M. S. M. Ardawi

The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells

The rates of utilization of both glucose and glutamine are high in rapidly dividing ceils such as enterocytes, lymphocytes, thymocytes, tumour cells; the oxidation of both glucose and glutamine is only partial, glucose to lactate and glutamine to glutamate , alanine or aspartate ; and these partial processes are termed glycolysis and glutaminolysis respectively . Both processes generate energy and also provide precursors for important biosynthetic processes in such cells. However, the rates of utilization of precursors for macromolecular biosynthesis are very low in comparison to the rates oi partial oxidation, and energy generation per se may not be the correct explanation for high rates of glycolysis and glutaminolysis in these cells since oxidation is only partial and other fuels can be used to generate energy. Both the high fluxes and the metabolic characteristics of these two processes can be explained by application of quantitative principles of control as applied to branched metabolic pathway s (Crabtree & Newsholme, 1985). If the flux through one branch is greatly in excess of the other, then the sensitivity of the flux of the low-flux pathway to regulators is very high. Hence, it is suggested that, in rapidly dividing ceils, high rates of glycolysis and gtutaminolysis are required not for energy or precursor provision per se but for high sensitivity of the pathways involved in the use of precursors for macromolecular synthesis to specific regulators to permithigh rates of proliferation when required for example, in lymphocytes in response to a massive infection.

Effect of Marginal or Severe Dietary Zinc Deficiency on Testicular Development and Functions of the Rat

The effects of marginal (MZD) and severe (SZD) zinc-deficient diets on testicular function and development were studied in rats maintained on dietary treatment for 6 weeks after weaning. SZD produced variable degrees of histological changes as compared with pair-fed controls, including a significant decrease in the diameter of seminiferous tubules (p < .05) with variable degree of maturation arrest in different stages of spermatogenesis. No significant histological changes were obtained in testes of MZD rats. MZD rats-exhibited significant decreases in serum levels of testosterone (62.6%, p < .001) and progesterone (18.2%, p < .05) with no changes in that of FSH or LH. SZD rats showed marked decreases in serum levels of testosterone (17.8-fold, p < .001) and progesterone (28.8%, p < .001), whereas FSH showed an increase (34.4%, p < .05) as compared with respective controls. In vitro acute stimulation by hCG on testicular tissue preparation obtained from MZD rats resulted in much less androgen production (sum of androstenedione, testosterone, and androstanediol) (72.4%, p < .001) as compared with controls. Testicular androgen contents (sum of androstenedione, testosterone, and androstanediol) decreased significantly in MZD and SZD rats, with the latter showing the greatest decrease. SZD rats were asospermic, whereas MZD rats exhibited marked decrease in sperm counts (by 22.9%, p < .05) as compared with respective controls. The results reflect a direct action of zinc deficiency on testicular steroidogenesis and strongly support the idea that hypogonadism of zinc deficiency results mainly from changes in testicular steroidogenesis or indirectly from Leydig cell failure.

Glutamine metabolism in skeletal muscle of septic rats

The metabolism of skeletal muscle glutamine was studied in rats made septic by cecal ligation and puncture technique. Blood glucose was not significantly different in septic rats, but lactate, pyruvate, glutamine, and alanine were markedly increased. Conversely, blood ketone body concentrations were markedly decreased in septic rats. Both plasma insulin and glucagon were markedly elevated in septic rats. Sepsis increased the rates of glutamine production in muscle, but without marked effects on skin and adipose tissue preparations, with muscle production accounting for over 87% of total glutamine produced by the hindlimb. Sepsis produced decreases in the concentrations of skeletal muscle glutamine, glutamate, 2-oxoglutarate, and adenosine monophosphate (AMP). The concentrations of ammonia, pyruvate, and inosine monophosphate (IMP) were increased. Hindlimb blood flow showed no marked change in response to sepsis, but was accompanied by an enhanced net release of glutamine and alanine. The maximal activity of glutamine synthetase was increased only in quadriceps muscles of septic rats, whereas that of glutaminase was decreased in all muscles studied. Tyrosine release from incubated muscle preparation was markedly increased in septic rats; however, its rate of incorporation was markedly decreased. It is concluded that there is an enhanced rate of production of glutamine from skeletal muscle of septic rats. This may be due to changes in efflux and/or increased intracellular formation of glutamine; these suggestions are discussed.

Serum Immunoglobulin Concentrations in Diabetic Patients

The relationship between glycated haemoglobin (an index of long‐term diabetic control), fructosamine (an index of intermediate‐term diabetic control), and serum IgA, IgG, and IgM was studied in 110 diabetic patients (41 Type 1 and 69 Type 2) and compared with 111 healthy non‐diabetic subjects. Significant increases in serum IgA (by 82.7%, p < 0.001) and IgG (by 35.2%, p< 0.001) concentrations were observed whereas the concentration of IgM was significantly decreased (by 46.7%, p < 0.001) in diabetic patients compared with non‐diabetic subjects. Using Spearmans rank correlations, IgA correlated with fructosamine (r = 0.77, p < 0.001), HbA1 (r = 0.76, p < 0.001), and albumin (r = −0.58, p < 0.001) for the entire population sample but only fructosamine (r = 0.19, p < 0.05) and HbA1 (r = 0.28, p < 0.001) correlated with IgA in diabetic patients, respectively. It is concluded that abnormal levels of IgA, IgG, and IgM are very common in diabetic patients in whom serum IgA concentrations are influenced by the degree of glycaemic control. Whether changes in IgA and other immunoglobulins are implicated in the pathogenesis of diabetic complications (such as susceptibility to infection) deserve further study.

Paediatric burn injuries in the Jeddah area of Saudi Arabia: A study of 197 patients

A prospective study was conducted on paediatric thermal injury patients admitted to the Burns Unit at King Fahd Hospital, Jeddah, Saudi Arabia over a 2-year period (December 1985 to December 1987). A total of 197 patients (out of 319) were paediatric, aged up to 18 years. Infants and toddlers accounted for 59.4 per cent and adolescents for 14.2 per cent. Scalding and flame injuries accounted for 98 per cent with most injuries occurring at home (97.5 per cent) and the overall paediatric mortality rate was 4.4 per cent.

Glutamine Metabolism in Lymphoid Tissues

When lymphocytes are suitably stimulated either specifically (by an antigen) or non-specifically (by mitogens), they are transformed into a state of high biochemical activity which initiates production of various mediators of immunity including antibodies if they are B-lymphocytes and the mediators of cellular immunity (e.g., lymphotoxin, chemotactic factors, mitogenic factors) if they are T-lymphocytes. To perform this activity lymphocytes require an increased rate of ATP generation and it has generally been assumed that glucose was the only quantitatively important fuel (see Hume and Weidemann 1980). Recently Ardawi and Newsholme (1982) have provided evidence to suggest that other fuels can be utilised by lymphocytes. This suggestion is based on the maximal activities of key enzymes of the energy-producing pathways in lymphocytes, the ability of these cells to utilise glutamine, ketone bodies (3-hydroxybutyrate and acetoacetate) and long-chain fatty acids (oleate and palmitate) (Table 1) and the effects of these fuels on oxygen consumption by lymphocytes. Of these fuels glutamine may be quantitatively the most important.

Determinants of pregnancy outcome in patients with gestational diabetes

Objectives: To describe the experience of management of gestational diabetes ‘GDM’ among a high‐risk population and to determine the relative contribution of maternal risk factors and some indices of glucose intolerance on pregnancy outcome. Methods: A total of 173 antenatal patients with GDM, matched to 337 non‐diabetic controls were evaluated. Incidences of fetal macrosomia, large birth weight (>4000 g), and operative delivery were noted. Patients with GDM were subgrouped into group I and II, according to the fasting blood glucose (FBG) level on the glucose tolerance test ‘GTT’, whether ≥ or < 5.8 mmol/l, respectively. A logistic regression model was then developed with predictive variables, i.e. maternal weight, height, parity, gestational week at diagnosis of GDM, degree of glucose tolerance, treatment and means of fasting and post‐prandial blood glucose measurements as independent variables against each of the outcome measures as dependent variables. Results: Compared with non‐diabetics, patients with GDM were older in age, weight and parity. The mean fetal birth weight, incidences of macrosomia and babies >4 kg were significantly higher among GDM patients. In patients with GDM the degree of glucose intolerance (determined by FBG on the GTT) and maternal weight were the only variables that significantly increased the risk of macrosomia and operative delivery. Within group I patients (FBG ≥ 5.8 mg/dl) only ‘maternal weight’ significantly increased the risk of both having a baby > 4 kg, and operative delivery. Conclusion: Among patients with gestational diabetes, a GTT with a FBG level ≥ 5.8 mmol/l is a strong predictor for perinatal outcome. Maternal weight is an independent risk factor that increases the risk of both macrosomia and operative delivery.

Autoantibodies to GAD and IA-2 in Saudi Arabian diabetic patients

Aims  To determine the prevalence of autoantibodies in sera of Saudi diabetic patients including Type 1 and Type 2 diabetes mellitus (DM) and gestational diabetes mellitus (GDM) living in Jeddah, Saudi Arabia. Apart from data on the prevalence of islet‐cell antibodies in patients in Ryhadh (Al‐Attas et al. Freqency of islet cell antibodies in adult newly diagnosed diabetic patients. Ann Saudi Med 1990; 10: 369–373) immunological markers of autoimmune diabetes have not been explored in Saudi Arabians.

Burn injuries in the Jeddah area of Saudi Arabia: a study of 319 cases

Three hundred and nineteen patients with different types of burns were studied at King Fahd Hospital, Jeddah, Saudi Arabia over a 2-year period (December, 1985 to December, 1987). Scalding was the most common cause (56.4 per cent) of burn injuries compared with 41.4 per cent of patients who sustained flame injury; 84.6 per cent of the thermal injuries occurred at home, with children (less than or equal to 18 years of age) being affected most frequently (61.8 per cent). The overall mortality was 9.4 per cent.

Effect of glutamine-supplemented total parenteral nutrition on the small bowel of septic rats

In order to study the effect of total parenteral nutrition (TPN) with or without glutamine supplementation in septic rats, septic Wistar albino rats were randomly assigned to receive 0.23 g of nitrogen and 113 kJ (100 g BW)(-1) per day in the form of amino acids with (group 2) or without (group 1) glutamine supplementation or 10% (w/v) glucose only (group 3). After 4 days of TPN treatments, rats receiving glutamine-supplemented TPN had a cumulative nitrogen balance of -24.4 +/- 3.3 mg N, which was significantly (P < 0.001) better compared to other TPN-treated groups. Septic rats of group 2 survived sepsis significantly (P < 0.001) better than those in groups 1 and 3. Glutamine-supplemented TPN treatment resulted in significant increases in jejunal weight (P < 0.001), DNA and protein contents (P < 0.001), villous height (P < 0.001) and crypt depth (P < 0.001) when compared with septic rats of group 1. Septic rats of group 2 extracted and metabolised glutamine by the small bowel at higher rates (P < 0.001) than that observed in septic rats of group 1. Increases in jejunal glutaminase (38.2%, P < 0.001) and decreases in glutamine synthetase (41.7%, P < 0.001) activities were observed in response to glutamine-supplemented TPN treatment. It is concluded that the administration of glutamine-supplemented TPN is beneficial to the small bowel of septic rats.