Biomedical subjects
Publications and source records attributed to C Pellecchia.
Ranitidine has been used extensively in a variety of gastrointestinal illnesses. To date only scattered reports of hematological side effects have appeared in the literature. We present a case report of leukocytosis and eosinophilia occurring in a patient receiving ranitidine therapy.
Specific binding sites for cholecystokinin (CCK) have been identified and characterized in fundic glands isolated by collagenase treatment from guinea pig gastric mucosa using a biologically active 125I-labeled derivative of the C-terminal octapeptide of CCK (125IIE-CCK-8). The time course of binding to these glands was rapid, temperature dependent and saturable. At 24, 30 and 37 degrees C, half-maximal binding was reached at 5 min and full binding at 30 min. The addition of a large excess of CCK-8 after 15 and 30 min of binding at 24 degrees C caused a prompt and rapid decline in radioligand bound showing that the interaction was reversible. There was a progressive decline in the amount of 125IIE-CCK-8 bound to fundic glands with increasing concentrations of CCK-8 and other structurally related peptides. Gastrin II displaced 50% of the radioligand at 1.6nM, CCK-8 at 3.2nM, gastrin I at 16nM, and desulfated-CCK-8 and pentagastrin at 59nM. Secretin did not displace the radioligand from fundic glands at 1.0uM. The binding was also tissue specific as glands isolated from the antral mucosa did not contain specific binding sites for 125IIE-CCK-8. This data provides evidence for specific receptors for CCK on gastric fundic glands that may be involved in the control of acid and pepsinogen secretion.
We treated two patients with laceration of the liver that was precipitated by cardiopulmonary resuscitation (CPR) and recognized antemortem. Both patients had myocardial infarctions and had received heparin sodium therapy. They had excruciating abdominal pain and bled massively, resulting in hypovolemic shock. When severe abdominal pain associated with hypovolemic shock occurs in a patient who has received CPR, hepatic laceration, hematoma, or both should be considered. This is even more imperative to recognize in the patient who has received anticoagulation therapy.
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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.
The distribution and elimination kinetics of cis-diamminedichloroplatinum (II) (DDP) in female BDF1 mice bearing 6-day P388 leukemia were investigated in the presence and absence of procaine hydrochloride (P.HCl) exposure. DDP was administered as a single i.p. dose of 8 mg/kg in a 0.9% NaCl solution 6 days after tumor inoculum. P.HCl was administered as a single i.v. dose of 40 mg/kg immediately after DDP. The combined treatment with P.HCl produced marked changes in the plasma concentration-time profile of Pt. The unbound fraction of Pt was significantly increased both in the ascites fluid and plasma following DDP + P.HCl administration. P.HCl treatment induced a significant reduction (P < 0.01) in the rate constant of the protein-bound of Pt in plasma of tumored mice. Urinary excretion of Pt was unaffected by P.HCl, and there was no significant P.HCl-induced modification in the concentrations of Pt in the P388 leukemic cells. A statistically significant reduction of kidney and spleen Pt content was observed in female mice exposed to a dose of 8 mg/kg DDP + P.HCl. A similar reduction was observed in kidneys and testes of tumored mice receiving 16 mg/kg DDP along with 40 mg/kg P.HCl, which also showed lower renal and testicular cisplatin-DNA adducts after DDP + P.HCl than after DDP treatment. Potential explanations for the ability of P.HCl to interfere with the pharmacokinetics and biodistribution of DDP are discussed.
Para-aminobenzoic acid (PABA) has been previously reported as being an inhibitor of DDP toxicity, and its use did not result in any observable loss in antitumor activity of DDP. The following studies investigated the effect of PABA on the pharmacokinetics and urinary excretion of cis-diamminedichloroplatinum(II) (DDP) in male Sprague-Dawley rats. DDP was injected i.p. at the dose of 7.5 mg/kg in normal saline alone and with a concurrent i.p. injection of PABA (100 mg/kg). The combined treatment with PABA produced a significant increase in the plasma concentrations of total platinum, without affecting the levels of platinum species in the plasma ultrafiltrate. Similar results were also obtained in additional studies in rats receiving the same dose of DDP plus PABA through different routes of administration (i.e. DDP i.v. and PABA i.p.). Both the area under the total platinum plasma concentration-time curve (AUC) up to 60 min and AUC0-120 min were increased by PABA by an average of 113% and 66% respectively. The administration of PABA in rats was followed by a substantial reduction in total urinary excretion of platinum (P < 0.05) and by a significant (P < 0.01) lower concentration of DDP derived platinum in the urine collected during the first 4 h after treatment. The renal clearance of filterable platinum was reduced by PABA by an average of 67.5% from 1.11 to 0.36 ml/min/100 g body wt. Total 24-h urinary excretion of platinum was also decreased, although not significantly, by PABA. Urine volumes from rats treated with DDP+PABA were similar to those from animals receiving DDP alone. HPLC studies indicate that PABA reacts readily with the species generated from DDP in vitro, while the agent is essentially unreactive toward the parent DDP and does not influence its decomposition rate. The overall data of this study suggest that the protective effect exerted by PABA on DDP toxicity may be at least partially due to its ability to interact with aquated DDP as well as to alter the renal excretion of platinum.