[Are herbs safe during pregnancy and breastfeeding].

The review rejects the popular understanding of the security and potential benefits of herbal products for pregnant or lactating women. The survey does not claim to be exhaustive, but presents a number of publications concerning cases of proven harmful impact after use of herbal preparations during pregnancy and breastfeeding. Most of these studies come from developing countries and relate to Asian herbal products that are increasingly marketed and used in Europe.

Telematics applications to support the role of the community pharmacists as self-medication advisors. TESEMED Consortium.

One of the applications developed within the EU-funded projects TESEMED and TESEMED-II is a program for the information and continuous training of community pharmacists, with the aim to empower them as advisors of the citizens about self-medication topics. Several programs are being developed on the basis of ad-hoc developed protocols about minor ailments (currently, cold and flu, haemorrhoids, constipation and cough). Each program includes three modules: a hypertextual version of the protocol, an interactive scheme of it, and an educational tool called Encounter Simulator, that trains the pharmacist about the protocol by means of simulated pharmacist-customer interactions.

Autoantibodies against a kidney--liver protein associated with quinolone-induced acute interstitial nephritis or hepatitis.

In the present study we report on four cases of acute interstitial nephritis (AIN) and two cases of hepatitis induced by quinolone. We show by immunoblotting analysis that all sera from these patients contained autoantibodies that recognize a 65-kDa protein expressed in normal human kidney and liver microsomes. Only 6% of sera from healthy individuals who did not ingest quinolone recognized the same protein.

Monitoring of azathioprine-induced immunosuppression with thiopurine methyltransferase activity in kidney transplant recipients.

Thiopurine methyltransferase (TPMT), one of the enzymes involved in azathioprine metabolism, exhibits a wide range of activity in the normal population. We prospectively evaluated the monitoring of erythrocyte TPMT activity (using a radiochemical method) in kidney transplant recipients with regard to the efficacy of azathioprine. Three patterns in TPMT activity variation were observed.

Anti-liver microsomes autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug.

Anti-liver microsomes (anti-LM) autoantibodies in patients with dihydralazine-induced hepatitis were found to react specifically with cytochrome P4501A2 (P4501A2) but not with P4501A1 expressed in yeast and bacteria. These results were confirmed by immunoinhibition of methoxyresorufin-O-demethylase activity (supported by the P4501A subfamily); anti-LM antibodies more strongly inhibited this activity in yeast expressing P4501A2 than in yeast expressing P4501A1. Anti-LM were shown to be specific to the disease; in three cases, these autoantibodies were present at high titers during disease, whereas the titers decreased upon recovery and became undetectable a few months after recovery.

Enhancement of adriamycin cytotoxicity in sensitive and resistant sublines of human tumor cells by calcium antagonists.

The effect of the calcium antagonists cepharanthine and verapamil on adriamycin-induced cytotoxicity against sensitive (K 562 and Ov 2780) and resistant (K 562/ADM and AD 10) sublines of human tumor cells was evaluated. Nontoxic concentrations of cepharanthine moderately enhanced adriamycin cytotoxicity against sensitive sublines (2.1-2.

Ryodipine-induced enhancement of farmarubicin cytotoxicity against human leukemia cells in vitro.

Ryodipine is a recently developed dihydropyridine calcium channel blocker, chemically similar to nifedipine but with some advantages: light stability, low toxicity, etc. In recent years calcium antagonists have attracted attention not only with their cardiovascular activity but also as drugs increasing the antitumor effect of some cytostatics. In the present work the potentiating effect of ryodipine on the farmarubicin-induced cytotoxicity against K 562 human leukemia cells in vitro was evaluated.

Effect of calcium influx blocker verapamil on adriamycin-induced cytotoxicity in leukemia cells in vitro.

The effect of verapamil (calcium influx blocker) on adriamycin-induced cytotoxicity against sensitive and resistant subline of K 562 acute myelogenous human leukemia cells has been evaluated. Verapamil by itself at a concentration of 0.5 microgram/ml did not affect the cell growth.

On the in vitro cytotoxicity of 1-chloroethyl-2-chloromethyl-2-imidazoline hydrochloride.

The cytotoxic activity of the monofunctional alkylating agent 1-chloroethyl-2-chloromethyl-2-imidazoline hydrochloride (chlorimidazine), synthesized according to predetermined properties, is characterized. The data obtained show that the substance has a cell-cycle state nonspecific cytotoxic effect. The interaction of chlorimidazine with cellular DNA is traced.

Dependence of bleomycin-induced cytotoxicity and DNA damage on the in vitro culture growth phase of mouse tumour cells.

EMT 6/Ca/VJAC cells have been treated with various doses of bleomycin and the effects of these treatments in terms of cell killing and DNA damage have been determined. The experiments have been carried out with exponentially growing and plateau-phase cultures. Dose-response curves have been obtained using a clonogenic cell survival assay.

Potentiation of sensitivity to bleomycin and the drug-induced DNA damage in EMT6 cells by the calmodulin inhibitor trifluoperazine.

It has been shown that inhibitors of calmodulin can increase the sensitivity of rodent cells to Bleomycin by interfering with DNA repair functions. As a result of this study we have found that treatment of plateau-phase EMT6 cells with Bleomycin causes a decrease in cell survival due to DNA damage. This toxic effect can be potentiated by the addition of a nonlethal dose of the calmodulin inhibitor Trifluoperazine.

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumor cells.

To improve the efficacy of thermochemotherapy we have investigated the individual and combined effects of hyperthermia (44 degrees C) and the calmodulin inhibitor trifluoperazine (30 micrograms/ml) on early plateau phase cultures of mouse EMT6 cells for simultaneous exposures to bleomycin. We found that a non-toxic combination of hyperthermia and trifluoperazine: enhanced the cytotoxicity of bleomycin, increased the frequency of long-lived attachment sites of cellular DNA at the nuclear matrix, and resulted in an accumulation of DNA damage (strand-breaks and alkali-labile lesions) caused by the inhibition of strand-break rejoining and the impaired processing of DNA sites involving base loss. Our findings implicate a role for calmodulin in the control of chromatin structural changes during DNA repair and the study provides a rational basis for the use of calmodulin inhibitors in thermochemotherapy.

The effect of a normal tissue radioprotector Adeturone on the radiation sensitivity of Lewis lung carcinoma: an enhanced response.

The effect of the normal tissue radioprotector Adeturone (S-2-aminoethylisothiuronium adenosine-5'-triphosphate) on the response of primary and metastatic Lewis lung carcinoma to radiation was evaluated. It was found that this compound enhanced the antitumor effect of whole-body and local radiation. In experiments with whole-body radiation Adeturone eliminated the lethality due to radiation toxicity (for a daily treatment schedule--10 X 1 Gy/fraction) or reduced it from 50% to 25% (for an intermittent schedule--3 X 3.

Modification of the balance between damage and repair of bleomycin-induced DNA-strand breakage by hyperthermia.

It is well recognized that hyperthermia can greatly enhance the cytotoxic effect of bleomycin. It has been suggested that the mechanism of hyperthermic potentiation of bleomycin toxicity involves the inhibition of DNA repair function. We have investigated how hyperthermia can modify the repair capacity of bleomycin treated cells by monitoring the induction of DNA damage and repair, using two essentially different techniques (DNA unwinding assay and nucleoid sedimentation assay).

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumour cells: I. In vitro cytotoxicity.

Evidence in the literature suggests that hyperthermia (HT) or inhibitors of calmodulin can increase the sensitivity of rodent cells to bleomycin (BLM) by interfering with DNA repair functions. In an attempt to explore methods of improving the efficacy of thermochemotherapy we have investigated the individual and combined effects of HT (44 degrees C) and the calmodulin inhibitor trifluoperazine (TFP, 30 micrograms ml-1) on early plateau phase monolayer cultures of mouse EMT6 tumour cells for simultaneous exposures to BLM. Early plateau phase cultures are relatively resistant both to HT and to BLM.

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumour cells: II. DNA damage, repair and chromatin changes.

We have reported in the preceding paper that the treatment of plateau phase mouse EMT6 tumour cells with a combination of hyperthermia (HT; 44 degrees C) and trifluoperazine (TFP; 30 micrograms ml-1; an inhibitor of calmodulin) greatly enhances the cytotoxicity of the antitumour drug belomycin (BLM). The cytotoxic action of BLM is thought to arise from the induction of DNA damage in a manner which reflects chromatin accessibility. Thus we have studied the effects of the two modifiers (HT and TFP) on chromatin structure and BLM-induced DNA damage.

Antitumour activity of chlorimidazine on transplantable mouse tumour systems.

The antitumour activity of the newly synthesized compound, chlorimidazine (1-chlorethyl-2-chlormethyl-2-imidazoline hydrochloride), has been investigated on mouse tumour systems including L 1210 and P 388 leukaemias and Lewis lung carcinoma. It has been found that optimum treatment schedules resulted in 153% T/C in mice with L 1210 leukaemia, 159% T/C in mice bearing P 388 leukaemia and 68% TWI for Lewis lung carcinoma. Due to the results obtained the compound acts as a novel potential antitumour agent that warrants further evaluation.

Testing of 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) in mouse L1210 leukemia and 37 sarcoma.

The antimetabolite 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) has been investigated in an attempt to elucidate its effects on survival time of DBA/2 and B6D2F1 mice with L1210 leukemia and of outbred albino mice with 37 sarcoma. A significant increase in survival time was observed in mice with 37 sarcoma and slight effects were observed in mice with L1210 leukemia when treated with 3 x 12.5 or 3 x 25 mg/kg of 3-oxauracil.

Effect of thaliblastine on transplantable tumours in mice.

The antitumour activity of the alkaloid thaliblastine was studied on 7 ascitic and solid transplantable tumours in mice. It was found that the compound has a pronounced antitumour effect on ascitic tumour of Ehrlich, NK/Ly lymphoma (i.p.