Tissue noradrenaline and the polyol pathway in experimentally diabetic rats.

1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression.

Effect of khat on the metabolism of erythrocytes.

The plant khat "Catha Edulis Forsk" is widely distributed among most East African countries, Yemen and many other areas of the world. Administration of khat extract by the intragastric route in rabbits affected the metabolism of erythrocytes. There is a significant decrease in pyruvate kinase and the level of reduced glutathione (P less than 0.001), and a highly significant increase in both glucose-6-phosphate dehydrogenase and glutathione reductase activities (P less than 0.001) in khat-fed rabbits as compared to controls. On the other hand the activity of uridyl transferase as well as the concentration of 2,3-diphosphoglycerate were not significantly changed in experimental khat-fed rabbits (P greater than 0.5).

Does pulsatile flow influence the incidence of postoperative hypertension?

Twenty patients undergoing primary elective aorta--coronary artery bypass were divided into two equal groups, both receiving identical premedication, anesthetic, and pump primes. The control patients received hypothermic nonpulsatile flow and the study patients received hypothermic pulsatile flow. Hypertension, defined as a pressure of 160/100 mm Hg or higher, was observed in 80% of the control patients and 20% of the patients receiving pulsatile flow (p less than 0.05). Serial renin measurements demonstrated maximum values in the intensive care unit and coincided with the onset of postoperative hypertension in the control patients. Those patients who had received pulsatile flow did not demonstrate notable renin stimulation. Catecholamines were markedly elevated during bypass and in the intensive care unit, but there was no significant difference between the two groups. Peripheral vascular resistance was not significantly lower with pulsatile flow, except in the first study performed in the intensive care unit. We conclude that catecholamines and the renin-angiotensin system contribute to the production of postoperative hypertension and that pulsatile flow diminishes renin stimulation. Pulsatile flow results in a decreased incidence of postoperative hypertension.

Incidence and some properties of an electrophoretically slow form of alkaline phosphatase in sera of patients with diseases of the intestine.

A zone of alkaline phosphatase activity migrating at about 40 percent of the rate of liver phosphatase in gel electrophoresis has been detected in sera from 2 out of 22 cases of ulcerative colitis and 1 out of 32 cases of Crohn's disease, but in no other specimen from 33 patients with other diseases of the digestive tract. This rare form of alkaline phosphatase was unlike small-intestinal alkaline phosphatase in several properties. Its appearance in association with diseases of the colon suggests that the rare isoenzyme may originate in that organ. However, the slowly migrating alkaline phosphatase was equally prominent in serum specimens taken before and after operation in one patient who underwent a pan-proctocolectomy for the alleviation of uncontrollable ulcerative colitis.

The influence of khat-chewing on birth-weight in full-term infants.

The leaves of the shrub Catha edulis (khat) are widely chewed as part of social life in several countries around the Red Sea and in East Africa. The leaves possess stimulant properties and are also used by pregnant women. The effect of khat on birth-weight has been studied, It was found that healthy full-term, singletons, born after uneventful pregnancies and deliveries, had a significantly lower average birth-weight when the mothers were khat-chewers, either habitually or occasionally (P less than 0.001). Khat-chewing appears to be one of several maternal practices adverse to the fetus.

Effect of khat on maternal food intake, maternal weight gain and fetal growth in the late-pregnant guinea pig.

Khat chewing is a widespread male social habit in countries around the southern shore of the Red Sea and in eastern Africa and is also practiced by women, even during pregnancy and lactation. In order to study the potentially adverse effects of khat chewing during pregnancy, guinea pigs were fed 2.2 g/kg of khat leaves daily throughout the third trimester. Control animals were given aspen leaves. Maternal daily food intake was significantly reduced during the first 10 days of feeding and maternal weight gain was slightly lower in the khat group. Khat feeding of the mother significantly reduced the mean birth weight of the offspring by 7% without any effect on litter size or length of gestational period. Since low birth weight is a well-established risk factor for both perinatal and young infant death, khat chewing during pregnancy may be one of the factors contributing to infant mortality.

Effect of khat on uteroplacental blood flow in awake, chronically catheterized, late-pregnant guinea pigs.

In order to investigate effects of khat chewing on uteroplacental blood flow, eight awake, chronically catheterized guinea pigs were fed 2.2 g khat leaves/kg in late pregnancy and regional blood flows were measured with the microsphere technique. Seven animals fed with aspen leaves in the same amounts served as controls. The mean concentration of (+)-norpseudoephedrine in urine 3 h after the end of the feeding was 4.6 micrograms/ml in the khat-fed group with no detectable amounts in the controls. Placental blood flow was reduced by 10% 75 min and by 24% 180 min after khat feeding. Since the khat dose used gave urinary concentrations of (+)-norpseudoephedrine of the same magnitude as those reported in khat chewing women, khat chewing in pregnancy may reduce placental blood flow and impair fetal growth.

Use of khat in lactating women: a pilot study on breast-milk secretion.

Nor-pseudoephedrine, one of the active ingredients of khat (Catha edulis), was found to be excreted in breast-milk in several lactating women who were chewing the leaves of the shrub according to the local customs. The compound could be traced in the urine of one breast-fed infant. It is concluded that the use of khat during lactation should be discouraged until further research has clearly elucidated the potential health hazards.

Biochemical effects of Catha edulis, cathine and cathinone on adrenocortical functions.

Catha edulis is a plant that grows in certain areas of East Africa and the Arab Peninsula. The stimulating properties of fresh material were described more than seven centuries ago and today the habit of inducing a state of euphoria and subjective well-being by chewing Catha edulis prevails among the inhabitants of these regions. Oral administration of this plant and its active constituents (cathine and cathione) on experimental animals might have stimulating effects on adrenocortical function. This was indicated by the significant decrease in adrenal cholesterol, ascorbic acid, glycogen, and the increase in adrenal phosphorylase activity. In addition, the level of urinary 17-hydroxycorticosteroids and plasma free fatty acids were increased.

Effect of Catha edulis on plasma glucose and C-peptide in both type 2 diabetics and non-diabetics.

In this study, the effect of regular khat chewing on serum glucose and C-peptide levels were investigated in both healthy male individuals and type 2 diabetic patients. The results presented show the levels of glucose and C-peptide of healthy individuals to be non-significantly different between khat and non-khat chewers which may be due to the rapid release of insulin which prevents the sympathetic khat effect on rising serum glucose. On comparing both diabetic groups, those of khat chewers showed a non-significant increase of glucose levels at 0, 1 and 2 h of khat chewing. However, the non-significant increase of serum glucose at 1 h of khat chewing corresponded with a significant increase of serum C-peptide (22%) levels. On selecting the base-line glucose of diabetic individuals between 200 and 450 mg/dl, both diabetic khat and non-khat chewers still showed no significant difference in serum glucose and C-peptide at 2 h post-meal. However, serum glucose was seen to be significantly higher in the khat chewers by 32.1 and 32.6% after 1 and 2 h of khat chewing, respectively. Along the same line, serum C-peptide was higher in the khat chewers by 39.4 and 12.9% at 1 and 2 h of khat chewing, though not significantly. In conclusion, chronic khat chewing does not affect serum glucose and C-peptide in healthy individuals while it increases glucose and C-peptide levels during the khat session in diabetic individuals especially those having serum glucose between 200 and 450 mg/dl at 2 h post-meal.

Emergency toxicology in a general hospital.

A study of all cases of attempted suicide by drug ingestion over a 6-month period was undertaken to evaluate the use of an emergency toxicology service and to establish the role of the emergency toxicology laboratory in the diagnosis and management of cases of attempted suicide. A total of 235 requests for emergency toxicologic analysis involving 259 specimens was received. Results of toxicologic screening were positive for 58% of all cases (range, 49% for patients who were drowsy to 90% for patients who were deeply unconscious). Barbiturate blood values did not correlate well with either the level of consciousness or the clinical state of the patient. In almost all patients who were drowsy or who were unconscious but had normal reflexes and vital signs there was no deterioration in the clinical state and no active treatment was required. The study demonstrated the need to educate all personnel involved in the care of patients with attempted suicide to limit laboratory investigations to the management of patients who benefit from such analyses. Quantitative drug analyses have a limited contribution to the management of such patients and should be performed only for patients with mixed drug overdosage and when the drugs require dialysis for their elimination from the body.

Effect of the khat alkaloid (+)norpseudoephedrine on uteroplacental blood flow in the guinea pig.

In order to investigate effects of khat chewing on uteroplacental blood flow (+)norpseudoephedrine (NPE) infusions were given to 11 anesthetized guinea pigs in late pregnancy (62-66 days) after unilateral uterine artery ligation at days 30-32. Regional blood flows were determined with radioactive microspheres. Mean arterial blood pressure increased with 25% and heart rate with 9% during NPE infusion. Myoendometrial blood flow was reduced by 31%. Placental vascular resistance (PVR) increased by 56% in the control horn (17 fetuses) and by 82% in the ligated horn (17 fetuses). This vasoconstriction was counteracted by the systemic vasopressor response since placental blood flow remained unchanged. When considering only the 13 growth-retarded fetuses, however, PVR increased by 98% and a 19% reduction of placental blood flow could be demonstrated. These results suggest that the placenta of the growth-retarded fetus may be more sensitive to adrenergic stimulation than the normal placenta. Furthermore, since one of the active constituents of khat, (+)norpseudoephedrine, causes vasoconstriction in the uteroplacental vascular bed it is possible that khat chewing could reduce placental blood flow and, as a consequence, impair fetal growth.

Khat chewing and bladder neck dysfunction. A randomized controlled trial of alpha 1-adrenergic blockade.

OBJECTIVE: To assess whether the effect of chewing khat leaves (Catha edulis) on the urodynamics of healthy males is altered by the selective alpha 1-adrenergic blocking agent indoramin in a prospective randomized double-blind controlled trial. SUBJECTS AND METHODS: The urodynamics of 11 healthy males were studied before and during a khat chewing session preceded by indoramin or placebo. RESULTS: Khat chewing produced a fall in average and maximum urine flow rate. This effect was inhibited by indoramin. CONCLUSIONS: The urinary side-effects of khat chewing are probably mediated through stimulation of alpha 1-adrenergic receptors.

Oesophageal and gastric carcinoma in the Republic of Yemen.

We conducted a preliminary survey on 3064 patients who underwent upper gastrointestinal endoscopy at the Al-Thawra Hospital in Sana'a, Republic of Yemen, between January and December 1991. The age/sex distribution, demographic features and social habits with respect to cigarette and water-pipe smoking and Qat chewing were compared for patients with oesophageal and gastric cancers (n = 183). A preponderance of women with carcinoma of the mid-oesophageal was noted, previously only recorded in areas of high prevalence. Unlike Western populations, smoking and alcohol consumption were not significant risk factors. A high frequency of Qat chewing and water-pipe smoking was found for both men and women and for a group with tumours of the gastro-oesophageal junction or cardia (chi 2 = 2.646, P > 0.05). Numbers were insufficient to identify independent effects of each factor individually. Dietary habits alone were insufficient to account for the excess of affected females. A case-control study is now underway to investigate further the role of dietary factors, social habits, demographic features and Helicobacter pylori infection on the development of upper gastrointestinal cancer in the Yemen.