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Heritability in type 2 diabetes mellitus (T2DM) is observed but not well understood.In this study, family history and clinical/biochemical data from 789 Bahrainis (418 T2DM, 371 controls) was analyzed. Fasting blood glucose (FBG) and HbA1c were measured and angiotensin-converting enzyme (ACE) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms (SNPs) were analyzed.Patients compared to controls have higher proportions of diabetic mothers (50.2% vs. 32.7%, p=0.005), fathers (35.2% vs. 12.1%, p0.001) and siblings (56% vs. 15.3%, p0.001). The proportions of diabetic mothers was higher than the proportions of diabetic fathers among the patients (50.2% vs. 35.2%, p0.001) and the controls (32.7% vs. 12.1%, p0.001). Patients born to diabetic mothers compared to the other patients were smaller in age at the time of enrollment in this study (p=0.005), and at onset of T2DM (p0.001), and also had higher FBG (p=0.033). Interestingly, the prevalence of T1DM was highest amongst the siblings of the controls compared to patients (p=0.04). Finally, the heterozygote I/D genotype of the ACE gene was over expressed in patients born to diabetic mothers when compared to patients born to diabetic fathers, p=0.007.there was strong clustering of T2DM in families, with significant dominant maternal role in transmission of T2DM and associated severity markers. Patients (T2DM) born to diabetic mothers were genetically and phenotypically different from the other patients.

We have previously shown that infection with Plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as second messengers mediating insulin action. The C57BL/Ks-db/db and C57BL/6J-ob/ob mice offer good models for studies on human obesity and Type 2 diabetes. In the present study, we show that a single iv injection of IPG-A or IPG-P extracted from P. yoelii significantly (P < 0.02) lowers the blood glucose in STZ-diabetic, db/db, and in ob/ob mice for at least 4--6 h. Using rat white adipocytes, IPG-P increased lipogenesis by 20--30% in the presence and absence of maximal concentrations of insulin (10(-8) M) (P < 0.01) and stimulated pyruvate dehydrogenase (PDH) phosphatase in a dose-related manner. Both IPG-A and IPG-P inhibited c-AMP-dependent protein kinase (PKA) in a dose-related manner. Compositional analysis of IPGs after 24 h hydrolysis revealed the presence of myo-inositol, phosphorus, galactosamine, glucosamine, and glucose in both IPG-A and IPG-P. However, hydrolysis of IPGs for 4 h highlighted differences between IPG-A and IPG-P. There are some functional similarities between P. yoelii IPGs and those previously described for mammalian liver. However, this is the first report of the hypoglycemic effect of IPGs in murine models of Type 2 diabetes. We suggest that IPGs isolated from P. yoelii, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes mellitus.

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 the impact of English language courses on students' performance in those subjects. The 1990 cohort of 84 students joined the College of Medicine after completing a 2-year programme in foundation sciences and English. A major part of the basic medical sciences is taught in a coordinated approach in two blocks. One block coordinates the teaching of cardiovascular, respiratory and urinary systems (CVRUS), and the other coordinates the basic medical sciences disciplines in the alimentary system. Final examination results of the foundation and basic medical sciences courses were correlated with English language using linear and multiple regression analysis. While significant positive correlation was found between results in English and the alim...

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 sulfonylurea, gliben-clamide.Lupinus termis exerted a significant hypoglycemic effect in non-diabetic and streptozotocin diabetic rats without apparent side effects. Eugenia jambolana treated rats exhibited aggressive behavior in addition to hypoglycemia. Peganum harmala resulted in high mortality and a moribund state and its use should be discouraged.

We have previously reported that infection with Plasmodium yoelii, Plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (STZ)-diabetic mice. P yoelii glycosylphosphatidylinositols (GPIs) were extracted in chloroform:methanol:water (CMW) (10:10:3), purified by high-performance thin layer chromatography (HPTLC) and tested for their insulin-mimetic activities. The effects of P yoelii GPIs on blood glucose were investigated in insulin-resistant C57BL/ks-db/db diabetic mice. A single intravenous injection of GPIs (9 and 30 nmol/mouse) induced a significant dose-related decrease in blood glucose (P < .001), but insignificantly increased plasma insulin concentrations. A single oral dose of 2.7 micromol GPIs per db/db mouse significantly lowered blood glucose (P < .01). P yoelii GPIs in vitro (0.062 to 1 micromol/L) significantly stimulated lipogenesis in rat adipocytes in a dose-dependent manner both in the presence and absence of 10(-8) mol/L insulin (P < .01). P yoelii GPIs stimulated pyruvate dehydrogenase phosphatase (PDH-Pase) and inhibited both cyclic adenosine monophosphate (cAMP)-dependent protein kinase A and glucose-6-phosphatase (G6Pase). P yoelii GPIs had no effect on the activity of the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). This is the first report of the hypoglycemic effect of P yoelii GPIs in murine models of type 2 diabetes. In conclusion, P yoelii GPIs demonstrated acute antidiabetic effects in db/db mice and in vitro. We suggest that P yoelii GPIs, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes.

We have previously shown that infection with Plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as second messengers mediating insulin action. The C57BL/Ks-db/db and C57BL/6J-ob/ob mice offer good models for studies on human obesity and Type 2 diabetes. In the present study, we show that a single iv injection of IPG-A or IPG-P extracted from P. yoelii significantly (P0.02) lowers the blood glucose in STZ-diabetic, db/db, and in ob/ob mice for at least 4--6 h. Using rat white adipocytes, IPG-P increased lipogenesis by 20--30% in the presence and absence of maximal concentrations of insulin (10(-8) M) (P0.01) and stimulated pyruvate dehydrogenase (PDH) phosphatase in a dose-related manner. Both IPG-A and IPG-P inhibited c-AMP-dependent protein kinase (PKA) in a dose-related manner. Compositional analysis of IPGs after 24 h hydrolysis revealed the presence of myo-inositol, phosphorus, galactosamine, glucosamine, and glucose in both IPG-A and IPG-P. However, hydrolysis of IPGs for 4 h highlighted differences between IPG-A and IPG-P. There are some functional similarities between P. yoelii IPGs and those previously described for mammalian liver. However, this is the first report of the hypoglycemic effect of IPGs in murine models of Type 2 diabetes. We suggest that IPGs isolated from P. yoelii, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes mellitus.

Basic medical sciences at Sultan Qaboos University (SQU) are taught in a systemsbased 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. © 1995 WiIey-Liss, Inc.

Rat diaphragm showed a nine to ten-fold increase in the dry and wet weights and a four-fold increase in its surface area between 21 and 540 days of age. The increase was the most rapid between days 21 and 90, thereafter a non-significant trend of increase was maintained at least up to 360 days of age followed by a tendency to decrease. The total collagen content of the diaphragm paralleled the increase in surface area with progressing age. The collagen content significantly dropped when expressed relative to the dry weight of the diaphragm, between 21 and 90 days of age. This trend was maintained till 180 days of age but thereafter significantly rise was seen. These later changes may be due to elenated synthesis and/or reduced degradation of collagen, and may contribute to the decline in contractility of the diaphragm as age advances.

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.

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.

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.

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.

The efficacy of a hypoglycaemic plant extract, in common use by Kuwaiti diabetic individuals, was evaluated using both streptozotocin-induced diabetic and normal rats. A significant decrease in blood glucose concentration was demonstrated on glucose tolerance tests, as compared to untreated animals. The sum of the fasting, 1 and 2 h blood glucose values, decreased from 18.5 +/- 0.72 to 13.6 +/- 0.62 mmol/l (p less than 0.001) and from 58.6 +/- 2.83 to 44.5 +/- 3.12 mmol/l (p less than 0.005) in normal and diabetic animals treated for 1 week, respectively. Treatment with the extract was not found to significantly alter insulin levels or intestinal glucose absorption. The mode of action of the hypoglycaemic preparation remains to be elucidated.

1. Fluid intake, urine output and evaporative water loss were measured and fluid balance calculated in sixteen subjects for 1 d before Ramadan, during weeks 1–5 of fasting and on the 10th day after the end of Ramadan.2. Plasma osmolality at 06.00 hours, the beginning of the fast, at 18.00 hours, before breaking the fast and at 19.00 hours, 1 h after breaking the fast, and urine osmolality during the day and night were measured before, during and after Ramadan.3. All subjects developed an initial negative fluid balance which was maximum at the beginning of week 3 of fasting and that deficit was compensated for during the later weeks.4. Compensation was brought about by an increase in urine concentration, a decrease in urine volume by day, and salt retention.5. No significant changes were observed in plasma osmolality during the days of fasting and the ‘setting’ of plasma osmolality during Ramadan also was not changed.6. It was concluded that healthy young adults maintain good control of fluid and electroytes during Ramadan.

The mechanism of the inhibitory effect of steroid hormones, progesterone and prednisolone on the incorporation of [3H]-thymidine into pancreatic islet cell DNA was investigated. Treatment with either hormone had no effect on the incorporation of 32P-orthophosphate into islet cell DNA. Both prednisolone (10 microM) and progesterone (3 microM) markedly stimulated the activity of the enzyme thymidylate synthetase of islet cells possibly leading to increased synthesis of endogenous thymidine which resulted in dilution of the [3H]-thymidine added to the islets in tissue culture. Prednisolone (10 microM) significantly increased both insulin biosynthesis and release, while at 5 microM it was effective in increasing only insulin release. In contrast, progesterone at the two concentrations employed did not affect insulin biosynthesis or release. The smaller doses of both hormones markedly stimulated the total protein biosynthesis.

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.

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.

Activities of the cysteine proteinases cathepsins B and H and of the chymotrypsin-like cathepsin G were determined in amniotic fluid of rats during the last third of gestation. Activities of cathepsins B and G were found to significantly increase with increasing gestational age while cathepsin H activity decreased. It was concluded that cathepsins may participate in the destabilization of fetal membranes and therefore may contribute to their rupture.

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.

This study aims at validating the use of 32P-orthophosphate as a probe for monitoring DNA replication instead of [3H]-thymidine where the specific activity of the latter is affected by perturbation of the cellular environment. It was found that to obtain a clean DNA fraction for determining the incorporation of the label, protein must be removed by the use of Proteinase K, and RNA by alkaline hydrolysis. Alkaline hydrolysis of RNA was found superior to RNAse digestion in not leaving behind large RNA fragments that may contaminate the DNA fraction.

Little is known of the blood sugar regulation in the camel and the morphology and function of its endocrine pancreas. The present paper describes the light microscopic structure and hormone content of the endocrine pancreas of the one-humped camel. Staining of pancreatic sections with haematoxylin-eosin or aldehyde-fuchsin showed numerous islets evenly distributed in all parts of the pancreas. Immunocytochemical staining for insulin or glucagon indicated that islets were predominantly composed of centrally located B-cells, surrounded by a peripheral rim of A-cells. Corresponding stainings for somatostatin or pancreatic polypeptide (PP) demonstrated that D-cells comprised only a small part of the islet volume while PP-cells were common both within and outside the islets. There were no obvious differences between the frequency of the various islet cells in different pancreatic regions. The pancreatic hormone concentrations roughly corresponded to the frequency of the different islet cell types. Insulin appeared most abundant followed by glucagon, PP and somatostatin in decreasing order. The concentrations of each of the hormones were similar in different regions of the gland. It is concluded that the endocrine pancreas of the one-humped camel is dispersed into islets of the same size and cellular composition as has been described in many other mammalian species.

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.

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.

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.