CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine

We have investigated several factors that might be related to the occurrence of toxic effects during the performance of a urinary test with caffeine (300  mg p.o), in 120 healthy volunteers. A total of 218 toxic effects were self-reported by eighty-two (68%) subjects. Females and nonsmokers were at the highest risk (chi-square test, P =0.01). Furthermore, two nonsmoking females experienced a symptomatology with delirium, restlessness, muscle tremor, vomiting and wakefulness. Among females and nonsmokers, those subjects who experienced toxic effects had lower caffeine N3-demethylation index (CYP1A2 activity) compared with unaffected females (1.87±0.51 vs 1.47±0.27, P <0.0005) and nonsmokers (1.69±0.23 vs 1.49±0.31, P <0.02). Caffeine N1- and N7-demethylations indices were also lower among females ( P <0.0005) and nonsmokers ( P <0.02) who reported toxic symptoms. We conclude that CYP1A2 activity, gender and smoking are variables to be considered as influencing the toxicity of caffeine.     

Giardia Lamblia

A case of chronic cholecystitis and duodenojejunitis secondary to Giardia lamblia is presented. Though well documented as a cause of duodenitis, this condition is not a common finding in the United States and hence the diagnosis is not made routinely. This case illustrates an instance where giarditic duodenojejunitis may have been masquerading as a chronic cholecystitis.     

Protective effect of pentoxifylline plus thalidomide against septic shock in mice

Mortality caused by septic shock in experimental animals is reduced by thalidomide, an inhibitor of tumour necrosis factor alpha. Another drug that could act on the pathophysiological mechanisms of septic shock is pentoxifylline, an inhibitor of platelet aggregation that increases the flexibility of the erythrocyte membrane and has fibrinolytic activity. We studied the effect of pentoxifylline alone and combined with thalidomide in septic shock; 97 NIH mice were injected with lipopolysaccharides of Salmonella abortus equi and D galactosamine. Animals were separated in 4 groups; group A (n = 20) was used as control, group B (n = 15) received thalidomide 50 mg/kg, group C (n = 20) received pentoxifylline 40 mg/kg, and group D (n = 15) received thalidomide plus pentoxifylline. Mortality was recorded every hour. Additionally, 5 animals from each group were sacrificed 8 h after the induction of septic shock for histological analysis of heart, lung, brain, kidney, small intestine, adrenal glands and liver. Microscopic findings were rated as absent, mild, moderate and severe damage. In control animals histological analysis showed intense haemorrhage and necrosis in all organs studied. When compared with controls, treatment with pentoxifylline plus thalidomide reduced mortality (P < 0.03). The tissue damage was less severe in animals from the groups that received pentoxifylline or pentoxifylline plus thalidomide (P < 0.05). Pentoxifylline seems to potentiate the beneficial effects of thalidomide, reducing mortality and attenuating the pathological changes produced by septic shock.     

ASSESSMENT OF ZINC NUTRITIONAL STATUS OF PELLAGRA PATIENTS

The objective of the present study was to assess zinc nutritionalstatus in alcoholic patients with pellagra using plasma, hair,urine and nail zinc levels, as well as the zinc tolerance test.The study was conducted on 81 patients, 73 males and eight females.Zinc parameters were compared with those of 84 individuals withno apparent disease aged 23–45 years. Plasma zinc levelswere lower in patients with pellagra than in the controls (P< 0.01). The results of the zinc tolerance test showed that:(1) basal zinc levels were 69.7 ± 16.8 µg/100 mlin pellagrins and 82.3 ± 34.0 µg/100 ml in thecontrols (P < 0.01); (2) after 1 h the increase in plasmalevels was similar in the pellagrin and control groups; (3)during the second hour the increase was more marked in the controls(P < 0.01), and the same was observed during the third andfourth hours (P < 0.05). Urinary zinc excretion (mg/24 h)was higher in pellagrins (P < 0.01). Zinc concentration inhair and toenails did not differ between pellagrins and controls.We conclude that pellagrins present zinc deficiency as demonstratedby plasma and urine zinc levels and by their abnormal responseto the zinc tolerance test. We suggest that hair and nail zinclevels should not be used to assess zinc nutritional statusin patients with pellagra.     

Leukemic Reticuloendotheliosis

The anatomical and functional featuresof the hairy cells of leukemic reticuloendothelisis were investigated by timelapse cinematography; phytohemagglutinin stimulation; adherence to siliconizedsurfaces; a variety of cytochemicalmethods; and phase, transmission, andscanning electron microscopy. The scanning electron microscopic image supportsthe morphologic evidence for a relationship between the hairy and the reticularcells.

Submitted on February 24, 1971 Revised on April 1, 1971 Accepted on April 13, 1971     

The Pancreas and Immunoglobulins

Immunoglobulin levels of pancreatic juice following secretin administrations were determined in 35 normal patients. The variation of levels was high. The means and standard errors were as follows: Ig–A–7.2 ± 7.0; Ig–M–1.5 ± 0.97; Ig–G–21.44 ± 16.10.