In vitro interactions between aged garlic extract and drugs used for the treatment of cardiovascular and diabetic patients

Background  

Disease preventing effects gained by garlic consumption have been recognized since early period of history, making commercially available garlic supplements attractive to the general public. Possible pharmacokinetic interactions which could occur between applied drugs and aged garlic extract (AGE) are unknown.     

Immune responses to Aspergillus antigen in IL‐4‐/‐ mice and the effect of eosinophil ablation

BACKGROUND: Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen-induced cytokines are thought to regulate the inflammatory and immune responses in these animals. METHODS: In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild-type and IL-4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti-IL-5 or anti-IFN-gamma. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. RESULTS: The results demonstrate similar lung inflammation in all wild-type and IL-4-/- animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. CONCLUSIONS: It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways.     

Dose response of BaFBrl: Eu2+ storage phosphor plates exposed to megavoltage photon beams

The BaFBrI:Eu2+ storage phosphor plate (SPP) is a reusable radiation image detector, widely used in diagnostic computed radiography, x-ray crystallography and radioactive tracer studies. When exposed to ionizing radiation, the SPP stores a latent image until it is scanned with a red reading laser which causes blue photostimulated luminescent (PSL) photons to be emitted. The mechanism of formation of the latent image is still poorly understood, especially for megavoltage photon beams. In order to gain insight into this mechanism and aid applications to high-energy beam dosimetry, the authors have directly determined the SPP generation efficiency, W, the energy required to produce one quantum of emitted PSL when it is irradiated by 60Co and 6 MV photon beams. This was done in four steps: 1. The SPP, in a water-equivalent plastic (WEP) phantom, was exposed to a 60Co or 6 MV beam, which had been calibrated to give a known absorbed dose to water in a water phantom at the position of the sensitive layer of the SPP. 2. Monte Carlo simulations were used to calculate the ratio of the dose to the sensitive layer in the WEP phantom to the dose to water at the same position in a water phantom. 3. A bleaching experiment was used to determine the number of photons emitted by a plate given a known dose. 4. The generation efficiency was calculated from the number of photons and the dose. This method is much more direct than previous calculations for kilovoltage x-ray beams based on quantum noise analysis. W was found, within experimental uncertainty, to be 190 eV for 60Co and 160 eV for 6 MV, independent of dose. The values for kilovoltage x-ray beams determined previously agree, within their large uncertainty, with these values for megavoltage beams.     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

Mechanism of interaction between cisplatin and human recombinant interferon gamma in human ovarian-cancer cell lines

Human ovarian carcinoma cells (2008 and its cisplatin-resistant sub-line 2008/C13*) were sensitized to cisplatin by treatment with human recombinant gamma interferon (IFNγ). IFNγ produced no significant change in the uptake of CDDP. Exposure of 2008 and 2008/C13* cells to IFNγ resulted in a time-dependent decrease of cellular glutathione and total glutathione-S-transferase activity, principally the π isoform. By contrast, the treatment of 2008 and 2008/C13* cell lines with IFNγ induced rather than suppressed metallothionein II_A mRNA levels. IFNγ changed neither the formation of total platinum-DNA adducts, nor DNA repair. A significant decrease in c-erbB-2 expression was observed both in sensitive and in resistant cell lines after treatment with IFNγ, and this decrease was dose-dependent. Our results indicate that the mechanism of IFNγ-induced sensitization in human ovarian-cancer cell lines is multifactorial. © 1995 Wiley-Liss, Inc.     

Histiocytosis-X in gynecology

(1) Histiocytosis-X can manifest itself in virtually every organ, but in gynecology it is an absolute curiosity. (2) Differential diagnosis must exclude specific and nonspecific ulcerations and granulations such as syphilis, tuberculosis, Boeck's disease, and also neoplastic processes like lymphomas, sarcomas, carcinomas, and malignant diseases of the hemopoietic system. (3) The diagnosis by light microscopy alone, as in our case, may be insufficient; therefore, electron microscopy should be used. As soon as the diagnosis is confirmed histologically, an extensive examination of all organs is necessary in order to establish an exact prognosis and an optimal plan of therapy. (4) Because of the unknown etiology of histiocytosis-X, a causal treatment is not yet possible. In spite of this, with a symptomatic, individualized therapy by means of excision, low-dose irradiation and cytotoxic agents a 5-year survival of 90% was obtained for the patients. (5) Because of its rarity and multidisciplinary character, histiocytosis-X is a challenge to interdisciplinary and interregional cooperation. Though not being a malignoma in the strict sense, diagnosis, therapy, and in part prognosis are not essentially different from a malignant disease.     

Treatment effects on nigrostriatal projection integrity in partial 6-OHDA lesions: comparison of L-DOPA and pramipexole

There is controversy over potential effects of dopaminergic replacement therapies on the partially lesioned nigrostriatal dopaminergic projection. We evaluated indirect (levodopa, L-DOPA) versus direct (pramipexole, PRA) dopaminergic treatment effects on nigrostriatal lesion severity as measured with vesicular monoamine transporter type-2 (VMAT2) binding. Prior studies have shown that striatal VMAT2 density provides an objective estimate of dopaminergic neuronal integrity, without confounding effects of compensatory regulation. Partial unilateral median forebrain bundle lesions were made by injection of 6-hydroxydopamine in adult male Sprague-Dawley rats. Lesion severity was estimated using rotational behavior after injections of apomorphine and amphetamine. Rats were ranked and matched in pairs by rotation and assigned to receive either PRA (1 mg/kg/day) or L-DOPA/benserazide (100/25 mg/kg/day) ip via osmotic pump. After 4 weeks of drug treatment, in vitro autoradiography was performed with [(3)H]methoxytetrabenazine to measure striatal VMAT2 binding density. Lesion-to-intact VMAT2 density correlated with rotation in both treatment groups. There was no treatment effect on VMAT2 expression in the partially lesioned striatum and thus no differential effect of indirect versus direct dopamimetic treatment on nigrostriatal integrity.