Evaluation of coronary atheroma by 64-slice multidetector computed tomography: Comparison with intravascular ultrasound and angiography.

BACKGROUND: Recent improvements in multidetector computed tomography (MDCT) with 64-slice scanners have allowed acquisition of a coronary study in 5 s to 6 s, with good temporal and spatial resolution. Previous studies have reported an underestimation of plaque burden by MDCT. Whether shorter scan times can allow correct assessment of plaque volume requires comparison with intravascular ultrasound (IVUS). METHODS: Patients (n=30) scheduled for coronary angiography also underwent MDCT and IVUS examinations within 96 h. MDCT examination was performed with a 64-slice scanner. Nitroglycerin was administered before all imaging procedures. MDCT, quantitative coronary angiography (QCA) and IVUS analyses were performed by observers blinded to other results. Plaque volumes were determined by MDCT and IVUS in one vessel, and maximum percentage diameter stenosis was identified in each coronary segment by MDCT and QCA. RESULTS: The mean (+ or - SD) plaque volume was determined to be 179.1 + or - 78.9 mm(3) by MDCT and 176.1 + or - 87.9 mm(3) by IVUS. There was a strong positive correlation for plaque volume between MDCT and IVUS (r=0.84, P<0.0001). Percentage diameter stenosis assessed by MDCT and QCA also correlated well (r=0.88 per patient and r=0.87 per vessel, P<0.0001 for both). The maximum percentage diameter stenosis per vessel was 38.1 + or - 30.2% with MDCT and 34.1 + or - 27.6% with QCA. The sensitivity and specificity of MDCT in detecting stenoses above 50% per vessel were 100% and 91.0%, respectively. CONCLUSIONS: Plaque volumes measured by 64-slice MDCT and IVUS correlate well, without systematic underestimation. The sensitivity and specificity of MDCT to detect stenoses greater than 50% by QCA are excellent with the administration of nitroglycerin before imaging.

Scintimammography with 11beta-methoxy-(17alpha,20Z)-[123I]iodovinylestrad iol: a complementary role to 99mTc-methoxyisobutyl isonitrile in the characterization of breast tumors.

UNLABELLED: The aim of this study was to investigate a possible relationship between 99mTc-methoxyisobutyl isonitrile (MIBI) uptake and the estrogen receptor (ER) status of breast tumors as determined by 11beta-methoxy-(17alpha,20Z)-[123I]iodovinylestradi ol (MIVE) scintimammography. METHODS: Thirteen patients referred for MIVE scintimammography after abnormal mammography or finding of a suspect mass on physical examination were injected intravenously with MIVE. Planar images of the breasts and axillary region were taken with both radiopharmaceuticals and compared with pathologic examination of the tumor tissue and in vitro ER quantification. RESULTS: The presence of cancerous tissue, as indicated by MIBI uptake, is a prerequisite for the accumulation of MIVE by the breast tumors. There was no statistically significant correlation between the MIBI and MIVE tumor uptake ratios. However, the latter correlate well with the presence of ER, as determined by an in vitro assay. CONCLUSION: MIVE scans add unique information concerning the tumor ER status in breast cancer patients, which could contribute to a better characterization of the tumor and aid in the selection of the most appropriate treatment protocol.

Photodynamic therapy: tumor targeting with adenoviral proteins.

A brief summary of the mechanisms involved in photodynamic therapy (PDT) and the role of delivery vehicles for photosensitizer targeting is addressed. Phthalocyanines (Pc) have been coupled to adenovirus type 2 capsid proteins including the hexon, the penton base and the fiber to enhance their target selectivity. Adenovirus penton base proteins contain the arginine-glycine-aspartic acid peptidic sequence (RGD) motif known to bind with great affinity and high specificity to integrin receptors, expressed by several types of cancer. Tetrasulfonated aluminum phthalocyanine (AlPcS4) was covalently coupled to the various capsid proteins via one or two caproic acid spacer chains (A1 or A2) in 7:1 up to 66:1 molar ratios. The capacity of the bioconjugates for singlet oxygen production, as measured by an L-tryptophan oxidation assay, was strongly reduced, likely reflecting scavenging by the carrier. Cell adsorption and in vitro photocytotoxicity assays were carried out using the A549 and HEp2 human cell lines expressing integrin receptors, and one murine, the EMT-6 cell line, which lacks receptors for the RGD sequence. The AlPcS4A2-protein complexes induced greater cytotoxicity as compared to the analogous AlPcS4A1 preparations. The penton base-AlPcS4A2 derivative was the more phototoxic for all cell lines tested. Tumor response studies using Balb/c mice with EMT-6 tumor implants demonstrated that the free AlPcS4A2 induced complete tumor regression at a dose of 1 mumol/kg and 400 J/cm2, which is comparable to the activity of the known AlPcS2adj. A mixture of adenovirus type 2 soluble proteins covalently labeled with AlPcS4A2 required 0.5 mumol/kg to induce the same response with the same light dose, suggesting that the high affinity RGD/receptor complex is able to target Pc for PDT.

Biodistribution, dosimetry and metabolism of 11beta-methoxy-(17alpha,20E/Z)-[123I]iodovinylestradiol in healthy women and breast cancer patients.

UNLABELLED: The biodistribution and dosimetry of the 20E and 20Z stereoisomers of 11 beta-methoxy-(17alpha,20)-[123I]iodovinylestradiol (MIVE) were evaluated in six healthy women. Tumor uptake and metabolism of the 20Z isomer were evaluated in 13 women referred after abnormal mammography or after discovery of a suspect mass at physical examination. METHODS: The radiopharmaceuticals were prepared from their corresponding stannyl intermediates and administrated intravenously. Blood samples were drawn at different time intervals and urine was collected for up to 24 h. Metabolites were detected by radiochromatography. Tissue distribution was followed for up to 24 h by scintigraphic imaging. The dosimetry was computed according to the Medical Internal Radiation Dose scheme. RESULTS: The 20E and 20Z isomers exhibit similar biodistribution and dosimetry patterns. Chromatographic analysis of plasma samples of healthy volunteers and cancer patients, as well as in vitro plasma incubations, confirmed the in vivo stability of (20Z)-[123I]MIVE. Radioactivity was rapidly cleared from the blood by the liver and excreted through the gut, which received the highest radiation dose (0.211 mGy/MBq). The effective doses for the adult female and male phantom were 0.054 and 0.046 mSv/MBq, respectively. Among the 13 patients imaged with (20Z)-[123I]MIVE, 3 had fibrocystic disease with no focal uptake, 8 had good agreement with in vitro estrogen receptor determination and 2 were false-positive. CONCLUSION: The radiation dose after intravenous administration of 20E- or (20Z)-[123I]MIVE at imaging dose levels is within acceptable limits. There was a good correlation between uptake of (20Z)-[123I]MIVE and the presence of estrogen receptors in breast cancer patients.

Water-soluble aluminium phthalocyanine-polymer conjugates for PDT: photodynamic activities and pharmacokinetics in tumour-bearing mice.

The potential use of unsubstituted aluminium phthalocyanine (AlClPc) as a sensitizer for photodynamic therapy (PDT) of cancer has not been fully exploited in spite of its higher efficiency as compared to the sulphonated derivatives. This is largely due to the strong hydrophobic character of AlClPc which renders the material difficult to formulate for in vivo administration. We prepared two water-soluble derivatives of AlClPc by axial coordination of polyethyleneglycol (PEG, MW 2000) or polyvinylalcohol (PVA, MW 13,000-23,000) to the central aluminium ion. Their photodynamic activities were evaluated in vitro against the EMT-6 mouse mammary tumour cells and in vivo against the EMT-6 and the colon carcinoma Colo-26 tumours implanted intradermally in Balb/c mice. Pharmacokinetics were studied in the EMT-6 tumour-bearing mice. After 1 h incubation, the light dose required to kill 90% of cells (LD90) was at least three times less for AlClPc (Cremophor emulsion) as compared to AlPc-PEG and AlPc-PVA, while after 24 h incubation all three preparations were highly phototoxic. All three dye preparations induced complete EMT-6 tumour regression in 75-100% of animals at a low drug dose (0.25 micromol kg(-1)) following PDT (400 J cm(-2), 650-700 nm) at 24 h pi. Complete tumour regression in the Colo-26 tumour model was obtained in 30% of mice at a dose of 2 micromol kg(-1). In the non-cured animals, AlPc-PVA induced the most significant tumour growth delay. This dye showed a prolonged plasma half-life (6.8 h) as compared to AlClPc (2.6 h) and AlPc-PEG (23 min), lower retention by liver and spleen and higher tumour-to-skin and tumour-to-muscle ratios. Our data demonstrate that addition of hydrophilic axial ligands to AlPc, while modifying in vitro and in vivo kinetics, does not reduce the PDT efficiency of the parent molecule. Moreover, in the case of the polyvinylalcohol derivative, axial coordination confers advantageous pharmacokinetics to AlPc, which makes this photosensitizer a valuable, water soluble candidate drug for clinical PDT of cancer.

Binding interactions and conformational changes induced by sulfonated aluminum phthalocyanines in human serum albumin.

Phthalocyanines (Pc), which are extensively studied as tumor localizing photosensitizers for photodynamic therapy, are transported by the blood circulatory system to target tissues. Binding interactions between human serum albumin and differently sulfonated aluminum phthalocyanines (AlPcSn; n = 1-4) were studied using optical and ESR spectroscopy. AlPcSn (n = 1-3) occupy one strong binding site and eight weaker sites. The high affinity binding site interactions differ with respect to the degree of sulfonation and isomeric composition of the Pc. Phthalocyanines without SO-3 groups on adjacent iso-indole rings exhibit a high affinity binding site constant of K approximately 3-4 x 10(7) M-1, while Pc with two or three adjacent SO-3 groups show binding for this high affinity site that is no longer independent, but cooperative (alpha = 2), with K approximately 2-6 x 10(6) M-1. Binding isotherms for AlPcS4 and its close analog, tempoyl spin-labeled SL-AlPcS3, do not approach saturation at high ligand concentrations. Competition analyses between AlPcSn and spin-labeled fatty acids (5- and 16-doxyl stearate isomers) reveal that all compounds participate in cooperative (allosteric) interactions with the high affinity binding site of 16-DS, while extruding 5-DS isomer from certain sites and increasing the binding affinity for the remaining. Protein conformational dynamics was studied by ESR spectroscopy using covalent (alkylation of Cys34 residue) and noncovalent spin labeling (employing SL-AlPcS3). Phthalocyanines perturb conformational dynamics parameters (tauc and S) depending on the degree of sulfonation and isomeric composition corresponding to the type of sites, i.e., independent or cooperative, occupied on the HSA molecule.

Receptor-mediated targeting of phthalocyanines to macrophages via covalent coupling to native or maleylated bovine serum albumin.

Targeted delivery of aluminum tetrasulfophthalocyanine (AlPcS4) to the scavenger receptor of macrophages, via coupling to maleylated bovine serum albumin (mal-BSA), was explored as a means to improve photodynamic efficacy. The AlPcS4 was covalently coupled to BSA (9:1 molar ratio) via one or two sulfonamide-hexanoic-amide spacer chains, followed by treatment with maleic anhydride to yield the mal-BSA-phthalocyanine conjugates. The latter were tested for singlet oxygen production, receptor-mediated cell uptake and phototoxicity toward J774 cells of macrophage origin and nonphagocytic EMT-6 cells. Cell uptake of 125I-mal-BSA showed specific binding for J774 cells but not for EMT-6 cells. Competition studies of the conjugates with 125I-mal-BSA showed that coupling of AlPcS4 to BSA resulted in recognition of the conjugate by the scavenger receptor, whereas coupling to mal-BSA further enhanced its binding affinity. This suggests that affinity for the scavenger receptor is related to the overall negative charge of the protein. Phototoxicity of the conjugates toward J774 cells paralleled their relative affinity, with mal-BSA-AlPcS4 coupled via two spacer chains showing the highest activity. The conjugates were less phototoxic toward the EMT-6 cell line. The activities in both cell lines of all conjugated AlPcS4 preparations were, however, lower than that of the free disulfonated AlPcS2. Possible implications for the in vivo use of protein-photosensitizer conjugates to target selectively various macrophage-associated disorders is discussed.

Efficacy and mechanism of aluminium phthalocyanine and its sulphonated derivatives mediated photodynamic therapy on murine tumours.

The efficacy of photodynamic therapy (PDT) mediated by aluminium phthalocyanine (AlPc) and its mono- and disulphonated derivatives (AlPcS1 and AlPcS2, respectively) on murine EMT-6 tumour were compared in vivo. AlPc (0.25 mumol/kg) PDT resulted in no tumour recurrence in all treated mice. In contrast, PDT with AlPcS1 (2 mumol/kg) and AlPcS2 (1 mumol/kg) only produced tumour cure in 75% and 86% of mice, respectively. Immediately after AlPc-PDT, tumour cells were found to be viable as determined by in vitro clonogenicity, but progressive cell death occurred thereafter. In contrast, AlPcS1 and AlPcS2 PDT produced substantial cell death (approximately 35% and 70%, respectively, of entire tumour) immediately after phototherapy, and yet further loss of tumour cell viability continued after PDT. In all cases, few vascular effects were observed at 0 h post-PDT, as indicated by the retention of 99mTc-MIBI in the tumour. However, the reduction of blood flow in tumours progressed with time, such that blood flow in tumours fell to approximately 25% of the control level by 24 h after both AlPc and AlPcS1 PDT. With AlPcS2, there was only an approximate 50% fall in tumour blood flow by 24 h. These results demonstrate a greater PDT efficiency with AlPc on tumour destruction, which is an indirect mechanism involving damage of tumour vasculature, whereas AlPcS2 has a greater effect on direct tumour cytotoxicity and AlPcS1 exerts both direct and indirect modes of action against tumours.

Prevention concerning mental health: the adolescent's perspective.

OBJECTIVE: To examine several subjective components of adolescents' behaviour concerning mental illness prevention. METHOD: Adolescents' knowledge, their attitudes and subjective norms, as well as their thoughts about how they would concretely handle a psychological problem were measured. A self-administered questionnaire was completed by 438 male and female adolescents in grades 8 and 11. RESULTS: Gender and age differences were revealed: girls and older adolescents were more attuned to prevention. Further, the influence on young people of peers and parents was also apparent. CONCLUSION: Adolescents perceive prevention concerning mental health as important.

Photodynamic activities and skin photosensitivity of the bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine in mice.

The photodynamic therapy (PDT) activity of the bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine (SiNc 8) was evaluated against the EMT-6 tumor implanted intradermally in BALB/c mice. The SiNc 8 was formulated in aqueous emulsions based on Cremophor EL or Solutol HS 15. The formulation was shown to affect plasma clearance and overall pharmacokinetics. Compared to Cremophor, Solutol promoted rapid plasma clearance and high liver retention of the dye, combined with a slight increase of dye tumor concentrations. The PDT action spectrum for tumor response of SiNc 8 in Cremophor (190 mW cm-2, 200 J cm-2, 24 h postinjection [p.i.] of 1 mumol kg-1) showed a maximum at 780 nm, which corresponds to the absorption maximum of the monomeric dye as well as the in vivo maximum change in the "diffuse optical density" produced by the dye. The extent of tumor necrosis increased with augmented dye and light doses. Regardless of the formulation, at 1 h p.i. of 0.1 mumol kg-1 SiNc 8, PDT efficiency (190 mW cm-2, 400 J cm-2) was high but accompanied by severe damage to normal tissues, at 24 h p.i. PDT resulted in complete tumor regression in 80% of the animals without adverse effects to adjacent tissues, while at 72 h p.i. PDT induced no tumor response with Cremophor and only a partial response with Solutol. At the latter time point, plasma dye clearance was nearly complete while tumor tissue levels remained high, suggesting that tumor response correlates with plasma rather than tumor dye levels. Skin sensitivity of SKhI mice to solar-simulated radiation was lower with SiNc 8 as compared to Photofrin. Our data suggest the potential of SiNc 8 as a far-red absorbing photosensitizer in clinical PDT.

[Mandibular permanent cuspids with two roots]. / Canines inférieures permanentes à deux racines.

When one reviews the literature, it is quite apparent that there seems to be many assumptions relative to the number of roots found in mandibular permanent canines. After having examined 806 specimens, the author of this article found that 95 per cent of mandibular canines had one root and five per cent had two roots.

Evaluation of 99mTc-labeled modified serum albumin for tumor detection.

Serum albumin (SA) modified and labeled with 131I-tyramine N-1'-desoxysorbitol (131I-TDS) has been shown to localize in tumors [Sinn et al., (1990) Nucl. Med. Biol. Part B 17, 819-827]. We prepared similar TDS complexes labeled with 99mTc and evaluated their potential for tumor imaging. Derivatization of SA with TDS was optimized using cyanuric chloride or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDAC) as coupling agents. A high TDS loading yield of 38 mol/mol SA was obtained with the latter reagent. Modified SA (8 and 38 mol TDS/mol SA) were labeled with 99mTc via the stannous reduction method and injected i.v. into EMT-6 tumor bearing mice. 125I-TDS-SA (8 mol 125I-TDS/mol SA) revealed a high tumor uptake of 10% ID/g at 3 h post-injection. The 99mTc-labeled SA and TDS-SA complexes lacked tumor specificity, instead TDS loading of SA resulted in increased liver/spleen uptake, suggesting colloid formation. This study confirms the potential of modified SA for tumor imaging but highlights the importance of choice of radioisotope, as well as site of attachment of the radiolabel to the modified SA for optimal tumor localization.

[How to predict the presence of three-rooted maxillary premolars]. / Comment prévoir les prémolaires supérieures à trois racines?

Sixty extracted maxillary premolars, 55 firsts and five seconds, were classified into three categories according to the beginning of their trifurcation. The mesiodistal dimensions of the buccal roots, at different levels, were compared with the mesiodistal diameter at the cervix. Among all teeth examined, the proximal profiles of the roots were parallel in the two cervical thirds, or the mesiodistal dimension at the middle third or apical third was greater than this at the cervix. If these observations are visualized on the radiograph, the dentist can presume that these teeth have three roots.

Synthesis and photodynamic activities of silicon 2,3-naphthalocyanine derivatives.

Bis(tert-butyldimethylsiloxy)- (7), bis(dimethylthexylsiloxy)- (8), bis(tri-n-hexylsiloxy)- (9), and bis(dimethyloctadecylsiloxy)silicon 2,3-naphthalocyanines (10) were prepared via substitution of the bis(hydroxy) precursor with the corresponding chlorosilane ligands and characterized by spectroscopic and combustion analyses. They show strong absorption around 780 nm where tissues exhibit optimal transparency. Compounds 7-10 are capable of producing singlet oxygen. They are relatively photostable although less stable than the analogous phthalocyanine, i.e., the bis-(dimethylthexylsiloxy)silicon phthalocyanine (12). They were evaluated as potential photosensitizers for the photodynamic therapy (PDT) of cancer in vitro against V-79 cells and in vivo against the EMT-6 tumor in Balb/c mice. In vitro all four dyes showed limited phototoxicity combined with substantial dark toxicity. Surprisingly, in vivo (i.v., 0.1 mumol/kg, 24 h prior to the photoirradiation of the tumor with 780-nm light, 190 mW/cm2, 400 J/cm2) all dyes induced tumor regression in at least 50% of mice whereas compound 8 gave a complete tumor response in 80% of mice without apparent systemic toxicity at doses as high as 10 mumol/kg. At 24 h postinjection, compound 8 showed a favorable tumor to muscle ratio of 7, assuring minimal damage to the healthy tissue surrounding the tumor during PDT. Our data confirm the potential of silicon naphthalocyanines as far-red-shifted photosensitizers for the PDT of cancer and indicate the importance of the selection of the two axial silicon ligands for optimal photodynamic efficacy.

In vivo photodynamic effects of phthalocyanines in a skin-fold observation chamber model: role of central metal ion and degree of sulfonation.

Six sulfonated metallophthalocyanines, chelated with either aluminum or zinc and sulfonated to different degrees, were studied in vivo for their photodynamic activity in a rat skin-fold chamber model. The chamber, located on the back of female WAG/Rij rats, contained a syngeneic mammary carcinoma implanted into a layer of subcutaneous tissue. Twenty-four hours after intravenous administration of 2.5 mumol/kg of one of the dyes, the chambers received a treatment light dose of 600 J/cm2 with monochromatic light of 675 nm at a power density of 100 mW/cm2. During light delivery and up to a period of 7 days after treatment, vascular effects of tumor and normal tissue were scored. Tumor cell viability was determined by histology and by reimplantation of the chamber contents into the skin of the same animal, either 2 h after treatment or after the 7 day observation period. Vascular effects of both tumor and subcutaneous tissue were strongest with dyes with the lowest degree of sulfonation and decreased with increasing degree of sulfonation. Tumor regrowth did not occur with aluminum phthalocyanine mono- and disulfonate and with zinc phthalocyanine monosulfonate. With the protocol that was used, complete necrosis without recovery was only observed when reimplantation took place at the end of the 7 day follow-up period. Reimplantation 2 h after treatment always resulted in tumor regrowth. At this interval, the presence of viable tumor cells was confirmed histologically. In general tumor tissue vasculature was more susceptible to photodynamic damage than vasculature of the normal tissue. The effect on the circulation of both tumor and normal tissue increased with decreasing degree of sulfonation.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo fluorescence kinetics of phthalocyanines in a skin-fold observation chamber model: role of central metal ion and degree of sulfonation.

The fluorescence pharmacokinetics of a series of metallosulfophthalocyanines, chelated with either aluminum or zinc and sulfonated to different degrees, was studied by fluorescence measurements in vivo. Dyes were administered systemically to female WAG/RIJ rats with an isogeneic mammary carcinoma transplanted into the subcutis in a transparent observation chamber located on their backs. Following an intravenous injection of 2.5 mumol/kg of the dye, fluorescence dynamics was observed up to 7 h postinjection. The phthalocyanines were excited at 610 nm with a power density of 0.1 mW/cm2 without causing photodynamic damage to the vasculature. Fluorescence was detected above 665 nm using a fluorescence imaging system based on an image intensifier. Dye retention in the blood vessels and tumor tissue was expressed as ratios relative to the fluorescence signal of the surrounding subcutaneous tissue. Phthalocyanines chelated with aluminum gave the highest fluorescence signal with tumor-over-subcutis ratios of up to a value of 4. The zinc complexes exhibited the highest vascular-over-subcutis ratios with maximum values exceeding a value of 6. They also displayed the longest retention times in the vascular system of well over 7 h. Overall, decreasing the degree of sulfonation of the metallophthalocyanines results in lower tumor-over-normal tissue fluorescence ratios, and furthermore aluminum-based dyes seem superior tumor localizers over zinc-based dyes. The advantages of phthalocyanines over porphyrins with respect to tumor localization and photodynamic therapy are discussed.

The effects of photodynamic therapy using differently substituted zinc phthalocyanines on vessel constriction, vessel leakage and tumor response.

The effects of four different zinc phthalocyanines were studied during and after photodynamic therapy (PDT). Measurements of vessel constriction, vessel leakage, tumor interstitial pressure, eicosanoid release, and tumor response of chondrosarcoma were made in Sprague-Dawley rats. Animals were injected intravenously with 1 mumol/kg of mono-, di-, or tetrasulfonated zinc phthalocyanine, or 1 mumol/kg of a zinc phthalocyanine substituted with four tertiary butyl groups. Tissues were exposed to 400 J/cm2 670 nm light 24 h after photosensitizer injection. An additional group of animals was given indomethacin before treatment. The use of the monosulfonated and tertiary butyl substituted zinc phthalocyanines in PDT caused the release of specific eicosanoids, caused vessel constriction, and induced venule leakage and increases in tumor interstitial pressure. Tumor cures of 27% and 7% were observed. Photodynamic therapy using the disulfonated zinc phthalocyanine did not induce vessel constriction or the release of eicosanoids, however, tumor cure was 43%. The use of the tetrasulfonated zinc phthalocyanine caused intermediate effects between the mono- and disulfonated compounds. The administration of indomethacin to animals completely inhibited the effects of PDT using the monosulfonated compound but had minimal effects on treatment using the disulfonated compound. This suggests that the monosulfonated and disulfonated compounds act by different mechanisms of destruction.

Profiles of alcoholics according to the SCL-90-R: a confirmative study.

The Symptom Checklist-90-Revised (SCL-90-R) has often been used in studies of alcoholic populations. Based on findings reported in the literature and data gathered on 712 alcoholics in treatment, this paper investigates the general trends in the responses of alcoholics to the SCL-90-R. On global measures as well as on each of the symptom scales, the scores of alcoholic groups reveal a symptomatology two to five times as severe as that observed in the general population. The Psychoticism dimension shows the most marked divergence with the general population. In almost each of the study groups, the Depression Scale registers the highest scores, followed by Obsessive-Compulsive, Interpersonal Sensitivity, and Anxiety.

Biodegradable nanospheres containing phthalocyanines and naphthalocyanines for targeted photodynamic tumor therapy.

Preparation methods of cyanoacrylic nanocapsules or nanoparticles containing phthalocyanines and naphthalocyanines are described. Nanocapsules were obtained by interfacial polymerization in an oil-in-water emulsion. Drug encapsulation efficiency depended upon drug concentration, ethanol concentration, and phthalocyanine sulfonation degree and reached 100% in some cases. Nanocapsules size ranged from 150 to 250 nm and varied with phthalocyanine sulfonation degree and pH of the aqueous phase. Nanoparticles were prepared by the addition of monomer to an aqueous phase containing hydrophilic phthalocyanine derivatives. Depending upon the pH, sizes ranged from 10 to 380 nm. Drug binding was between 75 and 80%. These new preparations could prove useful in the photodynamic treatment of tumors.

[Variability of enzyme activity and urinary orotic acid in ornithine transcarbamylase deficient spf/+ heterozygotic mice]. / Variabilité de l'activité enzymatique et de l'acidurie orotique chez les souris spf/+ hétérozygotes déficientes en ornithine transcarbamylase.

Urinary orotate excretion is used as a clinical parameter to distinguish female carriers of X-linked ornithine transcarbamylase deficiency. The value of this test has been considered doubtful due to a lack of knowledge about the true variability of hepatic enzyme activity and its effect on orotate synthesis. We have used a purebred population of spf/+ heterozygous females (n = 90), with an X-linked structural mutation of ornithine transcarbamylase, to study this variability in comparison with normal +/+ females (n = 19) and hemizygous spf/Y males (n = 20). Our results show that spf/+ heterozygotes have a mean hepatic enzyme activity equal to 64% of the normal group, as compared to 44-56% reported previously. They have a very wide variability (range 28-107 mumol/h/mg protein) which overlap the normal distribution curves of +/+ and spf/Y groups. Similar overlapping is shown in the distribution of urinary orotate excretion. The correlation studies indicate that the urinary orotate level as an index of hepatic enzyme deficiency is of value only in heterozygotes having an activity less than 50% of normal. This parameter cannot, therefore, be used to screen for all heterozygotes. However, it would still be valuable in distinguishing female-children at risk of developing hyperammonemic symptoms.