Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin.

The aim of the study was to characterize the platelet count (PLT) dynamics in peritoneal carcinomatosis patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal oxaliplatin (HIO). Data from patients treated with CRS alone (N = 18) or CRS and HIO (N = 62) were used to estimate the baseline platelet count (PLT0), rate constants for platelet maturation (k tr ) and platelet random destruction (k s ), feedback on progenitor cell proliferation (γ), and the drug-specific model parameters (α, ß). Plasma oxaliplatin concentrations, C p , reduced the proliferation rate of progenitor cells (k prol) according to a power function α × C p (ß) . The surgery effect on k prol and k s was explored. The typical values (between subject variability) of the PLT0, k tr , k s , γ, α, and ß were estimated to be 237 × 10(9) cells/L (32.9%), 7.09 × 10(-3) h(-1) (47.1%), 8.86 × 10(-3) h(-1) (80.0%), 0.621, 0.88 L/mg (56.9%), and 2.63. Surgery induced a maximal 2.09-fold increase in k prol that was attenuated with a half-life of 8.42 days. Splenectomy decreased k s by 47.5%. Age, sex, body surface area, sex, total proteins, and HIO carrier solution did not impact the model parameters. The model developed suggests that, following CRS and HIO, thrombocytopenia and thrombocytosis were reversible and short-lasting; the severity of the thrombocytopenia and thrombocytosis was inversely correlated, with splenectomized patients having thrombocytopenia of lower severity and thrombocytosis of higher severity; and the HIO dose and treatment duration determine the severity and duration of the thrombocytopenia. Higher HIO dose or longer treatment duration could be used without substantially increasing the risk of major hematological toxicity.

Preventive effects of Egyptian sweet marjoram (Origanum majorana L.) leaves on haematological changes and cardiotoxicity in isoproterenol-treated albino rats.

We made an attempt to evaluate/compare the cardioprotective activity of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) against isoproterenol (ISO)-induced myocardial infarcted rats (150 mg/kg body weight, twice at an interval of 24 h on days 29 and 30). The present study showed (probably for the first time) that both MLP and MLE (especially the high dose) significantly alleviated (P < 0.05-0.001) erythrocytosis, granulocytosis, thrombocytosis, shortened clotting time, the increase in relative heart weight, myocardial oxidative stress and the leakage of heart enzymes (creatine phosphokinase (CPK), CPK-MB isoenzyme, lactate dehydrogenase and aminotransferase) in ISO-treated rats through reactivating non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant defence system and inhibiting the production of nitric oxide and lipid peroxidation in heart tissues. The modulatory effects of marjoram leaves shown in the present study were dose-dependent in most cases and much higher in MLE (4.3-20.3 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, this study may have a significant impact on myocardial infarcted patients.

Acute and twenty-eight days repeated oral dose toxicity study of besifloxacin in Wistar albino rats.

The purpose of this study was to investigate the potential acute and 28-day repeated oral toxicities of besifloxacin (BAF) in Wistar albino rats. In oral acute and repeated dose study, BAF was administered to both sex of rats, at dose levels of 0, 300, 600, 900 mg/kg/day and 0, 100, 200, 500 mg/kg/day, respectively. In the acute study, total white blood cell (WBC) (male, 43.74%; female, 42.60%) and total bilirubin (T-BIL) (male, 80%; female, 60%) were significantly increase, total protein (TP) (male, 23.24%; 27.80%) was significantly decreased, and significant incidence of pericholangitis (male, 83.33%; female, 75%) was shown in males and females of high-dose groups. In repeated oral dose toxicity study, similar type effects were also observed after serum hematological and serum biochemical analysis, whereas additionally sever hepatic injury and focal ulceration in gastric mucosa also observed in high dose groups of both sexes after histopathological analysis. However these toxic effects of besifloxacin were transient and reversible and no-observed adverse effect level (NOAEL) were 300 mg/kg/day for acute and 100 mg/kg/day for repeated dose toxicity study, respectively.

Shiquandabutangjiaweibang inhibits tumor metastasis and angiogenesis via regulation of topoisomerase-1.

Shiquandabutangjiaweibang (SDJ) is a traditional medicine prescription used for increasing body resistance against cancer. In the present study, the effect of SDJ extract on tumor metastasis and angiogenesis was evaluated. SDJ showed cytotoxicity against P388 (leukemia cells) and B16-F10 (murine melanoma cells) to 60% of control at 1 mg. SDJ significantly inhibited lung metastasis and also restored the number of platelets in C57BL/6 mice with thrombocytopenia induced by intravenous injection of B16-F10 cells. SDJ significantly disrupted chick embryonic angiogenesis in the chorioallantoic membrane (CAM). Interestingly, SDJ suppressed DNA topoisomerase I in a concentration-dependent manner. These results suggest that SDJ can be a potent inhibitor of metastasis and angiogenesis, at least in part, via regulation of topoisomerase I.

Evaluation of toxicity of cypenhymustine, a new anticancer compound, in mice.

The toxicity of cypenhymustine, a potential anticancer compound 1 (Cancer Letters, 70 (1993) 1-6), was assessed in normal as well as in Ehrlich ascites carcinoma (EAC), Sarcoma-180 (S-180) and Dalton's lymphoma (DL)-bearing Swiss male mice by measuring drug-induced changes in (1) hematological parameters and (2) femoral bone marrow cellularity on day 9 following drug treatment at the optimum dose of 3.0 mg/kg body weight from days 1 to 7. Detailed studies were also made by noting sequential changes in the above parameters in normal and EAC-bearing mice on days 12, 15, 18 and 21, respectively. The results indicate that the compound did not adversely affect hematopoiesis. From the sequential studies, it was observed that after a mild initial decrease in hematological counts, particularly in EAC-bearing treated mice, normalcy was reached within 11-14 days after termination of drug therapy. Drug induced hepatotoxicity and nephrotoxicity were also sequentially evaluated in normal and EAC-bearing mice on days 9, 12 and 15 but no such toxicities were detected. Also, body weight, skin and hair texture, and behavioural pattern (food and water intake and activity) did not reflect any toxic reaction in the host mice at this optimum dose.

The effects of olive oil, hydrogenated palm oil, and omega-3 fatty acid-enriched diets on megakaryocytes and platelets.

Unsaturated fatty acids are thought to prevent thrombotic and arteriosclerotic disease, whereas saturated fatty acids are thought to increase the incidence of these disorders. However, the effects of these diets on megakaryocytes and platelets are not well understood. We compared the effects of diets enriched with 8.4% olive oil, 8.4% hydrogenated palm oil, or 10.2% omega-3 fatty acid ethyl esters on guinea pig megakaryocytes and platelets. In plasma, changes in fatty acid composition reflected the composition of each diet. However, in platelets and megakaryocytes, hydrogenated palm oil induced a decrease in 16:0 and an increase in 18:2 while the olive oil diet caused a marked increase in 18:1 and a decrease in most other fatty acids. The differences in the effects of the diets on cellular versus plasma fatty acids suggest that megakaryocytes and platelets have an extensive capacity to regulate their fatty acid composition. Thrombocytosis occurred with the omega-3 fatty acid-enriched diet: 12.9 +/- 1.78 x 10(5) compared with 7.45 +/- 1.08 x 10(5) platelets per microliter of platelet-rich plasma in control animals. There was an increase in megakaryocyte size, ploidy, and morphological stage (cytoplasmic maturation) with the omega-3 fatty acid-enriched diet but not with the other diets. The omega-3 fatty acid-enriched diet decreased platelet thromboxane production while the other diets had no effect. Platelet hypersensitivity was suggested in collagen aggregation studies with olive oil but not with the hydrogenated palm oil diet. Although saturated fatty acid diets are thought to be atherogenic, this diet had no affect on platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)