Effects of a low-insulin-response, energy-restricted diet on weight loss and plasma insulin concentrations in hyperinsulinemic obese females.

The effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic females were compared during a 12-wk period. The first diet (n = 15) was designed to evoke a low insulin response (ID), and the second (n = 15) was a conventionally balanced diet (ND). After a 12-wk washout period, seven and nine subjects who had been on the ID and ND, respectively, changed to the alternative diet for 12 wk. Variables studied were basal and 30- and 120-min concentrations of blood glucose, insulin, and C-peptide after an oral glucose load; body weight; and energy intake. Mean (+/- SD) weight was significantly reduced after ID and ND (9.35 +/- 2.49 and 7.41 +/- 4.23, respectively). The mean weight loss was more after ID. Fasting insulin concentrations decreased more after ID compared with ND (91.3 +/- 61.8 vs 21.0 +/- 71.5 pmol/L; P < 0.05). We conclude that ID significantly reduces serum insulin concentrations and weight in obese hyperinsulinemic females.

Localization of the human c-mos gene by in situ hybridization in two cases of acute nonlymphocytic leukemia type M2.

The t(8;21)(q22.1;q22.3) is specific for the FAB-M2 subtype of acute nonlymphocytic leukemia (ANLL). The human c-mos protooncogene is located near the site of rearrangement on chromosome #8, at a position corresponding to band 8q22. The present in situ hybridization studies were performed in order to establish if c-mos is transposed from chromosome #8 to chromosome #21, in two cases of M2-ANLL showing the typical t(8;21). A statistical analysis of the results revealed that the c-mos oncogene was definitely not translocated from chromosome #8 to #21 in one of these patients, and was inconclusive in the other patient. The findings in the former patient suggest that either c-mos is not involved in the etiology of M2-ANLL or, alternatively, if c-mos is important in the pathogenesis of this disease, it must be activated by some mechanism other than transposition of this oncogene to an aberrant position.

The PLC/PRF/5 human hepatoma cell line. II. Chromosomal assignment of hepatitis B virus integration sites.

The chromosomal sites at which hepatitis B virus (HBV) DNA is integrated into the genome of the hepatocellular carcinoma (HCC) cell line, PLC/PRF/5 were investigated in an attempt to understand the mechanisms by which hepatitis B virus may induce malignant transformation. In situ hybridization of an HBV DNA probe to metaphase chromosomes of the PLC/PRF/5 cell line, followed by statistical analysis, identified three integration sites; these were 15q22-q23, 11q22, and 18q12. In particular, hybridization to chromosome #15, which is present in four copies in complete metaphases of this cell line, was highly significant (p much less than 0.0005).

Observed relationship between ratios HDL-cholesterol/total cholesterol and apolipoprotein A1/apolipoprotein B.

Epidemiological evidence suggests that the ratio HDL-cholesterol (HDL-C)/total cholesterol (TC) or apolipoprotein A1 (apo A1)/apolipoprotein B (apo B) are good indicators of coronary heart disease risk. In investigating the distribution of these ratios in the typical population served by our routine laboratory, we analysed the lipid results of 541 serum samples submitted over a 2-month period for TC, HDL-C, apo A1, and apo B. Good correlation was observed between HDL-C and apo A1 (r = 0.664), and between TC and apo B (r = 0.674). Surprisingly, the correlation between the ratios HDL-C/TC (range: 0.05-0.40) and apo A1/apo B (range: 0.27-3.71) was even higher (r = 0.822). Similar significant correlations were observed in 31 heterozygous and 20 homozygous familial hypercholesterolemic subjects, viz. the correlations between HDL-C/TC (ranges: 0.04-0.24 and 0.02-0.12, respectively) and apo A1/apo B (ranges: 0.47-1.84 and 0.15-1.12, respectively) were r = 0.951 and r = 0.972, respectively.

The effect of desferal on rat heart mitochondrial function, iron content, and xanthine dehydrogenase/oxidase conversion during ischemia-reperfusion.

Cardiac mitochondrial function as measured by oxidative phosphorylation is impaired by ischemia; and, this deteriorates even further on reperfusion of the heart. Free oxygen radicals, especially the formation of hydroxyl radicals via the iron-catalyzed Haber-Weiss and Fenton reactions have been implicated in the reperfusion injury. In this study, the effect of desferrioxamine (desferal) in the perfusate on mitochondrial function of isolated rat hearts during different periods of normothermic ischemic cardiac arrest (NICA), and subsequent reperfusion was investigated. Mitochondrial functions measured were the QO2 (state 3); ADP/O ratio and oxidative phosphorylation; the mitochondrial, loosely bound (chelateable) iron (LB-iron); the xanthine dehydrogenase and xanthine oxidase activities. Inclusion of desferal in the perfusion solution significantly improved mitochondrial function during the different NICA periods, and prevented the deterioration of mitochondrial function resulting from reperfusion. Desferal did not significantly affect the LB-iron content of the mitochondria or the ratio of xanthine dehydrogenase/xanthine oxidase activities in the mitochondria during NICA or reperfusion. Our experiments suggest that iron, which is free to be chelated by desferal, plays a role in this injury to the rat myocardium.

Urinary thiamine excretion after oral physiological doses of the vitamin.

Urinary thiamine excretion has been measured in healthy subjects after oral physiological doses of the vitamin. There was a highly significant correlation between the oral dose and the urinary excretion. However, there was considerable overlap between the baseline values and the urinary excretion following doses up to 1000 micrograms. It is recommended that repeated daily measurements are made to differentiate baseline excretion from that recorded after oral physiological doses. This study may have relevance to the monitoring of dietary fortification programmes with thiamine.

Intravascular Hemolysis in Aerobic Dancing: The Role of Floor Surface and Type of Routine.

In brief: The effect of aerobic dancing on intravascular hemolysis was studied in 65 healthy women (aged 18 to 50 years) who were assigned to one of four groups according to the type of routine performed and the hardness of the floor surface. All subjects participated in a 60-minute dance session; a subgroup participated in five successive 60-minute sessions with one hour of rest between sessions. Blood was tested for both groups before and after exercise; urine was tested similarly for the subgroup only. The findings indicated that intravascular hemolysis occurred and that it was influenced by the type of routine, hardness of the surface, and duration of dancing. However, the degree of hemolysis was small and unlikely to contribute to the development of anemia.

Persistently elevated CKMB and negative troponin T in a patient at ischaemic risk with chest pain.

Analytical interference in laboratory assays is not only unpredictable but also an underestimated problem. Not recognising these interferences can lead to misdiagnosis and mismanagement of patients. We present a case of a patient with chest pain and ischaemic risk factors with incongruent biochemical results. These results were discovered to be due to the presence of macro-creatine kinase (macro-CK) in vivo interfering with the CKMB activity assay.

Gallstone disease among black South Africans. A review of the Baragwanath Hospital experience.

It has been suggested that gallstone disease is rare in Africa. The 118 cholecystectomies for this condition performed at Baragwanath Hospital over the 3-year period 1983-1985 were reviewed; 100 records were available. The male: female ratio was 1:4, the mean age 51 years. Fifty-one per cent of patients presented with acute cholecystitis, 18% with obstructive jaundice, 9% with pancreatitis and only 22% with biliary colic. The incidence of complicated presentation was higher in the over 60-year-old age group (P less than 0.05). The correct diagnosis was made on admission in only 41% of cases. The mean delay in diagnosis was 5 days; however, the delay was 8 days for patients admitted to the medical wards compared with 2 days in the surgical wards (P less than 0.001). Elective operations were performed on 82% of patients and 18% had urgent surgery. The incidence of common bile duct stones was 22%. The overall mortality rate was 10%; however, the mortality rate was 3.2% for the under-60-year-old group compared with 21% for patients 60 years and older (P = 0.006). This series, which is probably the largest reported in black patients, suggests that greater awareness of acute cholecystitis is necessary in the black patient since there is a rising in-hospital incidence.

Toxic cannabis psychosis is a valid entity.

One hundred black men admitted to hospital with acute psychiatric symptoms were investigated for the presence of urinary cannabis metabolites in order to delineate the psychiatric role played by 'dagga', the potent South African cannabinol, in the study population and to determine the diagnostic value of the entity 'toxic psychosis (dagga)'. Cannabinoids were present in 29% of patients, and 31% were discharged with a diagnosis of toxic psychosis (dagga). Clinical and demographic material was gathered for all patients and no consistent differences were found between dagga-positive and dagga-negative patients or toxic dagga psychotic patients and 'functional' psychotics other than a history of recent dagga use and the dagga screening test result. The latter measure was found to be both more sensitive and more specific than the history of dagga use alone. The findings support the routine use of a simple screening test for dagga in the sample population studied. The study demonstrated the heterogeneous nature of the toxic dagga psychosis syndrome by documenting a variety of different clinical presentations, which included schizophrenia (42%), paranoia (26%), maniform psychosis (16%) and organic psychosis (16%).

Exposure of rats to low concentration of cigarette smoke increases myocardial sensitivity to ischaemia/reperfusion.

It is suggested that passive smoking or smoke-exposure increase the risk of coronary heart disease. The same mechanisms as active smoking might play a role. The aim of this study was to determine whether exposure to smoke aggravated ischaemia/reperfusion injury. As a parameter of cellular function and integrity mitochondrial oxidative function was measured. Low molecular weight iron (LMWI) and alpha-tocopherol levels were determined to assess the possibility of toxic hydroxyl radical involvement in myocardial ischaemia/reperfusion injury of smoke-exposed rats. Rats were exposed to a small concentration of cigarette smoke for 2 months (the carboxyhemoglobin concentration did not increase), whereafter hearts were isolated and subjected to ischaemia and ischaemia followed by reperfusion. Mitochondrial oxidative function, low molecular weight iron and alpha-tocopherol were determined. The impairment in mitochondrial oxidative function, LMWI content elevation and the decrease in alpha-tocopherol concentration during ischaemia/reperfusion were significantly more severe in hearts of smoke-exposed rats than non-smokers. These results suggest that exposure to smoke increased the sensitivity of hearts to ischaemia/reperfusion injury, and that a free radical mechanism might participate.

The protective effect of desferal on rat myocardial mitochondria is not prolonged after withdrawal of desferal.

Reperfusion of ischaemic myocardium is necessary to sustain tissue viability (without it the tissue becomes necrotic), but reperfusion, on the other hand, can damage cells which have survived ischaemia. There is now considerable evidence that oxygen radicals, especially hydroxyl radicals produced via the Haber-Weiss and Fenton reactions, are responsible for reperfusion damage. Various investigators have reported that desferal, an iron chelator, has a beneficial effect on the myocardium during ischaemia and reperfusion. The aim of this study was two-fold: i) whether superoxide anions in the absence of LMWI can impair mitochondrial function, and ii) whether the protective effect of desferal on the mitochondrial function persists after withdrawal of desferal. Experiments were done on isolated rat hearts subjected to normothermic ischaemic cardiac arrest (NICA), with or without desferal, followed by 15-min reperfusion with desferal, followed by 15-min perfusion without desferal, or a hypoxanthine/xanthine oxidase medium that generates superoxide anions (with or without desferrioxamine (desferal) in the perfusate). Mitochondrial function (QO2 (state 3), ADP/O and OPR) as well as LMWI were measured. Our results indicated that i) superoxide anions and/or hydrogen peroxide can, independently of LMWI, damage the mitochondria, and ii) withdrawal of desferal after the respiratory burst resulted in the same or more severe mitochondrial damage than without any desferal.

Antioxidant vitamin supplementation of smoke-exposed rats partially protects against myocardial ischaemic/reperfusion injury.

Our previous studies showed that exposure of rats to limited periods of cigarette smoke resulted in more severe myocardial damage when their hearts were subjected to myocardial ischaemia/reperfusion. The aim of this study was to determine whether supplementation of rats with antioxidant vitamins alpha-tocopherol and beta-carotene was able to protect their hearts against the increase in ischaemia/reperfusion injury caused by smoke-exposure. The parameters measured were mitochondrial oxidative function, cellular levels of alpha-tocopherol and low molecular weight iron (LMWI). Supplementation with antioxidant vitamins resulted in significantly less mitochondrial functional oxidative damage compared to that observed in the controls. Supplementation did not affect the cellular LMWI content, suggesting that the generation rate of hydroxyl radicals was similar in both groups. The protective effect of alpha-tocopherol and beta-carotene supplementation on the mitochondrial function against ischaemia/reperfusion could be due to their free radical scavenging action. Supplementation with antioxidant vitamins, therefore, had a beneficial effect on the excessive myocardial ischaemia/reperfusion injury of smoke exposed rats.

The influence of long-term exposure of mice to randomly varied power frequency magnetic fields on their nocturnal melatonin secretion patterns.

Disruption of the normal melatonin rhythm has many implications in health and disease. Exposure to magnetic fields is alleged to suppress nocturnal melatonin production, which could implicate magnetic fields in the development of, for example, breast cancer. Magnetic fields of overhead powerlines allegedly pose a risk in the development of childhood leukemia, and the question arises whether changed pineal function could play a role here. In this study two strains of mice were exposed to a rms 50-Hz magnetic field which varied randomly between 0.5 and 77 microT with an average of 2.75 microT and compared to sham-exposed groups. The male mice were exposed for 24 h per day from conception until adult age. Nighttime plasma melatonin values were determined using radioimmunoassay (n=9 for each time point). Statistical comparison was done by nonparametric 95% confidence intervals for median differences to determine nocturnal elevated melatonin values. Although a shortcoming of the study was the small sample size, no statistically significant difference in the nocturnal median elevated melatonin values between exposed and sham-exposed groups could be demonstrated. Long-term and continuous exposure to simulated powerline magnetic fields did not result in a decreased nocturnal melatonin secretion in mice.

Ischemia/reperfusion injury is aggravated by an iron supplemented diet and is partly prevented by simultaneous antioxidant supplementation.

In humans high levels of storage iron as well as low iron binding capacity are considered risks for ischemic heart disease development. The aim of this study was to determine whether a diet containing iron to a concentration of the recommended upper limit alters the degree of myocardial ischemic/reperfusion injury on rats and whether simultaneous antioxidant supplementation had any effect. Results indicate that the iron supplemented diet increased the degree of oxidative injury while simultaneous antioxidant supplementation prevented much of this increase. The mechanism for this was probably an elevated hydroxyl radical production due to the enlarged transit iron pool.