Acute hepatic porphyria syndrome with porphobilinogen synthase defect

On the basis of metabolite and enzyme studies a new type of acute hepatic porphyria with porphobilinogen synthase defect and repeated intermittent acute manifestations, abdominal colics, tachycardia and hypertension, and a persistent neurological syndrome was found in two young male patients. The main characteristic features are the following:

• 1.1. High urinary δ-aminolevulinic acid excretion( ⪢ 1 mmol/24hr), slight increase of porphobilinogen (up to 25 μmol/24 hr) and high increase of porphyrins (up to 22 μmol/24 hr) with coproporphyrin dominance.
• 2.2. Normal fecal and liver porphyrins.
• 3.3. Slight increase of erythrocyte protoporphyrin.
• 4.4. Decrease of porphobilinogen synthase activity in erythrocytes in both cases below 1% of healthy and not lead-exposed persons; normal activities of uroporphyrinogen synthase and decarboxylase in erythrocytes.
• 5.5. Low-normal lead concentrations in blood and low-normal lead excretion in urine in both cases; normal lead content in bone.
• 6.6. Normal plasma and urinary amino acids.
• 7.7. Irrelevant hepatological (liver biopsy), general clinical chemical and hematological findings.
• 8.8. Diminished activity of porphobilinogen synthase in nearly all family members of both patients. From these investigations it can be concluded that there is no exogeneous, “toxic” cause of this porphyria. Porphobilinogen synthase in lead poisoning is not diminished to such an extent as demonstrated here; in contrast to lead intoxication, porphobilinogen synthase activity cannot be activated or reactivated by thiols. All clinical and pathobiochemical data point at a new enzymatic type of endogeneous acute hepatic porphyria with intermittent acute manifestations, clinically analogous to so-called acute intermittent porphyria. Porphyrin precursors and porphyrin excretion both reflects the enzymatic defect and the regulatory consequences starting with the induction of δ-aminolevulinic acid synthase.

     

Epidermal growth factor alters the electrolyte profile of lactating ewes Ovis aries

• 1.1. Lactating ewes were treated with mouse epidermal growth factor (EGF) at a dose rate of 0.5 mg/day for 4 days and its effects on the electrolyte profile were observed.
• 2.2. There was no effect of EGF on plasma concentrations of sodium or potassium, although urinary and total (in urine and milk) losses of both were reduced.
• 3.3. EGF-induced hypocalcaemia was associated with reduced milk calcium secretion and increased urinary calcium excretion whereas EGF-induced hypermagnesaemia was associated with reduced urinary and total magnesium losses.
• 4.4. Glomerular filtration rate was reduced during EGF infusion.
• 5.5. Chronic intravenous EGF infusion affects the electrolyte profile by altering electrolyte secretion by the mammary gland and renal electrolyte excretion.

     

The measurement of glutamate dehydrogenase activity in Praunus flexuosus and its role in the regulation of ammonium excretion

• 1.1. A strong correlation (r² = 0.916) was found between glutamate dehydrogenase (GDH) activity and ammonium excretion in Praunus flexuosus suggesting a key regulatory role for this enzyme.
• 2.2. The high level of GDH activity found in this mysid was sufficient to account for all the ammonium excreted.
• 3.3. Activator-inhibitor studies imply that GDH may regulate energy production and growth, in addition to ammonium excretion.
• 4.4. The GDH assay presented here appears useful as a technique for quantifying zooplankton ammonium excretion impacts in the world oceans.

     

Comparative hematology: Studies on cats including one with factor XII (hageman) deficiency

• 1.1. Cat plasma prothrombin and partial thromboplastin times are faster than human. Thromboplastin generation tests are very similar.
• 2.2. Factors VIII and V assay 24 and 13 times the human standard. Cat factors VII, X. IX, XI and XII assayed at 2.5 to 4 times human. Factors I, II and XIII fell within the human range and Fletcher was extremely low.
• 3.3. One cat lacked factor XII and showed a prolonged APTT and clotting time.
• 4.4. Cat profibrinolysin was activated by streptokinase but not by urokinase.
• 5.5. Cat platelets aggregated with the usual human aggregation agents with the exception of thrombin and ristocetin.
• 6.6. Cat erythrocytes were smaller and more numerous than human.
• 7.7. Leukocyte counts were quite variable.
• 8.8. Serum protein electrophoretic patterns differed from human in the greater migration of albumin and the presence of numerous unidentified bands.
• 9.9. Biochemical tests showed high sodium and chloride values.

     

The djungarian hamster,a laboratory animal with inappropriate hyperglycaemia

• 1.1. The physiology of the Djungarian hamster is described with special regard to breeding and development.
• 2.2. The metabolic abnormalities are studied with special regard to carbohydrate and lipid metabolism.
• 3.3. The data reveal this animal to exhibit a genetically determined inappropriate hyperglycaemia and to differ from all other species so far known by an early onset of urinary ketone body excretion.

     

Comparison of the porphyrin patterns in patients with porphyria cutanea tarda in Czechoslovakia and Denmark

• 1.1. The incidence of porphyria cutanea tarda (PCT) has increased considerably in Denmark during the last decade (Table 1) but is much higher in Czechoslovakia than in Denmark.
• 2.2. We therefore made a detailed study of the urinary porphyrin excretion pattern in 10 cases of PCT from Copenhagen and 10 from Prague.
• 3.3. The results are presented (Table 2). They show no simple pattern.
• 4.4. Comparison with the type subdivision of Doss et al. (Table 3) and the important findings of Piñol Aguade et al. show that such elaborate type division, involving considerable and time-consuming analytical work, belong to research and have limited value in clinical work.

     

Development of chronic hepatic porphyria (porphyria cutanea tarda) with inherited uroporphyrinogen decarboxylase deficiency under exposure to dioxin

• 1.1. Exposure to dioxin triggered a clinically manifest chronic hepatic porphyria (porphyria cutanea tarda) in two patients (brother and sister) with hereditary uroporphyrinogen decarboxylase deficiency.
• 2.2. The patients showed a decrease of erythrocyte uroporphyrinogen decarboxylase activity to ~ 50% of controls even in reinvestigations after three years, whereas clinical symptoms and porphyrinuria had improved considerably. Only a subclinical phase of chronic hepatic porphyria persisted. Subnormal uroporphyrinogen decarboxylase activity could be determined in altogether nine family members.
• 3.3. The remission of porphyria cutanea tarda into a subclinical phase occurred after chloroquine therapy. Subclinical phases of chronic hepatic porphyria (type A) in other family members remitted without special therapy.
• 4.4. Among the 60 persons dioxin-exposed by the Seveso accident, a secondary coproporphyrinuria was found in 22% of examined patients with transition to a subclinical chronic hepatic porphyria in 5 cases. The changes had subsided completely after one year. A persistence of the transition state in 3 cases is probably due to alcohol influence. None of these cases developed a porphyria cutanea tarda.
• 5.5. The investigations showed that a hereditary disposition is necessary for biochemical and clinical expression of chronic hepatic porphyria after a unique dioxin exposure. This is not given in the sporadic cases: after a unique dioxin exposure they indeed develop a symptomatic disturbance of porphyrin metabolism but not a clinically relevant chronic hepatic porphyria.
• 6.6. We conclude that a unique acute exposure to dioxin can trigger the chronic hepatic porphyria disease process in persons with an underlying genetic abnormality of uroporphyrinogen decarboxylase.

     

How the atmosphere and the presence of substrate affect the photo and non-photoinactivation of heme enzymes by uroporphyrin I

• 1.1. The effect of URO I on the activity of ALA-D, PBGase, deaminase and URO-D, both in aerobiosis and anaerobiosis, was studied.
• 2.2. Photoinactivation of the enzymes was much lower in an anaerobic than in an aerobic atmosphere.
• 3.3. Dark inactivation in the absence of oxygen was lower than its presence.
• 4.4. Preincubation in the presence of ALA or PBG protected the enzymic activity of ALA-D, PBGase and deaminase against URO I-inactivation both under u.v. light and in the dark.
• 5.5. Photoinactivating action of URO I would be mediated by reactive oxygen species generated by the excited porphyrin after its absorption of light. Dark inactivation, in aerobiosis, can also be partly mediated by amino acid oxidation, although to a lesser extent than that observed under u.v. light.

     

Renin activity in rainbow trout (salmo gairdneri rich.) and effects of environmental ammonia

• 1.1. A working model for renin assay in trout is described.
• 2.2. Renal renin activity increases in trout exposed to various un-ionized ammonia (UIA) environmental concentrations, with the only exception of 20 μgN/l UIA treated specimens.
• 3.3. Such effect of the toxic substance seems to be proportional to the logarithm of the environmental ammonia concentration and reaches a maximum in overturned specimens.
• 4.4. Results contribute new findings concerning correlation between renin activity and diuresis in fresh water fish.

     

The role of the skin of Rana pipiens in sulfate excretion

• 1.1. The intact whole skin of Rana pipiens excretes sulfate and this excretion is increased by sulfate loading of the animal,
• 2.2. Ninety-five percent of the excretion of sulfate seen following sulfate loading is via the skin, while a small amount is handled by the urinary system.

     

Main kinetic characteristics of acetylcholinesterase from brain of Hypostomus punctatus,a Brazilian bentonic fish (cascudo)

• 1.1. A potentiometric method for the assay of cholinesterase has been proposed and compared with a colorimetric assay.
• 2.2. Main kinetic parameters of cholinesterase from Hypostomus punctatus brain were determined indicating that true acetylcholinesterase is by far the predominant enzyme in the brain of this fish.
• 3.3. We have compared our data with published results described from other fish species.
• 4.4. The enzyme inhibition achieved after 3 hr incubation of brain homogenates with ethyl-parathion have indicated that this enzyme shows a characteristic organophosphorous sensitive behavior.

     

Main serum protein of rainbow trout (Salmo gairdnerii): its biological properties and significance

• 1.1. Main serum α₁-protein (α₁P) of rainbow trout was purified and its biochemical and physico-pathological properties were studied.
• 2.2. α₁P was suggested to be a primitive protein having both properties of albumin and AFP in serum proteins of mammals according to the following results.
• 3.3. Molecular weight (75,000), two kinds of molecules (pI 4.55 and 5.05) and amino acid composition.
• 4.4. Dye- or ConA binding activity.
• 5.5. Estrogen binding activity and inhibitory effect on lymphoblastoid-forming activity.
• 6.6. Possible osmotic regulator.
• 7.7. Significant elevation of blood α₁P level in the course of hepatoma induction.

     

Plasma lipid transport in the horse (Equus caballus)

• 1.1. Equine plasma contains lipoproteins corresponding to very low density (VLDL), low density (LDL) and high density lipoproteins (HDL).
• 2.2. HDL accounts for approximately 60% of plasma lipoprotein mass and consists of a single population of particles.
• 3.3. LDL is heterogeneous comprising three discrete subfractions.
• 4.4. Two proteins are found in the region of apolipoprotein (apo) B-100 in VLDL and LDL and a third similar to apo B-48 is in VLDL.
• 5.5. Lecithin:cholesterol acyl transferase is active in plasma and hepatic lipase and lipoprotein lipase are evident in post-heparin plasma.
• 6.6. There is no significant cholesteryl ester transfer protein activity.

     

Regulatory role of δ-aminolevulic acid dehydratase in the dimorphic fungus Mucor rouxii

• 1.1. With the aim of finding a possible relationship between the known dimorphism phenomenon existing in the fungus Mucor rouxii and the biosynthesis of respiratory pigments, the activity of aminolevulic acid synthetase (ALA-S) and ALA-dehydratase (ALA-D) was studied in crude extracts and in 15,000 g supernatants of both mycelium and yeast-like cells.
• 2.2. The activity of ALA-S was unusually high (3 nmol ALA/hr/mg protein) compared with that reported for other tissues and did not vary with the fungus morphology.
• 3.3. Instead, ALA-D specific activity was found to be 16.5 nmol PBG/hr/mg protein in mycelium extracts, that is 7-fold greater than that measured in the yeast-like morphology (2.6 nmol PBG/hr/mg protein).
• 4.4. It was of importance to determine the activity levels of ALA-D along with the morphogenic transition from yeast to mycelium. It was observed that the greatest change and enhancing of specific activity occurred 2 hr before the emergence of the germ tubes and was held constant up to the complete development of mycelium.
• 5.5. Both hyphae formation and enhancement of ALA-D activity were diminished when cAMP was added to the culture shifted from the anaerobic atmosphere to air.
• 6.6. These findings and preliminary studies on the characterization of M. rouxii ALA-D indicate that this enzyme plays a regulatory role in porphyrin biosynthesis in this fungus as well as a key function in the characteristic morphogenic transition.

     

Glucosyl and galactosyl transferase activities of diabetic (db/db) and obese (ob/ob) mice kidneys

• 1.1. Glucosyl and galactosyl activities were determined in kidney cortex tissue prepared from two strains of mice, genetically diabetic and obese mice.
• 2.2. These activities were measured as a function of ageing between 6 weeks and 13 months.
• 3.3. For both strains glucosyl transferase activity was shown to increase with respect to ageing whereas galactosyl transferase activity decreased at the same time.
• 4.4. These changes of enzymatic activities would suggest that a smaller increase of hydroxylysine-linked glycans than expected was observed under these pathological conditions.

     

Human urinary excretion of l-histidine-related compounds after ingestion of several meats and fish muscle

• 1.1. After oral administration of the muscle of skipjack tuna, about 90% of ingested anserine (Ans) was excreted quickly into urine as Ans (8%) and π-methylHis (82%), indicating the fast decomposition of Ans into π-methylHis. This was also the case for chicken muscle ingestion.
• 2.2. After eel muscle ingestion, carnosine (Car) excretion was only 1 % of the ingested whereas almost no increase was found in His, a constituent of Car, indicating the re-utilization of this essential amino acid. Similar results were also obtained from beef and pork ingestion.
• 3.3. In all cases, the urinary excretion of these compounds reached a maximum within 7 hr after ingestion and returned to the level of meat-free diet within 40 hr.

     

Sex-specific androgen binding in spotted hyaena (Crocuta crocuta) plasma

• 1.1. A charcoal adsorption assay demonstrated a large variance in androgen binding ability in female spotted hyaenas.
• 2.2. A positive correlation between plasma androgen binding ability and ovarian steroid concentrations was demonstrated in adult females.
• 3.3. The strong plasma binding affinity for testosterone and dihydrotestosterone (DHT) (nM) together with the lack of cortisol and weaker oestradiol-17β binding suggests that a specific androgen binding substance, possibly a protein, is present in adult females of this species.
• 4.4. The lack of high affinity binding in male spotted hyaenas is unusual and deserves further investigation.
• 5.5. Some androgen binding in all, including males and immature animals suggests that albumin may bind some plasma androgens in this species.

     

Development of a Gill Assay Library for Ecological Proteomics of Threespine Sticklebacks (Gasterosteus aculeatus)

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Highlights

• •Construction of threespine stickleback gill assay library using DDA proteomics
• •Population-specific gill proteome signatures of four ecotypes identified by DIA
• •HSP47 and extracellular matrix proteins highly elevated in warm-adapted sticklebacks
• •Inflammasome and proteolytic proteins highly elevated in freshwater sticklebacks

     

Volatile fatty acid excretion during anaerobiosis in the lugworm Arenicola marina

• 1.1. Accumulation and excretion of propionate and acetate during experimental anaerobiosis were investigated in the lugworm Arenicola marina.
• 2.2. The rate of accumulation and the ratio propionate/acetate were found to be tissue-specific.
• 3.3. The excretion of the volatile fatty acids showed a characteristic time course.
• 4.4. The results of experiments analyzing the role of different organs indicate that the excretion of these metabolites proceeded via the undifferentiated surface of the body.
• 5.5. The rate of excretion depended on the concentration gradient between animal and the ambient water, the chain-length of the fatty acid and the pH of the water. Propionate excretion was inhibited by butyrate.