ABSTRACT
OBJECTIVE: To investigate the effect of the fermented wheat germ extract (Avemar)in patients with severe rheumatoid arthritis (RA). METHODS: Fifteen female RA (Steinbrocker II-III) patients, who had unsuccessfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received Avemar as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used. RESULTS: At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of Avemar were observed. CONCLUSION: Supplementation of standard therapies with a continuous administration of Avemar is beneficial for RA patients.
Subject(s)
Arthritis, Rheumatoid/diet therapy , Plant Extracts/administration & dosage , Triticum , Arthritis, Rheumatoid/physiopathology , Dietary Supplements , Female , Health Status , Humans , Joints/drug effects , Joints/physiopathology , Pilot Projects , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.
Subject(s)
Colorectal Neoplasms/drug therapy , Plant Extracts/pharmacology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/radiotherapy , Colorectal Neoplasms/surgery , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Treatment Outcome , Triticum/chemistryABSTRACT
It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).
Subject(s)
Colonic Neoplasms/prevention & control , Lectins/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Triticum/therapeutic use , Animals , Azoxymethane/toxicity , Body Weight , Carcinogens/toxicity , Colon/drug effects , Colon/pathology , Colonic Neoplasms/chemically induced , Colonic Neoplasms/pathology , Kidney/drug effects , Liver/drug effects , Lung/drug effects , Male , Plant Lectins , Rats , Rats, Inbred F344ABSTRACT
Tenascin is generally classified as an anti-adhesive protein. Many cells do not adhere to tenascin or if they adhere they do not spread. In this study we analysed the stromal expression of tenascin-C in primary, second primary and recurrent breast carcinomas and the ability of tenascin-C to stimulate the focal adhesion plaques in MDA-MB-435 breast carcinoma cell line. To assess the tenascin-C expression formalin-fixed, paraffin-embedded specimens of 20 specially selected breast carcinomas and their recurrences (14) or a second primary breast cancer of the same patient (6) were examined with immunohistochemical methods. We also studied the effect of tenascin-C on focal adhesion plaques added to MDA-MB-435 breast carcinoma cell line. During a median 2,9-year patient follow up 14 local recurrences and 6-second primary breast carcinomas developed in the 20 patients. In 3 cases a second recurrence occurred. The presence of tenascin in tumor cells, in the proliferating and some normal ducts, near to the tumor cell nests, in the stroma and in ductal carcinoma in situ component of the invasive carcinoma may suggest the role of tenascin played in tumor cell migration. Soluble tenascin added to the cell culture had minimal or no effect on focal adhesion plaques. Tenascin only seems not to be of prognostic value in predicting the local recurrence of breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma/metabolism , Neoplasm Recurrence, Local/metabolism , Tenascin/metabolism , Tenascin/pharmacology , Tumor Cells, Cultured/drug effects , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma/pathology , Carcinoma/surgery , Female , Fluorescent Antibody Technique, Indirect , Focal Adhesions/metabolism , Focal Adhesions/pathology , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgeryABSTRACT
Replication and transformation by adenoviruses involve their interaction with several cellular regulatory mechanisms. Alterations in the phosphorylation of both cellular and viral polypeptides by secondary messenger cAMP and cGMP dependent protein kinases (PK) determining outcome of viral effects may be influenced by external physiological stimuli, among them by prostaglandins (PG). HEp-2 cells infected with representative serotypes of human adenovirus (Ad) groups and two temperature sensitive (ts) mutants were treated prior to and late postinfection at permissive (32 degrees C) and restrictive (39 degrees C) temperatures by different PGs. PGF2 alpha augmented replication of both oncogenic Ad-12 and latent Ad-1, Ad-5 serotypes as well as Ad-5 mutants at 32 degrees C and that of mutant ts18 (defective in pVI phosphorylation) but not that of ts19 (defective in pX phosphorylation) at 39 degrees C. PGE2 was shown to be inhibitory, but the replication of nononcogenic Ad-8 was not affected by PGs. PGI2 slightly enhanced all types, while indomethacin, inhibitor of endogenous PG synthesis with double unsaturated bonds moderately inhibited replication of all serotypes, except that of Ad-12. It is concluded that augmenting effects by PGF2 alpha during viral entry, cytoplasmic transport and late phase, but not in the early phase of adenovirus replication cycle, are due to enhancement of the non-specific cellular mechanisms, which support mitosis in the uninfected cells. Their activities are controlled by the late viral replication machinery, which process had been programmed in the early interaction of viral and cellular regulatory factors.
Subject(s)
Adenoviruses, Human/drug effects , Prostaglandins/pharmacology , Adenoviruses, Human/genetics , Adenoviruses, Human/physiology , Cell Line , Cyclic AMP/metabolism , Cyclic GMP/metabolism , Cytopathogenic Effect, Viral/drug effects , Dinoprost/pharmacology , Dinoprostone/pharmacology , Epoprostenol/pharmacology , Humans , Indomethacin/pharmacology , Mutation , Temperature , Virus Replication/drug effectsABSTRACT
Several prostaglandins are continuously produced in every cell. They activate protein kinases by regulating cyclic nucleotide synthesis. Modifications of the phosphorylation of virus polypeptides and alterations in the microtubular system of host cells can result in the reactivation of latent viruses. Prostaglandins have a very important role in directing cell cycle. Abnormal tyrosine kinase activities during viral cell transformation are responsible for the malignant changes and consequently severe alterations are observed in the endogenous prostaglandin production. External modification of this cascade can revert malignant signs to normal. Furthermore, virus infection or cell transformation could be promoted by the immunosuppressive effects of overproduced prostaglandins. They damage interferon release and co-operation between the different cell types of the immune system. Enzyme inhibitors of the prostaglandin cascade or prostaglandin analogues may exert influence on all of these phenomenon, providing future therapeutic agents.
Subject(s)
Prostaglandins/metabolism , Virus Diseases/metabolism , Animals , Cell Transformation, Viral , Humans , Immune System/metabolism , Nucleotides, Cyclic/metabolism , Virus Diseases/immunology , Virus ReplicationABSTRACT
The objective of this trial was to define the antitumor activity and toxicity of etoposide for second-line treatment of patients with bulky ovarian carcinoma. Between February 1, 1986 and November 1, 1988 we recruited 82 patients. Out of them 77 (93.9%) were evaluable for toxicity and 71 (86.6%) for response. Patient characteristics are as follows: median age 57 years (range 15-75), median performance status: WHO 1, prior chemotherapy with more than 3 drugs 24 patients, with previous cisplatin 63 patients, with previous adriamycin 47 patients, with previous irradiation plus chemotherapy 17 patients. The following treatment schedule was applied: each patient started with 150 mg/m2 of etoposide administered i.v. on days 1-3. If this first cycle was well tolerated the dosage was escalated to 200 mg/m2 days 1-3. This higher dosage was then repeated at 4-week intervals. For evaluation of response the WHO criteria were used. One patient (1.4%) achieved complete remission and 5 (7.0%) partial remission. In 48 patients (67.6%) minor response or stabilisation of the disease were observed. Seventeen patients (24%) showed no response. The median duration of remission was 5.5 months (range 2-20). The median duration of stabilisation was 3 months (range 2-24). The median survival time was 10 months with a range of 2-30 months. The myelotoxic side-effects are as follows: WBC less than 2,000 was recorded in 6 patients and greater than 1,000 in 2 patients. Thrombocytopaenia with platelet count less than 50,000 occurred in 1 patient. 26 patients had anaemia WHO grades 2 and 3. Non-haematological toxicity consisted of nausea and vomiting (WHO grade 2:20 patients and grade 3:2 patients), alopecia (WHO grades 2-3:14 and 24 patients, respectively). Though the remission rate in this trial was low, the 10-month median survival with an acceptable quality of life can be taken as a fairly good salvage therapy result.
Subject(s)
Etoposide/therapeutic use , Ovarian Neoplasms/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Clinical Trials as Topic , Doxorubicin/therapeutic use , Drug Evaluation , Etoposide/adverse effects , Female , Humans , Middle Aged , Ovarian Neoplasms/mortality , Remission InductionABSTRACT
443C81 is a synthetic enkephalin thought to act on peripheral opiate receptors. The analgesic, central, cardiovascular and endocrine effects of two i.v. doses of 443C81 were investigated in 12 healthy male volunteers. Its effects were compared with those of placebo and the classical opiate dipipanone given orally using a double dummy design. 443C81 produced dose-related analgesia; dipipanone 10 mg had a greater effect than the high dose 443C81. In contrast to dipipanone, 443C81 did not cause significant miosis or reduce minute volume on rebreathing CO2 and there was no evidence of sedation. Dry mouth was reported frequently and associated with reduced salivation after all active treatments. Both 443C81 and dipipanone increased circulating prolactin and growth hormone and reduced cortisol levels. This novel enkephalin appears to possess analgesic activity and some other properties of opiates but is devoid of clinically relevant narcotic effects.
Subject(s)
Analgesics , Central Nervous System/drug effects , Endocrine Glands/drug effects , Hemodynamics/drug effects , Adult , Amino Acid Sequence , Analgesics, Opioid/pharmacology , Blood Pressure/drug effects , Double-Blind Method , Enkephalins/pharmacology , Heart Rate/drug effects , Hormones/blood , Humans , Male , Methadone/analogs & derivatives , Methadone/pharmacology , Molecular Sequence Data , Pain/drug therapy , Pain/physiopathology , Pain Measurement , Pupil/drug effects , Random Allocation , Salivation/drug effectsABSTRACT
We have studied 16 healthy men to evaluate preliminary pharmacodynamics and kinetics of BW443C given by i.v. infusions. Four volunteers received escalating doses at weekly intervals, starting at 0.1 microgram.kg-1 for 60 min and increasing to a maximum of 2.0 micrograms.kg-1.min-1 for 180 min. Subsequently 12 different subjects received single i.v. infusions of 10 micrograms.kg-1.min-1 for 20 min. Subjective effects were reported and objective measurements made of central nervous and cardiovascular effects. Blood was sampled at intervals on all occasions, plasma concentrations were determined by radioimmunoassay and pharmacokinetic profiles were analysed using NONLIN. Dry mouth and some nasal stuffiness were reported and postural hypotension occurred in 5/16 subjects at plasma concentrations greater than 0.8 microgram.ml-1. Supine blood pressure was well maintained in all subjects and hypotension resolved within 60-90 min of discontinuing the infusion. There was no evidence of sedation, mood change, nausea, vomiting, miosis, change in accommodation or respiratory depression. Rapid infusions produced transient feelings of warmth, heavy eyelids, heavy legs, and increased bowel sounds, which resolved despite increasing plasma concentrations. The disposition of the peptide was adequately described by a 2-compartment model with a mean +/- SD plasma clearance of 123 +/- 18 ml.min-1 and a half-life of 2.0 +/- 0.4 h.
Subject(s)
Oligopeptides/pharmacokinetics , Adult , Blood Pressure/drug effects , Drug Administration Schedule , Drug Evaluation , Heart Rate/drug effects , Humans , Hypotension, Orthostatic/chemically induced , Infusions, Intravenous , Male , Oligopeptides/administration & dosage , Oligopeptides/adverse effects , Oligopeptides/blood , Oligopeptides/pharmacology , Time Factors , Xerostomia/chemically inducedABSTRACT
The mechanism of the pain relief produced by opiates in normal volunteers in the cold induced pain test has been investigated. In a double-blind placebo controlled study, hand skin temperature during a 3 min immersion in water at 1 degree C was not affected by either the opioid dipipanone 8 mg or the vasodilator nifedipine 10 and 20 mg. During this immersion, dipipanone produced significant pain relief. Nifedipine reduced pre-immersion blood pressures and raised heart rates, however, it did not significantly alter pain scores. It is concluded that vasodilatation and local warming do not play a role in the relief of pain by opiates in the cold immersion test.
Subject(s)
Analgesics, Opioid/pharmacology , Methadone/analogs & derivatives , Pain/drug therapy , Skin Temperature , Adult , Blood Pressure/drug effects , Cold Temperature , Double-Blind Method , Female , Heart Rate/drug effects , Hemodynamics/drug effects , Humans , Male , Methadone/pharmacology , Random Allocation , Skin Temperature/drug effectsABSTRACT
The sensitivity of the cold-induced pain (CP) model to the non-steroidal anti-inflammatory drug (NSAID) indomethacin was studied in healthy volunteers. Effects on the central nervous system were also sought. Subjects received single oral doses of indomethacin 50 and 100 mg, dipipanone 8 mg and placebo, according to a double-blind, randomised, balanced, cross-over design with an interval of 7 days between occasions. A test battery was performed before each treatment and then at 45, 105 and 165 min post treatment. Pain scores were unaltered by indomethacin at either dose, but the drug certainly affected the CNS, increasing respiratory drive and changing self-assessed mood. It is concluded that the CP model is insensitive to indomethacin, even in doses which have clear-cut CNS effects. The respiratory stimulant action of indomethacin may deserve further study.
Subject(s)
Central Nervous System/drug effects , Indomethacin/therapeutic use , Pain/drug therapy , Adult , Affect/drug effects , Central Nervous System/physiopathology , Clinical Trials as Topic , Cold Temperature , Double-Blind Method , Female , Humans , Male , Pain/etiology , Pain/physiopathology , Random Allocation , Respiration/drug effectsABSTRACT
1 Twelve healthy volunteers took part in a study of the interaction between the antihistamine triprolidine and the opioid dipipanone in the cold induced pain (CP) test and tests of sedation. They received placebo, triprolidine 2.5 mg, dipipanone 8 mg or the combination of the two active treatments according to a double-blind, randomised, balanced, crossover design. 2 Antihistamine activity was demonstrated by triprolidine reducing the size of wheals and flares produced by intradermal histamine 1.6 micrograms. However, triprolidine produced no analgesia in the CP test, nor did it enhance the analgesia produced by dipipanone alone. 3 Neither treatment alone produced statistically significant sedation, assessed by visual analogue scales (VAS), side effect check list, body sway and reaction times. However, the combination did cause significant sedation. 4 Dipipanone reduced pupil size, depressed respiration, and decreased salivation. Triprolidine had no effects on pupil size and respiration, but reduced salivation slightly. It was concluded that histaminergic (H1) mechanisms are unlikely to be involved in pain produced by cold.