K. Gumaa

Two areas of the Sudan known to be endemic to onchocerciasis were surveyed for skin and ocular changes, and serum vitamin A levels in patients and normal controls. In Southern Sudan severe eye lesions and blindness are common complications. In Northern Sudan skin lesions predominate, and no case of blindness was recorded. Serum vitamin A levels were found to be adequate in all groups studied. However, patients from Southern Sudan with both eye and skin lesions due to onchocerciasis had the lowest mean serum vitamin A level. The significance of these findings is discussed in relation to the possible aetiological role of vitamin A deficiency in the pathogenesis of ocular complications of onchocerciasis.

Free amino acid concentrations were determined in maternal plasma and amniotic fluid (AF) under standardized and unstressed conditions in four groups of women comprising 6 gestational and 13 type I diabetics, 10 women with small-for-gestational-age (SGA) infants, and 18 healthy control women between 36 and 39 weeks of gestation. Plasma values for branched chain amino acids (the sum of leucine, isoleucine and valine) did not differ significantly between the four groups. The corresponding values in AF were significantly higher (P less than 0.05) in the type I diabetic group and significantly lower (P less than 0.05) in the gestational diabetic group as compared to the control group. The mean AF C-peptide concentration was elevated but not significantly so in gestational (0.69 nmol/l) or type I diabetic (0.54 nmol/l) pregnancies and significantly lower (P less than 0.05) in women with SGA infants (0.28 nmol/l) as compared to the control group (0.38 nmol/l). There was a significant correlation between C-peptide in AF and branched chain amino acids in maternal plasma (r = 0.63; P less than 0.05) as well as to maternal blood glucose (r = 0.79; P less than 0.01) in the type I diabetic group, which merely suggests a greater beta cell reactivity to insulin secretagogues in offspring of diabetic mothers. The correlation between AF C-peptide and branched chain amino acids in maternal plasma was significantly inverse in women with SGA infants (r = -0.75; P less than 0.05). Both individual, branched chain, or total amino acid concentration in AF were unrelated to AF C-peptide.

This study describes the effects of prednisolone, oestradiol-17B and progesterone on DNA replication and insulin biosynthesis and release of cultured foetal rat islets. Prednisolone significantly inhibited the incorporation of [3H]-thymidine into DNA of islets cultured at a physiological (5.5 mmol/l) but not at a high (22 mmol/l) glucose concentration. It also increased insulin biosynthesis and release of islets cultured at 5.5 mmol/l glucose. Oestradiol-17B reduced the incorporation of [3H]-thymidine into islet DNA at both glucose concentrations, but had no effect on insulin biosynthesis and release. Progesterone had no effect on either the growth or the function of the cultured foetal islets. The observations show a clear dissociation between the action of prednisolone on islet growth versus islet function. They also support the view that neither progesterone nor oestradiol is directly involved in the high rate of B-cell replication previously observed in islets of pregnant rats.

1. The pentose phosphate pathway in Krebs ascites cells was investigated for regulatory reactions. For comparison, the glycolytic pathway was studied simultaneously. 2. Activities of the pentose phosphate pathway enzymes were low in contrast with those of the enzymes of glycolysis. The K(m) values of glucose 6-phosphate dehydrogenase for both substrate and cofactor were about four times the reported upper limit for the enzyme from normal tissues. Fructose 1,6-diphosphate and NADPH competitively inhibited 6-phosphogluconate dehydrogenase. 3. About 28% of the hexokinase activity was in the particulate fraction of the cells. The soluble enzyme was inhibited by fructose 1,6-diphosphate and ribose 5-phosphate, but not by 3-phosphoglycerate. The behaviour of the partially purified soluble enzyme in vitro in a system simulating the concentrations of ATP, glucose 6-phosphate and P(i) found in vivo is reported. 4. Kinetics of metabolite accumulation during the transient state after the addit...

1. The changes in serum levels of uric acid and lipids during 1 month of starvation-refeeding were measured in sixteen male volunteers. 2. Uric acid levels increased linearly with the duration of the experiment. The increase was positively correlated with the increase in serum triglycerides but not with cholesterol or phospholipids. 3. Triglycerides increased at a faster rate than uric acid implying that the increase in uric acid was secondary to that of the lipid. 4. It was concluded that the purine and lipid synthetic pathways are linked through a common small-molecular-weight effector rather than through the sharing of a common enzyme.

Coin^i. Biochem. Physiol,, 1972, fo;. 43A, ^p. 1053 (o 1055. Pergamon Press. Printed in Great Britain SHORT COMMUNICATION EVOLUTION OF CATALASE IN FISH FADIL RABIE,1 AM ABDEL MAGID,2 KHALID AHMED GUMA'A1 and OMER KARRAR1 department of ...

The collagen content of the diaphragm was measured in normal and dystrophic hamsters aged 130 and 270 days. The diaphragm collagen content was greater in dystrophic hamsters than in control hamsters of the same age. The effect was greater in the older hamsters whether the collagen content was expressed in terms of the percentage of dry weight, in relation to surface area, or as total collagen. This increase was apparently at the expense of muscle tissue and may be a major factor contributing to respiratory muscle weakness as dystrophy advances.

The extractability of collagen was examined in different sites of amnion and chorion from term deliveries. Sequential extraction with NaCl, acetic acid and CaCl2 showed that soluble collagen accounted for 1.5% of the proteins extracted. Saline extracted more collagen from the amnion than from the chorion. Acetic acid and CaCl2 extracted decreasing and increasing amounts of collagen from the amnion and chorion respectively. The concentration of collagen decreased linearly in the chorion as the rupture site was approached. The results indicate differences in the nature of collagen between amnion and chorion as well as in various sites in the latter.

Abstract The hypoglycemic effect of three orally administered agents of plant origin, Eugenia jambolana, Lupinus termis and Peganum harmala, was investigated in both normal and streptozocin-induccd diabetic rats, and the results were compared to those obtained using ...

The College of Medicine at Sultan Qaboos University has adopted English as the language of instruction though schooling in Oman is mostly in Arabic. Students of this new medical college are facing learning difficulties in their basic medical sciences. This paper studies ...

An association between inositol phosphoglycan P-type (P-IPG) and preeclampsia has been demonstrated over recent years. This molecule can mediate many of the metabolic and growth promoting effects of insulin. Dysregulation of the mediator family is associated with insulin resistance. An increased concentration of P-IPG has been reported in preeclamptic placenta, although its precursor (GPI) was undetectable in those placental samples. Insulin administration, that induces P-IPG release in normal human placenta, was shown not to cause production/release of the mediator from preeclamptic placental tissue as a consequence of a disturbed insulin signalling. Amniotic fluid is enriched of this mediator, with further increase during preeclampsia. We have found that the fetus released increasing amounts of P-IPG in the urine between 13 and 18 weeks of gestation, reaching a plateau beyond 20 weeks. Cord blood of infants of preeclamptic mothers showed an increased content of soluble P-IPG compared to controls and to the mother.

Reversible phosphorylation of proteins regulates numerous aspects of cell function, and abnormal phosphorylation is causal in many diseases. Pyruvate dehydrogenase complex (PDC) is central to the regulation of glucose homeostasis. PDC exists in a dynamic equilibrium between de-phospho-(active) and phosphorylated (inactive) forms controlled by pyruvate dehydrogenase phosphatases (PDP1,2) and pyruvate dehydrogenase kinases (PDK1-4). In contrast to the reciprocal regulation of the phospho-/de-phospho cycle of PDC and at the level of expression of the isoforms of PDK and PDP regulated by hormones and diet, there is scant evidence for regulatory factors acting in vivo as reciprocal "on-off" switches. Here we show that the putative insulin mediator inositol phosphoglycan P-type (IPG-P) has a sigmoidal inhibitory action on PDK in addition to its known linear stimulation of PDP. Thus, at critical levels of IPG-P, this sigmoidal/linear model markedly enhances the switchover from the inactive to the active form of PDC, a "push-pull" system that, combined with the developmental and hormonal control of IPG-P, indicates their powerful regulatory function. The release of IPGs from cell membranes by insulin is significant in relation to diabetes. The chelation of IPGs with Mn2+ and Zn2+ suggests a role as "catalytic chelators" coordinating the traffic of metal ions in cells. Synthetic inositol hexosamine analogues are shown here to have a similar linear/sigmoidal reciprocal action on PDC exerting push-pull effects, suggesting their potential for treatment of metabolic disorders, including diabetes.

In order to advise regarding the religious practice of withholding food, we studied the metabolic changes after successive 15 days of recurrent fasting of 13 hours every day in maternal plasma and liquor amnii of obese normal gravids and gestational diabetics in their third trimester. There were no significant differences between those who fasted that period for one day prior to elective cesarean section (CS) and those who fasted the same period repeatedly for 15 days. The fasted gravids had significant rises in glycerol, beta-hydroxybutyrate (BOHB) and nonesterified fatty acids (NEFA) (P less than 0.0001, P less than 0.005 and P less than 0.01, respectively) in maternal plasma, compared to unfasted gravid groups and ungravid fasted group. No significant metabolic difference was found in the liquor amnii withdrawn from fasted and unfasted groups. The influence of such short term of starvation on the fetal metabolic profile was studied in the cord blood during cesarean section (CS). Glucose, glycerol and NEFA were significantly lower in arterial than in venous cord plasma (P less than 0.05, P less than 0.01 and P less than 0.01, respectively) indicating that the fetus could utilize these substrates. Positive correlation was found between the levels of BOHB in the mother and venous cord plasma on the one hand and their levels in the arterial cord plasma and liquor amnii on the other hand implying that this substrate passes unutilized through the fetus to the liquor amnii. A pregnant woman in the third trimester should not withhold food for long periods.

Glibenclamide significantly stimulated the incorporation of [3H]thymidine into DNA of fetal rat pancreatic islets at a physiological (5.5 mM) but not at a high (22 mM) glucose concentration. There was no significant stimulation of insulin release under these conditions. In contrast, the drug-stimulated insulin release from adult islets cultured at 5.5 mM glucose but had no effect on their DNA synthesis. The observations suggest that insulin secretion and DNA synthesis may be dissociated in rat pancreatic islets.

The effects of the hypoglycaemia sulphonylurea glibenclamide (HB419) and the non-metabolizable leucine analogue beta-2-aminobicyclo(2.2.1)heptane-2-carboxylic acid (BCH) on insulin release and endogenous substrate metabolism were studied in isolated rat islets. Pre-labelling of the endogenous islet substrate was performed with [14C]glucose (20 mM) or [14C]glutamine (10 mM) during a 24 h tissue culture period before measurements of insulin release or 14CO2 production in short-term incubations. Both HB419 and BCH stimulated the insulin release of the cultured islets, although BCH only after culture of islets with glutamine. The rate of labelling of the islets with [14C]glucose reached an apparent plateau after 16 h in culture and the total islet accumulation of glucose carbon over the 24 h period averaged 12.9 +/- 3.0 nmol/25 islets. Less than 0.5% of the glucose residues was converted to glycogen whereas lipids represented about 2.5%. Fractionation of lipids showed 67% phospholipids, 18% triacylglycerols, 11% diacylglycerols and 6% non-esterified fatty acid. The islet accumulation of glutamine during 24 h corresponded to 11.5 +/- 1.5 nmol/25 islets. After pre-labelling of islets with [14C]glucose there was no effect on the 14CO2-evolution over a 30 min incubation period of either HB419 or BCH. There was also no effect of HB419 after pre-labelling with [14C]glutamine, whereas, in this latter situation, a significant stimulation was observed with BCH. It is concluded that the effects on the pancreatic B-cells by antidiabetic sulphonylureas are not mediated via nutrient receptors.

The controversial issue of the effects of prednisolone and 17 beta-estradiol on replication of fetal rat pancreatic islets in culture was studied using 32P and [3H]thymidine as probes for studying DNA synthesis. DNA synthesis was not affected by the steroid hormones, as was evident from the rate of incorporation of 32P into total DNA. Decreased incorporation of [3H]thymidine into DNA found in islets treated with either of these steroids seemed to reflect an inhibitory effect of these hormones on thymidine kinase, leading to decreased phosphorylation of labeled thymidine. In addition, the hormones stimulated the activity of thymidylate synthetase, thus enhancing the endogenous synthesis of thymidine and thereby diluting the specific activity of the [3H]thymidine added to the cultured islets. Further support for a lack of inhibition of growth of islet cells treated with steroid hormones was provided by the observation that prednisolone increased uridine kinase activity and RNA biosynthesis, both of which may participate in the growth of cells preceding mitosis and (the latter) in protein hormone biosynthesis.

Basic medical sciences at Sultan Qaboos University (SQU) are taught in a systems-based curriculum. During the development of the courses different formats have been used for the written examinations and also different types of questions. This paper compares students' performance in relation to examination format and to types of questions used. The formats were non-coordinated (NCAs), each discipline having a separate paper; coordinated (CAs), questions from various disciplines being given in the same paper but with separate sections for each discipline; and integrated assessments (IAs), questions being grouped under structure, function, and problem-based integrated long essays. The types of questions used were multiple choice (MCQs), short essays (SEQs), and structured integrated long essays (SILEQs). Students performed better in SEQs than in MCQs. Our analyses also show that SILEQs measure skills similar to those of MCQs and SEQs combined. Students performed best in NCAs. In CAs, students concentrated on those disciplines carrying most weight in the final grade. Currently we use IAs consisting of two parts: part I, comprising MCQs and SEQs, and part II, comprising SILEQs. To date, students are performing better in part II than in part I. We suggest that it is prudent to use different types of questions to measure students' knowledge and skills when IAs are used for systems-based courses.

Blood coagulation and fibrinolysis were assessed in 55 cases of heat stroke who presented with or without bleeding tendencies during the Makkah pilgrimage of 1983. 17 patients were identified to have evidence of disseminated intravascular coagulation (DIC). Bleeders with DIC had a higher incidence of shock and a higher mortality when compared to non-bleeders. Thrombocytopenia and liver cell damage were not limited to cases with DIC. Coagulation factors and serum enzyme studies suggested non-specific tissue damage as the trigger mechanism for DIC possibly proceeding through the extrinsic system of blood clotting. We conclude that the breakdown of haemostasis in heat stroke is multifactorial: thrombocytopenia, liver cell damage and DIC.

Thirty-eight patients in diabetic coma from four different centres were treated with a continuous low-dose intravenous infusion of insulin at an average dose of 7.2 IU/hr. All patients recovered rapidly except for one profoundly shocked patient who died. The mean fall in plasma glucose was 58% four hours after the start of insulin. Blood ketone bodies and plasma free fatty acids showed a similar response. There was no significant difference in plasma glucose response according to severity of acidosis or previous treatment with insulin. Hypokalaemia was uncommon. In the treatment of diabetic coma this technique has proved simple, safe, and effective.

Collagen from the chorioamnion units from premature and term pregnancies was solubilized by limited pepsin digestion and subjected to SDS-PAG electrophoresis. Collagen types were quantitated by densitometry. It was found that collagen type III decreases and collagen type V tends to increase as gestational age advances. Investigating the relative abundance of collagen types at various membrane sites from term pregnancies revealed that type V decreases in the amnion as the rupture site is approached. It is concluded that since type V collagen is more resistant to collagenases, its decrease may predispose that particular site to rupture.