Kinetics of porphyrin accumulation in cultured epithelial cells exposed to ALA

• 1.1. The kinetics of porphyrin accumulation in cultured mammalian epithelial cells (CNCM-I-221) during exposure to ALA was investigated.
• 2.2. The total porphyrin synthesized is a function of ALA concentration and the incubation time. The cellular porphyrin content exhibited a saturation pattern, reaching a plateau at about 0.04 fmol porphyrins/cell. A biphasic time-dependent increase in the total porphyrin synthesized was observed.
• 3.3. After 3 hr of exposure to ALA the rate of synthesis increased to ahnost twice the initial rate, reaching between 0.02 and 0.05 fmol porphyrins/cell/hr depending on serum concentration in the medium.
• 4.4. Two effects of FBS on ALA-stimulated porphyrin accumulation were observed. Greater total porphyrin synthesis was found when incubations were made in 10% FBS compared to those in 1% FBS.
• 5.5. The higher serum concentration also caused a greater release into the medium of the porphyrins generated in the cells with a calculated half-life of 24 min in 10% serum-supplemented medium compared with 62 min in 1% serum.
• 6.6. The results obtained from cell synchronization experiments suggest that there is little obvious cell cycle-dependent variation in the synthesis of porphyrins from ALA.
• 7.7. The small differences in the intracellular porphyrin content that were observed may be attributed to a slight reduction in the rate of loss of porphyrins in G2/M cells.

     

Biochemistry of porphyria

• 1.1. The porphyrias are a group of metabolic disorders arising from defects in the haem biosynthetic pathway. Most forms are inherited as Mendelian autosomal dominants, but some types are recessive and others acquired through exposure to porphyrinogenic drugs and chemicals. There is a linked group of diseases, which are not porphyrias, but have in common alterations of haem biosynthesis.
• 2.2. The processes of haem biosynthesis are now well understood and the molecular biology of the functions and dysfunctions in the porphyrias are currently an area of intensive investigation.
• 3.3. The acute porphyrias. Acute Intermittent Porphyria, Variegate Porphyria and Hereditary Coproporphyria are of most importance since attacks of these may be life-threatening.
• 4.4. These diseases that usually present with a neurovisceral attack are characterized by excess production of the porphyrin precursors, 5-aminolaevulinate and porphobilinogen because of lowered activity of Porphobilinogen deaminase.
• 5.5. A variety of factors may precipitate these attacks including various drugs, alcohol, smoking, dieting or fasting and variations in steroid hormone levels.
• 6.6. The non-acute porphyrias are largely dermatological conditions, which present clinically as cutaneous photosensitivity. The dermatological changes are caused by the photosensitizing properties of circulating porphyrins and are accompanied by systemic effects of these porphyrins.

     

The effect of fasting and protein calorie malnutrition on the liver porphyrins

• 1.1. Fractionation of the porphyrins extracted from the livers of fasting pigs shows a coproporphyrin to protoporphyrin ratio greater than unity, whereas the livers from normally fed pigs give a ratio less than unity.
• 2.2. Similar results are obtained when the liver porphyrins from guinea-pigs fed on protein deficient diet are compared with those from normally fed animals.
• 3.3. It is suggested that fasting causes a decrease in the ability of the liver to convert coproporphyrin to protoporphyrin, that is, inhibition of the enzyme coproporphyrinogen oxidase.

     

δ-Aminolevulinic acid dehydratase inactivation by uroporphyrin I in light and darkness

• 1.1. The action of uroporphyrin I on erythrocytic ALA-D activity under dark and light conditions was examined.
• 2.2. Photo and non-photoinactivation of ALA-D induced by uroporphyrin I were observed.
• 3.3. Both effects were dependent on uroporphyrin concentration, temperature and time of exposure of the protein to the porphyrin.
• 4.4. Light-dependent effect of uroporphyrin I is related with the phototoxicity of porphyrins and could be produced by primary amino acid photooxidation followed by secondary cross-linking of the protein.
• 5.5. Light-dependent effect of uroporphyrin I could be ascribed to a direct enzyme inhibition due to binding of the porphyrin to the protein inducing structural changes at or near its active site.

     

Protoporphyrin-induced Photohemolysis : Differences related to the subcellular distribution of protoporphyrin in erythropoietic protoporphyria and when added to normal red cells

• 1.1. When protoporphyrin is added to normal red cells it distributes to about 30% in the stroma and 70% in the cytosol. By comparison, in erythropoietic protoporphyria red cell protoporphyrin is found to more than 95% in the cytosol.
• 2.2. At equimolar concentrations of protoporphyrin the photohemolysis is much more severe in normal red cells with exogenous protoporphyrin than in red cells from patients with erythropoietic protoporphyria.
• 3.3. The photohemolysis is markedly enhanced when D₂O is used as solvent instead of H₂O.
• 4.4. The results suggest that the photodamage is determined by the ability of susceptible structures to accumulate porphyrins, the partition of porphyrins between lipophilic and hydrophilic structures and the longevity of singlet oxygen in lipophilic environments.

     

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.

     

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The role of lipoproteins in the delivery of tumour-targeting photosensitizers

• 1.I. Serum lipoproteins play an important role in the in vivo transport of several porphyrinoid derivatives having a moderate or high degree of hydrophobicity.
• 2.2. There appears to exist a correlation between the extent of photosensitizer association with low-density lipoproteins (LDL) and the efficiency of tumour targeting by some classes of photosensitizers, such as differently sulphonated porphyrins and phthalocyanines, haematoporphyrin dialkylethers and unsubstituted phthalocyanines and naphthalocyanines.
• 3.3. In all cases, LDL-carried photosensitizers are preferentially released to malignant cells; hence, direct cell damage appears to be the major determinant of tumour damage consequent to photodynamic therapy.
• 4.4. Present evidence suggests that the LDL-associated photosensitizer is accumulated by tumour cells largely via a receptor-mediated endocytotic process.
• 5.5. Thus, the use of delivery systems for orientating a systemically injected photosensitizer towards lipoproteins has been explored; promising results have been obtained by incorporation of the dye into liposomal vesicles, oil emulsions or inclusion complexes, as well as by precomplexation of the dye with LDL.
• 6.6. Moreover, a suitable choice of the chemical constituents of the delivery system and the experimental conditions allows one to modulate the photosensitizer distribution among the different lipoproteins.
• 7.7. The occurrence of tumour-targeting strategies other than the LDL pathway is briefly discussed.

     

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Oxygen consumption and production by tropical ascidians symbiotic with Prochloron

• 1.1. Oxygen consumption and production rates were measured in two species of colonial ascidians that contained the algal symbiont, Prochloron.
• 2.2. Despite differences in size and habitats, the colonies showed similar rates of oxygen consumption and production.
• 3.3. Oxygen production by the colonies was light dependent.
• 4.4. Based on the data presented, the symbiosis is similar to other algal-invertebrate symbioses in producing more oxygen than is consumed when illuminated.

     

The effect of osmotic and ion-osmotic stresses on the blood and urine composition and urine flow of rainbow trout (Salmo gairdneri)

• 1.1. Changes in urine and plasma concentrations (sodium, potassium, magnesium, calcium and total osmotic) and urine production were determined in fish exposed to various concentrations of an ionically active substance, sodium chloride, and a non-electrolyte, mannitol, as well as freshwater.
• 2.2. Responses occurred for the most part over a short crisis period preceeding establishment of new stable conditions.
• 3.3. It was shown that plasma homeostasis was not maintained in response to changing ion-osmotic and osmotic gradients.
• 4.4. Urinary osmotic and ionic concentrations were unaffected and urine production was shown to be inversely related to the external concentration.
• 5.5. It is suggested that ionic shifts between body compartments are an important aspect of ion-osmotic adaptation.

     

Superoxide dismutase,reduced glutathione and TBA-reactive products in erythrocytes of patients with multiple sclerosis

• 1.1. Superoxide dismutase, reduced glutathione and lipid peroxides levels were determined in the erythrocytes of multiple sclerosis patients.
• 2.2. Superoxide dismutase activity and the malonyldialdehyde production rate were found to be significantly enhanced.
• 3.3. The isoelectric focusing pattern of Superoxide dismutase from multiple sclerosis and normal subjects erythrocytes was substantially overlapping.
• 4.4. Our results indicate the occurrence of a higher susceptibility of multiple sclerosis erythrocytes to lipid peroxidation.

     

The effect of d2o on glycolysis by rat hepatocytes

• 1.1. The effect of incorporating D₂O into the incubation medium on glycolysis and gluconeogenesis by hepatocytes from fasted rats was examined.
• 2.2. The substitution by heavy water, D₂O, at concentrations from 10 to 40%, stimulated glucose uptake, lactate production and CO₂ yields from glucose. At 10 mM glucose, 40% D₂O doubled glucose uptake, increased CO₂ production by 40%, and increased lactate production by 350%.
• 3.3. The stimulation of lactate production decreased at higher glucose concentrations, but was still substantial even at 80 mM glucose.
• 4.4. There was no effect on CO₂ production above glucose concentrations of 30 mM.
• 5.5. Ten percent D₂O showed little inhibition of lactate uptake, its oxidation and gluconeogenesis. At 40% D₂O the inhibition ranged from 10 to 20%.
• 6.6. No effect of D₂O on the rate of glucokinase or glucose-6-phosphatase was observed.
• 7.7. The concentration of fructose, 2,6-P was not affected by D₂O

     

Purification and characterization of hatching enzyme of the pike (Esox lucius)

• 1.1. A choriolytic enzyme was isolated from the hatching medium of the pike, Esox lucius.
• 2.2. The enzyme is defined as hatching enzyme.
• 3.3. The molecular weight of the enzyme is 24,000.
• 4.4. The enzyme is a glycoprotein containing 2% carbohydrate.
• 5.5. Its isoelectric point is 6.5.
• 6.6. The pH optimum is around pH 8.
• 7.7. The enzyme molecule contains two disulfide bonds but no free cysteine.
• 8.8. Inhibitor studies and metal analysis show that the enzyme is a zinc-metalloprotease.

     

Heat production of fish: A literature review

• 1.1. Results of investigations on direct calorimetry and simultaneous measurements of oxygen consumption and carbon dioxide and ammonia production of fish are summarized.
• 2.2. By means of indirect calorimetric formulae, the heat production and the protein, carbohydrate and fat oxidation are calculated from the oxygen consumption and carbon dioxide and ammonia production.
• 3.3. The lowest heat production values are obtained by long-term monitoring of groups of fish during darkness and under fasting conditions.
• 4.4. It is concluded that the heat production of standard metabolism at 20°C is 700J/hr/MW (MW = metabolic weight, kg^0.85).

     

Hyaluronidase degradation of hyaluronic acid from different sources: Influence of the hydrolysis conditions on the production and the relative proportions of tetra- and hexasaccharide produced

• 1.1. Hyaluronic acid (HA) can be digested with a Streptomyces hyaluronidase.
• 2.2. The rate of production and the ratio of tetrasaccharide (T) and hexasaccharide (H), studied by HPLC, varied with the temperature and duration of hydrolysis.
• 3.3. The rates of production and the respective amounts of the two oligosaccharides depended on the rheological properties of the HA from different sources.
• 4.4. A close relationship was found between the initial rate of hydrolysis and the intrinsic viscosity of the HA (η_i).
• 5.5. Our data suggest that enzymatic degradation at a given pH value, temperature, and duration of hydrolysis is dependent on the conformation of HA.
• 6.6. Moreover, under given conditions, the relative proportions of the two oligosaccharides depend on the η_i and may also reflect the degree of hydrolysis of the substrate.

     

The role of citrate derived from glucose in the acetylcholine synthesis in rat brain synaptosomes

• 1.1. Synaptosomes utilizing glucose or glucose plus malate produced citrate with rates of 2.4 and 7.8 nmol/hr/mg of protein, respectively.
• 2.2. (−)Hydroxycitrate increased citrate net synthesis 4 times and inhibited acetylcholine synthesis by 40%.
• 3.3. Oxygen and glucose consumption as well as lactate and CO₂ production were not changed by this inhibitor.
• 4.4. (−)Hydroxycitrate inhibited utilization of exogenous citrate in synaptosomes by 50%.

     

Breast,hips, and buttocks revisited: Honest fatness for honest fitness

This paper comments on: Low, B. S., Alexander, R. D., and Noonan, K.M. Human hips, breast, and buttocks: Is fat deceptive? Ethology and Sociobiology 8: 249-247, 1987. In it I argue that:

• 1.1. Sexual selection has probably not been the most important selection pressure on
• 2.female human body shape.
• 3.2. Male humans in different cultures find different aspects of the female body attractive
• 4.and therefore are unlikely to have exerted consistent directional sexual selection on
• 5.the female body.
• 6.3. Breast size is not correlated with lactation success.
• 7.4. Visible hip width is not correlated with parturition success.
• 8.5. Women would lower their fitness if they tried to deceive men about their internal
• 9.pelvic dimensions.
• 10.6. There are many alternative hypothesis to explain the existence of fat onwomen's
• 11.breast, hips, and buttocks.