Porphyrin dimers as photosensitizers in photodynamic therapy

Porphyrin dimers 9 with either linkages and possible isomers bis[1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-2- vinylporphin-4-yl]ethyl] ether (10) bis[1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-4- vinylporphin-2-yl]ethyl] ether (11), and 1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-2-vinylporph in- 4-yl]ethyl 1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-4-vinylporph in- 2-yl]ethyl ether (12) were synthesized from the corresponding (1-hydroxyethyl)vinyldeuteroporphyrin IX dimethyl esters (Hvd). The pure Hvd isomers 2-(1-hydroxyethyl)-4-vinyldeuteroporphyrin IX dimethyl ester (7) and 4-(1-hydroxyethyl)-2-vinyldeuteroporphyrin IX dimethyl ester (8) were obtained from 2-acetyl-4-(1-hydroxyethyl) deuteroporphyrin IX dimethyl ester (3) and 4-acetyl-2-(1-hydroxyethyl)deuteroporphyrin IX dimethyl ester (4). Porphyrins 3 and 4 were prepared either by partial reduction of 2,4-diacetyldeuteroporphyrin IX dimethyl ester (2) or by oxidation of hematoporphyrin IX dimethyl ester (1) by using tetra-n-propylammonium perruthenate (Prn4N)(RuO4) with N-methylmorpholine N-oxide as an oxidizing agent. The in vivo photosensitizing ability and therapeutic ratios of dimers 9-12 were compared with that of Photofrin II in the SMT-F tumor growing subcutaneously in DBA/2 Ha mice. These dimers were found to have better tumoricidal activity than Photofrin II with reduced skin phototoxicity.     

Levodopa up-regulates platelet alpha 2-adrenoceptors

Treatment of dogs for 21 days with oral levodopa (100 mg b.i.d.) plus benserazide (25 mg b.i.d.) induced a significant increase in the number of platelet alpha 2-adrenoceptors labelled by [3H] yohimbine with no change in Kd. The rise was maximal at the end of the treatment and remained significant during the month following the cessation of treatment. Plasma catecholamine levels did not vary. Competition experiments showed a low affinity of both dopamine and levodopa for platelet alpha 2-adrenoceptors. These results suggest that levodopa treatment regulates alpha 2-adrenoceptor number in dog platelets.     

Reduction using an immunomodulator of the level of respiratory infections in chronic bronchitis

Fifty-six patients with recurrent bronchopulmonary infections associated with chronic bronchitis were randomly allocated to 2 groups, to assess whether treatment with an immunomodulator, Diribiotin CK, could enhance resistance to infection. The double-blind, placebo-controlled prospective trial over a 9 month period showed that this immunomodulator was well tolerated and significantly reduced the rate of respiratory tract infection. The drug also significantly reduced the prescribing of antibiotic medication and the rate of absenteism from work. These effects have been demonstrated in a rigorously designed clinical study. This is the first time that a clear clinical activity has been attributed to an inducer of soluble mediators of immunity.     

Alcoholism in patients with sexual disorders

The authors screened for alcoholism 145 consecutive patients who presented with sexual dysfunction or disorders. Using the Michigan Alcoholic Screening Test (MAST), 29% of the patients scored in the probable alcoholic range. Probable alcoholics were more likely to present without a partner and claimed higher sex drive than nonalcoholic patients. Probable alcoholic males reported less joy and vigor than probable alcoholic females, while the reverse held for the nonalcoholic groups. Blind to the MAST results, the staff made six alcohol-related diagnoses and referred one patient for alcohol treatment. The authors discussed the importance of training faculty and resident staff in the relationship of alcohol abuse associated with psychosexual dysfunctions.     

A case of a small hepatoma with multicentric development in precirrhotic fibrosis

Multicentricity of hepatocellular carcinoma (HCC) is considered, especially in patients with liver cirrhosis. This paper describes an operative case of a male patient with probable multicentric development of HCC in precirrhotic fibrosis. The main tumors inside the capsule were completely necrotic due to transarterial embolization (TAE). Histologic examination disclosed discrete tiny nodules of HCC that were not detected grossly. They showed highly differentiated trabecular arrangements: Edmondson I. A scirrhous type was noted in the center of the tumors. At the borders of the tumors the carcinoma cells exhibited replacing growth patterns and it was thought that they developed multicentrically. Partial resection must be performed as extensively as possible in a case such as the present one.     

Respiratory function and bronchial reactivity in mill workers

Professional exposure to vegetable dusts affect the respiratory function of the exposed subjects. A previous survey conducted in an industrial flour-mill demonstrated a higher frequency of respiratory symptoms in workers compared to a control group. Ten subjects employed in a work site particularly exposed to dust were studied. Each subject answered a questionnaire and performed on Mondays and Fridays, at the begenning and end of his work shift, a flow volume curve and an isocapnic hyperventilation test. The aerobiology of the professional environment was also measured. We noted: 1) in the flow volume curves: a drop in the FEV₁ during the Monday morning shift, a significant difference between the FEV₁ (p<0.05) and the MMEFR 25–75 (p<0.05) measured at 6 am on Monday and Friday, and between the MMEFR 25–75 values obtained at 12 noon on Monday and Friday (p<0.05). 2) after isocapnic hyperventilation, a significant drop in the MMEFR 25–75 at 6 am on Monday (p<0.01) and in the FEV₁ and MMEFR 25–75 at 12 noon on Mondays (p<0.05), a significant drop in the FEV₁ at 1 pm on Monday (p<0.01).     

A critical incident study in child health

The critical incident technique is an objective method of analysing doctors' professional behaviour. It extracts the skills which should be taught and assessed in any training programme. In such a study in child health, 438 incidents were collected from general practitioners, paediatricians and others, and analysed according to the problem, the disease, the setting, the skill and the attitude involved. Most of the problems concerned non-specific symptoms (e.g. 'unwell baby', 'fever') and the main skill categories (each with many subheadings) were clinical management (especially at home), the diagnostic process and interpersonal skills. Training of doctors in child health should emphasize the competencies highlighted in this study.     

ACETALDEHYDE ADDUCTS WITH HAEMOGLOBIN: DETERMINATION OF ACETALDEHYDE RELEASED FROM HAEMOGLOBIN BY ACID HYDROLYSIS

Acetaldehyde, the first metabolite of ethanol, reacts with haemoglobinin vitro to produce acetaldehyde—haemoglobin adducts.Some clinical studies on the minor haemoglobins have suggestedthat these adducts may be formed in people abusing alcohol.Under hydrolysis of haemoglobin, with oxalic acid at 100°Cin sealed vials, some acetaldehyde was released and then specificallydetermined by HPLC. The kinetics of hydrolysis were studiedusing haemoglobin previously labelled with ¹⁴[C] acetaldehyde.The maximum liberation of ¹⁴[C] acetaldehyde was obtained after3 hr 30 min hydrolysis and this time factor was then utilizedin the analysis of alcoholic and control haemoglobin. Thus,we have confirmed the formation of acetaldehyde haemoglobinadducts in vivo. It must be noted that the released acetaldehydecorresponds only to an index of the stable adducts. The levelswere higher in alcoholics than in controls (1.417±0.171and 1.295±0.139 nmol/mg Hb, respectively, P<0.001).In conclusion, this marker is not a convenient tool for themonitoring of alcohol exposure levels because of the low differencesbetween alcoholic and control haemoglobins.