R. Enríquez de Salamanca

Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus

The haem pathway is impaired in porphyrias and a frequent coexistence of diabetes mellitus and porphyria disease has been reported. We have therefore decided to investigate delta-aminolevulinate dehydratase, one of the more sensitive enzymes in the haem pathway, in both human diabetic patients and diabetic rats. We have studied 131 diabetes mellitus patients, 32 insulin dependent and 99 non-insulin dependent. The latter group was further subdivided according to treatment: diet alone (n = 24), diet plus oral hypoglycemic agents (n = 28) and diet plus insulin (n = 47). We have also performed similar studies in the rat model of diabetes mellitus, induced in 11 Wistar rats by streptozotocin. Control groups of both humans and animals were used. Erythrocytic aminolevulinate dehydratase activity was reduced in both insulin dependent and non-insulin dependent diabetic patients as compared to their controls (p < 0.001). This activity was only partially restored by addition of zinc and thiols to the incubation media. In insulin-dependent diabetes mellitus, reduction of enzyme activity was related to the glycosilated hemoglobin concentration (p < 0.05) and in non-insulin dependent diabetes mellitus to the glycemia (p < 0.01). In the diabetic rat, aminolevulinate dehydratase activity was diminished on both erythrocytes (p < 0.01) and hepatic tissue (p < 0.01) when compared to the control group. The decrease in activity of erythrocyte aminolevulinate dehydratase observed in diabetic patients, may represent an additional and useful parameter for the assessment of the severity of carbohydrate metabolism impairment.

Serum levels of coenzyme Q10 in patients with Parkinson's disease

Summary. We compared serum levels of coenzyme Q10 and the coenzyme Q10/cholesterol ratio in 33 patients with Parkinsons disease (PD) and 31 matched controls. The mean serum coenzyme Q10 levels did not differ significantly between the 2 study groups. Coenzyme Q10 levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale (UPDRS) or the Hoehn and Yahr staging in the PD group. The coenzyme Q10/cholesterol ratio had a significant correlation (although low) with duration of the disease (r = −0.46), total UPDRS score (r = −0.39), motor examination of the UPDRS (r = 0.45). These values were not influenced significantly by therapy with levodopa or dopamine agonists. The normality of serum coenzyme Q10 and coenzyme Q10/cholesterol ratio suggest that these values are not related with the risk for PD.

Association of porphyria cutanea tarda and primary liver cancer: report of ten cases.

Studies of the association between porphyria cutanea tarda (PCT) and primary liver cancer have produced conflicting reports. The incidence of this liver tumor was studied in 138 PCT patients (7.2%) and in 358 non‐porphyric cirrhotic patients (5.6%), and no statistically significant differences were found between them (p>0.5). Nevertheless the incidence of such association was significantly higher (chi square=10.91, p<0.001) in the PCT group (24.3%) than in the non‐porphyric cirrhotic group (6.7%) when only males with underlying liver cirrhosis were considered. These results suggest that the high incidence of liver tumor in PCT is not merely related to hepatic cirrhosis. The cause of such as association remains unclear. Primary liver cancer may reveal a prior deficiency in uroporphyrinogen‐decarboxylase, but the possibility that the enzyme abnormalities were caused by the liver carcinoma also exists.

The photodynamic and non-photodynamic actions of porphyrins

Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macro-molecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

Cerebrospinal fluid levels of alpha-tocopherol in amyotrophic lateral sclerosis

Summary. We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 30 patients with sporadic amyotrophic lateral sclerosis (SALS) and 78 matched controls. The mean CSF and serum vitamin E levels did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal versus bulbar) of SALS. CSF alpha-tocopherol levels did not correlate with age, age at onset, and duration of the disease. These results suggest that CSF and serum alpha-tocopherol concentrations are unrelated with the risk for ALS.

Clinical utility of fluorometric scanning of plasma porphyrins for the diagnosis and typing of porphyrias

The fluorometric emission scanning (using excitation at 405 nm) of plasma samples, simply diluted five‐fold in phosphate‐buffered saline, allows the differentiation of three conditions according to their porphyrin content. The emission maximum at 626–628 nm is a specific finding in variegate porphyria, while in erythropoietic protoporphyria a characteristic peak is found at 636 nm. A fluorescence emission maximum at 618–622 nm corresponds to a third group that includes normal subjects, non‐porphyria patients and patients suffering from acute intermittent porphyria, hereditary coproporphyria, congenital erythropoietic porphyria (Günther disease) and porphyria cutanea tarda.

Quantitative and qualitative porphyrin excretion in normal subjects

Abstract 1. 1. Normal males ( n = 103) excreted a greater amount of urinary porphyrins with a higher percentage of tetracarboxylic coproporphyrin and with a smaller percentage of octocarboxylic uroporphyrin than normal females ( n = 116). 2. 2. These differences were mainly observed in age groups from 21 to 40 yr and from 41 to 60 yr. 3. 3. Quantitative and qualitative faecal porphyrin excretion were similar in both sexes.

Porphyrinogenic properties of the anesthetic enflurane.

1. The effect of enflurane, a volatile anesthetic, on heme metabolism was studied. Different doses (0.5-6.0 ml/kg) of this anesthetic were administered i.p. to mice and animals sacrificed at different times after administration (5-240 min). 2. The dose of 2 ml/kg was chosen as the optimum anesthetic dose producing more alterations in the heme pathway. 3. ALA-S was significantly induced at earlier times of anesthesia. 4. Blood PBGase and deaminase was greatly reduced. 5. This diminution coupled with ALA-S induction are in accordance with the known biochemical changes occurring in acute intermittent porphyria and include enflurane in the list of porphyrinogenic drugs, the use of which is not recommended for the management of anesthesia in porphyric patients.

Hepatitis B Serum Markers in Porphyria Cutanea Tarda

Hepatitis B virus (HBV) infection was studied in 100 patients with porphyria cutanea tarda (PCT). The overall prevalence of HBV serologic markers was 57%: 6 patients had HBsAg, 9 had antiHBc alone, 2 had antiHBc associated with antiHBe and the remaining 40 patients had antiHBs.

Patterns of porphyrin excretion in porphyria cutanea tarda under venesection treatment.

Abstract Serial measurements of the individual porphyrins were done in 11 patients with porphyria cutanea tarda treated by repeated venesections. The effectiveness of this therapy was more prematurely reflected on faecal porphyrin pattern while the distribution pattern of the urinary porphyrins remained abnormally longer even when quantitative uroporphyrin excretion has decreased under 100 μg/1. Some patients showed quantitative and qualitative normal porphyrin excretion.