Stabilization of rat serum proteins following oral administration of fish oil

The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated by a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate that in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at 70 degrees C for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palmitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.     

Physicians and death: Comments and behaviour of 605 doctors in the north-east of Italy

The aim of this study was to determine the influence of socio-demographic and professional factors on physicians' attitudes to the terminally ill. Between May 1992 and May 1993, a survey was conducted in the province of Pordenone (north-east, Italy) in order to analyse a number of specific issues, such as emotional involvement, the need for aggressive treatments and the communication of diagnosis and prognosis. After obtaining a list of board-certified physicians from the Medical Association office in Pordenone, a modification of the cancer questionnaire of Haley and Blanchard (QSPT) was mailed to 916 doctors. Of these, 605 (60%; 487 male, 118 female; mean age 41 ± 11 SD) returned the completed questionnaire. Within the group of responders, we identified three main subgroups, according to their type of activity: general practitioners (175, 29%), hospital doctors (235, 39%) and other doctors (195, 32%). In age, sex and activity, the only significant difference between responders and non-responders was age (mean age 41 and 43 years respeetively). Most of the responders (77%) stated that they were able to deal with the terminally ill patient and his/her needs; 44%, however, admitted that patients' anxiety is sometimes unbearable. For the vast majority of the doctors polled (91%), providing a comfortable environment for an incurable patient was more important than pursuing aggressive treatment, but only 44% were convinced of the uselessness of aggressive care. To the question on whether to disclose information about imminent death to allow patients to prepare spiritually, 37% answered No, 38% Yes, and 25% were uncertain. Almost all responders (95%), however, believed in the beneficial effect of hope on the terminally ill. Ourresults suggest that doctors' professional and, most of all, sociodemographic and cultural factors determine the relationship with the patient on both the emotional and the clinical decision-making levels.     

Effects of long-term treatment in Wilson's disease withd-penicillamine and zinc sulphate

The results of treatment withd-penicillamine (d-P) or zinc sulphate (Zn) in 67 newly diagnosed cases of Wilson's disease have been compared. All patients (7 with hepatic, 1 with psychiatric and 59 with neurological or preclinical forms) were fully compliant. During 12 years of observation, 34 patients receivedd-P and 33 Zn as the primary treatment. Fifteen patients (44%) discontinuedd-P, in 10 cases owing to side effects. Four (12%) patients discontinued Zn, in 2 cases because of side-effects. One patient who received Zn deteriorated during the first few months after the initiation of therapy. The effectiveness of longterm treatment withd-P and Zn was similar in those patients who were able to continue the initial therapy. Zn was tolerated better thand-P; we suggest, therefore, that it may be recommended as an initial therapy for patients in the preclinical stage of Wilson's disease or with neurological presentation of the disease. More observation is needed for patients with the hepatic and psychiatric forms of the disease.     

Clinicopathological study of familial late infantile Hallervorden-Spatz disease: a particular form of neuroacanthocytosis

The cases of two sisters with late infantile Hallervorden-Spatz disease are reported, one of whom has died. Autopsy of the deceased patient showed typical pallidal lesions, such as axonal spheroids and iron deposits, without involvement of the substantia nigra. Ultrastructural examination revealed that pallidal axonal enlargements consisted of collecition of mitochondria, dense bodies, vesicles and amorphous material. In the living patient, brain MRI showed the classical tiger's eye appearance of the globus pallidus. Retinitis pigmentosa, acanthocytosis and slight neuromuscular involvement with an increase in serum creatine kinase were observed in both subjects. The appearance of the globus pallidus on MRI was in line with the pathological abnormalities. Ultrastructural differences between the principal disorders characterized by neuroaxonal dystrophy are compared and the clinical spectrum and similarities of the different forms of neuroacanthocytosis analysed.     

Morpholinylanthracyclines: cytotoxicity and antitumor activity of differently modified derivatives

Summary The relationship between different chemical modifications on morpholinylanthracyclines and their ability to overcome multidrug resistance (MDR) has been evaluated testing all compounds in vitro on LoVo and LoVo/DX human colon adenocarcinoma cells and in vivo on disseminated P388 and P388/DX murine leukemias.Results obtained led us to the following conclusions: 1) the insertion of the morpholinyl or the methoxymorpholinyl group on position 3 of the sugar moiety confers the ability to overcome MDR in vitro and in vivo; conversely, 4 morpholinyl compounds are effective on MDR cells only in vitro and result inactive in vivo on DX-resistant leukemia; 2) all chemical modifications performed on 3 morpholinyl or methoxymorpholinyl derivatives, that is substitutions on the aglycone or on position 2 of the morpholino ring, do not interfere with the activity of the compounds: all derivatives present in fact the same efficacy on sensitive and resistant models.It is concluded that position 3 in the sugar moiety plays a crucial role in the ability of morpholinylanthracyclines to overcome MDR.     

Possible correlation between low antigenic drift of A(H1N1) influenza viruses and induction of HI antibodies

This study examined whether, during a seven-year period of low A(H1N1) influenza virus antigenic drift (1988–1989 and 1994–1995, winters), humoral antibody response of elderly volunteers to influenza vaccines could suggest a lack of antibody pressure for drift. In all the years studied A/Taiwan/1/86, the A(HIN1) vaccine component, had a low ability to induce protective hemagglutination-inhibiting (HI) antibody titres ( 1:40). However a similar low immunogenicity was found for some of the different A(H3N2) strain variants of influenza virus, co-circulating in the same period and showing a regular extent of antigenic variations.Although our data could be at least in part explained by the type of study population (elderly and repeatedly vaccinated), postepidemic serological studies did not evidence a consistently lower ability in mounting protective immune response in elderly people as compared with younger against the influenza strains studied. Therefore, our present results did not exclude a true low immunogenicity of A/Taiwan and of some A(H3N2) influenza strains, circulating in the winters examined. This suggests that, besides the necessity to evade prior immunity, additional factors could influence the frequency of influenza viruses antigenic drifts.Abbreviation HI hemagglutination inhibiting     

Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy

Background: The anticancer role of tumor necrosis factor-alpha (TNF-) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-) activity to abrogate TNF- toxicity. Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF- and anti-IFN- antibody (Ab) to evaluate the effect on the acute lethality of TNF- and their efficacy as evaluated by tumor growth rate, tumor histology, and survival. Results: Anti-IFN- Ab decreased TNF- lethality. Anti-IFN- Ab alone increased tumor growth significantly more than did nonimmune IgG (p₂<0.0001). Tumor-bearing mice that received nonimmune IgG and TNF- had slower tumor growth (p₂<0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN- Ab abrogated the antitumor effect of TNF-, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN- Ab and high-dose TNF- were comparable with those in mice that received a lower, equitoxic dose of TNF- alone. Conclusions: Blocking endogenous IFN- accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF- equally. This suggests that blocking endogenous IFN- activity is not a useful strategy for limiting TNF- treatment toxicity.Presented in part at the 45th Annual Cancer Symposium of The Society of Surgical Oncology, New York, New York, March 15–18, 1992.     

Barriers to follow‐up of abnormal screening mammograms among low‐income minority women

Objective. To describe factors related to compliance diagnostic follow‐up among minority women of low socioeconomic status with abnormal screening mammograms.

Methods. A retrospective cross‐sectional survey using a structured telephone interview. Three cancer screening clinics at an urban inner‐city public hospital. All women with abnormal screening mammograms between September 1990 and January 1992 were eligible; women were interviewed in August 1992. Abnormal mammograms were those requiring specific, non‐routine clinical follow‐up; non‐compliance was defined as delayed follow‐up (four to six months after the date of the mammogram), or no follow‐up at the time of interview (more than 6 months after abnormal).

Results. Sixty‐two of 442 screened women had abnormal results; the overall rate of non‐compliance with follow‐up was 50%. Among the 42 (68%) women who agreed to be interviewed, non‐compliers were less likely to state that they had been told to receive follow‐up than compilers (65% versus 100%; p = 0.008). Non‐compliant women were less likely to have suspicious mammography interpretations (p = 0.05), and more likely to report barriers to follow‐up, such as cost of lost wages and medical care, system barriers, or fears, than compliant women (61.9% versus 9%, p = 0.01). There were no differences between the two groups for age, education, insurance, source of care, family history, knowledge or attitudes.

Conclusions. These preliminary results suggest that follow‐up of low income, minority women with abnormal screening mammograms could be enhanced by improved communication of results. Future studies should extend these findings with larger samples and in other settings and populations.     

Circadian rhythm of glucose utilization in the pineal body of rats of different ages

Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 mol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging.     

Ependymomas of the filum terminale in childhood: report of four cases and review of the literature

Four cases of ependymoma of the filum terminale occurring in childhood are reported. The clinical, therapeutic and prognostic features seen at this age and in adults were compared.