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At least 55 records · Page 3Linked to original sources
PubMed2002

Embryotoxicity of cisplatin and a cisplatin-procaine complex (DPR) studied in chick embryo.

Cisplatin is widely used as an antitumor drug. To reduce its toxic side effects in patients, cisplatin has been bound with procaine in a cisplatin-procaine complex (DPR). The lethal and teratogenic effects of cisplatin alone and of complexed cisplatin were determined in the chick embryo in ovo in order to compare their influence on rapidly proliferating embryonic tissues. The embryotoxic (lethal + teratogenic) effect was examined after a single intra-amniotic injection of one of six different doses, ranging from 0.03 to 30.0 microg, on embryonic days (ED) 3, 4 or 5. The minimal embryotoxic dose was lower for cisplatin alone (0.03-0.3 microg) than for cisplatin in the DPR complex (0.3-3.0 microg), suggesting that cisplatin alone is more embryotoxic than complexed cisplatin. Both substances caused malformations in the surviving embryos evaluated on ED 9. These malformations included microphthalmia, microcephaly, hypoplasia of the upper and lower jaw, cleft beak, and haemocephaly. Moreover, heart septum defects and limb reduction deformities were found after exposure to the DPR complex. The embryotoxicity of complexed cisplatin exhibited a stage-response effect. It was highest on day 3 and gradually decreased until ED 5. Such an apparent stage-response effect was not observed for cisplatin alone. The embryotoxicity of procaine hydrochloride - a component of the complex - was also tested. Procaine hydrochloride alone did not produce any embryotoxic effect, not even after a single injection of the maximal tested dose (100.0 microg per embryo). We also examined the protective effect of procaine hydrochloride, whose separate administration at ED 4 was followed by the injection of 0.3 microg cisplatin. We did not observe any protective effect of procaine hydrochloride if injected separately.

Abnormalities, Drug-Induced↗
PubMed1998

Neurotoxic effect of cisplatin and the cisplatin-procaine complex DPR studied in organotypic cultures of chick embryonic dorsal root ganglia.

Neurotoxic effects of cisplatin and the cisplatin-procaine complex cis-diaminechloro-[2-(diethylamino)ethyl 4-aminobenzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) were compared in organotypic cultures of chick embryonic dorsal root ganglia maintained in a semi-solid (soft agar) culture medium. The changes of two characteristics of the neurite outgrowth, the mean radial length of neuritic processes growing out from the ganglia and the area of neurite outgrowth around the ganglion, were used as parameters to evaluate the toxic effect of both compounds. The drugs were administered to the cultures at concentrations ranging from 13 to 120 microM. The half-maximum inhibition concentration (IC50) was determined from the concentration-response curves for both the mean radial length of neurites and the area of neurite outgrowth. An analysis of these parameters revealed that DPR was significantly less neurotoxic than cisplatin. In fact, considering the mean radial length of neurite processes, the IC50s of cisplatin were 56, 65 and 66 microM after 24, 48 and 72 h of exposure, respectively. By contrast, for DPR the IC50s were 116 microM after 24 h, and greater than 120 microM after 48 and 72 h of exposure. When we considered the area index (i.e. the area of neurite outgrowth normalized for the area of the ganglia), the IC50s for cisplatin were 41, 52 and 55 microM after 24, 48 and 72 h of exposure, respectively, whereas for DPR the IC50s were 59 microM after 24 h, and greater than 120 microM after 48 and 72 h of exposure. Our results support previous findings of lower toxicity of DPR to non-neoplastic tissues, as compared to cisplatin.

Animals↗
PubMed1996

Extract of the marine alga Prymnesium patelliferum induces release of acetylcholine from cholinergic nerves in the rat bronchial smooth muscle.

An extract of the marine algal flagellate Prymnesium patelliferum enhanced the spontaneous as well as the K+ evoked (51 mM K+) release of [3H]acetylcholine and endogenous acetylcholine from autonomic cholinergic nerves of rat bronchial smooth muscle. The effects were concentration-dependent and reversible. The enhancement of the K+ evoked release by the algal extract was partly dependent on extracellular Ca2+ and was significantly suppressed by the organic Ca2+ blockers omega-conotoxin GVIA (1 microM), diltiazem (100 microM), nifedipine (100 microM) and flunarizine (100 microM). The enhancement of the spontaneous release seemed Ca2+ independent and not sensitive to the Na+ channel blocker tetrodotoxin. Sphingosine (20 microM), a protein kinase C inhibitor, strongly potentiated the enhancement of spontaneous release of [3H]acetylcholine induced by the algal extract whereas another protein kinase C inhibitor. 1-(5-quinolinesulphonyl)-2-methylpiperazine (H-7) (20 microM), was without effect. A similar potentiation as seen with sphingosine was observed with procaine (100 microM) and flunarizine (100 microM). The results indicate that the enhancement of the K+ evoked release of [3H]acetylcholine by the toxic extract of P. patelliferum was partly caused by activation of voltage-dependent Ca2+ channels. The increase in the spontaneous release of [3H]acetylcholine and endogenous acetylcholine induced by the algal extract alone may be caused by an ionophore-like property of the algal extract. This effect of the algal extract may be enhanced by compounds that facilitate the interaction of the algal toxin with the plasma membrane such as the lipophilic compounds flunarizine, procaine and sphingosine.

Acetylcholine↗
PubMedDate not supplied

Effect of diethylenetriaminepentaacetic acid and procaine on hemorrhage induced by rattlesnake venom.

Nineteen compounds and seven combinations of compounds were tested for their ability to neutralize the hemorrhagic activity of Crotalus atrox venom in vitro and in vivo. Two compounds and four combinations were effective in reducing hemorrhage in an in vivo test in which the venom was injected before injection of compounds. DTPA plus procaine HCl was the most effective combination and reduced hemorrhage when injected 1, 5, or 15 minutes after injection of venom. DTPA-procaine reduced hemorrhage induced by injection of C. atrox venom into dogs as well as mice. DTPA in combination with procaine did not reduce myonecrosis or lethality resulting from injection of venom into mice, but it could be used in conjunction with antivenin to treat local tissue damage resulting from rattlesnake venom poisoning.

Animals↗
PubMed1976

[Effect of drugs affecting sodium permeability on the muscle spindle of frogs].

Afferent discharges of about 10 Hz were recorded in the nerve from the isolated muscle spindle of the m. extensor longus digiti IV of the bullfrog subjected to a sustained stretch. When grayanotoxin-I, ventridine or aconitine was added to the Ringer's solution, the rate of discharges markedly increased and thereafter decreased. In these terms of decrease of discharges, abortive spikes were observed. The rate of discharges was markedly decreased by the application of procaine, diphenylhydantoin, chlorpromazine or tetrodotoxin. With the latter three drugs, abortive spikes were observed in the course of decrease of discharges. Increase of the discharge rate induced by grayanotoxin-I, veratridine and aconitine was antagonized by procain. No alteration was evident in the conduction of afferent discharges, when test drugs were applied to the nerve trunk in concentrations sufficient to change the rate of discharges when applied to the muscle spindle. These results suggest that the rate of the muscle spindle discharges is closely related to sodium permeability of the membrane.

Aconitine↗
PubMed2003

Preclinical in vitro evaluation of hematotoxicity of the cisplatin-procaine complex DPR.

We evaluated in vitro the inhibitory effect of cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) on colony formation by granulocyte/macrophage (CFU-GM) peripheral blood progenitor cells, representing a method to quantitate the toxicity of drugs to the hematopoietic system, and human leukemic cell lines. The results were compared with those obtained exposing cells to cisplatin and carboplatin. Our data showed that while DPR had a significantly better cytotoxic activity than cisplatin and carboplatin against HL60 and K562, and than carboplatin against Molt 4 cells, it showed 12 and 43 times less inhibitory effect on CFU-GM than cisplatin and carboplatin, respectively. These results suggest that the myelosuppressive activity of DPR could be lower than that of cisplatin and carboplatin, and, furthermore, that leukemic cells represent a preferential target for its cytotoxic activity compared to normal committed hemopoietic progenitor cells. All our results speak in favor of a better therapeutic index for DPR than for the other platinum compounds considered here.

Antineoplastic Agents↗
PubMedDate not supplied

Synthesis and antitumor activity of a new cis-diammineplatinum (II) complex containing procaine hydrochloride.

This paper refers to some of the chemical and biological properties of a new platinum (II) complex where the aromatic amino group of procaine is involved in the coordination with platinum and whose structure was defined by UV, IR, 1H-NMR, and elemental analysis. This new cationic platinum-triamine complex (DPR) displays excellent solubility (> 50 mg/ml) and stability in water. DPR has significant in vitro cytotoxicity against murine P388 leukemic cell line, human K562 erythroleukemic cell line and human Jurkat T cell line. The in vitro cytotoxic effects of DPR on P388 and Jurkat leukemic cells were comparable to those of cis-diamminedichloroplatinum (II) (DDP), while its activity on K562 cells was significantly better than that of DDP [IC50 = 1.07 +/- 0.36 (SD) microM vs 2.62 +/- 0.23 (SD) microM, P < 0.01]. The in vitro Pt accumulation rate for P388 cells was twice as rapid after DPR than after DDP exposure, while no difference in cellular platinum efflux was observed. The antitumor activity of DPR was tested in vivo against P388 leukemic cells in BDF1 mice and gave a % ILS value (75%) similar to that of the maximum tolerated dose (MTD) of DDP (8 mg/Kg). A comparative study of plasma urea nitrogen (PUN) levels and kidney morphological analysis in tumor-bearing mice receiving the LD50 dose of both drugs (39.3 mg/Kg and 16.5 mg/Kg for DPR and DDP, respectively), showed DPR to be less nephrotoxic than DDP. These results indicate that this new cationic platinum-triamine complex containing primary amine ligand is surprisingly active both in vitro and in vivo. In summary, the good characteristics of DPR in terms of high solubility, encouraging anticancer activity and absence of nephrotoxic effects make DPR a promising new platinum anticancer agent for preclinical development.

Animals↗
PubMed1983

Myocardial preservation during anoxic arrest. Chemical cardioplegia.

Two types of cardioplegic solution--the potassium arrest and the Bretschneider solution, both at 4 degrees C--were compared with regard to protective effect against ischemic damage during 60 min of anoxic cardiac arrest in the dog heart. Both solutions provided equally good protection, which was superior to that given by hypothermia alone.

Animals↗
PubMed1987

The relative buffering power of cardioplegic solutions.

Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystalloid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate.

Buffers↗
PubMedDate not supplied

[The effect of multimodal pathogenetic therapy on microcirculatory function in combined craniocerebral trauma].

It is known that severe combined maxillocranial trauma causes impairment of microcirculatory vessels of bulbar conjunctiva as well as changes of local (cervical) and systemic blood flow, prevailing on the side of injury. New trigeminosympathetic regional block was used to produce chemical neurotomy of sympathetic and parasympathetic portions of autonomous nervous system in the neck. This blockade induced positive changes of minute CBF and microcirculation of CNS and facial area. Modified trigeminal sympathetic regional blockade along with intravenous infusion of dimephosphone improves both microcirculation and reparative-proliferative process in impacted area.

Adolescent↗