients with benign urologic diseases and for others with bladder cancer. All these patients showed elevation in the urinary enzyme activity over that given by healthy controls. Bilharzial and nonbilharzial bladder cancer patients exhibited significant increase in urinary enzyme activity as compared with corresponding groups with benign urologic diseases A level of 50 units of enzyme activity was taken as a limit to discriminate between bladder cancer patients and those patients with benign urologic diseases. The specificity and sensitivity of this urinary test exceeded 90% with low falsely positive and negative results. The data of the present study recommended the use of urinary alpha-naphthyl acetate esterases activity as a preliminary screening test for bilharzial and nonbilharzial bladder cancer patients.

Effect on prolonged use of oral contraceptive pills on the activity of serum and vaginal ribonuclease.

PIP: 39 longterm oral contraceptive (OC) users (12-15 years) and 30 women who have never used OCs were studied to determine the activity of free alkaline ribonuclease (RNase) in vaginal fluid and in serum. All women were of reproductive age. Of the 30 controls, 14 had cervical erosions, and the remainder were clinically healthy. Of the 39 cases, 12 were clinically free of cervicitis or cervical erosion, 21 had some sort of cervicitis, and 6 had trichomonal vaginitis. The group of women using OCs who had cervical infections showed a significant increase in the RNase activities compared with the clinically free pill users (P .025 and .005, respectively). The activity of serum and vaginal free alkaline RNase activity was higher and statistically significant in the controls with cervical erosion compared with clinically free controls (P .001). In addition, OC users with cervicitis showed a significant increase in vaginal RNase activity compared with clinically free pill users (P .001), whereas the difference in mean serum RNase was not significant between these 2 groups. Specifically, OC users with trichomonal vaginitis had significantly higher serum and vaginal RNase activity values than nonpill users who were clinically free or who had trichomonas. The OC users with trichomonas showed only a significant increase in serum free RNase compared with OC users with cervicitis (P .001).^ieng

In vitro studies of the effect of metal ions, EDTA and their mixtures on kynurenine aminotransferase and kynurenine hydrolase.

In the present study use was made of the chelating ability of EDTA and the activating property of some metal ions Ca(II), Mg(II) or Mn(II) to counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on the B6-dependent kynurenine hydrolase and on kynurenine aminotransferase. These may be of help in studying the therapeutic trials in the treatment of metal poisoning. EDTA was able to counteract the inhibitory effect of Cu(II) or Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on kynurenine hydrolase. The difference in the response of the two B6-dependent enzymes to EDTA is attributed to the difference in the functional groups involved in the active site(s) of the two apoenzymes. Moreover, Mn(II), Ca(II) and Mg(II) ions have the ability to counteract some of the inhibitory effect of these metal ions.

beta-Glucuronidase in schistosomal intestinal polypi of the colon.

The results of a clinical, histopathological and biochemical study on twenty patients with schistosomal polyposis of the large bowel and ten patients with normal colon as a control are reported. The biopsy showed clearly the absence of any malignant or premalignant changes in all the twenty bilharzial patients. Results of the biochemical study showed that there is a statistically significant increase in beta-glucuronidase activity in schistosomal polypi compared to normal mucosa. This enzymatic activity is absent in schistosoma ova. The causes of the increase in the enzyme activity have been attributed to leucocytic infiltration present in schistosomal granulomata and possible to some degree of liver disfunction. The protein content of the excess mucus present in the colon could also activate the enzyme. Our results also show that the increased enzyme activity does not necessarily have carcinogenic properties. We did not come across a single case of malignancy even in a patient with very high level of enzyme activity (11615 units) or in those patients with a prolonged history of the disease.

The spontaneous urinary excretion of tryptophan metabolites "via kynurenine" in women with regards to the prepuberty, sexual maturity and menopause.

High values of anthranilic acid, 3-OH-kynurenine, xanthurenic acid and 3-OH-anthranilic acid are observed in the spontaneous urinary excretion of tryptophan metabolites in girls in the prepubertal age. The highest differences are between the 3-hydroxy metabolites especially the 3-hydroxykynurenine. On the other hand, this metabolic excretion in postmenopausal women is statistically identical to that of women in sexual maturity.

beta-Glucuronidase activity in liver and spleen homogenates of mice experimentally infected with Schistosoma mansoni.

A study on the beta-glucuronidase activity in liver and spleen homogenates of mice infected with an Egyptian strain of Schistosoma mansoni and of non infected control animals was carried out for a follow up period of four months. A decreased enzyme activity was observed in the spleen up to the 40th day after infection. From the 60th day on, the enzyme level in both liver and spleen was found above that in the control. The possible causes for such changes in enzyme activity are discussed.

Biochemical studies on beta-glucuronidase in the urinary bladder of normal and Schistosoma mansoni infected mice treated with hycanthone.

beta-Glucuronidase activity is elevated in the urine of patients with bilharziasis hematobium. In the present study the enzyme level was estimated in whole urinary bladder tissue homogenates of mice experimentally infected with Schistosoma mansoni. In the infected mice the enzyme activity is significantly higher than in the controls. The effect of the schistosomicidal drug hycanthone was also evaluated. Treatment with the drug did not affect the level of the enzyme activity in the infected mice; it induced an increase in the enzyme activity of the controls.